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Acetazolamide Treatment Prevents Redistribution of Astrocyte Aquaporin 4 after Murine Traumatic Brain Injury
After traumatic brain injury (TBI), multiple ongoing processes contribute to worsening and spreading of the primary injury to create a secondary injury. One major process involves disrupted fluid regulation to create vascular and cytotoxic edema in the affected area. Although understanding of factor...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521570/ https://www.ncbi.nlm.nih.gov/pubmed/31187032 http://dx.doi.org/10.1155/2019/2831501 |
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author | Glober, Nancy K. Sprague, Shane Ahmad, Sadiya Mayfield, Katherine G. Fletcher, Lauren M. Digicaylioglu, Murat H. Sayre, Naomi L. |
author_facet | Glober, Nancy K. Sprague, Shane Ahmad, Sadiya Mayfield, Katherine G. Fletcher, Lauren M. Digicaylioglu, Murat H. Sayre, Naomi L. |
author_sort | Glober, Nancy K. |
collection | PubMed |
description | After traumatic brain injury (TBI), multiple ongoing processes contribute to worsening and spreading of the primary injury to create a secondary injury. One major process involves disrupted fluid regulation to create vascular and cytotoxic edema in the affected area. Although understanding of factors that influence edema is incomplete, the astrocyte water channel Aquaporin 4 (AQP4) has been identified as an important mediator and therefore attractive drug target for edema prevention. The FDA-approved drug acetazolamide has been administered safely to patients for years in the United States. To test whether acetazolamide altered AQP4 function after TBI, we utilized in vitro and in vivo models of TBI. Our results suggest that AQP4 localization is altered after TBI, similar to previously published reports. Treatment with acetazolamide prevented AQP4 reorganization, both in human astrocyte in vitro and in mice in vivo. Moreover, acetazolamide eliminated cytotoxic edema in our in vivo mouse TBI model. Our results suggest a possible clinical role for acetazolamide in the treatment of TBI. |
format | Online Article Text |
id | pubmed-6521570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-65215702019-06-11 Acetazolamide Treatment Prevents Redistribution of Astrocyte Aquaporin 4 after Murine Traumatic Brain Injury Glober, Nancy K. Sprague, Shane Ahmad, Sadiya Mayfield, Katherine G. Fletcher, Lauren M. Digicaylioglu, Murat H. Sayre, Naomi L. Neurosci J Research Article After traumatic brain injury (TBI), multiple ongoing processes contribute to worsening and spreading of the primary injury to create a secondary injury. One major process involves disrupted fluid regulation to create vascular and cytotoxic edema in the affected area. Although understanding of factors that influence edema is incomplete, the astrocyte water channel Aquaporin 4 (AQP4) has been identified as an important mediator and therefore attractive drug target for edema prevention. The FDA-approved drug acetazolamide has been administered safely to patients for years in the United States. To test whether acetazolamide altered AQP4 function after TBI, we utilized in vitro and in vivo models of TBI. Our results suggest that AQP4 localization is altered after TBI, similar to previously published reports. Treatment with acetazolamide prevented AQP4 reorganization, both in human astrocyte in vitro and in mice in vivo. Moreover, acetazolamide eliminated cytotoxic edema in our in vivo mouse TBI model. Our results suggest a possible clinical role for acetazolamide in the treatment of TBI. Hindawi 2019-05-02 /pmc/articles/PMC6521570/ /pubmed/31187032 http://dx.doi.org/10.1155/2019/2831501 Text en Copyright © 2019 Nancy K. Glober et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Glober, Nancy K. Sprague, Shane Ahmad, Sadiya Mayfield, Katherine G. Fletcher, Lauren M. Digicaylioglu, Murat H. Sayre, Naomi L. Acetazolamide Treatment Prevents Redistribution of Astrocyte Aquaporin 4 after Murine Traumatic Brain Injury |
title | Acetazolamide Treatment Prevents Redistribution of Astrocyte Aquaporin 4 after Murine Traumatic Brain Injury |
title_full | Acetazolamide Treatment Prevents Redistribution of Astrocyte Aquaporin 4 after Murine Traumatic Brain Injury |
title_fullStr | Acetazolamide Treatment Prevents Redistribution of Astrocyte Aquaporin 4 after Murine Traumatic Brain Injury |
title_full_unstemmed | Acetazolamide Treatment Prevents Redistribution of Astrocyte Aquaporin 4 after Murine Traumatic Brain Injury |
title_short | Acetazolamide Treatment Prevents Redistribution of Astrocyte Aquaporin 4 after Murine Traumatic Brain Injury |
title_sort | acetazolamide treatment prevents redistribution of astrocyte aquaporin 4 after murine traumatic brain injury |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521570/ https://www.ncbi.nlm.nih.gov/pubmed/31187032 http://dx.doi.org/10.1155/2019/2831501 |
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