OBJECTIVE To investigate the neuroprotective effect and possible mechanisms of lute.olin-7-O-β-D-glucuronide(LGU) against focalcerebral ischemic injury.METHODS The focal cerebral ischemic injury model was established...OBJECTIVE To investigate the neuroprotective effect and possible mechanisms of lute.olin-7-O-β-D-glucuronide(LGU) against focalcerebral ischemic injury.METHODS The focal cerebral ischemic injury model was established by middle cerebral artery occlusion(MCAO).Male Sprague Dawley rats were randomly divided into sham group,model group(MCAO),LGU group(0.24,0.72 and2.16 mg·kg^(-1)) and positive control group(Edaravone at 5 mg·kg^(-1)).LGU was injected intravenously 30 min after MCAO.Neurological severity score,infarct volume and brain water content were detected 24 h after MCAO and the levels of Na+-K+ ATPase,Ca2 + ATPase,TNF-α and IL-1β were detected to explore the possible mechanisms.For the therapeutic time window test,LGU(0.72 mg·kg^(-1)) was injected intrave.nously 0.5,2,4,6,8,10 and 12 h respectively after MCAO.To evaluate motion behavior,LGU were injected intravenously 30 min after MCAO and once per day during detection period.The changes of motor coordination were detected by rotating rod method and grip strength analysis,and the changes of gaits were detected using DigiGait Imaging System.RESULTS LGU improved the neurological severity score,infarct volume ratio and brain water content.The therapeutic time window of LGU for cerebral infarction and brain edema was at least 6 h and for neurological dysfunction was 12 h.LGU also prolonged the latency on rotarod,increased the forelimb tension and improved 8 gait parameters,including stance duration,stride length,stance width,paw area,paw area variability,gait symmetry,ataxia coefficient and tau propulsion.Furthermore,LGU increased Na^+-K^+-ATPase and Ca^(2+)-ATPase levels in the cortex and hippocampus in the ischemic side,reduced the levels of TNF-α and IL-1β in the serum.CONCLUSION LGU has a significant neuroprotective effect against cerebral ischemic injury via improving energy metabolism and reducing inflammation.展开更多
Aim Reduction of Sheng-Nao-Kang decoction （RSNK）, is a modified traditional Chinese medicinal formula of Sheng-Nao-Kang pill preparation, which is protective in rats against focal cerebral ischemia/reperfusion （I/R...Aim Reduction of Sheng-Nao-Kang decoction （RSNK）, is a modified traditional Chinese medicinal formula of Sheng-Nao-Kang pill preparation, which is protective in rats against focal cerebral ischemia/reperfusion （I/R） injury. In the current study, we investigate the protective effect of RSNK against apoptosis and oxidative damage induced by cerebral I/R and explore the underlying mechanisms. Cerebral I/R injury was induced by in- traluminal middle cerebral artery occlusion （MCAO） for 2 h followed by reperfusion for 24 h in adult male Sprague- Dawley rats. Rats were randomized into seven groups （n- 8）： Sham group, I/R group, RSNK-treated groups （ 0.7 g · kg ^- 1, 1 . 4 g · kg ^- 1 and 2. 8 g · kg^ - 1 ） , nimodipine （NMP） -treated group and Whitmania pigra Whitman （WW）-treated group. Neurological deficit scores, cerebral humidity content and cerebral infarction volume were measured after the 24 h reperfusion. Malondialdehyde （ MDA）, superoxide dismutase （ SOD）, catalase （ CAT）, inducible nitric oxide synthase （iNOS） and total nitric oxide synthase （TNOS） in serum were measured by assay kits for biochemical analysis. Histological structures of the cortex of the ipsilateral ischemic cerebral hemisphere in rats were observed by Nissl staining. The caspase-3 protein content in the hippocampus and cortex was detected by immunohistochemistry. Additionally, Bax and Bcl-2 protein expressions in the injured brain were evaluated by Western blot. RSNK administration not only markedly improved neurological deficit scores, but also reduced cere- bral humidity content and cerebral infarction volume, lowered MDA content, up-regulated SOD and CAT levels, down-regulated iNOS and TNOS levels, restrained the expression of caspase-3 positive protein and alleviated the Bax and Bcl-2 protein expressions.展开更多
