A Experimental Study On The Actiavation And Role Of MAPK Signal Transduction Pathway In The Hippocampus Of Epileptogenic Rat

Object:To investigate the spatiotemporal distribution pattern of active MAPKs in rat hippocampus following lithium-pilocarpine-induced status epilepticus(SE) and the potential role of the active kinases on epileptogenesis. Methods:Status epilepticus(SE) was induced by injecting lithium chloride and pilocarpine intraperitoneally(ip) to obseve the behavioural manifestation of the suvival animals,At 30 min,2h,6h,12h after induction of SE,the animals were processed for immunohistochemistry method and HE staining to evaluate phosphorylation forms of ERK1/2,p38,JNK and view the histopathology changes in hippocampus. Results: 1. Among the animals injected with pilocarpine,83 % (24 / 29) presented above stage â…£attack,3 rats were below stage â…¢,2 rats died,and no seizure were found in the saline control group. 2. Compared with the saline control group,there were no notable changes at 30 min and slight neurodegeneration in hippocampal neurons at 2h after induction of SE.At 6h neurons in the regions of CA1 and CA3 showed a remarkable degeneration and necrosis which aggravated with widerspread cell loss and gliosis at 12h.Granule cells in dentate gyrus preserved basically the integrity of cellular structure at 6h and showed degeneration at 12h. 3. The p-ERK1/2 immunoreactivity was observed only in neuritis of saline-treated rats hippocampus.In pilocarpine-treated rats,the hippocampal neurons showed a strong immunoreactivity of p-ERK1/2 in the body at 30 min with the maximum at 2h following induction of SE,which decreased markedly at 6h and returned basal level at 12h. 4. In saline-treated rats,p38 were extensively activated in pyramid cells of CA1,CA3 regions and granule cells of dentate gyrus.In pilocarpine-treated rats,the activation enhanced at 30 min, reached the peak at 2h, weakened at 6h and approached basal level at 12h. 5. After 30 min of inductin of SE,JNK were extensively activated in hippocampal neurons which scarcely express it in normoal rat.The activation peaked at 2h and decline to basal level at 6h. Conclusion:Lithium-pilocarpine-induced rats model of epilepsy can mimic features of human status epilepticus and temporal epilepsy in serzure behavior and histopathology findings.The injury of neurons in response to seizure in CA1,CA3 regions is more susceptible than that in dentate gyrus.MAPK signal transduction pathway can be activated inseizures by pilocarpine,and may play a critical role in the pathophysiological process of neuron injury and protection related to seizure,and even mediate further long-lasting morphological changes.