Neurotoxicity evoked by N-methyl-D-aspartate in the organotypic static slice cultures of rat cerebral cortices: effect of GABA(A) receptor activation.
We investigated the neurotoxicity evoked by N-methyl-D-aspartate (NMDA) receptor stimulation in the organotypic static slice cultures of rat cerebral cortices. We also examined whether the gamma-aminobutyric acid (GABA)A receptor agonist muscimol has a protective effect on the NMDA-mediated neurotoxicity in this culture system. NMDA-mediated cytotoxicity was evaluated histologically and quantified by the measurement of lactate dehydrogenase (LDH) release into the culture medium. There was an NMDA-induced, dose-dependent leakage of LDH release and neuronal cell death, which were not attenuated by muscimol treatment. The results suggested that NMDA neurotoxicity is reproduced in the organotypic culture, and that GABA(A) receptor activation exerted no protective action against the NMDA cytotoxicity.
Yoshikawa
M
M
Department of Neurosurgery, Kumamoto University Medical School, Japan.
Goto
S
S
Okamura
A
A
Hamasaki
T
T
Ushio
Y
Y
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000737:chemistry; D018755:GABA Agonists / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009118:Muscimol / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000032:analysis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology
D017077:Culture Media, Conditioned; D018755:GABA Agonists; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011963:Receptors, GABA-A; D009118:Muscimol; D016202:N-Methylaspartate; D007770:L-Lactate Dehydrogenase