OBJECTIVE To study the role of Ginkgo biloba extract-761(EGb-761)in the recovery of gait abnormality and its neuroprotective effect against the brain injury induced by permanent middle cerebral artery occlu-sion in ra...OBJECTIVE To study the role of Ginkgo biloba extract-761(EGb-761)in the recovery of gait abnormality and its neuroprotective effect against the brain injury induced by permanent middle cerebral artery occlu-sion in rats.METHODS Male Sprague Dawley rats(n=200,240-305 g)were anesthetized with 0.2%pentobarbital sodium diluted in physiological saline(2.0 m L·kg-1,ip).Then a monofilament coated with poly-L-lysine,was used to occlude the origin of the middle cerebral artery.It was inserted into the internal carotid artery lumen until it met mild resistance,approximately 20mm beyond the common carotid artery bifurcation.The suture was secured with a ligature and maintained in place until sacrifice.The same surgical procedure was conducted in sham-operated rats in which the middle cerebral artery was not occluded.Motor and behavioral changes were assessed after surgery using a five point scale.The rats securing the point scale above 2 were included in the study.The rats were randomly divided into control,and treated groups:EGb-761(20,50,and 100 mg·kg-1).The treated groups were oral y administered(10 mL·kg-1)for 28 d.On 7th,14th,21st,and 28th day the neurological scores,rotar rod test and gait assessment(the automated computer-assisted method)were performed.The brains were collected for TTC staining and histopathological analysis.RESULTS 1)Weight:On 28th day,EGb-761(20 mg·kg-1,)significantly increased the weight of the rat by^8%as compared to control(~300 g).However,at 50 mg·kg-1,and 100 mg·kg-1,a significant increase of^7-7.6%(control:~232 g),and^7.3-7%,respectively from 14 to 28 days was noted.2)Neurological scores:On 28thday,EGb-761(20,50,and 100 mg·kg-1)significantly decreased the neurological scores by^18%,~22%,~21%,respectively as compared to control(~2.07).3)Rotar rod test:On 28thday,EGb-761(50,and100 mg·kg-1)significantly increased by^69.1%,~74.1%,respectively as compared to control(~28.2).4)Gait assessment:On 7th,14th,21st,and 28thday,EGb-761(20,50,and 100 m·kg-1)significantly reduced the average body angle,on 7th,14th,21st,and 28thday,EGb-761(100 mg·kg-1)significantly increased the walk speed and reduced the average walking cycle,EGb-761(50,and 100 mg·kg-1)significantly the area of the left brain/right brain area percentage and reduced tissue pathologic neuron injury.CONCLUSION Ginkgo biloba extract EGb-761 has obvious improve behavior disorders,and has a protective neuroprotective effect against the brain injury induced by permanent middle cerebral artery occlusion.展开更多
Objective:To investigate the influence of electroacupuncture(EA) combined with repetitive transcranial magnetic stimulation(rTMS) on the temporal profile of nestin expression after induction of focal cerebral ischemia...Objective:To investigate the influence of electroacupuncture(EA) combined with repetitive transcranial magnetic stimulation(rTMS) on the temporal profile of nestin expression after induction of focal cerebral ischemia in adult rats and to explore the mechanism of EA combined with rTMS in treating ischemic brain injury.Method:The model of transient focal ischemia was produced by occlusion of middle cerebral artery.Seventy-five Wistar rats were randomly divided into normal group,model group,EA group,rTMS group and EA +rTMS group.The neurologic impairment rating and ability of learning and memory were observed at the 7th、14th and 28th d after infarction respectively.Meanwhile,Western blotting was used to observe the number of nestin expression positive cells.Result:Nestin-positive cells were found in cortex,subgranular zone(SGZ),subventricular zone(SVZ) of the ipsilateral side at different time points after cerebral ischemia.The number of nestin-positive cells peaked at the 7th d,began to decrease at the 14th d and was significantly higher in EA+rTMS group than that in model group(P< 0.05),then almost reached normal at the 28th d.The improvement of neural motor function deficits as well as the indexes of learning and memory were more obvious in EA+rTMS group compared with model group(P<0.01,P<0.05).These effects were most obvious in EA +rTMS group compared with the EA and rTMS group(P<0.05).Conclusion:EA and rTMS possess the potency of building up and can increase the number of nestin-positive cells in some brain regions after focal cerebral ischemia,which might be one of the important mechanisms of EA combined with rTMS in treating ischemia brain injury.展开更多
