胰岛素对大鼠脑缺血再灌注后Caspase-3表达及细胞凋亡的影响

目的探讨胰岛素对大鼠脑缺血再灌注后Caspase-3表达及细胞凋亡的影响。方法将动物随机分为假手术组、缺血组及干预组,参照zea longa线栓法建立大鼠左侧大脑中动脉闭塞（mid-dle cerebral artery occlusion,MCAO）再灌注模型,干预组大鼠在脑缺血即刻给予胰岛素及葡萄糖腹腔注射,分别在左侧MCAO2h再灌注不同时间点断头取脑,脑皮质神经元Caspase-3的表达通过免疫组化法来测定,并采用TUNEL法原位标记DNA片段,检测TUNEL阳性细胞的变化。结果缺血组大鼠脑皮质Caspase-3的表达较假手术组显著增强（P〈0.01）,TUNEL阳性细胞数较假手术组显著增多（P〈0.01）;给予胰岛素处理后,Caspase-3的表达较缺血组明显减弱（P〈0.01）,TUNEL阳性细胞数较缺血组明显减少（P〈0.01）,但两者均显著高于假手术组（P〈0.01）。结论短暂的脑缺血再灌注可导致脑皮质神经元Caspase-3的表达增加,促进细胞凋亡,胰岛素可下调脑皮质神经元Caspase-3的表达,发挥神经保护作用。     

大鼠脑缺血预处理对额叶神经细胞凋亡和P53蛋白表达的影响

目的探讨大鼠短暂性全脑缺血预处理对再次脑缺血额叶神经细胞凋亡和P53蛋白表达的影响.方法采用改良的Pulsinelli 4血管阻断(4VO)方法,建立SD大鼠急性全脑缺血及预处理模型.雄性SD大鼠随机分为三组预处理对照组,给予3min全脑缺血;预处理缺血组,先给予3min全脑缺血,48h后在给予全脑缺血15min;缺血组,仅给予全脑缺血15min.采用TUNEL方法观察额叶神经细胞凋亡,SP免疫组化方法检测P53蛋白的表达.结果预处理对照组未见TUNEL阳性细胞,仅见个别P53蛋白阳性细胞.预处理缺血组与缺血组相比,再灌注后48h、72h及7d额叶TUNEL阳性细胞数显著减少(P《0.01).预处理缺血组与缺血组相比,再灌注后48h、72h及7d额叶P53阳性细胞数显著减少(P《0.01).结论全脑缺血15 min后额叶神经细胞凋亡和P53蛋白表达增多.全脑缺血预处理能减少额叶缺血再灌注后神经细胞凋亡和P53蛋白的表达.     

重组人促红细胞生成素预处理对黑质多巴胺能神经元凋亡的影响

目的研究重组人促红细胞生成素(rhEPO)对离体帕金森病模型中黑质多巴胺神经元凋亡的影响。方法以6-羟基多巴胺(6-OHDA)为毁损剂建立大鼠离体帕金森病(PD)模型。用6u/mlrhEPO预处理黑质多巴胺神经元,然后用免疫组化方法观察黑质中酪氨酸羟化酶(TH)免疫反应阳性细胞数和半胱天冬酶-3(Caspase-3)免疫反应阳性细胞数的变化,TUNEL法观察黑质中多巴胺神经元的凋亡情况。结果与6-OHDA组(44.2±5.0)相比,rhEPO预处理组TH免疫反应阳性细胞(63.8±6.2,P<0.01)增多;与6-OHDA组(22.3±2.8)相比,rhEPO预处理组多巴胺神经元中Caspase-3表达减少,Caspase-3免疫反应阳性细胞染色较淡,数量减少(13.7±1.8,P<0.01);与6-OHDA组(20.3±3.1)相比,rhEPO预处理组TUNEL阳性细胞染色较淡,数量减少(10.7±1.5,P<0.01)。结论rhEPO预处理可以减轻6-OHDA对离体帕金森病模型中多巴胺神经元的损伤,其机制可能与rhEPO抑制黑质多巴胺神经元凋亡有关。     

