GANGLIOSIDE GM1 PREVENTS N-METHYL-D-ASPARTATE NEUROTOXICITY IN RABBITHIPPOCAMPUS IN-VIVO - EFFECTS ON CALCIUM HOMEOSTASIS

Microdialysis was used to apply 1 mM N-methyl-D-aspartate (NMDA) for 2 0 min to the hippocampus of rabbits, control and pretreated with GM1 g anglioside (im injections of 30 mg/kg for 3 d, twice a day). Concentra tions of ionized Ca2+ and 6-keto prostaglandin F-1 alpha (6-keto PGF(1 alpha))-immunoreactive material in the dialyzates and Ca-45 and [C-14 ] sucrose efflux from the prelabeled hippocampus were determined. Afte r 24 h, the morphology of the hippocampal neurons was examined. In con trol animals, the application of NMDA resulted in 25% decrease in Ca2 concentration and in 1000% increase in 6-keto PGF(1 alpha), concentra tion in the dialyzates. A 30% decrease in Ca-45 efflux was accompanied by 20% increase in [C-14] sucrose efflux, reflecting a corresponding reduction of the extracellular space volume. A degeneration of CA1 pyr amidal neurons in the vicinity of a microdialysis probe was observed. In GM1-treated rabbits the NMDA-induced decrease in Ca2+ concentration s in the dialyzates was not reduced significantly, whereas a 70% stimu lation of Ca-45 efflux was noted, with a concomitant 40% reduction of 6-keto-PG Fl, release. NMDA-evoked increase in [C-14]sucrose efflux di d not differ from the control. In these animals CA1 neurons were well preserved. These results indicate that the pretreatment with GM1 resul ts in activation of calcium extrusion from the NMDA-stimulated rabbit hippocampal neurons that alleviates destabilization of calcium homesta sis and reduces NMDA-evoked neuronal injury.