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  • 1. Aaro Jonsson, Catherine
    et al.
    Catroppa, Cathy
    Godfrey, Celia
    Smedler, Ann-Charlotte
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen.
    Anderson, Vicki
    Cognitive Recovery and Development after Traumatic Brain Injury in Childhood: A Person-Oriented, Longitudinal Study2013Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 30, nr 2, s. 76-83Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Influence of childhood traumatic brain injury (TBI) on cognitive recovery and subsequent development is poorly understood. In this longitudinal study we used cluster analysis to explore acute stage individual profiles of injury age and cognition in 118 children with traumatic brain injury. Repeated measures of cognitive function were conducted at 30 months, indicating recovery, and 10 years post-injury, indicating development. Nine clusters were identified. Recovery was evident in three clusters, two of them with low functioning profiles. Developmental gains occurred for three clusters and an acute profile of higher freedom from distractibility (FFD) and lower processing speed (PS) was related to positive differences. One cluster, average low functioning and especially low verbal comprehension, demonstrated a slower development than peers. This suggests that developmental change after TBI in childhood takes place on a continuum, with both chance of long-term catching up, and risk of poor development. An acute profile of higher FFD and lower PS seemed to reflect injury consequences and were followed by developmental gains. These results challenge previous findings, and warrant further investigation.

  • 2.
    Abu Hamdeh, Sami
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lannsjö, Marianne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Rehabiliteringsmedicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Howells, Tim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Raininko, Raili
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Extended anatomical grading in diffuse axonal injury using MRI: Hemorrhagic lesions in the substantia nigra and mesencephalic tegmentum indicate poor long-term outcome2017Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 5, nr 34, s. 341-352Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. In this study, three magnetic resonance imaging (MRI) sequences were used to quantify the anatomical distribution of lesions, to grade DAI according to the Adams grading system, and to evaluate the value of lesion localization in combination with clinical prognostic factors to improve outcome prediction. Thirty patients (mean 31.2 years ±14.3 standard deviation) with severe DAI (Glasgow Motor Score [GMS] <6) examined with MRI within 1 week post-injury were included. Diffusion-weighted (DW), T2*-weighted gradient echo and susceptibility-weighted (SWI) sequences were used. Extended Glasgow outcome score was assessed after 6 months. Number of DW lesions in the thalamus, basal ganglia, and internal capsule and number of SWI lesions in the mesencephalon correlated significantly with outcome in univariate analysis. Age, GMS at admission, GMS at discharge, and low proportion of good monitoring time with cerebral perfusion pressure <60 mm Hg correlated significantly with outcome in univariate analysis. Multivariate analysis revealed an independent relation with poor outcome for age (p = 0.005) and lesions in the mesencephalic region corresponding to substantia nigra and tegmentum on SWI (p  = 0.008). We conclude that higher age and lesions in substantia nigra and mesencephalic tegmentum indicate poor long-term outcome in DAI. We propose an extended MRI classification system based on four stages (stage I—hemispheric lesions, stage II—corpus callosum lesions, stage III—brainstem lesions, and stage IV—substantia nigra or mesencephalic tegmentum lesions); all are subdivided by age (≥/<30 years).

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  • 3.
    Abu Hamdeh, Sami
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Shevchenko, Ganna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Mi, Jia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Musunuri, Sravani
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Proteomic Differences Between Focal And Diffuse Traumatic Brain Injury In Human Brain Tissue2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A238-A239Artikkel i tidsskrift (Annet vitenskapelig)
  • 4. Cao, Y.
    et al.
    Sköld, Mattias K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Malm, E.
    Sonden, A.
    Risling, M.
    Hypothermia and in Vitro High-Energy Trauma2014Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, nr 12, s. A105-A105Artikkel i tidsskrift (Annet vitenskapelig)
  • 5.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Dahlin, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Chu, Jiangtao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Kaller, Bodil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    During, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Novel Microdialysis Method to Study The Acute Cytokine Response to Diffuse Traumatic Brain Injury in the Rat2014Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, nr 5, s. A19-A19Artikkel i tidsskrift (Fagfellevurdert)
  • 6.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hansson, Hans-Arne
    Gothenburg Univ, Biomed, Gothenburg, Sweden.
    Reduced Intracranial Pressure After Treatment With Anti-Secretory Factor 16 In A Rat Model Of Traumatic Brain Injury2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A195-A196Artikkel i tidsskrift (Annet vitenskapelig)
  • 7.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Lorant, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    T Lymphocyte trafficking: A novel target for neuroprotection in traumatic brain injury2007Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 24, nr 8, s. 1295-1307Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Infiltration of T lymphocytes is a key feature in transplant rejection and in several autoimmune disorders, but the role of T lymphocytes in traumatic brain injury (TBI) is largely unknown. Here we studied trafficking of immune cells in the brain after experimental TBI. We found that scavenging of reactive oxygen species (ROS) at the endothelial level dramatically reduced the infiltration of activated T lymphocytes. Immune cell infiltration was studied 12 h to 7 days after controlled cortical contusion in rats by ex vivo propagation of T lymphocytes (TcR+, CD8+), neutrophils (MPO+), and macrophages/microglia (ED-1+) from biopsies taken from injured cortex and analyzed by flow cytometry, as well as by quantitative immunohistochemistry. T lymphocyte and neutrophil infiltration peaked at 24 h and macrophages/microglia at 7 days post-injury. Pretreatment with 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) produced a dramatic reduction of TcR+ T lymphocytes and a significantly smaller attenuation of neutrophil infiltration at 24 h post-injury, but did not affect CD8+ T lymphocytes or macrophages/microglia. S-PBN significantly reduced the expression of the endothelial adhesion molecules ICAM-1 and VCAM at 24 h for following TBI. We conclude that ROS inhibition at the endothelial level influenced T lymphocyte and neutrophil infiltration following TBI. We submit that the reduction of T lymphocyte infiltration is a key feature in improving TBI outcome after S-PBN treatment. Our data suggest that targeting T lymphocyte trafficking to the injured brain at the microvascular level is a novel concept of neuroprotection in TBI and warrants further exploration.

  • 8.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Acute Inflammatory Biomarker Responses to Diffuse Traumatic Brain Injury in the Rat Monitored by a Novel Microdialysis Technique2019Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 36, nr 2, s. 201-211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuroinflammation is a major contributor to the progressive brain injury process induced by traumatic brain injury (TBI), and may play an important role in the pathophysiology of axonal injury. The immediate neuroinflammatory cascade cannot be characterized in the human setting. Therefore, we used the midline fluid percussion injury model of diffuse TBI in rats and a novel microdialysis (MD) method providing stable diffusion-driven biomarker sampling. Immediately post-injury, bilateral amphiphilic tri-block polymer coated MD probes (100 kDa cut off membrane) were inserted and perfused with Dextran 500 kDa-supplemented artificial cerebrospinal fluid (CSF) to optimize protein capture. Six hourly samples were analyzed for 27 inflammatory biomarkers (9 chemokines, 13 cytokines, and 5 growth factors) using a commercial multiplex biomarker kit. TBI (n = 6) resulted in a significant increase compared with sham-injured controls (n = 6) for five chemokines (eotaxin/CCL11, fractalkine/CX3CL1, LIX/CXCL5, monocyte chemoattractant protein [MCP]1α/CCL2, macrophage inflammatory protein [MIP]1α /CCL3), 10 cytokines (interleukin [IL]-1α, IL-1β, IL-4, IL-6, IL-10, IL-13, IL-17α, IL-18, interferon [IFN]-γ, tumor necrosis factor [TNF]-α), and four growth factors (epidermal growth factor [EGF], granulocyte-macrophage colony-stimulating factor [GM-CSF], leptin, vascular endothelial growth factor [VEGF]). Therefore, diffuse TBI was associated with an increased level of 18 of the 27 inflammatory biomarkers at one through six time points, during the observation period whereas the remaining 9 biomarkers were unaltered. The study shows that diffuse TBI induces an acute increase in a number of inflammatory biomarkers. The novel MD technique provides stable MD sampling suitable for further studies on the early neuroinflammatory cascade in TBI.

