细胞外信号调节激酶的磷酸化水平对星形胶质细胞增殖及其细胞周期的影响

目的 探讨细胞外信号调节激酶(ERK1/2)的磷酸化水平对体外星形胶质细胞(Ast)增殖及其细胞周期的影响.方法 将培养成熟的大鼠原代Ast分为两组,其中一组用ERK1/2磷酸化的特异性抑制剂U0126进行处理(U0126组),另一组不做处理,作为对照组.通过Western Blot技术、Click-iT Edu技术和流式细胞术分别检测两组Ast中ERK1/2磷酸化水平、Ast增殖细胞百分比及各期细胞百分比.结果 U0126组ERK1/2的磷酸化水平(39.13％±6.71％)明显低于对照组(100％).U0126处理24 h后,U0126组Ast增殖细胞百分比[(2.63±1.14)％]低于对照组[(21.43±3.81)％](t=21.13,P＜0.01).G1期U0126组Ast[(93.67±0.68)％]高于对照组[(84.63±1.00)％](t=12.91,P＜0.01);S期U0126组Ast[(2.90±0.23)％]低于对照组[(14.21±1.14)％] (t=16.87,P＜0.01);G2期U0126组Ast[(3.43±0.88)％]高于对照组[(2.08±0.21％)％](t=4.35,P＜0.05).结论 降低ERK1/2的磷酸化水平可抑制Ast的增殖,并将其阻断在G1期,抑制Ast从G1期向S期的转化,同时抑制其分裂将其阻断在G2期.     

少突胶质细胞的钙信号

钙是细胞内重要的第二信使,参与机体内多种生理过程,其胞内的钙信号传递依赖于胞内外的钙离子(Ca2+)浓度差,表现为胞质内钙的变化.Ca2+进入细胞内与钙的受体如钙调素(calmodulin,CaM)结合后发挥系列效应.以往认为Ca2+仅在兴奋性细胞中起传递信号作用,但近年来随着研究的深入,发现无论是兴奋性还是非兴奋性细胞,钙都作为第二信使参与信号转导及基因的表达调控.少突胶质细胞是中枢神经系统髓鞘形成细胞,被认为是中枢神经系统中一种非兴奋性细胞,其对于细胞外的刺激可表现为胞内钙浓度的变化从而调控细胞活动.     

银杏叶提取物对星形胶质细胞增殖周期的影响

目的:探讨银杏叶提取物(EGb)对体外培养的大鼠大脑皮质星形胶质细胞(Ast)增殖周期的影响。方法:体外培养、纯化及鉴定大鼠大脑皮质Ast;MTT比色法选择EGb作用浓度;1×10-7μL·L-1EGb50μL分别加入对照组和实验组培养液;利用流式细胞仪分析技术检测细胞周期。结果:随着Ast培养时间的延长,12h内EGb诱导Ast进入S期+G2/M期的细胞百分率有上升趋势,但24h后稍有下降。结论:EGb可通过影响Ast的细胞周期促进Ast的增殖。     

反应性星形胶质细胞增生在脑缺血中的作用

星形胶质细胞(AST)是中枢神经系统主要的细胞.当CNS受到损伤时,AST从静止状态下活化,形成反应性星形胶质细胞增生,如损伤严重将形成胶质疤.本文就星形胶质细胞的生理作用,反应性胶质细胞增生的定义、机制、作用以及在脑缺血中的治疗做一综述.     

