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  • 1.
    Agoston, Denes V.
    et al.
    Uniformed Serv Univ Hlth Sci, Dept Anat, Bethesda, MD 20814 USA.;Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Sköld, Mattias K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Editorial: When Physics Meets Biology; Biomechanics and Biology of traumatic Brain injury2016In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 7, article id 91Article in journal (Other academic)
  • 2.
    Almandoz-Gil, Leire
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Persson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lindström, Veronica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Erlandsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Bergström, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    In situ proximity ligation assay reveals co-localization of alpha-synuclein and SNARE proteins in murine primary neurons2018In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 180Article in journal (Refereed)
    Abstract [en]

    The aggregation of alpha-synuclein (alpha Syn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders. However, the physiological function of the protein and how this function relates to its pathological effects remain poorly understood. One of the proposed roles of aSyn is to promote the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly by binding to VAMP-2. The objective of this study was to visualize the co-localization between aSyn and the SNARE proteins (VAMP-2, SNAP-25, and syntaxin-1) for the first time using in situ proximity ligation assay (PLA). Cortical primary neurons were cultured from either non-transgenic or transgenic mice expressing human aSyn with the A30P mutation under the Thy-1 promoter. With an antibody recognizing both mouse and human aSyn, a PLA signal indicating close proximity between aSyn and the three SNARE proteins was observed both in the soma and throughout the processes. No differences in the extent of PLA signals were seen between non-transgenic and transgenic neurons. With an antibody specific against human aSyn, the PLA signal was mostly located to the soma and was only present in a few cells. Taken together, in situ PLA is a method that can be used to investigate the co-localization of aSyn and the SNARE proteins in primary neuronal cultures

  • 3.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Pettersson, Lars-Gunnar
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg , Gothenburg.
    Skilled reaching and grasping in the rat: lacking effect of corticospinal lesion2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 103Article in journal (Refereed)
    Abstract [en]

    The corticospinal system is a major motor pathway in the control of skilled voluntary movements such as reaching and grasping. It has developed considerably phylogenetically to reach a peak in humans. Because rodents possess advanced forelimb movements that can be used for reaching and grasping food, it is commonly considered that the corticospinal tract (CST) is of major importance for this control also in rodents. A close homology to primate reaching and grasping has been described but with obvious limitations as to independent digit movements, which are lacking in rodents. Nevertheless, it was believed that there are, as in the primate, direct cortico-motoneuronal connections. Later, it was shown that there are no such connections. The fastest excitatory pathway is disynaptic, mediated via cortico-reticulospinal neurons and in the spinal cord the excitation is mainly polysynaptically mediated via segmental interneurons. Earlier behavioral studies have aimed at investigating the role of the CST by using pyramidotomy in the brainstem. However, in addition to interrupting the CST, a pyramidal transection abolishes the input to reticulospinal neurons. It is therefore not possible to conclude if the deficits after pyramidotomy result from interruption of the CST or the input to reticulospinal neurons or both. We have re-investigated the role of the CST by examining the effect of a CST lesion in the C1-C2 spinal segments on the success rate of reaching and grasping. This lesion spares the cortico-reticulospinal pathway. In contrast to investigations using pyramidal transections, the present study did not demonstrate marked deficits in reaching and grasping. We propose that the difference in results can be explained by the intact cortical input to reticulospinal neurons in our study and thus implicate an important role of this pathway in the control of reaching and grasping in the rat.

  • 4.
    Bartek, Jiri, Jr.
    et al.
    Karolinska Univ Hosp, Dept Neurosurg, Stockholm, Sweden;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden;Karolinska Inst, Dept Med, Stockholm, Sweden;Copenhagen Univ Hosp, Rigshosp, Dept Neurosurg, Copenhagen, Denmark.
    Forander, Petter
    Karolinska Univ Hosp, Dept Neurosurg, Stockholm, Sweden.
    Thurin, Erik
    Sahlgrens Univ Hosp, Dept Neurol, Gothenburg, Sweden.
    Wangerid, Theresa
    Capio St Goran Hosp, Dept Neurol, Stockholm, Sweden.
    Henriksson, Roger
    Reg Canc Ctr Stockholm Gotland, Stockholm, Sweden;Univ Umea, Dept Radiat Sci & Oncol, Umea, Sweden.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Jakola, Asgeir Store
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden;Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden;St Olavs Univ Hosp, Dept Neurosurg, Trondheim, Norway.
    Short-Term Surgical Outcome for Vestibular Schwannoma in Sweden: A Nation-Wide Registry Study2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 43Article in journal (Refereed)
    Abstract [en]

    Background: Vestibular Schwannoma (VS) is a benign neoplasm arising from the 8th cranial nerve, with surgery one of the treatment modalities. In a nation-wide registry study, we describe the baseline, treatment characteristics, and short-term outcome in patients surgically treated for VS.

    Methods: We performed a nationwide study with data from the Swedish Brain Tumor Registry (SBTR) for all adults diagnosed with VS 2009-2015. Patient symptoms, tumor characteristics, and postoperative complications were analyzed.

    Results: In total 348 patients underwent surgery for VS. Mean age was 50.6 +/- 14.5 years and 165 patients (47.4%) were female. The most common symptom was focal neurological deficit (92.0%), with only 25 (7.2%) being asymptomatic prior to surgery, and 217 (63.6%) had no restriction in activity. Following surgery, 100 (28.7%) patients developed new deficit(s). In terms of postoperative complications; 11 (3.2%) had a hematoma, 35 (10.1%) an infection, 10 (2.9%) a venous thromboembolism, and 23 (6.6%) had a reoperation due to complication. There were no deaths within 30-days after surgery. When grouped according to tumor size (<4 vs. >= 4 cm), those with >= 4 cm tumors were more often males (p = 0.02), had more often ICP related symptoms (p = 0.03) and shorter time from imaging to surgery (p < 0.01). Analysis of the younger (<65 years) vs. elderly (>= 65 years) revealed no difference in outcome except increased 1-year mortality (p = 0.002) in elderly.

    Conclusion: In this nation-wide registry-study, we benchmark the 30-day complication rate after VS surgery as collected by the SBTR. Further, we present the current neurosurgical outcome data from both VS smaller than 40 mm compared to larger tumors, as well as younger vs. elderly VS patients. Since surgical decision making is a careful consideration of short term risk vs. long term benefit, this information can be useful in clinical decision making.

  • 5. Bartek, Jiri, Jr.
    et al.
    Förander, Petter
    Thurin, Erik
    Wangerid, Theresa
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Centre Stockholm/Gotland, Stockholm, Sweden.
    Hesselager, Göran
    Jakola, Asgeir Store
    Short-Term Surgical Outcome for Vestibular Schwannoma in Sweden: A Nation-Wide Registry Study2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 43Article in journal (Refereed)
    Abstract [en]

    Background: Vestibular Schwannoma (VS) is a benign neoplasm arising from the 8th cranial nerve, with surgery one of the treatment modalities. In a nation-wide registry study, we describe the baseline, treatment characteristics, and short-term outcome in patients surgically treated for VS.

    Methods: We performed a nationwide study with data from the Swedish Brain Tumor Registry (SBTR) for all adults diagnosed with VS 2009–2015. Patient symptoms, tumor characteristics, and postoperative complications were analyzed.

    Results: In total 348 patients underwent surgery for VS. Mean age was 50.6 ± 14.5 years and 165 patients (47.4%) were female. The most common symptom was focal neurological deficit (92.0%), with only 25 (7.2%) being asymptomatic prior to surgery, and 217 (63.6%) had no restriction in activity. Following surgery, 100 (28.7%) patients developed new deficit(s). In terms of postoperative complications; 11 (3.2%) had a hematoma, 35 (10.1%) an infection, 10 (2.9%) a venous thromboembolism, and 23 (6.6%) had a reoperation due to complication. There were no deaths within 30-days after surgery. When grouped according to tumor size (< 4 vs. ≥4 cm), those with ≥4 cm tumors were more often males (p = 0.02), had more often ICP related symptoms (p = 0.03) and shorter time from imaging to surgery (p < 0.01). Analysis of the younger (< 65 years) vs. elderly (≥65 years) revealed no difference in outcome except increased 1-year mortality (p = 0.002) in elderly.

    Conclusion: In this nation-wide registry-study, we benchmark the 30-day complication rate after VS surgery as collected by the SBTR. Further, we present the current neurosurgical outcome data from both VS smaller than 40 mm compared to larger tumors, as well as younger vs. elderly VS patients. Since surgical decision making is a careful consideration of short term risk vs. long term benefit, this information can be useful in clinical decision making.

  • 6.
    Cao, Yuli
    et al.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Risling, Marten
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Malm, Elisabeth
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Sonden, Anders
    Karolinska Inst Sodersjukhuset, Dept Clin Sci & Educ, Sect Surg, Stockholm, Sweden..
    Bolling, Magnus Frödin
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Sköld, Mattias K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Cellular High-Energy Cavitation Trauma - Description of a Novel In Vitro Trauma Model in Three Different Cell Types2016In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 7, article id UNSP 10Article in journal (Refereed)
    Abstract [en]

    The mechanisms involved in traumatic brain injury have yet to be fully characterized. One mechanism that, especially in high-energy trauma, could be of importance is cavitation. Cavitation can be described as a process of vaporization, bubble generation, and bubble implosion as a result of a decrease and subsequent increase in pressure. Cavitation as an injury mechanism is difficult to visualize and model due to its short duration and limited spatial distribution. One strategy to analyze the cellular response of cavitation is to employ suitable in vitro models. The flyer-plate model is an in vitro high-energy trauma model that includes cavitation as a trauma mechanism. A copper fragment is accelerated by means of a laser, hits the bottom of a cell culture well causing cavitation, and shock waves inside the well and cell medium. We have found the flyer-plate model to be efficient, reproducible, and easy to control. In this study, we have used the model to analyze the cellular response to microcavitation in SH-SY5Y neuroblastoma, Caco-2, and C6 glioma cell lines. Mitotic activity in neuroblastoma and glioma was investigated with BrdU staining, and cell numbers were calculated using automated time-lapse imaging. We found variations between cell types and between different zones surrounding the lesion with these methods. It was also shown that the injured cell cultures released S-100B in a dose-dependent manner. Using gene expression microarray, a number of gene families of potential interest were found to be strongly, but differently regulated in neuroblastoma and glioma at 24 h post trauma. The data from the gene expression arrays may be used to identify new candidates for biomarkers in cavitation trauma. We conclude that our model is useful for studies of trauma in vitro and that it could be applied in future treatment studies.

