星形胶质细胞及其炎症因子在CO中毒所致迟发性脑损伤中的作用

目的 探讨大鼠海马组织星形胶质细胞活化水平及炎症因子表达在急性一氧化碳中毒迟发性脑病(DEACMP)中的作用及可能的机制。方法 经Morris水迷宫训练筛选认知功能正常的SD雄性大鼠,随机分为实验组,对照组,实验组大鼠采用静态吸入法置备DEACMP模型。分别于中毒后7d、14d、21d各时间点通过Morris水迷宫比较两组学习记忆能力;苏木精-伊红染色观察海马病理损伤程度;免疫荧光法和Western blot法检测海马区星形胶质细胞特异性标志物(GFAP)的表达情况;ELSIA法检测海马组织中TNF-α、IL-1β、IL-6表达水平。结果①大鼠表现出典型的CO中毒症状;②Morris水迷宫结果表明,实验组第7天大鼠水迷宫逃避潜伏期无明显差异(P>0.05);实验组14d、21d水迷宫逃避潜伏期逐渐延长,与对照组相比差异有统计学意义(t=2.60、t=5.56,P<0.05);③苏木精-伊红染色与对照组相比,实验组海马细胞出现不同程度的细胞损伤;④免疫荧光结果统计显示,实验组第7天、14天、21天的海马CA1区GFAP表达明显增多,与对照组相比差异有统计学意义(t=-5.20...     

丙戊酸钠对慢性酒中毒模型大鼠学习记忆损害的影响

目的探讨慢性酒中毒对大鼠学习记忆的影响及丙戊酸钠(VPA)的干预效应及其可能机制。方法将56只SD大鼠随机分为酒中毒模型组、VPA干预组、VPA对照组和正常对照组。以乙醇浓度梯度递增式的方式灌胃8周制作慢性酒中毒模型,而第5周始酒中毒模型组腹腔注射生理盐水,VPA干预组于第5～8周腹腔注射VPA,VPA对照组灌注等体积的生理盐水4周后第5～8周给予VPA。8周后每组随机选取7只采用Morris水迷宫和Y迷宫检测大鼠的学习记忆功能,其余7只用Westernblot检测海马脑源性神经营养因子(BDNF)蛋白的表达含量。结果与正常对照组相比,酒中毒模型组大鼠水迷宫的逃避潜伏期显著延长(P0.05),空间探索次数显著减少(P0.05);Y迷宫中2d的错误次数显著增加(P0.01);海马BDNF含量下降(P0.05)。与酒中毒模型组相比,VPA干预组大鼠的行为学成绩均得到改善(P0.01),海马BDNF含量显著增加(P0.01),与正常对照组的差异无统计学意义(P0.05)。VPA对照组与正常对照组各项指标的差异均无统计学意义(P0.05)。结论慢性酒中毒可以导致大鼠学习记忆障碍,而VPA对酒精诱导的学习记忆损害有干预作用,海马BDNF表达增加可能是其作用机制之一。     

粒细胞集落刺激因子对血管性痴呆大鼠海马神经细胞凋亡的影响

背景：研究发现，粒细胞集落刺激因子可激活脑内成体神经干细胞，刺激其增殖和分化，还能促进脑内各种神经营养因子分泌，减小脑缺血动物模型的缺血灶，促进慢性脑卒中模型缺失神经功能的长期恢复。 目的：观察粒细胞集落刺激因子对血管性痴呆大鼠海马神经细胞凋亡的作用。 方法：采用永久性双侧颈总动脉结扎法建立大鼠血管性痴呆模型，抽签法随机分为4组：实验组(皮下注射粒细胞集落刺激因子干预治疗)、对照组(注射生理盐水)、假手术组(仅行颈前正中切开，不结扎颈总动脉)。采用Morris水迷宫进行定向航行观察大鼠逃避潜伏期，评价大鼠空间学习记忆能力，TUNEL染色和图像分析大鼠海马神经细胞的凋亡。 结果与结论：对照组和实验组大鼠脑缺血后7 d，大鼠平均逃避潜伏期较假手术组明显延长(P < 0.01)，海马组织TUNEL阳性凋亡细胞较假手术组显著增高(P < 0.01)，随着时间的延长，14，28 d时大鼠学习记忆功能障碍逐渐加重，相应海马组织TUNEL阳性凋亡细胞逐渐增加。14，28 d时实验组大鼠平均逃避潜伏期比对照组明显缩短，海马组织TUNEL阳性凋亡细胞也较对照组显著减少。说明脑缺血后早期给予外源性粒细胞集落刺激因子有助于减少海马组织神经细胞的凋亡，改善大鼠学习记忆能力。     

