on November 22, 2006
Published online before print November 22, 2006, doi: 10.1161/01.STR.0000252156.65953.a9
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Submitted on July 23, 2006
From the Laboratory of Molecular Biology (R.R.-L., R.S., I.V., D.K.G., A.A.-T., R.D.G.M.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; and the Department of Neurology (R.R.L.), Hadassah University Medical Center, Jerusalem, Israel. * To whom correspondence should be addressed. E-mail: leker{at}cc.huji.ac.il.
Background and Purpose--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.
Revised on August 23, 2006
Accepted on September 10, 2006
Long-Lasting Regeneration After Ischemia in the Cerebral Cortex
Ronen R. Leker MD*;
Key words: growth factors • neural progenitors • neural stem cells • neurogenesis • stroke