  • 9.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Oxidativ stress och inflammation.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Interstitial F2-Isoprostane 8-Iso-PGF As a Biomarker of Oxidative Stress after Severe Human Traumatic Brain Injury2012Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, nr 5, s. 766-775Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Oxidative stress is a major contributor to the secondary injury process after experimental traumatic brain injury (TBI). The importance of oxidative stress in the pathobiology of human TBI is largely unknown. The F(2)-isoprostane 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), synthesized in vivo through non-enzymatic free radical catalyzed peroxidation of arachidonic acid, is a widely used biomarker of oxidative stress in multiple disease states, including TBI and cerebral ischemia/reperfusion. Our hypothesis is that harvesting of biomarkers directly in the injured brain by cerebral microdialysis (MD) is advantageous because of its high spatial and temporal resolution compared to blood or cerebrospinal fluid sampling. The aim of this study was to test the feasibility of measuring 8-iso-PGF(2α) in MD, ventricular cerebrospinal fluid (vCSF), and plasma samples collected from patients with severe TBI, and to compare the MD signals with MD-glycerol, implicated as a biomarker of oxidative stress, as well as MD-glutamate, a biomarker of excitotoxicity. Six patients (4 men, 2 women) were included in the study, three of whom had a focal/mixed TBI, and three a diffuse axonal injury (DAI). Following the bedside analysis of routine MD biomarkers (glucose, lactate:pyruvate ratio, glycerol, and glutamate), two 12-h MD samples per day were used to analyze 8-iso-PGF(2α) from 24 h up to 8 days post-injury. The interstitial levels of 8-iso-PGF(2α) were markedly higher than the levels obtained from plasma and vCSF (p<0.05), supporting our hypothesis. The MD-8-iso-PGF(2α) levels correlated strongly (p<0.05) with MD-glycerol and MD-glutamate, which are widely used biomarkers of membrane phospholipid degradation/oxidative stress and excitotoxicity, respectively. This study demonstrates the feasibility of analyzing 8-iso-PGF(2α) in MD samples from the human brain. Our results support a close relationship between oxidative stress and excitotoxicity following human TBI. MD-8-iso-PGF(2α) in combination with MD-glycerol may be useful biomarkers of oxidative stress in the neurointensive care setting.

  • 10.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    The nitrone free radical scavenger NXY-059 is neuroprotective when administered after traumatic brain injury in the rat2008Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 25, nr 12, s. 1449-1457Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Reactive oxygen species (ROS) are important contributors to the secondary injury cascade following traumatic brain injury (TBI), and ROS inhibition has consistently been shown to be neuroprotective following experimental TBI. NXY-059, a nitrone free radical trapping compound, has been shown to be neuroprotective in models of ischemic stroke but has not been evaluated in experimental TBI. In the present study, a continuous 24-h intravenous infusion of NXY-059 or vehicle was initiated 30min following a severe lateral fluid percussion brain injury (FPI) in adult rats (n=22), and histological and behavioral outcomes were evaluated. Sham-injured animals (n=22) receiving identical drug infusion were used as controls. Visuospatial learning was evaluated in the Morris water maze at post-injury days 11–14, followed by a probe trial (memory test) at day 18. The animals were sacrificed at day 18, and loss of hemispheric brain tissue was measured in microtubule-associated protein (MAP)–2stained sections. Brain-injured, NXY-059-treated animals showed a significant reduction of visuospatial learning deficits when compared to the brain-injured, vehicle-treated control animals (p<0.05). NXY-059-treated animals significantly reduced the loss of hemispheric tissue compared to brain-injured controls (43.0±11mm3 versus 74.4±19mm3, respectively; p<0.01). The results show that post-injury treatment with NXY-059 significantly attenuated the loss of injured brain tissue and improved cognitive outcome, suggesting a major role for ROS in the pathophysiology of TBI.

  • 11. Cnossen, Maryse C.
    et al.
    van der Brande, Ruben
    Lingsma, Hester F.
    Polinder, Suzanne
    Lecky, Fiona
    Maas, Andrew I. R.
    Prehospital Trauma Care among 68 European Neurotrauma Centers: Results of the CENTER-TBI Provider Profiling Questionnaires2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 36, nr 1, s. 176-181Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The first hour following traumatic brain injury (TBI) is considered crucial to prevent death and disability. It is, however, not established yet how the prehospital care should be organized to optimize recovery during the first hour. The objective of the current study was to examine variation in prehospital trauma care across Europe aiming to inform comparative effectiveness analyses on care for neurotrauma patients. A survey on prehospital trauma care was sent to 68 neurotrauma centers from 20 European countries participating in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. The survey was developed using literature review and expert opinion and was pilot tested in 16 centers. All participants completed the questionnaire. Advanced life support was used in half of the centers (n = 35; 52%), whereas the other centers used mainly basic life support (n = 26; 38%). A mobile medical team (MMT) could be dispatched 24/7 in most centers (n = 66; 97%). Helicopters were used in approximately half of the centers to transport the MMT to the scene (n = 39; 57%) and the patient to the hospital (n = 31, 46%). Half of the centers used a stay-and-play approach at the scene (n = 37; 55%), while the others used a scoop-and-run approach or another policy. We found wide variation in prehospital trauma care across Europe. This may reflect differences in socio-economic situations, geographic differences, and a general lack of strong evidence for some aspects of prehospital care. The current variation provides the opportunity to study the effectiveness of prehospital interventions and systems of care in comparative effectiveness research.

  • 12.
    Dickens, Alex Mountfort
    et al.
    Turku Centre for Biotechnology, University of Turku, Turku, Finland .
    Posti, Jussi P.
    Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, Turku, Finland; Department of Neurology, University of Turku, Turku, Finland; Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, Turku, Finland .
    Takala, Riikka Sk.
    Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland .
    Ala-Seppälä, Henna Maria
    Department of Neurology,University of Turku, Turku, Finland .
    Mattila, Ismo
    Steno Diabetes Center AS, Gentofte, Denmark.
    Coles, Jonathan Coles
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Frantzén, Janek
    Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, Turku, Finland; Department of Neurology, University of Turku, Turku, Finland; Division of Clinical Neurosciences, Department of Neurosurgery,Turku University Hospital, Turku, Finland .
    Hutchinson, Peter John
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Katila, Ari J.
    Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland.
    Kyllönen, Anna
    Department of Neurology, University of Turku, Turku, Finland .
    Maanpää, Henna-Riikka
    Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
    Newcombe, Virginia
    Division of Anaesthesia, Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom of Great Britain and Norther Ireland.
    Outtrim, Joanne
    Division of Anaesthesia, Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Tallus, Jussi
    Division of Anaesthesia, Addenbrooke's Hospital, Hills Road, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Carpenter, Keri
    Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Menon, David
    Head, Division of Anaesthesia, Addenbrooke's Hospital, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Hyötyläinen, Tuulia
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Tenovuo, Olli
    Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, Turku, Finland; Department of Neurology, University of Turku, Turku, Finland .
    Oresic, Matej
    Örebro universitet, Institutionen för medicinska vetenskaper. Turku Centre for Biotechnology, University of Turku, Turku, Finland.
    Serum Metabolites Associated with Computed TomographyFindings after Traumatic Brain Injury2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 22, s. 2673-2683Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is a need to rapidly detect patients with traumatic brain injury (TBI) who require head computed tomography (CT). Given the energy crisis in the brain following TBI, we hypothesized that serum metabolomics would be a useful tool for developing a set of biomarkers to determine the need for CT and to distinguish between different types of injuries observed. Logistic regression models using metabolite data from the discovery cohort (n=144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and negative findings on head CT. The resultant models were then tested in the validation cohort (n=66, Cambridge, UK). The levels of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 were also quantified in the serum from the same patients. Despite there being significant differences in the protein biomarkers in patients with TBI, the model that determined the need for a CT scan validated poorly (AUC=0.64: Cambridge patients). However, using a combination of six metabolites (two amino acids, three sugar derivatives and one ketoacid) it was possible to discriminate patients with intracranial abnormalities on CT and patients with a normal CT (AUC=0.77 in Turku patients and AUC=0.73 in Cambridge patients). Furthermore, a combination of three metabolites could distinguish between diffuse brain injuries and mass lesions (AUC=0.87 in Turku patients and AUC=0.68 in Cambridge patients). This study identifies a set of validated serum polar metabolites, which associate with the need for a CT scan. Additionally, serum metabolites can also predict the nature of the brain injury. These metabolite markers may prevent unnecessary CT scans, thus reducing the cost of diagnostics and radiation load.

