化学致痫剂马桑内酯导致大鼠海马神经细胞内Ca^2＋升高

于培养的新生太鼠海马神经细胞,应用ｆｕｒａ－２荧光检测技术,观察了致痫剂马桑内酯对单个海马神经细胞内钙离子浓度（［Ｃａ＾２＋］ｉ）的影响。培养液内马桑内酯浓度达１０＾－８ｍｏｌ／Ｌ时可引起［Ｃａ＾２＋］ｉ增加,［Ｃａ＾２＋］ｉ随给药浓度的提高而升高。马桑内酯浓度达５×１０＾－６ｍｏｌ／Ｌ时,［Ｃａ＾２＋］ｉ维持于稳定的高水平上。当胞外无Ｃａ＾２＋时,马桑内酯仍可引起［Ｃａ＾２＋］ｉ的升高;Ｌ－型钙     

马桑内酯对神经元内游离钙作用的研究

目的研究致癫痫剂马桑内酯对大脑皮质神经元内游离钙（［Ｃａ２＋］ｉ）的作用及其作用途径，以探讨马桑内酯的致癫痫机制。方法利用培养１４天的大鼠大脑皮层神经元和ＡＲ－ＣＭ－ＭＩＣ阳离子检测系统，观察不同浓度的马桑内酯对［Ｃａ２＋］ｉ的作用，并分别用钙通道阻滞剂维拉帕米和２－氨基膦酸基戊酸（ＡＰ５）及钙螯合剂ＥＧＴＡ，观察马桑内酯作用的可能途径。结果马桑内酯使［Ｃａ２＋］ｉ水平升高，在（２５～５００）×１０－６ｍｏｌ／Ｌ范围内，呈明显的剂量效应关系；加入５×１０－３ｍｏｌ／ＬＥＧＴＡ至介质中后，马桑内酯作用消失，补充１０－３ｍｏｌ／Ｌ氯化钙后作用又出现；预先加入５×１０－６ｍｏｌ／Ｌ维拉帕米可明显拮抗其升钙作用，而加入１０－５ｍｏｌ／ＬＡＰ５则阻断作用不明显。结论致癫痫剂马桑内酯可使神经元内［Ｃａ２＋］ｉ升高，其升高［Ｃａ２＋］ｉ的作用依赖于细胞外钙，电压依赖性钙通道可能是其升高［Ｃａ２＋］ｉ的主要途径。     

血小板活化因子对神经细胞内游离钙离子作用的研究

目的观察脑损害时病理活性介质血小板活化因子（ｐｌａｔｅｌｅｔａｃｔｉｖａｔｉｎｇｆａｃｔｏｒ,ＰＡＦ）及其拮抗剂对神经细胞内游离钙离子（［Ｃａ２＋］ｉ）浓度的影响,探讨ＰＡＦ致使神经细胞内［Ｃａ２＋］ｉ超载的途径及其作用机制。方法采用ＡＲＣＭＭＩＣ阳离子检测系统,观察不同浓度的ＰＡＦ以及其特异性受体拮抗剂ＢＮ５２０２１和非特异性拮抗剂ＭＫ８０１对体外培养１４天的大鼠皮层神经元［Ｃａ２＋］ｉ浓度的影响。结果５×１０－６ｍｏｌ／Ｌ的ＰＡＦ可使培养神经细胞［Ｃａ２＋］ｉ浓度明显增高,与对照组比较差异有显著意义（Ｐ＜０．０１）;ＢＮ５２０２１可明显阻止ＰＡＦ所致的神经细胞内［Ｃａ２＋］ｉ超载,在此基础上加用ＭＫ８０１可使神经细胞内［Ｃａ２＋］ｉ水平下降的更为明显。结论ＰＡＦ可通过多种渠道致使神经细胞内钙离子超载。     

白细胞介素1β对谷氨酸诱导的培养海马神经元单细胞游离钙离子浓度的影响

目的研究白细胞介素１β（ＩＬ１β）促进癫痫发作和神经细胞损伤的细胞内机制。方法应用ＥＰＣ９光电联合检测系统检测ＩＬ１β对培养海马神经元单个细胞内游离钙离子（［Ｃａ２＋］ｉ）浓度的影响,以及ＩＬ１β与谷氨酸（Ｇｌｕ）共同作用对神经元［Ｃａ２＋］ｉ浓度的影响。结果不同浓度的ＩＬ１β（５、１０、２０、３０、５０及１００Ｕ／ｍｌ）均不能引起神经元［Ｃａ２＋］ｉ浓度的显著变化,而ＩＬ１β却能剂量依赖性地促进Ｇｌｕ对神经元［Ｃａ２＋］ｉ浓度的升高作用。ＭＫ８０１抑制了Ｇｌｕ的升钙作用,也抑制了ＩＬ１β对Ｇｌｕ升钙的促进作用,而ｖｅｒａｐａｍｉｌ对Ｇｌｕ和ＩＬ１β的作用均无明显影响。结论ＩＬ１β作为一种神经调质,促进Ｇｌｕ激活Ｎ甲基Ｄ天门冬氨酸（ＮＭＤＡ）受体,并介导细胞内游离钙离子浓度增高,提高神经细胞的兴奋性。     

