A Study On Effect And Mechanism Of Hyperglycemia On The Kindling Models In Rats

The kindling models, long-term potentiation (LTP) and long term depression (LTD) are the models of long-term memory storage in the brain. Besides used to screen for AEDs, the kindling models have already expanded into many fields and become an important tool for studying the plasticity of nerves as well as an entry point in brain researches. As the plasticity of the nerves are related to memory, addiction and withdrawal of drugs, psychological diseases etc, the kindling models are being used in these fields.Objective: To study the effect and the mechanism of hyperglycemia on amygdala kindling and pentylenetetrazole kindling in rats.Method: ① Female Wistar rats were randomly divided into three groups. Gucose group was injected ip 1g/kg glucose 30 minutes prior to each stimulation. Hyperglycemia group was induced by adminastration ip 35 mg/kg Streptozocin. Amygdala kindling stimulation was given to all the rats and the effect of hyperglycemia on the development of amygdala kindling was observed in rats. (2) Female Wistar rats were also categorized into three groups randomly. Drugs were administered in the same way mentioned above in glucose and hyperglycemia group. A subconvulsant dosage of PTZ 35mg/kg was administered to each rat at 24 hours interval and the effect of hyperglycemia on PTZ kindling development was observed. (3) Eight rats from each group( glucose, hyperglycemia and control PTZ group) were extracted and the expression of insulin receptors in the different brain regions of the rats was tested using immunohistochemistry .Results: ①Hyperglycemia models were made successfully, the blood glucose value in hyperglycemia group increased significantly a week after STZ 35mg/kg ip and still remained at high level to the end of the test (p<0.01) .② A dosage of 35 mg/kg Streptozocin ip induced severe hyperglycemia on amygdala kindling rats and the mean blood glucose value was 31.9±4.2mmol/l. The numbers of stimuli required to the first stage 5 seizure were 21.5±7.0,11.5±3.9 and 9.0±3.2 respectively in hyperglycemia group,control group and glucose group. Streptozocin induced hyperglycemia significantly inhibited amygdala kindling development (p<0.01) .③ The mean blood glucose value induced by the dosage of 35 mg/kg Streptozocin ip was 25.8±2.5mmol/. The numbers of stimuli required to the first stage 5 seizure were 39.2±2.1, 21.7±2.5 and 23.7±1.9 respectively in hyperglycemia group,control group and glucose group. Streptozocin induced hyperglycemia significantly retarded the PTZ kindling development (p<0.01) .?The numbers of positive insulin receptor cells in hyperglycemia group were higher than that in control group in cerebral cortex, hippocampas, thalamus and hypothalamus.Conclusion: Streptozocin induced hyperglycemia can significantly retard the development of amygdala and PTZ kindling in rats, which mechanism could be related to the functional defects of insulin/insulin receptors in the brain induced by hyperglycemia.