Mitogen-activated protein kinase is increased in the limbic structures of the rat brain during the early stages of status epilepticus

Systemic administration of pilocarpine (PILO) in adult rat produces acute limbic seizures leading to states epilepticus. Recent studies have shown the activation of mitogen-activated protein kinase (MAPK) cascades during experimentally induced seizures. MAPK activation may be triggered by glutamatergic stimulation and may play a key role in signal transduction pathways, In the present study, immunocytochemistry was used to analyze the spatiotemporal distribution pattern of the MARK protein and its active form (A-MAPK) following PILO-induced status epilepticus, MAPK and A-MARK immunoreactivities exhibited different patterns of distribution in the brain of normal and epileptic rats. The saline-treated rats, as well as the animals that received PILO but did not evolve to status epilepticus, showed a weak but selective MAPK immunoreactivity, detected in the hippocampal pyramidal neurons, dentate gyrus, hilus, CA3, CA1, and entorhinal, piriform, and cingulate cortices. A-MARK immunoreactivity was instead observed only in neurites of the CA3 and hilus and in cells of the entorhinal and piriform cortices, In PILO-treated rats, between 30 and 60 min after states epilepticus there was an increase of the immunoreactivity to both antibodies, which were differently distributed throughout several structures of the limbic system. The immunostaining showed a slight decrease after 5 h of states epilepticus, However, MARK and A-MARK immunopositivities decreased markedly after 12 h of states epilepticus, returning almost to the basal expression. These findings are consistent with a spatial and time-dependent MAPK expression in selected limbic structures, and its activation could represent an initial trigger for neuronal modifications that may take part in the mechanism underlying acute epileptogenesis and in longlasting neuropathological changes of the PILO model of epilepsy. (C) 1998 Elsevier Science Inc.