  • 7.
    Castelnuovo, Gianluca
    et al.
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy.;Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Giusti, Emanuele Maria
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy.;Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Manzoni, Gian Mauro
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy.;eCampus Univ, Fac Psychol, Novedrate, Italy..
    Saviola, Donatella
    Santo Stefano Rehabil Ist, Cardinal Ferrari Rehabil Ctr, Fontanellato, Italy..
    Gabrielli, Samantha
    San Pio X Clin, Pain Med Ctr, Humanitas, Milan, Italy..
    Lacerenza, Marco
    San Pio X Clin, Pain Med Ctr, Humanitas, Milan, Italy..
    Pietrabissa, Giada
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy.;Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Cattivelli, Roberto
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy.;Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Spatola, Chiara Anna Maria
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy.;Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Rossi, Alessandro
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Varallo, Giorgia
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Novelli, Margherita
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Villa, Valentina
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Luzzati, Francesca
    IRCCS Galeazzi Orthoped Inst, Milan, Italy..
    Cottini, Andrea
    IRCCS Galeazzi Orthoped Inst, Milan, Italy..
    Lai, Carlo
    Sapienza Univ Rome, Dept Dynam & Clin Psychol, Rome, Italy..
    Volpato, Eleonora
    Catholic Univ Milan, Dept Psychol, Milan, Italy.;IRCCS Fdn Don Carlo Gnocchi, HD Resp Rehabil Unit, Milan, Italy..
    Cavalera, Cesare
    Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Pagnini, Francesco
    Catholic Univ Milan, Dept Psychol, Milan, Italy.;Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA..
    Tesio, Valentina
    Univ Turin, Dept Psychol, Turin, Italy..
    Castelli, Lorys
    Univ Turin, Dept Psychol, Turin, Italy..
    Tavola, Mario
    ASST Lecco, Anesthesia & Intens Care, Lecce, Italy..
    Torta, Riccardo
    Univ Turin, Dept Neurosci Rita Levi Montalcini, Turin, Italy..
    Arreghini, Marco
    San Giuseppe Hosp, Rehabil Unit, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Zanini, Loredana
    San Giuseppe Hosp, Rehabil Unit, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Brunani, Amelia
    San Giuseppe Hosp, Rehabil Unit, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Seitanidis, Ionathan
    San Giuseppe Hosp, Rehabil Unit, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Ventura, Giuseppe
    San Giuseppe Hosp, Rehabil Unit, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Capodaglio, Paolo
    San Giuseppe Hosp, Rehabil Unit, Ist Auxol Italiano IRCCS, Verbania, Italy..
    D'Aniello, Guido Edoardo
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy.;Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Scarpina, Federica
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Brioschi, Andrea
    San Giuseppe Hosp, Dept Neurol & Neurorehabil, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Bigoni, Matteo
    San Giuseppe Hosp, Dept Neurol & Neurorehabil, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Priano, Lorenzo
    Univ Turin, Dept Neurosci Rita Levi Montalcini, Turin, Italy.;San Giuseppe Hosp, Dept Neurol & Neurorehabil, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Mauro, Alessandro
    Univ Turin, Dept Neurosci Rita Levi Montalcini, Turin, Italy.;San Giuseppe Hosp, Dept Neurol & Neurorehabil, Ist Auxol Italiano IRCCS, Verbania, Italy..
    Riva, Giuseppe
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy.;Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Di Lernia, Daniele
    Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Repetto, Claudia
    Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Regalia, Camillo
    Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Molinari, Enrico
    San Giuseppe Hosp, Psychol Res Lab, Ist Auxol Italiano IRCCS, Verbania, Italy.;Catholic Univ Milan, Dept Psychol, Milan, Italy..
    Notaro, Paolo
    AO Osped Niguarda Ca Granda, Anesthesiol Dept, Pain Med, Milan, Italy..
    Paolucci, Stefano
    Fdn Santa Lucia IRCCS, Rome, Italy..
    Sandrini, Giorgio
    C Mondino Natl Neurol Inst, Pavia, Italy.;Univ Pavia, Dept Brain & Behav Sci, Pavia, Italy..
    Simpson, Susan
    Univ South Australia, Adelaide, SA, Australia.;NHS Lothian, Reg Eating Disorders Unit, Livingston, Scotland..
    Wiederhold, Brenda Kay
    Virtual Real Med Inst, Brussels, Belgium..
    Gaudio, Santino
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Jackson, Jeffrey B.
    Virginia Tech, Falls Church, VA USA..
    Tamburin, Stefano
    Univ Verona, Dept Neurosci Biomed & Movement Sci, Verona, Italy..
    Benedetti, Fabrizio
    Univ Turin, Dept Neurosci Rita Levi Montalcini, Turin, Italy..
    What Is the Role of the Placebo Effect for Pain Relief in Neurorehabilitation?: Clinical Implications From the Italian Consensus Conference on Pain in Neurorehabilitation2018In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 310Article, review/survey (Refereed)
    Abstract [en]

    Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use.

    Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form.

    Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results.

    Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy.

  • 8.
    Clausen, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hansson, Hans-Arne
    Univ Gothenburg, Inst Biomed, Gothenburg, Sweden..
    Raud, Johan
    Lantmannen AS Faktor AB, Stockholm, Sweden..
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Intranasal Administration of the Antisecretory Peptide AF-16 Reduces Edema and Improves Cognitive Function Following Diffuse Traumatic Brain Injury in the Rat2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 39Article in journal (Refereed)
    Abstract [en]

    A synthetic peptide with antisecretory activity, antisecretory factor (AF)-16, improves injury-related deficits in water and ion transport and decreases intracranial pressure after experimental cold lesion injury and encephalitis although its role in traumatic brain injury (TBI) is unknown. AF-16 or an inactive reference peptide was administrated intranasally 30 min following midline fluid percussion injury (mFPI; n = 52), a model of diffuse mild-moderate TBI in rats. Sham-injured (n = 14) or naive (n = 24) animals were used as controls. The rats survived for either 48 h or 15 days post-injury. At 48 h, the animals were tested in the Morris water maze (MWM) for memory function and their brains analyzed for cerebral edema. Here, mFPI-induced brain edema compared to sham or naive controls that was significantly reduced by AF-16 treatment (p < 0.05) although MWM performance was not altered. In the 15-day survival groups, the MWM learning and memory abilities as well as histological changes were analyzed. AF-16-treated brain-injured animals shortened both MWM latency and swim path in the learning trials (p < 0.05) and improved probe trial performance compared to brain-injured controls treated with the inactive reference peptide. A modest decrease by AF-16 on TBI-induced changes in hippocampal glial acidic fibrillary protein (GFAP) staining (p = 0.11) was observed. AF-16 treatment did not alter any other immunohistochemical analyses (degenerating neurons, beta-amyloid precursor protein (beta-APP), and Olig2). In conclusion, intranasal AF-16-attenuated brain edema and enhanced visuospatial learning and memory following diffuse TBI in the rat. Intranasal administration early post-injury of a promising neuroprotective substance offers a novel treatment approach for TBI.

  • 9. Crippa, Sylvain, V
    et al.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kawasaki, Aki
    Chromatic pupillometry in children2018In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 669Article in journal (Refereed)
    Abstract [en]

    Chromatic pupillometry is a technique that is increasingly used to assess retinal disorders. As age may be one of the various factors which can influence the pupillary light reaction, this study aimed to evaluate the pupil responses to colored light stimuli in the pediatric population. Fifty-three children with normal vision and without any history of ocular disorders were tested with a portable pupillometer. Four test sequences were used: five dim blue (470 nm) stimuli presented in half log steps ranging from -3.15 to -1.15 log cd/m(2) after 3 min of dark adaptation, five red (622 nm) stimuli of -1.15, -0.7, -0.15, 0.3, and 0.85 log cd/m(2) after 1 min light adaptation, one bright blue stimulus of 2.2 log cd/m(2) and one bright red of 2 log cd/m(2). The results were grouped by age: a younger group included 27 children aged from 3 to 10 years old and an older group included 26 from 10 and 1 month to 18 years old. The younger group had a smaller pupil diameter after dark adaptation compared with the older group. A linear regression defining the photopic threshold showed that younger subjects had a higher threshold, e.g., needed a brighter red stimulus to evoke a threshold pupil response comparable that of subjects. Age thus seems to influence outer retinal sensitivity at least as evaluated by the pupillary photopic threshold intensity. The post-illumination pupillary reaction was used as a marker of intrinsic melanopsin activity and did not show any difference between the two age groups.

  • 10. Dahlin, Lars B.
    et al.
    Andersson, Gert
    Backman, Clas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery. Department of Hand Surgery, University Hospital of Northern Sweden, Umeå University, Umeå, Sweden.
    Svensson, Hampus
    Bjorkman, Anders
    Rehabilitation, Using Guided Cerebral plasticity, of a Brachial plexus Injury treated with Intercostal and phrenic Nerve transfers2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 72Article in journal (Refereed)
    Abstract [en]

    Recovery after surgical reconstruction of a brachial plexus injury using nerve grafting and nerve transfer procedures is a function of peripheral nerve regeneration and cerebral reorganization. A 15-year-old boy, with traumatic avulsion of nerve roots C5-C7 and a non-rupture of C8-T1, was operated 3 weeks after the injury with nerve transfers: ( a) terminal part of the accessory nerve to the suprascapular nerve, (b) the second and third intercostal nerves to the axillary nerve, and (c) the fourth to sixth intercostal nerves to the musculocutaneous nerve. A second operation-free contralateral gracilis muscle transfer directly innervated by the phrenic nerve-was done after 2 years due to insufficient recovery of the biceps muscle function. One year later, electromyography showed activation of the biceps muscle essentially with coughing through the intercostal nerves, and of the transferred gracilis muscle by deep breathing through the phrenic nerve. Voluntary flexion of the elbow elicited clear activity in the biceps/gracilis muscles with decreasing activity in intercostal muscles distal to the transferred intercostal nerves (i.e., corresponding to eighth intercostal), indicating cerebral plasticity, where neural control of elbow flexion is gradually separated from control of breathing. To restore voluntary elbow function after nerve transfers, the rehabilitation of patients operated with intercostal nerve transfers should concentrate on transferring coughing function, while patients with phrenic nerve transfers should focus on transferring deep breathing function.

  • 11.
    Elgh, Eva
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Hu, Xiaolei
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Dynamic Trajectory of Long-Term Cognitive Improvement Up to 10 Years in Young Community-Dwelling Stroke Survivors: A Cohort Study2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 97Article in journal (Refereed)
    Abstract [en]

    Background and objective: The trajectories of long-term and domain-specific cognitive alterations over a decade after stroke are largely unknown. This study aims to investigate the dynamic alterations of domain-specific cognitive performance among young stroke survivors over 10 years after their first stroke.

