Interleukin-1 receptor 1 deletion in focal and diffuse experimental traumatic brain injury in mice

Abstract Important differences in the biology of focal and diffuse traumatic brain injury (TBI) subtypes may result in unique pathophysiological responses to shared molecular mechanisms. Interleukin-1 (IL-1) signaling has been tested as a potential therapeutic target in preclinical models of cerebral contusion and diffuse TBI, and in a phase II clinical trial, but no published studies have examined IL-1 signaling in an impact/acceleration closed head injury (CHI) model. We hypothesized that genetic deletion of IL-1 receptor-1 (IL-1R1 KO) would be beneficial in focal (contusion) and CHI in mice. Wild type and IL-1R1 KO mice were subjected to controlled cortical impact (CCI), or to CHI. CCI produced brain leukocyte infiltration, HMGB1 translocation and release, edema, cell death, and cognitive deficits. CHI induced peak rotational acceleration of 9.7 × 105 ± 8.1 × 104 rad/s2, delayed time to righting reflex, and robust Morris water maze deficits without deficits in tests of anxiety, locomotion, sensorimotor...