Cyanide-induced chronic partial asphyxia in vitro: neurochemical abnormalities and reversal by magnesium.
Neuronal cortical cell cultures obtained from fetal mice were subjected to increasing concentrations of sodium cyanide (10-500 microM) for 6 days in order to simulate prolonged partial asphyxia. Various neurochemical assays were performed to determine if certain cell types were preferentially more affected. Choline acetyltransferase activity was reduced significantly from control values at cyanide concentrations greater than 100 microM; there were similar reductions on a percentage basis in high-affinity uptake of beta-alanine and GABA and in clonazepam-displaceable benzodiazepine (BDZ) binding which reflected the neuronal BDZ receptor population. Ro5-4864-displaceable BDZ binding, a nonneuronal marker, was increased significantly. More modest reductions were apparent in specific BDZ binding and in protein content. Although a particular vulnerability of a specific cell type was not demonstrated, there was more neurochemical than morphologic evidence of cellular dysfunction. Co-exposure of the cultures to magnesium along with the highest concentrations of cyanide substantially prevented both neurochemical and morphologic abnormalities. These results lend further support to the concept that excitatory neurotransmitters may be implicated in the neuronal damage produced by hypoxia.
Sher
P K
PK
Division of Pediatric Neurology, University of Minnesota Medical School; Minneapolis.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D003486:Cyanides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008274:Magnesium / Q000494:pharmacology*; D051379:Mice; D010101:Oxygen Consumption / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects; D012966:Sodium Cyanide / Q000633:toxicity*
D003486:Cyanides; D011963:Receptors, GABA-A; D008274:Magnesium; D012966:Sodium Cyanide