Blast shockwaves propagate Ca2+ activity via purinergic astrocyte networks in human central nervous system cells

Rea Ravin, Paul S. Blank, Brad Busse, Nitay Ravin, Shaleen Vira, Ludmila Bezrukov, Hang Waters, Hugo Guerrero-Cazares, Alfredo Quinones-Hinojosa, Philip R. Lee, R. Douglas Fields, Sergey M. Bezrukov, Joshua Zimmerberg

Research output: Contribution to journalArticle

Abstract

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 Ca2+. 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.

Original languageEnglish (US)
Article number25713
JournalScientific Reports
Volume6
DOIs
StatePublished - May 10 2016

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Astrocytes
Central Nervous System
Calcium Signaling
Glial Fibrillary Acidic Protein
Metalloproteases
Purinergic P2 Receptor Antagonists
Calcium
Purinergic P2 Receptors
Peptide Hydrolases
Brain
Traumatic Brain Injury
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Ravin, R., Blank, P. S., Busse, B., Ravin, N., Vira, S., Bezrukov, L., ... Zimmerberg, J. (2016). Blast shockwaves propagate Ca2+ activity via purinergic astrocyte networks in human central nervous system cells. Scientific Reports, 6, [25713]. https://doi.org/10.1038/srep25713

Blast shockwaves propagate Ca2+ 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.

In: Scientific Reports, Vol. 6, 25713, 10.05.2016.

Research output: Contribution to journalArticle

Ravin, R, Blank, PS, Busse, B, Ravin, N, Vira, S, Bezrukov, L, Waters, H, Guerrero-Cazares, H, Quinones-Hinojosa, A, Lee, PR, Fields, RD, Bezrukov, SM & Zimmerberg, J 2016, 'Blast shockwaves propagate Ca2+ activity via purinergic astrocyte networks in human central nervous system cells', Scientific Reports, vol. 6, 25713. https://doi.org/10.1038/srep25713
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 Ca2+ activity via purinergic astrocyte networks in human central nervous system cells. In: Scientific Reports. 2016 ; Vol. 6.
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