THE EXPRESSION OF CASPASE-1 IL-18 IN THE HIPPOCAMPUS OF THE DEVELOPING RAT AFTER RECURRENT SEIZURES AND THE INTERVENTION ROLE OF LIGUSTRAZINE

Objectives: The study was to investitage the expression of caspase-1 IL-18 in the hippocampus of the developing rats following recurrent seizures and the effects of Ligustrazine on them, and to evaluate the role of caspase-1 IL-18 in developing brain injury induced by seizures and the possible mechanism of neural protection with Ligustrazine.

Methods: 132 postnatal day 20 Sprague-Dawley rats were divided randomly into three groups: the control group, the seizure group and the Ligustrazine treated group. Seizure in rats were induced by inhalant flurothyl daily in six consecutive days. Brain tissue was sampled at different time points (6h,1d,3d,7d) in each group after last seizure. The expression of caspase-1 IL-18 mRNA in the hippocampus were detected by reverse transcription-polymerase chain reaction (RT-PCR), and the expression of IL-18 protein were measured by enzyme-linked immunosorbent assay (ELISA).

Results: The expression of caspase-1,IL-18 mRNA and IL-18 protein are rare in the hippocampus of the control rat pup. The caspase-1 and IL-18 mRNA levels at postseizure 6h,1d,3d,7d in the hippocampus of the rat pup in seizure group were higher obviously than those in control group (at 6h, P<0.05, at 1d, 3d, 7d, P<0.01). The expression of IL-18 protein and IL-18 mRNA were similar after recurrent seizures. In Ligustrazine treated group, neuropathological score and water content of the rat brain and the expression of caspase-1,IL-18 mRNA and IL-18 protein in the hippocampus at different time points obviously lower than those in seizure group (p<0.05). Degeneration and necrosis of nerve cells in the hippocampus of the rat were also significantly decreased.

Conclusion: After recurrent seizures, the levels of caspase-1, IL-18 mRNA and IL-18 protein are markedly increased in the hippocampus of the developing rats and accompanied by brain edema and neuron injuries of the rat hippocampus, suggesting inflammatory couse is participated in the developing brain injury after recurrent seizures. Ligustrazine can decrease brain edema and neuron injuries of the hippocampus and also downregulate the abnormal expression of caspase-1,IL-18 in the hippocampus after seizures. That is the suppression of the abnormal levels of caspase-1,IL-18 in the hippocampus is probably related to the protective effects of Ligustrazine on the developing brain injury induced by seizures.