Enlarged infarct volume and loss of BDNF mRNA induction following brain ischemia in mice lacking FGF-2

FGF-2, a potent multifunctional and neurotrophic growth factor, is widely expressed in the brain and upregulated in cerebral ischemia. Previous studies have shown that intraventricularly or systemically administered FGF-
FGF-2, a potent multifunctional and neurotrophic growth factor, is widely expressed in the brain and upregulated in cerebral ischemia. Previous studies have shown that intraventricularly or systemically administered FGF-2 reduces the size of cerebral infarcts. Whether endogenous FGF-2 is beneficial for the outcome of cerebral ischemia has not been investigated. We have used mice with a null mutation of the fgf2 gene to explore the relevance of endogenous FGF-2 in brain ischemia. Focal cerebral ischemia was produced by occlusion of the middle cerebral artery (MCAO). We found a 75% increase in infarct volume in fgf2 knock-out mice versus wild type littermates (P < 0.05). This difference in the extent of ischemic damage was observed after 24 h, and correlated with decreased viability in fgf2 mutant mice following MCA occlusion. Increased infarct volume in fgf2 null mice was associated with a loss of induction in hippocampal BDNF and trkB mRNA expression. These findings indicate that signaling through trkB may contribute to ameliorating brain damage following ischemia and that bdnf and trkB may be target genes of FGF-2. Together, our data provide the first evidence that endogenous FGF-2 is important in coping with ischemic brain damage suggesting fgf2 as one crucial target gene for new therapeutic strategies in brain ischemia.
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Author:Irina Kiprianova, Katharina Schindowski, Oliver von Bohlen und Halbach, Sonja Krause, Rosanna Dono, Markus Schwaninger, Klaus Unsicker
URN:urn:nbn:de:hebis:30-34407
DOI:http://dx.doi.org/10.1016/j.expneurol.2004.06.004
ISSN:1090-2430
ISSN:0014-4886
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=15380477
Parent Title (German):Experimental neurology
Publisher:Elsevier ; Academic Press
Place of publication:Amsterdam [u. a.] ; Orlando, Fla.
Document Type:Article
Language:English
Date of Publication (online):2006/11/29
Year of first Publication:2004
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2006/11/29
Tag:BDNF; Cerebral ischemia; FGF-2 KO; Hippocampus; Parietal cortex; trkB
Volume:189
Issue:2
Pagenumber:9
First Page:252
Last Page:260
Note:
Copyright © 2004 Elsevier Inc. All rights reserved.
Source:In: Exp Neurol. 2004 Oct;189(2):252-60. http://www.elsevier.com/locate/issn/0014-4886
HeBIS PPN:191520403
Institutes:Pharmazie
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
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Licence (German):License Logo Veröffentlichungsvertrag für Publikationen

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