目的:探讨通窍活血汤对外伤后水瘀互结型脑积水患者血清神经生化标志物及脑脊液p73,p38表达和认知功能的影响。方法:选取新乡医学院第一附属医院就诊并诊断为外伤后脑积水患者74例,按照随机数字表法分为两组,对照组(37例)给予常规对症...目的:探讨通窍活血汤对外伤后水瘀互结型脑积水患者血清神经生化标志物及脑脊液p73,p38表达和认知功能的影响。方法:选取新乡医学院第一附属医院就诊并诊断为外伤后脑积水患者74例,按照随机数字表法分为两组,对照组(37例)给予常规对症及支持治疗,观察组(37例)在对照组基础上予通窍活血汤治疗,观察并记录两组患者治疗前后人脑髓鞘碱性蛋白(myelin basic protein,MBP),中枢神经特异蛋白(Protein S100β),神经元特异性烯醇化酶(neuron-specificenolase,NSE)水平,脑脊液p73,p38水平,术前简易精神状态评价量表(minimum mental state examination,MMSE),格拉斯哥昏迷评分(Glasgow coma scale,GCS),同时对比临床疗效及不良反应发生情况。结果:对照组治疗有效率低于观察组(P<0.05);与治疗前比较,两组治疗后血清MBP,S100β,NSE水平均较治疗前明显降低(P<0.05),且观察组显著低于对照组(P<0.05);两组治疗后患者的脑脊液p73,p38蛋白表达均升高(P<0.05),且观察组高于对照组(P<0.05);两组治疗后患者的MMSE,GCS评分均升高(P<0.05),且观察组高于对照组(P<0.05)。结论:通窍活血汤能有效改善患者临床症状,可能与其降低外伤后水瘀互结型脑积水患者血清MBP,S-100β,NSE水平,提高脑脊液p73,p38蛋白表达水平有关。展开更多
Objective: To investigate the therapeutic effect of nerve growth factor (NGF) on changes of myelin basic protein (MBP) and functional repair of sensory and motor nerve following sciatic nerve injury. Methods: The scia...Objective: To investigate the therapeutic effect of nerve growth factor (NGF) on changes of myelin basic protein (MBP) and functional repair of sensory and motor nerve following sciatic nerve injury. Methods: The sciatic nerves of rats were injured by sectioning with shaver,and divided into 3 groups: NGF group (Group A), group of normal saline solution (Group B), untreated group (Group C). The time point of observation was at the 4th week after operation. Sensory evoked potential (SEP) and motor evoked potential (MEP) were detected by Model WD 4000 nerve potential working diagnosis system. Immunohistochemical analysis was used for identification of MBP.Results: The latency of SEP in the Group A at the 4th week after operation was shorter than that in the Group B (P< 0.05 ). The MEP was elicited in 76% of the Group A and was higher than that in the Group B. Results of immunohistochemistry showed that there were less MBP positive cells in the Group A than in the Group B in one and four weeks respectively.Conclusions: NGF can improve the conductive function of injured peripheral nerve and facilitate regeneration of nerve.展开更多
Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocy...Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage,in this study,we investigated the role of Piezo1 in intracerebral hemorrhage.We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon(within 48 hours)after intracerebral hemorrhage,primarily in oligodendrocytes.Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema,myelin sheath loss,and degeneration in injured tissue,a substantial reduction in oligodendrocyte apoptosis,and a significant improvement in neurological function.In addition,we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway.These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage,as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath,thereby improving neuronal function after intracerebral hemorrhage.展开更多
Objective： To study the role and effect of Schwann cells （SCs） remyelination in contused spinal cord. Methods： Green fluorescence protein expressing-SCs were transplanted into the epicenter, rostral and caudal ti...Objective： To study the role and effect of Schwann cells （SCs） remyelination in contused spinal cord. Methods： Green fluorescence protein expressing-SCs were transplanted into the epicenter, rostral and caudal tis- sues of the injury site at 1 week after the spinal cords were contused. At 6 weeks, the spinal cords were removed for cryosections, semithin sections and ultrathin sections, and then immunocytochemical staining of myelin basic protein （MBP）, P0 protein （P0） and S 100 protein （S 100） was carried out on the cryosections. Qualitative and semiquantitative analyses were performed on the cryosections