SCG10在癫痫苔藓纤维出芽中的作用

苔藓纤维出芽(mossy fiber sprouting.MFS)是癫痫后最重要的形态学改变之一,与痫性活动的反复自发性发作密切相关.MFS和突触重塑是难治性癫痫的主要病理基础,而MFS又是突触重塑的主要形式,在难治性颞叶癫痫患者标本和癫痫动物模型中普遍存在.     

癫痫大鼠海马出芽苔藓纤维突触的超微结构特征

目的:探讨匹罗卡品颞叶癫痫大鼠海马出芽苔藓纤维突触的超微结构特征及其在颞叶癫痫发病机制中的作用。方法:采用Timm组化染色标记出芽苔藓纤维突触末端,在电镜下观察新生突触的类型、比例、定位、以及突触后靶成分。结果:颞叶癫痫大鼠齿状回内分子层可见到银标记的突触末端,出芽苔藓纤维突触主要是轴棘型非对称性突触,其次是轴树型非对称性突触,偶可看到出芽轴突和颗粒细胞体形成突触联系。结论:轴棘型非对称性突触是颞叶癫痫大鼠海马出芽苔藓纤维突触的主要类型,出芽苔藓纤维突触的超微结构特性支持重组突触形成重复的兴奋性环路,而且形成的新的兴奋性环路可能在颞叶癫痫的发生与发展中起重要作用。     

苔藓纤维出芽机制研究进展

苔藓纤维出芽（mossy fiber sprouting，MFS）是癫痫发作后最常见的病理改变之一，与癫痫的反复自发性发作密切相关。在痫性损伤后由于门区神经元和CA3区锥体细胞大量死亡，齿状回内分子层（IML）失神经传人，同时颗粒细胞也失去投射靶，因此苔藓纤维芽生侧枝进入颗粒体层、IML以及CA3区始层，重建海马神经网络。虽然MFS也可形成抑制性突触，但兴奋性突触的形成占优势，同时齿状回对兴奋的滤过作用降低，冲动便在再生神经回路中迅速传播，最终导致癫痫反复发作。MFS的过程十分复杂，目前认为神经细胞死亡和痫性发作是促使出芽的两大因素，但其具体机制尚未明确，本文就MFS相关的分子因素以及信号转导通路与出芽关系的研究现状作一综述。     

颞叶癫痫海马突触重组及其与钙调控的关系

苔藓纤维出芽是颞叶癫痫突触重组的主要表现.出芽的苔藓纤维在颗粒细胞间形成兴奋性环路,使颗粒细胞产生同步化电活动的阈值降低,也可经海马结构内的传导通路,使海马结构在传出途径上的电活动增强,从而导致反复自发性癫痫发作的发生.钙离子作为一种信使参与多种细胞功能活动的调节,钙通道功能的改变可引起细胞内外钙离子浓度的变化,而细胞内高钙和细胞外低钙均可诱发神经电活动紊乱,因此钙稳态在癫痫发生发展及海马突触重组的形成中起重要作用.     

颞叶癫痫患者海马苔藓纤维发芽的实验研究

目的观察颞叶癫痫病人海马齿状回和CA3区苔藓纤维出芽情况。方法癫痫组样本来自12例颞叶癫痫病例的手术切除标本包含海马齿状回和CA3区的脑组织，对照组脑组织样本来自4例非癫痫病的尸检脑组织。应用Timm组织化学染色方法在光镜和电镜水平进行海马结构苔藓纤维发芽的研究。结果光镜下癫痫组可见苔藓纤维穿越海马齿状回颗粒细胞层到达内分子层．CA3区也可见明显的苔藓纤维发芽。癫痫组CA3区和齿状回内分子层苔藓纤维发芽评分高于对照组．统计学上差异有显著性意义。电子显微镜下观察显示癫痫组患者齿状回内分子层可见到银标记的突触末端，主要和树突形成突触连接，所形成的突触为非对称性突触。结论颞叶癫痫可致海马齿状回和CA3区苔藓纤维发芽增加，这可能是难治性癫痫形成的重要机制。     

海马苔藓纤维出芽与颞叶癫痫

海马颗粒细胞苔藓纤维出芽(MFS)导致局部环路重建,在颞叶癫痫的发生与发展过程中起关键性作用。本文综述了近年有关海马MFS的病理解剖生理学特点、出芽机理及其与颞叶癫痫关系的最新研究成果,以期为探讨颞叶癫痫的形成机制提供新的思路。     

突触素与癫痫

癫痫（epilepsy）是最常见的神经系统疾病之一，其发病机制复杂，目前认为癫痫发病是由于中枢神经系统兴奋与抑制性不平衡导致大脑神经元异常放电所致。近年研究表明，这种兴奋与抑制间的不平衡主要与离子通道、突触传递及神经胶质细胞的改变有关。癫痫发生时大脑海马部位出现的苔藓纤维异常出芽及伴随的突触重建被认为是其细胞机制之一。近年来研究的热点之一是海马结构的可塑性重建，这种可塑性主要表现在突触上。     

匹罗卡品癫痫大鼠海马TrkB受体表达与苔藓纤维突触重建的关系

目的 探讨匹罗卡品诱导慢性癫痫大鼠海马齿状颗粒细胞苔藓纤维突触重建与神经营养素受体TrkB表达的关系。方法 取匹罗卡品诱导大鼠急性癫痫持续状态及慢性自发性颞叶癫痫发作期大鼠脑片，用免疫组织化学方法检测TrkB及突触体素(P38，一种突触形成标志物)在大鼠海马的表达。结果 急性癫痫持续状态诱导颗粒细胞表达TrkB一过性增高，第2次表达高峰呈现在7～30d；P38免疫反应性在齿状回内分子层则呈进行性增加，与neo-Timm显示的异常苔藓纤维出芽相一致。结论 TrkB受体激活有助于海马齿状回苔藓纤维轴突生长及突触形成从而有利于颞叶癫痫的发生。     

癫痫发作后海马结构GABA受体亚单位变化的研究

γ-氨基丁酸(GABA)是中枢神经系统主要的抑制性神经递质,其功能变化几乎影响各类癫痫的发生发展,颞叶内侧的海马结构在癫痫发作中起重要作用。本文着重介绍海马结构中GABA受体各亚型亚单位在癫痫发作后发生的重要的选择性变化,以了解其在癫痫中发生发展机理,为筛选针对受体亚单位水平发生作用的新的抗痫药提供途径。     

癫痫苔藓纤维出芽的研究进展

癫痫的发病机制非常复杂．迄今尚未完全阐明。苔藓纤维出芽（mossy fiber sprouting，MFS）作为癫痫发作后最常见的病理改变之一，与癫痫的反复自发性发作密切相关。近年来，已有不少的研究从苔藓纤维出芽的角度探讨癫痫的发生、发展．并为癫痫的治疗提出新的观点。现就癫痫苔藓纤维出芽的研究进展做一综述。[第一段]     

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.     

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.     

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.     

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.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.