Neuroprotective effect of GMP in hippocampal slices submitted to an in vitro model of ischemia.

1. Guanosine-5'-monophosphate (GMP) was evaluated as a neuroprotective agent against the damage observed in rat hippocampal slices submitted to an in vitro model of ischemia with or without the presence of the ionotropic glutamate receptor agonist, Kainic acid (KA). 2. Cellular injury was evaluated by MTT reduction, lactate dehydrogenase(LDH) release assay, and measurement of intracellular ATP levels. 3. In slices submitted to ischemic conditions, 1 mM GMP partially prevented the decrease in cell viability induced by glucose and oxygen deprivation and the addition of KA. 4. KA or N-methyl-D-aspartate (NMDA) receptor antagonists, gamma-D-glutamylamino-methylsulfonate (GAMS) or (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801, 20 microM) also prevented toxicity in hippocampal slices under ischemic conditions, respectively. 5. The association of GMP with GAMS or MK-801 did not induce additional protection than that observed with GMP or that classical glutamate receptor antagonists alone. 6. GMP, probably by interacting with ionotropic glutamate receptors, attenuated the damage caused by glucose and oxygen deprivation in hippocampal slices. This neuroprotective action of GMP in this model of excitotoxicity is of outstanding interest in the search for effective therapies against ischemic injury.