and semithin sections. Ultrastructure ofmyelinated fibers was observed on the ultrathin sections under electron microscope. Results： Transplanted SCs and myelinated fibers im- munocytochemically labeled by MBP, PO as well as S 100 distributed in whole injured area. The quantity of myeli- nated fibers labeled by the three myelin proteins showed no statistical difference, however, which was significantly larger than that of controls. On the semithin sections, the experi- mental group demonstrated more myelinated fibers in the injured area than the controls, but the fibers had smaller diameter and thinner myelin sheath under electron microscope. Conclusion： SCs can promote regeneration of injured nerve fibers and enhance remyelination, which may be his- tological basis of SCs-mediated functional repair of injured spinal cords.展开更多
OBJECTIVE: To evaluate the effect of Tanreqing injection on axon myelin in the mouse brain of experimental autoimmune encephalomyelitis(EAE).METHODS: An EAE model was established by myelin oligodendrocyte glycoprotein...OBJECTIVE: To evaluate the effect of Tanreqing injection on axon myelin in the mouse brain of experimental autoimmune encephalomyelitis(EAE).METHODS: An EAE model was established by myelin oligodendrocyte glycoprotein(MOG)35-55 immunization in C57BL/6 mice. Mice were randomly divided into the following groups: normal, model,prednisone acetate(PA)(6 mg/kg), Tanreqing high dose(5.14 m L/kg), Tanreqing low dose(2.57 m L/kg). On the day of immunization, both Tanreqing groups were treated by intraperitoneal injection,with the PA group treated by intragastrical perfusion after T cell response, and the other groups treated with saline. Changes in body weight, neurological deficit score, incidence rate, mortality rate,and course of disease were observed for all mice.Brain tissue was isolated and stained with hematoxylin-eosin, and pathological investigations performed to evaluate axon myelin damage by transmission electron microscopy(TEM). Myelin basic protein and microtubule associated protein-2 were analyzed by immunohistochemistry.RESULTS: Tanreqing injection significantly prolonged EAE latency and decreased the neurological deficit score, alleviated infiltration of inflammatory cells in the focus area, up-regulated hippocampal MBP expression at the acute stage and the remission stage, and increased microtubule associated protein-2 expression in the EAE brain to varying degrees in the acute stage. TEM analysis indicated that Tanreqing injection alleviates myelin damage in the EAE mouse and maintains the integrity of circular layer structures and alleviates axon mitochondrial swelling.CONCLUSION: Tanreqing injection alleviates EAE symptoms.展开更多
目的探讨牛乳清碱性蛋白对实验大鼠和人体骨密度的影响。方法将44只雌性SD 大鼠分为4个组。具体设置为:对照组、A 组(每天给以每 kg 体重10 mg 乳清碱性蛋白)、B 组(每天给以每 kg 体重20 mg 乳清碱性蛋白)和 C 组(每天给以每 kg 体重30...目的探讨牛乳清碱性蛋白对实验大鼠和人体骨密度的影响。方法将44只雌性SD 大鼠分为4个组。具体设置为:对照组、A 组(每天给以每 kg 体重10 mg 乳清碱性蛋白)、B 组(每天给以每 kg 体重20 mg 乳清碱性蛋白)和 C 组(每天给以每 kg 体重30 mg 乳清碱性蛋白)。连续灌胃90 d 后,分离股骨,分别测定股骨远心端,股骨干中段和股骨近心端骨密度。募集健康育龄女性志愿者63名[(37.9±4.3)岁],随机分为对照组、甲组、乙组3组,其中:对照组饮用普通牛奶、甲组饮用含30 mg 乳清碱性蛋白的牛奶、乙组饮用含60 mg 乳清碱性蛋白的牛奶,每日1次,连续24周;于干预前后分别采用双能 X 射线测量腰椎(12～L4)、左侧股骨近端(股骨颈、大转子和 Ward 三角区)及右足跟骨骨密度;ELISA 法测量血清骨特异碱性磷酸酶(BAP)、Ⅰ型胶原交联 N 末端肽(NTx)。结果 A 组大鼠的股骨远端骨密度高于对照组,而添加本试验剂量的乳清碱性蛋白牛奶对育龄女性受试者骨密度未见明显影响。结论本实验条件下,每日每 kg 体重10 mg 乳清碱性蛋白能提高实验大鼠的股骨密度,但未观察到对人体骨密度的影响。展开更多
