依达拉奉对大鼠脑创伤后神经细胞凋亡信号通路的影响

目的 探讨依达拉奉对脑创伤后神经细胞凋亡信号通路的影响.方法 135只雄性SD大鼠随机分为对照组(25只)、创伤组(60只)和依达拉奉组(50只).Marmarou's法建立SD大鼠弥漫性脑创伤模型;依达拉奉组大鼠伤后即刻经尾静脉注射依达拉奉10 mg/kg,每天1次,共3 d;分别于伤后1 h、6 h、24 h、48h和72 h采用硫代巴比妥酸法检测大脑皮质中丙二醛(MDA)含量;免疫组化法和Western Blot法检测皮质区磷酸化细胞外信号调节激酶(ERK1/2)及细胞色素C(CytC)的表达;原位缺口末端标记法(TUNEL)检测神经细胞凋亡.伤后24 h、48 h、72 h对大鼠综合运动功能进行评定.结果 与对照组比较,创伤组大鼠脑组织MDA水平(6 h、24 h、48 h、72 h)、磷酸化ERK1/2(1 h、6 h、24 h、48 h)和CytC(6 h、24 h、48 h、72 h)表达明显增高,细胞凋亡数(6 h、24 h、48 h、72 h)增多;综合运动能力评分下降(均P＜0.05).与创伤组比较,依达拉奉组大鼠脑组织MDA含量、磷酸化ERK1/2和CytC表达、神经细胞凋亡数下降;大鼠的运动功能评分回升(均P＜0.05).结论 依达拉奉通过清除氧自由基、抑制ERK1/2信号途径活化、减少神经细胞凋亡而发挥对脑创伤的保护作用.     

依达拉奉和尼莫地平联合应用对脑缺血大鼠脑组织血管内皮生长因子表达的影响

目的 探讨依达拉奉与尼莫地平联合应用对脑缺血大鼠脑组织血管内皮生长因子(VEGF)表达的影响.方法 90只Wistar大鼠随机分为5组:正常对照组、脑缺血组、依达拉奉组、尼莫地平组和依达拉奉+尼莫地平组(依尼组),各组又分为缺血12 h、24 h、48 h亚组.用线栓法制作大鼠大脑中动脉堵塞(MCAO)脑缺血模型.制模后1 h,各药物干顶组分别注射依达拉奉3 mg/kg、尼莫地平2 mg/kg和依达拉奉+尼莫地平,正常对照组和脑缺血组大鼠分别腹腔注射生理盐水.各组大鼠分别于预定时间点处死,用逆转录-聚合酶链反应(RT-PCR)法检测脑组织VEGFmRNA水平.结果 各组缺血24 h、48 h亚组脑组织VEGF mRNA水平明显低于正常对照组(均P＜0.01),各药物干预组脑组织VEGF mRNA水平显著高于脑缺血组(均P＜0.01);依尼组脑组织VEGF mRNA水平又显著高于依达拉奉组和尼莫地平组(均P＜0.01).结论 依达拉奉和尼莫地平能上调缺血脑组织VEGF的表达水平,联合应用效果更好.     

依达拉奉对大鼠创伤性脑损伤的早期保护作用

目的探讨大鼠脑创伤后依达拉奉对脑组织的早期保护作用。方法选择雄性成年SD大鼠54只,随机分3组:假手术组18只,仅开骨窗,不损伤;损伤组18只,制大鼠自由落体脑撞击伤模型;依达拉奉组18只,行依达拉奉注射液处理。在伤后24h、48h及72h测量各组脑组织含水量、血脑屏障(BBB)通透性、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力。结果依达拉奉与损伤组比较,各时间点脑含水量减少、BBB通透性降低、MDA含量降低及SOD活力升高,差异有统计学意义(P0.05)。结论依达拉奉对创伤性脑损伤早期有保护作用。     

甲基强的松龙对大鼠颅脑损伤后一氧化氮合成酶活性的影响

目的观察甲基强的松龙对大鼠颅脑损伤后血、脑组织中NOS含量的影响,并探讨其作用机制。方法将45只SD大鼠随机分为3组:实验组(20只)、对照组(20只)、正常组(5只),均采用骨窗形成后硬膜外打击法造成鼠脑挫裂伤。正常组麻醉后,只行开颅手术,不作头颅打击,治疗组大鼠致伤后即刻腹腔内注射30mg/kg甲基强的松龙,对照组则注射30mg/kg生理盐水。对照组和治疗组大鼠分别在伤后1h、6h、12h、24h断头取脑,对大鼠脑外伤后脑组织中一氧化碳合成酶(NOS)含量进行检测。结果大鼠脑皮质中的NOS活性在伤后1h较正常组显著性升高(P <0.01),6h开始下降,12～24h降至基础水平。甲基强的松龙治疗组在伤后1h(P <0.01)、6h(P <0.05)NOS活性较损伤组显著性降低。结论颅脑损伤后,受损脑组织中NOS活性升高,甲基强的松龙可通过抑制损伤后NOS活性起到保护创伤神经元的作用。     

