Excessive hydrogen sulfide-induced activation of NMDA receptors in the colon participates in anxiety- and compulsive-like behaviors in a rodent model of hemorrhagic shock and resuscitation.

The bidirectional communication pathway between the gut and the central nervous system is referred to as the gut-brain axis. The intestinal tract of HSR mice produces excessive H2S, the intestinal mucosal barrier is damaged, and intestinal inflammation occurs, which leads to the activation of microglia in the amygdala. At the same time, NMDA receptors are activated, and inflammatory factors are released, eventually leading to the occurrence of anxiety and compulsive-like behaviors. [Display omitted] • Hemorrhage shock and resuscitation (HSR) causes repetitive compulsive behaviors. • HSR induces intestinal inflammation, which is associated with Hydrogen sulfide. • HSR induces neuroinflammatory response. • DL-Propargylglycine (PAG) intragastrically as an H2S scavenger improved above symptoms in HSR mice. • MK-801, an NMDA receptor inhibitor, significantly reversed H2S-induced intestinal and cerebral injury. Hemorrhagic shock and resuscitation (HSR) cause inflammatory responses in the gastrointestinal tract and is associated with substantial morbidity and mortality rates. Hydrogen sulfide (H 2 S), a gasotransmitter with pleiotropic activity, exhibits anti-inflammatory benefits at physiological levels. However, deleterious effects are observed when its concentration increases. In this investigation, we employed a mouse model of HSR to examine the effects of an H 2 S scavenger on the gastrointestinal tract and brain, with emphasis on N-Methyl- d -Aspartate (NMDA) receptor function. Mice were immediately administered dl -propargylglycine (PAG) intragastrically as an H 2 S scavenger after HSR exposure. The O-maze and buried beads tests were used to assess compulsive- and anxiety-like behaviors. Pathological changes in the intestine were evaluated at 24 and 30 days after HSR. Subsequently, at 30 days after HSR, we examined electrophysiological and pathological changes in the amygdala. Within 24 h of HSR exposure, animals treated with PAG showed significantly lower colonic injury. Additionally, compared to the HSR-treated mice 30 days after HSR, the PAG-treated mice displayed reduced buried beads, increased open-arm time, lower blood levels of Diamine Oxidase (DAO) and considerably improved ZO-1 intensity, a stronger association between the delta rhythm phase and beta activity amplitude, and lower neuroinflammatory response in the amygdala. MK-801, an NMDA receptor inhibitor, significantly reversed H 2 S-induced intestinal and cerebral injury. This experimental data suggests that H 2 S-induced excessive activation of NMDA receptors contributes to anxiety- and compulsive-like behaviors caused by HSR. [ABSTRACT FROM AUTHOR]