The pathology of fetal alcohol syndrome and the less severe fetal alcohol spectrum disorders includes brain dysmyelination.Recent studies have shed light on the molecular mechanisms underlying these white matter abnor...The pathology of fetal alcohol syndrome and the less severe fetal alcohol spectrum disorders includes brain dysmyelination.Recent studies have shed light on the molecular mechanisms underlying these white matter abnormalities.Rodent models of fetal alcohol syndrome and human studies have shown suppressed oligodendrocyte differentiation and apoptosis of oligodendrocyte precursor cells.Ethanol exposure led to reduced expression of myelin basic protein and delayed myelin basic protein expression in rat and mouse models of fetal alcohol syndrome and in human histopathological specimens.Several studies have reported increased expression of many chemokines in dysmyelinating disorders in central nervous system,including multiple sclerosis and fetal alcohol syndrome.Acute ethanol exposure reduced levels of the neuroprotective insulin-like growth factor-1 in fetal and maternal sheep and in human fetal brain tissues,while ethanol increased the expression of tumor necrosis factor α in mouse and human neurons.White matter lesions have been induced in the developing sheep brain by alcohol exposure in early gestation.Rat fetal alcohol syndrome models have shown reduced axon diameters,with thinner myelin sheaths,as well as reduced numbers of oligodendrocytes,which were also morphologically aberrant oligodendrocytes.Expressions of markers for mature myelination,including myelin basic protein,also were reduced.The accumulating knowledge concerning the mechanisms of ethanol-induced dysmyelination could lead to the development of strategies to prevent dysmyelination in children exposed to ethanol during fetal development.Future studies using fetal oligodendrocyte-and oligodendrocyte precursor cell-derived exosomes isolated from the mother's blood may identify biomarkers for fetal alcohol syndrome and even implicate epigenetic changes in early development that affect oligodendrocyte precursor cell and oligodendrocyte function in adulthood.By combining various imaging modalities with molecular studies,it may be possible to determine展开更多
文摘目的:探讨通窍活血汤对外伤后水瘀互结型脑积水患者血清神经生化标志物及脑脊液p73,p38表达和认知功能的影响。方法:选取新乡医学院第一附属医院就诊并诊断为外伤后脑积水患者74例,按照随机数字表法分为两组,对照组(37例)给予常规对症及支持治疗,观察组(37例)在对照组基础上予通窍活血汤治疗,观察并记录两组患者治疗前后人脑髓鞘碱性蛋白(myelin basic protein,MBP),中枢神经特异蛋白(Protein S100β),神经元特异性烯醇化酶(neuron-specificenolase,NSE)水平,脑脊液p73,p38水平,术前简易精神状态评价量表(minimum mental state examination,MMSE),格拉斯哥昏迷评分(Glasgow coma scale,GCS),同时对比临床疗效及不良反应发生情况。结果:对照组治疗有效率低于观察组(P<0.05);与治疗前比较,两组治疗后血清MBP,S100β,NSE水平均较治疗前明显降低(P<0.05),且观察组显著低于对照组(P<0.05);两组治疗后患者的脑脊液p73,p38蛋白表达均升高(P<0.05),且观察组高于对照组(P<0.05);两组治疗后患者的MMSE,GCS评分均升高(P<0.05),且观察组高于对照组(P<0.05)。结论:通窍活血汤能有效改善患者临床症状,可能与其降低外伤后水瘀互结型脑积水患者血清MBP,S-100β,NSE水平,提高脑脊液p73,p38蛋白表达水平有关。
基金ThisworkwassupportedbytheMajorStateBasicResearchDevelopmentProgramofChina (No .G19990 5 42 0 6 )
文摘Objective: To investigate the therapeutic effect of nerve growth factor (NGF) on changes of myelin basic protein (MBP) and functional repair of sensory and motor nerve following sciatic nerve injury. Methods: The sciatic nerves of rats were injured by sectioning with shaver,and divided into 3 groups: NGF group (Group A), group of normal saline solution (Group B), untreated group (Group C). The time point of observation was at the 4th week after operation. Sensory evoked potential (SEP) and motor evoked potential (MEP) were detected by Model WD 4000 nerve potential working diagnosis system. Immunohistochemical analysis was used for identification of MBP.Results: The latency of SEP in the Group A at the 4th week after operation was shorter than that in the Group B (P< 0.05 ). The MEP was elicited in 76% of the Group A and was higher than that in the Group B. Results of immunohistochemistry showed that there were less MBP positive cells in the Group A than in the Group B in one and four weeks respectively.Conclusions: NGF can improve the conductive function of injured peripheral nerve and facilitate regeneration of nerve.