OBJECTIVE To investigate the effects of kaempferol(KAE)on chronic cerebral ischemia in rats.METHODS Chronic cerebral ischemia was induced in rats by permanent occlusion of bilateral common carotid arteries(2VO).Then,t...OBJECTIVE To investigate the effects of kaempferol(KAE)on chronic cerebral ischemia in rats.METHODS Chronic cerebral ischemia was induced in rats by permanent occlusion of bilateral common carotid arteries(2VO).Then,the rats with chronic cerebral ischemia were randomly divied into three groups:model group,KAE 10 and 30 mg·kg-1group.Another group rats without occlusion of common carotid arteries were used as the sham-operation group.Memory behavior was investigated by Morris water maze test.Prehensile ability was investigated by prehensile traction test.The structure of hippocampus and cortex neurons was observed with Nissel staining.In addition,the SOD activity and MDA content in brain tissue were determined.The DJ-1protein level was determined by Western blotting.RESULTS KAE 10 and 30 mg·kg-1could significantly improve cognitive impairment and prehensile traction ability(P<0.01)induced by chronic cerebral ischemia in rats.The results of the pathological analysis also suggested that KAE could ameliorate the pathological damage induced by chronic cerebral ischemia.In addition,KAE 30 mg·kg-1significantly increased the activity of SOD(P<0.05),but had no effect on the content of MDA in rat brain tissue.Western-blotting confirmed that KAE 10 and30 mg·kg-1could increase the expression of anti-oxidation proteins DJ-1 in hippocampus(P<0.01).CONCLUSION KAE may attenuate the chronic cerebral ischemic injury in rats.展开更多
OBJECTIVE To investigate the effects of IMM-H004 on permanent focal cerebral ischemia injury and associated cardiopulmonary complications,further elucidating the molecular mechanisms.METHODS The effects of IMM-H004 we...OBJECTIVE To investigate the effects of IMM-H004 on permanent focal cerebral ischemia injury and associated cardiopulmonary complications,further elucidating the molecular mechanisms.METHODS The effects of IMM-H004 were investigated in wild-type(WT) and CKLF1-/-rats.The effects of IMM-H004 on ischemic stroke injury and its cardiopulmonary complications were determined using 2,3,5-triphenyltetrazolium chloride(TTC) staining,behavior tests,magnetic resonance imaging(MRI)scans,enzyme-linked immunosorbent assay(ELISA),Nissl staining,and histo-pathological examination.Multiple molecular experiments including immunohistological staining,immunofluorescence staining,quantitative RT-PCR,Western blotting,and co-immunoprecipitation assays were used to elucidate the underlying mechanisms.RESULTS IMM-H004 treatment provided significant protection against ischemic stroke-induced brain injury and associated cardiopulmonary complications,through CKLF1-depedent-anti-inflammation pathway in rats.IMM-H004 downregulated the amount of CKLF1 and disturbed the combination between CKLF1 and C-C chemokine receptor type 4,suppressing the inflammatory response and protecting the damaged organs in ischemic setting.CONCLUSION This preclinical study established efficacy of IMM-H004 as a potential therapeutic medicine for ischemic stroke and associated cardiopulmonary complications.The protective effects of IMM-H004 may due to its specific mechanism through CKLF1.These results support further efforts to develop IMM-H004 for human clinical trials in acute cerebral ischemia,especially for patients who are not suitable for reperfusion therapy.展开更多
Objective:To investigate the effects of electro-acupuncture preconditioning on focal cerebral blood flow(CBF)in artery and vein of rats with middle cerebral artery occlusion(MCAO),and to provide experimental evidences...Objective:To investigate the effects of electro-acupuncture preconditioning on focal cerebral blood flow(CBF)in artery and vein of rats with middle cerebral artery occlusion(MCAO),and to provide experimental evidences for primary prevention of ischemic stroke.Method:Eighteen male Sprague-Dawley rats(two months old)were divided into 3 groups:electro-acupuncture preconditioning group(EA group),ischemia group(Is group)and Dazhui and Baihui sham group(six rats per group).The rats in the EA group were given electro-acupuncture preconditioning at Dazhui and Baihui with 2/15 density wave current for 30 minutes per day,5 days consecutively.After preconditioning,enhanced laser speckle contrast analysis was implemented to get false color images before making middle cerebral ischemia occlusion model.Then getting false color images two hours during ischemia by laser speckle contrast analysis again.Result:④Relative CBF in focal cortical artery:There were significant differences at every time point in EA group and Is group(P<0.01,P<0.05)comparing with that before occlusion respectively.Compared with that before ischemia,there was significant difference at 120 min after ischemia in sham group(P<0.05);compared with that at 30 min after occlusion,there was significant difference at every time point in EA group from the time point 60 min after occlusion;there was significant difference at every time point in EA group and Is group(P<0.05)comparing with sham group;Compared with sham group,there was significant difference at 30min and 60 min after ischemia in EA group(P<0.05).