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.
Li
Qin
Q
Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, China.
Li
Zhen
Z
Mei
Yuanwu
Y
Guo
Yunliang
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D020890:Neuregulin-1 / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
D051401:Aquaporin 4; D020890:Neuregulin-1; D012333:RNA, Messenger; D051636:X-Linked Inhibitor of Apoptosis Protein; C117467:neuregulin beta