  • 13.
    Dyhrfort, Philip
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Enblad: Neurokirurgi.
    Shen, Qiujin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Uppsala Univ, Dept Neurosci, Sect Neurosurg, Uppsala, Sweden.
    Eriksson, Måns
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Statistiska institutionen. Uppsala Univ, Dept Stat, Uppsala, Sweden;Univ Edinburgh, Sch Math, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Maxwell Inst Math Sci, Edinburgh, Midlothian, Scotland.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Enblad: Neurokirurgi.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Enblad: Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Monitoring of Protein Biomarkers of Inflammation in Human Traumatic Brain Injury Using Microdialysis and Proximity Extension Assay Technology in Neurointensive Care2019Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 36, nr 20, s. 2872-2885Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) is followed by secondary injury mechanisms strongly involving neuroinflammation. To monitor the complex inflammatory cascade in human TBI, we used cerebral microdialysis (MD) and multiplex proximity extension assay (PEA) technology and simultaneously measured levels of 92 protein biomarkers of inflammation in MD samples every three hours for five days in 10 patients with severe TBI under neurointensive care. One mu L MD samples were incubated with paired oligonucleotide-conjugated antibodies binding to each protein, allowing quantification by real-time quantitative polymerase chain reaction. Sixty-nine proteins were suitable for statistical analysis. We found five different patterns with either early (<48 h; e.g., CCL20, IL6, LIF, CCL3), mid (48-96 h; e.g., CCL19, CXCL5, CXCL10, MMP1), late (>96 h; e.g., CD40, MCP2, MCP3), biphasic peaks (e.g., CXCL1, CXCL5, IL8) or stable (e.g., CCL4, DNER, VEGFA)/low trends. High protein levels were observed for e.g., CXCL1, CXCL10, MCP1, MCP2, IL8, while e.g., CCL28 and MCP4 were detected at low levels. Several proteins (CCL8, -19, -20, -23, CXCL1, -5, -6, -9, -11, CST5, DNER, Flt3L, and SIRT2) have not been studied previously in human TBI. Cross-correlation analysis revealed that LIF and CXCL5 may play a central role in the inflammatory cascade. This study provides a unique data set with individual temporal trends for potential inflammatory biomarkers in patients with TBI. We conclude that the combination of MD and PEA is a powerful tool to map the complex inflammatory cascade in the injured human brain. The technique offers new possibilities of protein profiling of complex secondary injury pathways.

    Fulltekst (pdf)
    FULLTEXT01
  • 14.
    Ekmark-Lewén, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Meyerson, Bengt J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Farmakologi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    The Multivariate Concentric Square Field Test Reveals Behavioral Profiles of Risk Taking, Exploration, and Cognitive Impairment in Mice Subjected to Traumatic Brain Injury2010Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 27, nr 9, s. 1643-1655Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is a need for more efficient tests to evaluate functional outcome following experimental traumatic brain injury (TBI), reflecting deficits in cognitive, sensory, and motor functions that are seen in TBI patients. The Multivariate Concentric Square Field (TM) (MCSF) test is a relatively new behavioral model that measures exploration, risk taking, risk assessment, and shelter seeking, all of which are evolutionarily-conserved strategies for survival. The multivariate design enables scoring of different functional domains in a single test situation, with a free choice of optional environmental settings. Furthermore, repeated trials permits cognitive effects to be measured. In the present study, 11 anesthetized C57BL6 mice received controlled cortical injury (CCI) (0.5mm and 3.3 m/sec) over the right parietal cerebral cortex or sham surgery (n - 12). Naive mice (n 12) not subjected to any surgical procedure were also included. The animals were evaluated in the MCSF test at 2 and 7 days post-surgery, and behavioral profiles were analyzed. The results revealed differences in risk taking and explorative behavior between the sham animals and the animals subjected to trauma. Animals subjected to trauma were characterized by taking more risks and had a higher level of exploration activity, but they sought less shelter. Repeated exposure to the MCSF caused a general decrease in activity in the naive and sham group, while a more specific behavioral impairment was seen in injured mice, suggesting cognitive dysfunction. We submit that the MCSF test is a useful complementary tool for functional outcome evaluation in experimental TBI.

  • 15. Ercole, A.
    et al.
    Thelin, E.
    Holst, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Bellander, B.
    Nelson, D.
    BAYESIAN MODEL OF TRAUMATIC BRAIN INJURY BIOMARKER KINETICS2016Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, nr 3, s. A39-A39Artikkel i tidsskrift (Annet vitenskapelig)
  • 16. Falci, S
    et al.
    Holtz, A
    Akesson, E
    Azizi, M
    Ertzgaard, P
    Hultling, C
    Kjaeldgaard, A
    Richard, Levi
    Ringden, O
    Westgren, M
    Lammertse, D
    Seiger, A
    Obliteration of a posttraumatic spinal cord cyst with solid human embryonic spinal cord grafts: first clinical attempt.1997Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 14, nr 11, s. 875-84Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cystic lesions of the spinal cord (syringomyelia) may occur after spinal cord injury. Posttraumatic syringomyelia may result in a myelopathy causing symptoms of sensory and motor loss, as well as worsening spasticity, pain, hyperhidrosis, and autonomic dysreflexia. Shunting of the cyst cavity along with untethering of the scarred spinal cord is widely accepted as the treatment of choice. However, the long-term stabilization of the progressive myelopathy caused by a posttraumatic cyst is suboptimal because of arachnoidal rescarring, shunt tube blockage, and cyst reexpansion. A new neurosurgical strategy to overcome the complication of cyst reexpansion was designed. Experimental studies have shown the successful use of embryonic spinal cord grafts, including human grafts, to obliterate induced spinal cord cavities in rats. The authors report the first use of solid human embryonic spinal cord grafts to successfully obliterate 6 cm of a large cyst cavity in a patient becoming myelopathic from a posttraumatic cyst. The grafts are well visualized by MRI to the 7-month postoperative follow-up and cyst obliteration is seen in the region where the grafts were placed.

  • 17.
    Falci, S
    et al.
    Department of Neurosurgery, Craig Hospital, Denver, Colorado.
    Holtz, A
    Department of Neurosurgery, Academic Hospital, University of Uppsala, Sweden.
    Akesson, E
    department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Stockholm, Sweden.
    Azizi, M
    Department of Neurosurgery, Academic Hospital, University of Uppsala, Sweden.
    Ertzgaard, Per
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Rehabiliteringsmedicin. Linköpings universitet, Medicinska fakulteten.
    Hultling, C
    The Spinalis SCI Research Unit, Karolinska Institute, Stockholm, Sweden.
    Kjaeldgaard, A
    Department of Clinical Science, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.
    Levi, Richard
    department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Stockholm, Sweden.
    Ringden, O
    Department of Transplantation Immunology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.
    Westgren, M
    Department of Clinical Science, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.
    Lammertse, D
    department of Physical Medicine and Rehabilitation, Craig Hospital, Denver, Colorado.
    Seiger, A
    department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Stockholm, Sweden.
    Obliteration of a posttraumatic spinal cord cyst with solid human embryonic spinal cord grafts: first clinical attempt.1997Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 14, nr 11, s. 875-884Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cystic lesions of the spinal cord (syringomyelia) may occur after spinal cord injury. Posttraumatic syringomyelia may result in a myelopathy causing symptoms of sensory and motor loss, as well as worsening spasticity, pain, hyperhidrosis, and autonomic dysreflexia. Shunting of the cyst cavity along with untethering of the scarred spinal cord is widely accepted as the treatment of choice. However, the long-term stabilization of the progressive myelopathy caused by a posttraumatic cyst is suboptimal because of arachnoidal rescarring, shunt tube blockage, and cyst reexpansion. A new neurosurgical strategy to overcome the complication of cyst reexpansion was designed. Experimental studies have shown the successful use of embryonic spinal cord grafts, including human grafts, to obliterate induced spinal cord cavities in rats. The authors report the first use of solid human embryonic spinal cord grafts to successfully obliterate 6 cm of a large cyst cavity in a patient becoming myelopathic from a posttraumatic cyst. The grafts are well visualized by MRI to the 7-month postoperative follow-up and cyst obliteration is seen in the region where the grafts were placed.

