脑缺血再灌注拟血管性痴呆小鼠皮层及海马细胞病理形 …

目的 观察脑缺血再灌注拟血管性痴呆小鼠大脑皮层及海马细胞病理形态学的较长期演变。方法 复制脑缺血再灌注拟血管性痴呆小鼠模型，分别于术后７ｄ，１５ｄ，３０ｄ脑部取材，石蜡切片，ＨＥ与Ｎｉｓｓｌ染色，对皮层及海马细胞病理形态学进行较长期动态观察。结果 ７ｄ模型小鼠大脑皮质变薄，部分神经细胞核固缩，局限性神经元数目减少，出现筛网状结构，胶质细胞增生，１５ｄ，３０ｄ镜下与７ｄ基本相同。海马ＣＡ１区细胞脱失     

脑缺血再灌注拟血管性痴呆小鼠皮层及海细胞病理形态学动态观察

目的观察脑缺血再灌注拟血管性痴呆小鼠大脑皮层及海马细胞病理形态学的较长期演变.方法复制脑缺血再灌注拟血管性痴呆小鼠模型,分别于术后7d、15d、30d脑部取材,石蜡切片,HE与Nissl染色,对皮层及海马细胞病理形态学进行较长期动态观察.结果 7d模型小鼠大脑皮质变薄,部分神经细胞核固缩,局限性神经元数目减少,出现筛网状结构,胶质细胞增生,15d、30d镜下与7d基本相同.海马CA1区细胞脱失,随时间推移逐渐加重,至术后30d,海马CA1区细胞几乎完全脱失,胶质细胞大量增生,形成结节,CA2、CA3区细胞也严重脱失,呈现海马硬化.结论海马锥体细胞的迟发性坏死是缺血性脑血管病致痴呆的病理学基础.     

小檗碱对小鼠海马CA1区迟发性神经元坏死的影响

本文采用Ｐｕｌｓｉｎｅｌｌｉ－Ｂｒｉｅｒｌｅｙ４血管结扎致ＳＤ大鼠全脑缺血（１０ｍｉｎ）再灌流模型，分别观察了早期不同再灌流时间（１２、２４、４８ｈ）点上，大鼠海马ＣＡ１区神经元的超微结构以及早灌７ｄ时光镜结构变化，同时观察了小檗碱对ＣＡ１区迟发性神经元坏死的影响。结果显示脑缺血再灌流早期，ＣＡ１区神经元超微结构发生明显改变，７ｄ时光镜下绝大部分细胞脱失，而用药组大鼠海马ＣＡ１区神经元在相应时间点     

小檗碱对大鼠海马CA_1区迟发性神经元坏死的影响

本文采用Ｐｕｌｓｉｎｅｌｌｉ－Ｂｒｉｅｒｌｅｙ４血管结扎致ＳＤ大鼠全脑缺血（１０ｍｉｎ）再灌流模型，分别观察了早期不同再灌流时间（１２、２４、４８ｈ）点上，大鼠海马ＣＡ１区神经元的超微结构以及再灌７ｄ时光镜结构变化，同时观察了小檗碱对ＣＡ１区迟发性神经元坏死的影响。结果显示脑缺血再灌流早期，ＣＡ１区神经元超微结构发生明显改变，７ｄ时光镜下绝大部分细胞脱失；而用药组大鼠海马ＣＡ１区神经元在相应时间点上超微结构变化相对较轻，７ｄ时仍有绝大多数（８２％）细胞存活，细胞密度为１７２±１２．２个／ｍｍ，显著高于缺血对照组２７±７．６个／ｍｍ，Ｐ＜０．００１。提示小檗碱对大鼠短暂脑缺血再灌流造成的海马ＣＡ１区迟发性神经元坏死具有显著的对抗作用。     

脑缺血选择性海马CA1区神经元损害的实验研究

采用Ｐｕｌｓｉｎｅｌｉ－Ｂｒｉｅｒｌｅｙ４血管阻塞脑缺血模型观察了大鼠全脑缺血２０ｍｉｎ再灌流８ｈ，ｃ－ｆｏｓ基因表达及再灌流７ｄ海马ＣＡ１区迟发性神经元损害。在缺血再灌流早期（８ｈ）海马ＣＡ１区极少ｃ－ｆｏｓ表达，而齿状回、海马ＣＡ３区、杏仁核大量ｃ－ｆｏｓ表达。缺血再灌流晚期（７ｄ）镀银染色显示海马ＣＡ１区神经元及其突触终末带呈黑色溃变相，而齿状回、海马ＣＡ３区、杏仁核呈金黄色正常相。相邻切片ＨＥ染色示缺血组海马ＣＡ１区核完整的锥体细胞数（５±２．６个／２００μｍ）与对照组（４０±２．９个／μｍ）比较差异有显著意义（Ｐ＜０．０１）。脑缺血诱导的ｃ－ｆｏｓ基因表达对于缺血易损海马ＣＡ１区迟发性神经元坏死可能起直接的调控作用。     

