Effects of excitatory neurotransmitter amino acids on swelling of rat brain cortical slices.

Abstract

Abstract— With the single rat brain cortical slice serving as an in vitro bio‐assay system, the effects of neurotransmitter amino acids (1 mm) on brain swelling, water, sodium and potassium content, inulin space, and lactate production were studied. The putative dicarboxylic amino acid neurotransmitters, l‐glutamic acid and l‐aspartic acids, greatly increased intracellular brain swelling with increased intracellular Na+, water content and lactate production, and decreased inulin space and intracellular K+. Equimolar GABA, taurine, glycine, the putative inhibitory neurotransmitter amino acids, and equimolar α‐amino‐isobutyric acid had no effect. Brain swelling and intracellular Na+/K+ ratios were greatly increased by l‐glutamate and l‐aspartate at a concentration of 10 mm. However, l‐aspartate at these concentrations greatly depleted the K+ content and lactate production as compared to l‐glutamate.Further studies indicated that only the structural analogs and isomers of the dicarboxylic amino acids possessing two acidic groups and an α‐amino group had a similar effect on the induction of brain swelling. Among the analogs of glutamic acid, dl‐homocysteic acid and kainic acid had a greater effect on brain swelling, as observed from the total adenosine 5′‐triphosphate (ATP) levels and the time‐course and dose‐response. A biphasic response in lactate production was induced by dl‐homocysteic acid and kainic acid, suggesting that these analogs had a neurotoxic effect on cellular metabolism at higher concentrations.