title: Protection of erythropoietin against ischemic neurovascular unit injuries through the effects of connexin43.
abstract: Erythropoietin (EPO) has protective effects on many neurological diseases, including cerebral ischemia. Here, we aimed to test EPO's effects on ischemic neurovascular unit (NVU) injuries and examine whether the effects were dependent on connexin43 (Cx43) mediated gap junctional intercellular communication (GJIC). We detected the expression of Cx43 and phosphorylation of Cx43 (p-Cx43) at 1 d, 3 d, and 7 d after middle cerebral artery occlusion (MCAO). Meanwhile, we examined the effects of EPO on NVU injuries including neuronal survival, astrocyte activation and regeneration of endothelial cells as well as whether the effects were Cx43 dependent by using multiple inhibitors. We found EPO highly increased p-Cx43, but not total Cx43 at all chosen times. Importantly, EPO led to neurological and blood-brain barrier functions improvement by associating with promotion of angiogenesis as well as reduction of neuronal death, astrocyte activation and neurotoxic substances levels. Moreover, these effects were significantly weakened by the inhibitors blocking GJIC, Cx43 communicative function, phosphorylation and expression, only Cx43 redistribution inhibitor excluded. Our data suggest the protective effects of EPO on NUV injuries are highly associated with the increase of p-Cx43, which improves GJIC to reduce neurotoxic substances.
authors: Department of Neurology, Second Affiliated Hospital, Guangzhou University of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, No. 111 Dade Road, Guangzhou 510120, China.
authors: Ziyi
authors: Z
authors: Zhou
authors: Department of Chinese Integrative Medicine, Huashan Hospital, Fudan University, No.12 Mid. Wulumuqi Road, Shanghai 200040, China.
authors: Xiaobai
authors: X
authors: Wei
authors: Laboratory for Neurological Research of the Institute of Chinese Integrative Medicine, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai 200032, China.
authors: Jun
authors: J
authors: Xiang
authors: Department of Chinese Integrative Medicine, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1 Panfu Road, Guangzhou 510180, China.
authors: Junpeng
authors: J
authors: Gao
authors: Department of Neurology, Second Affiliated Hospital, Guangzhou University of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, No. 111 Dade Road, Guangzhou 510120, China.
authors: Lixin
authors: L
authors: Wang
authors: Department of Neurology, Second Affiliated Hospital, Guangzhou University of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, No. 111 Dade Road, Guangzhou 510120, China.
authors: Jinsong
authors: J
authors: You
authors: Department of Neurology, Second Affiliated Hospital, Guangzhou University of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, No. 111 Dade Road, Guangzhou 510120, China. Electronic address: caiyefeng@126.com.
authors: Yefeng
authors: Y
authors: Cai
authors: Laboratory for Neurological Research of the Institute of Chinese Integrative Medicine, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai 200032, China. Electronic address: caidingfang@163.com.
authors: Dingfang
authors: D
authors: Cai
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D018031:Connexin 43 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004921:Erythropoietin / Q000627:therapeutic use*; D017629:Gap Junctions / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D018698:Glutamic Acid / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017207:Rats, Sprague-Dawley
chemical_list: D018031:Connexin 43; D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; D004921:Erythropoietin; D018698:Glutamic Acid; D002118:Calcium
keywords: Cerebral ischemia; Connexin43; Erythropoietin; Gap junctional intercellular communication; Neurovascular unit