国家神经系统疾病临床医学研究中心数据管理与共享系统
Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Protective Functions of PJ34, a Poly(ADP-ribose) Polymerase Inhibitor, Are Related to Down-Regulation of Calpain and Nuclear Factor-kappa B in a Mouse Model of Traumatic Brain Injury
第一作者：Tao, Xiaogang
通讯作者：Liu, Baiyun
基本信息
- 负责人：Tao, Xiaogang
- 数据来源： OTHERS
- 论文编号：OTHERS20190574
- 发表时间：2017-11-01
2017-11-01
已发表文章
主要研究背景及目的
方法
PJ34 (10 mg/kg), a selective PARP inhibitor, was administered intraperitoneally 5 minutes and 8 hours after experimental CCI. We then performed a histopathologic analysis, and we measured calpain activity and protein levels in all animals. The cytosolic, mitochondria, and nuclear fractions were prepared and used to determine the levels of PARP, calpastatin, NF-κB p65, inhibitory-κB-α, tumor necrosis factor-α, interleukin-1β, intracellular adhesion molecule-1, inducible nitric oxide synthase, and cyclooxygenase-2. We then measured blood-brain barrier disruption using electron microscopy at 6 and 24 hours after CCI.
结论
PARP inhibition by PJ34 suppresses the overactivation of calpain and the production of inflammatory factors that are caused by NF-κB activation and attenuates neuronal cell death in a mouse model of CCI.
主要结果
Treatment with PJ34 markedly reduced the extent of both cerebral contusion and edema, improved neurologic scores, and attenuated blood-brain barrier damage resulting from CCI. Our data showed that the cytosolic and nuclear fractions of calpain and NF-κB were up-regulated in the injured cortex and that these changes were reversed by PJ34. Moreover, PJ34 significantly enhanced the calpastatin and inhibitory-κB levels and decreased the levels of inflammatory mediators.