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Disruption of the alox5ap gene ameliorates focal ischemic stroke: possible consequence of impaired leukotriene biosynthesis
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
2012 (English)In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 13, 146- p.Article in journal (Refereed) Published
Abstract [en]

Background

Leukotrienes are potent inflammatory mediators, which in a number of studies have been found to be associated with ischemic stroke pathology: gene variants affecting leukotriene synthesis, including the FLAP (ALOX5AP) gene, have in human studies shown correlation to stroke incidence, and animal studies have demonstrated protective properties of various leukotriene-disrupting drugs. However, no study has hitherto described a significant effect of a genetic manipulation of the leukotriene system on ischemic stroke. Therefore, we decided to compare the damage from focal cerebral ischemia between wild type and FLAP knockout mice. Damage was evaluated by infarct staining and a functional test after middle cerebral artery occlusion in 20 wild type and 20 knockout male mice.

Results

Mortality-adjusted median infarct size was 18.4 (3.2-76.7) mm3 in the knockout group, compared to 72.0 (16.7-174.0) mm3 in the wild type group (p < 0.0005). There was also a tendency of improved functional score in the knockout group (p = 0.068). Analysis of bone marrow cells confirmed that knockout animals had lost their ability to form leukotrienes.

Conclusions

Since the local inflammatory reaction after ischemic stroke is known to contribute to the brain tissue damage, the group difference seen in the current study could be a consequence of a milder inflammatory reaction in the knockout group. Our results add evidence to the notion that leukotrienes are important in ischemic stroke, and that blocked leukotriene production ameliorates cerebral damage.

Place, publisher, year, edition, pages
BioMed Central, 2012. Vol. 13, 146- p.
Keyword [en]
Brain infarction, Leukotrienes, Alox5ap protein, FLAP, Mice, Middle cerebral artery occlusion
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-89759DOI: 10.1186/1471-2202-13-146ISI: 000314271500001PubMedID: 23194405OAI: oai:DiVA.org:liu-89759DiVA: diva2:609332
Note

Funding Agencies|Elvar and Annette Theodorsson||Marta Lundqvists stiftelse||County Council of Ostergotland||

Available from: 2013-03-05 Created: 2013-03-05 Last updated: 2017-12-06Bibliographically approved

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