④Relative CBF in focal cortical vein:There was significant difference at every time point in sham group comparing with that before occlusion(P<0.05);compared with that before occlusion,there was significant difference from 45 min after occlusion in EA group(P<0.05);compared with that before occlusion,there was significant difference from 105 min after occlusion in sham group(P<0.05);there was significant difference at 120 min after occlusion comparing with 60 min after occlusion in EA group;compared with sham group,there was significant difference at every time point in EA group and Is group(except 30 min after occlusion)(P<0.05),respectively;compared with Is group,there was significant difference at 30,45,60 min after occlusion in EA group(P<0.05).④The infarct brain volume detected 24 h after reperfusion in EA group was significantly smaller comparing with that in Is group(P<0.05).Conclusion:Electro-acupuncture preconditioning could increase CBF velocity in artery and vein of focal cortex in rats with MCAO,which also had time-dependence.Additionally,electro-acupuncture preconditioning could decrease the infarct volume detected 24h after reperfusion,which possibly was correlated with the blood supply in ischemic penumbra.展开更多
OBJECTIVE To study the treatment effect of Gastrodia elata and Uncaria rhynchophylla water extract(GUW)against cerebral ischemia,and the metabolomic profile of cerebrospinal fluid in GUW treated cerebral ischemia in r...OBJECTIVE To study the treatment effect of Gastrodia elata and Uncaria rhynchophylla water extract(GUW)against cerebral ischemia,and the metabolomic profile of cerebrospinal fluid in GUW treated cerebral ischemia in rat model.METHODS Middle cerebral artery occlusion was performed in male SD rat.GUW or control(PBS)was administered orally for 7d post-operationally.At day 7,the brain of the rat was harvested.The infarct volume of the brain was measured after TTC staining.The brain was subjected to H&E and cresyl violet staining in histological analysis.The cerebrospinal fluid(CSF)of another set of animals was aspirated.The CSF samples were labeled with 13 C-dansyl and 12C-dansyl chloride.The reaction mixture was put into liquid chromatography Fourier-transform ion cyclotron resonance mass spectrometry for analysis of the CSF metabolome.Multivariate statistical analysis will be carried out to determine the differences of metabolomic profile in CSF of GUW versus control group.RESULTS After GUW treatment,the neurological deficit score was significantly improved from day 3 to 7(P<0.001).GUW treated group significantly reduced 55.7%infarct volume on MCAO rats in TTC stained brain slices(P<0.001)and preserved brain histological structure observed in H&E and cresyl violet staining.On the other hand,according to various statistical analyses to compare CSF metabolite in the GUW and control group,volcano plot analysis showed 48 metabolites(P<0.001);OPLS-DA analysis showed 129 metabolites(VIP score >2.0)and 45 metabolites in ROC curve analysis.Among identified metabolites,L-aspartic acid(60%)and glycine(62%)decreased in GUW while threoninyl-alanine increased by 1.6 fold significantly.CONCLUSION GUW ameliorated cerebral ischemic injury,and the metabolomic approach may be a potential means to find biomarker of the Chinese medicine treatment on cerebral ischemia.展开更多
目的观察不同针灸介入时机对大脑中动脉供血区急性脑梗死神经功能预后的影响。方法回顾性选取2020年1月—2022年8月收治的116例大脑中动脉供血区急性脑梗死患者的临床资料进行分析,根据针灸介入时机分为两组。两组均进行静脉溶栓及常规...目的观察不同针灸介入时机对大脑中动脉供血区急性脑梗死神经功能预后的影响。方法回顾性选取2020年1月—2022年8月收治的116例大脑中动脉供血区急性脑梗死患者的临床资料进行分析,根据针灸介入时机分为两组。两组均进行静脉溶栓及常规药物治疗,观察组61例患者于发病72 h内给予针灸治疗,对照组55例患者于发病2周时给予针灸治疗。检测两组不同时间点侧支循环代偿情况、脑损伤标志物的水平,评估两组不同时间点简易精神状态检查(Mini-mental state examination,MMSE)评分、神经功能评分、Barthel指数(Barthel index,BI)评分、肢体运动功能评分、中医症状评分的差异,统计两组疗效。结果治疗前,两组侧支循环代偿情况比较,差异无统计学意义(P>0.05)。治疗4周和随访时,两组患侧大脑前动脉平均血流速度与对侧大脑中动脉平均血流速度的比值(Ratio of the average flow ve⁃locity of the affected anterior cerebral artery to the average flow velocity of the contralateral middle cerebral artery,iVACA/cVM⁃CA)较治疗前升高,观察组同时间点较对照组更高(P<0.05);两组患侧大脑后动脉平均血流速度与对侧大脑中动脉平均血流速度的比值(Ratio of the average flow velocity of the affected posterior cerebral artery to the average flow velocity of the contralateral middle cerebral artery,iVPCA/cVMCA)与治疗前比较,差异无统计学意义(P>0.05)。治疗前,两组脑损伤标志物比较,差异无统计学意义(P>0.05)。治疗4周和随访时,两组脑源性神经营养因子(Brain-derived neurotrophic factor,BDNF)较治疗前升高,观察组同时间点较对照组更高(P<0.05);两组钙结合蛋白β(Calcium binding proteinβ,S100β)、神经胶质纤维酸性蛋白(Glial fibrillary acid protein,GFAP)较治疗前下降,观察组同时间点较对照组更低(P<0.05)。治疗前,两组Fugl-Meyer评分、中医症状评分等相关评分比较,差异无统计学意义(P>0.05)。治疗4周和随访时,两组MMSE评分、BI评分及上肢和下肢Fugl-Meyer评分较治疗前升高,观察组同时间点较对照组更高(P<0.05);两组美国国立卫生院神经功能缺损(National institutes of health stroke scale,NIHSS)评分、中医症状评分较治疗前下降,观察组同时间点较对照组更低(P<0.05)。观察组总有效率为88.52%(54/61)高于对照组的72.73%(40/55),差异有统计学意义(P<0.05)。结论发病72h内采用针灸治疗可改善大脑中动脉供血区急性脑梗死脑损伤标志物的表达,改善脑血流,促进神经功能的恢复,有利于疾病的康复。展开更多
