Inhibiting the CD38/cADPR pathway protected rats against sepsis associated brain injury

• Published in: Brain research 2018-01, Vol.1678, p.56-63
• Main Authors: Peng, Qian-Yi, Wang, Yi-Min, Chen, Cai-Xia, Zou, Yu, Zhang, Li-Na, Deng, Song-Yun, Ai, Yu-Hang
• Format: Article
• Language: English
• Subjects: CD38; Cyclic ADP-ribose; Nicotinamide adenine dinucleotide; Sepsis associated brain injury
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2017.09.029

•The CD38/cADPR pathway was activated in sepsis associated brain injury.•Inhibiting this pathway protected against apoptosis and oxidative stress.•Inhibiting this pathway attenuated ultrastructural morphology damages in brain. The CD38/cADPR pathway has been found to play roles in various inflammatory conditions. However, whether CD38 plays a protective or detrimental effect in the central nervous system (CNS) is controversial. The aim of this study was to determine the effect of CD38/cADPR pathway in sepsis associated brain injury. Male Sprague-Dawley rats were undergone cecal ligation and puncture (CLP) or sham laparotomies. NAD+, cADPR and CD38 were measured in the hippocampus of septic rats at 0, 6, 12, 24, and 48h after CLP surgery. Rats were divided into the sham, CLP group, CLP+ CD38 expression lentivirus (CLP+ CD38 LV), CLP+ CD38 interference lentivirus (CLP+ CD38 Ri), CLP+ negative control lentivirus (CLP+NC) and the CLP+8-Br-cADPR groups. The Western blots of Bcl-2, Bax and iNOS, TUNEL assays, malondialdehyde (MDA) and superoxide dismutase (SOD) assays, transmission electron microscope analysis were performed in the hippocampus of rats. NAD+, cADPR and CD38 levels increased significantly in the hippocampus of septic rats as early as 12–24h after CLP surgery. CD38 knockdown or blocking cADPR with 8-Br-cADPR significantly reduced apoptosis, MDA and SOD activity, iNOS expression and ultrastructural morphology damages in the hippocampus of septic rats. In this study, we found that the CD38/cADPR pathway was activated in sepsis associated brain injury. Blocking this pathway protected the hippocampus from apoptosis, oxidative stress and ultrastructural morphology damages in septic rats.