  • 18.
    Feng, Junfeng
    et al.
    Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Shanghai Institute of Head Trauma, Shanghai, People's Republic of China.
    van Veen, Ernest
    Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Intensive Care, Erasmus University Medical Center, Rotterdam, the Netherlands.
    Yang, Chun
    Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Shanghai Institute of Head Trauma, Shanghai, People's Republic of China.
    Huijben, Jilske A.
    Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands.
    Lingsma, Hester F.
    Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands..
    Gao, Guoyi
    Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Shanghai Institute of Head Trauma, Shanghai, People's Republic of China.
    Jiang, Jiyao
    Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Shanghai Institute of Head Trauma, Shanghai, People's Republic of China.
    Maas, Andrew I. R.
    Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium.
    Collaborative European Neuro Trauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Investigators and Participants, -
    Comparison of Care System and Treatment Approaches for Patients with Traumatic Brain Injury in China versus Europe: A CENTER-TBI Survey Study2020Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) poses a huge public health and societal problem worldwide. Uncertainty exists on how care system and treatment approaches for TBI worked in China may differ from those in Europe. Better knowledge on this is important to facilitate interpretation of findings reported by Chinese researchers and to inform opportunities for collaborative studies. We aimed to investigate concordance and variations in TBI care between Chinese and European neurotrauma centers. Investigators from 52 centers in China and 68 in Europe involved in the Collaborative European Neuro Trauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study were invited to complete provider profiling (PP) questionnaires, which covered the main aspects of care system and treatment approaches of TBI care. Participating Chinese and European centers were mainly publicly funded and academic. More centers in China indicated available dedicated neuro-intensive care than those in Europe (98% vs. 60%), and treatment decisions in the ICU were mainly determined by neurosurgeons (58%) in China while in Europe, (neuro)intensivists often took the lead (61%). The ambulance dispatching system was automatic in half of Chinese centers (49%), whereas selective dispatching was more common in European centers (74%). For treatment of refractory intracranial hypertension, a decompressive craniectomy was more frequently regarded as general policy in China compared with in Europe (89% vs. 45%). We observed both concordance and substantial variations with regard to the various aspects of TBI care between Chinese and European centers. These findings are fundamental to guide future research and offer opportunities for collaborative comparative effectiveness research to identify best practices.

  • 19.
    Flygt, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ruscher, Karsten
    Novartis Inst Biomed Res, Basel, Switzerland.
    Norberg, Amanda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Mir, Anis
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden.
    Gram, Hermann
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden.
    Neutralization of Interleukin-1 beta following Diffuse Traumatic Brain Injury in the Mouse Attenuates the Loss of Mature Oligodendrocytes2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 23, s. 2837-2849Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) commonly results in injury to the components of the white matter tracts, causing post-injury cognitive deficits. The myelin-producing oligodendrocytes (OLs) are vulnerable to TBI, although may potentially be replaced by proliferating oligodendrocyte progenitor cells (OPCs). The cytokine interleukin-1 beta (IL-1 beta) is a key mediator of the complex inflammatory response, and when neutralized in experimental TBI, behavioral outcome was improved. To evaluate the role of IL-1 beta on oligodendrocyte cell death and OPC proliferation, 116 adult male mice subjected to sham injury or the central fluid percussion injury (cFPI) model of traumatic axonal injury, were analyzed at two, seven, and 14 days post-injury. At 30 min post-injury, mice were randomly administered an IL-1 beta neutralizing or a control antibody. OPC proliferation (5-ethynyl 2 '- deoxyuridine (EdU)/Olig2 co-labeling) and mature oligodendrocyte cell loss was evaluated in injured white matter tracts. Microglia/macrophages immunohistochemistry and ramification using Sholl analysis were also evaluated. Neutralizing IL-1 beta resulted in attenuated cell death, indicated by cleaved caspase-3 expression, and attenuated loss of mature OLs from two to seven days post-injury in brain-injured animals. IL-1 beta neutralization also attenuated the early, two day post-injury increase of microglia/macrophage immunoreactivity and altered their ramification. The proliferation of OPCs in brain-injured animals was not altered, however. Our data suggest that IL-1 beta is involved in the TBI-induced loss of OLs and early microglia/macrophage activation, although not the OPC proliferation. Attenuated oligodendrocyte cell loss may contribute to the improved behavioral outcome observed by IL-1 beta neutralization in this mouse model of diffuse TBI.

    Fulltekst (pdf)
    fulltext
  • 20. Foks, Kelly A.
    et al.
    Cnossen, Maryse C.
    Dippel, Diederik W. J.
    Maas, Andrew I.R.
    Menon, David
    van der Naalt, Joukje
    Steyerberg, Ewout W.
    Lingsma, Hester F.
    Polinder, Suzanne
    Koskinen, Lars-Owe
    Management of mild traumatic brain injury at the emergency department and hospital admission in Europe: A survey of 71 neurotrauma centers participating in the CENTER-TBI study2017Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 34, nr 17, s. 2529-2535Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous studies have indicated that there is no consensus about management of mild traumatic brain injury (mTBI) at the emergency department (ED) and during hospital admission. We aim to study variability between management policies for TBI patients at the ED and hospital ward across Europe. Centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study received questionnaires about different phases of TBI care. These questionnaires included 71 questions about TBI management at the ED and at the hospital ward. We found differences in how centers defined mTBI. For example, 40 centers (59%) defined mTBI as a Glasgow Coma Scale (GCS) score between 13-15 and 26 (38%) as a GCS score between 14-15. At the ED various guidelines for the use of head CT in mTBI patients were used; 32 centers (49%) used national guidelines, 10 centers (15%) local guidelines and 14 centers (21%) used no guidelines at all. Also differences in indication for admission between centers were found. After ED discharge, 7 centers (10%) scheduled a routine follow-up appointment, while 38 (54%) did so only after ward admission. In conclusion, large between-center variation exists in policies for diagnostics, admission and discharge decisions in patients with mTBI at the ED and in hospital. Guidelines are not always operational in centers, and reported policies systematically diverge from what is recommended in those guidelines. The results of this study may be useful in the understanding of mTBI care in Europe and show the need for further studies on the effectiveness of different policies on outcome.

  • 21.
    Glushakova, Olena Y.
    et al.
    Virginia Commonwealth Univ, Neurosurg, Richmond, VA USA.
    Glushakov, Andriy O.
    Univ S Florida, Neurosurg, Coll Med, Tampa, FL USA.
    Korol, Tetyana Y.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Acosta, Sandra
    Univ S Florida, Neurosurg, Coll Med, Tampa, FL USA.
    Borlongan, Cesar V.
    Univ S Florida, Neurosurg, Coll Med, Tampa, FL USA.
    Valadka, Alex B.
    Virginia Commonwealth Univ, Neurosurg, Richmond, VA USA.
    Hayes, Ronald L.
    Banyan Biomarkers Inc, Alachua, FL USA.
    Glushakov, Alexander V.
    Single Breath Inc, Midlothian, VA USA.
    Cleaved-Caspase-3, Caspase-3-Cleaved Tau And Chronic Microvascular Reorganization In The Thalamus After Tbi2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A119-A120Artikkel i tidsskrift (Annet vitenskapelig)
  • 22.
    Gravesteijn, Benjamin Y.
    et al.
    Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
    Sewalt, Charlie A.
    Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
    Ercole, Ari
    Division of Anaesthesia, University of Cambridge, Cambridge, United Kingdom.
    Akerlund, Cecilia
    Department of Physiology and Pharmacology, Section of Perioperative Medicine and Intensive Care, Karolinska Institutet, Stockholm, Sweden.
    Nelson, David
    Department of Physiology and Pharmacology, Section of Perioperative Medicine and Intensive Care, Karolinska Institutet, Stockholm, Sweden.
    Maas, Andrew I. R.
    Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium.
    Menon, David
    Division of Anaesthesia, University of Cambridge, Cambridge, United Kingdom.
    Lingsma, Hester F.
    Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
    Steyerberg, Ewout W.
    Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Centre Leiden, The Netherlands.
    Collaborative European NeuroTrauma Effectiveness Research for Traumatic Brain Injury, Colaborators
    Toward a New Multi-Dimensional Classification of Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research for Traumatic Brain Injury Study2020Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 37, nr 7, s. 1002-1010Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) is currently classified as mild, moderate, or severe TBI by trichotomizing the Glasgow Coma Scale (GCS). We aimed to explore directions for a more refined multidimensional classification system. For that purpose, we performed a hypothesis-free cluster analysis in the Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI) database: a European all-severity TBI cohort (n = 4509). The first building block consisted of key imaging characteristics, summarized using principal component analysis from 12 imaging characteristics. The other building blocks were demographics, clinical severity, secondary insults, and cause of injury. With these building blocks, the patients were clustered into four groups. We applied bootstrap resampling with replacement to study the stability of cluster allocation. The characteristics that predominantly defined the clusters were injury cause, major extracranial injury, and GCS. The clusters consisted of 1451, 1534, 1006, and 518 patients, respectively. The clustering method was quite stable: the proportion of patients staying in one cluster after resampling and reclustering was 97.4% (95% confidence interval [CI]: 85.6-99.9%). These clusters characterized groups of patients with different functional outcomes: from mild to severe, 12%, 19%, 36%, and 58% of patients had unfavorable 6 month outcome. Compared with the mild and the upper intermediate cluster, the lower intermediate and the severe cluster received more key interventions. To conclude, four types of TBI patients may be defined by injury mechanism, presence of major extracranial injury and GCS. Describing patients according to these three characteristics could potentially capture differences in etiology and care pathways better than with GCS only.