基金supported by Young and Middle-aged Teacher Career Development Support Plan of Shenyang Pharmaceutical University(ZQN2016002) and Science and Technology Funds from Department of Education of Liaoning province(2016101633L3)
文摘OBJECTIVE To investigate the neuroprotective effect and possible mechanisms of lute.olin-7-O-β-D-glucuronide(LGU) against focalcerebral ischemic injury.METHODS The focal cerebral ischemic injury model was established by middle cerebral artery occlusion(MCAO).Male Sprague Dawley rats were randomly divided into sham group,model group(MCAO),LGU group(0.24,0.72 and2.16 mg·kg^(-1)) and positive control group(Edaravone at 5 mg·kg^(-1)).LGU was injected intravenously 30 min after MCAO.Neurological severity score,infarct volume and brain water content were detected 24 h after MCAO and the levels of Na+-K+ ATPase,Ca2 + ATPase,TNF-α and IL-1β were detected to explore the possible mechanisms.For the therapeutic time window test,LGU(0.72 mg·kg^(-1)) was injected intrave.nously 0.5,2,4,6,8,10 and 12 h respectively after MCAO.To evaluate motion behavior,LGU were injected intravenously 30 min after MCAO and once per day during detection period.The changes of motor coordination were detected by rotating rod method and grip strength analysis,and the changes of gaits were detected using DigiGait Imaging System.RESULTS LGU improved the neurological severity score,infarct volume ratio and brain water content.The therapeutic time window of LGU for cerebral infarction and brain edema was at least 6 h and for neurological dysfunction was 12 h.LGU also prolonged the latency on rotarod,increased the forelimb tension and improved 8 gait parameters,including stance duration,stride length,stance width,paw area,paw area variability,gait symmetry,ataxia coefficient and tau propulsion.Furthermore,LGU increased Na^+-K^+-ATPase and Ca^(2+)-ATPase levels in the cortex and hippocampus in the ischemic side,reduced the levels of TNF-α and IL-1β in the serum.CONCLUSION LGU has a significant neuroprotective effect against cerebral ischemic injury via improving energy metabolism and reducing inflammation.
文摘Aim Reduction of Sheng-Nao-Kang decoction （RSNK）, is a modified traditional Chinese medicinal formula of Sheng-Nao-Kang pill preparation, which is protective in rats against focal cerebral ischemia/reperfusion （I/R） injury. In the current study, we investigate the protective effect of RSNK against apoptosis and oxidative damage induced by cerebral I/R and explore the underlying mechanisms. Cerebral I/R injury was induced by in- traluminal middle cerebral artery occlusion （MCAO） for 2 h followed by reperfusion for 24 h in adult male Sprague- Dawley rats. Rats were randomized into seven groups （n- 8）： Sham group, I/R group, RSNK-treated groups （ 0.7 g · kg ^- 1, 1 . 4 g · kg ^- 1 and 2. 8 g · kg^ - 1 ） , nimodipine （NMP） -treated group and Whitmania pigra Whitman （WW）-treated group. Neurological deficit scores, cerebral humidity content and cerebral infarction volume were measured after the 24 h reperfusion. Malondialdehyde （ MDA）, superoxide dismutase （ SOD）, catalase （ CAT）, inducible nitric oxide synthase （iNOS） and total nitric oxide synthase （TNOS） in serum were measured by assay kits for biochemical analysis. Histological structures of the cortex of the ipsilateral ischemic cerebral hemisphere in rats were observed by Nissl staining. The caspase-3 protein content in the hippocampus and cortex was detected by immunohistochemistry. Additionally, Bax and Bcl-2 protein expressions in the injured brain were evaluated by Western blot. RSNK administration not only markedly improved neurological deficit scores, but also reduced cere- bral humidity content and cerebral infarction volume, lowered MDA content, up-regulated SOD and CAT levels, down-regulated iNOS and TNOS levels, restrained the expression of caspase-3 positive protein and alleviated the Bax and Bcl-2 protein expressions.
