title: Valproate doubles the anoxic survival time of normal developing mice: possible relevance to valproate-induced decreases in cerebral levels of glutamate and aspartate, and increases in taurine.
abstract: We have previously reported that chronic administration of valproate in developing mice decreased brain aspartic and glutamic acid levels and increased the brain taurine content. The direction of the valproate-induced changes in the cerebral levels of these neurotransmitter amino acids - excitatory in the case of aspartate and glutamate, inhibitory in the case of taurine - appeared relevant to the mechanism of its anticonvulsant action. Since the neuropathology of hypoxia-ischemia also appears to be mediated by release of glutamate/aspartate at the synapse, the valproate-induced reduction of the levels of these neuroexcitatory/neurotoxic amino acids suggested that valproate might increase the tolerance of young mice to anoxia. A doubling of the length of survival of the intact animal in an atmosphere of pure nitrogen gas and a three-fold increase in the duration of respiratory activity (gasping) of the isolated head after chronic administration of valproate support the speculation.
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, Missouri 63110.
authors.forename: J H
authors.initials: JH
authors.lastname: Thurston
authors.forename: R E
authors.initials: RE
authors.lastname: Hauhart
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D001224:Aspartic Acid / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D051379:Mice; D013654:Taurine / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D005971:Glutamates; D013654:Taurine; D001224:Aspartic Acid; D014635:Valproic Acid; D005947:Glucose