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Study of ERK Signal Transduction Pathway in Rats with Pentylenetetrazole(PTZ)-induced Seizures

ZHAO Xiu-he~*,CHI Zhao-fu,WANG Sheng-jun,WU Wei.~*Department of Neurology,Qilu Hospital,Shandong University,Jinan 250012,China  
Objective: To investigate the expression of ERK signal transduction pathway and its significance in the cerebral cortex of rats after epileptic seizures.Methods: A pentylenetetrazole(PTZ)-induced seizure model was established to evaluate the expression of ERK1 and ERK2 as well as the phosphorylation form of ERK1/2-p-ERK1/2 in cerebral cortex by immunohistochemistry and Western blot at 30 min,1.5h,5h and 8h respectively after seizures.Neuronal damage was evaluated by histopathology.Results: p-ERK1/2 immunoreactivity(IR) was not detected in the brain of saline-treated rats while ERK1 and ERK2 showed a little IR.IR of p-ERK1/2 began to be observed in the affected rats at 30 min following PTZ injection(IR=9.68±1.29,compared with the empty control group,P0.05),and reached the peak at 1.5h(IR=21.68±3.09,compared with the empty control group,P0.05).Both ERK1 and ERK2 IR also began to increase in(30 min) group and had obvious increase in 1.5 h groups when compared with the control group(P0.05).They all declined 5h after PTZ injection and dropped to a lower level 8h later.Injured neurons were also present in histopathological examination.Western blots showed that the level of ERK1,ERK2 and p-ERK1/2 in cerebral cortex of epileptic rats all increased remarkably compared with the saline-treated rats(P0.05) in different time groups.The expression of the all three proteins was higher in 1.5h group than in the other groups.Conclusion: ERK pathway in cerebral cortex was activated to take part in the pathophysiological mechanism in PTZ-induced epilepsy model,and the pathway might play an important role in initiating seizures.
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