文摘目的:观察半夏白术天麻汤对外伤后脑积水患者血清碱性蛋白(myelin basic protein,MBP)、S100β及p73因子表达的影响。方法:60例外伤所致脑积水患者随机分成对照组和观察组,每组30例。对照组给予甘露醇联合乙酰唑胺治疗,观察组在对照组治疗基础上再予半夏白术天麻汤治疗。比较两组治疗前后血清MBP、S100β水平及p73因子表达的变化,测定美国国立卫生院神经功能缺损评分(national institutes of health stroke scale,NIHSS)、巴氏指数评分(barthel index,BI)及中医证候积分的变化,观察临床疗效,并进行随访。结果:与治疗前比较,两组血清MBP及S100β水平均显著降低(P<0.01),p73因子表达情况无明显变化(P>0.05),NIHSS评分及中医证候积分均显著降低(P<0.01),BI评分显著升高(P<0.01);与对照组比较,观察组血清MBP及S100β水平均较低(P<0.01),NIHSS评分及中医证候积分较低(P<0.01),BI评分较高(P<0.01);与对照组比较,观察组有效率较高(P<0.05);与对照组比较,随访时观察组脑积水严重程度较轻(P<0.05)。结论:半夏白术天麻汤治疗外伤所致脑积水在缓解症状及控制病情发展等方面具有一定优势,可能与降低MBP及S100β水平有关。
基金supported by the National Natural Science Foundation of China,Nos.81901193(to HLZ)and 81901267(to YY)。
文摘Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage,in this study,we investigated the role of Piezo1 in intracerebral hemorrhage.We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon(within 48 hours)after intracerebral hemorrhage,primarily in oligodendrocytes.Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema,myelin sheath loss,and degeneration in injured tissue,a substantial reduction in oligodendrocyte apoptosis,and a significant improvement in neurological function.In addition,we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway.These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage,as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath,thereby improving neuronal function after intracerebral hemorrhage.
文摘Objective： To study the role and effect of Schwann cells （SCs） remyelination in contused spinal cord. Methods： Green fluorescence protein expressing-SCs were transplanted into the epicenter, rostral and caudal tis- sues of the injury site at 1 week after the spinal cords were contused. At 6 weeks, the spinal cords were removed for cryosections, semithin sections and ultrathin sections, and then immunocytochemical staining of myelin basic protein （MBP）, P0 protein （P0） and S 100 protein （S 100） was carried out on the cryosections. Qualitative and semiquantitative analyses were performed on the cryosections and semithin sections. Ultrastructure ofmyelinated fibers was observed on the ultrathin sections under electron microscope. Results： Transplanted SCs and myelinated fibers im- munocytochemically labeled by MBP, PO as well as S 100 distributed in whole injured area. The quantity of myeli- nated fibers labeled by the three myelin proteins showed no statistical difference, however, which was significantly larger than that of controls. On the semithin sections, the experi- mental group demonstrated more myelinated fibers in the injured area than the controls, but the fibers had smaller diameter and thinner myelin sheath under electron microscope. Conclusion： SCs can promote regeneration of injured nerve fibers and enhance remyelination, which may be his- tological basis of SCs-mediated functional repair of injured spinal cords.
基金Supported by the Research on the Effect of Catalpol on the OPCs' Proliferation and Differentiation(No.81173237)Research on the Impact of OPCs and Remyelination via the Method of Bushenyisu with EAE mice(No.81072765)of National Natural Science Foundation
文摘OBJECTIVE: To evaluate the effect of Tanreqing injection on axon myelin in the mouse brain of experimental autoimmune encephalomyelitis(EAE).METHODS: An EAE model was established by myelin oligodendrocyte glycoprotein(MOG)35-55 immunization in C57BL/6 mice. Mice were randomly divided into the following groups: normal, model,prednisone acetate(PA)(6 mg/kg), Tanreqing high dose(5.14 m L/kg), Tanreqing low dose(2.57 m L/kg). On the day of immunization, both Tanreqing groups were treated by intraperitoneal injection,with the PA group treated by intragastrical perfusion after T cell response, and the other groups treated with saline. Changes in body weight, neurological deficit score, incidence rate, mortality rate,and course of disease were observed for all mice.Brain tissue was isolated and stained with hematoxylin-eosin, and pathological investigations performed to evaluate axon myelin damage by transmission electron microscopy(TEM). Myelin basic protein and microtubule associated protein-2 were analyzed by immunohistochemistry.RESULTS: Tanreqing injection significantly prolonged EAE latency and decreased the neurological deficit score, alleviated infiltration of inflammatory cells in the focus area, up-regulated hippocampal MBP expression at the acute stage and the remission stage, and increased microtubule associated protein-2 expression in the EAE brain to varying degrees in the acute stage. TEM analysis indicated that Tanreqing injection alleviates myelin damage in the EAE mouse and maintains the integrity of circular layer structures and alleviates axon mitochondrial swelling.CONCLUSION: Tanreqing injection alleviates EAE symptoms.
