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

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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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Ravin, R., Blank, P. S., Busse, B., Ravin, N., Vira, S., Bezrukov, L., Waters, H., Guerrero-Cazares, H., Quinones-Hinojosa, A., Lee, P. R., Fields, R. D., Bezrukov, S. M., & 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