一氧化氮合酶抑制剂对大鼠学习记忆能力的影响及尼莫地平的作用研究

目的：研究一氧化氮合酶抑制剂对大鼠学习记忆障碍的影响，和其海马一氧化氮(NO)变化及尼莫地平的作用。方法：大鼠双侧海马注入N-ω-硝基—L精氨酸(LNA)建立学习记忆障碍模型，注完L-NA后再给大鼠腹腔内注射尼莫地平，用Y型电迷宫进行学习记忆能力测试。取大鼠海马部位组织检测N0含量。结果：模型组大鼠的学习记忆能力明显低于对照组大鼠，干预组大鼠的学习记忆能力与模型组无差异；模型组大鼠的海马N0含量明显低于对照组，干预组大鼠海马N0含量与模型组无显著差异。结论：双侧海马注入L-NA可使大鼠出现学习记忆障碍，海马N0浓度降低。尼莫地平对L-NA所致的学习记忆障碍无治疗作用。     

一氧化氮对大鼠学习功能的影响

为探讨一氧化氮（NO）在学习过程中的可能作用，采用荧光分光光度法检测隔-海马通路损伤的大鼠以及海马微量注射一氧化氮合酶（NOS）抑制剂NG-硝基-L-精氨酸（NNLA）大鼠的海马和大脑皮层及外周血中NO含量的变化，并采用水迷宫和跳台试验同时观察大鼠学习能力的改变，结果表明隔-海马通路损伤或海马微量注射NNLA大鼠，海马中NO含量均明显下降并出现学习功能障碍，提示NO在学习过程中起重要作用。     

胰岛素治疗对糖尿病大鼠学习记忆功能障碍及大脑皮层额叶和海马神经肽含量变化的影响

目的观察胰岛素治疗对糖尿病大鼠学习记忆功能障碍及大脑皮层、海马内生长抑素(SS)、血管活性肠肽(VIP)含量变化的作用。方法采用链脲菌素制备雄性WiStar大鼠糖尿病模型，设正常对照组、胰岛素治疗糖尿病组、未治疗糖尿病组。3个月后采用T型水迷宫试验测定大鼠学习记忆功能，采用放免法测定皮层额叶、海马区脑组织SS、VIP含量。结果与正常对照组比较，未治疗糖尿病大鼠游迷宫时间显著延长、正确次数显著减少，额叶皮层、海马区脑组织SS含量显著降低，VIP含量无显著变化；胰岛素治疗组大鼠上述变化无显著意义。结论糖尿病引起大鼠学习记忆功能障碍和SS下降；SS下降与学习记忆功能障碍有关；早期胰岛素治疗可使学习记忆功能和SS含量恢复正常。     

铝盐致大鼠学习记忆功能障碍的β—APP、SS作用机制研究

目的：观察β－淀粉样前体蛋白（APP）、生长抑素（SS）在铝盐致大鼠学习记忆功能障碍模型脑内海马区表达的改变,并探讨其作用机制。方法：采用免疫组织化学方法检测β-APP、SS在大鼠脑内海马区的表达,HE染色观察实验组与对照组海马区锥体细胸层神经元形态结构,结果：实验组大鼠学习记忆功能较对照组明显降低（P＜0．01）;实验组海马区β－APP表达较对照组明显增加（P＜0．01）;SS免疫反应性神经元数目却显著减少（P＜0．01）;β-APP阳性度与SS阳性度之间存在等级负相关（P＜0．05）,实验组与对照组海马区神经元形态结构均基本 正常,数目无明显差异,结论：铝盐致大鼠海学记忆障碍的病理机制可能与脑内β-APP、SS表达的改变相关。     

