Neurochemical correlates of cyanide-induced hypoxic neuronal damage in vitro.
Neuronal cortical cell cultures obtained from fetal mice were subjected to an hypoxic insult produced by sodium cyanide (1 mM) for 24 h. Neurochemical assays were performed 13-14 days after plating on intact cells in situ to determine if there was a specific pattern of cellular dysfunction in addition to morphologic change. Ro5-4864-displaceable benzodiazepine (BDZ) binding and high-affinity [3H] beta-alanine uptake were not reduced when compared to control values. However, specific and clonazepam-displaceable BDZ binding (81 +/- 4% and 50 +/- 9% of control values, respectively), high-affinity [3H]GABA uptake (75 +/- 2%), and choline acetyltransferase activity (82 +/- 2%) were significantly lower. When the data were expressed in terms of protein content, high-affinity [3H] beta-alanine uptake was significantly increased in cyanide-exposed and magnesium-treated cultures (123 +/- 5% and 117 +/- 3%, respectively) as was R05-4864-displaceable BDZ binding (152 +/- 14%), consistent with stimulation of nonneuronal BDZ binding and increased glial neurotransmitter uptake. Moreover, pretreatment of the cultures with magnesium effectively prevented both the morphologic and neurochemical evidence of hypoxic injury. These data lend further support to the notion that the release of excitatory neurotransmitters may mediate neurotoxicity in developing brain.
Sher
P K
PK
Division of Pediatric Neurology, University of Minnesota Medical School, Minneapolis.
D000409:Alanine / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011963:Receptors, GABA-A / Q000378:metabolism; D012966:Sodium Cyanide / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D012966:Sodium Cyanide; D000409:Alanine