ABSTRACT
A growing number of studies have identified sex differences in response to general anesthesia; however, the underlying neural mechanisms are unclear. The medial preoptic area (MPA), an important sexually dimorphic structure and a critical hub for regulating consciousness transition, is enriched with estrogen receptor alpha (ERα), particularly in neuronal clusters that participate in regulating sleep. We found that male mice were more sensitive to sevoflurane. Pharmacological inhibition of ERα in the MPA abolished the sex differences in sevoflurane anesthesia, in particular by extending the induction time and facilitating emergence in males but not in females. Suppression of ERα in vitro inhibited GABAergic and glutamatergic neurons of the MPA in males but not in females. Furthermore, ERα knockdown in GABAergic neurons of the male MPA was sufficient to eliminate sex differences during sevoflurane anesthesia. Collectively, MPA ERα positively regulates the activity of MPA GABAergic neurons in males but not in females, which contributes to the sex difference of mice in sevoflurane anesthesia.
Subject(s)
Animals , Female , Male , Mice , Anesthesia , Estrogen Receptor alpha/metabolism , Preoptic Area , Sevoflurane/pharmacology , Sex CharacteristicsABSTRACT
Post-traumatic stress disorder(PTSD) caused by various natural disasters and man-made events has gradually become the highlight of neuroscientists. Sleep disorders after PTSD can impair the effect of treatment and affect the patient's prognosis. In addition, treatment for sleep problems can be effective in improving outcomes for people with PTSD, which indicates that it is significant to pay attention to sleep disorders after PTSD. However, current studies have focused more on the incidence of PTSD and severity of related symptoms after a traumatic event, and less on the occurrence and mechanism of sleep disorders after PTSD. A number of articles on stress and sleep disorders published in recent years provide reliable clues to understand the probable mechanisms of sleep disorders after PTSD. After summarizing the latest research results, this article finds that the occurrence of sleep disorder after PTSD may be related to the changes of connectivity between insula, hippocampus and medial-prefrontal cortex. Apart from that, decline in the mean phase difference of slow spindles in PTSD patients may reflect pathological changes in the thalamic cortical circuit, which may contribute to the objective diagnosis of PTSD and the development of sleep-focused interventions. This paper provides a systematic review of changes in sleep characteristics and possible neural circuitry mechanisms after PTSD from clinical and basic perspectives, which may provide potential directions for future researches on the pathological mechanism of sleep disorders after PTSD and screening novel intervention targets.
ABSTRACT
The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.
ABSTRACT
Objective To evaluate the effect of TanshinonneⅡA preconditioning on nuclear factor kappa B ( NF-κB ) signaling pathway in N9 cells subjected to oxygen-glucose deprivation and restoration ( OGD∕R) . Methods N9 cells cultured in vitro were divided into 4 groups ( n=16 each) by using a ran-dom number table method: control group ( C group) , OGD∕R group, vehicle group ( V group) and Tanshi-none ⅡA preconditioning group ( TP group) . N9 cells were subjected to O2-glucose deprivation for 4 h fol-lowed by restoration of O2-glucose supply for 24 h to establish the OGD∕R model. Group C receive no treat-ment. In group TP, N9 cells were cultured in medium containing Tanshinone ⅡA ( final concentration 5 mg∕L) for 24 h before the model was established. Dimethyl sulfoxide was added to the culture medium in group V. At the 24 h of reoxygenation, the level of lactate dehydrogenase ( LDH) and nitric oxide ( NO) in culture medium was detected by spectrophotometry, cell apoptosis was assessed by using TUNEL, and the expression of NF-κB in nucleus was detected by Western blot. The apoptosis rate was calculated. Results Compared with group C, the levels of LDH, IL-β, TNF-α and NO in culture medium and apoptosis rate were significantly increased, and the expression of NF-κB in nucleus was up-regulated in OGD∕R, V and TP groups ( P<0. 05) . Compared with group OGD∕R, the levels of LDH, IL-β, TNF-αand NO in culture me-dium and apoptosis rate were significantly decreased, and the expression of NF-κB in nucleus was down-reg-ulated in group TP ( P<0. 05) , and no significant change was found in the parameters mentioned above in group V ( P>0. 05 ) . Conclusion The mechanism by which Tanshinonne ⅡA preconditioning reduces OGD∕R injury to N9 cells is related to inhibiting NF-κB signaling pathway.
ABSTRACT
Objective To investigate the role of N-myc downstream regulated genes 2 (NDRG2) in attenuation of focal cerebral ischemic-reperfusin injury by sevoflurane preconditioning in rats.Methods Forty-eight healthy male SD rats weighing 280-320 g were randomly divided into 3 groups ( n =16 each):sham operation group (group S),ischemia-reperfusion injury group (group I/R) and sevoflurane preconditioning group (group Sev).Focal cerebral ischemia-reperfusion injury was induced by right middle cerebral artery occlusion (MCAO)for 120 min followed by 24 h reperfusion.In group Sev,2.0％ sevoflurane was inhaled 1 h once a day for 5 consecutive days at 24 h before MCAO.The neurologic function was evaluated at 24 h of reperfusion and than the rats were sacrificed,and the brain was removed for determination of infarct volume percentage,NDRG2 and activated Caspase-3 expression in ischemic penumbra by Western Blot and NDRG2 expression and location by immunohistochemistry.Results The infarct volume percentage,NDRG2 and activated Caspase-3 expression were higher,and neurologic function score was lower in groups I/R and Sev then in group S( P ＜ 0.05).The infarct volume percentage,NDRG2 and activated Caspase-3 expression were lower,and neurologic function score was higher in group Sev then in group I/R ( P ＜ 0.05).The intranuclear NDRG2 positive staining was decreased in group Sev than in group I/R.Conclusion Sevoflurane preconditioning can reduce focal cerebral ischemia-reperfusion injury by inhibiting the expression and activity of NDRG2 and apoptosis in rats.