Ziprasidone attenuates brain injury after focal cerebral ischemia induced by middle cerebral artery occlusion in rats

Ziprasidone is an atypical antipsychotic drug used for the treatment of schizophrenia. Recent studies have reported that atypical antipsychotics have neuroprotective effects against brain injury. In the present study, the effect of ziprasidone on ischemic brain injury was investigated. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in rats. All the animals experienced ischemia for 1 h and then underwent reperfusion. The infarct size induced by MCAO was significantly reduced in the animals that received acute treatment with 5 mg/kg ziprasidone and subchronic treatment with 2.5 mg/kg ziprasidone for 7 days compared with that in the vehicle-treated animals. The acute treatment with ziprasidone significantly improved neurological functions, as measured by the modified neurological severity score, in a dose-dependent manner. The subchronic treatment produced more rapid recovery from functional deficits than the vehicle treatment. The immunohistochemical investigation revealed that the subchronic treatment prevented severe loss of neuronal marker intensity and attenuated the increased in microglial marker intensity in the infarcted cortical area. These results suggest that ziprasidone has neuroprotective effects in a rat model of ischemic stroke and provide new insight for its clinical applications.

► An acute treatment of ziprasidone reduced ischemic infarct size. ► A treatment of ziprasidone for 7 days reduced ischemic infarct size. ► A treatment of ziprasidone reduced accumulation of microglia in the infarct area. ► A treatment of ziprasidone facilitated functional recovery after MCAO.