title: Overexpression of caveolin-1 attenuates brain edema by inhibiting tight junction degradation.
abstract: Cerebral edema from the disruption of the blood-brain barrier (BBB) after cerebral ischemia is a major cause of morbidity and mortality as well as a common event in patients with stroke. Caveolins (Cavs) are thought to regulate BBB functions. Here, we report for the first time that Cav-1 overexpression (OE) decreased brain edema from BBB disruption following ischemic insult. Edema volumes and Cav-1 expression levels were measured following photothrombosis and middle cerebral artery occlusion (MCAO). Endothelial cells that were transduced with a Cav-1 lentiviral expression vector were transplanted into rats. BBB permeability was quantified with Evans blue extravasation. Edema volume was determined from measures of the extravasation area, brain water content, and average fluorescence intensity after Cy5.5 injections. Tight junction (TJ) protein expression was measured with immunoblotting. Cav-1 expression levels and vasogenic brain edema correlated strongly after ischemic insult. Cav-1 expression and BBB disruption peaked 3 d after the MCAO. In addition, intravenous administration of endothelial cells expressing Cav-1 effectively increased the Cav-1 levels 3 d after the MCAO ischemic insult. Importantly, Cav-1 OE ameliorated the vasogenic edema by inhibiting the degradation of TJ protein expression in the acute phase of ischemic stroke. These results suggested that Cav-1 OE protected the integrity of the BBB mainly by preventing the degradation of TJ proteins in rats. These findings need to be confirmed in a clinical setting in human subjects.
authors.affiliation: Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea.|Department of Neurology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Kang-Ho
authors.initials: KH
authors.lastname: Choi
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Neurology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Man-Seok
authors.initials: MS
authors.lastname: Park
authors.affiliation: Department of Neurology, Chonnam National University Medical School, Gwangju, Korea.|Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Eun-Bin
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jung-Kil
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Neurology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Joon-Tae
authors.initials: JT
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Ja-Hae
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Medical Research Institute, Chungang University College of Medicine, Seoul, Korea.
authors.forename: Hong-Joon
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Neurology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Ki-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications; D002199:Capillary Permeability; D051242:Caveolin 1 / Q000378:metabolism*; D015151:Immunoblotting; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000378:metabolism*
chemical_list: D051242:Caveolin 1
keywords: Pathology Section; blood-brain barrier permeability; caveolin; cerebral edema; overexpression