The Establish And Mechanism Study Of Rapidly Recurring Hippocampal Kindling In Rats

Rapidly recurring hippocampal kindling models in rats were discovered in late 1980's .Before that ,it is well known that rats will turn to habituation and couldn't be kindled unless the interstimulus interval is as long as 12h. The arbitrary ideas wre denied since the were established. Now, traditional kindling models are firstly adopted to screen AEDs. However, rapidly recurring hipplcampal kindling models are definitely become an effective and efficient screening model for anti-kindled drugs since it is easily established within one day. But the mechanism of the models still remain unknown.Objective: To establish s in rats in a better way. To evaluate the models pharmacologily .To investigate the mechanism of the models primarily.Methods: Establish rapidly recurring hippocampal kindling models in different parameter and record the stages of behavior and after discharge duration .The effect of general anti-kindled drugs such as diazepam and phenobarbital and a novel anti-kindled drug, succinate on rapidly recurring hippocampal kindling models were observed. The number of c-fos immune-positive cells in CA3 of hippocampus and specific cerebral cortex immunohistochemistrily in rapidly recurring hippocampal kindling and amygdala kindling models was caculated. Applying CHX 2h before the kindling stimulus,caculate the number of c-fos immune-positive cells in the same zone.Results: Rapidly recurring hippocampal kindling models were established successfully. We found that the kindled ratio was decided by stimulus parameters.During the process of the kindled models development, ADD was longer as more stimulus were given to the rats. Diazepam at doses of 2,5mg-kg-1ip and Phenobarbital at doses of 20,50 mg-kg-1ip, can decrease the Racine's stages and in rapidly recurring hippocampal kindled rats (P<0.05). Succinate can also decrease ADD and increase V stage threshold rapidly recurring hippocampal kindled rats (P<0.05). The immunohistochemistry experiment suggest t in CA3 of hippocampus and specific cerebral cortex increase in and amygdala kindling rats in comparison with control rats(P<0.05) and that the number of c-fos immune-positive cells in the same zone in rapidly recurring hippocampal kindled rats applied CHX decrease obviously in comparison with the kindled rats and still more than the controlrats(P<0.05).Conclusion: Rapidly recurring hippocampal kindling models were established successfully. We found that the kindled ratio was decided by stimulus parameters. We found that rapidly recurring hippocampal kindling model was a good anti-kindled drugs screening model. We also found an entrance to study the mechanism of rapidly recurring hippocampal kindling model in special zone because of different expression in different zone.