颈迷走神经脉冲电刺激对大鼠点燃速度及杏仁？…

定量研究颈迷走神经刺激对大鼠癫痫形成速度及杏仁核放电的影响。方法用频率１６Ｈｚ,波宽１．０ｍｓ,串长１０ｓ,串隔７ｍｉｎ,强度３．０ｍＡ的恒流脉冲电刺激１８只大鼠的左颈迷走神经,同时用强度０．４ｍＡ的恒流脉冲电诱发刺激大鼠的杏仁核。以１８只仅刺激杏仁核的大鼠作对照,观察其癫痫行为及杏仁核放电情况。     

癫痫电点燃的研究进展

癫痫作为神经系统的一种常见病,极大地影响着患者的健康。为进一步研究癫痫,近年来建立了多种动物模型。癫痫点燃(kindling)的动物模型具有诱导致痫和自发性发作模型的优点。我们将电点燃现象、点燃方法、点燃机制、点燃的动物及部位进行综述。1.电点燃的概念电点燃的概念是通过重复不变的亚抽搐剂量的电刺激,导致癫痫活动强度逐渐增加,最终出现全身性癫痫发作称为点燃。点燃目前被公认为是一种理想的癫痫动物模型,其致痫性增高具有永久的保留能力,较好地模拟了人类癫痫的进行性发展和长期反复的自限性发作形式。目前,主要的癫痫模型有化学点燃、脑内点燃、光或电点燃、脑组织片点燃等模型。用电刺激鼠杏仁核点燃,一般经历以下过程:1面部抽搐,2点头,3前技阵挛,4站立,5站立和摔倒。Wada[1]将点燃过程分为6个阶段:(1)同侧面部抽搐;(2)两侧面部抽搐;(3)点头;(4)对侧前肢出现阵挛,并且头向对侧旋转;(5)站立时出现阵挛性跳跃;(6)摔倒,并全身抽搐(强直-阵挛发作)。在试验中一旦出现摔倒伴全身性抽搐,就被认为已制成点燃模型。这种作用是持续的,动物点燃后停止刺激12个月,再次用原第一次的剂量刺激,仍能出现摔倒伴全身抽搐。目前尚没...     

癫痫动物模型点燃的研究进展

<正>癫痫作为神经系统的一种常见病,极大地影响着人类的健康和经济发展。为进一步研究癫痫,近年来建立了多种动物模型。依据研究目的、内容和方法不同,采用的癫痫动物模型也不同。按采用动物,可分为鼠模型、兔模型、猴模型、猿模型等;按诱发方式,可分为电点燃和化学点燃动物模型。癫痫点燃的动物模型是具有诱导致痫和自发性发作优点的致痫模型。本文将对点燃的现象、概念、点燃方法、可被点燃的动物、点燃的电生理基础机制等进行综述。1.点燃的概念点燃(kindling)原始概念是指通过重复不变的亚抽搐剂量的电刺激,导致癫痫活动的强度逐渐增加,最终出现全身性癫痫发作称为点燃。此外,用化学和药物周期性的亚抽搐剂量稳定刺激也能逐渐诱发出癫痫,并且癫痫的程度逐渐加重,这个过程也称之为点燃。点燃目前被公认为是一种理想的癫痫动物模型,其致痫性增高具有永久的保留能力,较好地模拟了人类癫痫的进行性发展和长期反复的自限性发作形式。目前,主要的癫痫模型有化学点燃、脑内点燃、光或电点燃、脑组织片点燃等模型。后三种致痫方法对动物或实验设备要求高。脑内点燃或脑组织片点燃因损伤脑组织不宜进行脑生化研究。化学点燃致癫痫模型因不损伤脑组织,实验设备要求简单,结果稳定,已被广泛应用于抗癫痫药物敏感性和耐药性实验以及癫痫基础研究,特别适用于神经生物化学和形态结构方面的研究。Wada将点燃过程分为6个阶段(1)同侧面部抽搐;(2)两侧面部抽搐;(3)点头;(4)对侧前肢出现阵挛.并且头向对侧旋转;(5)站立时出现阵挛性跳跃(6)摔倒,并全身抽搐(强直-阵挛发作)。在试验中,一旦动物出现摔倒伴全身性抽搐,就被认为已制成点燃模型。这种作用是持续的,动物点燃后停止刺激12个月,再次用原第一次的剂量刺激,仍能出现摔倒伴全身抽搐。目前尚没有方法可逆转点燃作用。点燃的癫痫发作的几个特征支持其作为人类癫痫发作的模型。第一,点燃的癫痫发作行为类似于人类复杂部分性癫痫发作伴继发全身强直-阵挛发作;第二,点燃癫痫发作期间的脑电图异常类似于人复杂部分性癫痫发作期间杏仁核和海马结构电极描记的结果;第三,发作间期脑电图都可记录到棘波;第四,抗癫痫药物(苯妥英钠除外)能够有效阻止点燃。     

癫痫的点燃动物模型

癫痫点燃的动物模型是具有诱导致癫和自发性发作模型两者优点的致癫模型。我们将点燃现象、点燃方法、点燃机制、点燃与人类癫痫的关系进行综述。一、点燃现象重复不变的亚抽搐剂量的电刺激，导致癫痫活动强度逐渐增加，最终出现全身性癫痫发作称为点燃。许多动物能建立点...     

