侧脑室微量注射左旋多巴治疗大鼠帕金森病

目的观察经侧脑室注射左旋多巴对帕金森病（PD）大鼠的影响。方法应用“羟基多巴胺立体定向脑内注射制备偏侧损毁的PD大鼠模型，并用阿扑吗啡（APO）皮下注射诱发大鼠向健侧旋转。将24只PD大鼠随机分为4组（n=6），经侧脑室注入生理盐水组为对照组，余3组分别经侧脑室注射浓度为0．1μg／μl、1μg／μl和5μg／μl的左旋多巴1μl，4μl／d，连续1周；观察在注射后不同时间大鼠旋转行为以及中脑黑质多巴胺能神经元数量的变化。结果经侧脑室注射1μg/μl和5μg/μl的左旋多巴后。与对照组相比，PD大鼠向健侧的旋转圈数明显减少（P〈0．01），左旋多巴效果在2h左右达到高峰，且中脑黑质多巴胺能神经元的数量也明显增多（P〈0．01）。结论经侧脑室注射适当剂量的左旋多巴可有效地改善PD大鼠的旋转行为，并增加中脑黑质多巴胺能神经元数量。     

白介素6在脂多糖致大鼠脑水肿中的表达

目的 探讨白介素6（IL-6）在脂多糖（LPS）致大鼠脑水肿发病过程中的表达及纳洛酮对其干预作用。方法 SD大鼠84只，对照组（NS组）28只，0．2ml生理盐水颈内动脉注射；内毒素组（LPS组）28只，颈内动脉注射LPS 200μg；纳洛酮治疗组（NAL组）28只，颈内动脉注射LPS后10min、1h、2h、6h、12h及处死前2h腹腔注射纳洛酮lmg／kg。于不同时间点测定脑组织匀浆IL-6的含量。干湿法测定脑组织含水量，甲酰胺法测定伊文思兰（EB）含量。结果 LPS组脑组织含水量和EB含量显著高于NS组（P〈0．01）。NAL组脑组织含水量和EB含量显著低于LPS组（P〈0．01），但仍较NS组高（P〈0．01）。注射LPS后4h，LPS组脑组织IL-6含量即增加，于6h达高峰，与NS组比较，差异有统计学意义（P〈0．01）。NAL组IL-6含量低于LPS组（P〈0．05或P≤O．01），但高于NS组（P〈0．01）。LPS组脑组织含水量和EB含量呈正相关（r=0．743，P〈0．01），IL-6含量与含水量呈正相关（r=0．459，P〈0．05），IL-6含量与EB含量呈正相关（r=0．568，P〈0．05）。结论IL-6参与脑水肿的发生发展，纳洛酮可以抑制IL-6的生成，减轻脑水肿。     

亚低温对局灶性脑缺血大鼠血清白细胞介素和缺血局部细胞间黏附分子-1表达的影响

目的观察亚低温对局灶性脑缺血大鼠缺血局部细胞间黏附分子-1（ICAM-1）表达和血清白细胞介素-6（IL-6）含量的影响，探讨亚低温对脑缺血性损害的神经保护作用机制。方法将30只体质量在250-300g的雌性Sprague—Dawley大鼠随机分为亚低温组（n=151和对照组（n=15），采用线栓法阻断大鼠一侧大脑中动脉制作局灶性脑缺血模型，制模成功后，将亚低温组和对照组大鼠分别置于冰毯机和常温操作台上，使其肛温保持在（33±1）℃和（37±0．5）℃。12h后，自左心室取血，断头取脑，采用免疫组化方法检测缺血区ICAM-1阳性血管数目和应用免疫放射测定法（IRMA）检测血清IL-6含量。结果免疫组化分析示缺血局部ICAM-1的表达较对照组下降，IRMA检测的血清IL-6含量亚低温组较对照组降低。结论亚低温可降低局灶性脑缺血大鼠血清IL-6含量和减少缺血局部ICAM—1的表达，推测亚低温降低IL-6和ICAM—1的表达为亚低温减轻脑缺血性损害的神经保护作用之一。     

