title: 21-Aminosteroids attenuate excitotoxic neuronal injury in cortical cell cultures.
abstract: We studied the protective efficacy of novel 21-aminosteroids against several forms of neuronal injury in murine cortical cell cultures. Concentrations of 200 nM to 20 microM partially attenuated the damage induced by glucose deprivation, combined oxygen-glucose deprivation, or exposure to NMDA; maximal protection was less than that produced by NMDA antagonists, but the combination of a 21-aminosteroid plus an NMDA antagonist produced a greater benefit than either drug alone. 21-Aminosteroid addition did not attenuate NMDA-induced whole-cell current, but did block almost all of the damage induced by exposure to iron, a protective action consistent with inhibition of free radical-mediated lipid peroxidation. Lipid peroxidation may be a downstream event mediating a portion of the injury triggered by excess stimulation of NMDA receptors.
authors.affiliation: Department of Neurology, Stanford University Medical Center, California 94305.
authors.forename: H
authors.initials: H
authors.lastname: Monyer
authors.forename: D M
authors.initials: DM
authors.lastname: Hartley
authors.forename: D W
authors.initials: DW
authors.lastname: Choi
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008564:Membrane Potentials; D051379:Mice; D016202:N-Methylaspartate; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011281:Pregnatrienes / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism
chemical_list: D008054:Lipid Peroxides; D011281:Pregnatrienes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate; C053356:U 74500A; D005947:Glucose; C053355:tirilazad