Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral Ischemia
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 th...
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doaj-6e73607ec683480698a80e245517f70b2020-11-25T03:30:16ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-05-01810.3389/fcell.2020.00371547014Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral IschemiaIrina Filchenko0Irina Filchenko1Irina Filchenko2Camille Blochet3Camille Blochet4Lara Buscemi5Lara Buscemi6Melanie Price7Melanie Price8Jerome Badaut9Jerome Badaut10Lorenz Hirt11Lorenz Hirt12Service of Neurology, Department of Clinical Neurosciences, CHUV, Lausanne, SwitzerlandNorth-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg, RussiaDepartment of Fundamental Neurosciences, University of Lausanne, Lausanne, SwitzerlandService of Neurology, Department of Clinical Neurosciences, CHUV, Lausanne, SwitzerlandDepartment of Fundamental Neurosciences, University of Lausanne, Lausanne, SwitzerlandService of Neurology, Department of Clinical Neurosciences, CHUV, Lausanne, SwitzerlandDepartment of Fundamental Neurosciences, University of Lausanne, Lausanne, SwitzerlandService of Neurology, Department of Clinical Neurosciences, CHUV, Lausanne, SwitzerlandDepartment of Fundamental Neurosciences, University of Lausanne, Lausanne, SwitzerlandBrain Molecular Imaging Lab, CNRS UMR 5287, INCIA, University of Bordeaux, Bordeaux, FranceBasic Science Department, Loma Linda University School of Medicine, Loma Linda, CA, United StatesService of Neurology, Department of Clinical Neurosciences, CHUV, Lausanne, SwitzerlandDepartment of Fundamental Neurosciences, University of Lausanne, Lausanne, SwitzerlandEdema 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.Significance StatementSevere 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.https://www.frontiersin.org/article/10.3389/fcell.2020.00371/fullstrokeaquaporin (AQP)-4caveolin-1 (CAV1)recoveryastrocyctesendfeet |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Irina Filchenko Irina Filchenko Irina Filchenko Camille Blochet Camille Blochet Lara Buscemi Lara Buscemi Melanie Price Melanie Price Jerome Badaut Jerome Badaut Lorenz Hirt Lorenz Hirt |
spellingShingle |
Irina Filchenko Irina Filchenko Irina Filchenko Camille Blochet Camille Blochet Lara Buscemi Lara Buscemi Melanie Price Melanie Price Jerome Badaut Jerome Badaut Lorenz Hirt Lorenz Hirt Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral Ischemia Frontiers in Cell and Developmental Biology stroke aquaporin (AQP)-4 caveolin-1 (CAV1) recovery astrocyctes endfeet |
author_facet |
Irina Filchenko Irina Filchenko Irina Filchenko Camille Blochet Camille Blochet Lara Buscemi Lara Buscemi Melanie Price Melanie Price Jerome Badaut Jerome Badaut Lorenz Hirt Lorenz Hirt |
author_sort |
Irina Filchenko |
title |
Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral Ischemia |
title_short |
Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral Ischemia |
title_full |
Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral Ischemia |
title_fullStr |
Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral Ischemia |
title_full_unstemmed |
Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral Ischemia |
title_sort |
caveolin-1 regulates perivascular aquaporin-4 expression after cerebral ischemia |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2020-05-01 |
description |
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.Significance StatementSevere 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. |
topic |
stroke aquaporin (AQP)-4 caveolin-1 (CAV1) recovery astrocyctes endfeet |
url |
https://www.frontiersin.org/article/10.3389/fcell.2020.00371/full |
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