Exogenous hydrogen sulfide alleviates surgery-induced neuroinflammatory cognitive impairment in adult mice by inhibiting NO signaling

Abstract

Background: To investigate the effect and mechanisms of exogenous hydrogen sulfide in surgery-induced neuroinflammatory cognitive dysfunction. Methods: C57BL/6 J male mice (n = 140) were used and randomly divided into seven groups: the sham group, surgery group, GYY4137 group, L-NAME group, surgery+GYY4137 group, surgery +L-NAME group, and surgery+GYY4137 + L-NAME group. After the interventions, open field tests (OFT) and the Morris water maze (MWM) test were conducted to evaluate learning and memory abilities in the mice. ELISAs, nitrate reductase assays, and Western blots (WB) were conducted to evaluate interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and antioxidant enzyme superoxide dismutase (SOD) levels. Furthermore, the expression level of microglial marker ionized calcium binding adaptor molecule 1 (IBA) in the hippocampal CA1 and CA3 areas was detected by an immunohistochemical (IHC) assay and apoptotic cells were observed using terminal deoxynucleotidyl transferase dUTP end-labeling (TUNEL) staining kits. Results: We found that surgery induced neuroinflammatory cognitive dysfunction, oxidative stress, microglial activation, and cell apoptosis in the hippocampus. Moreover, following surgery, NO and iNOS levels were elevated in the hippocampus. Notably, all the effects caused by surgery were reversed by the H 2 S donor GYY4137 or the iNOS inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME). However, the combined application of GYY4137 and L-NAME was not superior to treatment with either agent alone and the effect of GYY4137 was similar to that of L-NAME. Conclusion: The long-acting hydrogen sulfide donor GYY4137 had an ability to reversed the cognitive deficits and inflammation caused by carotid artery exposure surgery. This implies that NO signaling pathways might participate in this process. These results indicate that exogenous H 2 S may be a promising therapy for POCD.

Detection of H2S using a novel fluorescent nanoprobe in plasma and tissue samples from ASD patients and model mice

“…, and neuroinflammatory cognitive impairment induced by surgery in adult mice. 31,32 The above findings suggest that H 2 S is involved in neurocentral protection and can improve cognition and other functions.…”

MD2 contributes to the pathogenesis of perioperative neurocognitive disorder via the regulation of α5GABAA receptors in aged mice

“…PND has been recognized for more than 100 years, and many studies aiming to elucidate the pathogenesis of PND from different perspectives, including impaired synaptic function, neuroinflammation, oxidative stress in the central nervous system, and the microbiota-gutbrain axis, have been performed [45][46][47][48]. Although these studies have helped to exploit pharmacologic agents to treat PND, few pharmacologic agents have been developed.…”

Adiponectin Mediates the Protection of H2S Against Chronic Restraint Stress-Induced Cognitive Impairment via Attenuating Hippocampal Damage

“…CRS induces hippocampal lesions and learning and memory dysfunction associated with apoptosis (H. Zhang et al, 2020). Our previous studies reveal that exogenous H 2 S alleviates surgery- (Yin et al, 2020), formaldehyde- (Li et al, 2019), and diabetes- (Ma et al, 2017) induced cognitive dysfunction through inhibiting apoptosis in the hippocampus. Our recent study also reveals that H 2 S blocks CRS-led to cognitive impairment involved in attenuating hippocampal apoptosis (Xiao-Na et al, 2017).…”