甲基强的松龙对兔实验性脑血管痉挛的作用

目的探讨大剂量甲基强的松龙对蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的作用。方法将24只雄性新西兰白兔随机分成2组:SAH对照组和SAH 大剂量甲基强的松龙(MP,18mg/kg)治疗组。通过枕大池二次注血法构建SAH模型,观察MP对脑基底动脉的影响。应用酶联免疫生化技术检测各组兔基底动脉血管平滑肌细胞膜蛋白激酶C(PKC)活性。结果经脑血管造影证实该剂量甲基强的松龙明显减轻实验性脑血管痉挛的严重程度,与对照组相比,PKC活性在大剂量甲基强的松龙治疗组没有明显提高。结论大剂量甲基强的松龙能够明显减轻脑血管痉挛程度,通过抑制血管平滑肌细胞来防治脑血管痉挛的发生发展。     

Trapidil对蛛网膜下腔出血后脑血管痉挛作用的实验研究

目的 探讨蛛网膜下腔出血（SAH）后脑血管痉挛的发生机制及其可能的治疗方法。方法 利用家兔枕大池内注血构建SAH模型，观察血小板衍生生长因子（PDGF）拮抗剂trapidil对脑基底动脉的影响。结果 脑基底动脉于SAH后48h明显变细；静脉或动脉内持续灌注trapidil 15min（1．5mg／min）后，数字减影脑血管造影（DSA）显示痉挛血管已明显扩张变粗，30min时达高峰。结论 PDGF可能参与脑血管痉挛发生的病理过程，PDGF拮抗剂trapidil可有效缓解实验性SAH后脑血管痉挛，有望成为脑血管痉挛的治疗药物。     

酪氨酸激酶抑制剂对大鼠蛛网膜下腔出血后脑血管痉挛的作用研究

目的 探讨酪氨酸激酶（Src）在蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）中的作用和机制，以及应用Src抑制剂PP2对脑血管痉挛的治疗作用。方法 枕大池二次注血法制作大鼠SAH模型，造模后第1天至第5天腹腔注射10mmol/L Src抑制剂PP20．1ml，对照组注射等体积DMSO。第5天处死动物，H-E染色观察大鼠基底动脉血管直径。Westernblot检测基底动脉Src、Ras、MAPK蛋白表达，Real-timePCR检测基底动脉IL-1β、IL-6mRNA表达。结果 枕大池二次注血法成功制作SAH模型，基底动脉发生了明显血管痉挛。SAH组基底动脉Src、Ras、MAPK表达显著增高，IL-1β、IL-6细胞因子mRNA表达增加。应用PP2后血管痉挛减轻，基底动脉Src、Ras、MAPK表达下降，IL-1β、IL-6mRNA表达减少。结论 Src与SAH后脑血管痉挛发生有关。Src抑制剂PP2能够缓解脑血管痉挛，其机制一部分通过MAPK信号通路起作用，另外可能通过减少IL-1β、ILl6等细胞因子表达，抑制炎症反应起作用，针对该信号通路可能对脑血管痉挛的治疗有效。     

钾离子通道激动剂对蛛网膜下腔出血后脑血管痉挛的作用

目的 观察早期使用不同剂量特异性钾离子通道激活剂对蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）的作用。方法 将24只雄性新西兰白兔随机等分为4组：①对照组：枕大池注入生理盐水；②SAH组；③SAH＋小剂量钾离子通道激活剂Cromakalin组（0．1mg／kg）；④SAH＋大剂量Cromakalin组（0．3mg／kg）。采用枕大池注血法建立兔SAH模型，1h后开始静脉输注Cromakalin，每12h给药1次，共4次。注血后48h采用灌注固定法处死动物动物，留取基底动脉标本，通过测定基底动脉血管横截面积来评价CVS的程度。结果 基底动脉横截面积测定的结果提示SAH组较对照组明显缩小（P〈0．01），而SAH＋小剂量Cromakalin组及SAH＋大剂量Cromakalin组均较SAH组痉挛明显改善（P〈0．05）。结论 早期使用特异性钾离子通道激活剂Cromakalin能改善兔SAH模型的基底动脉血管痉挛。     

蛛网膜下腔出血后白细胞介素-8基因在兔脑基底动脉中表达的变化

目的探讨实验性蛛网膜下腔出血（SAH）诱发脑血管痉挛时,白细胞介素-8（IL-8）基因在兔脑基底动脉中表达的变化及在诱发脑血管痉挛中的作用。方法35只健康日本大耳白兔随机分为生理盐水组、SAH组。SAH组根据第一次注血时间又分为四组,分别为第一次注血后第1、4、7、14天。以枕大池二次注血法构建迟发性脑血管痉挛模型,采用RT—PCR法观察兔基底动脉中细胞因子IL-8mRNA表达的变化。结果IL-8mRNA在SAH组第一次注血后第4—7天升高,14天趋于正常。SAH组IL-8的表达水平与基底动脉的狭窄程度呈正相关（r=0．642,P〈0．01）。结论IL．8在基底动脉中的表达水平与脑血管痉挛的程度紧密相关,提示IL-8可能作为免疫／炎症因素因素参与了SAH后迟发性脑血管痉挛的发生。     

