MiR-214-3p Prevents the Development of Perioperative Neurocognitive Disorders in Elderly Rats

Objective:This study aimed to identify microRNAs(miRNAs)involved in the development of perioperative neurocognitive disorders(PND).Methods:Plasma exosomal miRNA expression was examined in patients before and after cardiopulmonary bypass(CPB)using microarray and qRT-PCR and these patients were diagnosed as PND later.Elderly rats were subjected to CPB,and the cognitive functions were examined.Bioinformatics analysis was conducted to predict the targets of miR-214-3p.Rats were administered rno-miR-214-3p agomir before or after CPB to investigate the role of miR-214-3p in PND development.Results:We identified 76 differentially expressed plasma exosomal miRNAs in PND patients after surgery(P<0.05,|log2FC|>0.58),including the upregulated hsa-miR-214-3p(P=0.002399392).Prostaglandin-endoperoxide synthase 2(PTGS2)was predicted as a miR-214-3p target.In rats,CPB reduced the platform crossing numbers and target quadrant stay time,accompanied with hippocampal neuronal necrosis.The rno-miR-214-3p level was significantly increased in plasma exosomes but decreased in rat hippocampus after surgery,exhibiting a negative correlation(P<0.001,r=-0.762).A negative correlation between miR-214-3p and PTGS2 protein expression was also observed in the hippocampus after surgery.Importantly,rno-miR-214-3p agomir treatment,before or after surgery,significantly increased the platform crossing numbers(P=0.035)and target quadrant stay time(P=0.029)compared with negative control.Hippocampal PTGS2 protein level was increased in the untreated surgery group and decreased in response to rno-miR-214-3p agomir treatment before or after surgery(both P<0.05 vs.negative control).Conclusion:These data suggest that miR-214-3p/PTGS2 signaling contributes to the development of PND,serving as a potential therapeutic target for PND.

Impact of edaravone on serum CXC chemokine ligand-13 levels and perioperative neurocognitive disorders in elderly patients with hip replacement

Background:Perioperative neurocognitive disorders(PND)are a series of severe complications in the perioperative and anesthetic periods with a decline in memory,execution ability,and information processing speed as the primary clinical manifestation.This study aimed to evaluate the impact of edaravone(EDA)on PND and peripheral blood C-X-C motif chemokine ligand 13(CXCL13)levels in elderly patients with hip replacement.Methods:A total of 160 elderly patients undergoing hip arthroplasty in Affiliated Dongguan People’s Hospital of Southern Medical University(from March 2016 to March 2018)were randomly and double-blindly categorized into an EDA group and a control group(CON).Group EDA was administered intravenously EDA 30 min before surgery,and group CON was administered intravenously saline.The cognitive function of the two groups was evaluated 1-day before the operation and at 1 and 12 months after surgery,and the incidence of post-operative delirium was tested on days 1,3,and 7 after surgery using the Chinese version of the confusion assessment method.Serum CXCL13 and interleukin(IL)-6 concentrations were measured before anesthesia,during surgery(30 min after skin incision),and on days 1,3,and 7 after surgery.The continuous variables in accordance with normal distribution were tested using the Student’s t test,the continuous variables without normal distribution using the Mann-Whitney U test,and categorical variables by the x 2 test or Fisher exact test.Results:The incidence of post-operative delirium within 7 days after surgery was significantly higher in group CON than that in group EDA(31.3%vs.15.0%,t=-5.6,P<0.001).The modifiedtelephone interview for cognitive status andactivities of daily life scores were significantly higher in the group EDA than those in the group CON at 1 month(39.63±4.35 vs.33.63±5.81,t=-2.13,P<0.05and 74.3±12.6 vs.61.2±13.1,t=-1.69,P<0.05)and 12 months(40.13±5.93 vs.34.13±5.36,t=-3.37,P<0.05 and 79.6±11.7 vs.65.6±16.6,t=-2.08,P<0.05)after surgery;and the incidence of neurocognitive dysfunction was significantly lower in the group EDA than that in the group CON(P<0.05).Serum CXCL13 and IL-6 concentrations were significantly lower in the group EDA than those in the group CON during and after surgery(P<0.05).Conclusion:EDA can significantly reduce the serum concentrations of CXCL13 and IL-6 and improve the PND of patients.

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells.Oligodendrocytes perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity regulation.They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and apoptosis.Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes.These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function.In this review,we summarize the effects of general anesthetic agents on oligodendrocytes.We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

Effect of Nalmefene on Delayed Neurocognitive Recovery in Elderly Patients Undergoing Video-assisted Thoracic Surgery with One Lung Ventilation

The intravenous use of nalmefene has been found to exert neuroprotective effect in patients with severe traumatic brain injury and acute cerebral infarction;nonetheless,it is unknown whether nalmefene alleviates delayed neurocognitive recovery.Our purpose of the current research was to clarify the impact of nalmefene on delayed neurocognitive recovery in aged patients experiencing video-assisted thoracic surgery(VATS)with intraoperative use of one lung ventilation(OLV).The present study involved 120 paticents undergoing selective VATS,randomized to accept low-dose nalmefene(N1 group,n=40),high-dose nalmefene(N2 group,1n=40)or equal volume of physiologic saline(control group,1=40).A battery of neuropsychological tests were used to estimate cognitive function I day before surgery(o)and 10 days after surgery or before discharge(t).Regional cerebral oxygen saturation(rSO2)was detected 5 min before induction(t),5 min after induction(1),15 and 60 min after onset of OLV(62 and 13),and 15 min after termination of OLV(4).The plasma values of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-a1 and adiponectin(ADP)were also detected prior to induction of anesthesia(T0),1 h,2 h and 6 h after surgery(TI,T2,T3).On 1,delayed neurocognitive recovery occurred in 5/40(12.5%)patients of NI group,in 5/40(12.5%)patients of N2 group and in 13/40(32.5%)patients of control group(P<0.05).There were no statistical differences in rSO2 among three groups at different time points.At Tl,T2 and T3,IL-1β,IL-6 and TNF-a values significantly increased and ADP value significantly decreased(P<0.05)in control group.In contrast,at TI,T2 and T3,IL-1β,IL-6 and TNF-a values decreased and ADP value decreased less in N1 and N2 groups(P<0.05).At TI,T2 and T3,IL-1β,IL-6 and TNF-a concentrations presented a trend of N2 group<N1 group<control group and ADP presented a trend of N2 group>Nl group>control group(P<0.05).The result of our present research supports the hypothesis that the perioperative intravenous treatment with nalmefene to VATS with OLV ameliorates postoperative cognitive function and decreases the incidence of delayed neurocognitive recovery,most likely by suppression of inflammatory responses.