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 bilateral carotid ligation lasting 5 min. A noncompetitive antagonist of NMDA receptors, MK-801, 0.8 mg/kg, was injected i.p. 30 min before ischemia, or the ganglioside GM1, 30 mg/kg, was given i.p. for 3 days, twice a day. The morphology of the hippocampal CA1 neurones and the brain content of cyclooxygenase metabolites of arachidonic acid: prostaglandin 6-keto PGF1 alpha and thromboxane Tx B2 were studied. Untreated ischemia induced the accumulation in brain of the 6-keto PGF1 alpha and Tx B2 immunoreactive materials, and resulted in a lesion of 70% of CA1 neurones. In the MK-801- and GM1-pretreated groups the postischemic levels of Tx B2 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 hypothermic, MK-801 treated gerbils. The results of this study indicate that NMDA receptors may participate in the mechanism of postischemic release of eicosanoids in brain. They also confirm a potential modulatory role of gangliosides. These results are discussed in terms of the involvement of cyclooxygenase metabolites of arachidonic acid in the mechanism of a selective delayed neuronal damage to the hippocampus CA1 after ischemia.
Lazarewicz
J W
JW
Department of Neurochemistry, Polish Academy of Sciences, Warsaw.
Salińska
E
E
Speina
E
E
Gadamski
R
R
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000473:pathology*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism
D011453:Prostaglandins; D005677:G(M1) Ganglioside; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D016291:Dizocilpine Maleate