高血压对大鼠局灶性脑缺血再灌注损伤组织病理结构的影响

目的研究高血压对脑缺血性损伤的病理及其超微结构的影响。方法用线栓法将肾性高血压大鼠和正常大鼠制成局灶性脑缺血再灌注模型；TTC染色及图像分析系统测定局部脑缺血后不同时间的梗死灶体积．同时HE染色及透射电镜观察大鼠局灶脑缺血再灌注后及假手术组的组织病理及超微结构的变化。结果高血压大鼠与正常血压大鼠相比局部缺血再灌注在同等时间内梗死灶的面积较大，超微结构改变也较明显。结论高血压引起脑内微小动脉的改变．侧支循环减少．加重脑缺血损伤。     

两种局灶性脑缺血再灌注模型的比较

目的比较两种大鼠大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)局灶性脑缺血再灌注模型,寻找一种更加理想、稳定和可靠的模型。方法将22只SD大鼠随机分为颈外动脉插线组和颈总动脉插线组,采用线栓法建立大鼠脑缺血再灌注模型,MCAO2h再灌注24h,采用TTC染色和NF-κB免疫组化染色,并分别测定脑梗死体积和NF-κB表达量。结果两种插线方法都能造成大鼠局灶性脑梗死,颈外动脉插线组再灌注状态优于颈总动脉插线组,且脑梗死体积和NF-κB表达量均高于颈总动脉插线组。结论颈外动脉插线闭塞大脑中动脉是一种较为理想和可靠的大鼠MCAO局灶性脑缺血再灌注模型制作方法。     

大鼠局灶性脑缺血再灌注后iNOS的表达时程及行为学变化

目的 观察大鼠局灶性脑缺血再灌注后不同时间点iNOS表达及行为学变化。方法 线栓法制备大鼠大脑中动脉闭塞再灌注模型，术后不同时间点进行神经功能缺损评分，并动态检测iNOS活性变化。结果 缺血后6h大鼠神经功能缺损程度最严重，iNOS表达在缺血后6h开始出现，缺血后48h达峰，7d时基本降至基线水平。结论 由iNOS产生的NO参与了脑缺血再灌注后的迟发性病理损伤过程。     

丁苯酞预处理对大鼠脑缺血再灌注损伤的神经保护作用

目的研究丁苯酞预处理对大鼠局灶性脑缺血再灌注损伤的神经保护作用。方法健康成年SD雄性大鼠48只,随机分为假手术组、缺血再灌注组、丁苯酞预处理组,每组各16只。各组均灌胃5d后,采用线栓法制作大鼠局灶性脑缺血再灌注(MCAO)模型,缺血2h、再灌注24h,进行神经功能缺损评分,TTC染色及图像分析观察脑梗死体积,免疫组化法检测脑组织caspase-3、bcl-2表达的变化。结果与缺血再灌注组相比,丁苯酞预处理组神经缺损程度改善,梗死灶体积减少,caspase-3阳性细胞数量减少,bcl-2表达上调。结论丁苯酞可减轻缺血性脑血管病的发作,具有一定的神经保护作用。     

促红细胞生成素对大鼠局灶性脑缺血CAPSASE-3蛋白的影响

目的　研究促红细胞生成素 (erythropoietin ,rhEPO)在大鼠局灶性脑缺血再灌注损伤中对Caspase - 3蛋白的影响 ,探讨rhEPO的脑保护机制。 方法　线栓法建立大鼠局灶性脑缺血再灌注损伤模型 ,NISS染色观察缺血半暗区的病理形态变化 ,免疫组织化学方法检测活化的Caspase - 3的表达 ,TTC染色观察缺血损伤面积。结果　Caspase - 3阳性细胞在对照组脑组织内散在分布 ,缺血组和治疗组在大脑皮层较为密集。缺血组阳性细胞数显著高于对照组 (P<0 .0 1) ,治疗组阳性细胞数显著低于缺血组 (P <0 .0 1)。结论　Caspase- 3在大鼠局灶性脑缺血再灌注中活性显著增高 ,rhEPO能有效抑制Caspase - 3激活 ,从而抑制大鼠局灶性脑缺血再灌注损伤中缺血损伤及细胞凋亡 ,在大鼠局灶性脑缺血再灌注中脑损伤中起到保护作用     