苯妥英钠、苯巴比妥钠诱导建立难治性癫痫动物模型及其脑组织P糖蛋白表达的研究

目前，全球大约20％～30％的癫痫患者应用一线的抗癫痫药物（antiepileptic drugs，AEDs）无法达到有效的治疗效果，成为难治性癫痫（refractory epilepsy，RE）。难治性癫痫患者致残率高，对社会及家庭造成影响大，因此建立稳定的难治性癫痫动物模型，从中寻找有效的治疗药物已成为广大神经科医生面临的急待解决的问题。近年国内外文献报道，难治性癫痫模型可通过电刺激杏仁核点燃，同时应用一线的AED进行动物筛选建立。     

运动诱发电位刺激方法的实验研究

术中使用体感诱发电位（ＳＥＰ）并不能监护脊髓全部的功能，本组实验拟采用经硬膜外腔脊髓单刺激和串刺激（ｔｒａｉｎｓｔｉｍｕｌａｔｉｏｎ），肌肉记录的方法来检测运动诱发电位（ＭＥＰ），为临床使用ＭＥＰ监护脊髓手术提供实验室数据。１　材料与方法　Ｄａｎｔｅｃ的ＫｅｙｐｏｉｎｔＰ诱发电位仪记录ＭＥＰ，单刺激：波宽０２ｍｓ方波，滤波范围１０～５ｋＨｚ，串刺激：３、５个电泳冲（图１），每个脉冲波宽为０５ｍｓ，波间期为４ｍｓ。刺激强度２～２５ｍＡ，滤波范围５００～１０ｋＨｚ，观察时间为５０～１００ｍｓ。…     

杏仁核点燃癫痫鼠模型脑内不同神经结构FOS蛋白的表达

目的 观察杏仁核点燃癫痫鼠模型脑内不同核团FOS蛋白表达顺序及强度以探讨癫痫的传播途径。方法 选择健康Wistar大鼠60只制作杏仁核点燃癫痫模型，分别在点燃后0．5h、1h、2h、4h及24h用免疫组织化学方法观察癫痫大鼠脑内梨状皮质、杏仁核、海马、齿状回、尾壳核、皮质、皮质下结构、小脑Purkinje细胞、小脑齿状核、脑桥网状结构共10个核团FOS蛋白表达情况。结果 杏仁核点燃后0．5h梨状皮质、齿状回、小脑Purkinje细胞开始出现FOS表达，然后表达逐渐增强，杏仁核、海马、小脑齿状核、皮质、皮质下结构、尾状核及脑桥网状核在发作后1～2h开始表达，4h表达明显，癫痫发作24h后大多数核团FOS蛋白表达低于4h但仍高于1h～2h。结论 杏仁核点燃大鼠癫痫发作后可引起脑内FOS蛋白区域性一过性表达。梨状皮质表达最早，是首先被激活的结构之一，而杏仁核、海马、小脑Purkinje细胞、皮质可能为杏仁核点燃模型癫痫传播途径的重要组成部分。     

癫痫点燃模型的研究进展

<正>癫痫是一种慢性的、反复发作性的短暂脑功能失调综合征。多年来人们对癫痫的基础研究主要依靠动物模型,癫痫的点燃模型,是癫痫研究中常用的局灶性癫痫动物模型。点燃是指以阈下电信号或者化学信号反复的、间歇性刺激动物,使其惊厥阈值不断下降、异常脑电发放及行为反应进行     

脉冲电刺激迷走神经对大鼠复杂部分性发作的影响

目的：定量研究迷走神经刺激（ＶＮＳ）对癫痫复杂部分性发作的频度和强度的影响，方法：３０只大鼠被随机分为实验组和一。用频率１６Ｈｚ，波宽１．０ｍｓ，串长１０秒，强度３．５ｍＡ的恒流，方波脉冲电反复刺激１８只实验组大鼠的颈迷走神经，同时观察其部分点燃过程中０－３级行为及仁核放电的变化，结果：ＶＮＳ可抑帛蛎鼠的复杂部分性发作，发作强诉 无于发作频度的降低。在ＶＮＳ次数积累到一定量后发作频度才获得显著性下     

颈迷走神经脉冲电刺激对大鼠点燃速度及杏仁核放电的影响

目的　定量研究颈迷走神经刺激对大鼠癫痫形成速度及杏仁核放电的影响。方法　用频率 16 Hz,波宽1.0 ms,串长 10 s,串隔 7min,强度 3.0 m A的恒流脉冲电刺激 18只大鼠的左颈迷走神经 ,同时用强度 0 .4m A的恒流脉冲电诱发刺激大鼠的杏仁核。以 18只仅刺激杏仁核的大鼠作对照 ,观察其癫痫行为及杏仁核放电情况。结果　实验组有 16 / 18只大鼠被点燃 ,对照组有 17/ 18只点燃 ,组间差异无显著性 (P>0 .0 5)。比之于对照组 ,实验组点燃所需杏仁核平均刺激次数及杏仁核平均后放电阈值均显著增高 (P<0 .0 5) ,但杏仁核平均后放电时间两组差异无显著性 (P>0 .0 5)。结论　迷走神经刺激虽最终难以阻断大鼠点燃的发生 ,但可减缓大鼠点燃发生速度 ,提高杏仁核后放电阈值。其抗痫效应可能主要与提高全脑抑制水平 ,抑制痫性放电扩布有关 ,而对痫灶本身放电影响相对较小。     

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.     

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.     

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.     

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.     

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.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.     

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.