    Methods: A prospective cohort study was carried out on 38 young stroke survivors (aged 18-65 at stroke onset) living in the community at 10 years after their first stroke. The cognitive outcomes were assessed repeatedly at 1 week, 7 months, and 10 years after their first stroke on the sub-domains: process speed (Symbol search and Coding from WAIS, TMT-A), visual attention (Bells test), visuospatial function (Block design from WAIS, RCFT), executive function (TMT-B, verbal fluency), verbal function [Letter fluency (FAS) from D-KEFS and CD], working memory (Digit Span from WAIS), immediate memory (RCFT and CD), and delayed memory (RCFT and CD). Global cognition was evaluated with Mini mental state examination at the two later time-points.

    Results: We found a delayed significant improvement of working memory with total recovery 10 years after participants' stroke. Visuospatial function recovered already at 7 months and remained stable at 10-year follow-up. Process speed demonstrated a significant decrease at 10 years compared to 7 months after stroke onset, a decrease which could be compensated by enhancements of other cognitive domains. No further deterioration was found in verbal function, immediate-, and delayed memory, and executive function during 10-year follow-up. Global cognition improved by on average two points between 7 months and 10 years. Education level and fatigue showed low to moderate positive correlations with cognitive improvements.

    Conclusions: The concordance of cognitive improvements between domain-specific and global cognitions strongly suggest that some young stroke survivors do improve their cognitive outcome over a 10-year period following their first stroke. This finding fills a gap of knowledge with respect to the dynamic trajectory of post-stroke cognition, with important implications in clinical practice.

  • 12.
    Engström, Maria
    et al.
    Linkoping Univ, Dept Med & Hlth Sci IMH, Div Radiol Sci, Linkoping, Sweden; Linkoping Univ, Ctr Med Image Sci & Visualizat CMIV, Linkoping, Sweden.
    Hallböök, Tove
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Pediat, Gothenburg, Sweden.
    Szakacs, Attila
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Pediat, Gothenburg, Sweden; Halmstad Cty Hosp, Dept Pediat, Halmstad, Sweden.
    Karlsson, Thomas
    Linkoping Univ, Ctr Med Image Sci & Visualizat CMIV, Linkoping, Sweden; Linkoping Univ, Div Disabil Res, Linkoping, Sweden; Linkoping Univ, Linnaeus Ctr HEAD, Dept Behav Sci & Learning, Linkoping, Sweden.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Linkoping Univ, Ctr Med Image Sci & Visualizat CMIV, Linkoping, Sweden; Linkoping Univ, Dept Neurol, Dept Clin & Expt Med IKE, Linkoping, Sweden; Linkoping Univ, Dept Med & Hlth Sci, Dept Med Specialist, Motala, Sweden.
    Functional magnetic resonance imaging in narcolepsy and the Kleine-Levin syndrome2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 105Article in journal (Refereed)
    Abstract [en]

    This work aims at reviewing the present state of the art when it comes to understanding the pathophysiology of narcolepsy and the Kleine-Levin syndrome (KLS) from a neuroimaging point of view. This work also aims at discussing future perspectives of functional neuroimaging in these sleep disorders. We focus on functional magnetic resonance imaging (fMRI), which is a technique for in vivo measurements of brain activation in neuronal circuitries under healthy and pathological conditions. fMRI has significantly increased the knowledge on the affected neuronal circuitries in narcolepsy and the Kleine-Levin syndrome. It has been shown that narcolepsy is accompanied with disturbances of the emotional and the closely related reward systems. In the Kleine Levin syndrome, fMRI has identified hyperactivation of the thalamus as a potential biomarker that could be used in the diagnostic procedure. The fMRI findings in both narcolepsy and the Kleine-Levin syndrome are in line with previous structural and functional imaging studies. We conclude that fMRI in combination with multi-modal imaging can reveal important details about the pathophysiology in narcolepsy and the Kleine-Levin syndrome. In the future, fMRI possibly gives opportunities for diagnostic support and prediction of treatment response in individual patients.

  • 13.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Hallböök, Tove
    Sahlgrenska Academy, University of Gothenburg, Sweden.
    Szakacs, Attila
    Sahlgrenska Academy, University of Gothenburg. Sweden; Halmstad County Hospital, Sweden.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Functional magnetic resonance imaging in narcolepsy and the Kleine–Levin syndrome2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, no 105Article in journal (Refereed)
    Abstract [en]

    This work aims at reviewing the present state of the art when it comes to understanding the pathophysiology of narcolepsy and the Kleine–Levin syndrome (KLS) from a neuroimaging point of view. This work also aims at discussing future perspectives of functional neuroimaging in these sleep disorders. We focus on functional magnetic resonance imaging (fMRI), which is a technique for in vivo measurements of brain activation in neuronal circuitries under healthy and pathological conditions. fMRI has significantly increased the knowledge on the affected neuronal circuitries in narcolepsy and the Kleine–Levin syndrome. It has been shown that narcolepsy is accompanied with disturbances of the emotional and the closely related reward systems. In the Kleine Levin syndrome, fMRI has identified hyperactivation of the thalamus as a potential biomarker that could be used in the diagnostic procedure. The fMRI findings in both narcolepsy and the Kleine–Levin syndrome are in line with previous structural and functional imaging studies. We conclude that fMRI in combination with multi-modal imaging can reveal important details about the pathophysiology in narcolepsy and the Kleine–Levin syndrome. In the future, fMRI possibly gives opportunities for diagnostic support and prediction of treatment response in individual patients.

  • 14. Engström, Maria
    et al.
    Karlsson, Thomas
    Landtblom, Anne-Marie
    Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
    Reduced thalamic and pontine connectivity in kleine-levin syndrome2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, p. 42-Article in journal (Refereed)
    Abstract [en]

    The Kleine-Levin syndrome (KLS) is a rare sleep disorder, characterized by exceptionally long sleep episodes. The neuropathology of the syndrome is unknown and treatment is often inadequate. The aim of the study was to improve understanding of the underlying neuropathology, related to cerebral networks, in KLS during sleep episodes. One patient with KLS and congenital nystagmus was investigated by resting state functional magnetic resonance imaging during both asymptomatic and hypersomnic periods. Fourteen healthy subjects were also investigated as control samples. Functional connectivity was assessed from seed regions of interest in the thalamus and the dorsal pons. Thalamic connectivity was normal in the asymptomatic patient whereas the connectivity between the brain stem, including dorsal pons, and the thalamus was diminished during hypersomnia. These results suggest that the patient's nystagmus and hypersomnia might have their pathological origin in adjacent dorsal pontine regions. This finding provides additional knowledge of the cerebral networks involved in the neuropathology of this disabling disorder. Furthermore, these findings regarding a rare syndrome have broad implications, and results could be of interest to researchers and clinicians in the whole field of sleep medicine.

  • 15.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Reduced thalamic and pontine connectivity in Kleine–Levin syndrome2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, no 42Article in journal (Refereed)
    Abstract [en]

    The Kleine–Levin syndrome (KLS) is a rare sleep disorder, characterized by exceptionally long sleep episodes. The neuropathology of the syndrome is unknown and treatment is often inadequate. The aim of the study was to improve understanding of the underlying neuropathology, related to cerebral networks, in KLS during sleep episodes. One patient with KLS and congenital nystagmus was investigated by resting state functional magnetic resonance imaging during both asymptomatic and hypersomnic periods. Fourteen healthy subjects were also investigated as control samples. Functional connectivity was assessed from seed regions of interest in the thalamus and the dorsal pons. Thalamic connectivity was normal in the asymptomatic patient whereas the connectivity between the brain stem, including dorsal pons, and the thalamus was diminished during hypersomnia. These results suggest that the patient’s nystagmus and hypersomnia might have their pathological origin in adjacent dorsal pontine regions. This finding provides additional knowledge of the cerebral networks involved in the neuropathology of this disabling disorder. Furthermore, these findings regarding a rare syndrome have broad implications, and results could be of interest to researchers and clinicians in the whole field of sleep medicine.

  • 16.
    Hillered, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Chu, Jiangtao
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cerebral microdialysis for protein biomarker monitoring in the neurointensive care setting - a technical approach2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, p. 245-Article in journal (Refereed)
    Abstract [en]

    Cerebral microdialysis (MD) was introduced as a neurochemical monitoring method in the early 1990s and is currently widely used for the sampling of low molecular weight molecules, signaling energy crisis, and cellular distress in the neurointensive care (NIC) setting. There is a growing interest in MD for harvesting of intracerebral protein biomarkers of secondary injury mechanisms in acute traumatic and neurovascular brain injury in the NIC community. The initial enthusiasm over the opportunity to sample protein biomarkers with high molecular weight cut-off MD catheters has dampened somewhat with the emerging realization of inherent methodological problems including protein-protein interaction, protein adhesion, and biofouling, causing an unstable in vivo performance (i.e., fluid recovery and extraction efficiency) of the MD catheter. This review will focus on the results of a multidisciplinary collaborative effort, within the Uppsala Berzelii Centre for Neurodiagnostics during the past several years, to study the features of the complex process of high molecular weight cut-off MD for protein biomarkers. This research has led to new methodology showing robust in vivo performance with optimized fluid recovery and improved extraction efficiency, allowing for more accurate biomarker monitoring. In combination with evolving analytical methodology allowing for multiplex biomarker analysis in ultra-small MD samples, a new opportunity opens up for high-resolution temporal mapping of secondary injury cascades, such as neuroinflammation and other cell injury reactions directly in the injured human brain. Such data may provide an important basis for improved characterization of complex injuries, e.g., traumatic and neurovascular brain injury, and help in defining targets and treatment windows for neuroprotective drug development.

  • 17. Hånell, Anders
    et al.
    Hedin, Johanna
    Clausen, Fredrik
    Marklund, Niklas
    Facilitated assessment of tissue loss following traumatic brain injury.2012In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 3Article in journal (Refereed)
    Abstract [en]

    All experimental models of traumatic brain injury (TBI) result in a progressive loss of brain tissue. The extent of tissue loss reflects the injury severity and can be measured to evaluate the potential neuroprotective effect of experimental treatments. Quantitation of tissue volumes is commonly performed using evenly spaced brain sections stained using routine histochemical methods and digitally captured. The brain tissue areas are then measured and the corresponding volumes are calculated using the distance between the sections. Measurements of areas are usually performed using a general purpose image analysis software and the results are then transferred to another program for volume calculations. To facilitate the measurement of brain tissue loss we developed novel algorithms which automatically separate the areas of brain tissue from the surrounding image background and identify the ventricles. We implemented these new algorithms by creating a new computer program (SectionToVolume) which also has functions for image organization, image adjustments and volume calculations. We analyzed brain sections from mice subjected to severe focal TBI using both SectionToVolume and ImageJ, a commonly used image analysis program. The volume measurements made by the two programs were highly correlated and analysis using SectionToVolume required considerably less time. The inter-rater reliability was high. Given the extensive use of brain tissue loss measurements in TBI research, SectionToVolume will likely be a useful tool for TBI research. We therefore provide both the source code and the program as attachments to this article.

