Long-lasting regeneration after ischemia in the cerebral cortex.
OBJECTIVE
Because fibroblast growth factor 2 is a mitogen for central nervous system stem cells, we explored whether long-term fibroblast growth factor 2 delivery to the brain can improve functional outcome and induce cortical neurogenesis after ischemia.


METHODS
Rats underwent permanent distal middle cerebral artery occlusion resulting in an ischemic injury limited to the cortex. We used an adeno-associated virus transfection system to induce long-term fibroblast growth factor 2 expression and monitored behavioral and histological changes.


RESULTS
Treatment increased the number of proliferating cells and improved motor behavior. Neurogenesis continued throughout 90 days after the ischemia, and the occurrence of newly generated cells with characteristics of neural precursors and immature neurons was most evident 90 days after treatment.


CONCLUSIONS
Focal cortical ischemia elicits an ongoing neurogenic response that can be enhanced with fibroblast growth factor 2 leading to improved functional outcome.
Leker
Ronen R
RR
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. leker@cc.huji.ac.il
Soldner
Frank
F
Velasco
Ivan
I
Gavin
Denise K
DK
Androutsellis-Theotokis
Andreas
A
McKay
Ronald D G
RD
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D020520:Brain Infarction / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D002545:Brain Ischemia / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009416:Nerve Regeneration / Q000235:genetics* / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D020127:Recovery of Function / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome
D015415:Biomarkers; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine