title: Excitatory amino acid antagonist administered via microdialysis attenuates lactate accumulation during cerebral ischemia and subsequent hippocampal damage.
abstract: Our previous studies have shown that kynurenic acid (KYN), a broad-spectrum antagonist of excitatory amino acids (EAAs), administered in situ through a dialysis probe can delay the massive ionic fluxes in the rat hippocampus during cerebral ischemia. The present experiments demonstrated that the same procedure attenuates the increase in extracellular concentration of lactate ([lactate]e) during ischemia as measured by microdialysis. This finding suggests that the lactate accumulation is partially caused by a sudden increase in energy demand due to the rapid ionic fluxes through EAA-coupled ion channels. This inference is consistent with the hypothesis that the earlier ionic event during ischemia is a cause of energy depletion, rather than the result merely of energy failure. The present experiments also revealed that KYN administered by the same procedure attenuates death of hippocampal CA1 pyramidal cells after 5-min transient ischemia in gerbils. Since lactate accumulation is likely to be an important factor affecting cell viability, the protective effect of KYN may be attributable, in part, to inhibition of lactate accumulation.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Katayama
authors.forename: T
authors.initials: T
authors.lastname: Kawamata
authors.forename: T
authors.initials: T
authors.lastname: Kano
authors.forename: T
authors.initials: T
authors.lastname: Tsubokawa
mesh_terms: D000596:Amino Acids / Q000037:antagonists & inhibitors*; D000818:Animals; D003956:Dialysis; D005849:Gerbillinae; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006651:Histocytochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D007736:Kynurenic Acid / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000596:Amino Acids; D007773:Lactates; D007736:Kynurenic Acid; D005947:Glucose