Abstract | OBJECTIVE:
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-induced endogenous NPCs in SVZ. METHODS: RESULTS:
PFT-alpha enhanced functional recovery as assessed by a significant increase in multiple behavioral measurements. Delayed PFT-alpha 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-alpha inhibited the expression of a p53-dependent proapoptotic gene, termed PUMA (p53-upregulated 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-alpha dose-dependently increased the number and size of new neurosphere formation. INTERPRETATION:
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Authors | Yu Luo, Chi-Chung Kuo, Hui Shen, Jenny Chou, Nigel H Greig, Barry J Hoffer, Yun Wang |
Journal | Annals of neurology
(Ann Neurol)
Vol. 65
Issue 5
Pg. 520-30
(May 2009)
ISSN: 1531-8249 [Electronic] United States |
PMID | 19475672
(Publication Type: Journal Article, Research Support, N.I.H., Intramural)
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Chemical References |
- Benzothiazoles
- Glial Fibrillary Acidic Protein
- Proliferating Cell Nuclear Antigen
- Tumor Suppressor Protein p53
- Toluene
- pifithrin
- Bromodeoxyuridine
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Topics |
- Adult Stem Cells
(drug effects)
- Analysis of Variance
- Animals
- Benzothiazoles
(pharmacology)
- Brain
(drug effects, pathology, physiopathology)
- Bromodeoxyuridine
(metabolism)
- Cell Differentiation
(drug effects)
- Cell Movement
(drug effects)
- Cells, Cultured
- Cerebral Ventricles
(pathology)
- Disease Models, Animal
- Embryo, Mammalian
- Glial Fibrillary Acidic Protein
(metabolism)
- In Situ Nick-End Labeling
(methods)
- Infarction, Middle Cerebral Artery
(drug therapy, pathology)
- Male
- Mice
- Motor Activity
(drug effects)
- Neurogenesis
(drug effects)
- Proliferating Cell Nuclear Antigen
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Recovery of Function
(drug effects)
- Time Factors
- Toluene
(analogs & derivatives, pharmacology)
- Tumor Suppressor Protein p53
(antagonists & inhibitors)
- Up-Regulation
(drug effects)
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