| In recent years,with the progress of surgery and anesthesia technology,more and more elderly patients can choose surgery to treat diseases.Forelderly patients,due to the self-regulation of brain function decline,postoperative neurocognitive disorders probability increased dramatically.perioperative cognitive decline includes postoperative delirium(POD)and postoperative cognitive dysfunction(POCD).POD is common in elderly patients early after surgery and is typically characterized by dramatic changes in mental state,inattention,confusion,and altered consciousness.POCD is a more durable form of cognitive change that includes short-term and long-term memory(that is,a reduction in the ability to learn or recall information),mood,consciousness and circadian rhythm changes.Both were associated with increased perioperative mortality,nursing dependency,hospitalization costs,and length of stay.At present,its specific mechanism is not clear,there is no effective prevention and treatment.The neuroinflammation may be one of the important causes of perioperative neurocognitive dysfunction.Therefore,a number of studies have demonstrated that reducing peripheral and central system inflammatory response can effectively prevent and treat postoperative cognitive decline.Electroacupuncture is an adjunctive alternative medicine technique that uses acupuncture by applying an electric current to the needles.The effectiveness of electroacupuncture in improving cognitive performance in Alzheimer’s disease and vascular dementia has been demonstrated in various clinical and animal studies.In animal studies,electroacupuncture has been shown to reduce cognitive impairment in animal models of Alzheimer’s disease through anti-neuroinflammation.The neuroprotective effect induced by electroacupuncture is related to its anti-inflammatory activity.A large number of studies have suggested that its anti-inflammatory effect may be related to the activation of cholinergic anti-inflammatory pathway.Therefore,we speculated that electroacupuncture pretreatment can improve postoperative cognitive dysfunction in elderly patients induced by surgery,and the mechanism may be related to the activation of cholinergic anti-inflammatory pathway to reduce postoperative neuroinflammation.Part one Effect of electroacupuncture pretreatment on postoperative cognitive function in aged ratsObjective:To investigate the effect of electroacupuncture pretreatment on cognitive dysfunction after tibial fracture in aged rats.Methods:Male Sprague-Dawley rats(20 months old)were randomly assigned to three groups:control group(n=12),POCD group(n=12)and EA group(n=12).Rats in the POCD group were subjected to tibial fracture surgery.EA pretreatment was performed once a day for 5 days and were subjected to POCD 24 h after the last treatment.The rats in the vehicle group were only treated with a skin incision and suture on the left-hind paw following anesthesia.30 days after the operation,a novel objective recognition test was conducted to record the cognitive index,preference index,distance and speed of the rats.The Morris water maze were performed 31-35 days after operation,and the escape latency,crossing platform times,swimming speed and distance of the rats were recorded.Results:Compared with Con group,the cognitive index(RI)and cross-platform times of POCD group and EA group were significantly decreased(P<0.0001),and the escape latency of POCD group was significantly prolonged(P<0.0001).Compared with EA group,The cognitive index(RI)of POCD group was significantly decreased(P<0.05),and the escape latency of POCD group was significantly prolonged(P<0.0001).Conclusion:Tibial fracture surgery leads to postoperative cognitive dysfunction in aging rats,Electroacupuncture pretreatment can ameliorates postoperative cognitive dysfunction in aging rats induced by tibial fracture surgery.Part two Electroacupuncture Pretreatment Ameliorates Surgery-Ind uced Cognitive Dysfunction via Activation of α7-nAChR/H MGB1/NF-κB pathway in Aged RatsObjective:To investigate the mechanism of electroacupuncture pretreatment in ameliorates cognitive dysfunction after tibial fracture in aged rats.Methods:Male Sprague-Dawley rats(20 months old)were randomly assigned to the following 5 groups(n=12):vehicle;POCD(tibial fracture surgery);EA plus POCD;EA plus POCD and alpha-bungarotoxin(α-BGT);and POCD plus α-BGT groups.Rats in the POCD group were subjected to tibial fracture surgery.EA pretreatment was performed once a day for 5 days and were subjected to POCD 24 h after the last treatment.The rats in the vehicle group were only treated with a skin incision and suture on the left-hind paw following anesthesia.Alpha-bungarotoxin(1 μg/kg),a selective antagonist of α7-nAChR,was administrated via intraperitoneal injection before EA.Thirty days post Surgery,the Morris water maze and a novel objective recognition test were used to evaluate cognitive function.Neuronal amount,apoptosis,microglial activation,percentage of high mobility group box 1(HMGB1)-andnuclear factor-κB(NF-κB)-positive microglia,and levels of HMGB-1 downstream factors,including NF-κB,interleukin-6(IL-6),and IL-1β,were detected by Nissl staining,immunofluorescence,and Western blot assays.Results:EA pretreatment significantly increased crossing platform times and elevated the time with a novel object,restored the quantity of neurons,decreased TUNEL-positive neurons,alleviated activation of microglia,downregulated expression of HMGB1 and NF-κB in the microglia,and reduced levels of phosphor-NF-κB,IL-6,and IL-1β 35 days after surgery,while α-BGT partially reversed these changes.Conclusion:Electroacupuncture pretreatment can attenuate the neuroinflammatory response in the brain after tibial fracture in rats,and the underlying mechanism may be associated with inhibition of HMGB1-NF-κB via an α7-nAChR signal in the microglia.Part three Effect of transcutaneous electrical acupoint stimulation on delirium and heart rate variability after total knee replacement in elderly patientsObjective:Postoperative delirium(POD)is a complication that occurs frequently after Total knee arthroplasty(TKA)in patients older than 65 years.Our paper aimed to explore the effects and mechanisms of using transcutaneous electrical acupoint stimulation(TEAS)on delirium after TKA in the elderly.Methods:Participants(n=120)scheduled for TKA were randomly assigned to TEAS(TEAS group)or control group(Con group).In TEAS,on acupoints Zusanli(ST36)and Sanyinjiao(SP6)of non-operative limb,the patients received stimulation from 30 minutes before anesthesia until the end of the surgery.The patients in the control group received a sham stimulation.The incidence of Postoperative delirium is assessed twice a day using the 3-minute Diagnostic Interview for CAM(3D-CAM)in the first 3 postoperative days.Serum HMGB1 and IL-6 were measured before the onset of TEAS(baseline,T0),30min after skin incision(T1),30min after completion of surgery(T2),6h(T3),1d(T4)and 3d after surgery(T5).The electrocardiogram(ECG)were recorded for 30 min at 24 hours before surgery(Baseline),24h,48h and 72h post-operatively to assess autonomic functions.Results:The incidence of POD was significantly lower in the TEAS group(8[14.5%]of 55 patients)than in the control group(18[30.5%]of 59 patients;P=0.042).Compared with the baseline value at T0,the serum concentrations HMGB1 at T1-T5 and IL-6 levels at T2-T5 significantly increased in both groups(P<0.001).Compared with TEAS group,the serum concentrations of HMGB1 and IL-6 were higher at T2-T5 in the control group(P<0.001).TEAS significantly increased Vagal activity(HF)and decreased sympathovagal ratio(LF/HF)than those in the Con group 24-72 hours postoperatively(P<0.001).Conclusion:The application of TEAS significantly reduced the incidence of POD in elderly patients undergoing TKA following general anesthesia.The mechanism may be related to the modulation of the vagally-mediated anti-inflammatory pathway. |
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