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Blast shockwaves propagate Ca(2+) activity via purinergic astrocyte networks in human central nervous system cells

In a recent study of the pathophysiology of mild, blast-induced traumatic brain injury (bTBI) the exposure of dissociated, central nervous system (CNS) cells to simulated blast resulted in propagating waves of elevated intracellular Ca(2+). Here we show, in dissociated human CNS cultures, that these...

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Autores principales: Ravin, Rea, Blank, Paul S., Busse, Brad, Ravin, Nitay, Vira, Shaleen, Bezrukov, Ludmila, Waters, Hang, Guerrero-Cazares, Hugo, Quinones-Hinojosa, Alfredo, Lee, Philip R., Fields, R. Douglas, Bezrukov, Sergey M., Zimmerberg, Joshua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861979/
https://www.ncbi.nlm.nih.gov/pubmed/27162174
http://dx.doi.org/10.1038/srep25713
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author Ravin, Rea
Blank, Paul S.
Busse, Brad
Ravin, Nitay
Vira, Shaleen
Bezrukov, Ludmila
Waters, Hang
Guerrero-Cazares, Hugo
Quinones-Hinojosa, Alfredo
Lee, Philip R.
Fields, R. Douglas
Bezrukov, Sergey M.
Zimmerberg, Joshua
author_facet Ravin, Rea
Blank, Paul S.
Busse, Brad
Ravin, Nitay
Vira, Shaleen
Bezrukov, Ludmila
Waters, Hang
Guerrero-Cazares, Hugo
Quinones-Hinojosa, Alfredo
Lee, Philip R.
Fields, R. Douglas
Bezrukov, Sergey M.
Zimmerberg, Joshua
author_sort Ravin, Rea
collection PubMed
description In a recent study of the pathophysiology of mild, blast-induced traumatic brain injury (bTBI) the exposure of dissociated, central nervous system (CNS) cells to simulated blast resulted in propagating waves of elevated intracellular Ca(2+). Here we show, in dissociated human CNS cultures, that these calcium waves primarily propagate through astrocyte-dependent, purinergic signaling pathways that are blocked by P2 antagonists. Human, compared to rat, astrocytes had an increased calcium response and prolonged calcium wave propagation kinetics, suggesting that in our model system rat CNS cells are less responsive to simulated blast. Furthermore, in response to simulated blast, human CNS cells have increased expressions of a reactive astrocyte marker, glial fibrillary acidic protein (GFAP) and a protease, matrix metallopeptidase 9 (MMP-9). The conjoint increased expression of GFAP and MMP-9 and a purinergic ATP (P2) receptor antagonist reduction in calcium response identifies both potential mechanisms for sustained changes in brain function following primary bTBI and therapeutic strategies targeting abnormal astrocyte activity.
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spelling pubmed-48619792016-05-23 Blast shockwaves propagate Ca(2+) activity via purinergic astrocyte networks in human central nervous system cells Ravin, Rea Blank, Paul S. Busse, Brad Ravin, Nitay Vira, Shaleen Bezrukov, Ludmila Waters, Hang Guerrero-Cazares, Hugo Quinones-Hinojosa, Alfredo Lee, Philip R. Fields, R. Douglas Bezrukov, Sergey M. Zimmerberg, Joshua Sci Rep Article In a recent study of the pathophysiology of mild, blast-induced traumatic brain injury (bTBI) the exposure of dissociated, central nervous system (CNS) cells to simulated blast resulted in propagating waves of elevated intracellular Ca(2+). Here we show, in dissociated human CNS cultures, that these calcium waves primarily propagate through astrocyte-dependent, purinergic signaling pathways that are blocked by P2 antagonists. Human, compared to rat, astrocytes had an increased calcium response and prolonged calcium wave propagation kinetics, suggesting that in our model system rat CNS cells are less responsive to simulated blast. Furthermore, in response to simulated blast, human CNS cells have increased expressions of a reactive astrocyte marker, glial fibrillary acidic protein (GFAP) and a protease, matrix metallopeptidase 9 (MMP-9). The conjoint increased expression of GFAP and MMP-9 and a purinergic ATP (P2) receptor antagonist reduction in calcium response identifies both potential mechanisms for sustained changes in brain function following primary bTBI and therapeutic strategies targeting abnormal astrocyte activity. Nature Publishing Group 2016-05-10 /pmc/articles/PMC4861979/ /pubmed/27162174 http://dx.doi.org/10.1038/srep25713 Text en Copyright © 2016, Macmillan Publishers Limited 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/
spellingShingle Article
Ravin, Rea
Blank, Paul S.
Busse, Brad
Ravin, Nitay
Vira, Shaleen
Bezrukov, Ludmila
Waters, Hang
Guerrero-Cazares, Hugo
Quinones-Hinojosa, Alfredo
Lee, Philip R.
Fields, R. Douglas
Bezrukov, Sergey M.
Zimmerberg, Joshua
Blast shockwaves propagate Ca(2+) activity via purinergic astrocyte networks in human central nervous system cells
title Blast shockwaves propagate Ca(2+) activity via purinergic astrocyte networks in human central nervous system cells
title_full Blast shockwaves propagate Ca(2+) activity via purinergic astrocyte networks in human central nervous system cells
title_fullStr Blast shockwaves propagate Ca(2+) activity via purinergic astrocyte networks in human central nervous system cells
title_full_unstemmed Blast shockwaves propagate Ca(2+) activity via purinergic astrocyte networks in human central nervous system cells
title_short Blast shockwaves propagate Ca(2+) activity via purinergic astrocyte networks in human central nervous system cells
title_sort blast shockwaves propagate ca(2+) activity via purinergic astrocyte networks in human central nervous system cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861979/
https://www.ncbi.nlm.nih.gov/pubmed/27162174
http://dx.doi.org/10.1038/srep25713
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