  • 18.
    Johansson, Anna-Maria
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Domellöf, Erik
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Rönnqvist, Louise
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Timing training in three children with diplegi ccerebral palsy: short- and long-term effects on upper-limb movement organization and functioning2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 38Article in journal (Refereed)
    Abstract [en]

    Despite the great need of interventions to maintain and improve motor functions in children with diplegic cerebral palsy (DCP), scientific evaluations of existing training methods are rare. This study aimed to explore individual effects of synchronized metronome training (SMT) on motor timing, spatio-temporal movement organization, and subjective experiences of changes in upper-limb functions in three children with DCP. All children participated in an individualized 4-week/12 session SMT training regime. Measurements before training (Pre), after training (Post1), and at 6 months post completed training (Post2) were made by the applied SMT training equipment, optoelectronic registrations of goal-directed upper-limb movements, and a questionnaire assessing subjective experiences of changes in upper-limb functions and usability. In general, the training regime was shown to have little effect on motor timing. However, some positive changes in spatio-temporal movement organization were found. Two children also reported substantial long-lasting positive changes in subjective experiences of hand/arm functionality in terms of increased movement control and reduced muscle tone. For these children, parallel kinematic findings also indicated smoother and faster movement trajectories that remained at Post2. Although highly individualized, the shown improvements in upper-limb kinematics and subjective experiences of improved functionality of the hands/arms for two of the cases warrant further explorations of SMT outcomes in children with DCP.

  • 19.
    Kakooza-Mwesige, Angelina
    et al.
    Makerere Univ, Uganda;Mulago Hosp, Uganda.
    Mohammed, Abdul K. H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Kristensson, Krister
    Karolinska Institutet.
    Juliano, Sharon L.
    Uniformed Serv Univ Hlth Sci, USA.
    Lutwama, Julius J.
    Uganda Virus Res Inst, Uganda.
    Emerging Viral Infections in Sub-Saharan Africa and the Developing Nervous System: A Mini Review2018In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 82Article, review/survey (Refereed)
    Abstract [en]

    The global public health concern is heightened over the increasing number of emerging viruses, i.e., newly discovered or previously known that have expanded into new geographical zones. These viruses challenge the health-care systems in sub-Saharan Africa (SSA) countries from which several of them have originated and been transmitted by insects worldwide. Some of these viruses are neuroinvasive, but have been relatively neglected by neuroscientists. They may provide experiments by nature to give a time window for exposure to a new virus within sizeable, previously non-infected human populations, which, for instance, enables studies on potential long-term or late-onset effects on the developing nervous system. Here, we briefly summarize studies on the developing brain by West Nile, Zika, and Chikungunya viruses, which are mosquito-borne and have spread worldwide out of SSA. They can all be neuroinvasive, but their effects vary from malformations caused by prenatal infections to cognitive disturbances following perinatal or later infections. We also highlight Ebola virus, which can leave surviving children with psychiatric disturbances and cause persistent infections in the non-human primate brain. Greater awareness within the neuroscience community is needed to emphasize the menace evoked by these emerging viruses to the developing brain. In particular, frontline neuroscience research should include neuropediatric follow-up studies in the field on long-term or late-onset cognitive and behavior disturbances or neuropsychiatric disorders. Studies on pathogenetic mechanisms for viral-induced perturbations of brain maturation should be extended to the vulnerable periods when neurocircuit formations are at peaks during infancy and early childhood.

  • 20.
    Kiiski, Heikki
    et al.
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland..
    Jalkanen, Ville
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland..
    Ala-Peijari, Marika
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland..
    Hamalainen, Mari
    Univ Tampere, Tampere Univ Hosp, Fac Med & Life Sci, Immunopharmacol Res Grp, Tampere, Finland..
    Moilanen, Eeva
    Univ Tampere, Tampere Univ Hosp, Fac Med & Life Sci, Immunopharmacol Res Grp, Tampere, Finland..
    Peltola, Jukka
    Univ Tampere, Tampere Univ Hosp, Dept Neurol, Tampere, Finland..
    Tenhunen, Jyrki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland..
    Plasma soluble Urokinase-Type Plasminogen activator receptor is not associated with neurological Outcome in Patients with aneurysmal subarachnoid hemorrhage2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 144Article in journal (Refereed)
    Abstract [en]

    Object: Aneurysmal subarachnoid hemorrhage (aSAH) is a common cause of death or long-term disability. Despite advances in neurocritical care, there is still only a very limited ability to monitor the development of secondary brain injury or to predict neurological outcome after aSAH. Soluble urokinase-type plasminogen activator receptor (suPAR) has shown potential as a prognostic and as an inflammatory biomarker in a wide range of critical illnesses since it displays an association with overall immune system activation. This is the first time that suPAR has been evaluated as a prognostic biomarker in aSAH. Methods: In this prospective population-based study, plasma suPAR levels were measured in aSAH patients (n = 47) for up to 5 days. suPAR was measured at 0, 12, and 24 h after patient admission to the intensive care unit (ICU) and daily thereafter until he/ she was transferred from the ICU. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at 6 months after aSAH. Results: suPAR levels (n = 47) during the first 24 h after aSAH were comparable in groups with a favorable (mRS 0-2) or an unfavorable (mRS 3-6) outcome. suPAR levels during the first 24 h were not associated with the findings in the primary brain CT, with acute hydrocephalus, or with antimicrobial medication use during 5-days' follow-up. suPAR levels were associated with generally accepted inflammatory biomarkers (C-reactive protein, leukocyte count). Conclusion: Plasma suPAR level was not associated with either neurological outcome or selected clinical conditions. While suPAR is a promising biomarker for prognostication in several conditions requiring intensive care, it did not reveal any value as a prognostic biomarker after aSAH.

  • 21.
    Landtblom, Anne-Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Engström, Maria
    Brain circuitries involved in sleep disorders2015In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, article id UNSP 66Article in journal (Refereed)
  • 22.
    Landtblom, Anne-Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Brain circuitries involved in sleep disorders2015In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, no UNSP 66Article in journal (Refereed)
    Abstract [en]

    n/a

  • 23.
    Landtblom, Anne-Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    The sleepy teenager – diagnostic challenges2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, no 140Article in journal (Refereed)
    Abstract [en]

    The sleepy teenager puts the doctor in a, often tricky, situation where it must be decided if we deal with normal physiology or if we should suspect pathological conditions. What medical investigations are proper to consider? What differential diagnoses should be considered in the first place? And what tools do we actually have? The symptoms and problems that usually are presented at the clinical visit can be both of medical and psychosocial character - and actually they are often a mixture of both. Subsequently, the challenge to investigate the sleepy teenager often includes the examination of a complex behavioral pattern. It is important to train and develop diagnostic skills and to realize that the physiological or pathological conditions that can cause the symptoms may have different explanations. Research in sleep disorders has shown different pathological mechanisms congruent with the variations in the clinical picture. There are probably also different patterns of involved neuronal circuits although common pathways may exist. The whole picture remains to be drawn in this interesting and challenging area.

  • 24.
    Landtblom, Anne-Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Linkoping Univ, Div Neurol, Dept Clin & Expt Med, IKE,Cty Council, Linkoping, Sweden; Linkoping Univ, Cty Council, IMM,Neurol Unit, Dept Med Specialties, Motala, Sweden; Linkoping Univ, Dept Med & Hlth Sci, Div Radiol Sci, Linkoping, Sweden.
    Engström, Maria
    Linkoping Univ, Dept Med & Hlth Sci, Div Radiol Sci, Linkoping, Sweden.
    The sleepy teenager: diagnostic challenges OCR V262014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 140Article in journal (Refereed)
    Abstract [en]

    The sleepy teenager puts the doctor in a, often tricky, situation where it must be decided if we deal with normal physiology or if we should suspect pathological conditions. What medical investigations are proper to consider? What differential diagnoses should be considered in the first place? And what tools do we actually have? The symptoms and problems that usually are presented at the clinical visit can be both of medical and psychosocial character - and actually they are often a mixture of both. Subsequently, the challenge to investigate the sleepy teenager often includes the examination of a complex behavioral pattern. It is important to train and develop diagnostic skills and to realize that the physiological or pathological conditions that can cause the symptoms may have different explanations. Research in sleep disorders has shown different pathological mechanisms congruent with the variations in the clinical picture. There are probably also different patterns of involved neuronal circuits although common pathways may exist. The whole picture remains to be drawn in this interesting and challenging area.

  • 25.
    Leng, Yan
    et al.
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Rehabil Med, Guangzhou, Guangdong, Peoples R China..
    Wang, Zhu
    Sun Yat Sen Univ, Inst Diagnost & Intervent Ultrasound, Affiliated Hosp 1, Dept Med Ultrason, Guangzhou, Guangdong, Peoples R China..
    Bian, Ruihao
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Rehabil Med, Guangzhou, Guangdong, Peoples R China..
    Lo, Wai Leung Ambrose
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Rehabil Med, Guangzhou, Guangdong, Peoples R China..
    Xie, Xiaoyan
    Sun Yat Sen Univ, Inst Diagnost & Intervent Ultrasound, Affiliated Hosp 1, Dept Med Ultrason, Guangzhou, Guangdong, Peoples R China..
    Wang, Ruoli
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, School of Engineering Sciences (SCI), Centres, BioMEx. Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Huang, Dongfeng
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Rehabil Med, Guangzhou, Guangdong, Peoples R China.;Sun Yat Sen Univ, Affiliated Hosp 7, Dept Rehabil Med, Shenzhen, Peoples R China..
    Li, Le
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Rehabil Med, Guangzhou, Guangdong, Peoples R China..
    Alterations of Elastic Property of Spastic Muscle With Its Joint Resistance Evaluated From Shear Wave Elastography and Biomechanical Model2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 736Article in journal (Refereed)
    Abstract [en]

    This study aims to quantify passive muscle stiffness of spastic wrist flexors in stroke survivors using shear wave elastography (SWE) and to correlate with neural and non-neural contributors estimated from a biomechanical model to hyper-resistance measured during passive wrist extension. Fifteen hemiplegic individuals after stroke with Modified Ashworth Scale (MAS) score larger than one were recruited. SWE were used to measure Young's modulus of flexor carpi radialis muscle with joint from 0 degrees (at rest) to 50 degrees flexion (passive stretch condition), with 10 degrees interval. The neural (NC) and non-neural components i.e., elasticity component (EC) and viscosity component (VC) of the wrist joint were analyzed from a motorized mechanical device NeuroFlexor (R) (NF). Combining with a validated biomechanical model, the neural reflex and muscle stiffness contribution to the increased resistance can be estimated. MAS and Fugl-Meyer upper limb score were also measured to evaluate the spasticity and motor function of paretic upper limb. Young's modulus was significantly higher in the paretic side of flexor carpi radialis than that of the non-paretic side (p < 0.001) and it increased significantly from 0 degrees to 50 degrees of the paretic side (p < 0.001). NC, EC, and VC on the paretic side were higher than the non-paretic side (p < 0.05). There was moderate significant positive correlation between the Young's Modulus and EC (r = 0.565, p = 0.028) and VC (r = 0.645, p = 0.009) of the paretic forearm flexor muscle. Fugl-Meyer of the paretic forearm flexor has a moderate significant negative correlation with NC (r = -0.578, p = 0.024). No significant correlation between MAS and shear elastic modulus or NF components was observed. This study demonstrated the feasibility of combining SWE and NF as a non-invasive approach to assess spasticity of paretic muscle and joint in stroke clinics. The neural and non-neural components analysis as well as correlation findings of muscle stiffness of SWE might provide understanding of mechanism behind the neuromuscular alterations in stroke survivors and facilitate the design of suitable intervention for them.

