EFFECTS OF MK-801 AND GANGLIOSIDE GM1 ON POSTISCHEMIC PROSTANOID RELEASE AND HIPPOCAMPAL LESION IN GERBIL BRAIN

In this study Mongolian gerbils were submitted to a normothermic bilat eral carotid ligation lasting 5 min. A noncompetitive antagonist of NM DA receptors, MK-801, 0.8 mg/kg, was injected i.p. 30 min before ische mia, or the ganglioside GM1, 30 mg/kg, was given i.p. for 3 days, twic e a day. The morphology of the hippocampal CA1 neurones and the brain content of cyclooxygenase metabolites of arachidonic acid: prostagland in 6-keto PGF(1 alpha) and thromboxane Tx B-2 were studied. Untreated ischemia induced the accumulation in brain of the 6-keto PGF(1 alpha) and Tx B-2 immunoreactive materials, and resulted in a lesion of 70% o f CA1 neurones. In the MK-801- and GM1-pretreated groups the postische mic levels of Tx B-2 were significantly decreased. However MK-801 and GM1 did not prevent damage to the CA1 neurones in gerbils normothermic after ischemia, whereas a partial neuroprotection was observed in hyp othermic, MK-801 treated gerbils. The results of this study indicate t hat NMDA receptors may participate in the mechanism of postischemic re lease of eicosanoids in brain. They also confirm a potential modulator y role of gangliosides. These results are discussed in terms of the in volvement of cyclooxygenase metabolites of arachidonic acid in the mec hanism of a selective delayed neuronal damage to the hippocampus CA1 a fter ischemia.