PMID- 24938625 OWN - NLM STAT- MEDLINE DCOM- 20150511 LR - 20211021 IS - 1097-4547 (Electronic) IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 92 IP - 11 DP - 2014 Nov TI - Pericyte protection by edaravone after tissue plasminogen activator treatment in rat cerebral ischemia. PG - 1509-19 LID - 10.1002/jnr.23420 [doi] AB - Pericytes play a pivotal role in contraction, mediating inflammation and regulation of blood flow in the brain. In this study, changes of pericytes in the neurovascular unit (NVU) were examined in relation to the effects of exogenous tissue plasminogen activator (tPA) and a free radical scavenger, edaravone. Immunohistochemistry and Western blot analyses showed that the overlap between platelet-derived growth factor receptor beta-positive pericytes and N-acetylglucosamine oligomers (NAGO)-positive endothelial cells increased significantly at 4 days after 90 min of transient middle cerebral artery occlusion (tMCAO). The number of pericytes and the overlap with NAGO decreased with tPA but recovered with edaravone 4 days after tMCAO with proliferation. Thus, tPA treatment damaged pericytes, resulting in the detachment from astrocytes and a decrease in glial cell line-derived neurotrophic factor secretion. However, treatment with edaravone greatly improved tPA-induced damage to pericytes. The present study demonstrates that exogenous tPA strongly damages pericytes and destroys the integrity of the NVU, but edaravone treatment can greatly ameliorate such damage after acute cerebral ischemia in rats. CI - Copyright (c) 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. FAU - Deguchi, Kentaro AU - Deguchi K AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Liu, Ning AU - Liu N FAU - Liu, Wentao AU - Liu W FAU - Omote, Yoshio AU - Omote Y FAU - Kono, Syoichiro AU - Kono S FAU - Yunoki, Taijun AU - Yunoki T FAU - Deguchi, Shoko AU - Deguchi S FAU - Yamashita, Toru AU - Yamashita T FAU - Ikeda, Yoshio AU - Ikeda Y FAU - Abe, Koji AU - Abe K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140617 PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Free Radical Scavengers) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Ki 6896) RN - 0 (Quinolines) RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta) RN - EC 3.4.21.68 (Tissue Plasminogen Activator) RN - S798V6YJRP (Edaravone) RN - T3CHA1B51H (Antipyrine) RN - V956696549 (Acetylglucosamine) SB - IM MH - Acetylglucosamine/metabolism MH - Animals MH - Antipyrine/*analogs & derivatives/pharmacology MH - Astrocytes/drug effects/metabolism MH - Brain Ischemia/*drug therapy/*pathology MH - Cell Proliferation/drug effects MH - Disease Models, Animal MH - Edaravone MH - Free Radical Scavengers/*pharmacology MH - Glial Cell Line-Derived Neurotrophic Factor/metabolism MH - Glial Fibrillary Acidic Protein/metabolism MH - Male MH - Pericytes/*drug effects MH - Quinolines/metabolism MH - Rats MH - Rats, Wistar MH - Receptor, Platelet-Derived Growth Factor beta/metabolism MH - Reperfusion MH - Time Factors MH - Tissue Plasminogen Activator/*adverse effects PMC - PMC4263311 OTO - NOTNLM OT - cerebral ischemia OT - edaravone OT - neurovascular unit OT - pericyte OT - tPA EDAT- 2014/06/19 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/06/19 06:00 PHST- 2014/02/01 00:00 [received] PHST- 2014/04/16 00:00 [revised] PHST- 2014/04/27 00:00 [accepted] PHST- 2014/06/19 06:00 [entrez] PHST- 2014/06/19 06:00 [pubmed] PHST- 2015/05/12 06:00 [medline] AID - 10.1002/jnr.23420 [doi] PST - ppublish SO - J Neurosci Res. 2014 Nov;92(11):1509-19. doi: 10.1002/jnr.23420. Epub 2014 Jun 17.