大鼠局灶性脑缺血再灌注后iNOS的表达时程及行为学变化

目的观察大鼠局灶性脑缺血再灌注后不同时间点iNOS表达及行为学变化。方法线栓法制备大鼠大脑中动脉闭塞再灌注模型,术后不同时间点进行神经功能缺损评分,并动态检测iNOS活性变化。结果缺血后6h大鼠神经功能缺损程度最严重,iNOS表达在缺血后6h开始出现,缺血后48h达峰,7d时基本降至基线水平。结论由iNOS产生的NO参与了脑缺血再灌注后的迟发性病理损伤过程。     

雌二醇对大鼠脑缺血再灌注损伤的保护作用

目的探讨雌二醇对大鼠局灶性脑缺血再灌注损伤的改善作用及其脑保护机制。方法线栓法建立大鼠局灶性脑缺血再灌注损伤模型，通过HE染色在光镜下观察神经细胞损伤变化，TTC染色测脑梗死体积．免疫组化法检测bel-2阳性表达。结果与脑缺血再灌注组相比，雌二醇用药组大鼠脑标本光镜下细胞损伤变性程度轻．脑梗死体积显著缩小（P〈0．01），bel-2阳性细胞数明显上升（P〈0．01）。结论雌二醇对大鼠局灶性脑缺血再灌注损伤有保护作用，雌二醇可通过促进bcl-2的上调发挥脑保护作用。     

大鼠线栓法局灶性脑缺血模型的改良

目的对大鼠线栓法局灶性脑缺血再灌注模型的制备方法进行优化。方法采用线栓法建立SD大鼠局灶性脑缺血模型,从局部脑血流、神经功能缺损和梗死体积方面评价尼龙线包被材料、麻醉、翼腭动脉(PPA)结扎等因素对该模型的影响。结果在牙用树脂、聚赖氨酸和硅酮3种包被材料中,以硅酮效果最佳;与水合氯醛麻醉相比,异氟烷麻醉能明显提高模型的成功率;结扎PPA可提高模型的稳定性。结论采用气体吸入麻醉和硅酮包被的尼龙线,同时结扎PPA,可提高大鼠线栓法局灶性脑缺血模型的成功率。     

脑缺血再灌注损伤模型大鼠大脑皮质BDNF mRNA表达减少

目的制备局灶性脑缺血再灌注损伤大鼠模型,并观察大脑皮质脑源性神经营养因子(BDNF)mR-NA表达的变化。方法雄性SD大鼠,采用线栓法闭塞大脑中动脉2h后进行再灌注3d,制备局灶性脑缺血再灌注损伤模型。采用神经缺失评分观察大鼠的行为学表现;TTC染色检查脑组织梗死情况;HE染色观察大鼠脑组织形态结构;RT-PCR技术检测大鼠大脑皮质BDNF mRNA的表达。结果假手术组大鼠无神经功能障碍表现;脑组织未见梗死灶;脑组织神经细胞形态规则;大脑皮质BDNF mRNA的相对表达量,与正常组相比,未见明显变化。与假手术组相比,局灶性脑缺血再灌注损伤模型大鼠出现神经功能障碍;左侧半球可见梗死灶;梗死侧脑组织形态学观察显示神经细胞大量坏死脱落、胞质呈空泡变性、疏松、胞核浓缩深染;大脑皮质BDNF mRNA表达量明显减少。结论大脑中动脉闭塞2h后进行再灌注3d可造成脑缺血再灌注损伤,可能与大脑皮质BDNF mRNA的表达减少有关。     

NE1反义抑制剂对局灶性脑缺血作用的初步研究

目的 探讨NR1反义寡核苷酸对局灶性脑缺血的治疗作用。方法 于大鼠大脑中动脉闭塞后2小时、24小时分别经侧脑室注射磷酸缓冲液（PBS）、错义寡核苷酸（MSODN）及反义寡核苷酸（ASODN），然后在不同时间点进行神经功能缺损评分，术后第5天进行Nissl染色、TTC染色及梗死体积比测定。结果 各组局灶性脑缺血的神经功能缺损评分无显著性差异；反义寡核苷酸治疗组的梗死体积比显著低于单纯缺血组；反义寡核苷酸治疗海马各区神经元损伤轻，神经元丢失相对较少。结论 局灶性脑缺血后侧脑室注入NR1反义寡核苷酸，可以减轻缺血脑组织病理学损害，具有脑保护作用。     

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.     

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.     

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.     

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.     

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.     

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.