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Effects Of BDNF Signaling Pathway On POCD In Mice And Effects Of Tidal Volume On The Prognosis Of Patients Undergoing One-lung Ventilation

Posted on:2018-09-07Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z LiuFull Text:PDF
GTID:1314330518967971Subject:Anesthesiology
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Background and ObjectivePostoperative cognitive dysfunction(POCD)is a decline of cognitive function,such as cognitive flexibility,attention and working memory,that arises after anesthesia and surgery.Surgical incision-induced nociception is involved in the occurrence of POCD.The exact mechanisms involved remain unclear.As an important factor regulating neuron survival,brain-derived neurotrophic factor(BDNF)has been demonstrated to increase neurogenesis and decrease the neuron apoptosis in a brain ischemic model.Additionally,BDNF expression can be influenced by peripheral nociceptive stimulation.In this study,we employed the plantar incision model in mice to investigate the effect of surgical incision-induced nociception on postoperative learning ability,the expression of BDNF and the activation of BDNF signaling pathway.Changes in BDNF expression and the activation of BDNF signaling pathway were compared in different groups to observe whether BDNF signaling pathway was involved in surgical incision-induced learning impairment.Methods1.Differences on postoperative learning ability,the expression of BDNF,the activation of BDNF signaling pathway and the expression of pro-inflammation cytokines were compared between the control group,the isoflurane group,the surgery group and the postoperative analgesia group.9 months old C57BL/6 male mice weighting 35?40 g were divided randomly into 4 groups as following:(1)the control group(Contorl);(2)the isoflurane group(Isoflurane),mice in this group received anesthesia under inhalation of 1.5%isoflurane for 15 min;(3)the surgery group(Surgery),mice in this group received plantar incision under anesthesia;(4)the postoperative analgesia group(Surgery +EMLA),mice in this group received surgery and postoperative analgesia(smearing of a mixture cream of lidocaine and prilocaine every 8 h.Learning ability of mice was determined by the fear condition test at 3 and 7 d after surgery.Mechanical nociception thresholds were examined by the von Frey filament test at 1 to 7 d after surgery.Spontaneous locomotor activity was explored by the open field test at 3 d after surgery.The expression of BDNF in hippocampus and amygdala was explored at 3 d after surgery by ELISA.The expression of TrkB,pTrkB,Bcl-2 and Bax were observed by Western-blot.Neurogenesis and astrogenesis in dentate gyrus were evaluated by immunofluorescence.The expression of IL-6 and IL-1? in hippocampus and amygdala was tested by ELISA.2.Differences on postoperative leaning ability and activation of BDNF signaling pathway were compared between the vehicle group and the antagonist group.9 months old C57BL/6 male mice weighting 35?40 g were divided randomly into 2 groups as following:(1)the vehicle group(Surgery + EMLA + Vehicle);(2)the antagonist group(Surgery + EMLA + ANA).Mice in the vehicle group received intraperitoneal injection of vehicle of ANA-12 after surgery.Mice in the ANA-12 group received intraperitoneal injection of ANA-12 after surgery.Learning ability was examined in both groups at 3 d after surgery by the fear condition test.The expression of TrkB,pTrkB,Bcl-2 and Bax was evaluated by Western-blot.Neurogenesis and astrogenesis in dentate gyrus was observed by immunofluorescence.Results1.In comparison with the isofluarne group and the control group,the freezing time in fear condition test at 3 d after surgery significantly decreased in the surgical group.In comparison with the isoflurane group and the control group,no significant differences were found in the postoperative analgesia group.2.In comparison with the isoflurane group,the nociceptive threshold in the surgery group but not the postoperative analgesia group significant decreased from 1 to 5 d after surgery.The expression of BDNF in hippocampus and amygdala significantly decreased as well in the surgery group but not the postoperative analgesia group compared with the isoflurane group.In comparison with the isoflurane group,the expression of TrkB,pTrkB,Bcl-2/Bax ratio as well as neurogenesis and astrogenesis in dentate gyrus significant decrease in the surgery group but not the postoperative analgesia group.The expression of IL-6 and IL-1? in hippocampus and amygdala significantly increased in hippocampus and amygdala in the surgery group but not the postoperative analgesia group compared with the isoflurane group.3.In comparison with the vehicle group,the freezing time in the antagonist group significantly decreased as well as the phosphorylation of TrkB,Bcl-2/Bax ratio,neurogenesis and astrogenesis in dentate gyrus.Conclusion1.Plantar incision-induced nociception can cause the decrease in postoperative learning ability.2.Inhibition of BDNF signaling pathway is involved in the plantar incision-induced learning impairment.3.Surgical incision-induced nociception causes neuroinflammation in hippocampus and amygdala.Increase in pro-inflamation cytokines may underlie surgical incision-induced decrease in BDNF expression.Background and Objective Postoperative pulmonary complications are not uncommon in one-lung ventilation,which are also among the main causes of postoperative death after lung surgery.Ventilation strategies may influence the incidence of postoperative pulmonary complications.Protective ventilation lead to improved survival in patients with acute lung injury(ALI),but its effect on intraoperative one-lung ventilation is controversial.Methods Systematic search(PubMed,EMBASE,the Cochrane Library,OVID Medline;in May2015)was performed for randomized trials comparing protective ventilation(PV)with conventional ventilation(CV)in one-lung ventilation.Methodological quality was estimated by using the Cochrane tool for risk.Outcomes included postoperative pulmonary complications,length of hospital stay,intraoperative plateau airway pressure(Ppiateau),and mean arterial pressure(MAP).Results Eleven studies(657 patients)comparing PV with CV were included in this meta-analysis.In comparison with CV,PV decreased the incidence of postoperative pulmonary complications(OR,0.29;95% Cl,0.15?0.57;P<0.01)and intraoperative Ppiateau(MD,-3.75;95% CI,-5.74?-1.76;P<0.01)but had no influence on length of hospital stay and MAP.Conclusion PV with PEEP can decrease the incidence of postoperative pulmonary complications and should be encouraged in one-lung ventilation during surgery.More RCTs focusing on postoperative respiratory outcomes are still needed.
Keywords/Search Tags:POCD, BDNF, surgical incision-induced nociception, protective ventilation, mechanical ventilation, one lung ventilation, postoperative pulmonary complications
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