The role of p53-induced apoptosis in cerebral ischemia: effects of the p53 inhibitor pifithrin α

Abstract

No neuroprotective compounds are clinically available for the treatment of ischemic stroke. The potential salutary effect of pifithrin α, 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 α-treated animals. Pifithrin α 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.