睡眠节律紊乱复制Alzheimer样大鼠模型的研究探讨

目的探讨睡眠节律紊乱对大鼠记忆能力、超微结构、海马Aβ含量和tau蛋白磷酸化的影响及机制,评价一种非创伤性老年性痴呆大鼠模型的构建方法。方法雄性Wistar大鼠36只,随机均分为正常对照组、弱光组(照度400 lux,24 h持续光照)、强光组(照度800 lux,24 h持续光照),每组12只。光照30 d后,Morris水迷宫检测大鼠空间记忆能力,透射电镜观察海马超微结构的改变,放射免疫法检测海马Aβ含量,免疫组织化学法和Western blot检测海马tau蛋白磷酸化水平。结果与正常对照组比较,弱光组和强光组大鼠寻台潜伏期均显著延长;正常对照组大鼠海马组织超微结构正常;弱光组和强光组大鼠海马组织线粒体肿胀,线粒体嵴模糊或消失,结构破坏;神经突触减少甚至缺失,突触间隙模糊,突触小泡数量减少;海马组织Aβ含量增高,海马CA3区神经纤维tau蛋白磷酸化阳性细胞个数增加,蛋白表达水平增高,差异具有统计学意义(P<0.05)。结论睡眠节律紊乱诱导的老年性痴呆动物模型在一定程度上模拟其发病特点,可以用于Alzheimer’s发病机制及其治疗药物的研究。     

P2Y1受体介导星形胶质细胞的激活在急性一氧化碳中毒迟发性脑病中的作用

目的 探讨P2Y1受体和星形胶质细胞在急性一氧化碳(CO)中毒迟发性脑病(DEACMP)中的作用以及DEACMP可能的发病机制。方法 经水迷宫实验筛选认知功能合格的雄性SD大鼠，随机分为两组：对照组、CO中毒组，CO中毒组制作DEACMP模型，分别于造模后第7天、第14天、第21天、第28天对比两组行为学改变，神经元变化以及海马组织中P2Y1受体和星型胶质细胞的表达。结果 通过水迷宫发现与对照组相比，造模后第21天、第28天CO中毒组大鼠逃避潜伏期均明显延长(P<0.05);HE染色发现造模后第14天、第21天、第28天模型组大鼠海马锥体细胞及神经元坏死明显，结合水迷宫可表明大鼠在21 d时出现DEACMP;与对照组相比，Western blot法检测提示各时间点CO中毒组海马区P2Y1及GFAP蛋白表达均增多(P<0.05),呈先升高后降低的趋势；免疫荧光表明海马区P2Y1和GFAP存在共表达，相对于对照组，中毒后各时间点海马CA₁区P2Y1和GFAP都有表达上调(P<0.05)。结论 P2Y1受体对星形胶质细胞的激活可能是DEACMP的发病机...     

C-Jun氨基末端激酶信号通路在急性一氧化碳中毒迟发性脑病中的作用

目的探讨c-Jun氨基末端激酶(c-Jun N-terminal kinas,JNK)信号通路在急性一氧化碳中毒迟发性脑病中的作用。方法 120只雄性SD大鼠随机分成空白对照组(BC组)、急性一氧化碳中毒迟发性脑病组(CO组)和JNK抑制剂SP600125组(SP组)3组,每组40只,采用静态吸入式染毒法复制急性一氧化碳中毒迟发性脑病大鼠模型,选取染毒后1、3、7、14、28 d为时相点,应用Morris水迷宫试验检测平均潜伏期等学习记忆能力,免疫组化法检测海马区p-JNK表达,Tunel法检测海马区锥体细胞凋亡。结果 CO组大鼠平均潜伏期较BC组明显延长(P0.01),SP组较CO组明显缩短(P0.01),但仍比BC组延长(P0.01);p-JNK在CO组大鼠海马区表达较BC组明显增强(P0.01),SP组较CO组表达明显减弱(P0.01),较BC组明显增强(P0.01);CO组海马区锥体细胞第3天已经有凋亡增多(9.94%±1.22%),第7和14天增多最明显(39.77%±1.91%,29.72%±4.89%),第28天仍然增多(5.88%±0.55%),凋亡指数与BC组相比有明显增高(P0.01),而SP组凋亡指数与CO组相比明显降低(P0.01)。结论 JNK信号通路参与了急性一氧化碳中毒迟发性脑病的发生,应用其特异性抑制剂SP600125阻断其转导可减少海马区神经元的凋亡,减轻急性CO中毒对学习记忆能力的损害。     