水通道蛋白-4的研究进展

水通道蛋白-4(AQP4)主要在脑组织中表达,起着调节脑内水转运的重要功能,参与脑水肿的病理生理过程。其参与星形细胞对K+摄取和释放,神经胶质细胞迁移,神经胶质瘢痕形成的生理过程。AQP4参与了许多疾病病理过程,如癫、视神经脊髓炎。AQP4可能为中枢神经系统疾病治疗提供新的途径。     

人脑梗死后神经元与星形胶质细胞细胞骨架蛋白的改变

急性脑梗死后的病理生理机制包括细胞骨架蛋白的降解、细胞凋亡的发生、胶质细胞的反应和微循环损害等。其中 ,细胞骨架蛋白维持真核细胞的空间结构 ,包括微管、微丝或肌动蛋白丝以及中间丝 3种类型 ,参与细胞内物质转运、细胞运动、信息传递、能量转换、细胞分裂等活动 [1 ] 。其变化反映了神经细胞的存活和功能状态 ,可提示梗死后不同区域的功能状态 [2 ]。1　细胞骨架概述细胞骨架 (cytoskeleton)是由蛋白纤维交织成的立体网状结构 ,如同一种内部框架 ,充满整个细胞质的空间 ,与外侧的细胞膜和内侧的核膜存在一定的结构联系 [3]。由 3种…     

星形胶质细胞与癫痫

星形胶质细胞是中枢神经系统的主要支持成分，参与多种生理、病理功能。星形胶质细胞具有对各种神经损害产生强烈反应的特性。在病理条件下，星形胶质细胞内多种细胞因子表达增加．对疾病的神经损害具有重要影响。近年来，星形胶质细胞在癫痫发生、发展中的作用日益受到重视。１星形胶质细胞解剖、生理星形胶质细胞起源于外胚层，分布于中枢神经系统的各个部分。星形胶质细胞发出突起附着在毛细血管壁上或脑和脊髓表面形成胶质界膜，将中枢神经系统与中胚层组织分开。在中枢神经系统内部，胶质细胞充填于神经元胞体及其突起之间，并将突触结…     

伽玛刀照射后胶质细胞CX43和GFAP表达变化及意义

目的研究伽玛刀照射后胶质细胞缝隙连接蛋白43(Connexin43,Cx43)和胶质纤维酸蛋白(glial fibrillary acid protein,GFAP)表达的变化。方法体外培养原代星形胶质细胞(astrocytes,Ast)分为正常对照组和γ刀照射组,后者经γ刀照射(边缘剂量4～36Gy),培养72小时后检测GFAP,Cx43。结果4～12Gy组与正常对照组无显著差异,至16Gy组胶质细胞开始增生GFAP表达阳性细胞数大于正常对照组且呈剂量依赖性增高至32Gy组GFAP表达达最大值。Cx43表达在12Gy组即开始明显下降且Cx43表达呈计量依赖性减低,在24～32Gy降低尤为显著至32Gy组达最低值。结论原代培养Ast经伽玛刀照射后GFAP表达增高,同时Cx43表达减低。Cx43的异常低表达可能是胶质增生及放射损伤的重要原因。     

影响神经干细胞定向分化因素的研究进展

神经干细胞(NSC)具有自我更新和多分化潜能属性,可分化产生神经元、星形胶质细胞和少突胶质细胞,这使得NSC移植替代神经系统疾病中丢失的细胞成为可能.NSC在胚胎和成体中枢神经系统均存在.NSC移植在体内环境下(尤其是非神经发生区域)绝大多数分化成胶质细胞(星形胶质细胞),有可能会加重胶质瘢痕形成.在中枢神经系统疾病的NSC细胞替代治疗策略中,NSC分化成合适的细胞类型显得格外重要.现就影响NSC定向分化的因素作一综述.     

小胶质细胞体外培养的研究新进展

组成中枢神经系统的细胞大部分是神经胶质细胞,包括大胶质细胞(星型胶质细胞和少突胶质细胞)和小胶质细胞;小胶质细胞是中枢神经系统的主要免疫细胞,具有提呈抗原、分泌多种细胞因子、吞噬病原体和坏死组织的作用,被认为是脑内的单核巨噬细胞.由于小胶质细胞在颅内免疫反应中的重要作用,对于小胶质细胞的研究已成为热点;小胶质细胞的体外培养是小胶质细胞功能研究的重要途径,本文将对近年来小胶质细胞的体外培养研究进展作一综述.     

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.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

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.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

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.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.