Journalartikel

Jahr der Veröffentlichung: 2015

Seiten: 963-973

Zeitschrift: European Journal of Neuroscience

Bandnummer: 41

Heftnummer: 7

ISSN: 0953-816X

eISSN: 1460-9568

DOI Link: https://doi.org/10.1111/ejn.12830

Verlag: Wiley

Abstract: 
Factor VII activating protease (FSAP) is a circulating protease with a putative role in hemostasis, remodeling and inflammation. A polymorphism giving rise to low proteolytic activity has been associated with an increased risk of stroke and carotid stenosis. To date, no in vivo studies or mechanistic information is available to explain these results. Based on the polymorphism data we hypothesize that a lack of endogenous FSAP will increase the severity of stroke. Stroke was induced by applying thrombin in the middle cerebral artery in wild-type (WT) and FSAP(-/-) mice. Increased stroke volume and worsened neurological deficit were observed in FSAP(-/-) mice. Raised levels of FSAP protein were detected in the infarcted area of WT mice together with enhanced leukocyte infiltration and apoptosis in FSAP(-/-) mice. There was a concomitant increase in the activation of the NFB pathway and decrease in expression of the PI3K/AKT pathway proteins. At a cellular level, FSAP increased cell survival and decreased apoptosis in primary cortical neurons and astrocytes exposed to tPA/NMDA excitotoxicity or oxygen glucose deprivation (OGD)/reoxygenation, respectively. This was mediated via the PI3K/AKT pathway with involvement of the protease activated receptor-1. To corroborate the human epidemiological data, which link FSAP with stroke, we now show that the lack of FSAP in mice worsens the outcome of stroke. In the absence of FSAP there was a stronger inflammatory response and lower cell survival due to insufficient activation of the PI3K/AKT pathway.

Harvard-Zitierstil: Joshi, A., Orset, C., Engelhardt, B., Baumgart-Vogt, E., Gerriets, T., Vivien, D., et al. (2015) Deficiency of Factor VII activating protease alters the outcome of ischemic stroke in mice, European Journal of Neuroscience, 41(7), pp. 963-973. https://doi.org/10.1111/ejn.12830

APA-Zitierstil: Joshi, A., Orset, C., Engelhardt, B., Baumgart-Vogt, E., Gerriets, T., Vivien, D., & Kanse, S. (2015). Deficiency of Factor VII activating protease alters the outcome of ischemic stroke in mice. European Journal of Neuroscience. 41(7), 963-973. https://doi.org/10.1111/ejn.12830