急性脑缺血再灌注大鼠不同脑区乙酰胆碱酯酶活性的变化

本文旨在探讨胆碱能神经在脑缺血再灌注时的变化和意义。采用双侧颈总动脉夹闭（CCAO）的大鼠脑缺血动物模型,用改良的Ellman法测定大脑皮层、海马、间脑、纹状体和脑子五个脑区乙酰胆碱酯酶（AChE）活性,观察脑缺血30分钟和再灌注30分钟不同脑区AChE活性的变化。结果发现：在生理状态下不同胞区AChE活性不同,纹状体最高（181．8±1．7μ／g）,皮层最低（24．1±0．4μ／g）,CCAO30分钟皮层、海马、间脑、纹状体的AChE活性均明显下降,较正常大鼠分别降低278％、26．3％、16．9％、23．6％（P＜0．01）,再灌注30分钟后分别回升18.4％、17.6％、10．2％、23．7％（P＜0．01）。而脑干在缺血和再灌注中无显著变化。结果提示不同胞区胆碱能活性程度不同;脑AChE活性对缺血和再灌注是敏感的,推测胆碱能神经可能在缺血性脑损伤中起重要作用。     

脑缺血对阿尔茨海默病大鼠认知功能的影响及炎性机制探讨

目的：探讨脑缺血对阿尔茨海默病（AD）大鼠认知功能的影响及可能机制。方法：大鼠海马注射Aβ1-40成功建立AD大鼠模型后，于AD大鼠右侧纹状体注射内皮素-1建立脑缺血模型，Morris水迷宫检测脑缺血后AD大鼠认知功能的变化，免疫组化、原位杂交和RT-PCR检测海马内星形胶质细胞和IL-1、TNF—α的变化。结果；脑缺血后AD大鼠认知功能明显下降（P〈0．01），海马内星形胶质细胞和炎性细胞因子IL-1、TNF—α的表达都较单纯AD显著增加（P〈0．01）。结论：脑缺血加重了AD大鼠的认知功能障碍，炎性机制参与了脑缺血促进AD进展的过程。     

降钙素基因相关肽对大鼠局灶性脑缺血保护作用的研究

线栓法建立大鼠局灶脑缺血动物模型，定量研究降钙素基因相关肽（CGRP）对大鼠局灶脑缺血体积的影响。结果：模型建立前1小时使用CGRP预防性治疗可明显减小脑缺血体积，与对照组比较减幅达54％（P＜0．01）；模型建立后2小时CGRP治疗组脑缺血体积仅比对照组减少12％（P＞0．05）。提示：CGRP对缺血神经组织有保护作用，但治疗时间窗较短。     

血红素加氧酶-1基因转染对神经元损伤的保护作用

目的观察腺病毒介导的血红素加氧酶-1（HO—1）基因转染大鼠后对脑缺血再灌注损伤的保护作用。方法雄性SD大鼠随机分为4组：假手术对照组（SH）、生理盐水组（V）、空载体组（Ad）和Ad—HO-1转染组（HO）。后三组在缺血前3d于右侧脑室部分别注射20μl生理盐水、含1μl空载体腺病毒（1．0×10^10plaque-forming unit／ml,PFU／ml）的生理盐水或含1μl重组HO-1腺病毒（1．0×10^10PFU／ml）的生理盐水,连续注射3d后,采用右侧大脑中动脉栓塞法（MCAO）建立脑缺血再灌注模型。每组大鼠测定神经功能后,处死大鼠并取全脑标本,测定右脑梗死体积及细胞凋亡指标,荧光显微镜下观察脑组织荧光蛋白的表达情况,Western blot检测脑组织HO-1的表达。结果HO组中HO-1表达量明显高于Ad组和V组,Ad组和HO组可见有荧光蛋白表达,转染率为34．5％±3．4％。HO组神经功能显著优于Ad组和V组（P〈0．001）。与SH组比较,V组、Ad组脑梗死体积、神经细胞凋亡明显升高。与V组及Ad组比较,HO组脑梗死体积显著减小（P〈0．01）、神经元凋亡显著减少（P〈0．01）。结论腺病毒携带的HO-1基因能有效的转染脑组织,并在脑内稳定表达;HO-1基因转染显著减轻脑缺血再灌注后神经细胞损伤。     

