HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Delayed treatment with a p53 inhibitor enhances recovery in stroke brain.

AbstractOBJECTIVE:
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:
Adult rats were subjected to a 90-minutes middle cerebral artery occlusion. A p53 inhibitor pifithrin-alpha (PFT-alpha) 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-mediated dUTP nick-end labeling, and immunohistochemistry.
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:
Delayed treatment with a p53 inhibitor PFT-alpha is able to modify stroke-induced endogenous neurogenesis and improve the functional recovery in stroke animals.
AuthorsYu Luo, Chi-Chung Kuo, Hui Shen, Jenny Chou, Nigel H Greig, Barry J Hoffer, Yun Wang
JournalAnnals of neurology (Ann Neurol) Vol. 65 Issue 5 Pg. 520-30 (May 2009) ISSN: 1531-8249 [Electronic] United States
PMID19475672 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References
  • Benzothiazoles
  • Glial Fibrillary Acidic Protein
  • Proliferating Cell Nuclear Antigen
  • Tumor Suppressor Protein p53
  • Toluene
  • pifithrin
  • Bromodeoxyuridine
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: