To investigate the inhibiting effect of β-Aescin on nuclear factor-κB (NF-κB) activation and the expression of tumor necrosis factor-α (TNF-α) protein after traumatic brain injury (TBI) in the rat brain, 62 SD ra...To investigate the inhibiting effect of β-Aescin on nuclear factor-κB (NF-κB) activation and the expression of tumor necrosis factor-α (TNF-α) protein after traumatic brain injury (TBI) in the rat brain, 62 SD rats were subjected to lateral cortical impact injury caused by a free-falling object and divided randomly into four groups: (1) sham operated (Group A); (2) injured (Group B); (3) β-Aescin treatment (Group C); (4) pyrrolidine dithocarbamate (PDTC) treatment (Group D). β-Aescin was administered in Group C and PDTC treated in Group D immediately after injury. A series of brain samples were obtained directly 6h, 24 h and 3 d respectively after trauma in four groups. NF-κB activation was examined by Electrophoretic Mobility Shift Assay (EMSA); the levels of TNF-α protein were measured by radio-immunoassay (RIA); the water content of rat brain was measured and pathomorphological observation was carried out. NF-κB activation, the levels of TNF-α protein and the water content of rat brain were significantly increased (P＜0.01) following TBI in rats. Compared with Group B, NF-κB activation (P＜0.01), the levels of TNF-α protein (P＜0.01) and the water content of brain (P＜0.05) began to decrease obviously after injury in Groups C and D.β-Aescin could dramatically inhibit NF-κB activation and the expression of TNF-α protein in the rat brain, alleviate rat brain edema, and that could partially be the molecular mechanism by which β-Aescin attenuates traumatic brain edema.展开更多
Objective Sevoflurane preconditioning has been demonstrated to reduce cerebral ischemia–reperfusion（IR） injury,but the underlying mechanisms have not been fully elucidated.Besides,different protocols would usually ...Objective Sevoflurane preconditioning has been demonstrated to reduce cerebral ischemia–reperfusion（IR） injury,but the underlying mechanisms have not been fully elucidated.Besides,different protocols would usually lead to different results.The objective of this study was to determine whether dual exposure to sevoflurane improves the effect of anesthetic preconditioning against oxygen and glucose deprivation（OGD）injury in vitro.Methods Rat hippocampal slices under normoxic conditions（95%O2/5%CO2）were pre-exposed to sevoflurane 1,2 and 3 minimum alveolar concentration （MAC）for 30 min,once or twice,with 15-min washout after each exposure.The slices were then subjected to 13-min OGD treatment（95%N2/5%CO2,glucose-free）,followed by 30-min reoxygenation.The population spikes（PSs）were recorded in the CA1 region of rat hippocampus.The percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment was calculated,since it could indicate the recovery degree of neuronal function.In addition,to assess the role of mitogen-activated protein kinases（MAPKs）in preconditioning,U0126,an inhibitor of extracellular signal–regulated protein kinase（MEK-ERK1/2,ERK1/2 MAPK）,and SB203580,an inhibitor of p38 MAPK,were separately added 10 min before sevoflurane exposure.Results Preconditioning once with sevoflurane 1,2,and 3 MAC increased the percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment,from（15.13±3.79）%（control）to（31.88±5.36）%, （44.00±5.01）%,and（49.50±6.25）%,respectively,and twice preconditioning with sevoflurane 1,2,and 3 MAC increased the percentage to（38.53±4.36）%,（50.74±7.05）%and（55.86±6.23）%,respectively.The effect of duplicate preconditioning with sevoflurane 3 MAC was blocked by U0126[（16.23±4.62）%].Conclusion Sevoflurane preconditioning can induce neuroprotection against OGD injury in vitro,and preconditioning twice enhances this effect.Besides,the activation of extracellular signal–regulated protein kinase（MEK-ERK1/2,ERK1/2 MAPK）may be involved in this process.展开更多
Objective： Though sevoflurane has been widely used as an anesthetic in surgery, recent studies have shown that exposure to sevoflurane alone could lead to postoperative cognitive dysfunction （POCD）, of which the me...Objective： Though sevoflurane has been widely used as an anesthetic in surgery, recent studies have shown that exposure to sevoflurane alone could lead to postoperative cognitive dysfunction （POCD）, of which the mechanisms still remain largely unknown. The medial prefrontal cortex （mPFC） is known to be implicated in various cognitive impairments, including working memory and attentional processes. In the present study, we tried to identify dysregulated gene expression in mPFC and investigate the underlying mechanisms involved in POCD. Methods： Behavioral tests, including elevated plus-maze, O-maze, and Y-maze tests, were performed on Wistar rats exposed to sevoflurane. Whole-genome mRNA profiling of mPFC from Wistar rats after exposure to sevoflurane was carried out. Real-time polymerase chain reaction （PCR） was done to verify the differentially expressed genes. Results： Significant impairment of working memory of rats after exposure to sevoflurane was observed. A total of 119 of 7319 detected mRNAs showed significantly different expression between rats with and without sevoflurane exposure （fold change （FC）〉2.0, P〈0.05, and false discovery rate （FDR）〈0.05）, among which 74 mRNAs were down-regulated and 45 mRNAs were up-regulated. Postsynaptic density-95 （PSD95, also named DLG4） showed the most significantly de- creased expression in mPFC and further investigation indicated that PSD95 expression level was correlated with spatial working memory performance. Conclusions： Our study revealed that PSD95 might be involved in the mecha- nism of POCD, which could provide clues for preventing POCD in clinical operations.展开更多
