Abstract # 3078 Contributions of astrocytic IL-1R1 signaling in blast-induced traumatic brain injury

Traumatic Brain Injury (TBI) is a leading cause of disability in the United States with an annual economic cost of $76.5 billion. TBI results in profound astrogliosis, the generation of neuropsychiatric complications and an increased incidence of seizures. TBI increases CNS proinflammatory cytokine expression and recent reports have shown that interleukin-1alpha ( IL-1alpha ) signaling is a requirement for the generation of neurotoxic astrocytes. We hypothesize that IL-1alpha and interleukin-1beta ( IL-1beta ) signal through functional type 1 interleukin-1 receptors (IL-1R1’s) on astrocytes post-injury thereby contributing to negative functional outcomes post-TBI. Using a murine model of blast-induced TBI (bTBI), we detected increased mRNA expression and immunoreactivity of the astrocytic marker glial fibrillary acidic protein (GFAP) in the ipsilateral cortex as compared to sham animals, signifying the presence of reactive astrocytes. Increases in il-1beta , il-1alpha and tnf-alpha mRNA were detected post-TBI, indicating increased CNS production of proinflammatory cytokines post-TBI. Mice exposed to bTBI exhibited increased impulsive-like behaviors in the elevated plus maze (EPM) and an increase in the propensity for kainic acid (KA)-induced seizures. Future studies will utilize murine models affording the conditional restoration and elimination of IL-1R1 (Robson et al. 2016) in astrocytes in conjunction with bTBI to study neuroinflammatory profiles and functional outcomes post-injury. Understanding the molecular and temporal requirements for the negative consequences of IL-1R1 signaling post-injury may lead to therapeutic options for those with TBI.