线粒体通透性转换孔在缺血预处理脑保护中的作用及机制

目的观察线粒体通透性转换孔(mitochondrial permeability transition pore,MPTP)在缺血再灌注及缺血预处理脑保护中的作用。方法将体外培养8 d的海马神经元分为五组,正常对照组(A组),缺血再灌注组(B组),缺血预处理+缺血再灌注组(C组),苍术苷+缺血再灌注组(D组),缺血预处理+苍术苷+缺血再灌注组(E组)。使用流式细胞术检测各组细胞凋亡率,罗丹明123染色流式细胞术检测线粒体膜电位,Western-blot检测Bcl-2,Bax的表达水平。结果与A组比较,其余四组线粒体膜电位均降低,神经元凋亡率升高(P<0.05);与B组比较,C组线粒体膜电位升高,神经元凋亡率升高,Bcl-2表达上调,Bax表达下调(P<0.05);与C组比较,E组粒体膜电位降低,神经元凋亡率升高,Bcl-2表达下调,Bax表达上调(P<0.05)。结论缺血预处理能有效减轻海马神经元缺血再灌注损伤,抑制缺血再灌注后神经细胞凋亡,其机制可能与抑制MPTP的开放有关。     

胰岛素对大鼠脑缺血再灌注后Bcl-2表达及细胞凋亡的影响

目的 探讨胰岛素对大鼠脑缺血再灌注后Bcl-2表达及细胞凋亡的影响.方法 将动物随机分为假手术组、缺血组及干预组,参照Zea Longa线栓法建立大鼠左侧大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)再灌注模型,干预组大鼠在脑缺血即刻给予胰岛素及葡萄糖腹腔注射,分别在左侧MCAO2h再灌注不同时间点断头取脑,脑皮质神经元Bcl-2的表达通过免疫组化法来测定,并采用TUNEL法原住标记DNA片段,检测TUNEL阳性细胞的变化.结果 缺血组大鼠脑皮质Bcl-2的表达较假手术组显著增强(P＜0.01),TUNEL阳性细胞数较假手术组显著增多(P＜0.01);给予胰岛素处理后,Bcl-2的表达较缺血组显著增强(P＜0.01),TUNEL阳性细胞数较缺血组明显减少(P＜0.01),但两者均显著高于假手术组(P＜0.01).结论 短暂的脑缺血再灌注可导致脑皮质神经元中Bcl-2的表达增加,抗细胞凋亡;胰岛素可上调脑皮质神经元中Bcl-2的表达,发挥神经保护作用.     

川芎嗪、黄芪对脑缺血再灌注后神经细胞凋亡及Fos蛋白表达的影响

目的探讨川芎嗪、黄芪对脑缺血再灌注后神经细胞凋亡及Fos蛋白表达的影响.方法48只雄性SD大鼠,随机等分成4组,每组12只.A组:假手术组;B组:生理盐水对照组;C组:川芎嗪治疗组;D组:黄芪治疗组.采用TUNEL法及免疫组化法分别检测各组大鼠脑组织神经细胞凋亡及Fos蛋白的表达.结果与A组比较,B组大鼠神经细胞凋亡数目及Fos蛋白阳性细胞数目增多,Fos蛋白阳性细胞平均灰度值下降(P＜0.01);与B组比较,C组、D组大鼠神经细胞凋亡数目及Fos蛋白阳性细胞数目下降,Fos蛋白阳性细胞平均灰度值升高(P＜0.01).结论川芎嗪、黄芪均可能通过抑制脑缺血再灌注后Fos蛋白表达而减少神经细胞凋亡.     

补阳还五汤和依达拉奉联用对小鼠急性脑缺血损伤后脑保护机制的研究

目的探讨补阳还五汤和依达拉奉联用对急性脑缺血损伤后神经细胞凋亡及凋亡相关蛋白表达的影响,探讨其可能的脑保护机制。方法将60只小鼠随机分假手术组、模型组、补阳还五汤组、依达拉奉组以及补阳还五汤+依达拉奉组,每组12只。采用改良线栓法制作小鼠大脑中动脉缺血再灌注模型,给予补阳还五汤及依达拉奉药物干预。分别于再灌注后1d和7d,采用TUNEL法观察小鼠脑皮质缺血区神经细胞凋亡率,采用免疫组化方法观察小鼠脑皮质缺血区B淋巴细胞瘤2基因(bcl-2)、bcl-2相关X蛋白(bax)和半胱氨酸蛋白酶3(caspase-3)表达的阳性细胞数。结果与假手术组比较,模型组小鼠脑皮质缺血区凋亡指数升高(P0.01),且bcl-2、bax和caspase-3表达的阳性细胞亦均升高(P0.01);经补阳还五汤和(或)依达拉奉干预后,各药物组小鼠脑组织的凋亡指数及bax和caspase-3阳性细胞均较模型组下降(P0.01),而脑组织bcl-2阳性细胞均较模型组增加(P0.01),且补阳还五汤+依达拉奉联合用药组较单一用药组改变明显(P0.05)。结论补阳还五汤与依达拉奉联用能抑制脑缺血再灌注损伤后脑细胞中促凋亡蛋白bax、caspase-3的表达;促进具有神经元保护作用的bcl-2蛋白的表达,从而抑制神经细胞凋亡,协同发挥脑保护作用。     

