脾非淋巴细胞条件培养液作用于颈上节的实验观察

探讨脾非淋巴细胞是否能够产生具有生物活性的神经营养因子.分离BALB/c小鼠非淋巴细胞并进行原代培养,收集培养上清液作为条件培养液孵育新生小鼠颈上节60 h.结果显示,与对照培养液相比,条件培养液能够显著地促进体外培养中颈上节交感神经生长锥的发育,且这一作用在不同程度上可被抗NGF和NT-3抗体特异性阻断.免疫组化染色证实培养的脾非淋巴细胞中有抗神经生长因子(NGF)和神经营养素 -3(NT-3)免疫反应产物的存在.结果表明,脾非淋巴细胞能够产生具有生物活性的神经营养因子,后者可能在维持交感神经形态和功能方面起作用.     

变应性鼻炎患者外周血中神经营养因子mRNA的表达

目的检测变应性鼻炎患者外周血中神经生长因子(NGF)、脑源性神经营养因子(BDNF)、神经营养蛋白-3(NT-3)mRNA的表达水平,并分析基因表达与鼻炎病情严重程度的关系。方法采用成组对照试验,抽提变应性鼻炎患者外周血总RNA,以正常成人为对照组。使用实时定量RT-PCR检测NGF、BDNF、NT-3mRNA的表达水平,2-ΔΔCt法计算实验组基因表达的变化倍数。结果相较于正常成人,变应性鼻炎患者的外周血中NGF、BDNF、NT-3mRNA的2-ΔΔCt值依次为2.4368、4.4588、1.7818;NT-3mRNA表达的2-ΔΔCt值随着鼻炎严重程度加重呈递增趋势。结论相较于正常成人,变应性鼻炎患者外周血中NGF、BDNF、NT-3mRNA的表达量上调,可能与变应性鼻炎发病有关;NT-3可作为评价变应性鼻炎严重程度的分子生物学指标。     

神经营养因子-3研究进展

神经营养因子主要有神经生长因子(nerve growth factors,NGF)、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)、神经营养因子-3(nerve neurotrophic factor 3,NT-3)、神经营养因子-4(nerve neurot-rophic factor4/5,NT-4/5)等,由靶细胞分泌并逆向经神经转运至胞体的小分     

BDNF在神经系统疾病中的作用机制

1背景 神经营养因子是一种对神经细胞生长、分化起重要作用的由靶器官提取的多肽激素,BDNF,NT-3,NT-4是神经营养因子家族成员,脑源性神经营养因子（brain-derivedneuro—trophic factor,BDNF）是仅次于NGF被发现的,1982年Barde等首次从猪脑提取液中获得,他们从3kg猪脑提取液中分离出2μgBDNF,相对分子质量为12．3ku的碱性蛋白。     

LFPEMF刺激腓总神经损伤的疗效

目的观察低频脉冲电磁场(LFPEMF)刺激治疗腓总神经损伤的疗效,并探讨对神经营养因子-3(NT-3)和神经生长因子(NGF)表达的影响。方法新西兰雄性白兔90只随机分为正常组(n=30),模型组(n=30),治疗组(n=30)。治疗组予LFPEMF刺激,正常组和模型组每天同治疗组一样置于无电磁圈的载物台,不做LFPEMF刺激,治疗前后对患肢进行运动神经传导速度(MCV)、复合肌肉动作电位(CMAP)测定,并应用免疫组织化学S-P法对90只兔受损腓神经组织中的NT-3和NGF的表达进行检测和统计学分析。结果模型组及治疗组腓总神经钳夹后MCV、CMAP波幅较正常组明显下降(P0.01),经过3w治疗,治疗组的患肢MCV和CMAP波幅明显优于模型组(P0.05),NT-3和NGF在治疗组腓神经组织中的表达显著高于模型组(均P0.01)。结论 LFPEMF刺激治疗能够加快受损神经修复,刺激内源性NT-3和NGF分泌,对腓总神经损伤的运动功能恢复有明显改善。     

星形胶质细胞与Aβ1-40诱导凋亡的PC12细胞共育条件培养液对神经干细胞分化的影响机制

目的 将星形胶质细胞与β-淀粉样蛋白(Aβ1-40)诱导凋亡的PCI2细胞共育,观察星形胶质细胞条件培养液(ACM)对胚胎大鼠皮层神经干细胞(NSCs)体外定向分化为神经元的比例影响及机制,探讨神经营养素家族蛋白[包括脑源性神经营养因子(BDNF)、神经生长因子(NGF)、神经营养素-3(NT-3)]是否参与此过程. 方法 PC12细胞分别经10 μg/mLAβ1-40诱导不同时间(0、4、6、12、24h)后分为两部分,第一部分应用流式细胞技术检测不同时间点PC12细胞凋亡率;第二部分分别与星形胶质细胞共育2 d,将收集的ACM分为两部分.一部分应用ELISA法检测ACM中BDNF、NGF、NT-3蛋白含量,另一部分以1;3比例同DMEM/F12堵养基混合,对NSCs进行体外诱导分化,应用激光共聚焦显微镜、NSE免疫荧光技术鉴定和计数神经元分化比例. 结果 在Aβ1-40作用6 h时间点,PC12细胞凋亡率达高峰,与其共育的ACM中BDNF蛋白总量明显增高,诱导的NSCs神经元分化比例明显升高,与其他组比较,差异均有统计学意义(P<0.05). 结论 星形胶质细胞与Aβ1-40诱导凋亡的PCI2细胞共育后.ACM提高了NSCs向神经元的分化比例,ACM中BDNF可能参与了这一过程.     

