Abstract
No neuroprotective compounds are clinically available for the treatment of ischemic stroke. The potential salutary effect of pifithrin alpha, a novel-specific inhibitor of the transcription factor p53, administered 1-6 h following focal reversible cerebral ischemia, was investigated. Studies measuring histological, motor, and behavioral outcomes showed significant improvements in pifithrin alpha-treated animals. Pifithrin alpha reduced the number of apoptotic cells in the ischemic brain by inhibiting the binding of p53 to its DNA sites as it reduced the expression of the p53-related gene p21(WAF) without changing the amount of p53 protein itself.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology*
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Benzothiazoles
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Blotting, Western
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Brain / drug effects*
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Brain / metabolism
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Brain / pathology
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Brain Ischemia / drug therapy*
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Brain Ischemia / pathology
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Brain Ischemia / physiopathology
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Cell Count
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Disability Evaluation
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Immunohistochemistry
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Male
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Motor Activity / drug effects
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Neuroprotective Agents / pharmacology
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Rats
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Rats, Sprague-Dawley
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Thiazoles / pharmacology*
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Time Factors
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Toluene / analogs & derivatives*
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Toluene / pharmacology*
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Tumor Suppressor Protein p53 / antagonists & inhibitors*
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Tumor Suppressor Protein p53 / metabolism
Substances
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Benzothiazoles
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Neuroprotective Agents
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Thiazoles
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Tumor Suppressor Protein p53
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Toluene
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pifithrin