辛伐他汀对兔蛛网膜下腔出血后迟发性脑血管痉挛中血管壁增殖的影响

目的 探讨辛伐他汀对兔蛛网膜下腔出血(SAH)后迟发性脑血管痉挛(CVS)中血管壁增殖的影响.方法 36只新西兰大白兔随机分为3组:①对照组,常规饲养并枕大池二次注入0.9%生理盐水;②SAH组,通过二次枕大池注血建立SAH模型;③辛伐他汀+SAH组,每日胃灌辛伐他汀5 ms/kg,连续7 d后建立SAH模型.各组兔模型前后行两次脑血管造影.灌注后取基底动脉组织制作病理切片,分别于光镜和透射电镜下观察其显微以及超微结构.采用免疫组化及免疫荧光方法检测基底动脉组织中增殖细胞核抗原(PCNA)及α-平滑肌肌动蛋白(α-SMA)表达量的变化,同时采用Real-Time PCR检测其血小板源性生长因子-B(PDGF-B)基因表达量的变化.采用SPSS10.0软件进行统计分析.结果 通过脑血管造影可以观察到二次注血后兔基底动脉出现明显的痉挛,管径变细;而给予辛伐他汀后,痉挛减轻.SAH组兔基底动脉壁略有增厚,电镜显示平滑肌细胞内合成旺盛;而给予辛伐他汀预处理后这些变化明显减轻.SAH组兔基底动脉管壁平滑肌细胞内α-SMA、PCNA、PDGF-B表达明显高于对照组(P＜0.05),而给予辛伐他汀后三者表达量明显降低(P＜0.05).结论 辛伐他汀可能通过抑制迟发性CVS中血管壁平滑肌细胞的增殖来缓解SAH后迟发性CVS.     

腰穿枕大池置管2次注血的迟发性脑血管痉挛动物模型

目的 :制作一种操作简便、重复性好的蛛网膜下腔出血 (SAH)脑血管痉挛 (CV)动物模型。方法 :选取家猪 12头 ,随机分成SAH组和生理盐水对照组 ;SAH组经腰穿枕大池置管 2次注血 ,制成SAH模型 ,对照组注入生理盐水 ;以脑血管造影和基底动脉组织学改变判定脑血管痉挛。结果 :SAH组双侧颈内动脉和基底动脉明显痉挛 (P <0 0 1) ,基底动脉有典型病理改变 ,对照组未见异常。结论 :腰穿枕大池置管 2次注血法 ,是一种简便、可靠的SAH诱发CV动物模型制作方法。     

内皮素-1在实验性脑血管痉挛中的作用

目的：探讨内皮素－1（endothelin-1,ET-1)在脑血管痉挛中的作用及其信号传导机制。方法：在建立犬脑血管痉挛动物模型基础上应用免疫生化技术直接对脑基底动脉血管ET－1生物活性和血管平滑肌细胞PKC活性进行检测。同时，应用体外血管张力性研究方法进一步观察了ET－1以及ETA受体阻断剂BQ123和ETA／ETB受体阻断剂TAK044对血管张力的作用。结果：造影显示脑血管痉挛程度与PKC激活程度密切相关，基底动脉血管ET－1免疫生物活性仅仅在脑血管痉挛早期一过性增高，体外实验显示ET－1具有强烈的致血管痉挛和明显激活PKC作用，这种作用能被ET受体阻断剂BQ123和TAK044明显阻断。结论：ET－1仅仅在脑血管痉挛早期起致血管痉挛作用，这种作用是通过ET受体启动、激活PKC而实现的，而在维持脑血管痉挛过程中ET－1不起主要作用。     

缝隙连接阻断剂1-庚醇对脑血管痉挛的抑制作用

目的探讨缝隙连接在脑血管痉挛中的作用及观察其阻断剂在动物实验中的治疗作用。方法建立兔二次蛛网膜下腔出血模型,通过脑血管造影观察经动脉或池内注入缝隙连接阻断剂heptanol,对脑血管痉挛的抑制和治疗作用,并观察基底动脉的形态学变化。结果枕大池注血后血管造影显示基底动脉出现痉挛。在脑血管痉挛后,动脉给予heptanol对急、慢性脑血管痉挛有显著的治疗作用。预先枕大池注入heptanol再注血,造影显示基底动脉痉挛不明显(P>0.05),heptanol枕大池预处理后能显著抑制急、慢性期脑血管痉挛的形成。形态学检查发现,对照组第7d的基底动脉光镜见内皮细胞核染色质聚集,内弹力膜波纹状,平滑肌细胞分布稀疏等。动脉给药组和池内给药组也有类似变化,但范围局限、程度轻。结论缝隙连接阻断剂heptanol能有效抑制兔蛛网膜下腔出血后急性和慢性脑血管痉挛,体内试验表明缝隙连接在脑血管痉挛中可能发挥重要作用,应用其阻断剂heptanol具有显著的治疗作用。     

高压氧对蛛网膜下腔出血后脑血管痉挛的影响

目的探讨高压氧（hyperbaric oxygen,HBO）对蛛网膜下腔出血（SAH）后迟发性脑血管痉挛的影响及机制。方法采用枕大池2次注血法建立迟发性脑血管痉挛模型,将60只模型动物随机等分为SAH组和SAH＋HBO组,用显微测量法测量基底动脉管径,比色法测定血清中一氧化氮（NO）及一氧化氮合酶（NOS）含量,原子吸收分光光度计测定脑组织中的Ca^2＋含量。结果模型制作成功后96h测量基底动脉直径,结果显示：经HBO治疗后,脑血管痉挛的程度明显缓解。SAH组NO、NOS含量在术后24h及96h均降低,而经HBO治疗后则增高。SAH组Ca^2＋含量在术后24h及96h增高,经HBO治疗后则降低。结论高压氧能够缓解SAH后脑血管痉挛程度,改善受损的脑功能。     

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.