脑源性神经生长因子功能及细胞内信号传导通路

<正>神经营养因子包括神经生长因子(nerve groth factoe,NGF),脑源性神经生长因子(brain-derived neurotrophic factor,BDNF),神经营养因子-3(neurotrophin-3,NT-3),神经营养因子-4/5(neurotrophin-4/5,NT-4/5)等。这些因子可以作为信号传导通路的配体与其受体酪氨酸蛋白激酶(Trk)高亲和力结合,也可以与分子量为75KDNT受体(75KDNT receptor,p75)以低亲和力结合。Trk包括TrkA、TrkB、TrkC等3种,神经营养因子与其Trk结合具有明显的选择性,其中NGF可与TrkA特异性结合,     

人脐带间充质干细胞中神经营养因子的表达

目的 通过检测人脐带间充质干细胞(hUC-MSCs)的神经营养因子谱,以进一步认识hUC-MSCs通过分泌神经营养因子治疗神经损伤的作用. 方法 组织块培养法分离培养hUC-MSCs,流式细胞仪鉴定干细胞表面标记物,Raybio人细胞因子抗体芯片检测hUC-MSCs神经营养因子表达情况,RT-PCR检测hUC-MSCs神经营养因子的基因表达,ELISA法定量检测hUC-MSCs上清液中分泌的脑源性神经营养因子(BDNF)、胶质细胞源性神经营养因子(GDNF)、肝细胞生长因子(HGF)、神经营养因子3(NT-3)含量. 结果 流式细胞分析结果显示hUC-MSCs表面标记物CD29、CD44、CD90阳性(94.05％、90.75％、98.12％),CD34、CD45阴性(3.09％、0.80％).Raybio人细胞因子抗体芯片结果显示,与神经营养相关的因子BDNF、表皮生长因子(EGF)、GDNF、HGF、NT-3、血管内皮细胞生长因子(VEGF)、胰岛素样生长因子-1(IGF-1)、神经营养因子4(NT-4)在hUC-MSCs中均有表达.RT-PCR检验也证实IGF-1、VEGF、神经生长因子(NGF)、HGF、GDNF、NT-4、BDNF和NT-3基因在hUC-MSCs表达.ELISA检测细胞上清液中BDNF、GDNF、HGF、NT-3的含量分别为(475.20±32.22) pg/mL、(82.33±3.39) pg/mL、(704.50±12.86) pg/mL、(230.41±16.66) pg/mL,分别与空白对照组相比,差异均有统计学意义(P＜0.05). 结论 hUC-MSCs富含神经营养因子,是一种理想的用于神经损伤治疗的种子细胞.     

维持性血液透析患者抑郁焦虑与神经营养因子的相关性分析

目的研究维持性血液透析(MHD)患者抑郁、焦虑与神经营养因子的相关性。方法选择2012-01—2014-10在我院接受MHD的肾病患者172例为观察组,选择我院职工及部分志愿者50例为对照组。对2组进行SDS、SAS评分的评定,并对比2组抑郁、焦虑情况,脑源性神经营养因子(BDNF)、神经营养素-3(NT-3)以及血清相关水平。再根据抑郁、焦虑评分将观察组分组,对影响抑郁、焦虑的因素进行对比分析。结果观察组SDS、SAS评分及抑郁、焦虑、抑郁合并焦虑患者所占比例均显著高于对照组,且BNDF、Hb、ALb以及Cre等水平低于对照组,NT-3高于对照组。根据抑郁评分分组发现,观察组中抑郁组患者NT-3水平高于非抑郁患者,且BNDF、Hb、ALb、Ca水平低于非抑郁患者。根据焦虑评分分组发现,观察组焦虑组NT-3水平高于非焦虑患者,差异均有统计学意义(均P0.05)。其他水平均未发现显著差异(P0.05)。经相关性分析,MHD患者抑郁与NT-3存在显著的正相关,与BNDF、Hb、ALb、Ca水平存在显著的负相关。而MHD病患焦虑仅与NT-3存在显著的正相关。结论 MHD患者出现抑郁焦虑的比例明显更高,且抑郁、焦虑的发生与神经营养因子存在较大的相关性。尤其是NT-3可作为诊断MHD患者抑郁、焦虑的标准,以便对其实施干预措施保证治疗效果。     

proNGF-p75NTR-sortilin三聚体在神经细胞凋亡中的作用

神经营养素(neurotrophic,NT)是一种分泌性的二聚体蛋白家族,可以影响动物神经细胞的存活、发育、形态及功能.在哺乳动物中,已知的NT包括以下4种:神经生长因子(nevre growthfactor,NGF)、脑源性营养因子(brain-derived neurotrophic factor,BDNF)、神经营养因子-3(NT3)和神经营养因子-4/5,6(NT4/5,6).     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Pediatric Epilepsy Surgery

Summary: The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.