人尿激肽原酶对大鼠脑缺血再灌注后神经细胞凋亡的影响

目的观察人尿激肽原酶(HUK)对大鼠脑缺血再灌注(I/R)后大脑皮质缺血灶周围区Caspase-3、凋亡诱导因子(AIF)的时相表达及对神经细胞凋亡的影响。方法将Wistar大鼠随机分为假手术组、模型组、HUK干预组,应用线栓法建立大鼠大脑中动脉阻塞(MCAO)再灌注模型。假手术组于术后,模型组、HUK干预组于缺血2h后再灌注6h、24h、48h、72h,应用免疫组化技术和原位末端标记法(TUNEL)检测不同时相各组缺血灶周围脑区Caspase-3、AIF和TUNEL阳性细胞的表达。结果大鼠I/R后在缺血灶周围区各个时间点均可见到Caspase-3、AIF和TUNEL阳性细胞的表达,HUK组与模型组相比较,两组Caspase-3、AIF和TUNEL阳性细胞的表达趋势基本一致,Caspase-3、AIF和TUNEL的表达高峰均在I/R后24h。HUK组各时间点Caspase-3、AIF和TUNEL阳性细胞的光密度值较模型组明显降低(均为P<0.05)。结论HUK对大鼠脑缺血再灌注损伤有保护作用,其作用机制可能与HUK抑制Caspase-3、AIF的表达,减轻迟发性神经元的凋亡有关。     

大鼠全脑缺血再灌注后额叶神经细胞凋亡与P53蛋白表达的实验研究

目的 探讨大鼠全脑缺血再灌注后不同时间对额叶神经细胞凋亡及P~(53)蛋白表达的影响。方法采用改良的Pulsineli 4-血管阻断(4-VO)方法建立SD大鼠急性全脑缺血模型,随机分为3组:正常组(n=7);假手术组(n=49);手术组(n=49)。缺血15min,分别于再灌注1、6、12、24、48、72h和7d断头取脑,采用TUNEL方法检测神经细胞凋亡,SP免疫组化方法观察额叶P~(53)蛋白的表达。结果 全脑缺血再灌注24h,可见少量TUNEL阳性细胞,再灌注48h可见较多TUNEL阳性细胞,72h出现大量TUNEL阳性细胞,7d明显减少。免疫组化染色:缺血组于再灌注24h可见少量P~(53)蛋白表达,48h达高峰,72h有所下降,7d明显下降,这种表达主要在细胞核内。结论 急性全脑缺血再灌注后的迟发性神经元坏死是以凋亡的方式发生的,全脑缺血再灌注后,额叶P~(53)蛋白表达增加,神经细胞凋亡和P~(53)蛋白的表达在一定时间内呈正相关。     

人尿激肽原酶对大鼠局灶性脑缺血再灌注损伤的保护作用及对Caspase-3表达的影响

目的 观察人尿激肽原酶(HUK)对局灶性脑缺血再灌注损伤大鼠神经细胞凋亡及Caspase-3表达的影响. 方法 66只SD大鼠按随机数字表法分为假手术组(n=6)、缺血再灌注损伤组和HUK处理组,后两组又按不同观察时间点分为再灌注6h、12h、24 h、72 h、168 h共5个亚组(n=6).缺血再灌注损伤组和HUK处理组采用线栓法建立大鼠大脑中动脉局灶性脑缺血再灌注损伤模型,HUK处理组按浓度17.5×10-3PNAU/mL,1.0 mL/kg,于再灌注后3h尾静脉注射给药,1次/d.采用TUNEL法及免疫组化染色检测各组大鼠脑组织中凋亡细胞及Caspase-3阳性细胞的数量变化. 结果 脑缺血再灌注损伤后6h即有细胞凋亡,于24 h达到高峰,至168 h仍可见凋亡细胞.Caspase-3阳性细胞表达均于再灌注24 h达高峰,至168 h仍有较多表达.除168 h时间点外,其余各时间点HUK处理组大鼠神经细胞凋亡数量、Caspase-3阳性细胞数量均明显低于缺血再灌注损伤组,差异均有统计学意义(P＜0.05). 结论 HUK在大鼠局灶性脑缺血再灌注损伤早期(6～72h)时能抑制细胞凋亡,推测与其减少Caspase-3的表达有关.     