依达拉奉激活Nrf2通路减轻脑出血后继发性损伤

目的探讨自由基清除剂依达拉奉对大鼠脑出血神经功能与脑水肿的疗效,并通过检测核因子相关因子2（Nrf2）通路及其下游抗氧化酶的表达变化,探索依达拉奉在脑出血中的抗氧化治疗机制。方法采用自体血立体定向注射建立大鼠脑出血模型,依达拉奉干预后24h分别行神经行为学评分及脑含水量测定,并检测Nrf2通路表达变化,脑组织切片行免疫荧光双标染色,判定Nrf2表达的细胞来源。结果依达拉奉干预脑出血大鼠后24h,前肢抬起及前肢对称实验较对照组均明显改善,脑含水量亦明显降低。依达拉奉组Nrf2及其下游抗氧化酶血红素加氧酶1（HO-1）、硫氧还蛋白（TRX）、谷胱甘肽-S-转移酶a1（GST-a1）、醌氧化还原酶1（NQ01）转录水平较对照组明显上调,依达拉奉组Nrf2及HO-1蛋白表达较对照组明显升高。脑组织切片免疫荧光双标染色表明,Nrf2主要在神经元中特异性表达。结论依达拉奉可明显减轻大鼠脑出血后神经功能障碍及脑水肿程度,其机制可能与激活内源性抗氧化系统Nrf2通路发挥对神经元的保护作用有关。     

依达拉奉对局灶性脑缺血大鼠脑组织水通道蛋白-9mRNA表达的影响

目的探讨大鼠局灶性脑缺血后脑内水通道蛋白-9（AQP-9mRNA）表达与脑水肿动态变化的关系,评价依达拉奉的干预作用。方法216只雄性Sprague—Dawley（SD）大鼠随机分为3组：假手术组（A组,6只）,生理盐水组（B组,大脑中动脉阻断后6h、12h、24h、48h、72h、5d、7d7个时点,各6只）,依达拉奉处理组（C组,同B组）,术后即刻予以依达拉奉干预。分别测定脑组织含水量;实时荧光定量PCR（realtime quantitative polymerase chain reaction,RT—PCR）法检测mRNA表达;用HE染色方法观察病理形态学改变。结果B组大鼠MCAO后脑组织含水量呈上升趋势,48h达高峰,各时点均高于与A组（P〈0．05）。同时,AQP-9mRNA表达量与脑含水量呈相同趋势改变,相关性分析表明AQP-9mRNA表达量（r=0．788,P〈0．05）与脑组织含水量呈正相关。B组与C组相比,各时点脑组织含水量明显下降（P〈0．05）;AQP-9mRNA表达显著下调（P〈0．05）;组织病理提示脑水肿及神经元损伤程度减轻。结论大鼠脑缺血后脑内AQP-9mRNA表达与脑水肿变化呈正相关,提示AQP-9可能参与大脑中动脉阻断后的脑水肿形成。依达拉奉干预可减少AQP-9mRNA的表达,从而减轻大鼠大脑中动脉阻断后脑水肿,减少神经元坏死,改善神经功能预后。     

依达拉奉对少突胶质细胞缺血性反应的保护作用研究

目的观察依达拉奉对脑缺血大鼠脑内少突胶质细胞（OLG）的影响。方法将雄性SD大鼠50只随机分为假手术组、对照组、依达拉奉组。采用四血管闭塞全脑缺血模型，制模后依达拉奉组大鼠分别按剂量0．3、1．0和3．0mg／kg依达拉奉腹腔注射每日1次，连续7d；构建缺血性脑损伤大鼠脑组织芯片，用免疫组化法检测皮质A285、少突胶质细胞表面标志物4（04）、2’，3’-环磷核苷酸水解酶（CNPase）蛋白表达变化。结果与假手术组比较，对照组皮质A285阳性细胞数增多，04、CNPase阳性细胞数减少（均P（0．05）；与对照组比较，依达拉奉干预后A285阳性细胞数有不同程度减少，O4、CNPase阳性细胞数有不同程度增加（1mg／kgP〈0．05，3mg／kgP〈0．01）。结论一定剂量的依达拉奉对OLG缺血性反应有保护作用，呈现剂量依赖性。     

依达拉奉对大鼠脑缺血再灌注后IL-1β表达的影响

目的 观察依达拉奉对IL-1β表达的影响,探讨它的保护作用及机制.方法 Wistar雌、雄性大鼠共42只,随机分为假手术组、盐水对照组及依达拉奉用药组,对照组及用药组再进一步分为3h、6h、24h组,根据Koizumi线栓法建立大鼠左侧大脑中动脉缺血再灌注模型(MCAO),用免疫组化方法检测IL-1β表达的变化.结果 鼠脑缺血再灌注后缺血区脑组织 IL-1β含量,假手术组几乎无表达,盐水组IL-1β表达3h开始升高,于6h到高峰,后逐渐下降.用药组IL-1β的含量较盐水组减少(P＜0.05).结论 依达拉奉可减少大鼠脑缺血再灌注后IL-1β表达,起到脑保护作用.     

