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[Effect of branched-chain amino acids on glutamate neurotoxicity in primary cultured rat cerebral neurons].

The neurotoxicity of glutamate has recently been postulated to participate in the pathogenesis of amyotrophic lateral sclerosis (ALS), and branched-chain amino acids have been proposed as possible therapeutic compounds for this disease. This study was undertaken to investigate whether branched-chain amino acids have any protective effect on cultured neurons exposed to glutamate. Primary cultures of cerebral neurons were prepared from fetal rats, using an established technique. For the assessment of glutamate toxicity, photomicrographs were taken before and after glutamate exposure both with phase-contrast and with bright field following incubation in trypan blue, a dye normally excluded by healthy cells. The activity of lactate dehydrogenase released from damaged cells was also measured. Exposure to glutamate in various concentrations was carried out, and leucine, isoleucine and varine, each separately, were added in advance to culture dishes. Glutamate neurotoxicity was confirmed, but no protective effect of branched-chain amino acids was observed. Although possible clinical benefit of branched-chain amino acids in ALS may not be denied, they do not prevent glutamate neurotoxicity in cultured cerebral neurons.