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

Abstract

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 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.

RESULTS:

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.

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 ultrastructural morphology damages in septic rats.

• Authors: Qian-Yi Peng, Yi-Min Wang, Cai-Xia Chen, Yu Zou, Li-Na Zhang, Song-Yun Deng, Yu-Hang Ai
• Journal: Brain research (Brain Res) Vol. 1678 Pg. 56-63 (Jan 01 2018) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 29030054 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier B.V.

Chemical References

• 8-bromo-cyclic-ADP-ribose
• Membrane Glycoproteins
• Cyclic ADP-Ribose
• Superoxide Dismutase
• ADP-ribosyl Cyclase
• Cd38 protein, rat
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase (antagonists & inhibitors, metabolism)
• ADP-ribosyl Cyclase 1 (antagonists & inhibitors, metabolism)
• Animals
• Apoptosis
• Brain Injuries (complications, metabolism)
• Cecum (surgery)
• Cyclic ADP-Ribose (analogs & derivatives, antagonists & inhibitors, metabolism, pharmacology)
• Disease Models, Animal
• Hippocampus (metabolism)
• Male
• Membrane Glycoproteins (antagonists & inhibitors, metabolism)
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Sepsis (metabolism, prevention & control)
• Superoxide Dismutase (metabolism)