Interleukin-1 (IL-1) has many roles in the brain in addition to mediating inflammatory processes in the glia, and has also been implicated in neurodegenerative disease. Traumatic brain injury (TBI) is one of the most prevalent causes of morbidity and mortality in young persons. We conducted a study to assess the effect of IL-1 on the TBI-induced death of hippocampal neurons. After TBI was induced in adult male Sprague-Dawley rats under anesthesia, we evaluated neuronal damage score through microscopic examination and Pulsinelli's grading system. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to measure the levels of IL-1α and IL-1β in brain tissue at different points after the induction of TBI. Over a 4-day period, the specific sites of release of IL-1α and IL-1β in the brain were elucidated by immunocytochemistry with double-labeling. TBI to the hippocampus was followed by disruption of the blood-brain barrier and severe neuronal loss. Levels of IL-1α RNA and protein were significantly elevated at 3 h after TBI, peaked at 12 h, and remained elevated for 168 h. IL-1β RNA and protein expression were also elevated at 3 h after TBI, but remained so only for 48 h. Our findings indicate that the observed TBI-induced increases in IL-1α and IL-1β occur largely through release of these cytokines from neurons and astrocytes, respectively. Intraventricular administration of antibodies to IL-1α and IL-1β before TBI significantly attenuated the TBI-induced loss of hippocampal neurons. These results show that IL-1α and IL-1β play important roles in the TBI-induced loss of hippocampal neurons.
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