基金The project supported by Hunan province Science and Technology Plan Projects of China(2015DK3010)
文摘OBJECTIVE To study the role of Ginkgo biloba extract-761(EGb-761)in the recovery of gait abnormality and its neuroprotective effect against the brain injury induced by permanent middle cerebral artery occlu-sion in rats.METHODS Male Sprague Dawley rats(n=200,240-305 g)were anesthetized with 0.2%pentobarbital sodium diluted in physiological saline(2.0 m L·kg-1,ip).Then a monofilament coated with poly-L-lysine,was used to occlude the origin of the middle cerebral artery.It was inserted into the internal carotid artery lumen until it met mild resistance,approximately 20mm beyond the common carotid artery bifurcation.The suture was secured with a ligature and maintained in place until sacrifice.The same surgical procedure was conducted in sham-operated rats in which the middle cerebral artery was not occluded.Motor and behavioral changes were assessed after surgery using a five point scale.The rats securing the point scale above 2 were included in the study.The rats were randomly divided into control,and treated groups:EGb-761(20,50,and 100 mg·kg-1).The treated groups were oral y administered(10 mL·kg-1)for 28 d.On 7th,14th,21st,and 28th day the neurological scores,rotar rod test and gait assessment(the automated computer-assisted method)were performed.The brains were collected for TTC staining and histopathological analysis.RESULTS 1)Weight:On 28th day,EGb-761(20 mg·kg-1,)significantly increased the weight of the rat by^8%as compared to control(~300 g).However,at 50 mg·kg-1,and 100 mg·kg-1,a significant increase of^7-7.6%(control:~232 g),and^7.3-7%,respectively from 14 to 28 days was noted.2)Neurological scores:On 28thday,EGb-761(20,50,and 100 mg·kg-1)significantly decreased the neurological scores by^18%,~22%,~21%,respectively as compared to control(~2.07).3)Rotar rod test:On 28thday,EGb-761(50,and100 mg·kg-1)significantly increased by^69.1%,~74.1%,respectively as compared to control(~28.2).4)Gait assessment:On 7th,14th,21st,and 28thday,EGb-761(20,50,and 100 m·kg-1)significantly reduced the average body angle,on 7th,14th,21st,and 28thday,EGb-761(100 mg·kg-1)significantly increased the walk speed and reduced the average walking cycle,EGb-761(50,and 100 mg·kg-1)significantly the area of the left brain/right brain area percentage and reduced tissue pathologic neuron injury.CONCLUSION Ginkgo biloba extract EGb-761 has obvious improve behavior disorders,and has a protective neuroprotective effect against the brain injury induced by permanent middle cerebral artery occlusion.
基金Supported by the National Nature Science Foundation of China(No.30672216)Project of Wuhan Hygiene Bureau(No.WX08A01,No.WZ08B02)
文摘Objective:To investigate the influence of electroacupuncture(EA) combined with repetitive transcranial magnetic stimulation(rTMS) on the temporal profile of nestin expression after induction of focal cerebral ischemia in adult rats and to explore the mechanism of EA combined with rTMS in treating ischemic brain injury.Method:The model of transient focal ischemia was produced by occlusion of middle cerebral artery.Seventy-five Wistar rats were randomly divided into normal group,model group,EA group,rTMS group and EA +rTMS group.The neurologic impairment rating and ability of learning and memory were observed at the 7th、14th and 28th d after infarction respectively.Meanwhile,Western blotting was used to observe the number of nestin expression positive cells.Result:Nestin-positive cells were found in cortex,subgranular zone(SGZ),subventricular zone(SVZ) of the ipsilateral side at different time points after cerebral ischemia.The number of nestin-positive cells peaked at the 7th d,began to decrease at the 14th d and was significantly higher in EA+rTMS group than that in model group(P< 0.05),then almost reached normal at the 28th d.The improvement of neural motor function deficits as well as the indexes of learning and memory were more obvious in EA+rTMS group compared with model group(P<0.01,P<0.05).These effects were most obvious in EA +rTMS group compared with the EA and rTMS group(P<0.05).Conclusion:EA and rTMS possess the potency of building up and can increase the number of nestin-positive cells in some brain regions after focal cerebral ischemia,which might be one of the important mechanisms of EA combined with rTMS in treating ischemia brain injury.
基金The project supported by National Natural Science Foundation of China(81473383,81573645)
文摘OBJECTIVE To investigate the effects of kaempferol(KAE)on chronic cerebral ischemia in rats.METHODS Chronic cerebral ischemia was induced in rats by permanent occlusion of bilateral common carotid arteries(2VO).Then,the rats with chronic cerebral ischemia were randomly divied into three groups:model group,KAE 10 and 30 mg·kg-1group.Another group rats without occlusion of common carotid arteries were used as the sham-operation group.Memory behavior was investigated by Morris water maze test.Prehensile ability was investigated by prehensile traction test.The structure of hippocampus and cortex neurons was observed with Nissel staining.In addition,the SOD activity and MDA content in brain tissue were determined.The DJ-1protein level was determined by Western blotting.RESULTS KAE 10 and 30 mg·kg-1could significantly improve cognitive impairment and prehensile traction ability(P<0.01)induced by chronic cerebral ischemia in rats.The results of the pathological analysis also suggested that KAE could ameliorate the pathological damage induced by chronic cerebral ischemia.In addition,KAE 30 mg·kg-1significantly increased the activity of SOD(P<0.05),but had no effect on the content of MDA in rat brain tissue.Western-blotting confirmed that KAE 10 and30 mg·kg-1could increase the expression of anti-oxidation proteins DJ-1 in hippocampus(P<0.01).CONCLUSION KAE may attenuate the chronic cerebral ischemic injury in rats.
