Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Glober, Nancy K., Sprague, Shane, Ahmad, Sadiya, Mayfield, Katherine G., Fletcher, Lauren M., Digicaylioglu, Murat H., Sayre, Naomi L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
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
_version_ 1783418989286785024
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
work_keys_str_mv AT globernancyk acetazolamidetreatmentpreventsredistributionofastrocyteaquaporin4aftermurinetraumaticbraininjury
AT spragueshane acetazolamidetreatmentpreventsredistributionofastrocyteaquaporin4aftermurinetraumaticbraininjury
AT ahmadsadiya acetazolamidetreatmentpreventsredistributionofastrocyteaquaporin4aftermurinetraumaticbraininjury
AT mayfieldkatherineg acetazolamidetreatmentpreventsredistributionofastrocyteaquaporin4aftermurinetraumaticbraininjury
AT fletcherlaurenm acetazolamidetreatmentpreventsredistributionofastrocyteaquaporin4aftermurinetraumaticbraininjury
AT digicaylioglumurath acetazolamidetreatmentpreventsredistributionofastrocyteaquaporin4aftermurinetraumaticbraininjury
AT sayrenaomil acetazolamidetreatmentpreventsredistributionofastrocyteaquaporin4aftermurinetraumaticbraininjury