低频脉冲磁场对全脑缺血再灌注大鼠脑电图及海马神经细胞的作用

目的探讨经颅低频脉冲磁场对全脑缺血再灌注大鼠海马神经细胞的作用。方法将24只SD大鼠随机分成对照组和磁辐射组，每组各12只，应用改良的Pulsineli4-VO法制做大鼠全脑缺血再灌注模型，磁辐射组在脑缺血模型完成后立即将其头颈部置磁场（20mT、10Hz）中轴中央，身体顺磁场方向放置，辐射45min，每天1次，作用4次后将大鼠记录脑电图后断头取脑，对照组同时处死断头取脑，应用Nissl染色及免疫组织化学方法进行海马神经细胞计数及凋亡相关基因caspase-3蛋白表达检测。结果磁疗组较对照组神经元数量多（P〈0．05），脑电图频率和波幅增高（P〈0．05），caspase-3蛋白表达低（P〈0．05）。结论低频脉冲磁场（20mT、10Hz）可以抑制大鼠脑缺血再灌注海马神经元的凋亡，对脑缺血再灌注损伤有保护作用。     

银杏叶提取物对缺血再灌注大鼠脑梗死体积及半胱氨酸蛋白酶表达的影响

目的研究银杏叶提取物(EGb)对缺血再灌注大鼠脑梗死体积及半胱氨酸蛋白酶(caspase)-3表达的影响。方法用线栓法制作脑缺血再灌注大鼠模型。小剂量EGb组及大剂量EGb组大鼠于实验前30min和缺血后1h分别予以EGb50mg/kg、100mg/kg腹腔注射。用氯化三苯四氮唑染色和免疫组化染色法观察大鼠脑梗死体积与脑组织caspase-3阳性细胞数;并与缺血再灌注组比较。结果小剂量EGb组和大剂量EGb组大鼠脑梗死体积[(83.4±2.9)mm3,(37.0±2.5)mm3]明显小于缺血再灌注组[(138.8±6.1)mm3](均P<0.01);脑组织caspase-3阳性细胞数[(12.15±1.42)、(7.41±1.55)个/高倍视野]明显少于缺血再灌注组[(26.85±1.63)个/高倍](均P<0.01);大剂量EGb组脑梗死体积及脑组织caspase-3阳性细胞数比小剂量EGb组明显减少(均P<0.01)。结论EGb可以减小缺血再灌注大鼠的脑梗死体积以及抑制caspase-3蛋白的表达;并且大剂量EGb的效果比小剂量EGb的更好。     

脑缺血后脑室内注射胰岛素减轻大鼠学习记忆力损害的实验研究

目的探讨经脑室直接注射胰岛素对全脑缺血后大鼠学习记忆力的影响.方法以4-VO法建立大鼠全脑缺血再灌注模型.全脑缺血20min后行再灌注,于再灌注即刻经脑室注入1U胰岛素,缺血再灌注后8周利用三等分Y型迷宫箱测试大鼠的学习记忆功能,并对大鼠海马CA1区神经元的病理改变进行观察.结果经Y型迷宫测试,对照组、治疗组及缺血组大鼠达9/10正确反应所需电击数分别为5.6±1.2,8.6±1.3,19.6±2.6;对照组、治疗组及缺血组大鼠海马CA1区神经元计数分别为176.5±10.6,112.4±11.7,10.5±0.4.结论全脑缺血后脑室内注射胰岛素可明显减少大鼠海马CA1区神经元的死亡,进而减轻大鼠学习记忆力损害.     

达纳康抑制大鼠局灶性脑缺血再灌注损伤后P^53蛋白表达及细胞凋亡的研究

目的研究达纳康在大鼠局灶性脑缺血再灌注损伤中的脑保护作用及其分子机制.方法采用线栓法建立大鼠大脑中动脉(MCAO)缺血1h再灌注24h模型,18只雄性大鼠随机分为假手术组、生理盐水对照组和达纳康治疗组,每组6只.采用Zea-Longa评分法观察神经功能缺损程度,采用免疫组织化学方法、TUNEL法分别观察各组P53蛋白表达和细胞凋亡.结果假手术组神经功能缺失评分为0分,高倍视野下无P53蛋白染色阳性细胞及凋亡细胞;达纳康治疗组神经功能缺失评分(0.48±0.37分)、P53蛋白染色阳性细胞数(5.16±1.84个/高倍视野)、凋亡细胞数(4.18±1.21个/高倍视野)均较生理盐水对照组(2.76±0.82分、10.43±1.56个/高倍视野、8.16±1.50个/高倍视野)显著减少(P<0.01).结论达纳康可明显减轻局灶性脑缺血再灌注损伤,其抑制神经细胞P53蛋白的表达,进而抑制细胞凋亡,是其脑保护作用的分子机制之一.     