缺血预处理上调TROY表达诱导大鼠局灶性脑缺血耐受

目的研究缺血预处理（IPC）对局灶性脑缺血的保护作用以及对TNFRSF expressed on the mouse embryo（TROY）表达的影响。方法33只雄性成年SD大鼠，随机分为预处理6h组（IVC-6组，11只）、预处理72h组（IPC-72组，11只）和缺血组（CI组，11只）。利用线栓法建立大脑中动脉栓塞（MCAO）致局灶性脑缺血模型。MCAO 10min作为IPC,IPC-6和IPC-72组分别在IPC后6h和72h制作短暂性局灶性脑缺血模型。再灌注24h后，对所有动物行神经功能缺损评分（NDS），并处死大鼠取脑，应用2％TTC染色测定梗死容积、TUNEL染色研究细胞凋亡情况和免疫组化观察TROY表达变化。结果与CI组比较，IPC-72组显著改善局灶性脑缺血24h后大鼠神经功能损害[两组评分分别为2（1．5-3），1（0—2）]，减少脑梗死容积[（299．33±70．98）mm^3，（69．25±47．66）mm^3]，抑制细胞凋亡和增强TROY的表达（阳性细胞数分别为42±11，87±17）（P〈0．01）。结论IPC对其后局灶性脑缺血有明显的保护作用．能诱导脑缺血耐受，可能与TROY表达上调相关。     

侧脑室注射质粒pLXSN介导bcl-2基因对大鼠脑梗死及BDNF影响的研究

目的 研究大鼠短暂大脑中动脉闭塞（MCAO）模型经侧脑室注射质粒pLXSN介导bcl-2基因后，该基因对脑梗死及脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）表达的影响。方法取135只Wistar大鼠随机分配为3组,每组45只．对照组为脑室注射生理盐水和空质粒两组．治疗组为脑室注射Bcl-质粒pLXSN介导bcl-2基因。以改良线栓法制备短暂缺血2h脑梗死模型。每组分别于缺血后3、6、24、48、72h为时间点。分别测量梗死体积变化以及BDNF蛋白的表达。结果MCAO后24、48、72h．梗死体积治疗组显著小于对照组（P〈0．05）；3、6h时间点无显著变化（P〉0．05）。MCAO后24、48、72h。治疗组Bcl-2和BDNF蛋白的表达较对照组显著增加（P〈0．01）．而3、6h时间点无显著改变（P〉0．05）。结论脑室注射质粒pLXSN介导bcl-2基因对短暂脑缺血有治疗作用．并可增加BDNF表达。上调BDNF表达所起的神经保护作用可能是短暂脑缺血后bcl-2基因的治疗作用机制之一。     

脑蛋白水解液对大鼠神经胶质细胞间缝隙连接通讯的研究

目的探讨脑蛋白水解液对大鼠神经胶质细胞间缝隙连接通讯功能的影响。方法由大鼠神经干细胞诱导培养神经胶质细胞至致密单层，分为脑蛋白水解液组、对照组及佛波酯阴性对照组继续培养，利用划痕标记染料示踪技术，以荧光黄染料在细胞间的扩散距离作为评价缝隙连接通讯的指标，测定脑蛋白水解液对大鼠胶质细胞间缝隙连接通讯的影响；采用逆转录-聚合酶链反应法检测脑蛋白水解液组和对照组细胞Cx43 mRNA表达的变化。结果脑蛋白水解液组荧光黄染料5min扩散距离为（189．80±6．56）μm，对照组扩散距离为（154．70±6．02）μm，组间差异有统计学意义（P〈0．01）；逆转录．聚合酶链反应检测显示脑蛋白水解液组细胞中Cx43mRNA相对表达量为0．89±0．13，高于对照组细胞的0．67±0．10，两组比较差异有统计学意义（P〈0．01）。结论脑蛋白水解液可通过上调胶质细胞Cx43基因的表达水平，增强大鼠胶质细胞间缝隙连接通讯，这可能是其在机体损伤修复过程中对胶质细胞起保护作用的重要机制。     

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.     

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.