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

Background: 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. Materials and methods: 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 48 h 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. Results: NAD(+), cADPR and CD38 levels increased significantly in the hippocampus of septic rats as early as 12-24 h after CLP surgery. CD38 knockdown or blocking cADPR with 8-Br-cADPR significantly reduced apoptosis, MDA and SOD activity, iNOS expression and ultra structural morphology damages in the hippocampus of septic rats. Conclusions: 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 ultra structural morphology damages in septic rats. (C) 2017 Published by Elsevier B.V.