Involvement of PARP in calpain and NF-κB activation during traumatic brain injury in mice

• 作 者: XiaogangTao[1]XuetaoChen[1]XiangMao[2]RunfaTian[1]ZonggangHou[1]ShuyuHao[1]ZhendanZhu[2]MingSun[3]BaiyunLiu[4]
• 机 构: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing,100050, Ch
• 出 处: 2014全国神经损伤大会暨第三届天坛全国神经创伤学术研讨会
• 发表日期: 2014年期

　　Poly(ADP-ribose)polymerase (PARP), calpain and nuclear factor-κB (NF-κB) are reported to participate in inflammatory reaction under pathological conditions, and they are involved in traumatic brain injury.The objective of this study was to investigate whether PARP participated in the inflammation related to calpain and NF-κB in a mouse model of controlled cortical impact (CCI).PJ34 (10 mg/kg), a selective of PARP inhibitor, was administered intraperitoneally at 5 min and 8 h after experimental CCI.Treatment with PJ34 markedly reduced neurological deficits, decreased the contusion volume, and attenuated the necrotic and apoptotic neuronal cell death at 24 h after CCI.Our data showed the up-regulation of calpain and NF-κB in cytosolic fractions and nuclear fractions in the injured cortex, and these changes were reversed by P J34.Moreover, P J34 significantly enhanced the levels of calpastatin and Iκ B, and lessened the levels of tumor necrosis factor-a, interleukin-1β, intracellular adhesion molecule-l, inducible nitric oxide synthase, and cyclooxygenase-2.These data suggest the involvement of PARP in the inflammatory reaction through up-regulating calpain and NF-κB -driven expression of inflammatory factors during CCI.