Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a...

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Main Authors:	Sturdivant, Nasya M., Smith, Sean G., Ali, Syed F., Wolchok, Jeffrey C., Balachandran, Kartik
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022024/

id	pubmed-5022024
recordtype	oai_dc
spelling	pubmed-50220242016-09-20 Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury Sturdivant, Nasya M. Smith, Sean G. Ali, Syed F. Wolchok, Jeffrey C. Balachandran, Kartik Article Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality. Nature Publishing Group 2016-09-14 /pmc/articles/PMC5022024/ /pubmed/27623738 http://dx.doi.org/10.1038/srep33330 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Sturdivant, Nasya M. Smith, Sean G. Ali, Syed F. Wolchok, Jeffrey C. Balachandran, Kartik
spellingShingle	Sturdivant, Nasya M. Smith, Sean G. Ali, Syed F. Wolchok, Jeffrey C. Balachandran, Kartik Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury
author_facet	Sturdivant, Nasya M. Smith, Sean G. Ali, Syed F. Wolchok, Jeffrey C. Balachandran, Kartik
author_sort	Sturdivant, Nasya M.
title	Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury
title_short	Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury
title_full	Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury
title_fullStr	Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury
title_full_unstemmed	Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury
title_sort	acetazolamide mitigates astrocyte cellular edema following mild traumatic brain injury
description	Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022024/
_version_	1613650799301230592

Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

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