  • 23.
    Gutierrez, Elena
    et al.
    Chalmers University of Technology, Crash Safety Division.
    Huang, Yinglai
    Department of Anatomy and Cell Biology, Göteborg University.
    Haglid, Kenneth
    Department of Anatomy and Cell Biology, Göteborg University.
    Bao, Feng
    Department of Anatomy and Cell Biology, Göteborg University.
    Hansson, Hans-Arne
    Department of Anatomy and Cell Biology, Göteborg University.
    Hamberger, Anders
    Department of Anatomy and Cell Biology, Göteborg University.
    Viano, David
    Crash Safety Division, Chalmers University of Technology.
    A New Model for Diffuse Brain Injury by Rotational Acceleration: I. Model, Gross Appearance, and Astrocytosis2001Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 18, nr 3, s. 247-257Artikkel i tidsskrift (Fagfellevurdert)
  • 24.
    Gutierrez, Elena M
    KTH, Skolan för teknikvetenskap (SCI), Mekanik, Biomekanik. Chalmers University of Technology.
    A new model for diffuse brain injury by rotational acceleration: I model, gross appearance, and astrocytosis2001Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 18, nr 3, s. 247-257Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rapid head rotation is a major cause of brain damage in automobile crashes and falls. This report details a new model for rotational acceleration about the center of mass of the rabbit head. This allows the study of brain injury without translational acceleration of the head. Impact from a pneumatic cylinder was transferred to the skull surface to cause a half-sine peak acceleration of 2.1 × 105 rad/s2 and 0.96-ms pulse duration. Extensive subarachnoid hemorrhages and small focal bleedings were observed in the brain tissue. A pronounced reactive astrogliosis was found 8-14 days after trauma, both as networks around the focal hemorrhages and more diffusely in several brain regions. Astrocytosis was prominent in the gray matter of the cerebral cortex, layers II-V, and in the granule cell layer and around the axons of the pyramidal neurons in the hippocampus. The nuclei of cranial nerves, such as the hypoglossal and facial nerves, also showed intense astrocytosis. The new model allows study of brain injuries from head rotation in the absence of translational influences.

  • 25.
    Hanell, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Djupsjö, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Vallstedt, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
    Patra, Kalicharan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
    Israelsson, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Larhammar, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
    Björk, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Paixao, Sonia
    Kullander, Klas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Functional and Histological Outcome after Focal Traumatic Brain Injury Is Not Improved in Conditional EphA4 Knockout Mice2012Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, nr 17, s. 2660-2671Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We investigated the role of the axon guidance molecule EphA4 following traumatic brain injury (TBI) in mice. Neutralization of EphA4 improved motor function and axonal regeneration following experimental spinal cord injury (SCI). We hypothesized that genetic absence of EphA4 could improve functional and histological outcome following TBI. Using qRT-PCR in wild-type (WT) mice, we evaluated the EphA4 mRNA levels following controlled cortical impact (CCI) TBI or sham injury and found it to be downregulated in the hippocampus (p < 0.05) but not the cortex ipsilateral to the injury at 24 h post-injury. Next, we evaluated the behavioral and histological outcome following CCI using WT mice and Emx1-Cre-driven conditional knockout (cKO) mice. In cKO mice, EphA4 was completely absent in the hippocampus and markedly reduced in the cortical regions from embryonic day 16, which was confirmed using Western blot analysis. EphA4 cKO mice had similar learning and memory abilities at 3 weeks post-TBI compared to WT controls, although brain-injured animals performed worse than sham-injured controls (p < 0.05). EphA4 cKO mice performed similarly to WT mice in the rotarod and cylinder tests of motor function up to 29 days post-injury. TBI increased cortical and hippocampal astrocytosis (GFAP immunohistochemistry, p < 0.05) and hippocampal sprouting (Timm stain, p < 0.05) and induced a marked loss of hemispheric tissue (p < 0.05). EphA4 cKO did not alter the histological outcome. Although our results may argue against a beneficial role for EphA4 in the recovery process following TBI, further studies including post-injury pharmacological neutralization of EphA4 are needed to define the role for EphA4 following TBI.

  • 26. Hanell, Anders
    et al.
    Hedin, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Facilitated assessment of tissue loss following experimental traumatic brain injury2012Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, nr 10, s. A154-A154Artikkel i tidsskrift (Annet vitenskapelig)
  • 27. Hernandez, F.
    et al.
    Wu, L. C.
    Yip, M. C.
    Hoffman, A. R.
    Lopez, J.
    Grant, G.
    Kleiven, Svein
    KTH, Skolan för teknik och hälsa (STH), Medicinsk teknik, Neuronik.
    Camarillo, D. B.
    Finite Element Simulation Of Brain Deformation From Six Degree Of Freedom Acceleration Measurements Of Mild Traumatic Brain Injury2014Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, nr 12, s. A124-A124Artikkel i tidsskrift (Annet vitenskapelig)
  • 28. Hernandez, Fidel
    et al.
    Giordano, Chiara
    KTH, Skolan för teknik och hälsa (STH), Medicinsk teknik, Neuronik.
    Kleiven, Svein
    KTH, Skolan för teknik och hälsa (STH), Medicinsk teknik, Neuronik.
    Camarillo, David
    CORONAL HEAD ROTATION, FALX CEREBRI DISPLACEMENT, AND CORPUS CALLOSUM STRAIN ARE RELATED AND IMPLICATED IN SPORTS-RELATED MTBI2016Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, nr 13, s. A34-A35Artikkel i tidsskrift (Annet vitenskapelig)
  • 29.
    Hillered, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Dahlin, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Purins, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Wetterhall, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Hjort, Klas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    New Microdialysis Method for Protein Biomarker Sampling in the Neurointensive Care Setting2014Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, nr 5, s. A22-A22Artikkel i tidsskrift (Fagfellevurdert)
  • 30.
    Huie, J. Russell
    et al.
    Brain and Spinal Injury Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
    Mondello, Stefania
    Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
    Lindsell, Christopher J.
    Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Antiga, Luca
    Orobix Srl, Bergamo, Italy.
    Yuh, Esther L.
    Brain and Spinal Injury Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
    Zanier, Elisa R.
    Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
    Masson, Serge
    Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
    Rosario, Bedda L.
    Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA.
    Ferguson, Adam R.
    Brain and Spinal Injury Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA; San Francisco Veterans Affairs Medical Center (SFVAMC), San Francisco, California, USA.
    The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators
    Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations2020Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.

