Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 24, Issue 4, Pages 441-448Publisher
SAGE PUBLICATIONS INC
DOI: 10.1097/00004647-200404000-00009
Keywords
focal cerebral ischemia; neural stem cells; subventricular zone; migration; neuro-genesis; rats
Categories
Funding
- NHLBI NIH HHS [R01HL 64766] Funding Source: Medline
- NINDS NIH HHS [P01 NS42345, P01 NS23393, R01NS38292] Funding Source: Medline
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Stroke increases neurogenesis. The authors investigated whether neural stem cells or progenitor cells in the adult subventricular zone (SVZ) of rats contribute to stroke-induced increase in neurogenesis. After induction of stroke in rats, the numbers of cells immunoreactive to doublecortin, a marker for immature neurons, increased in the ipsilateral SVZ and striatum. Infusion of an antimitotic agent (cytosine-beta-D-arabiofuranoside, Ara-C) onto the ipsilateral cortex eliminated more than 98% of actively proliferating cells in the SVZ and doublecortin-positive cells in the ipsilateral striatum. However, doublecortin-positive cells rapidly replenished after antimitotic agent depletion of actively proliferating, cells. Depleting the numbers of actively proliferating cells in vivo had no effect oil the numbers of neurospheres formed in vitro, yet the numbers of neurospheres derived from stroke rats significantly (P < 0.05) increased. Neurospheres derived from stroke rats self-renewed and differentiated into neurons and glia. In addition, doublecortin-positive cells generated in the SVZ migrated in a chainlike structure toward ischemic striatum. These findings indicate that in the adult stroke brain, increases in recruitment of neural stem cells contribute to stroke-induced neurogenesis, and that newly generated neurons migrate from the SVZ to the ischemic striatum.
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