title: Regulation of Caveolin-1 Expression Determines Early Brain Edema After Experimental Focal Cerebral Ischemia.
abstract: Most patients with cerebral infarction die of brain edema because of the breakdown of the blood-brain barrier (BBB) in ischemic tissue. Caveolins (a group of proteins) are key modulators of vascular permeability; however, a direct role of caveolin-1 (Cav-1) in the regulation of BBB permeability during ischemic injury has yet to be identified.
  
  
  
  Cav-1 expression was measured by immunoblotting after photothrombotic ischemia. A direct functional role of Cav-1 in cerebral edema and BBB permeability during cerebral ischemia was investigated by genetic manipulation (gene disruption and re-expression) of Cav-1 protein expression in mice.
  
  
  
  There was a significant correlation between the extent of BBB disruption and the Cav-1 expression. In Cav-1-deficient (Cav-1(-/-)) mice, the extent of BBB disruption after cerebral ischemia was increased compared with wild-type (Cav-1(+/+)) mice, whereas the increase in cerebral edema volume was ameliorated by lentiviral-mediated re-expression of Cav-1. Furthermore, Cav-1(-/-) mice had significantly higher degradation of tight junction proteins and proteolytic activity of matrix metalloproteinase than Cav-1(+/+) mice. Conversely, re-expression of Cav-1 in Cav-1(-/-) mice restored tight junction protein expression and reduced matrix metalloproteinase proteolytic activity.
  
  
  
  These results indicate that Cav-1 is a critical determinant of BBB permeability. Strategies for regulating Cav-1 represent a novel therapeutic approach to controlling BBB disruption and subsequent neurological deterioration during cerebral ischemia.
authors.affiliation: From the Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea (K.-H.C.); Departments of Neurology (K.-H.C., M.-S.P., J.-T.K., K.-H.C.), Forensic Medicine (H.-S.K.), Nuclear Medicine (J.-H.K.), Biochemistry and Molecular Biology (K.-A.C.), and Pathology, Chonnam National University Medical School, Gwangju, Korea (M.-C.L.); and Medical Research Institute, Chungang University College of Medicine, Seoul, Korea (H.-J.L.).
authors.forename: Kang-Ho
authors.initials: KH
authors.lastname: Choi
authors.affiliation: From the Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea (K.-H.C.); Departments of Neurology (K.-H.C., M.-S.P., J.-T.K., K.-H.C.), Forensic Medicine (H.-S.K.), Nuclear Medicine (J.-H.K.), Biochemistry and Molecular Biology (K.-A.C.), and Pathology, Chonnam National University Medical School, Gwangju, Korea (M.-C.L.); and Medical Research Institute, Chungang University College of Medicine, Seoul, Korea (H.-J.L.). veritas@jnu.ac.kr mspark@chonnam.ac.kr.
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Kim
authors.affiliation: From the Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea (K.-H.C.); Departments of Neurology (K.-H.C., M.-S.P., J.-T.K., K.-H.C.), Forensic Medicine (H.-S.K.), Nuclear Medicine (J.-H.K.), Biochemistry and Molecular Biology (K.-A.C.), and Pathology, Chonnam National University Medical School, Gwangju, Korea (M.-C.L.); and Medical Research Institute, Chungang University College of Medicine, Seoul, Korea (H.-J.L.). veritas@jnu.ac.kr mspark@chonnam.ac.kr.
authors.forename: Man-Seok
authors.initials: MS
authors.lastname: Park
authors.affiliation: From the Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea (K.-H.C.); Departments of Neurology (K.-H.C., M.-S.P., J.-T.K., K.-H.C.), Forensic Medicine (H.-S.K.), Nuclear Medicine (J.-H.K.), Biochemistry and Molecular Biology (K.-A.C.), and Pathology, Chonnam National University Medical School, Gwangju, Korea (M.-C.L.); and Medical Research Institute, Chungang University College of Medicine, Seoul, Korea (H.-J.L.).
authors.forename: Joon-Tae
authors.initials: JT
authors.lastname: Kim
authors.affiliation: From the Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea (K.-H.C.); Departments of Neurology (K.-H.C., M.-S.P., J.-T.K., K.-H.C.), Forensic Medicine (H.-S.K.), Nuclear Medicine (J.-H.K.), Biochemistry and Molecular Biology (K.-A.C.), and Pathology, Chonnam National University Medical School, Gwangju, Korea (M.-C.L.); and Medical Research Institute, Chungang University College of Medicine, Seoul, Korea (H.-J.L.).
authors.forename: Ja-Hae
authors.initials: JH
authors.lastname: Kim
authors.affiliation: From the Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea (K.-H.C.); Departments of Neurology (K.-H.C., M.-S.P., J.-T.K., K.-H.C.), Forensic Medicine (H.-S.K.), Nuclear Medicine (J.-H.K.), Biochemistry and Molecular Biology (K.-A.C.), and Pathology, Chonnam National University Medical School, Gwangju, Korea (M.-C.L.); and Medical Research Institute, Chungang University College of Medicine, Seoul, Korea (H.-J.L.).
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Cho
authors.affiliation: From the Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea (K.-H.C.); Departments of Neurology (K.-H.C., M.-S.P., J.-T.K., K.-H.C.), Forensic Medicine (H.-S.K.), Nuclear Medicine (J.-H.K.), Biochemistry and Molecular Biology (K.-A.C.), and Pathology, Chonnam National University Medical School, Gwangju, Korea (M.-C.L.); and Medical Research Institute, Chungang University College of Medicine, Seoul, Korea (H.-J.L.).
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Lee
authors.affiliation: From the Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea (K.-H.C.); Departments of Neurology (K.-H.C., M.-S.P., J.-T.K., K.-H.C.), Forensic Medicine (H.-S.K.), Nuclear Medicine (J.-H.K.), Biochemistry and Molecular Biology (K.-A.C.), and Pathology, Chonnam National University Medical School, Gwangju, Korea (M.-C.L.); and Medical Research Institute, Chungang University College of Medicine, Seoul, Korea (H.-J.L.).
authors.forename: Hong-Joon
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: From the Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea (K.-H.C.); Departments of Neurology (K.-H.C., M.-S.P., J.-T.K., K.-H.C.), Forensic Medicine (H.-S.K.), Nuclear Medicine (J.-H.K.), Biochemistry and Molecular Biology (K.-A.C.), and Pathology, Chonnam National University Medical School, Gwangju, Korea (M.-C.L.); and Medical Research Institute, Chungang University College of Medicine, Seoul, Korea (H.-J.L.).
authors.forename: Ki-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001929:Brain Edema / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout
chemical_list: C495541:Cav1 protein, mouse; D051242:Caveolin 1
keywords: blood-brain barrier; brain edema; brain ischemia; caveolin-1; tight junction proteins