TY - JOUR
T1 - Blast shockwaves propagate Ca2+ activity via purinergic astrocyte networks in human central nervous system cells
AU - Ravin, Rea
AU - Blank, Paul S.
AU - Busse, Brad
AU - Ravin, Nitay
AU - Vira, Shaleen
AU - Bezrukov, Ludmila
AU - Waters, Hang
AU - Guerrero-Cazares, Hugo
AU - Quinones-Hinojosa, Alfredo
AU - Lee, Philip R.
AU - Fields, R. Douglas
AU - Bezrukov, Sergey M.
AU - Zimmerberg, Joshua
PY - 2016/5/10
Y1 - 2016/5/10
N2 - 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.
AB - 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.
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U2 - 10.1038/srep25713
DO - 10.1038/srep25713
M3 - Article
C2 - 27162174
AN - SCOPUS:84968623874
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 25713
ER -