  • 26.
    Lindholm, Tomas
    et al.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;Helsa Foretagshalsovard Ostermalm, Stockholm, Sweden..
    Risling, Marten
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Carlstedt, Thomas
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;UCL, Hammersmith Hosp, London WC1E 6BT, England.;Imperial Coll, London, England.;Soder Sjukhuset, Dept Hand Surg, Stockholm, Sweden.;Soder Sjukhuset, Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden..
    Hammarberg, Henrik
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;Soder Sjukhuset, Dept Hand Surg, Stockholm, Sweden.;Soder Sjukhuset, Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden..
    Wallquist, Wilhelm
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;Vasteras Gen Hosp, Dept Anesthesiol & Intens Care, Vasteras, Sweden..
    Cullheim, Staffan
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Sköld, Mattias K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Expression of Semaphorins, Neuropilins, VEGF, and Tenascins in Rat and Human Primary Sensory Neurons after a Dorsal Root Injury2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 49Article in journal (Refereed)
    Abstract [en]

    Dorsal root injury is a situation not expected to be followed by a strong regenerative growth, or growth of the injured axon into the central nervous system of the spinal cord, if the central axon of the dorsal root is injured but of strong regeneration if subjected to injury to the peripherally projecting axons. The clinical consequence of axonal injury is loss of sensation and may also lead to neuropathic pain. In this study, we have used in situ hybridization to examine the distribution of mRNAs for the neural guidance molecules semaphorin 3A (SEMA3A), semaphorin 3F (SEMA3F), and semaphorin 4F (SEMA4F), their receptors neuropilin 1 (NP1) and neuropilin 2 (NP2) but also for the neuropilin ligand vascular endothelial growth factor (VEGF) and Tenascin J1, an extracellular matrix molecule involved in axonal guidance, in rat dorsal root ganglia (DRG) after a unilateral dorsal rhizotomy (DRT) or sciatic nerve transcetion (SNT). The studied survival times were 1-365 days. The different forms of mRNAs were unevenly distributed between the different size classes of sensory nerve cells. The results show that mRNA for SEMA3A was diminished after trauma to the sensory nerve roots in rats. The SEMA3A receptor NP1, and SEMA3F receptor NP2, was significantly upregulated in the DRG neurons after DRT and SNT. SEMA4F was upregulated after a SNT. The expression of mRNA for VEGF in DRG neurons after DRT showed a significant upregulation that was high even a year after the injuries. These data suggest a role for the semaphorins, neuropilins, VEGF, and J1 in the reactions after dorsal root lesions.

  • 27.
    Liu, Wei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kämpfe Nordström, Charlotta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Danckwardt-Lillieström, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Human Inner Ear Immune Activity: A Super-Resolution Immunohistochemistry Study2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 728Article in journal (Refereed)
    Abstract [en]

    Background: Like the brain, the human inner ear was long thought to be devoid of immune activity. Only the endolymphatic sac (ES) was known to be endowed with white blood cells that could process antigens and serve as an immunologic defense organ for the entire inner ear. Unexpectedly, the cochlear and vestibular organs, including the eighth cranial nerve, were recently shown to contain macrophages whose functions and implication in ear disease are somewhat undefined. Here, we review recent inner ear findings in man and extend the analyses to the vestibular nerve using super-resolution structured illumination microscopy (SR-SIM).

    Materials and Methods: Human ESs and cochleae were collected during surgery to treat patients with vestibular schwannoma and life-threatening petro-clival meningioma compressing the brainstem. The ESs and cochleae were placed in fixative, decalcified, and rapidly frozen and cryostat sectioned. Antibodies against ionized calcium-binding adaptor molecule 1-expressing cells (IBA1 cells), laminin beta 2 and type IV collagen TUJ1, cytokine fractalkine (CX3CL1), toll-like receptor 4 (TLR4), CD68, CD11b, CD4, CD8, the major histocompatibility complex type II (MHCII), and the microglial marker TEME119 were used.

    Results: IBA1-positive cells were present in the ESs, the cochlea, central and peripheral axons of the cochlear nerve, and the vestibular nerve trunk. IBA1 cells were found in the cochlear lateral wall, spiral limbus, and spiral ganglion. Notable variants of IBA1 cells adhered to neurons with "synapse-like" specializations and cytoplasmic projections. Slender IBA1 cells occasionally protracted into the basal lamina of the Schwann cells and had intimate contact with surrounding axons.

    Discussion: The human eighth nerve may be under the control of a well-developed macrophage cell system. A small number of CD4+ and CD8+ cells were found in the ES and occasionally in the cochlea, mostly located in the peripheral region of Rosenthal's canal. A neuro-immunologic axis may exist in the human inner ear that could play a role in the protection of the auditory nerve. The implication of the macrophage system during disease, surgical interventions, and cell-based transplantation should be further explored.

  • 28.
    Manouchehrinia, Ali
    et al.
    Karolinska Inst, Karolinska Univ Hosp Solna, Dept Clin Neurosci, Stockholm, Sweden..
    Hedstrom, Anna Karin
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Alfredsson, Lars
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Olsson, Tomas
    Karolinska Inst, Karolinska Univ Hosp Solna, Dept Clin Neurosci, Stockholm, Sweden..
    Hillert, Jan
    Karolinska Inst, Karolinska Univ Hosp Solna, Dept Clin Neurosci, Stockholm, Sweden..
    Ramanujam, Ryan
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.). Karolinska Inst.
    Association of Pre-Disease Body Mass Index With Multiple Sclerosis Prognosis2018In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 232Article in journal (Refereed)
    Abstract [en]

    Both high body mass index (BMI) and smoking tobacco are known risk factors for developing multiple sclerosis (MS). However, it is unclear whether BMI, like smoking, is a risk factor for the secondary progressive (SP) course. We, therefore, sought to determine if high/low BMI at age 20 is associated to risk of SP development, in the context of smoking status. Using data from MS patients with BMI and smoking information available, we examined relapsing onset patients with MS onset after 20 years of age. Cox regressions were conducted on smokers and non-smokers, with BMI as the main exposure. In total, 5,598 relapsing onset MS patients were included. The models demonstrated that BMI > 30 was associated to increased risk of SPMS in smokers (hazard ratio 1.50, p = 0.036). This association of obesity at age 20 with increased risk of SP was not observed in non-smokers (hazard rate 0.97, p = 0.900). Since the risk is confined to smokers, the interaction observed may give insight to disease driving mechanisms.

  • 29.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Lund Univ, Lund, Sweden.
    The Neurological wake-up Test-A Role in Neurocritical Care Monitoring of Traumatic Brain injury Patients?2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 540Article, review/survey (Refereed)
    Abstract [en]

    The most fundamental clinical monitoring tool in traumatic brain injury (TBI) patients is the repeated clinical examination. In the severe TBI patient treated by continuous sedation in a neurocritical care (NCC) unit, sedation interruption is required to enable a clinical evaluation (named the neurological wake-up test; NWT) assessing the level of consciousness, pupillary diameter and reactivity to light, and presence of focal neurological deficits. There is a basic conflict regarding the NWT in the NCC setting; can the clinical information obtained by the NWT justify the risk of inducing a stress response in a severe TBI patient? Furthermore, in the presence of advanced multimodal monitoring and neuroimaging, is the NWT necessary to identify important clinical alterations? In studies of severe TBI patients, the NWT was consistently shown to induce a stress reaction including brief increases in intracranial pressure (ICP) and changes in cerebral perfusion pressure (CPP). However, it has not been established whether these short-lived ICP and CPP changes are detrimental to the injured brain. Daily interruption of sedation is associated with a reduced ventilator time, shorter hospital stay and reduced mortality in many studies of general intensive care unit patients, although such clinical benefits have not been firmly established in TBI. To date, there is no consensus on the use of the NWT among NCC units and systematic studies are scarce. Thus, additional studies evaluating the role of the NWT in clinical decision-making are needed. Multimodal NCC monitoring may be an adjunct in assessing in which TBI patients the NWT can be safely performed. At present, the NWT remains the golden standard for clinical monitoring and detection of neurological changes in NCC and could be considered in TBI patients with stable baseline ICP and CPP readings. The focus of the present review is an overview of the existing literature on the role of the NWT as a clinical monitoring tool for severe TBI patients.

  • 30.
    Montanino, Annaclauida
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Neuronic Engineering.
    Kleiven, Svein
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Neuronic Engineering.
    Utilizing a Structural Mechanics Approach to Assess the Primary Effects of Injury Loads Onto the Axon and Its Components2018In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, no 643, p. 1-12Article in journal (Refereed)
    Abstract [en]

    Diffuse axonal injury (DAI) occurs as a result of the transmission of rapid dynamic loads from the head to the brain and specifically to its neurons. Despite being one of the most common and most deleterious types of traumatic brain injury (TBI), the inherent cell injury mechanism is yet to be understood. Experimental observations have led to the formulation of different hypotheses, such as mechanoporation of the axolemma and microtubules (MTs) breakage. With the goal of singling out the mechanical aspect of DAI and to resolve the ambiguity behind its injury mechanism, a composite finite element (FE) model of a representative volume of an axon was developed. Once calibrated and validated against published experimental data, the axonal model was used to simulate injury scenarios. The resulting strain distributions along its components were then studied in dependence of strain rate and of typical modeling choices such as the applied MT constraints and tau proteins failure. Results show that oversimplifying the MT bundle kinematic entails a systematic attenuation (cf = 2.33) of the computed maximum MT strain. Nevertheless, altogether, results support the hypothesis of axolemma mechanoporation as a cell-injury trigger. Moreover, for the first time the interconnection between the axolemma and the MT bundle is shown to play a role in damage localization. The proposed FE axonal model is a valuable tool to understand the axonal injury mechanism from a mechanical perspective and could be used in turn for the definition of well-informed injury criteria at the tissue and organ level.

