The role and mechanism of TIGAR in intracerebral hemorrhage

• 1、Department of Pharmacy, Soochow University, Suzhou, Jiangsu 215123

Abstract：This study aimed to investigate the role of TIGAR (TP53-induced glycolysis and apoptosis regulator) in intracerebral hemorrhage (ICH) injury and the underlying mechanisms.Methods:ICH was induced by injecting collagenase into the right striatum of 8-10-week-old male C57 mice using brain stereotactic techniques. Brain tissues were collected at various time points after ICH. The protein levels of TIGAR following ICH were assessed through Western blotting. Wild-type mice, TIGAR overexpression (TG) mice and TIGAR knockout (KO) mice were utilized to evaluate the effect of TIGAR on ICH injury by measuring cerebral hematoma volume, neurological deficit score and forelimb placement experiment. Additionally, Western blotting along with real-time quantitative fluorescent PCR (qPCR) techniques were employed to measure the expression levels of NOD-like receptor thermal protein domain protein 3 (NLRP3), cysteine protease-1 (caspase1), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Results: TIGAR protein levels are markedly elevated, particularly at 6 hours post-ICH. In addition, inflammatory response were enhanced after ICH as evidenced by elevated levels of NLRP3, cleaved-caspase-1, IL-1β and IL-6. TIGAR overexpression attenuated neurological deficits and decreasing hematoma volume following ICH. Conversely, TIGAR knockout exacerbated neurological deficits and increases hematoma volume. Additonally, TIGAR inhibited the expression of inflammasome NLRP3 and cleaved-caspase1, and reduced the mRNA levels of inflammatory cytokines IL-1β and IL-6. Conclusions: TIGAR protein levels are upregulated post-ICH. TIGAR may attenuate ICH injury by inflammation.

Keywords： TIGAR intracerebral hemorrhage inflammation NLRP3