N-精氨酸和硝普钠对大鼠学习记忆能力的影响

目的 观察脑室内注射一氧化氮合酶抑制剂(NOS)N-ω-硝基-L-精氨酸(N-Arg)和一氧化氮(NO)供体药物硝普钠对大鼠学习记忆的影响。方法 应用Y迷宫法观察N-Arg和硝普钠对大鼠学习记忆能力的影响．应用分光光度法测定注射后大鼠大脑皮质、海马NOS生物活性的变化。结果 与注射人工脑脊液的对照组相比，双侧脑室内注射N-Arg后，除5mg组外，10mg、15mg和20mg组大鼠Y迷宫学习能力均有不同程度下降，下降程度与脑室内注射N-Arg的剂量相关。各N-Arg注射组大鼠的记忆保持率与对照组比较没有显著差异。注射N-Arg 48h后可观察到海马NOS生物活性降低。脑室内注射N-Arg以后所引起的学习能力的降低可以被腹腔内注射1mg／kg的硝普钠所逆转。结论 中枢神经系统内NO-NOS参与了学习记忆的某些过程。     

神经生长因子对脑缺血大鼠学习与记忆的影响

目的为了观察神经生长因子（NGF）对脑缺血大鼠学习与记忆的影响和海马内N-甲基-D-天门冬氨酸受体NR2A/B亚zhanghaopeng（NR2A/B）表达的变化。方法本研究将48只成年雄性SD大鼠分为正常组（n=12）、假手术组（n=12）、慢性脑缺血组（n=12）、NGF处理组（n=12）。于造模后开始腹腔注射0.25 ug/100 g NGF,假手术组和慢性脑缺血组腹腔注射等量生理盐水,均1次/d,共21 d。用Morris水迷宫和＂＂Y＂迷宫作业测试其空间学习与记忆成绩,再采用Western blot方法分析海马的NR2A、NR2B的表达。结果①Morris水迷宫测试：模型组大鼠寻找平台的潜伏期较假手术组明显延长,NGF处理组大鼠寻找平台的潜伏期较模型组明显缩短;＂Y＂迷宫测试：模型组大鼠学会躲避电击的正确次数较假手术组明显减少,NGF处理组大鼠学会躲避电击的正确次数较模型组明显增多;②模型组NR2A表达水平较假手术组明显降低,而NR2B明显升高;NGF处理组海马内NR2A表达水平较模型组明显上调,而NR2B明显下调。结论神经生长因子可增强学习与记忆,海马内N-甲基-D-天门冬氨酸（NMDA）受体表达变化可能是影响学习与记忆的机制之一。     

睡眠剥夺大鼠大脑皮层和海马nNOS表达的改变在其学习记忆损伤中的作用

目的观察睡眠剥夺（SD）后,大鼠学习记忆能力及大脑皮层和海马神经元型一氧化氮合酶（nNOS）蛋白表达的变化。方法采用小平台水环境法建立大鼠SD模型。观察大鼠经过不同时间SD后,各组“Y”迷宫成绩及大脑皮层和海马nNOS阳性神经元的变化情况。结果（1）“Y”迷宫实验：3组SD组的迷宫成绩较正常笼养对照组（CC）分别下降了24．3％、17．6％和41．9％（P〈0．01）。（2）nNOS阳性神经元数目：在皮层,SDld组较CC组增加了8．7％（P〈0．01）,SD2d组和SD3d组较CC组则减少了9．0％和16．0％（P〈0．01）;在海马CA。区,3个SD组较CC组分别减少了9．4％、16．0％和22．0％（P〈0．01）。结论SD可能通过改变大鼠大脑皮层和海马CA．区nNOS蛋白的表达来损害大鼠学习记忆能力。     

NO-cGMP-Glu-[Ca~(2 )]i途径在隔-海马通路损伤的大鼠学习功能障碍中的作用

为探讨海马中一氧化氮影响大鼠学习能力的机制，观察海马中一氧化氮（NO）降低后海马cGMP、谷氨酸（Glu）、胞内游离钙离子（[Ca2 ]i）含量的变化。结果表明海马中NO降低的同时cGMP、Glu和[Ca2 ]i也降低。提示海马中NO可能是通过NO－cGMP－Gin-[Ca2 ]i途径影响大鼠的学习能力。     