基金The project supported by ZYBZH-Y-HUN-24National Natural Science Foundation of China(81730096+6 种基金U1402221)National Mega-project for Innovative Drugs(2018ZX09711001-002-0072018ZX09711001-003-0052018ZX09711001-009-013)CAMS Innovation Fund for Medical Sciences(2016-I2M-1-004)Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study(BZ0150)PUMC Graduate Educationand Teaching Reform Project(10023201600801)
文摘OBJECTIVE To investigate the effects of IMM-H004 on permanent focal cerebral ischemia injury and associated cardiopulmonary complications,further elucidating the molecular mechanisms.METHODS The effects of IMM-H004 were investigated in wild-type(WT) and CKLF1-/-rats.The effects of IMM-H004 on ischemic stroke injury and its cardiopulmonary complications were determined using 2,3,5-triphenyltetrazolium chloride(TTC) staining,behavior tests,magnetic resonance imaging(MRI)scans,enzyme-linked immunosorbent assay(ELISA),Nissl staining,and histo-pathological examination.Multiple molecular experiments including immunohistological staining,immunofluorescence staining,quantitative RT-PCR,Western blotting,and co-immunoprecipitation assays were used to elucidate the underlying mechanisms.RESULTS IMM-H004 treatment provided significant protection against ischemic stroke-induced brain injury and associated cardiopulmonary complications,through CKLF1-depedent-anti-inflammation pathway in rats.IMM-H004 downregulated the amount of CKLF1 and disturbed the combination between CKLF1 and C-C chemokine receptor type 4,suppressing the inflammatory response and protecting the damaged organs in ischemic setting.CONCLUSION This preclinical study established efficacy of IMM-H004 as a potential therapeutic medicine for ischemic stroke and associated cardiopulmonary complications.The protective effects of IMM-H004 may due to its specific mechanism through CKLF1.These results support further efforts to develop IMM-H004 for human clinical trials in acute cerebral ischemia,especially for patients who are not suitable for reperfusion therapy.
基金supported by the Natural Science Foundation of China(NSFC,NO.81171856,81171855)the Development Program of China(863 program,NO.2007AA02Z482)the Key projects of Shanghai Science and Technology on Biomedicine(NO.10DZ1950800)
文摘Objective:To investigate the effects of electro-acupuncture preconditioning on focal cerebral blood flow(CBF)in artery and vein of rats with middle cerebral artery occlusion(MCAO),and to provide experimental evidences for primary prevention of ischemic stroke.Method:Eighteen male Sprague-Dawley rats(two months old)were divided into 3 groups:electro-acupuncture preconditioning group(EA group),ischemia group(Is group)and Dazhui and Baihui sham group(six rats per group).The rats in the EA group were given electro-acupuncture preconditioning at Dazhui and Baihui with 2/15 density wave current for 30 minutes per day,5 days consecutively.After preconditioning,enhanced laser speckle contrast analysis was implemented to get false color images before making middle cerebral ischemia occlusion model.Then getting false color images two hours during ischemia by laser speckle contrast analysis again.Result:④Relative CBF in focal cortical artery:There were significant differences at every time point in EA group and Is group(P<0.01,P<0.05)comparing with that before occlusion respectively.Compared with that before ischemia,there was significant difference at 120 min after ischemia in sham group(P<0.05);compared with that at 30 min after occlusion,there was significant difference at every time point in EA group from the time point 60 min after occlusion;there was significant difference at every time point in EA group and Is group(P<0.05)comparing with sham group;Compared with sham group,there was significant difference at 30min and 60 min after ischemia in EA group(P<0.05).④Relative CBF in focal cortical vein:There was significant difference at every time point in sham group comparing with that before occlusion(P<0.05);compared with that before occlusion,there was significant difference from 45 min after occlusion in EA group(P<0.05);compared with that before occlusion,there was significant difference from 105 min after occlusion in sham group(P<0.05);there was significant difference at 120 min after occlusion comparing with 60 min after occlusion in EA group;compared with sham group,there was significant difference at every time point in EA group and Is group(except 30 min after occlusion)(P<0.05),respectively;compared with Is group,there was significant difference at 30,45,60 min after occlusion in EA group(P<0.05).④The infarct brain volume detected 24 h after reperfusion in EA group was significantly smaller comparing with that in Is group(P<0.05).Conclusion:Electro-acupuncture preconditioning could increase CBF velocity in artery and vein of focal cortex in rats with MCAO,which also had time-dependence.Additionally,electro-acupuncture preconditioning could decrease the infarct volume detected 24h after reperfusion,which possibly was correlated with the blood supply in ischemic penumbra.
