Interleukin-18 Involvement in Hypoxic–Ischemic Brain Injury
Copyright policy )Interleukin-18 Involvement in Hypoxic–Ischemic Brain Injury
Inflammation is a critical factor for development of hypoxic–ischemic (HI) brain injury. Interleukin-18 (IL-18) is a proinflammatory cytokine expressed in microglia and processed by caspase-1. Our aim was to characterize the expression of IL-18 and its receptor in relation to caspase-1 and IL-1β 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-1β), 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-1β 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-1β was primarily found in microglia in the habenular nucleus of the thalamus. The infarct volume was reduced by 21% (p= 0.01), and the neuropathology score was significantly decreased in the cerebral cortex (−35%), hippocampus (−22%), striatum (−18%), and thalamus (−17%) 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.
- University of Gothenburg Sweden
Brain Chemistry, Male, Mice, Knockout, Blotting, Western, Caspase 1, Interleukin-18, Brain, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Mice, Inbred C57BL, Disease Models, Animal, Mice, Animals, Newborn, Hypoxia-Ischemia, Brain, Disease Progression, Animals, Female, Microglia, Interleukin-18 Receptor alpha Subunit, Interleukin-1
Brain Chemistry, Male, Mice, Knockout, Blotting, Western, Caspase 1, Interleukin-18, Brain, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Mice, Inbred C57BL, Disease Models, Animal, Mice, Animals, Newborn, Hypoxia-Ischemia, Brain, Disease Progression, Animals, Female, Microglia, Interleukin-18 Receptor alpha Subunit, Interleukin-1
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