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.

Objective: 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.
Methods: 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.
Results: 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.
Conclusion: This experimental data suggests that H ₂ S-induced excessive activation of NMDA receptors contributes to anxiety- and compulsive-like behaviors caused by HSR.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)