  • 31.
    Möller, Marika C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Univ Dept Rehabil Med, Danderyd Hosp, Stockholm, Sweden.; Karolinska Inst, Div Rehabil Med, Dept Clin Sci, Stockholm, Sweden..
    Nordin, Love Engström
    Karolinska Univ Hosp Huddinge, Dept Diagnost Med Phys, Stockholm, Sweden.; Karolinska Inst, Div Clin Geriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Bartfai, Aniko
    Univ Dept Rehabil Med, Danderyd Hosp, Stockholm, Sweden.; Karolinska Inst, Div Rehabil Med, Dept Clin Sci, Stockholm, Sweden..
    Julin, Per
    Karolinska Inst, Div Clin Geriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Li, Tie-Qiang
    Karolinska Univ Hosp Huddinge, Dept Diagnost Med Phys, Stockholm, Sweden.; Karolinska Inst, Div Med Imaging & Technol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Fatigue and Cognitive Fatigability in Mild Traumatic Brain Injury are Correlated with Altered Neural Activity during Vigilance Test Performance.2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 496Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Fatigue is the most frequently reported persistent symptom following a mild traumatic brain injury (mTBI), but the explanations for the persisting fatigue symptoms in mTBI remain controversial. In this study, we investigated the change of cerebral blood flow during the performance of a psychomotor vigilance task (PVT) by using pseudo-continuous arterial spin labeling (PCASL) MRI technique to better understand the relationship between fatigability and brain activity in mTBI.

    MATERIAL AND METHODS: Ten patients (mean age: 37.5 ± 11.2 years) with persistent complaints of fatigue after mTBI and 10 healthy controls (mean age 36.9 ± 11.0 years) were studied. Both groups completed a 20-min long PVT inside a clinical MRI scanner during simultaneous measurements of reaction time and regional cerebral blood flow (rCBF) with PCASL technique. Cognitive fatigability and neural activity during PVT were analyzed by dividing the performance and rCBF data into quintiles in addition to the assessment of self-rated fatigue before and after the PVT.

    RESULTS: The patients showed significant fatigability during the PVT while the controls had a stable performance. The variability in performance was also significantly higher among the patients, indicating monitoring difficulty. A three-way ANOVA, modeling of the rCBF data demonstrated that there was a significant interaction effect between the subject group and performance time during PVT in a mainly frontal/thalamic network, indicating that the pattern of rCBF change for the mTBI patients differed significantly from that of healthy controls. In the mTBI patients, fatigability at the end of the PVT was related to increased rCBF in the right middle frontal gyrus, while self-rated fatigue was related to increased rCBF in left medial frontal and anterior cingulate gyri and decreases of rCBF in a frontal/thalamic network during this period.

    DISCUSSION: This study demonstrates that PCASL is a useful technique to investigate neural correlates of fatigability and fatigue in mTBI patients. Patients suffering from fatigue after mTBI used different brain networks compared to healthy controls during a vigilance task and in mTBI, there was a distinction between rCBF changes related to fatigability vs. perceived fatigue. Whether networks for fatigability and self-rated fatigue are different, needs to be investigated in future studies.

  • 32.
    Namer, Barbara
    et al.
    Univ Erlangen Nurnberg, Dept Physiol & Pathophysiol, Erlangen, Germany.;Heidelberg Univ, Dept Anesthesiol, Mannheim, Germany..
    Ørstavik, Kirstin
    Oslo Univ Hosp, Sect Clin Neurophysiol, Dept Neurol, Rikshosp, Oslo, Norway..
    Schmidt, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Mair, Norbert
    Med Univ Innsbruck, Div Physiol, Dept Physiol & Med Phys, Innsbruck, Austria..
    Kleggetveit, Inge Petter
    Oslo Univ Hosp, Sect Clin Neurophysiol, Dept Neurol, Rikshosp, Oslo, Norway..
    Zeidler, Maximillian
    Med Univ Innsbruck, Div Physiol, Dept Physiol & Med Phys, Innsbruck, Austria..
    Martha, Theresa
    Med Univ Innsbruck, Div Physiol, Dept Physiol & Med Phys, Innsbruck, Austria..
    Jorum, Ellen
    Heidelberg Univ, Dept Anesthesiol, Mannheim, Germany.;Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway..
    Schmelz, Martin
    Heidelberg Univ, Dept Anesthesiol, Mannheim, Germany..
    Kalpachidou, Theodora
    Med Univ Innsbruck, Div Physiol, Dept Physiol & Med Phys, Innsbruck, Austria..
    Kress, Michaela
    Med Univ Innsbruck, Div Physiol, Dept Physiol & Med Phys, Innsbruck, Austria..
    Langeslag, Michiel
    Med Univ Innsbruck, Div Physiol, Dept Physiol & Med Phys, Innsbruck, Austria..
    Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 335Article in journal (Refereed)
    Abstract [en]

    The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of a-galactosidase A (Gla(-/0)). The skin innervation of Gla(-/0) mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla(-/0) mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla(-/0) nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla(-/0) nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons.

  • 33. Nordström, Carl-Henrik
    et al.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olivecrona, Magnus
    Aspects on the Physiological and Biochemical Foundations of Neurocritical Care2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 274Article, review/survey (Refereed)
    Abstract [en]

    Neurocritical care (NCC) is a branch of intensive care medicine characterized by specific physiological and biochemical monitoring techniques necessary for identifying cerebral adverse events and for evaluating specific therapies. Information is primarily obtained from physiological variables related to intracranial pressure (ICP) and cerebral blood flow (CBF) and from physiological and biochemical variables related to cerebral energy metabolism. Non-surgical therapies developed for treating increased ICP are based on knowledge regarding transport of water across the intact and injured blood-brain barrier (BBB) and the regulation of CBF. Brain volume is strictly controlled as the BBB permeability to crystalloids is very low restricting net transport of water across the capillary wall. Cerebral pressure autoregulation prevents changes in intracranial blood volume and intracapillary hydrostatic pressure at variations in arterial blood pressure. Information regarding cerebral oxidative metabolism is obtained from measurements of brain tissue oxygen tension (PbtO2) and biochemical data obtained from intracerebral microdialysis. As interstitial lactate/pyruvate (LP) ratio instantaneously reflects shifts in intracellular cytoplasmatic redox state, it is an important indicator of compromised cerebral oxidative metabolism. The combined information obtained from PbtO2, LP ratio, and the pattern of biochemical variables reveals whether impaired oxidative metabolism is due to insufficient perfusion (ischemia) or mitochondrial dysfunction. Intracerebral microdialysis and PbtO2 give information from a very small volume of tissue. Accordingly, clinical interpretation of the data must be based on information of the probe location in relation to focal brain damage. Attempts to evaluate global cerebral energy state from microdialysis of intraventricular fluid and from the LP ratio of the draining venous blood have recently been presented. To be of clinical relevance, the information from all monitoring techniques should be presented bedside online. Accordingly, in the future, the chemical variables obtained from microdialysis will probably be analyzed by biochemical sensors.

  • 34.
    Nordström, Carl-Henrik
    et al.
    Department of Neurosurgery, Odense University Hospital, Odense, Denmark.
    Koskinen, Lars-Owe
    Department of Clinical Neuroscience, Division of Neurosurgery, Umeå University, Umeå, Sweden.
    Olivecrona, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Anesthesia and Intensive Care, Section for Neurosurgery, Örebro University Hospital, Örebro, Sweden.
    Aspects on the Physiological and Biochemical Foundations of Neurocritical Care2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 274Article, review/survey (Refereed)
    Abstract [en]

    Neurocritical care (NCC) is a branch of intensive care medicine characterized by specific physiological and biochemical monitoring techniques necessary for identifying cerebral adverse events and for evaluating specific therapies. Information is primarily obtained from physiological variables related to intracranial pressure (ICP) and cerebral blood flow (CBF) and from physiological and biochemical variables related to cerebral energy metabolism. Non-surgical therapies developed for treating increased ICP are based on knowledge regarding transport of water across the intact and injured blood-brain barrier (BBB) and the regulation of CBF. Brain volume is strictly controlled as the BBB permeability to crystalloids is very low restricting net transport of water across the capillary wall. Cerebral pressure autoregulation prevents changes in intracranial blood volume and intracapillary hydrostatic pressure at variations in arterial blood pressure. Information regarding cerebral oxidative metabolism is obtained from measurements of brain tissue oxygen tension (PbtO2) and biochemical data obtained from intracerebral microdialysis. As interstitial lactate/pyruvate (LP) ratio instantaneously reflects shifts in intracellular cytoplasmatic redox state, it is an important indicator of compromised cerebral oxidative metabolism. The combined information obtained from PbtO2, LP ratio, and the pattern of biochemical variables reveals whether impaired oxidative metabolism is due to insufficient perfusion (ischemia) or mitochondrial dysfunction. Intracerebral microdialysis and PbtO2 give information from a very small volume of tissue. Accordingly, clinical interpretation of the data must be based on information of the probe location in relation to focal brain damage. Attempts to evaluate global cerebral energy state from microdialysis of intraventricular fluid and from the LP ratio of the draining venous blood have recently been presented. To be of clinical relevance, the information from all monitoring techniques should be presented bedside online. Accordingly, in the future, the chemical variables obtained from microdialysis will probably be analyzed by biochemical sensors.

  • 35. Penner, Iris-Katharina
    et al.
    Sivertsdotter, Eva Catharina
    Celius, Elisabeth G.
    Fuchs, Siegrid
    Schreiber, Karen
    Berko, Sara
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Improvement in fatigue during natalizumab treatment is linked to improvement in depression and day-time sleepiness2015In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, article id UNSP 18Article in journal (Refereed)
    Abstract [en]

    Background: Fatigue is a frequent symptom in multiple sclerosis (MS) and often interrelated with depression and sleep disorders making symptomatic treatment decisions difficult. In the single-arm, observational phase IVTYNERGY study, relapsing remitting MS patients showed a clinically meaningful decrease in fatigue over 1 year of treatment with natalizumab. Objective: To evaluate whether fatigue improvement might be directly linked to improved depression and day-time sleepiness. Methods: Patients were assessed regarding fatigue, depression, and day-time sleepiness. The relation between changes of the two latter symptoms and changes in fatigue was analyzed. Results: After 1 year of natalizumab treatment, the majority of patients (>92%) remained stable or improved in total, motor, and cognitive fatigue. Proportion of patients without depression increased by 17% while proportions of mildly depressed patients or patients with potential major depression decreased by 5 and 12%, respectively. Proportion of patients classified as not being sleepy increased by 13% while proportions of sleepy and very sleepy patients decreased by 11 and 2%, respectively. Most importantly, improved depression and sleepiness were significantly related to improved fatigue. Conclusion: Our findings highlight the importance of patient-reported outcomes in identifying potential benefits of drug treatment beyond its well-established effects on disease activity and disability progression.

