title: Urokinase-type plasminogen activator receptor (uPAR) augments brain damage in a murine model of ischemic stroke.
abstract: Urokinase-type plasminogen activator receptor (uPAR) is a key component of the plasminogen activation system at the cell surface. Recent studies showed that uPAR is expressed in the ischemic damaged brain, suggesting its involvement in brain damage. In this study, we evaluated the role of uPAR in ischemic brain damage induced by permanent middle cerebral artery (MCA) occlusion in mice with genetic deficiency of uPAR (uPAR(-/-)) or of uPA (uPA(-/-)). Brain damage at 3 days was smaller in uPAR(-/-) mice (4.5+/-1.0mm(3)) than in littermate wild-type mice (uPAR(+/+)) (9.1+/-1.8mm(3), p<0.05), whereas it was comparable in uPA(-/-) (8.0+/-4.1mm(3)) and uPA(+/+) (6.9+/-2.6mm(3)) mice. uPAR expression was upregulated in the ipsilateral cerebral cortex within 12h, and remained elevated for up to 3 days. At 1 or 2 days after MCA occlusion, uPAR expression was selectively localized in vessels at the border of the damaged area. These findings suggest that uPAR expressed by endothelial cells augments the ischemic brain damage via a uPA-independent mechanism.
authors.affiliation: Department of Physiology, Kinki University School of Medicine, Ohnohigashi 377-2, Osakasayama, Osaka 589-8511, Japan. nagainnn@me.kindai.ac.jp
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nagai
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okada
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kawao
authors.forename: Chikako
authors.initials: C
authors.lastname: Ishida
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ueshima
authors.forename: Desire
authors.initials: D
authors.lastname: Collen
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014568:Urokinase-Type Plasminogen Activator