白细胞介素1β对谷氨酸诱导的培养海马神经元单细胞游离钙离子？…

目的 研究白细胞介素１β（ＩＬ－１β）促进癫痫发作和神经细胞损伤的细胞内机制。方法 应用ＥＰＣ－９光电联合检测系统检测ＩＬ－１β对培养海马神经元单个细胞内游离钙离子（［Ｃａ＾２＋］ｉ）浓度的影响,以及ＩＬ－１β与谷氨（Ｇｌｕ）共同作用对神经元［Ｃａ＾２＋］ｉ浓度的影响。结果 不同浓度的ＩＬ－１β（５、１０、２０、３０、５０及１００Ｕ／ｍｌ）均不能引起神经元［Ｃａ＾２＋］ｉ浓度的显著变化,而ＩＬ－１     

改良Fura—2双波长荧光法测定兔脑缺血脑片[Ca^2＋]i

采用新型Ｃａ２＋荧光指示剂Ｆｕｒａ－２建立双波长法测定兔ＭＣＡＯ局灶脑缺血脑片游离钙（［Ｃａ２＋］ｉ），结果显示脑缺血后神经细胞内［Ｃａ２＋］ｉ明显升高。     

NO—cGMP—Glu—[Ca^2＋]i途径在隔—海马通路损伤的…

为探讨海马中一氧化氮影响大鼠学习能力的机制，观察海马中一氧化氨（ＮＯ）降低后海马ｃＧＭＰ、谷氨酸（Ｇｌｕ）、胞内游离钙离子（［Ｃａ＾２＋］ｉ含量的变化。结果表明海马中ＮＯ降低的同时ｃＧＭＰ、Ｇｌｕ和［Ｃａ＾２＋］ｉ也降低。提示海马中ＮＯ可能是通过ＮＯ－ｃＧＭＰ－Ｇｌｕ－［Ｃａ＾２＋］ｉ途径影响大鼠的学习能力。     

脑缺血病人血小板肌球蛋白轻链激酶和Ca2+、Mg2+-ATP酶活性及其与[Ca2+]i关系的研究

目的探讨急性缺血性脑血管病血小板肌球蛋白轻链激酶（ＭＬＣＫ）和Ｃａ２＋、Ｍｇ２＋－ＡＴＰ酶活性的变化及与血小板胞浆游离钙浓度［Ｃａ２＋］ｉ的关系。方法用３２Ｐ同位素掺入法和比色法分别测定５８例脑缺血病人，及３５名健康对照者血小板ＭＬＣＫ和Ｃａ２＋、Ｍｇ２＋－ＡＴＰ酶活性。用荧光钙指示剂Ｆｕｒａ－２负载血小板扫描的方法，测定脑缺血病人血小板［Ｃａ２＋］ｉ浓度。结果ＴＩＡ组和脑梗死组ＭＬＣＫ活性与对照组相比均有明显增加（Ｐ＜０．０１），而Ｃａ２＋Ｍｇ２＋－ＡＴＰ酶活性均低于对照组（Ｐ＜０．０５，Ｐ＜０．０１）。ＴＩＡ组和脑梗死组血小板静息［Ｃａ２＋］ｉ；均高于对照组；血小板静息［Ｃａ２＋］ｉ与血小板ＭＬＣＫ活性呈显著正相关（Ｐ＜０．０１），而与血小板Ｃａ２＋、Ｍｇ２＋－ＡＴＰ酶活性呈负相关（Ｐ＜０．０５）。结论血小板ＭＬＣＫ和Ｃａ２＋、Ｍｇ２＋－ＡＴＰ酶活性与急性缺血性脑血管病的发生有密切关系，ＭＬＣＫ活性的变化可能是脑缺血病人血小板活化的分子基础。     

脑缺血再灌流［~3H］—三磷酸肌醇放射活性及突触体游离Ca~（2＋）的变化

本文研究了大鼠脑缺血再灌流时［３Ｈ］—三磷酸肌醇（［３Ｈ］－ＩＰ３）放射活性及突触体游离Ｃａ２＋（［Ｃａ２＋］ｉ）的变化，并用苯甲基磺酰氟化物（ＰＭＳＦ）治疗，观察其对［３Ｈ］－ＩＰ３放射活性及突触体［Ｃａ２＋］ｉ的影响。结果：脑缺血１ｍｉｎ［３Ｈ］－ＩＰ３放射活性非常显著地增高。缺血２０ｍｉｎ、缺血２０ｍｉｎ再灌流１ｈ、６ｈ、２ｄ［３Ｈ］－ＩＰ３放射活性非常显著地降低。缺血２０ｍｉｎ突触体［Ｃａ２＋］ｉ非常显著地增高，至再灌流６ｈ达到最高水平。应用ＰＭＳＦ治疗能显著地抑制突触体［Ｃａ２＋］ｉ的升高。     

脑缺血再灌注[^3H]——三磷酸肌醇放射活性及突触体游离C …

本文研究了大鼠脑缺血再灌流时［＾３Ｈ］－三磷酸肌醇［＾３Ｈ］－ＩＰ３）放射活性及突触体游离Ｃａ＾２＋（［Ｃａ＾２＋］ｉ）的变化，并用苯甲基磺酰氟化物（ＰＭＳＦ）治疗，观察其对［＾３Ｈ］－ＩＰ３放射活性及突触体［Ｃａ＾２＋］ｉ的影响。结果：脑缺血１ｍｉｎ［＾３Ｈ］－ＩＰ３放射活性非常显著地增高。缺血２０ｍｉｎ、缺血２０ｍｉｎ再灌注１ｈ、６ｈ、２ｄ［＾３Ｈ］－ＩＰ３放射活性非常显著地降低。缺血２０ｍ，     

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.