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.     

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.     

Clobazam for Treatment of Intractable Epilepsy: A Critical Assessment

Summary: Clobazam (CLB), a 1,5-benzodiazepine, is a remarkably effective add-on drug for individual patients with refractory partial epilepsy. CLB has an excellent safety record. As with all benzodiazepines used for treating epilepsy, sedation and withdrawal effects, together with the development of tolerance, limit its usefulness. Recent efforts to prevent or reverse tolerance with intermittent administration of CLB or periodic injection of a benzodiazepine antagonist, flumazenil, are encouraging and justify further investigations.     

La passion de Torquemada et le terrorisme islamique : quelques points de comparaison

This original research compares the doctrinal, psychopathological and operational standpoints of the 15th century Spanish Inquisition (Torquemada) with those of radical Islamism from 1988 to 2005 (Al-Qaeda). The following are reviewed: (a) the main texts codifying the procedure for conducting the criminal investigation of a Holy Office trial (Directorium inquisitorum); (b) the life and work of the grand inquisitor Tomás de Torquemada (1420–1498); (c) the psychopathological relations between passion (passionate psychoses, passionate idealism, paranoid personality) and fanaticism; (d) “the madmen, the enlightened and the criminals” of Islamic terrorism; (e) the cognitive and emotional motives for engagement in the jihadist radicalization of young people; (f) the common principles of monotheistic fanaticism (Inquisition, Al-Qaeda) and the particular dogmas of Islamic terrorism in our time; (g) the operating modes of the Inquisition and the Jihadist holy war. The author concludes that the rigour and seriousness of the inquisitorial judicial procedure, which was precise, individual and personalized, contrasts with the revolutionary pamphlets of Al-Qaeda, which only provide broad guidelines for the modus operandi of the fight against infidels, who are usually random victims.     

Claustration et collectionnisme : réflexions à propos d’un cas de syndrome de Diogène avec vols kleptomaniaques et vengeurs

Social withdrawal is a pathognomonic behaviour that is consistently associated with mental illnesses. Compulsive hoarding can also be interpreted as a pathological behaviour, even when it does not involve kleptomania. Diogenes syndrome (DS) was first described in 1975, and is characterized by both behaviours - social withdrawal and compulsive hoarding. Even though it is often the manifestation of a psychiatric condition, its aetiology is diverse. The most frequent ones are however: dementia, schizophrenia and mental retardation. In this study, we describe an atypical case presenting with DS. Il consists of a young man, seen in a forensic setting, who had been diagnosed with kleptomania in the past, presents with compulsive hoarding, and whose recent thefts were fuelled by revenge. Finally, to our knowledge, the way social withdrawal is viewed is seldom taken into account. We analyse its implication on social withdrawal.     

Neurological soft signs and schizophrenia: a review of current knowledge

Schizophrenia is a frequent and disabling disorder emerging during adolescence or early adulthood. The identification of underlying processes has been hampered by the complex clinical expression and the probable etiological heterogeneity. The frequency of neurological soft signs (NSS) in patients with schizophrenia and their presence early in life (during the first two years) in high risk subjects support the hypothesis that schizophrenia is a "brain disease" reflecting pre- or perinatal insults during development. The growing interest for NSS has lead to multiple studies that are often difficult to compare. The objective of this review is to summarize the current knowledge on NSS, methodological issues and the future perspectives.     

Lacan, lecteur de Minkowski : l'approche structurale

The notion of structure occupies a predominant place in the theory of Lacan. He indicates that was developed from the work of Minkowski. In fact, through his phenomeno-structural approach, Minkowski does not limit himself to purely observable phenomena, but attempts to determine the underlying structure. He refers to the comprehensive phenomenology and psychopathology, and this method provides him with clinical finesse and another means of determining a diagnosis. Thus Lacan has used this as a basis for his approach to structure to develop a theory regarding the individual. This implies that the structure of the individual is based on his relation to language. From this concept, he then develops the clinical structures of neurosis, psychosis, and perversion. These structural landmarks also have an effect on the course of treatment.