Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral Ischemia.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_FEC7C7EC2CCC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral Ischemia.
Journal
Frontiers in cell and developmental biology
Author(s)
Filchenko I., Blochet C., Buscemi L., Price M., Badaut J., Hirt L.
ISSN
2296-634X (Print)
ISSN-L
2296-634X
Publication state
Published
Issued date
2020
Peer-reviewed
Oui
Volume
8
Pages
371
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Edema is a hallmark of many brain disorders including stroke. During vasogenic edema, blood-brain barrier (BBB) permeability increases, contributing to the entry of plasma proteins followed by water. Caveolae and caveolin-1 (Cav-1) are involved in these BBB permeability changes. The expression of the aquaporin-4 (AQP4) water channel relates to brain swelling, however, its regulation is poorly understood. Here we tested whether Cav-1 regulates AQP4 expression in the perivascular region after brain ischemia in mice. We showed that Cav-1 knockout mice had enhanced hemispheric swelling and decreased perivascular AQP4 expression in perilesional and contralateral cortical regions compared to wild-type. Glial fibrillary acidic protein-positive astrocytes displayed less branching and ramification in Cav-1 knockout mice compared to wild-type animals. There was a positive correlation between the area of perivascular AQP4-immunolabelling and branch length of Glial fibrillary acidic protein-positive astrocytes in wild-type mice, not seen in Cav-1 knockout mice. In summary, we show for the first time that loss of Cav-1 results in decreased AQP4 expression and impaired perivascular AQP4 covering after cerebral ischemia associated with altered reactive astrocyte morphology and enhanced brain swelling. Therapeutic approaches targeting Cav-1 may provide new opportunities for improving stroke outcome.
Severe brain edema worsens outcome in stroke patients. Available treatments for stroke-related edema are not efficient and molecular and cellular mechanisms are poorly understood. Cellular water channels, aquaporins (AQPs), are mainly expressed in astrocytes in the brain and play a key role in water movements and cerebral edema, while endothelial caveolins have been suggested to play a role in vasogenic edema. Here we used an integrative approach to study possible interaction between AQP4 and caveolin-1 (Cav-1) after stroke. Absence of Cav-1 was associated with perivascular changes in AQP4 expression and enhanced brain swelling at 3 days after cerebral ischemia. The present work indicates a direct or indirect effect of Cav-1 on perivascular AQP4, which may lead to novel edema therapy.
Keywords
aquaporin (AQP)-4, astrocyctes, caveolin-1 (CAV1), endfeet, recovery, stroke
Pubmed
Web of science
Open Access
Yes
Create date
25/06/2020 15:25
Last modification date
12/01/2022 7:15
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