Study On The Expression Of Caspase-1 And Interleukin-18 After Hypoxic-Ischemic Brain Damage In Neonatal Rats

Objective In our study, we measured the expression of caspase-1 and IL-18 mRN A and protein in cerebral cortex of neonatal rats at different time points after HIBD, in order to investigate their change and correlation and to determine their effect on the pathogenesis of HIBD. Our experiment will be sure to provide a fine theoretical foundation for clinical diagnosis and therapy of neonatal HIE. Methods 84 seven-rday-old Wistar rats were randomly assigned to control group, HEBD3h, 8h, 24h, 3d, 6d and 14d group (n=12 per group), and the model of HEBD was established. In each group, 6 rats were used to measure the mRNA for caspase-1 and IL-18 in the cerebral cortex by semi-quantitative RT-PCR, another 6 rats were used to study histological change and the protein expression for caspase-1 and IL-18 by HE staining and irnmunohistochemistry. Results 1. The expression of caspase-1 mRNA and protein: The expression of caspase-1 mRNA and protein was observed both in control and HIBD groups. The level of caspase-1 mRNA and protein in ischemic cortex began to increase within 24 h (P<0.01 vs control), peaked at 6 d after HIBD (P<0.01 vs other groups) and decreased after this. But the mRN A/protein for caspase-1 was still higher than the normal level (P<0.01 vs control) at 14 d of reperfusion.2. The expression of IL-18 mRNA and protein: The level of IL-18 mRNA and protein was low in control group. After HIBD, the expression of mRN A/protein for IL-18 in ischemic cortex increased progressively at 24 h to 6 d (P<0.01 vs control), reached its greatest level at 6 d (P<0.01 vs other groups), and then decreased significantly.3. Histological study; There was no obvious sign of neuronal damage incontrol group. The degenerated and necrotic neurons increased progressively at 1to 6 d after HEBD, at the same time the proliferation of glial cells appeared. At 14d following HD3D, the existent neurons decreased in number, and hypertrophicastrocytes filled the vacant space instead of them.Conclusion The expression of caspase-1 and EL-18 that increased after HIBD inneonatal rats showed a close correlation in time and was consistent with thedevelopment of brain injury. The data here suggest a role for caspase-1 and one ofits substrates, EL-18 in the pathophysiology of cellular damage in the immaturebrain and provide the rational for neuroprotective strategies employing theirinhibitors.