Dexmedetomidine prevents desflurane‐induced motor neuron death through NF‐KappaB pathway

Abstract

Desflurane is one of the commonly used general anaesthetics. Recently, it was reported that desflurane caused neurotoxicity, raising concerns in clinical use. In this study, we found desflurane could affect viability and maturation in motor neurons.Dexmedetomidine, a α2-adrenergic receptor agonist, could attenuate the effect of desflurane on motor neurons. This process was mediated by NF-KappaB signalling.Interestingly, we also found that dexmedetomidine could recover the lesion in motor function and memory impaired by desflurane. Collectively, our results showed the neurotoxic effect of desflurane in motor neurons. More importantly, this process was alleviated by dexmedetomidine, potentially showing its application in protecting motor neuron from neurotoxic agents.Significance of the study: This work provides the evidence to support the protective role of dexmedetomidine in desflurane-induced motor neuron death. Since desflurane is a widely used anaesthetic in surgery and leads to neuron death, the neuroprotective effect of dexmedetomidine holds promising clinical application.

Feasibility study of use of desflurane combined with dexmedetomidine in inhibiting postoperative neurocognitive disorders in elderly patients under general anesthesia: A perspective study

“…Interestingly, Des was found to have neurotoxic effects on motor neurons, and more importantly, Dex mitigated this process, which may indicate its application in protecting motor neurons from neurotoxic effects. This study provides evidence for the protective effect of Dex on Des‐induced motor neuron death 10 In a pediatric study, Dex reduced the incidence of sudden irritation, postoperative nausea and vomiting, postoperative pain, and Oculocardiac reflex in patients who had undergone pediatric strabismus surgery. 11 Compared with the use of propofol + Des and Des + Dex, we found that the postoperative extubation time of Dex was significantly shortened, indicating that the use of Dex + Des can achieve rapid extubation.…”

“…A meta‐analysis in 2021 of 15 randomized control study, contains a total of 2183 patients, including 1079 cases of patients who used the Dex, 1104 cases did not receive Dex, the results showed whether the inhalation anesthesia or systemic intravenous anesthesia in adult patients undergoing heart surgery, Dex administration reduced the likelihood of postoperative cognitive and behavioral dysfunction by at least 43% 24 . Des has been found to affect Moto neuron viability and maturation in vitro, but the α2‐adrenergic receptor agonist Dex attenuates the effects of Des on motor neurons, and this process is mediated by nuclear factor‐κB (NF‐κB) signaling 10 . In pediatric patients undergoing tonsillectomy or adenoidectomy, maintenance of anesthesia with Des and Dex can effectively prevent emergence agitation 25 .…”

“…(3) preoperative patients with cognitive dysfunction and hearing impairment; (4) patients with a history of long-term use of narcotic analgesics, sedatives, and antidepressants; (5) patients with a body mass index (BMI) ≥ 35 kg/m 2 ; (6) patients with a preoperative acute infection; (7) patients who could not comply with followup evaluations; (8) patients who had participated in other clinical trials within 3 months before the current study; (9) patients with a history of severe cardiovascular disease (e.g., coronary heart disease, congenital heart disease, and ≥Grade 3 cardiac function); (10) patients with a history of alcohol and drug use; (11) patients with mental disorders; and (12) patients who could not communicate.…”

Dexmedetomidine alleviates propofol-induced pyroptosis of hippocampal neurons through NLRP3 inflammasome pathway

“…Data are accumulating that propofol is a contributor to neurotoxicity and neuron damage to the developing nervous system, raising widespread concern about the usage and safety of propofol in anesthesia, particularly in pediatrics [25,26]. On the other side, dexmedetomidine, an adjuvant drug widely utilized in anesthesia, antagonizes neurotoxicity posed by anesthetic drugs by modulating neuronal viability, maturation, and death [27]. The present study expounded on the neuroprotective function of dexmedetomidine on propofol-induced pyroptosis of hippocampal neurons through cooperation with the HOXA5/NLRP3 axis.…”

Dexmedetomidine regulates sevoflurane‐induced neurotoxicity through the miR‐330‐3p/ULK1 axis

“…[ 8 ] Dex regulates the NF‐κB pathway to protect against desflurane‐triggered motor neuron death. [ 9 ] Besides this, Dex attenuates lidocaine‐mediated neurotoxicity through SIRT1 suppression‐mediated FOXO3a activation. [ 10 ] In addition, the protective effects of Dex on Sev‐induced neurotoxicity were also confirmed in different studies.…”