Role of nitric oxide in neuronal injury induced by exposure to glutamate or combined oxygen-glucose deprivation

• Published in: Japanese Journal of Pharmacology Vol. 64; no. suppl.1; p. 63
• Main Authors: Murota, Sei-itsu, Ikeda, Junichi, Morita, Ikuo
• Format: Journal Article
• Language: Japanese; English
• Published: The Japanese Pharmacological Society 1994
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)49943-5

Nitric oxide (NO), which was first described as a chemical candidate for an endothelial derived relaxing factor, is also synthesized in the central nervous system. Besides its role as a neuronal messenger, accumulating evidence suggests that nitric oxide which is produced and released upon the increase in intracellular calcium concentration is involved in glutamate neurotoxicity. By contrast, neurons which have nitric oxide synthase (NOS) have been reported to be spared in NMDA neurotoxicity, suggesting NO may play a role in reducing neuronal damage. Cortical cell cultures prepared from 18-day-old rat embryos were exposed to combined oxygen-glucose deprivation. Evaluation of cellular viability with fluorescent dye (propidium iodide and fluorescent diacetate) under an interactive laser cytometer revealed that severe neuronal damage was produced within 24 hours after the insult. Addition of each one of the NMDA receptor antagonists. NOS inhibitors, and free radical scavengers (MCI 186) prior to the insult produced significant reduction in these neuronal injuries. Intracellular calcium concentration monitored by fluo-3 showed a prompt elevation responded to glutamate in most of the neurons, while this response was significantly reduced in NOS containing neurons. Surprisingly, with the inhibitor of NOS, this distinct class of neurons lost their ability to regulate cytosolic calcium level. Our results indicate that biosynthesis and liberation of NO are involved in neuronal injury induced by combined oxygen-glucose deprivation. In addition, NO may protect NOS containing neurons from glutamate neurotoxicity by inhibiting glutamate-induced calcium influx.