  • 36.
    Pinto, Susana
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine. Faculdade de Medicina, Instituto de Fisiologia e Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal; Department of Neurosciences and Mental Health, Hospital de Santa Maria-Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
    de Carvalho, Mamede
    SVC Is a Marker of Respiratory Decline Function, Similar to FVC , in Patients With ALS2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 109Article in journal (Refereed)
    Abstract [en]

    Introduction: Respiratory function is a critical predictor of survival in amyotrophic lateral sclerosis (ALS). We aimed to determine if slow vital capacity (SVC) is a predictor of functional loss in ALS as compared to forced vital capacity (FVC). Methods: Consecutive ALS patients in whom respiratory tests were performed at baseline and 6 months later were included. All patients were evaluated with revised ALS functional rating scale (ALSFRS-R) and the respiratory tests, SVC, and FVC. Significant independent variables of functional decay were assessed by univariate Kaplan-Meier log-rank test and multivariate Cox proportional hazards model. A monthly decay not exceeding 0.92 in ALSFRS was considered as the time event. Results: We included 232 patients (134 men; mean onset-age 59.1 +/- 11.23 years; mean disease duration from first symptoms to first visit: 14.5 +/- 12.9 months; 166 spinal and 66 bulbar onset). All variables studied declined significantly between the two evaluations (p < 0.001). FVC and SVC were strongly correlated at study entry (r2 = 0.98, p < 0.001) and FVC and SVC decays between first evaluation and 6 months after were the only significant prognostic variables of functional decay (p < 0.001). Conclusion: FVC and SVC decay are inter-changeable in predicting functional decay in ALS. Pharmacological interventions reducing the decline rate of FVC and SVC can have a positive impact on the global functional impairment, with relevant implications for clinical trials' design and interpretation.

  • 37.
    Posti, Jussi P.
    et al.
    Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, Turku, Finland; Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, Turku, Finland; Department of Neurology, University of Turku, Turku, Finland.
    Dickens, Alex M.
    Turku Centre for Biotechnology, University of Turku, Turku, Finland.
    Orešič, Matej
    Turku Centre for Biotechnology, University of Turku, Turku, Finland.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology. Department of Chemistry.
    Tenovuo, Olli
    Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, Turku, Finland; Department of Neurology, University of Turku, Turku, Finland.
    Metabolomics Profiling As a Diagnostic Tool in Severe Traumatic Brain injury2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 398Article, review/survey (Refereed)
    Abstract [en]

    Traumatic brain injury (TBI) is a complex disease with a multifaceted pathophysiology. Impairment of energy metabolism is a key component of secondary insults. This phenomenon is a consequence of multiple potential mechanisms including diffusion hypoxia, mitochondrial failure, and increased energy needs due to systemic trauma responses, seizures, or spreading depolarization. The degree of disturbance in brain metabolism is affected by treatment interventions and reflected in clinical patient outcome. Hence, monitoring of these secondary events in peripheral blood will provide a window into the pathophysiological course of severe TBI. New methods for assessing perturbation of brain metabolism are needed in order to monitor on-going pathophysiological processes and thus facilitate targeted interventions and predict outcome. Circulating metabolites in peripheral blood may serve as sensitive markers of pathological processes in TBI. The levels of these small molecules in blood are less dependent on the integrity of the blood-brain barrier as compared to protein biomarkers. We have recently characterized a specific metabolic profile in serum that is associated with both initial severity and patient outcome of TBI. We found that two medium-chain fatty acids, octanoic and decanoic acids, as well as several sugar derivatives are significantly associated with the severity of TBI. The top ranking peripheral blood metabolites were also highly correlated with their levels in cerebral microdialyzates. Based on the metabolite profile upon admission, we have been able to develop a model that accurately predicts patient outcome. Moreover, metabolomics profiling improved the performance of the well-established clinical prognostication model. In this review, we discuss metabolomics profiling in patients with severe TBI. We present arguments in support of the need for further development and validation of circulating biomarkers of cerebral metabolism and for their use in assessing patients with severe TBI.

  • 38.
    Purins, Karlis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Brain tissue oxygenation and cerebral metabolic patterns in focal and diffuse traumatic brain injury2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 64Article in journal (Refereed)
    Abstract [en]

    Introduction: Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. There are reasons to believe that knowledge of brain tissue oxygenation (BtipO2) would add information with the potential of improving patient outcome. The aim of this study was to examine BtipO2 and cerebral metabolism using the Neurovent-PTO probe and cerebral microdialysis (MD) in TBI patients.

    Methods: Twenty-three severe TBI patients with monitoring of physiological parameters, ICP, CPP, BtipO2, and MD for biomarkers of energy metabolism (glucose, lactate, and pyruvate) and cellular distress (glutamate, glycerol) were included. Patients were grouped according to injury type (focal/diffuse) and placement of the Neurovent-PTO probe and MD catheter (injured/non-injured hemisphere).

    Results: We observed different patterns in BtipO2 and MD biomarkers in diffuse and focal injury where placement of the probe also influenced the results (ipsilateral/contralateral). In all groups, despite fairly normal levels of ICP and CPP, increased MD levels of glutamate, glycerol, or the L/P ratio were observed at BtipO2 <5 mmHg, indicating increased vulnerability of the brain at this level.

    Conclusion: Monitoring of BtipO2 adds important information in addition to traditional ICP and CPP surveillance. Because of the different metabolic responses to very low BtipO2 in the individual patient groups we submit that brain tissue oximetry is a complementary tool rather than an alternative to MD monitoring.

  • 39.
    Righetti, Ludovic
    et al.
    Max Planck Inst Intelligent Syst, Autonomous Mot Dept, D-72076 Tubingen, Germany..
    Nylén, Anna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Iispeert, Auke Jan
    Ecole Polytech Fed Lausanne, Sch Engn, Interfac Inst Bioengn, Biorobot Lab, Lausanne, Switzerland..
    Kinematic and gait similarities between crawling human infants and other quadruped mammals2015In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, article id UNSP 17Article in journal (Refereed)
    Abstract [en]

    Crawling on hands and knees is an early pattern of human infant locomotion, which offers an interesting way of studying quadrupedalism in one of its simplest form. We investigate how crawling human infants compare to other quadruped mammals, especially primates. We present quantitative data on both the gait and kinematics of seven 10-month-old crawling infants. Body movements were measured with an optoelectronic system giving precise data on 3-dimensional limb movements. Crawling on hands and knees is very similar to the locomotion of non-human primates in terms of the quite protracted arm at touch-down, the coordination between the spine movements in the lateral plane and the limbs, the relatively extended limbs during locomotion and the strong correlation between stance duration and speed of locomotion. However, there are important differences compared to primates, such as the choice of a lateral-sequence walking gait, which is similar to most non-primate mammals and the relatively stiff elbows during stance as opposed to the quite compliant gaits of primates. These finding raise the question of the role of both the mechanical structure of the body and neural control on the determination of these characteristics.

  • 40. Risling, Marten
    et al.
    Ochsman, Thomas
    Carlstedt, Thomas
    Lindå, Hans
    Plantman, Stefan
    Rostami, Elham
    Angeria, Maria
    Sköld, Mattias K
    On acute gene expression changes after ventral root replantation.2011In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 1, article id 159Article in journal (Refereed)
    Abstract [en]

    Replantation of avulsed spinal ventral roots has been show to enable significant and useful regrowth of motor axons in both experimental animals and in human clinical cases, making up an interesting exception to the rule of unsuccessful neuronal regeneration in central nervous system. Compared to avulsion without repair, ventral root replantation seems to rescue lesioned motoneurons from death. In this study we have analyzed the acute response to ventral root avulsion and replantation in adult rats with gene arrays combined with cluster analysis of gene ontology search terms. The data show significant differences between rats subjected to ventral replantation compared to avulsion only. Even though number of genes related to cell death is similar in the two models after 24 h, we observed a significantly larger number of genes related to neurite growth and development in the rats treated with ventral root replantation, possibly reflecting the neuroregenerative capacity in the replantation model. In addition, an acute inflammatory response was observed after avulsion, while effects on genes related to synaptic transmission were much more pronounced after replantation than after avulsion alone. These data indicate that the axonal regenerative response from replantation is initiated at an earlier stage than the possible differences in terms of neuron survival. We conclude that this type of analysis may facilitate the comparison of the acute response in two types of injury.

  • 41.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Glucose and the injured brain-monitored in the neurointensive care unit2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 91Article in journal (Refereed)
    Abstract [en]

    Brain has a continuous demand for energy that is met by oxidative metabolism of oxygen and glucose. This demand is compromised in the injured brain and if the inadequate supply persists it will lead to permanent tissue damage. Zero values of cerebral glucose have been associated with infarction and poor neurological outcome. Furthermore, hyperglycemia is common in patients with neurological insults and associated with poor outcome. Intensive insulin therapy (IIT) to control blood glucose has been suggested and used in neurointensive care with conflicting results. This review covers the studies reporting on monitoring of cerebral glucose with microdialysis in patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) and ischemic stroke. Studies investigating IIT are also discussed. Available data suggest that low cerebral glucose in patients with TBI and SAH provides valuable information on development of secondary ischemia and has been correlated with worse outcome. There is also indication that the location of the catheter is important for correlation between plasma and brain glucose. In conclusion considering catheter location, monitoring of brain glucose in the neurointensive care not only provides information on imminent secondary ischemia it also reveals the effect of peripheral treatment on the injured brain.

  • 42. Rostami, Elham
    On acute gene expression changes after ventral root replantation.2011In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 4, no 1, p. 159-Article in journal (Refereed)
  • 43. Rostami, Elham
    et al.
    Davidsson, Johan
    Ng, Kian Chye
    Lu, Jia
    Gyorgy, Andrea
    Walker, Johan
    Wingo, Daniel
    Plantman, Stefan
    Bellander, Bo-Michael
    Agoston, Denes V.
    Risling, Mårten
    A Model for Mild Traumatic Brain Injury that Induces Limited Transient Memory Impairment and Increased Levels of Axon Related Serum Biomarkers2012In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 3, p. 115-Article in journal (Refereed)
    Abstract [en]

    Mild traumatic brain injury (mTBI) is one of the most common neuronal insults and can lead to long-term disabilities. mTBI occurs when the head is exposed to a rapid acceleration-deceleration movement triggering axonal injuries. Our limited understanding of the underlying pathological changes makes it difficult to predict the outcome of mTBI. In this study we used a scalable rat model for rotational acceleration TBI, previously characterized for the threshold of axonal pathology. We have analyzed whether a TBI just above the defined threshold would induce any detectable behavioral changes and/or changes in serum biomarkers. The effect of injury on sensory motor functions, memory and anxiety were assessed by beam walking, radial arms maze and elevated plus maze at 3–7 days following TBI. The only behavioral deficits found were transient impairments in working and reference memory. Blood serum was analyzed at 1, 3, and 14 days after injury for changes in selected protein biomarkers. Serum levels of neurofilament heavy chain and Tau, as well as S100B and myelin basic protein showed significant increases in the injured animals at all time points. No signs of macroscopic injuries such as intracerebral hematomas or contusions were found. Amyloid precursor protein immunostaining indicated axonal injuries at all time points analyzed. In summary, this model mimics some of the key symptoms of mTBI, such as transient memory impairment, which is paralleled by an increase in serum biomarkers. Our findings suggest that serum biomarkers may be used to detect mTBI. The model provides a suitable foundation for further investigation of the underlying pathology of mTBI.