β-胡萝卜素对阻塞性睡眠呼吸暂停综合征大鼠学习记忆及海马区caspase-3 、磷酸化tau表达的影响

目的探讨β-胡萝卜素(β-C)对阻塞性睡眠呼吸暂停综合征(OSAS)大鼠学习记忆及海马区caspase-3、磷酸化tau蛋白表达的影响。方法将24只成年SD大鼠随机分为正常对照组、单纯OSAS模型组(模型组)和OSAS模型组+β-C干预组(干预组),每组8只。采用低氧舱建立OSAS大鼠动物模型。模型组及干预组小鼠于造模前给予β-C灌胃,正常组不做任何处理。造模完成后,采用Morris水迷宫检测实验大鼠的学习和记忆能力,HE染色观察大鼠海马组织的病理学改变,采用Western Blotting法检测海马组织中caspase-3、p-tau的蛋白表达变化。结果模型组大鼠各时间点逃避潜伏期时间较正常对照组显著延长(均P 0. 05);干预组第2～5 d逃避潜伏期较模型组显著缩短(均P 0. 05)。模型组穿越平台次数明显少于正常对照组和干预组(均P 0. 05)。与模型组比较,正常对照组与干预组caspase-3、p-tau蛋白表达显著降低(均P 0. 05)。结论β-C可减轻OSAS所致的学习记忆能力受损,其机制可能与其抑制caspase-3、p-tau的蛋白表达有关。     

行为训练对双侧海马梗死大鼠学习记忆与NCAM的影响

目的探讨行为训练对双侧海马梗死大鼠空间学习记忆功能恢复及海马神经细胞粘附因子(NCAM)的影响及其作用机制。方法30只SD大鼠采用光化学诱导法制作双侧海马CA1区梗死模型,于24h后随机分为行为训练组和制动组,于造模3d后分别给予行为训练或制动,在大鼠造模后3d、行为训练后7d、14d和21d时进行学习记忆能力测试。并于不同时间取脑进行免疫组织化学染色,观察其梗死灶海马周围NCAM含量的变化。结果行为训练组学习记忆能力评估均优于制动组(P<0.05),海马NCAM含量均较制动组增多。结论行为训练可促进大鼠空间学习记忆能力的恢复,其作用机制可能与海马NCAM的增多有关。     

灵芝多糖对模拟AD学习记忆障碍大鼠海马白细胞介素-6表达的影响

目的 研究灵芝多糖对模拟AD学习记忆障碍大鼠脑组织白细胞介素-6表达（IL-6）的影响。方法 采用双侧海马内一次性注射β-淀粉样多肽25～35片段（Aβ25～35）制作模拟AD学习记忆障碍大鼠模型，造模24h后治疗组腹腔注射灵芝多糖注射液，其余各组分别注射等量的生理盐水，1次/d，疗程7d，并于第8d开始进行Morris水迷宫实验观察其学习记忆能力，行为学检测后再通过免疫组化SABC法检测各组大鼠海马IL-6表达水平。结果 模型组大鼠较对照组学习记忆能力降低，海马IL-6表达明显增强；治疗组大鼠较模型组学习记忆能力显著提高，海马IL-6表达显著下调。结论 灵芝多糖可提高Aβ25-35诱导的模拟AD学习记忆障碍大鼠的学习记忆能力，抑制海马IL-6表达。     

高原环境对睡眠剥夺大鼠学习记忆的影响

目的探讨高原环境对睡眠剥夺(SD)大鼠学习记忆及海马5-HT表达的影响。方法64只大鼠被随机分为可可西里组(海拔4767m)和兰州组(海拔1520m)。各组大鼠又分为正常睡眠及SD1d、3d和5d4个亚组。采用小平台水环境法(flowerpot)建立大鼠SD模型。各组大鼠行Morris水迷宫测试,免疫组化法检测海马组织中5-HT的含量。结果Morris水迷宫显示,在可可西里组和兰州组中,与正常睡眠大鼠比较SD1d、3d及5d大鼠的潜伏期延长(P0.05),游泳路程增加(P0.05);以及穿越平台次数减少(P0.05)。与兰州组比较,可可西里组的正常睡眠及SD1d、3d和5d大鼠的潜伏期延长(P0.05),游泳路程增加(P0.05),穿越平台次数减少(P0.05或P0.01)。海马5-HT含量检测中可可西里组SD1d、3d及5d大鼠的含量均高于正常睡眠大鼠(P0.05);兰州组SD3d及5d大鼠的含量均高于正常睡眠大鼠(P0.05);与兰州组相比,可可西里组正常睡眠、SD1d、3d和5d大鼠的5-HT含量增加(P0.05)。结论高原环境暴露可使SD大鼠学习记忆能力进一步降低,其机制可能与海马中5-HT含量增高有关。     

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.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

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.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

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.