血管性痴呆大鼠脑区和血浆中β－内啡肽含量的变化

采用Ｐｕｌｓｉｎｅｌｌｉ４血管闭塞法（４ＶＯ）的改良法建立大鼠血管性痴呆（ＶＤ）动物模型，用Ｔ型水迷宫试验检查动物的学习和记忆能力，并以放射免疫测定法测定ＶＤ大鼠４个脑区（额叶皮质、海马、丘脑和纹状体）和周围血浆中β－内啡肽（β－ＥＰ）含量。结果表明，ＶＤ组大鼠出现严重的学习、记忆障碍的同时其额叶皮质、海马丘脑和纹状体中β－ＥＰ含量分别为相应对照组的４１％、６６％、６８％和４３％，比对照组显著降低（降低３２％～５９％，Ｐ＜０．０５）。血浆β－ＥＰ含量在两组间则无显著差异。提示ＶＤ动物学习与记忆障碍可能与脑缺血后多脑区内β－ＥＰ含量降低有关。     

血管性痴呆大鼠学习记忆障碍及脑组织生长抑素的变化

目的探讨生长抑素（SS）参与血管性痴呆（VD）大鼠学习记忆障碍的作用机制。方法采用双侧颈总动脉结扎法制备慢性前脑缺血动物模型，随机分为假手术组（S）、模型组（M）。造模2月后进行水迷宫试验，观察2组大鼠空间学习记忆能力的差异，应用免疫组化方法检测造模2月后VD大鼠海马及颞叶皮层生长抑素表达变化。结果与假手术组比较，大鼠水迷宫学习记忆能力在造模2月后差异有显著性意义（P〈0．05），大鼠海马及颞叶皮层SS表达在造模2月后降低（P〈0．05）。结论脑组织SS表达降低，导致血管性痴呆大鼠学习记忆障碍。     

Cultural Identity and Experiences of Prejudice and Discrimination of Afghan and Iranian Immigrant Youth

In culturally diverse and immigrant receiving societies, immigrant youth can be subject to prejudice and discrimination. Such experiences can impact on immigrant youth’s cultural identity and influence their psychosocial outcomes. This paper presents findings of a study that examined cultural identity and experiences of prejudice and discrimination among Afghan (N = 9) and Iranian (N = 17) immigrant youth in Canada. The study had a prospective, comparative, longitudinal qualitative design. Data was gathered through focus groups, interviews, journals and field logs. Four main themes emerged on participants’ experiences of prejudice and discrimination: (a) societal factors influencing prejudice; (b) personal experiences of discrimination; (c) fear of disclosure and silenced cultural identity; and (d) resiliency and strength of cultural identity. Drawing from Rosenberg’s (Conceiving the self, Basic Books, New York, 1979) self-concept framework and Romero and Roberts (J. Adolesc., 21:641–656, 1998) distinction between prejudice and discrimination, results indicated that youth’s extant and presenting cultural identity were affected. Inclusive policies and practices are needed to promote youth integration in multicultural and immigrant receiving settings.

癫痫共病抑郁的机制及临床诊疗

本文目的是探讨癫痫共病抑郁的可能机制及临床诊疗。癫痫是一种常见的、慢性的、致残性的神经疾病,癫痫患者生活质量下降,存在明显的负性情绪,常伴发各种精神疾病。癫痫与抑郁具有共同的神经生物学基础,可能存在共同的发病机制。本文从癫痫共病抑郁的发病机制、临床诊断及治疗方面予以总结归纳。     