保精增智液对大鼠迟发性神经元坏死海马CA_1区光镜和电镜改变的影响

本研究采用Ｗｉｓｔａｒ大鼠４血管关闭法制成全脑缺血１０ｍｉｎ再灌流动物模型造成迟发性神经元坏死（ＤＮＤ），分别观察了海马ＣＡ１区再灌流后３ｄ和５ｄ的普通病理和超微结构改变，同时观察了中药保精增智液对ＤＮＤ的保护作用，结果显示再灌流３ｄ时电镜下ＣＡ１区神经元内亚细胞结构改变明显，５ｄ时光镜下出现明显的神经元脱失，造模前８ｄ给药组可明显改善再灌流３ｄ时的亚细胞结构的改变，使５ｄ时神经细胞存活数上升（１８１．６±１５．１个／ｍｍ，对照组４１．４±４．０，Ｐ＜０．０１）。该药对大鼠短暂全脑缺血再灌流造成的ＤＮＤ有保护作用。     

神经节苷脂对缺血性大鼠脑损伤作用的研究

目的 探讨神经节苷脂（ＧＭ１）的脑保护作用及其可能机制。方法 用四血管闭塞４ＶＯ）全脑缺血再灌注模型,用高效液相色谱仪柱前衍生色谱法测定假手术组,缺血３０ｍｉｎ再灌注６０ｍｉｎ生理盐水（ＮＳ）处理组、缺血３０ｍｉｎ再灌注６０ｍｉｎＧＭ１处理组的海马组织兴奋性氨基酸（ＥＡＡ）含量,并观察缺血３０ｍｉｎ再灌注４ｄ海马ＣＡ１区病理变化。结果 缺血再灌注ＮＳ处理组海马组ＥＡＡ含量显著性降低,海马ＣＡ１区多     

"聪圣胶囊"对智力低下大鼠海马CA1区氨基酸含量的影响

目的　观察脑反复缺血再灌注后智力低下大鼠海马ＣＡ１ 区氨基酸含量及用“聪圣胶囊”治疗后的变化。方法　反复夹闭双侧颈总动脉制成智力低下大鼠，分别于术后１ｄ、７ｄ、１５ｄ、３０ｄ 检测海马ＣＡ１ 区氨基酸含量。结果　模型组氨基酸含量出现了先增加后减少的显著改变；用“聪圣胶囊”干预组的氨基酸含量亦有波动，但较模型组明显减轻；假手术组的含量无变化。结论　“聪圣胶囊”对神经细胞具有一定的保护作用。     

神经节苷脂对缺血性大鼠脑保护作用的研究

目的探讨神经节苷脂（ＧＭ１）的脑保护作用及其可能机制。方法用四血管闭塞（４ＶＯ）全脑缺血再灌注模型,用高效液相色谱仪柱前衍生色谱法测定假手术组、缺血３０ｍｉｎ再灌注６０ｍｉｎ生理盐水（ＮＳ）处理组、缺血３０ｍｉｎ再灌注６０ｍｉｎＧＭ１处理组的海马组织兴奋性氨基酸（ＥＡＡ）含量,并观察缺血３０ｍｉｎ再灌注４ｄ海马ＣＡ１区病理变化。结果缺血再灌注ＮＳ处理组海马组织ＥＡＡ含量显著性降低（Ｐ＜０．０１）,海马ＣＡ１区多数神经元坏死,残存神经元呈较严重缺血性改变,ＧＭ１处理组上述生化病理改变明显为轻。结论推测ＧＭ１可调控缺血再灌注早期ＥＡＡ的过度释放和（或）重摄取受阻,减轻其在细胞外堆聚引起的兴奋毒性损伤,具有脑保护作用。     

宽叶缬草对血管性痴呆小鼠学习记忆及海马区神经元病理学改变的影响

目的:观察宽叶缬草对血管性痴呆模型小鼠学习记忆及海马区神经元病理学改变的影响。方法:采用反复夹闭双侧颈总动脉结合腹腔注射硝普钠的方法复制小鼠拟血管性痴呆的模型。健康昆明小鼠54只,随机分为3组:假手术组、血管性痴呆模型组、宽叶缬草组。分别于术后7、15、30 d,跳台实验检测其痴呆程度;透射电镜、HE和Nissl染色对海马区神经元病理学改变进行观察。结果:宽叶缬草组跳台实验潜伏期明显短于模型组(P<0.01),受电击总时间少于模型组(P<0.01);宽叶缬草组海马CA1区神经元数量明显多于模型组(P<0.01);模型组可见神经元脱失、部分神经细胞核固缩并有胶质细胞增生等病理学改变。结论:宽叶缬草能明显减轻血管性痴呆小鼠海马CA1区神经元损伤,改善脑缺血引起的学习记忆障碍。     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.     

