Hydrogen Sulfide Inhalation Improves Neurological Outcome via NF-κB-Mediated Inflammatory Pathway in a Rat Model of Cardiac Arrest and Resuscitation

Abstract

Background/Aims: The effects of H 2 S on cerebral inflammatory reaction after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) remain poorly understood. In this study, we investigated the effects of exogenous 40 ppm and 80 ppm H 2 S gas on inflammatory reaction and neurological outcome after CA/CPR. Methods: CA was induced by ventricular fibrillation and followed by CPR. Forty or 80 ppm H 2 S was inhaled for 1 h immediately following CPR. The levels of IL-1β, IL-6 and TNF-α, the myeloperoxidase (MPO) activity, the expression of iNOS and ICAM-1, and the phosphorylation and translocation of NF-κB were evaluated at 24 h after CA/CPR. The tape removal test, survival rate and hippocampal neuronal counts were investigated at 14 d after CA/CPR. Results: CA/CPR induced significant increases in IL-1β, IL-6, TNF-α and MPO activity. The phosphorylation and translocation of NF-κB, and the expression of iNOS and ICAM-1 were increased significantly. Inhalation of 40 or 80 ppm H 2 S gas decreased these inflammatory cytokines. Furthermore, 40 or 80 ppm H 2 S inhibited the activation of NF-κB and the downstream proinflammatory mediators iNOS and ICAM-1. H 2 S inhalation also improved neurological function, 14-d survival rate, and reduced hippocampal neuronal loss. Conclusion: These results indicated that inhalation of H 2 S protected against brain injury after CA/CPR. The mechanisms underlying protective effects of H 2 S were associated with the inhibition of CA/CPR-induced inflammation reactions by reducing IL-1β, IL-6 and TNF-α, and concomitantly inhibiting the activation and infiltration of neutrophils. The beneficial effects of H 2 S might be mediated by downregulation of NF-κB and the downstream proinflammatory signaling pathway.