沙盘游戏疗法在地中海贫血患儿心理干预中的应用

本文目的是对沙盘游戏疗法在地中海贫血患儿心理干预中的应用进行综述,以期为地中海贫血患儿的心理康复提供参考。地中海贫血是以珠蛋白生成障碍为主要特征的遗传性疾病,由于长期输血治疗,患儿存在较多的心理和行为问题。沙盘游戏疗法作为一种有效、实用的儿童心理治疗方法,对提高地中海贫血患儿的康复效果、改善生存质量有重要的临床意义。     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

小胶质细胞和少突胶质细胞前体的培养和鉴定

目的 探讨新生大鼠脑组织小胶质细胞(MG)和少突胶质细胞(OL)前体的分离和体外培养方法 . 方法 取新生2 d SD大鼠脑组织,体外原代培养混合胶质细胞7 d后,分别采用"改良振荡伴差速贴壁"法和"营养缺失伴振荡"法纯化培养MG和OL前体,并分别应用免疫荧光染色异凝集素-B4(IB4)和OL前体标记物(O4)进行鉴定.结果 混合胶质细胞培养7 d后呈明显三层增长,其中MG位于上层,星型胶质细胞位于底层,两者之间为2型少突星型(O2A)祖细胞.纯化培养后OL前体胞体呈小圆形,有双极或三极突起,MG则以阿米巴形、圆形居多,或边缘呈毛刺状.免疫荧光染色IB4显示绿色荧光,MG纯度达到90%以上.免疫荧光染色O4显示棕黄色荧光,OL前体纯度达到95%以上. 结论 采用"改良振荡伴差速贴壁"法以及"营养缺失伴振荡"法分别成功获取大量纯度高、活力好的MG和OL前体.     

发作性睡病与异态睡眠的诊治

本文目的是探讨发作性睡病与异态睡眠的诊断与治疗。发作性睡病被漏诊和误诊的几率较高,危害较大,共患异态睡眠比例高。文章从发作性睡病临床特征、REM睡眠的作用、发作性睡病与异态睡眠(睡眠瘫痪、睡眠幻觉、快眼动睡眠期行为障碍)共病特征及治疗这四个方面进行了讨论。     

Neurological and neuropsychological consequences of electrical and lightning shock:review and theories of causation

Injuries from lightning and electrical injuries involve multiple systems of the body, however neurological symptoms are very widely reported. A disabling neuropsychological syndrome is also noted.This paper presents a comprehensive review of neurological and neuropsychological symptoms. Partial theories of causation for these injuries have been advanced, however, there is no convincing explanation for both delay in onset of symptoms and also the genesis of the neuropsychological syndrome. A theory of causation is proposed which satisfies both these constraints.This theory suggests circulating hormones such as cortisol, together with nitric oxide and oxidant free radicals from glutamatergic hyper-stimulation, act on tissues remote from the injury path including the hippocampus.This theory opens a research path to explore treat-ment options.     

Design and pharmacological activity of glycinamide and N-methoxy amide derivatives of analogs and constitutional isomers of valproic acid

A series of glycinamide conjugates and N-methoxy amide derivatives of valproic acid (VPA) analogs and constitutional isomers were synthesized and evaluated for anticonvulsant activity. Of all compounds synthesized and tested, only N-methoxy-valnoctamide (N-methoxy-VCD) possessed better activity than VPA in the following anticonvulsant tests: maximal electroshock, subcutaneous metrazol, and 6-Hz (32-mA) seizure tests. In mice, the ED₅₀ values of N-methoxy-VCD were 142 mg/kg (maximal electroshock test), 70 mg/kg (subcutaneous metrazol test), and 35 mg/kg (6-Hz test), and its neurotoxicity TD₅₀ was 118 mg/kg. In rats, the ED₅₀ of N-methoxy-VCD in the subcutaneous metrazol test was 36 mg/kg and its protective index (PI = TD₅₀/ED₅₀) was > 5.5. In the rat pilocarpine-induced status epilepticus model, N-methoxy-VCD demonstrated full protection at 200 mg/kg, without any neurotoxicity. N-Methoxy-VCD was tested for its ability to induce teratogenicity in a mouse strain susceptible to VPA-induced teratogenicity and was found to be nonteratogenic, although it caused some resorptions. Nevertheless, a safety margin was still maintained between the ED₅₀ values of N-methoxy-VCD in the mouse subcutaneous metrazol test and the doses that caused the resorptions. On the basis of these results, N-methoxy-VCD is a good candidate for further evaluation as a new anticonvulsant and central nervous system drug.     