Pediatric Epilepsy Surgery

Summary: The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.     

Un nouveau cadre conceptuel de travail pour une psychiatrie revisitée ? Introduction à deux articles de E. Kandel

In two articles which appeared in the American Journal of Psychiatry and that were subsequently translated for Évolution Psychiatrique, E. Kandel examines the bases for a reinterpreted psychiatry that is prepared to confront the major challenge of the 3rd millenium: that of insight into the mind and brain. This requires a major reorganization of the discipline, which involves a reinvestment of the scientific approach and a critical  assessment of the data provided by psychoanalytical psychiatry and cognitive neurosciences. Seven concepts have therefore been proposed for interactive re-examination: consciousness, the unconscious, memory, emotion, development, desire, impulse. The dynamic relations existing between genetics and the environment allow one to see how evolutions are possible from actions at different levels, both psychotherapeutic and pharmacological. Imaging and other techniques provide additional objective information to the process of human interaction which remains the basis of psychiatry. A common framework for psychiatry and the neurosciences, a reconsideration and renewal of the psychoanalytical approach are both possible and necessary.     

Opioids and the developing organism: A comprehensive bibliography, 1984–1988

A comprehensive bibliography of the literature concerned with opioids and the developing organism for 1984-1988 is presented. Utilized with companion papers (Neurosci. Biobehav. Rev. 6:439-479; 1982; 8:387-403; 1984), these articles cover the clinical and laboratory references beginning in 1875. For the years 1984, 1985, 1986, 1987, and 1988, a total of 877 citations were recorded. A series of indexes accompanies the citations in order to make the literature more accessible. These indexes are divided into clinical and laboratory topics, and subdivided into such topics as the type of opioid explored and the general area of biological interest (e.g., physiology).     

La biologie et le futur de la psychanalyse : un nouveau cadre conceptuel de travail pour une psychiatrie revisitée

The American Journal of Psychiatry has received a number of letters in response to my earlier “Framework” article (1). Some of these are reprinted elsewhere in this issue, and I have answered them briefly there. However, one issue raised by some letters deserves a more detailed answer, and that relates to whether biology is at all relevant to psychoanalysis. To my mind, this issue is so central to the future of psychoanalysis that it cannot be addressed with a brief comment. I therefore have written this article in an attempt to outline the importance of biology for the future of psychoanalysis.     

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.     

Facteurs de risque environnementaux à la schizophrénie

Schizophrenia is currently a major concern, its prevalence being estimated at around 1% and its social consequences being severe. The elucidation of the pathophysiology of the disease is difficult due to the great variability of clinical expressions, the instability of the clinical symptoms during the evolution and the absence of reliable biological markers. The existence of a familial aggregation in schizophrenia is well known, the risk of presenting the disease for first-degree relatives of patients being 5 to 10 times higher than the risk observed in the general population. The genetic component was further confirmed by twin and adoption studies. Although the concordance for the disease is higher (40 to 70%) among monozygotic twins as compared with dizygotic twins (15%) it does not reach 100%, which implies that environmental factors modulate the effects of the genotype. However, the role of these factors and especially their interaction with genetic factors remain unclear but the implications of some specific environmental factors are well documented by recent research data. The current literature on sex differences in schizophrenia is consistent. Several studies have suggested that male and female patients may differ in age at the onset and expression of clinical symptoms. Complications during pregnancy or birth-giving may increase the risk of developing schizophrenia later in life. The major complications are oxygen deprivation during pregnancy, bleeding, maternal malnutrition or infection (exposure to influenza, for example). A low birth weight is associated with an increased risk of schizophrenia. Psychoses are more common among people living in an urban environment and among those born during winter months. Schizophrenia is probably more prevalent in people who are living promiscuously, are subject to toxic abuse, poor nutrition and stress but here more precise data are needed. Moreover, immigrants have a higher risk of developing psychotic disorders. In addition, head traumas are associated with an increased risk of schizophrenia. Though they are contentious, some studies suggest that substance abuse (cannabis use in European countries) is related to the development of schizophrenia, especially in people with genetic vulnerability. Moreover, substance misuse may worsen the symptoms. If the environment is sufficiently stressful, people with a high genetic vulnerability will develop some degree of mental illness, including schizophrenia. Conversely, a less stressful or a protective environment may decrease the risk of its onset in persons with a predisposition to schizophrenia.