0155 Persistent Activation of TXNIP and NLRP3 Inflammasomes in Cortical Glia and Neurons after Mild Traumatic Brain Injury

Abstract Introduction Mild traumatic brain injuries (TBI) induce persistent dysregulated sleep, reactive oxygen species (ROS), and inflammation. Nucleotide-binding domain leucine rich family pyrin containing 3 (NLRP3) inflammasomes are protein complexes that stimulate caspase-1 to activate the somnogenic pro-inflammatory cytokines IL-1β IL-18. ROS thioredoxin interacting (TXNIP) NLRP3 by inhibiting which inhibits ROS. We previously found mice lacking have increased non-rapid-eye movement (NREM) sleep slow-wave activity (SWA) 24 h after mild TBI, but at 2 months post-injury theses values reduced. Following up on this, we sought determine of in glia neurons TBI. Methods Two-month-old NLRP3, wild-type received a craniectomy TBI via controlled cortical impact or sham. Frontal somatosensory cortices were collected without post-TBI. Microglia, astrocytes, isolated using fluorescent-activated cell sorting, RNA quantified RT-PCR ELISAs. Significance was set p < 0.05. Results RNA, protein, control treatment similar for both genotypes microglia, neurons. In mice, IL-1β, IL-18, caspase-1, TXNIP expression along with significantly greater less levels these types vs. Wild-type levels, areas Mice showed significant reduced post-TBI no differences other measures. Conclusion Our findings suggest induces oxidative stress, TXNIP, inflammasome activation likely contributes dysregulation. Support (if any) Merit Review Award (I01BX005379)(MRZ) SPiRE (I21RX003722)(GBK) Department Veterans Affairs