亚低温对局灶性脑缺血-再灌注大鼠脑皮质脑源性神经营养因子表达及神经元凋亡的影响

目的 观察局灶性脑缺血-再灌注后亚低温干预对大鼠脑源性神经营养因子表达及神经元凋亡的影响，并探讨脑源性神经营养因子在亚低温脑保护机制中的作用。方法 采用线栓法制备成年雄性SD大鼠左侧大脑中动脉闭塞局灶性脑缺血-再灌注改良模型，缺血时间2h。随机分为常温缺血组和亚低温缺血组。常温时大鼠脑温控制于36．5℃～37．5℃，肛温为35．9℃～36．9℃；亚低温时脑温维持于32．5℃～33．5℃，肛温为32．2℃～33．1℃。两组大鼠分别于脑缺血一再灌注及亚低温干预后2、6、24和72h进行神经功能缺损评分，并同时行三苯基氯化四唑（1TC）染色、HE染色、TUNEL染色、免疫组化染色及免疫组化与TUNEL双重染色，从而评估大鼠神经功能缺损状况；检测脑梗死体积及脑源性神经营养因子表达水平；观察组织病理学变化和神经元凋亡数量。结果 与常温缺血组相比，亚低温缺血组大鼠神经功能缺损评分低（P〈0．01），脑梗死体积小（P〈0．01），缺血灶周围脑皮质中的脑源性神经营养因子表达水平增高（P〈0．01），而且神经元凋亡数量少（P〈0．01）。在脑源性神经营养因子免疫组化染色呈阳性反应的神经元细胞核中，未发现TUNEL染色阳性者。结论 亚低温干预治疗可促进缺血灶周围的脑皮质对脑源性神经营养因子的表达，从而抑制神经元凋亡，减少大鼠脑梗死体积，改善神经功能缺损体征。     

缺血再灌注蛋白激酶C同工酶表达与神经元凋亡关系的研究

目的 研究局灶脑缺血／再灌注大鼠蛋白激酶C（PKC）同工酶表达在缺血性脑损害中可能的作用机制。方法 采用线栓法制备大鼠局灶脑缺血／再灌注模型。于缺血1．5h再灌注4h、24h、72h观察PKCγ、δ表达及神经元坏死、凋亡的变化规律。结果 再灌注4h PKCγ、δ及神经元凋亡明显升高，PKCγ在24h达高峰，72h开始下降（P＜0．05）；PKCδ在再灌注24h、72h仍保持一高水平（P＞0．05），神经元凋亡的变化规律同PKCγ（P〈0.05)；神经元坏死在再灌注各时相点无显著性差异（P＞0．05）。结论 PKCγ、δ的异常表达与神经元坏死、凋亡有密切的联系。     

Pinacidil抑制线粒体和死亡受体通路减少大鼠脑缺血再灌注后神经元凋亡

目的探讨ATP敏感性钾通道开放剂pinacidil对大鼠脑缺血再灌注后神经元凋亡的保护作用及信号转导机制。方法100只Wistar雄性大鼠随机分为四组：A组（假手术组）、B组（缺血组）、C组（KATP开放剂处理组）及D组（KATP 开放剂和阻断剂处理组）。用线栓法制备大鼠大脑中动脉缺血（middle cerebral artery occlusion,MCAO）模型,用DNA断端末端标记法（tenninal-deoxynucleotidytransferase-mediated dUTP—biotin nick end labeling,TUNEL）检测神经元凋亡,用原位杂交方法检测caspase-3、caspase-8及caspase-9mRNA的表达。结果（1）C组12h、24h、48h、72h时间点的凋亡细胞数较B、D组显著减少（P〈0．05或P〈0．01）;B组和D组之间无显著性差异fP〉0．05）。（2）C组caspase-3mRNA和caspase-8mRNA在各时间点及caspase-9mRNA在12h、24h、48h、72h时间点的表达显著少于B组和D组（P〈0．01或P〈0．05）,B组和D组之间无显著性差异（P〉0．05）。结论K通道开放剂能显著减少大鼠脑缺血再灌注后的细胞凋亡及caspase-3、caspase-8及caspase-9 mRNA的表达。K通道开放剂可能通过抑制线粒体通路和死亡受体通路降低神经元凋亡,保护缺血再灌注损伤后的脑组织。     

国产降纤酶对大鼠局灶性脑缺血/再灌注后行为学和梗死体积的影响

目的：探讨国产降纤酶对大鼠局灶性脑缺血／再灌注动物模型的神经行为学和脑梗死体积的影响，以证明其是否有脑保护作用。方法：采用线检法制作大鼠大脑中动脉闭塞模型，用Zea Longa 5分制评分和TTC染色法评价神经行为学和脑梗死体积。由吉林大学第一医院和复旦大学华山医院共同进行实验研究，每部分实验动物各做一半。动物随机分为缺血3h及再灌注3h,6h,24h和72h；缺血6h及再灌注3h,6h,24h;缺血24h等共10组。降纤酶采用8U／kg腹腔注射给药。结果：行为学结果：在10组中仅于缺血6h再灌注6h组Zea Longa评分有明显改善（P＜0．05），其余各组与盐水对照组比较无显著性差异。梗死体积测定结果：在缺血3h各组中，只有缺血3h再灌注72h这个时间点比盐水组无明显缩小（P＞0．05），其余各时间点梗死体积均明显缩小（P分别＜0．05、0．01和0．001）。在缺血6h和24h组中，各时间点与盐水组比较均明显缩小（分别为P＜0．01和P＜0．05）。结论：国产降纤酶对大鼠局灶性脑缺血及再灌注损伤有一定的保护作用。     

