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Abstract Ischemic stroke is a major cause of death and motor disabilities all over the world. It is associated with inflammatory, apoptotic, and oxidative responses. Nateglinide (NAT), an insulinotropic agent used for the treatment of type 2 diabetes mellitus, recently showed potential anti-inflammatory and anti-apoptotic effects. Eprosartan (EPRO) is an angiotensin type 1 receptor (AT1R) antagonist, used in treatment of hypertension which can also block AT1R of the brain and alleviate some of the pathophysiologic basis of stroke.The aim of our study was to elucidate the neuroprotective role of EPRO and NAT in the middle cerebral artery occlusion (MCAO)-induced stroke in rats. Ninety six male rats were divided to 6 groups (n = 16 in each group): the sham-operated group, sham receiving EPRO (60 mg/kg/day, p.o) group, sham receiving NAT (50 mg/kg/day, p.o) group, ischemia/reperfusion (IR) group, IR receiving EPRO group (60 mg/kg/day, p.o) and IR receiving NAT group (50 mg/kg/day, p.o). MCAO caused deficits in the motor functions of the rats with an increase of inflammation and apoptotic biomarkers has been observed in IR rats. Pretreatment with EPRO or NAT preserved some of the rats{u2019} behavioral and motor functions |