Ganglioside GM1 prevents N-methyl-D-aspartate neurotoxicity in rabbit hippocampus in vivo. Effects on calcium homeostasis.

Microdialysis was used to apply 1 mM N-methyl-D-aspartate (NMDA) for 20 min to the hippocampus of rabbits, control and pre-treated with GM1 ganglioside (im injections of 30 mg/kg for 3 d, twice a day). Concentrations of ionized Ca2+ and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha)-immunoreactive material in the dialyzates and 45Ca and [14C]sucrose efflux from the prelabeled hippocampus were determined. After 24 h, the morphology of the hippocampal neurons was examined. In control animals, the application of NMDA resulted in 25% decrease in Ca2+ concentration and in 1000% increase in 6-keto PGF 1 alpha concentration in the dialyzates. A 30% decrease in 45Ca efflux was accompanied by 20% increase in [14C]sucrose efflux, reflecting a corresponding reduction of the extracellular space volume. A degeneration of CA1 pyramidal neurons in the vicinity of a microdialysis probe was observed. In GM1-treated rabbits the NMDA-induced decrease in Ca2+ concentrations in the dialyzates was not reduced significantly, whereas a 70% stimulation of 45Ca efflux was noted, with a concomitant 40% reduction of 6-keto-PG F1 alpha release. NMDA-evoked increase in [14C]sucrose efflux did not differ from the control. In these animals CA1 neurons were well preserved. These results indicate that the pretreatment with GM1 results in activation of calcium extrusion from the NMDA-stimulated rabbit hippocampal neurons that alleviates destabilization of calcium homeostasis and reduces NMDA-evoked neuronal injury.