Neuregulin attenuated cerebral ischemia-Creperfusion injury via inhibiting apoptosis and upregulating aquaporin-4.

It has been demonstrated that neuregulin-1beta (NRG-1beta) plays a neuroprotective role in cerebral ischemic injury, however, its defined mechanisms and the perfect treatment window are still elusive. Therefore, we established the animal model of MCAO/R to evaluate cerebral damage. As a result, neurological deficit scores were increased, and a small infarction focus could be seen in ischemic cortex in the control group at ischemic 0.5h/reperfusion 24h. With the duration of ischemia time, deficit scores and infarction sizes obviously elevated in the control group. A large number of positive-apoptotic cells were widespread in the ischemic cortex. Simultaneously, the expression of AQP-4 mRNA and its protein increased. NRG-1beta significantly improved neurological function, decreased the infarction volume, and elevated the expression levels of AQP-4 compared with that in the control group. The therapeutic effect of NRG-1beta was notable, especially at the ischemic 1.0h. These results demonstrate that NRG-1beta might play a neuroprotective effect on cerebral ischemia and reperfusion by inhibiting mitochondrial apoptosis pathway and regulating the activation of AQP-4. The perfect treatment window is at ischemic 1.0h after MCAO.