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Heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling
INTRODUCTION: Ischemic stroke, a major cause of mortality, is frequently accompanied by life-threatening cerebral edema. Aquaporin-4 (Aqp4), an astrocytic transmembrane water channel, is an important molecular contributor to cerebral edema formation. Past studies of Aqp4 expression and localization...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588314/ https://www.ncbi.nlm.nih.gov/pubmed/26419740 http://dx.doi.org/10.1186/s40478-015-0239-6 |
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author | Stokum, Jesse A. Mehta, Rupal I. Ivanova, Svetlana Yu, Edward Gerzanich, Volodymyr Simard, J. Marc |
author_facet | Stokum, Jesse A. Mehta, Rupal I. Ivanova, Svetlana Yu, Edward Gerzanich, Volodymyr Simard, J. Marc |
author_sort | Stokum, Jesse A. |
collection | PubMed |
description | INTRODUCTION: Ischemic stroke, a major cause of mortality, is frequently accompanied by life-threatening cerebral edema. Aquaporin-4 (Aqp4), an astrocytic transmembrane water channel, is an important molecular contributor to cerebral edema formation. Past studies of Aqp4 expression and localization after ischemia examined grey matter exclusively. However, as white matter astrocytes differ developmentally, physiologically, and molecularly from grey matter astrocytes, we hypothesized that functionally important regional heterogeneity exists in Aqp4 expression and subcellular localization following cerebral ischemia. RESULTS: Subcellular localization of Aqp4 was compared between cortical and white matter astrocytes in postmortem specimens of patients with focal ischemic stroke versus controls. Subcellular localization and expression of Aqp4 was examined in rats subjected to experimental stroke. Volumetric analysis was performed on the cortex and white matter of rats subjected to experimental stroke. Following cerebral ischemia, cortical astrocytes exhibited reduced perivascular Aqp4 and unchanged Aqp4 protein abundance. In contrast, white matter astrocytes exhibited increased perivascular and plasmalemmal Aqp4 and a 2.2- to 6.2-fold increase in Aqp4 isoform abundance. Ischemic white matter swelled by approximately 40 %, while cortex swelled by approximately 9 %. CONCLUSIONS: The findings reported here raise the possibility that cerebral white matter may play a heretofore underappreciated role in the formation of cerebral edema following ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0239-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4588314 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45883142015-10-01 Heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling Stokum, Jesse A. Mehta, Rupal I. Ivanova, Svetlana Yu, Edward Gerzanich, Volodymyr Simard, J. Marc Acta Neuropathol Commun Research INTRODUCTION: Ischemic stroke, a major cause of mortality, is frequently accompanied by life-threatening cerebral edema. Aquaporin-4 (Aqp4), an astrocytic transmembrane water channel, is an important molecular contributor to cerebral edema formation. Past studies of Aqp4 expression and localization after ischemia examined grey matter exclusively. However, as white matter astrocytes differ developmentally, physiologically, and molecularly from grey matter astrocytes, we hypothesized that functionally important regional heterogeneity exists in Aqp4 expression and subcellular localization following cerebral ischemia. RESULTS: Subcellular localization of Aqp4 was compared between cortical and white matter astrocytes in postmortem specimens of patients with focal ischemic stroke versus controls. Subcellular localization and expression of Aqp4 was examined in rats subjected to experimental stroke. Volumetric analysis was performed on the cortex and white matter of rats subjected to experimental stroke. Following cerebral ischemia, cortical astrocytes exhibited reduced perivascular Aqp4 and unchanged Aqp4 protein abundance. In contrast, white matter astrocytes exhibited increased perivascular and plasmalemmal Aqp4 and a 2.2- to 6.2-fold increase in Aqp4 isoform abundance. Ischemic white matter swelled by approximately 40 %, while cortex swelled by approximately 9 %. CONCLUSIONS: The findings reported here raise the possibility that cerebral white matter may play a heretofore underappreciated role in the formation of cerebral edema following ischemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0239-6) contains supplementary material, which is available to authorized users. BioMed Central 2015-09-30 /pmc/articles/PMC4588314/ /pubmed/26419740 http://dx.doi.org/10.1186/s40478-015-0239-6 Text en © Stokum et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Stokum, Jesse A. Mehta, Rupal I. Ivanova, Svetlana Yu, Edward Gerzanich, Volodymyr Simard, J. Marc Heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling |
title | Heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling |
title_full | Heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling |
title_fullStr | Heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling |
title_full_unstemmed | Heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling |
title_short | Heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling |
title_sort | heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588314/ https://www.ncbi.nlm.nih.gov/pubmed/26419740 http://dx.doi.org/10.1186/s40478-015-0239-6 |
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