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Our aim was to characterize the expression of IL-18 and its receptor in relation to caspase-1 and IL-1\u03b2 after HI and to evaluate to what extent IL-18 contributes to HI brain injury. Seven-day-old rats were subjected to HI, and brain tissue was sampled at different time points (3 hr to 14 d) after insult. The mRNA for IL-18 and caspase-1 were analyzed with reverse transcriptase PCR, protein was analyzed by Western blot (IL-18, caspase-1) or ELISA (IL-1\u03b2), and the regional distribution was assessed by immunohistochemistry. HI was also induced in C57BL\/6 mice, and brain injury in IL-18-deficient animals was compared with that in wild-type animals. The expression of mRNA\/protein for caspase-1 and IL-18 in brain homogenates increased progressively at 12 hr to 14 d after HI, whereas IL-1\u03b2 peaked at 8 hr. A widespread expression of caspase-1 and IL-18 protein in microglia was found in the HI hemisphere. The IL-18 receptor was expressed on neurons of the cerebral cortex and thalamus. IL-1\u03b2 was primarily found in microglia in the habenular nucleus of the thalamus. The infarct volume was reduced by 21% (<jats:italic>p<\/jats:italic>= 0.01), and the neuropathology score was significantly decreased in the cerebral cortex (\u221235%), hippocampus (\u221222%), striatum (\u221218%), and thalamus (\u221217%) in mice with IL-18 deficiency compared with wild-type mice. In conclusion, we found that IL-18 expression in microglia was markedly increased after HI and that IL-18 appears to be important for the development of HI brain injury.<\/jats:p>","DOI":"10.1523\/jneurosci.22-14-05910.2002","type":"journal-article","created":{"date-parts":[[2018,4,3]],"date-time":"2018-04-03T19:25:25Z","timestamp":1522783525000},"page":"5910-5919","source":"Crossref","is-referenced-by-count":238,"title":["Interleukin-18 Involvement in Hypoxic\u2013Ischemic Brain 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