PMID- 25684187 OWN - NLM STAT- MEDLINE DCOM- 20150512 LR - 20181020 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 458 IP - 3 DP - 2015 Mar 13 TI - Protection of erythropoietin against ischemic neurovascular unit injuries through the effects of connexin43. PG - 656-662 LID - S0006-291X(15)00236-3 [pii] LID - 10.1016/j.bbrc.2015.02.020 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Zhou, Ziyi AU - Zhou Z AD - 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. FAU - Wei, Xiaobai AU - Wei X AD - Department of Chinese Integrative Medicine, Huashan Hospital, Fudan University, No.12 Mid. Wulumuqi Road, Shanghai 200040, China. FAU - Xiang, Jun AU - Xiang J AD - Laboratory for Neurological Research of the Institute of Chinese Integrative Medicine, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai 200032, China. FAU - Gao, Junpeng AU - Gao J AD - Department of Chinese Integrative Medicine, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1 Panfu Road, Guangzhou 510180, China. FAU - Wang, Lixin AU - Wang L AD - 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. FAU - You, Jinsong AU - You J AD - 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. FAU - Cai, Yefeng AU - Cai Y AD - 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. FAU - Cai, Dingfang AU - Cai D AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150213 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Connexin 43) RN - 0 (Neuroprotective Agents) RN - 0 (RNA, Small Interfering) RN - 11096-26-7 (Erythropoietin) RN - 3KX376GY7L (Glutamic Acid) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/metabolism MH - Cell Communication/drug effects MH - Connexin 43/analysis/*genetics/metabolism MH - Erythropoietin/*therapeutic use MH - Gap Junctions/drug effects/genetics/metabolism/pathology MH - Gene Expression MH - Glutamic Acid/metabolism MH - Infarction, Middle Cerebral Artery/*drug therapy/genetics/metabolism/pathology MH - Male MH - Neurons/drug effects/metabolism/pathology MH - Neuroprotective Agents/*therapeutic use MH - RNA Interference MH - RNA, Small Interfering/genetics MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Cerebral ischemia OT - Connexin43 OT - Erythropoietin OT - Gap junctional intercellular communication OT - Neurovascular unit EDAT- 2015/02/17 06:00 MHDA- 2015/05/13 06:00 CRDT- 2015/02/17 06:00 PHST- 2015/01/29 00:00 [received] PHST- 2015/02/04 00:00 [accepted] PHST- 2015/02/17 06:00 [entrez] PHST- 2015/02/17 06:00 [pubmed] PHST- 2015/05/13 06:00 [medline] AID - S0006-291X(15)00236-3 [pii] AID - 10.1016/j.bbrc.2015.02.020 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2015 Mar 13;458(3):656-662. doi: 10.1016/j.bbrc.2015.02.020. Epub 2015 Feb 13.