文摘目的探讨牛乳清碱性蛋白对实验大鼠和人体骨密度的影响。方法将44只雌性SD 大鼠分为4个组。具体设置为:对照组、A 组(每天给以每 kg 体重10 mg 乳清碱性蛋白)、B 组(每天给以每 kg 体重20 mg 乳清碱性蛋白)和 C 组(每天给以每 kg 体重30 mg 乳清碱性蛋白)。连续灌胃90 d 后,分离股骨,分别测定股骨远心端,股骨干中段和股骨近心端骨密度。募集健康育龄女性志愿者63名[(37.9±4.3)岁],随机分为对照组、甲组、乙组3组,其中:对照组饮用普通牛奶、甲组饮用含30 mg 乳清碱性蛋白的牛奶、乙组饮用含60 mg 乳清碱性蛋白的牛奶,每日1次,连续24周;于干预前后分别采用双能 X 射线测量腰椎(12～L4)、左侧股骨近端(股骨颈、大转子和 Ward 三角区)及右足跟骨骨密度;ELISA 法测量血清骨特异碱性磷酸酶(BAP)、Ⅰ型胶原交联 N 末端肽(NTx)。结果 A 组大鼠的股骨远端骨密度高于对照组,而添加本试验剂量的乳清碱性蛋白牛奶对育龄女性受试者骨密度未见明显影响。结论本实验条件下,每日每 kg 体重10 mg 乳清碱性蛋白能提高实验大鼠的股骨密度,但未观察到对人体骨密度的影响。
基金supported by NIH grants R01NS97846,R01NS097846-02S1 and R01NS092876 awarded to MESShriners research grant SHC-85400 awarded to MESUSA Pennsylvania State Department grant Project 10:420491-04400-02 to ND。
文摘The pathology of fetal alcohol syndrome and the less severe fetal alcohol spectrum disorders includes brain dysmyelination.Recent studies have shed light on the molecular mechanisms underlying these white matter abnormalities.Rodent models of fetal alcohol syndrome and human studies have shown suppressed oligodendrocyte differentiation and apoptosis of oligodendrocyte precursor cells.Ethanol exposure led to reduced expression of myelin basic protein and delayed myelin basic protein expression in rat and mouse models of fetal alcohol syndrome and in human histopathological specimens.Several studies have reported increased expression of many chemokines in dysmyelinating disorders in central nervous system,including multiple sclerosis and fetal alcohol syndrome.Acute ethanol exposure reduced levels of the neuroprotective insulin-like growth factor-1 in fetal and maternal sheep and in human fetal brain tissues,while ethanol increased the expression of tumor necrosis factor α in mouse and human neurons.White matter lesions have been induced in the developing sheep brain by alcohol exposure in early gestation.Rat fetal alcohol syndrome models have shown reduced axon diameters,with thinner myelin sheaths,as well as reduced numbers of oligodendrocytes,which were also morphologically aberrant oligodendrocytes.Expressions of markers for mature myelination,including myelin basic protein,also were reduced.The accumulating knowledge concerning the mechanisms of ethanol-induced dysmyelination could lead to the development of strategies to prevent dysmyelination in children exposed to ethanol during fetal development.Future studies using fetal oligodendrocyte-and oligodendrocyte precursor cell-derived exosomes isolated from the mother's blood may identify biomarkers for fetal alcohol syndrome and even implicate epigenetic changes in early development that affect oligodendrocyte precursor cell and oligodendrocyte function in adulthood.By combining various imaging modalities with molecular studies,it may be possible to determine
