Background: Cerebral ischemia and reperfusion (I/R) is a pathological condition that arises by reduction or cessation in cerebral blood flow and return of oxygen and metabolites to brain cells, which cause oxidative damage.

Objectives: The aim of this study was to investigate the neuroprotective effects of Withania coagulans (WC) extract on brain cortex in a rat model of I/R.

Materials and Methods: Thirty-two adult male Wistar rats weighing 280 - 300 g were used in this study. Animals were randomly divided to four groups (n = 8) as follow: sham operated group (I), I/R group (II), WCE500 + I/R (III) and WCE1000 + I/R groups (IV). Pretreatment with WC extract (500, 1000 mg/kg) was done by oral gavage for 30 days and global brain ischemia was induced by the common carotid occlusion for 30 minutes. After 72 hours, the animals were perfused transcardially and then the brains were prepared for histological study (H & E and TUNEL staining).

Results: The I/R group showed a significant increase in pycnotic (dying) neurons and pretreatment with WC at doses of 500 mg/kg and 1000 mg/kg significantly reduced pycnotic and TUNEL positive neurons, in a dose dependent manner in ischemic brain cortex.

Conclusions: Our findings indicated that WC has neuroprotective effects and is able to reduce histopathological alterations and apoptosis in brain cortex I/R in rats.