高血糖对大鼠脑缺血再灌注后碱性成纤维因子表达的影响

目的观察高血糖条件下大鼠脑缺血再灌注后碱性成纤维细胞生长因子（basic fibroblast growth factor,bFGF）表达的情况。方法以链脲佐菌素诱导产生实验性糖尿病大鼠,饲养6周左右,经测定血糖〉16.7mmol/L确定糖尿病模型的建立。以线栓法制作大鼠脑缺血再灌注模型,进行梗死体积测定,采用免疫组化方法观察大鼠脑缺血再灌注6h、12h、24h、48h时程bFGF的表达情况,比较糖尿病大鼠及正常大鼠脑缺血再灌注后脑内bFGF的表达的差异。结果（1）相同时间点糖尿病组大鼠脑梗死体积明显大于正常血糖组。（2）正常血糖组大鼠及糖尿病组大鼠脑缺血后bFGF的表达均增加,糖尿病组大鼠脑缺血再灌注后各时间点bFGF的表达均低于正常血糖组（P〈0.01）。结论脑缺血再灌注损伤可以诱导bFGF表达增强,提示bFGF对缺血性脑损伤有保护作用。糖尿病加重了大鼠脑缺血再灌注损伤,造成bFGF的表达不足。     

大鼠脑缺血再灌注后梗死体积的动态变化

目的观察大鼠大脑中动脉缺血再灌注后梗死灶体积的变化规律。方法线栓法制作大鼠局灶性脑缺血再灌注模型,观察脑缺血2h再灌注3h、24h、3d、7d、14d及21d后的神经功能缺损评分及2％氯化三苯基四氮唑(TTC)标记的梗死体积。结果缺血2h再灌注3h组已经出现较明显的梗死灶(梗死体积占前脑体积14．4％),再灌注24h组梗死体积最大(24．3％),显著大于再灌注3h、7d、14d、21d组(P<0．05)。再灌注3d组梗死灶仍较大 (23．8％),再灌注7d组梗死体积缩小(5．0％),再灌注14d组梗死灶进一步缩小(1．2％),再灌注21d组梗死灶基本消失(0．2％)。大鼠神经功能缺损评分与梗死体积之间呈显著相关(r=0．61,P<0．01)。结论脑缺血再灌注后梗死体积于24h达最大,21d时基本消失。脑缺血再灌注后神经功能缺损评分与梗死体积之间显著相关。     

神经生长因子对大鼠前脑缺血再灌注后细胞凋亡及FaS蛋白表达的影响

目的：研究神经生长因子（NGF）对大鼠前脑缺血再灌注后海马CA1区Fas蛋白表达和细胞凋亡的影响。方法：夹闭大鼠双侧颈总动脉造成前脑缺血，30min后松夹再灌注，NGF组和生理盐水组于再灌注开始时分别肌肉注射NGF30μg·mL^-1和生理盐水0．1mL，应用免疫组化法和TUNEL法检测各组大鼠海马CA1区Fas蛋白表达和细胞凋亡。结果：再灌注后6和24h，NGF组Fas蛋白平均吸光度值小于生理盐水组（P〈0．001和P〈0．05）。再灌注后48h两组比较差异无统计学意义（P〉0．5）。再灌注后6、24和48h，NGF组TUNEL阳性细胞率均低于生理盐水组，差异有统计学意义（P〈0．005）。结论：NGF可以减少大鼠脑缺血再灌注后海马CA1区Fas蛋白表达，抑制细胞凋亡，从而发挥其神经保护作用。     

局灶性脑缺血预适应后大鼠血浆皮质醇含量变化

目的探讨脑缺血预适应后糖皮质激素与皮层神经元损伤的关系。方法利用线栓法建立大鼠大脑中动脉脑缺血再灌注模型,通过放射免疫方法测定脑缺血再灌注后各组大鼠再灌注3h、12h、24h和48h各时点的血浆皮质醇含量变化。结果缺血组和预缺血组在再灌注4个时点糖皮质激素含量均有增高,同对照组、假手术组相比有显著差异（P〈0．01）。预缺血组与缺血组相比,预缺血组在再灌注4个时点糖皮质激素含量低于缺血组（P〈0．05）。HE染色皮层神经元损伤显著,预缺血组明显轻于缺血组。结论脑缺血预适应导致缺血再灌注后血浆糖皮质激素含量降低,这可能是其减轻皮层神经元损伤的原因之一。     

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。     

亚低温对局灶性脑缺血再灌注后不同时间点Akt、NF-κB变化规律的影响

目的 通过检测Akt及NF-κB蛋白的表达，探讨亚低温对局脑缺血再灌注后神经元存活的影响。方法 用线拴法制作大鼠大脑中动脉闭塞（MCA0）局脑缺血再灌注模型，将44只SD大鼠随机分成假手术组、常温缺血组和亚低温缺血组，缺血组分别缺血2h、6h，再灌注4h、24h、72h、1周、2周后处死，亚低温组于缺血后13～14min实施病灶倒亚低温持续4h。免疫组织化学法检测Akt、NF—κB蛋白的表达。结果 相同缺血再灌注时闾点，亚低温组比常温组缺血侧Akt表达水平显著增高（P〈0．05），NF—κBP65核内移明显降低（P〈0．01）。结论 病灶侧亚低温通过促进缺血半暗带脑组织Akt表达，抑制NF—κB的核内移，从而抑制神经元凋亡，促进脑缺血后神经功能恢复。     

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.