基金The project supported by the Health and Medical Research Fund,Hong Kong(11120381)
文摘OBJECTIVE To study the treatment effect of Gastrodia elata and Uncaria rhynchophylla water extract(GUW)against cerebral ischemia,and the metabolomic profile of cerebrospinal fluid in GUW treated cerebral ischemia in rat model.METHODS Middle cerebral artery occlusion was performed in male SD rat.GUW or control(PBS)was administered orally for 7d post-operationally.At day 7,the brain of the rat was harvested.The infarct volume of the brain was measured after TTC staining.The brain was subjected to H&E and cresyl violet staining in histological analysis.The cerebrospinal fluid(CSF)of another set of animals was aspirated.The CSF samples were labeled with 13 C-dansyl and 12C-dansyl chloride.The reaction mixture was put into liquid chromatography Fourier-transform ion cyclotron resonance mass spectrometry for analysis of the CSF metabolome.Multivariate statistical analysis will be carried out to determine the differences of metabolomic profile in CSF of GUW versus control group.RESULTS After GUW treatment,the neurological deficit score was significantly improved from day 3 to 7(P<0.001).GUW treated group significantly reduced 55.7%infarct volume on MCAO rats in TTC stained brain slices(P<0.001)and preserved brain histological structure observed in H&E and cresyl violet staining.On the other hand,according to various statistical analyses to compare CSF metabolite in the GUW and control group,volcano plot analysis showed 48 metabolites(P<0.001);OPLS-DA analysis showed 129 metabolites(VIP score >2.0)and 45 metabolites in ROC curve analysis.Among identified metabolites,L-aspartic acid(60%)and glycine(62%)decreased in GUW while threoninyl-alanine increased by 1.6 fold significantly.CONCLUSION GUW ameliorated cerebral ischemic injury,and the metabolomic approach may be a potential means to find biomarker of the Chinese medicine treatment on cerebral ischemia.
文摘目的观察不同针灸介入时机对大脑中动脉供血区急性脑梗死神经功能预后的影响。方法回顾性选取2020年1月—2022年8月收治的116例大脑中动脉供血区急性脑梗死患者的临床资料进行分析,根据针灸介入时机分为两组。两组均进行静脉溶栓及常规药物治疗,观察组61例患者于发病72 h内给予针灸治疗,对照组55例患者于发病2周时给予针灸治疗。检测两组不同时间点侧支循环代偿情况、脑损伤标志物的水平,评估两组不同时间点简易精神状态检查(Mini-mental state examination,MMSE)评分、神经功能评分、Barthel指数(Barthel index,BI)评分、肢体运动功能评分、中医症状评分的差异,统计两组疗效。结果治疗前,两组侧支循环代偿情况比较,差异无统计学意义(P>0.05)。治疗4周和随访时,两组患侧大脑前动脉平均血流速度与对侧大脑中动脉平均血流速度的比值(Ratio of the average flow ve⁃locity of the affected anterior cerebral artery to the average flow velocity of the contralateral middle cerebral artery,iVACA/cVM⁃CA)较治疗前升高,观察组同时间点较对照组更高(P<0.05);两组患侧大脑后动脉平均血流速度与对侧大脑中动脉平均血流速度的比值(Ratio of the average flow velocity of the affected posterior cerebral artery to the average flow velocity of the contralateral middle cerebral artery,iVPCA/cVMCA)与治疗前比较,差异无统计学意义(P>0.05)。治疗前,两组脑损伤标志物比较,差异无统计学意义(P>0.05)。治疗4周和随访时,两组脑源性神经营养因子(Brain-derived neurotrophic factor,BDNF)较治疗前升高,观察组同时间点较对照组更高(P<0.05);两组钙结合蛋白β(Calcium binding proteinβ,S100β)、神经胶质纤维酸性蛋白(Glial fibrillary acid protein,GFAP)较治疗前下降,观察组同时间点较对照组更低(P<0.05)。治疗前,两组Fugl-Meyer评分、中医症状评分等相关评分比较,差异无统计学意义(P>0.05)。治疗4周和随访时,两组MMSE评分、BI评分及上肢和下肢Fugl-Meyer评分较治疗前升高,观察组同时间点较对照组更高(P<0.05);两组美国国立卫生院神经功能缺损(National institutes of health stroke scale,NIHSS)评分、中医症状评分较治疗前下降,观察组同时间点较对照组更低(P<0.05)。观察组总有效率为88.52%(54/61)高于对照组的72.73%(40/55),差异有统计学意义(P<0.05)。结论发病72h内采用针灸治疗可改善大脑中动脉供血区急性脑梗死脑损伤标志物的表达,改善脑血流,促进神经功能的恢复,有利于疾病的康复。
