title: Pericyte protection by edaravone after tissue plasminogen activator treatment in rat cerebral ischemia.
abstract: 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 β-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.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Deguchi
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Wentao
authors.initials: W
authors.lastname: Liu
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Omote
authors.forename: Syoichiro
authors.initials: S
authors.lastname: Kono
authors.forename: Taijun
authors.initials: T
authors.lastname: Yunoki
authors.forename: Shoko
authors.initials: S
authors.lastname: Deguchi
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D020286:Pericytes / Q000187:drug effects*; D011804:Quinolines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015424:Reperfusion; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000009:adverse effects*
chemical_list: D016166:Free Radical Scavengers; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; C116120:Ki 6896; D011804:Quinolines; D020797:Receptor, Platelet-Derived Growth Factor beta; D010959:Tissue Plasminogen Activator; D000077553:Edaravone; D000983:Antipyrine; D000117:Acetylglucosamine
keywords: cerebral ischemia; edaravone; neurovascular unit; pericyte; tPA