  • 31. Huijben, Jilske A.
    et al.
    van der Jagt, Mathieu
    Cnossen, Maryse C.
    Kruip, Marieke J. H. A.
    Haitsma, Iain K.
    Stocchetti, Nino
    Maas, Andrew I. R.
    Menon, David K.
    Ercole, Ari
    Maegele, Marc
    Stanworth, Simon J.
    Citerio, Giuseppe
    Polinder, Suzanne
    Steyerberg, Ewout W.
    Lingsma, Hester F.
    Variation in Blood Transfusion and Coagulation Management in Traumatic Brain Injury at the Intensive Care Unit: A Survey in 66 Neurotrauma Centers Participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study2017Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 2, s. 323-332Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Our aim was to describe current approaches and to quantify variability between European intensive care units (ICUs) in patients with traumatic brain injury (TBI). Therefore, we conducted a provider profiling survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The ICU Questionnaire was sent to 68 centers from 20 countries across Europe and Israel. For this study, we used ICU questions focused on 1) hemoglobin target level (Hb-TL), 2) coagulation management, and 3) deep venous thromboembolism (DVT) prophylaxis. Seventy-eight participants, mostly intensivists and neurosurgeons of 66 centers, completed the ICU questionnaire. For ICU-patients, half of the centers (N = 34; 52%) had a defined Hb-TL in their protocol. For patients with TBI, 26 centers (41%) indicated an Hb-TL between 70 and 90 g/L and 38 centers (59%) above 90 g/L. To treat trauma-related hemostatic abnormalities, the use of fresh frozen plasma (N = 48; 73%) or platelets (N = 34; 52%) was most often reported, followed by the supplementation of vitamin K (N = 26; 39%). Most centers reported using DVT prophylaxis with anticoagulants frequently or always (N = 62; 94%). In the absence of hemorrhagic brain lesions, 14 centers (21%) delayed DVT prophylaxis until 72 h after trauma. If hemorrhagic brain lesions were present, the number of centers delaying DVT prophylaxis for 72 h increased to 29 (46%). Overall, a lack of consensus exists between European ICUs on blood transfusion and coagulation management. The results provide a baseline for the CENTER-TBI study, and the large between-center variation indicates multiple opportunities for comparative effectiveness research.

  • 32.
    Hussain, Zubair Muhammad
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Fitting, Sylvia
    Watanabe, Hiroyuki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Usynin, Ivan
    Yakovleva, Tatjana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Knapp, Pamela E.
    Scheff, Stephen W.
    Hauser, Kurt F.
    Bakalkin, Georgy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Lateralized Response of Dynorphin A Peptide Levels after Traumatic Brain Injury2012Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, nr 9, s. 1785-1793Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) induces a cascade of primary and secondary events resulting in impairment of neuronal networks that eventually determines clinical outcome. The dynorphins, endogenous opioid peptides, have been implicated in secondary injury and neurodegeneration in rodent and human brain. To gain insight into the role of dynorphins in the brain's response to trauma, we analyzed short-term (1-day) and long-term (7-day) changes in dynorphin A (Dyn A) levels in the frontal cortex, hippocampus, and striatum, induced by unilateral left-side or right-side cortical TBI in mice. The effects of TBI were significantly different from those of sham surgery (Sham), while the sham surgery also produced noticeable effects. Both sham and TBI induced short-term changes and long-term changes in all three regions. Two types of responses were generally observed. In the hippocampus, Dyn A levels were predominantly altered ipsilateral to the injury. In the striatum and frontal cortex, injury to the right (R) hemisphere affected Dyn A levels to a greater extent than that seen in the left (L) hemisphere. The R-TBI but not L-TBI produced Dyn A changes in the striatum and frontal cortex at 7 days after injury. Effects of the R-side injury were similar in the two hemispheres. In naive animals, Dyn A was symmetrically distributed between the two hemispheres. Thus, trauma may reveal a lateralization in the mechanism mediating the response of Dyn A-expressing neuronal networks in the brain. These networks may differentially mediate effects of left and right brain injury on lateralized brain functions.

  • 33.
    Hånell, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Björk, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Jansson, Kristine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Philipson, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Nilsson, Lars N. G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Weinreb, Paul H.
    Lee, Daniel
    McIntosh, Tracy K.
    Gimbel, David A.
    Strittmatter, Stephen M.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Genetic Deletion and Pharmacological Inhibition of Nogo-66 Receptor Impairs Cognitive Outcome after Traumatic Brain Injury in Mice2010Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 27, nr 7, s. 1297-1309Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Functional recovery is markedly restricted following traumatic brain injury (TBI), partly due to myelin-associated inhibitors including Nogo-A, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), that all bind to the Nogo-66 receptor-1 (NgR1). In previous studies, pharmacological neutralization of both Nogo-A and MAG improved outcome following TBI in the rat, and neutralization of NgR1 improved outcome following spinal cord injury and stroke in rodent models. However, the behavioral and histological effects of NgR1 inhibition have not previously been evaluated in TBI. We hypothesized that NgR1 negatively influences behavioral recovery following TBI, and evaluated NgR1(-/-) mice (NgR1(-/-) study) and, in a separate study, soluble NgR1 infused intracerebroventricularly immediately post-injury to neutralize NgR1 (sNgR1 study) following TBI in mice using a controlled cortical impact (CCI) injury model. In both studies, motor function, TBI-induced loss of tissue, and hippocampal beta-amyloid immunohistochemistry were not altered up to 5 weeks post-injury. Surprisingly, cognitive function (as evaluated with the Morris water maze at 4 weeks post-injury) was significantly impaired both in NgR1(-/-) mice and in mice treated with soluble NgR1. In the sNgR1 study, we evaluated hippocampal mossy fiber sprouting using the Timm stain and found it to be increased at 5 weeks following TBI. Neutralization of NgR1 significantly increased mossy fiber sprouting in sham-injured animals, but not in brain-injured animals. Our data suggest a complex role for myelin-associated inhibitors in the behavioral recovery process following TBI, and urge caution when inhibiting NgR1 in the early post-injury period.

  • 34.
    Israelsson, Charlotte
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Bengtsson, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Kylberg, Annika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Kullander, Klas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ebendal, Ted
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Distinct cellular patterns of upregulated chemokine expression supporting a prominent inflammatory role in traumatic brain injury2008Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 25, nr 8, s. 959-974Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cerebral gene expressions change in response to traumatic brain injury (TBI), and future trauma treatment may improve with increased knowledge about these regulations. We subjected C57BL/6J mice to injury by controlled cortical impact (CCI). At various time points post-injury, mRNA from neocortex and hippocampus was isolated, and transcriptional alterations studied using quantitative real-time polymerase chain reaction (PCR) and gene array analysis. Spatial distribution of enhanced expression was characterized by in situ hybridization. Products of the upregulated transcripts serve functions in a range of cellular mechanisms, including stress, inflammation and immune responses, and tissue remodeling. We also identified increased transcript levels characterizing reactive astrocytes, oligodendrocytes, and microglia, and furthermore, we demonstrated a novel pattern of scattered cell clusters expressing the chemokine Cxcl10. Notably, a sustained increase in integrin alpha X (Itgax), characterizing antigen-presenting dendritic cells, was found with the transcript located to similar cell clusters. In contrast, T-cell receptor alpha transcript showed only a modest increase. The induced P-selectin (Selp) expression level in endothelial cells, and chemokines from microglia, may guide perivascular accumulation of extravasating inflammatory monocytes differentiating into dendritic cells. In conclusion, our study shows that following TBI, secondary injury chiefly involves inflammatory processes and chemokine signaling, which comprise putative targets for pharmaceutical neuroprotection.

  • 35.
    Israelsson, Charlotte
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Wang, Yun
    Kylberg, Annika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Pick, Chaim G
    Hoffer, Barry
    Ebendal, Ted
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Closed head injury in a mouse model results in molecular changes indicating inflammatory responses2009Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 26, nr 8, s. 1307-1314Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cerebral gene expression changes in response to traumatic brain injury will provide useful information in the search for future trauma treatment. In order to characterize the outcome of mild brain injury, we studied C57BL/6J mice in a weight-drop (30 g), closed head injury model. At various times post-injury, mRNA was isolated from neocortex and hippocampus and transcriptional alterations were studied using quantitative reverse transcriptase PCR and gene array analysis. At three days post-injury, the results showed unilateral injury responses, both in neocortex and hippocampus, with the main effect seen on the side of the skull hit by the dropping weight. Upregulated transcripts encoded products characterizing reactive astrocytes, phagocytes, microglia and immune-reactive cells. Markers for oligodendrocytes and T-cells were not altered. Notably, strong differences in the responses among individual mice were seen, e.g. for the Gfap transcript expressed by reactive astrocytes and the chemokine Ccl3 transcript expressed by activated microglial cells. In conclusion, mild TBI chiefly activates transcripts leading to tissue remodeling, inflammatory processes and chemokine signalling, as in focal brain injury, suggesting putative targets for drug development.

