title: Blast shockwaves propagate Ca(2+) activity via purinergic astrocyte networks in human central nervous system cells.
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 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.
authors.affiliation: Section on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA.|Celoptics Inc., Rockville, MD 20852, USA.
authors.forename: Rea
authors.initials: R
authors.lastname: Ravin
authors.affiliation: Section on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Blank
authors.affiliation: Section on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Busse
authors.affiliation: Section on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA.|Celoptics Inc., Rockville, MD 20852, USA.
authors.forename: Nitay
authors.initials: N
authors.lastname: Ravin
authors.affiliation: Section on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA.
authors.forename: Shaleen
authors.initials: S
authors.lastname: Vira
authors.affiliation: Section on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Bezrukov
authors.affiliation: Section on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Waters
authors.affiliation: Department of Neurosurgery, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Hugo
authors.initials: H
authors.lastname: Guerrero-Cazares
authors.affiliation: Department of Neurosurgery, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quinones-Hinojosa
authors.affiliation: Section on Nervous System Development and Plasticity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3713, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Lee
authors.affiliation: Section on Nervous System Development and Plasticity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3713, USA.
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Fields
authors.affiliation: Section on Molecular Transport, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-0924, USA.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Bezrukov
authors.affiliation: Section on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Zimmerberg
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001753:Blast Injuries; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D005107:Explosions; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical
chemical_list: D005904:Glial Fibrillary Acidic Protein; D011983:Receptors, Purinergic; D020780:Matrix Metalloproteinase 9; D002118:Calcium