Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling Pathway

Abstract

Dexmedetomidine (Dex), widely used as a sedative in surgical procedures and intensive care units, induces sympatholytic, anxiolytic, analgesic, and sedative effects. Postoperative cognitive dysfunction (POCD) is routinely observed in postoperative care following surgery and general anesthesia. The NLRP3 inflammasome complex plays a critical role in innate immune response by detecting pathogenic microorganisms and activating pro-inflammatory cytokines. Although there are numerous protective effects of Dex among the neurological diseases, specific mechanisms including NLRP3 inflammasome-mediated neuroinflammation via oxidative stress response in a POCD model are not fully understood. Here, we investigated whether Dex exhibits neurocognitive effects through the NLRP3 inflammasome signaling in a POCD mouse model using a neurobehavioral test and ELISA analysis. We also confirmed the level of oxidative stress-related response in the in vitro system in the POCD model. Furthermore, we evaluated the NLRP3 inflammasome complex by immunoprecipitation analysis. In summary, the results of the present study indicated that Dex showed a neuroprotective effect in the POCD model by reducing oxidative stress response through NLRP3 inflammasome-mediated neuroinflammation.

Clinical characteristics of postoperative cognitive dysfunction after local balloon compression for trigeminal neuralgia: a retrospective study

“…It also inhibits oxygen free radicals, reduces the permeability of blood vessels, reduces the permeability of blood vessels local edema, and reduces blood viscosity and other functions. It has an excellent therapeutic effect on ischemic brain disease, severe craniocerebral injury, coronary heart disease, spinal cord injury, carbon monoxide poisoning, and other diseases [29][30][31][32][33][34]. This study treated 8 patients with postoperative cognitive dysfunction with HBO and revealed that compared with the patients without HBO treatment, the MMSE score of these patients increased rapidly and signi cantly, and cognitive dysfunction symptoms improved more signi cantly after HBO treatment, with no obvious postoperative cognitive dysfunction.…”

Knowledge mapping and research trends on perioperative neurocognitive disorder from 1990 to 2022: a bibliometric analysis

“…The common keywords in cluster #3 were cardiac surgery, blood flow, graft surgery, off-pump, vascular surgery, coronary-artery bypass, etc., which indicated that this cluster was mainly concentrated on the investigation of the correlation between cardiovascular surgery and PND. In cardiovascular surgery, low heart expulsion and secondary cellular metabolic stress and neuroinflammatory response may cause cerebral insufficiency 30 , 31 . Furthermore, the exploration of PND predictive models has proven crucial for the management of PND following cardiovascular surgery 32 .…”

Effects of dexmedetomidine combined with etomidate on postoperative cognitive function in older patients undergoing total intravenous anaesthesia: a randomized, double-blind, controlled trial

“…The activation of microglia induced by the administration of etomidate created an inflammatory environment and stimulated A1-specific astrocyte response, which induced persistent synaptic inhibition and cognitive deficits [ 15 ]. Cho et al [ 24 ] reported that the administration of dexmedetomidine improved the cognitive impairment and reduced pro-inflammatory cytokines by regulating ASC and NLRP3 expression in the POCD model. In our study, after administration of dexmedetomidine, the decrease of etomidate dosage during surgery attenuated the postoperative memory loss and cognitive dysfunction induced by etomidate and central nervous system inflammation was inhibited, which led to the improvement of POCD in older patients under etomidate anesthesia.…”