  • 36.
    Kleiven, Svein
    KTH, Tidigare Institutioner                               , Farkost- och flygteknik.
    Influence of Impact Direction on the Human Head in Prediction of Subdural Hematoma2003Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 20, nr 4, s. 365-379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective of the present study was to analyze the effect of different loading directions following impact, and to evaluate existing global head injury criteria. Detailed and parameterized models of the adult human head were created by using the Finite Element Method (FEM). Loads corresponding to the same impact power were imposed in different directions. Furthermore, the Head Injury Criterion (HIC) and the recently proposed Head Impact Power (HIP) criterion were evaluated with respect to the relative motion between the skull and the brain, as well as the strain in the bridging veins. It was found that the influence of impact direction had a substantial effect on the intracranial response. The largest relative skull-brain motion and strain in the bridging veins occurred with the anterior-posterior (AP) and posterior-anterior (PA) rotational impulses. HIC was unable to predict consequences of a pure rotational impulse while HIP needed individual scaling coefficients for the different terms to account for difference in load direction. When using the proposed scaling procedure, a better prediction of subdural hematoma (SDH) was obtained. It is thus suggested that an evaluation of the synergistic terms is necessary to further improve the injury prediction. These variations should be considered when developing new head injury criteria.

  • 37.
    Koskinen, Lars-Owe D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Hägglund, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Olivecrona, Magnus
    The relation between brain interstitial clycerol and pressure reactivity in TBI is prostacyclin dependent2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A185-A185Artikkel i tidsskrift (Annet vitenskapelig)
  • 38.
    Koskinen, Lars-Owe D.
    et al.
    Clinical Neuroscience-neurosurgery, Umeå University, Umeå, Sweden.
    Sundström, Nina
    Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden.
    Hägglund, Linda
    Clinical Neuroscience-neurosurgery, Umeå University, Umeå, Sweden.
    Eklund, Anders
    Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden.
    Olivecrona, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Anaesthesia and Intensive Care, Section for Neurosurgery.
    THE RELATION BETWEEN BRAIN INTERSTITIAL GLYCEROL AND PRESSURE REACTIVITY IN TBI IS PROSTACYCLIN DEPENDENT2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A185-A185Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: Cerebral injury may alter the autoregulation of cerebral blood flow. Pressure reactivity (PR) is considered as a surrogate measure of autoregulation. Little is known whether PR is associated with measures of brain metabolism and indicators of ischemia and cell damage. We speculate that prostacyclin may affect extracellular glycerol levels (a measure of cell membrane degradation), measured by microdialysis in the brain, and thus glycerol’s association with PR.

    Material and Methods: The study is a randomized, double-blinded placebo-control study on the effect of prostacyclin treatment (0.5 ng/kg/min) in severe traumatic brain injury (sTBI). The basic treatment was an intracranial pressure (ICP) targeted therapy based on the Lund concept. Inclusion criteria were verified blunt head trauma, GCS£8, age 15 -70 yrs, and a first measured cerebral perfusion pressure of ‡10 mmHg. Multimodal monitoring was applied. Samples from a brain microdialysis catheter placed on the worst affected side, close to the penumbra zone, were analysed. Mean (glycerolmean) and maximal glycerol (glycerolmax) during the 96 hrs sampling period were calculated. The mean PR was calculated as the ICP/MAP regression coefficient based on hourly mean ICP and MAP (mean arterial blood pressure) during the first 96 hrs.

    Results: 45 patients, mean age 35.5–2.2 yrs, GCS 6 (3-8) and ISS 29 (9-50) were included. In the placebo group there was a positive correlation between glycerolmean (r=0.503, p=0.01), glycerolmax (r=0.490, p=0.015) levels and PR levels. This correlation was attenuated/abolished in the prostacyclin group. Glycerol tended to be higher and PR was higher in the placebo group (p=0.0164) as compared to the prostacyclin group.

    Conclusion: PR is correlated to the glycerol level in patients suffering from sTBI. Prostacyclin attenuates this correlation. Glycerol is associated with membrane degradation and may support glycerol as a biomarker for vascular endothelial breakdown. Such a breakdown may impair the regulation of cerebrovascular pressure reactivity. We suggest that prostacyclin counteracts the breakdown and beneficially affect the cerebral blood flow autoregulation measured as PR.

  • 39.
    Koskinen, Lars-Owe
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundstrom, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Brorsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Olivecrona, M.
    SECONDARY PEAK OF S-100B IS ASSOCIATED WITH DECOMPRESSIVE HEMICRANIECTOMY2016Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, nr 3, s. A27-A27Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    S-100B is a tissue biomarker for brain injury and secondary peak of S-100B (SP) is associated with outcome. Little is known whether SP is associated with decompressive hemicraniectomy (DC).

  • 40.
    Koskinen, L-O
    et al.
    Dept of Pharmacology and Clinical Neuroscience, Div of Neurosurgery, Umeå University, Umeå, Sweden.
    Sundström, N.
    Dept o Radiatio Sciences-Biomedical Engineering and Centre of Biomedical Engineering and Physics, Umeå University, Umeå, Sweden.
    Brorsson, C.
    Dept of Anaesthesia and Intensive Care, Inst of Surgery and Perioperative Sciences, Umeå University, Umeå , Sweden.
    Olivecrona, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Dept of Anaesthesiology, Örebro University Hospital, Örebro, Sweden.
    Secondary peak of S-100b is associated with decompressive hemicraniectomy2016Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, nr 3, s. A27-A27Artikkel i tidsskrift (Annet vitenskapelig)
  • 41.
    Lewén, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Dyhrfort, Philip
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    A Dedicated 21-Plex Pea Panel For High-Sensitive Protein Biomarker Detection Using Micro-Dialysis In Traumatic Brain Injury2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A130-A130Artikkel i tidsskrift (Annet vitenskapelig)
  • 42.
    Linder, Lars Kihlstrom Burenstam
    et al.
    Karolinska Inst, Neurosurg, Stockholm, Sweden.
    Birgersson, Ulrik
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Thomsen, Peter
    Univ Gothenburg, Dept Biomat, Gothenburg, Sweden.
    Engstrand, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Käkkirurgi.
    In-Situ Bone Regeneration Of Cranial Defects Using Synthetic Ceramic Implant2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A79-A80Artikkel i tidsskrift (Annet vitenskapelig)
  • 43.
    Lukoyanov, Nikolay
    et al.
    Univ Porto, Fac Med, Dept Biomed, Porto, Portugal.
    Carvalho, Liliana
    Univ Porto, Fac Med, Inst Invest & Inovacao Saude, Inst Biol Mol & Celular,Dept Biomed, Porto, Portugal.
    Watanabe, Hiroyuki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Zhang, Mengliang
    Lund Univ, Dept Expt Med Sci, Neuronano Res Ctr, Lund, Sweden.
    Sarkisyan, Daniil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Kononenko, Olga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Bazov, Igor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Iakovleva, Tatiana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Schouenborg, Jens
    Lund Univ, Dept Expt Med Sci, Neuronano Res Ctr, Lund, Sweden.
    Bakalkin, Georgy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Contralesional Hindlimb Motor Response Induced By Unilateral Brain Injury: Evidence For Extra Spinal Mechanism2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A201-A201Artikkel i tidsskrift (Annet vitenskapelig)
  • 44.
    Lööv, Camilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nadadhur, Aishwarya
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Erlandsson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Extracellular Ezrin - a Novel Biomarker for Traumatic Brain Injury2015Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 32, nr 4, s. 244-251Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) is a heterogeneous disease, and the discovery of diagnostic and prognostic TBI biomarkers is highly desirable in order to individualize patient care. We have previously published a study in which we identified possible TBI biomarkers by mass spectrometry 24 h after injury in a cell culture model. Ezrin-radixin-moesin (ERM) proteins were found abundantly in the medium after trauma, and in the present study we have identified extracellular ezrin as a possible biomarker for brain trauma by analyzing cell culture medium from injured primary neurons and glia and by measuring ezrin in cerebrospinal fluid (CSF) from both rats and humans. Our results show that extracellular ezrin concentration was substantially increased in cell culture medium after injury, but that the intracellular expression of the protein remained stable over time. Controlled cortical impact injured rats showed an increased amount of ezrin in CSF at both day 3 and day 7 after trauma. Moreover, ezrin was present in all ventricular CSF samples from seven humans with severe TBI. In contrast to intracellular ezrin, which is distinctly activated following TBI, extracellular ezrin is nonphosphorylated. This is the first report of extracellular ERM proteins in human and experimental models of TBI, providing a scientific foundation for further assessment of ezrin as a potential biomarker.