川芎嗪对脑挫伤大鼠脑组织MDA、SOD、NO及含水量影响的研究

目的 观察川芎嗪对脑挫伤大鼠脑组织中丙二醛（MDA）、超氧化物歧化酶（SOD）、一氧化氮（NO）含量及脑组织含水量的影响，探讨川芎嗪在治疗脑挫伤中的应用。方法 建立自由落体大鼠脑挫伤模型，治疗组脑挫伤后第2天开始应用川芎嗪腹腔注射治疗，对照组腹腔注射等量生理盐水．连续应用6d。正常组不致伤。检测治疗组、对照组及正常组大鼠脑组织中MDA、SOD、NO含量及脑组织含水量，并进行统计分析。结果 脑挫伤后大鼠脑组织中MDA、NO含量及脑组织含水量较正常组增高，SOD含量较正常组降低（P〈0．05）。川芎嗪治疗组大鼠脑组织中MDA、NO含量及脑组织含水量较对照组显著降低，SOD含量较对照组显著上升（P〈0．05）。结论 川芎嗪能够有效提高挫伤后脑组织中SOD含量，减少MDA及NO含量产生．有效改善脑水肿，从而发挥治疗作用。     

依达拉奉对脑出血大鼠脑组织丙二醛含量、超氧化物歧化酶活力及脑水含量的影响

目的研究依达拉奉对实验性脑出血大鼠氧自由基反应及脑水含量的影响。方法采用立体定向自体血注入法制作实验性脑出血大鼠模型,依达拉奉组在制作模型前后给予依达拉奉腹腔注射;脑出血组大鼠不予干预;脑组织氧自由基丙二醛(MDA)含量测定采用硫代巴比妥酸法,超氧化物歧化酶(SOD)活力测定采用黄嘌呤氧化法,脑水含量测定采用干湿重法。并与假手术大鼠(对照组)比较。结果脑出血组MDA含量较对照组显著增加(P<0.01)、SOD活力显著降低(P<0.01)、脑水含量增加(P<0.05～0.01)。依达拉奉治疗组与脑出血组比较,在脑出血后1d、3d、7dMDA含量均显著降低(P<0.05～0.01),SOD活力显著提高(P<0.05～0.01),脑水含量降低(均P<0.05)。结论依达拉奉能降低实验性脑出血大鼠脑组织MDA含量、提高SOD活力、减轻脑水肿,对实验性脑出血大鼠有脑保护效应。     

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。     

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。     

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.     

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.

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.     

Effects of Agonists and Antagonists of Cholecystokinin on Contractile and Myoelectric Activity of Isolated Muscle of Colon and Ileum in the Dog and Guinea Pig

This study evaluates the effects of agonists and antagonists of cholecystokinin (CCK) on contractile and myoelectrical activity in isolated longitudinal muscle strips from colon or ileum of guinea pigs or beagle dogs. Caerulein and CCK-8 caused a dose-dependent increase of contractile and myoelectrical spike activity in both species with maximal effects seen between 10⁻⁸ and 3 × 10⁻⁸ M. The dose responses were identical for both CCK agonists and species. The dose-related effects of CCK compounds on colonic muscle were slightly shifted to the right when compared to ileum in both species. All antagonists, the proglumide-derivatives CR1409, CR1392, and CR1505, as well as the nonpeptide substances asperlicin and L-364,718, caused a parallel rightward shift of CCK's dose-dependent motor activity response, indicating the competitive nature of inhibition. The antagonists displayed a rank order of potency in antagonizing CCK's action on intestinal motility similar to their ability to antagonize CCK's action on pancreas and gallbladder. L-364,718 was the most potent antagonist, followed by CR1409, CR1505, CR1392, asperlicin, and proglumide. The antagonists did not affect contractile or myoelectrical responses to acetylcholine, histamine, motilin, or substance P. Thus compounds that have been described as CCK antagonists for pancreas and gallbladder also act as specific and competitive antagonists of CCK's action on contractile and myoelectrical activity of Heal and colonie muscle.     

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.     

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.     

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.