Review and meta-analysis of the phenomenology and clinical characteristics of mania in children and adolescents

OBJECTIVE: Using predetermined criteria for study quality and methods, a literature review and meta-analysis of seven reports about pediatric bipolar disorder (BPD) was conducted to determine if there is a consistent picture of the phenomenology and clinical characteristics of BPD in children and adolescents. METHODS: Searches were conducted in MedLine and PsycINFO using the terms mania, BPD, children and adolescents, and was limited to published articles in peer-reviewed journals. Seven reports were selected that met the following criteria: a systematic method for the elicitation and reporting of symptoms and clinical characteristics of subjects; subjects were interviewed by a trained researcher or clinician; ages 5-18 years; use of a diagnostic system, either DSM or RDC for categorization; a consensus method for the establishment of the diagnosis of BPD. RESULTS: Most DSM-IV symptoms of mania were common in the children and adolescents with BPD with the most common symptoms being increased energy, distractibility, and pressured speech. On average, four of five bipolar cases also showed threshold levels of irritable mood and grandiosity, and more than 70% of all cases showed elated/euphoric mood, decreased need for sleep, or racing thoughts. Roughly 69% of cases also showed poor judgment, whereas only half of bipolar cases demonstrated flight of ideas, and slightly more than one-third showed hypersexuality or psychotic features. CONCLUSIONS: The clinical picture that emerges is that of children or adolescents with periods of increased energy (mania or hypomania), accompanied by distractibility, pressured speech, irritability, grandiosity, racing thoughts, decreased need for sleep and euphoria/elation.     

The neuroendocrinology of stress and the pathophysiology and therapy of depression and anxiety

Clinical and preclinical studies have gathered substantial evidence that stress response alterations play a major role in the development of major depression, panic disorder, and post-traumatic stress disorder. The stress response, the hypothalamic pituitary adrenocortical (HPA) system and its modulation by corticotropin-releasing hormones (CRH),corticosteroids,and their receptors, and the roles of natriuretic peptides and neuroactive steroids are described. We review the role of the HPA system in major depression, panic disorder, and post-traumatic stress disorder and its possible relevance for treatment. Impaired glucocorticoid receptor function in major depression is associated with an excessive release of neurohormones such as CRH, to which a number of signs and symptoms characteristic of depression can be ascribed. In panic disorder, a role of central CRH in panic attacks has been suggested. Atrial natriuretic peptide (ANP) is causally involved in sodium lactate-induced panic attacks. Furthermore, preclinical and clinical data on its anxiolytic activity suggest that nonpeptidergic ANP receptor ligands may be potentially useful in the treatment of anxiety disorders. Post-traumatic stress disorder is characterized by a peripheral hyporesponsive HPA system and elevated CRH concentrations in the CSF. This dissociation is probably related to an increased risk of this disorder. We further review recent data that describe an important role of GABA(A)-receptor modulatory,3 alpha-reduced neuroactive steroids in major depression, anxiety, and its treatment. Antidepressants are effective in both depression and anxiety disorders and have major effects on the HPA system,especially on glucocorticoid and mineralocorticoid receptors. Normalization of HPA system abnormalities is a strong predictor of the clinical course, at least in major depression and panic disorder. Currently,CRH-R1 or glucocorticoid receptor antagonists and ANP receptor agonists are being studied and may provide future treatment options more closely related to the pathophysiology of these disorders.