  • 45.
    Marklund, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Farrokhnia, Nina
    Hanell, Anders
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Zetterberg, Henrik
    Blennow, Kaj
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Monitoring of amyloid-beta dynamics after human traumatic brain injury2012Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, nr 10, s. A185-A185Artikkel i tidsskrift (Annet vitenskapelig)
  • 46.
    Marklund, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Farrokhnia, Nina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hånell, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Vanmechelen, Eugeen
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Zetterberg, Henrik
    Blennow, Kaj
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Monitoring of beta-Amyloid Dynamics after Human Traumatic Brain Injury2014Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, nr 1, s. 42-55Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epidemiological evidence links severe or repeated traumatic brain injury (TBI) to the development of Alzheimer's disease (AD). Accumulation of amyloid precursor protein (APP) occurs with high frequency after TBI, particularly in injured axons, and APP may be cleaved to amyloid- (A) peptides playing key pathophysiological roles in AD. We used cerebral microdialysis (MD) to test the hypothesis that interstitial A levels are altered following TBI and are related to the injury type, cerebral energy metabolism, age of the patient, and level of consciousness. In the present report, we evaluated 10 mechanically ventilated patients (7 male, 3 female, ages 18-76 years) with a severe TBI, who had intracranial pressure and MD monitoring. Each MD sample was analyzed for hourly routine energy metabolic biomarkers (MD-lactate, MD-pyruvate, MD-glucose, and MD-lactate/pyruvate ratio), cellular distress biomarkers (MD-glutamate, MD-glycerol), and MD-urea. The remaining MD samples were analyzed for A1-40 (A40; n=765 samples) and A1-42 (A42; n=765 samples) in pooled 2h fractions up to 14 days post-injury, using the Luminex xMAP technique, allowing detection with high temporal resolution of the key A peptides A40 and A42. Data are presented using medians and 25th and 75th percentiles. Both A40 and A42 were consistently higher in patients with predominately diffuse axonal injury compared with patients with focal TBI at days 1-6 post- injury, A42 being significantly increased at 113-116h post-injury (p<0.05). The A levels did not correlate with the interstitial energy metabolic situation, age of the patient, or the level of consciousness. These results support that interstitial generation of potentially toxic A species may occur following human TBI, particularly related to axonal injury.

  • 47.
    Marklund, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Sihver, Sven
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Farmakologi.
    Hovda, David
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Watanabe, Yasuyoshi
    Ronquist, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Bergström, Mats
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Increased Cerebral Uptake of [18F]Fluoro-Deoxyglucose but not [1-14C]Glucose Early following Traumatic Brain Injury in Rats2009Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 26, nr 8, s. 1281-1293Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Following experimental and clinical traumatic brain injury (TBI), the local cerebral metabolic rate of glucose (lCMRGlc) is commonly estimated using the 2-[18F]fluoro-2-deoxy-D-glucose (FDG) method. The adequate estimation of lCMRGlc using FDG requires a correction factor, the lumped constant (LC), to convert FDG net uptake into lCMRGlc. The LC, and thus lCMRGlc calculations, requires a "steady state" that may be disrupted following TBI. In the present report, we hypothesized that [1-14C]glucose uptake would accurately reflect glucose dynamics early post-injury and was compared to the regional uptake of FDG in 44 rats subjected to moderate (2.4-2.6 atm) lateral fluid percussion brain injury (FPI) or sham injury. Cortical energy state and adenylate (ATP, ADP, AMP) levels were also measured. Early (7-42 min) after FPI, FDG uptake was increased in the ipsilateral cortex and hippocampus (p<0.05). In contrast, no change in [1-14C]glucose uptake (7 and 17 min) or cortical adenylate content (42 min post-injury) was observed. At 12 hours following FPI, the ipsilateral FDG and [1-14C]glucose uptake was decreased in the cortex and hippocampus and the ipsilateral cortical ATP concentration was decreased in comparison to sham-injured controls (p<0.05). Under the present experimental conditions, the rate of cerebral uptake of FDG and of [1-14C]glucose differs, and indicate that following TBI, regional changes in the LC may occur in the immediate, but not in the late, post-injury phase. These results should be considered when interpreting results obtained using FDG for the estimation of lCMRGlc early following experimental TBI.

  • 48. Mattsson, Per
    et al.
    Aldskogius, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuroanatomi.
    Svensson, Mikael
    The novel pyrrolopyrimidine PNU-101033-E improves facial motor neuron survival following intracranial axotomy of the facial nerve in the adult rat1999Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 16, nr 9, s. 793-803Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuronal survival is important to functional restitution following axotomy. Proximal lesions of the facial nerve, due to head trauma or tumor growth, for example, may cause long-standing or even permanent facial nerve palsy. Betamethasone has been used by several neurosurgical clinics for the treatment of postoperative facial nerve palsy; however, this practice is based only on clinical experience. The aim of the present study was to explore the putative effect on facial motor neuron survival of a novel lazaroid (pyrrolopyrimidine, PNU-101033-E) and furthermore to compare the effects with those of betamethasone, following intracranial transection of the facial nerve in adult rats. Both agents are known to inhibit lipid peroxidation by free radical scavenging. The lesion model used has recently been reported to induce massive neuronal cell death with a relative survival of 26.8 +/- 11.3% 1 month after lesion. Oral administration of lazaroids or daily injections of betamethasone followed surgery for 1 month, after which quantification of motor neuronal profiles was performed in the facial nucleus. Lazaroid-treated animals showed a significantly enhanced neuronal survival (68.0 +/- 9.8%), whereas no significant difference was found in betamethasone-treated animals (33.1 +/- 11.7%). The microglial and astrocytic responses in the facial nucleus were intense on the operated sides in betamethasone-treated as well as lazaroid-treated animals, and no differences in comparison with untreated animals were found. In conclusion, we found that the novel pyrrolopyrimidine PNU-101033-E, but not betamethasone, significantly enhanced nerve cell survival. This agent may therefore serve as a useful neuroprotective agent following intracranial trauma to the facial nerve and should be further evaluated for clinical use.

  • 49.
    Mellergard, Pekka
    et al.
    Östergötlands Läns Landsting, Sinnescentrum, Neurokirurgiska kliniken US.
    Sjögren, Florence
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Hillman, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurokirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Neurokirurgiska kliniken US.
    The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury2012Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, nr 1, s. 112-118Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Old age is associated with a poor recovery from traumatic brain injury (TBI). In a retrospective study we investigated if the biochemical response following TBI is age dependent. Extracellular fluids were continuously sampled by microdialysis in 69 patients admitted to our NSICU following severe TBI. The concentrations of glycerol, glutamate, lactate, pyruvate, and eight different cytokines (IL-1 beta, IL-6, IL-10, IL-8, MIP-1 beta, RANTES, FGF2, and VEGF) were determined by fluorescence multiplex bead technology. Patients in the oldest age group (andgt;= 65 years) had significantly higher microdialysate concentrations of glycerol and glutamate compared to younger patients: the mean microdialysate concentration of glycerol increased from 55.9 mu mol/L (25-44 year) to 252 mu mol/L (andgt;= 65 years; p andlt; 0.0001); similarly glutamate increased from 15.8 mmol/L to 92.2 mmol/L (p andlt; 0.0001). The lactate-pyruvate ratio was also significantly higher in the patients andgt;= 65 years of age (63.9) compared with all the other age groups. The patterns of cytokine responses varied. For some cytokines (IL-1b, IL-10, and IL-8) there were no differences between age groups, while for others (MIP-1b, RANTES, VEGF, and IL-6) some differences were observed, but with no clear correlation with increasing age. For FGF2 the mean microdialysate concentration was 43 pg/mL in patients andgt;= 65 years old, significantly higher compared to all other age groups (p andlt; 0.0001). Increased concentrations of glycerol and glutamate would indicate more extensive damaging processes in the elderly. An increase in concentration of FGF2 could serve a protective function, but could also be related to a dysregulation of the timing in the cellular response in elderly patients.

    Fulltekst (pdf)
    fulltext
  • 50.
    Olivecrona, Magnus
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Anaesthesia and Intensive Care, Section for Neurosurgery, Örebro University Hospital, Örebro, Sweden.
    Olivecrona, Z.
    Department of Anaesthesia and Intensive Care, Sect for Neurosurgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Koskinen, L.
    Dept of Pharmacology and Clinical Neuroscience, Div of Neurosurgery, Örebro University Hospital, Örebro, Sweden.
    The Stockholm score for the prediction of outcome in persons with severe traumatic brain injury treated with an ICP-targeted therapy2016Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, nr 3, s. A34-A34Artikkel i tidsskrift (Annet vitenskapelig)
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