文摘To investigate the inhibiting effect of β-Aescin on nuclear factor-κB (NF-κB) activation and the expression of tumor necrosis factor-α (TNF-α) protein after traumatic brain injury (TBI) in the rat brain, 62 SD rats were subjected to lateral cortical impact injury caused by a free-falling object and divided randomly into four groups: (1) sham operated (Group A); (2) injured (Group B); (3) β-Aescin treatment (Group C); (4) pyrrolidine dithocarbamate (PDTC) treatment (Group D). β-Aescin was administered in Group C and PDTC treated in Group D immediately after injury. A series of brain samples were obtained directly 6h, 24 h and 3 d respectively after trauma in four groups. NF-κB activation was examined by Electrophoretic Mobility Shift Assay (EMSA); the levels of TNF-α protein were measured by radio-immunoassay (RIA); the water content of rat brain was measured and pathomorphological observation was carried out. NF-κB activation, the levels of TNF-α protein and the water content of rat brain were significantly increased (P＜0.01) following TBI in rats. Compared with Group B, NF-κB activation (P＜0.01), the levels of TNF-α protein (P＜0.01) and the water content of brain (P＜0.05) began to decrease obviously after injury in Groups C and D.β-Aescin could dramatically inhibit NF-κB activation and the expression of TNF-α protein in the rat brain, alleviate rat brain edema, and that could partially be the molecular mechanism by which β-Aescin attenuates traumatic brain edema.
基金supported by theScience Foundation of Shihezi University,Xinjiang Province,China(No.RCZX200688)
文摘Objective Sevoflurane preconditioning has been demonstrated to reduce cerebral ischemia–reperfusion（IR） injury,but the underlying mechanisms have not been fully elucidated.Besides,different protocols would usually lead to different results.The objective of this study was to determine whether dual exposure to sevoflurane improves the effect of anesthetic preconditioning against oxygen and glucose deprivation（OGD）injury in vitro.Methods Rat hippocampal slices under normoxic conditions（95%O2/5%CO2）were pre-exposed to sevoflurane 1,2 and 3 minimum alveolar concentration （MAC）for 30 min,once or twice,with 15-min washout after each exposure.The slices were then subjected to 13-min OGD treatment（95%N2/5%CO2,glucose-free）,followed by 30-min reoxygenation.The population spikes（PSs）were recorded in the CA1 region of rat hippocampus.The percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment was calculated,since it could indicate the recovery degree of neuronal function.In addition,to assess the role of mitogen-activated protein kinases（MAPKs）in preconditioning,U0126,an inhibitor of extracellular signal–regulated protein kinase（MEK-ERK1/2,ERK1/2 MAPK）,and SB203580,an inhibitor of p38 MAPK,were separately added 10 min before sevoflurane exposure.Results Preconditioning once with sevoflurane 1,2,and 3 MAC increased the percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment,from（15.13±3.79）%（control）to（31.88±5.36）%, （44.00±5.01）%,and（49.50±6.25）%,respectively,and twice preconditioning with sevoflurane 1,2,and 3 MAC increased the percentage to（38.53±4.36）%,（50.74±7.05）%and（55.86±6.23）%,respectively.The effect of duplicate preconditioning with sevoflurane 3 MAC was blocked by U0126[（16.23±4.62）%].Conclusion Sevoflurane preconditioning can induce neuroprotection against OGD injury in vitro,and preconditioning twice enhances this effect.Besides,the activation of extracellular signal–regulated protein kinase（MEK-ERK1/2,ERK1/2 MAPK）may be involved in this process.
基金supported by the Anhui Education Department(No.KJ2015 B004by)the Bengbu Medical College(No.BYKY1424ZD),China
文摘Objective： Though sevoflurane has been widely used as an anesthetic in surgery, recent studies have shown that exposure to sevoflurane alone could lead to postoperative cognitive dysfunction （POCD）, of which the mechanisms still remain largely unknown. The medial prefrontal cortex （mPFC） is known to be implicated in various cognitive impairments, including working memory and attentional processes. In the present study, we tried to identify dysregulated gene expression in mPFC and investigate the underlying mechanisms involved in POCD. Methods： Behavioral tests, including elevated plus-maze, O-maze, and Y-maze tests, were performed on Wistar rats exposed to sevoflurane. Whole-genome mRNA profiling of mPFC from Wistar rats after exposure to sevoflurane was carried out. Real-time polymerase chain reaction （PCR） was done to verify the differentially expressed genes. Results： Significant impairment of working memory of rats after exposure to sevoflurane was observed. A total of 119 of 7319 detected mRNAs showed significantly different expression between rats with and without sevoflurane exposure （fold change （FC）〉2.0, P〈0.05, and false discovery rate （FDR）〈0.05）, among which 74 mRNAs were down-regulated and 45 mRNAs were up-regulated. Postsynaptic density-95 （PSD95, also named DLG4） showed the most significantly de- creased expression in mPFC and further investigation indicated that PSD95 expression level was correlated with spatial working memory performance. Conclusions： Our study revealed that PSD95 might be involved in the mecha- nism of POCD, which could provide clues for preventing POCD in clinical operations.
