[Expression of and relationship between caspase-1 and interleukin-18 mRNA in brain tissue of hypoxic-ischemic neonatal rats].

OBJECTIVE

Caspase-1 is a member of cysteinyl aspartate specific protease family and it plays important roles in the pathophysiology of many diseases for its proinflammatory and proapoptotic peculiarity. Interleukin (IL)-18, one of its substrates, is a pleiotropic cytokine and processed by caspase-1 to become fully bioactive. The aim of this study was to investigate the relationship and effect of caspase-1 and IL-18 mRNA expressions after hypoxic-ischemic brain damage (HIBD) in neonatal rats.

METHODS

Totally 112 seven-day-old Wistar rats were assigned to control group, HIBD 3 h, 8 h, 24 h, 3 d, 6 d and 14 d groups via complete randomization (n = 16 per group), and the model of HIBD was induced by unilateral carotid ligation followed by timed exposure to 8% oxygen. In each group, 8 rats were used for measuring the mRNA for caspase-1 and IL-18 in the cerebral cortex by semi-quantitative RT-PCR, and the brains of another 8 rats were observed for light microscopic changes by HE staining.

RESULTS

The expression of caspase-1 mRNA was low in control group (0.2918 +/- 0.0809). After HIBD, the level of caspase-1 mRNA in ischemic cortex began to increase at 24 h (0.5222 +/- 0.0941, P < 0.01 vs. control), peaked at 6 d (0.7886 +/- 0.0480, P < 0.01 vs. the other groups) and decreased at 14 d (0.5314 +/- 0.1272). The level of IL-18 mRNA was 0.3218 +/- 0.0466 in control group. After HIBD, the expression of mRNA for IL-18 increased progressively at 24 h to 6 d (24 h: 0.5823 +/- 0.0740; 3 d: 0.6976 +/- 0.1073; 6 d: 0.9110 +/- 0.0647, P < 0.01 vs. control), reached its greatest level at 6 d (P < 0.01 vs. other groups). The expression of IL-18 mRNA after HIBD showed a close correlation to caspase-1 in time (r = 0.871, P < 0.01). Histological study showed that the degenerated and necrotic neurons increased progressively at 1 d to 6 d after HIBD, at the same time the proliferation of glial cells appeared.

CONCLUSION

The increased expression of caspase-1 and IL-18 mRNA after HIBD, regularity of which was consistent with the time frame for development of brain injury, implied that they may play important roles in the pathogenesis of HIBD in neonatal rats.