title: Intracellular calcium and cell death during ischemia in neonatal rat white matter astrocytes in situ.
abstract: The major pathological correlate of cerebral palsy is ischemic injury of CNS white matter. Histological studies show early injury of glial cells and axons. To investigate glial cell injury, I monitored intracellular Ca2+ and cell viability in fura-2-loaded neonatal rat white matter glial cells during ischemia. Fura-2 fixation combined with immunohistochemistry revealed that fura-2-loaded cells were GFAP+/O4(-) and were therefore a population of neonatal white matter astrocytes. Significant ischemic Ca2+ influx was found, mediated by both L- and T-type voltage-gated Ca2+ channels. Ca2+ influx via T-type channels was the most important factor during the initial stage of ischemia and was associated with significant cell death within 10-20 min of the onset of ischemia. The Na+-Ca2+ exchanger acted to remove cytoplasmic Ca2+ throughout the ischemic and recovery periods. Neither the release of Ca2+ from intracellular stores nor influx via glutamate-gated channels contributed to the rise in intracellular Ca2+ during ischemia. Ischemic cell death was reduced significantly by removing extracellular Ca2+ or by blocking voltage-gated Ca2+ channels. The exclusively voltage-gated Ca2+ channel nature of the Ca2+ influx, the role played by T-type Ca2+ channels, the protective effect of the Na+-Ca2+ exchanger, and the lack of significant Ca2+ release from intracellular stores are features of ischemia that have not been reported in other CNS cell types.
authors.affiliation: Department of Neurology, University of Washington, Seattle, Washington 98195, USA.
authors.forename: R
authors.initials: R
authors.lastname: Fern
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D016257:Fura-2; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D015640:Ion Channel Gating / Q000502:physiology; D007811:Lanthanum / Q000494:pharmacology; D009412:Nerve Fibers / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D009900:Optic Nerve / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D017470:Receptors, Glutamate; D019831:Sodium-Calcium Exchanger; D002104:Cadmium; D007811:Lanthanum; D009532:Nickel; D002118:Calcium; D016257:Fura-2