IGF-1 And NNOS Expression In The Amygdala Kindled Rats And The Effects Of Antiepilepsy Drugs

Objectives Our work aimed to address the involvement of the neuronal nitric oxide synthase (nNOS) and insulin-like growth factor I (IGF-1) in epilepsy,specifically,to construct a rat model of basolateral amygdala kindling, quantify the nNOS and IGF-1 expression in hippocampus, test the effects of commonly used anti-epilepsy drugs on the preceding factors, and discuss the possible pathogenesis of epilepsy and the mechanisms for therapies. Methods Bipolar electrodes were implanted in the left side of the rat basolateral amygdala, chronic electric stimuli were delivered to reach the kindling threshold. A blank control group,a sham group,an electrically kindled epilepsy group,and three therapy groups with topiramate, sodium valproic acid and carbamazepine,respectively, were set up. Semi-quantitative RT-PCR was employed to examine the nNOS and IGF-1 mRNA levels in the hippocampus of each group, and immunohistochemistry methods were used to determine the hippocampal expression of nNOS and IGF-1 in each group. Results Hippocampal expression of nNOS and IGF-1 was significantly higher in the kindled group than in the blank control and the sham group. The semi-quantitative RT-PCR results revealed an positive correlation between levels of nNOS and IGF-1 expression in the epilepsy group. In the therapy group,nNOS expression was significantly downregulated relative to the epilepsy group,and the topiramate group exhibited noticeable difference in contrast to the other two therapy groups. The immunohistochemistry results located the nNOS expression in the neuronal cytosol,and the high positive expression rate was shown to be higher for both of the epilepsy and the topiramate group than the sham control,blank control and the other two therapy groups. Strong IGF-1 expression was located in the capillary reticulum in hippocampus. Conclusions The large increase of nNOS expression in the amygdala kindled rat hippocampus implies the possible involvement of nNOS in amygdala kindled epilepsy. Routine anti-epilepsy medicines were observed to be effective in decreasing hippocampal nNOS expression, and thus might be beneficial to the protection of normal neuronal functions in epilepsy. As a neuronal protection factor,IGF-1 could contribute to the downregulation of nNOS and play a protective role in the amygdala kindled epilepsy,or to a larger extent in general epilepsy and related conditions. IGF-1 in the peripheral blood can enter the CNS through blood brain barrier.