Disruption of the alox5ap gene ameliorates focal ischemic stroke: possible consequence of impaired leukotriene biosynthesis
2012 (English)In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 13, 146- p.Article in journal (Refereed) Published
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.
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.
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.
Brain infarction, Leukotrienes, Alox5ap protein, FLAP, Mice, Middle cerebral artery occlusion
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-89759DOI: 10.1186/1471-2202-13-146ISI: 000314271500001PubMedID: 23194405OAI: oai:DiVA.org:liu-89759DiVA: diva2:609332
Funding Agencies|Elvar and Annette Theodorsson||Marta Lundqvists stiftelse||County Council of Ostergotland||2013-03-052013-03-052016-02-29Bibliographically approved