title: Enlarged infarct volume and loss of BDNF mRNA induction following brain ischemia in mice lacking FGF-2.
abstract: 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.
authors.affiliation: Interdisciplinary Center for Neurosciences, Department of Neuroanatomy, University of Heidelberg, D-69120 Heidelberg, Germany. Kipiranova@ana.uni-heidelberg.de
authors.forename: Irina
authors.initials: I
authors.lastname: Kiprianova
authors.forename: Katharina
authors.initials: K
authors.lastname: Schindowski
authors.forename: Oliver
authors.initials: O
authors.lastname: von Bohlen und Halbach
authors.forename: Sonja
authors.initials: S
authors.lastname: Krause
authors.forename: Rosanna
authors.initials: R
authors.lastname: Dono
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaninger
authors.forename: Klaus
authors.initials: K
authors.lastname: Unsicker
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000172:deficiency* / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism*; D020813:Receptor, trkB / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D020813:Receptor, trkB