  • 44.
    Rostami, Elham
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Engquist, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Imaging of cerebral blood flow in patients with severe traumatic brain injury in the neurointensive care2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 114Article in journal (Refereed)
    Abstract [en]

    Ischemia is a common and deleterious secondary injury following traumatic brain injury (TBI). A great challenge for the treatment of TBI patients in the neurointensive care unit (NICU) is to detect early signs of ischemia in order to prevent further advancement and deterioration of the brain tissue. Today, several imaging techniques are available to monitor cerebral blood flow (CBF) in the injured brain such as positron emission tomography (PET), single-photon emission computed tomography, xenon computed tomography (Xenon-CT), perfusion-weighted magnetic resonance imaging (MRI), and CT perfusion scan. An ideal imaging technique would enable continuous non-invasive measurement of blood flow and metabolism across the whole brain. Unfortunately, no current imaging method meets all these criteria. These techniques offer snapshots of the CBF. MRI may also provide some information about the metabolic state of the brain. PET provides images with high resolution and quantitative measurements of CBF and metabolism; however, it is a complex and costly method limited to few TBI centers. All of these methods except mobile Xenon-CT require transfer of TBI patients to the radiological department. Mobile Xenon-CT emerges as a feasible technique to monitor CBF in the NICU, with lower risk of adverse effects. Promising results have been demonstrated with Xenon-CT in predicting outcome in TBI patients. This review covers available imaging methods used to monitor CBF in patients with severe TBI.

  • 45.
    Rostami, Elham
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Engquist, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    The Correlation between Cerebral Blood Flow Measured by Bedside Xenon-CT and Brain Chemistry Monitored by Microdialysis in the Acute Phase following Subarachnoid Hemorrhage2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 369Article in journal (Refereed)
    Abstract [en]

    Cerebral microdialysis (MD) may be used in patients suffering from subarachnoid hemorrhage (SAH) to detect focal cerebral ischemia. The cerebral MD catheter is usually placed in the right frontal lobe and monitors the area surrounding the catheter. This generates the concern that a fall in cerebral blood flow (CBF) and ischemic events distant to the catheter may not be detected. We aimed to investigate if there is a difference in the association between the MD parameters and CBF measured around the MD catheter compared to global cortical CBF and to CBF in the vascular territories following SAH in the early acute phase. MD catheter was placed in the right frontal lobe of 30 SAH patients, and interstitial glucose, lactate, pyruvate, glycerol, and lactate/pyruvate ratio were measured hourly. CBF measurements were performed during day 0-3 after SAH. Global cortical CBF correlated strongly with CBF around the microdialysis catheter (CBF-MD) (r = 0.911, p ≤ 0.001). This was also the case for the anterior, middle, and posterior vascular territories in the right hemisphere. A significant negative correlation was seen between lactate and CBF-MD (r = -0.468, p = 0.009). The same relationship was observed between lactate and CBF in anterior vascular territory but not in the middle and posterior vascular territories. In conclusion, global CBF 0-3 days after severe SAH correlated strongly with CBF-MD. High lactate level was associated with low global CBF and low regional CBF in the right anterior vascular territory, when the MD catheter was placed in the right frontal lobe.

  • 46.
    Rostami, Elham
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Engquist, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Johnson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Monitoring of Cerebral Blood Flow and Metabolism Bedside in Patients with Subarachnoid Hemorrhage - A Xenon-CT and Microdialysis Study2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 89Article in journal (Refereed)
    Abstract [en]

    Cerebral ischemia is the leading cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Although 70% of the patients show angiographic vasospasm only 30% develop symptomatic vasospasm defined as delayed cerebral ischemia (DCI). Early detection and management of reversible ischemia is of critical importance in patients with SAH. Using a bedside Xenon enhanced computerized tomography (Xenon-CT) scanner makes it possible to measure quantitative regional Cerebral blood flow (CBF) bedside in the neurointensive care setting and intracerebral microdialysis (MD) is a method that offers the possibility to monitor the metabolic state of the brain continuously. Here, we present results from nine SAH patients with both MD monitoring and bedside Xenon-CT measurements. CBF measurements were performed within the first 72 h following bleeding. Six out of nine patients developed DCI at a later stage. Five out of six patients who developed DCI had initial global CBF below 26 ml/100 g/min whereas one had 53 ml/100 g/min. The three patients who did not develop clinical vasospasm all had initial global CBF above 27 ml/100 g/min. High lactate/pyruvate (L/P) ratio was associated with lower CBF values in the area surrounding the catheter. Five out of nine patients had L/P ratio ≥25 and four of these patients had CBF ≤ 22 ml/100 g/min. These preliminary results suggest that patients with initially low global CBF on Xenon-CT may be more likely to develop DCI. Initially low global CBF was accompanied with metabolic disturbances determined by the MD. Most importantly, pathological findings on the Xenon-CT and MD could be observed before any clinical signs of DCI. Combining bedside Xenon-CT and MD was found to be useful and feasible. Further studies are needed to evaluate if DCI can be detected before any other signs of DCI to prevent progress to infarction.

  • 47.
    Sandvig, Axel
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway.
    Sandvig, Ioanna
    Connectomics of Morphogenetically Engineered Neurons as a Predictor of Functional Integration in the Ischemic Brain2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 630Article, review/survey (Refereed)
    Abstract [en]

    Recent advances in cell reprogramming technologies enable the in vitro generation of theoretically unlimited numbers of cells, including cells of neural lineage and specific neuronal subtypes from human, including patient-specific, somatic cells. Similarly, as demonstrated in recent animal studies, by applying morphogenetic neuroengineering principles in situ, it is possible to reprogram resident brain cells to the desired phenotype. These developments open new exciting possibilities for cell replacement therapy in stroke, albeit not without caveats. Main challenges include the successful integration of engineered cells in the ischemic brain to promote functional restoration as well as the fact that the underlying mechanisms of action are not fully understood. In this review, we aim to provide new insights to the above in the context of connectomics of morphogenetically engineered neural networks. Specifically, we discuss the relevance of combining advanced interdisciplinary approaches to: validate the functionality of engineered neurons by studying their self-organizing behavior into neural networks as well as responses to stroke-related pathology in vitro; derive structural and functional connectomes from these networks in healthy and perturbed conditions; and identify and extract key elements regulating neural network dynamics, which might predict the behavior of grafted engineered neurons post-transplantation in the stroke-injured brain.

  • 48.
    Sarkanen, Tomi
    et al.
    Cent Finland Cent Hosp, Dept Neurol, Jyvaskyla 40620, Finland; Vitalmed Res Ctr, Helsinki Sleep Clin, Helsinki, Finland.
    Niemelä, Valter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Linkoping Univ Hosp, Dept Neurol, S-58185 Linkoping, Sweden.
    Partinen, Markku
    Vitalmed Res Ctr, Helsinki Sleep Clin, Helsinki, Finland; Univ Helsinki, Dept Clin Neurosci, Helsinki, Finland.
    Psychosis in patients with narcolepsy as an adverse effect of sodium oxybate2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 136Article in journal (Refereed)
    Abstract [en]

    AIM: Hypnagogic and hypnopompic hallucinations are characteristic symptoms of narcolepsy, as are excessive daytime sleepiness, cataplexy, and sleep paralysis. Narcolepsy patients may also experience daytime hallucinations unrelated to sleep-wake transitions. The effect of medication on hallucinations is of interest since treatment of narcolepsy may provoke psychotic symptoms. We aim to analyze the relation between sodium oxybate (SXB) treatment and psychotic symptoms in narcolepsy patients. Furthermore, we analyze the characteristics of hallucinations to determine their nature as mainly psychotic or hypnagogic and raise a discussion about whether SXB causes psychosis or if psychosis occurs as an endogenous complication in narcolepsy.

    METHOD: We present altogether four patients with narcolepsy who experienced psychotic symptoms during treatment with SXB. In addition, we searched the literature for descriptions of hallucinations in narcolepsy and similarities and differences with psychotic symptoms in schizophrenia.

    RESULTS: Three out of four patients had hallucinations typical for psychosis and one had symptoms that resembled aggravated hypnagogic hallucinations. Two patients also had delusional symptoms primarily associated with mental disorders. Tapering down SXB was tried and helped in two out of four cases. Adding antipsychotic treatment (risperidone) alleviated psychotic symptoms in two cases.

    CONCLUSION: Psychotic symptoms in narcolepsy may appear during SXB treatment. Hallucinations resemble those seen in schizophrenia; however, the insight that symptoms are delusional is usually preserved. In case of SXB-induced psychotic symptoms or hallucinations, reducing SXB dose or adding antipsychotic medication can be tried.

  • 49.
    Sköld, Mattias K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Fehlings, Michael G.
    Univ Toronto, Dept Neurosurg, Toronto, ON, Canada.;Toronto Western Hosp, Spine Program, Toronto, ON, Canada..
    Editorial: Karolinska Institutet 200-Year Anniversary Symposium on Injuries to the Spinal Cord and Peripheral Nervous System: An Update on Recent Advances in Regenerative Neuroscience2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 510Article in journal (Other academic)
  • 50. Smits, Anja
    et al.
    Zetterling, Maria
    Lundin, Margareta
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Fahistrom, Markus
    Grabowska, Anna
    Larsson, Eina-Marie
    Berntsson, Shale Ghaderi
    Neurological impairment linked with cortico-subcortical infiltration of diffuse low-grade gliomas at initial diagnosis supports early brain plasticity2015In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, article id UNSP 137Article in journal (Refereed)
    Abstract [en]

    Diffuse low-grade gliomas (DLGG) are slow-growing brain tumors that in spite of an indolent behavior at onset show a continuous expansion over time and inevitably transform into malignant gliomas. Extensive tumor resections may be performed with preservation of neurological function due to neuroplasticity that is induced by the slow tumor growth. However, DLGG prefer to migrate along subcortical pathways, and white matter plasticity is considerably more limited than gray matter plasticity. Whether signs of functional decompensating white matter that may be found as early as at disease presentation has not been systematically studied. Here, we examined 52 patients who presented with a DLGG at the time of radiological diagnosis. We found a significant correlation between neurological impairment and eloquent cortico-subcortical tumor localization, but not between neurological function and tumor volume. These results suggest that even small tumors invading white matter pathways may lack compensatory mechanisms for functional reorganization already at disease presentation.

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