{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:11:05Z","timestamp":1789589465593,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,3,18]],"date-time":"2009-03-18T00:00:00Z","timestamp":1237334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2009,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Cerebral ischemia can activate endogenous reparative processes, such as proliferation of endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ). Most of these new cells die shortly after injury. The purpose of this study was to examine a novel strategy for treatment of stroke at 1 week after injury by enhancing the survival of ischemia\u2010induced endogenous NPCs in SVZ.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult rats were subjected to a 90\u2010minutes middle cerebral artery occlusion. A p53 inhibitor pifithrin\u2010\u03b1 (PFT\u2010\u03b1) was administered to stroke rats from days 6 to 9 after middle cerebral artery occlusion. Locomotor behavior was measured using an activity chamber. Proliferation, survival, migration, and differentiation of endogenous NPCs were examined using quantitative reverse transcription polymerase chain reaction, terminal deoxynucleotidyl transferase\u2010mediated dUTP nick\u2010end labeling, and immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PFT\u2010\u03b1 enhanced functional recovery as assessed by a significant increase in multiple behavioral measurements. Delayed PFT\u2010\u03b1 treatment had no effect on the cell death processes in the lesioned cortical region. However, it enhanced the survival of SVZ progenitor cells, and promoted their proliferation and migration. PFT\u2010\u03b1 inhibited the expression of a p53\u2010dependent proapoptotic gene, termed <jats:italic>PUMA<\/jats:italic> (p53\u2010upregulated modulator of apoptosis), within the SVZ of stroke animals. The enhancement of survival\/proliferation of NPCs was further found in SVZ neurospheres in tissue culture. PFT\u2010\u03b1 dose\u2010dependently increased the number and size of new neurosphere formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Delayed treatment with a p53 inhibitor PFT\u2010\u03b1 is able to modify stroke\u2010induced endogenous neurogenesis and improve the functional recovery in stroke animals. 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