达纳康抑制大鼠局灶性脑缺血再灌注损伤后P~(53)蛋白表达及细胞凋亡的研究

目的　研究达纳康在大鼠局灶性脑缺血再灌注损伤中的脑保护作用及其分子机制。方法　采用线栓法建立大鼠大脑中动脉 ( MCAO)缺血 1h再灌注 2 4 h模型 ,18只雄性大鼠随机分为假手术组、生理盐水对照组和达纳康治疗组 ,每组 6只。采用 Zea- L onga评分法观察神经功能缺损程度 ,采用免疫组织化学方法、TUNEL 法分别观察各组 P53蛋白表达和细胞凋亡。结果　假手术组神经功能缺失评分为 0分 ,高倍视野下无 P53蛋白染色阳性细胞及凋亡细胞 ;达纳康治疗组神经功能缺失评分 ( 0 .4 8± 0 .3 7分 )、P53蛋白染色阳性细胞数 ( 5 .16± 1.84个 /高倍视野 )、凋亡细胞数 ( 4 .18± 1.2 1个 /高倍视野 )均较生理盐水对照组 ( 2 .76± 0 .82分、10 .4 3± 1.5 6个 /高倍视野、8.16± 1.5 0个 /高倍视野 )显著减少 ( P<0 .0 1)。结论　达纳康可明显减轻局灶性脑缺血再灌注损伤 ,其抑制神经细胞P53蛋白的表达 ,进而抑制细胞凋亡 ,是其脑保护作用的分子机制之一。     

经颅磁刺激对脑梗死大鼠学习记忆与健侧海马锥体细胞树突和突触结构的影响

目的研究经颅磁刺激(TMS)对脑梗死后大鼠学习记忆功能,以及海马锥体细胞树突和突触结构的影响。方法将48只雄性SD大鼠随机分为正常组、模型组和TMS组,每组16只。采用线栓法对模型组和TMS组大鼠制作一侧大脑中动脉闭塞的脑梗死模型,并在制模后第2天,对TMS组给予每天2次、每次30个脉冲的TMS治疗,疗程4周;观察各组大鼠治疗后在Y-迷宫中的学习记忆成绩和梗死对侧海马锥体细胞树突和突触结构变化。结果(1)TMS组大鼠学习尝试次数[(18.4±4.8)次]少于模型组[(26.4±5.4)次;P<0.01],记忆再现次数[(6.1±1.3)次]多于模型组[(3.7±1.2)次;P<0.01];(2)TMS组海马CA3区锥体细胞树突顶树突总长度[(196±35)μm]长于模型组(175±33)μm;P<0.01]。(3)TMS组的突触后致密物质厚度[(68±11)nm]宽于模型组[(62±10)nm],穿孔性突触百分比(27.5%)高于模型组(10.0%),突触间隙[(16.7±1.8)nm]窄于模型组[(21.3±2.3)nm],均P<0.01和P<0.05。结论TMS能促进脑梗死大鼠学习记忆功能的恢复,其机制可能与海马锥体细胞树突和突触结构的改变有关。     

脑梗死患者海马β-淀粉样蛋白的表达

目的研究人脑梗死后β-淀粉样蛋白(Aβ)1-40和Aβ1-42在海马CA1区神经元中的表达。方法选取因脑梗死而死亡的尸检脑标本43例,并按缺血时间(发病至死亡时间)分为7组,选取因其他疾病死亡(非脑缺血)的尸检脑标本6例为对照组;应用苏木素-伊红(HE)染色方法观察海马神经元形态变化;应用Aβ1-40和Aβ1-42免疫组织化学方法检测人脑梗死后海马CA1区两种蛋白在神经元中的表达情况;用末端脱氧核糖转移酶介导的dUTP缺口末端标记技术(TUNEL)标记凋亡神经元。结果海马CA1区,对照组Aβ1-40和Aβ1-42在神经元中均有微量表达,并且于缺血2 h后表达均迅速增加,Aβ1-40在72 h后达高峰[(36.30±2.67)个/高倍视野],Aβ1-42在24~47 h达高峰[(30.87±4.62)个/高倍视野],以后有所回落,但仍高于对照组。缺血6~23 h可检测到TUNEL阳性细胞,48~71 h达高峰[(27.56±6.76)个/高倍视野]。2~5 h受损神经元形态基本正常,24~47 h神经元形态学变化较为明显,72 h后,大部分神经元出现坏死特征。结论人脑梗死后海马CA1区Aβ1-40和Aβ1-42在神经元中的表达均增加,表明脑缺血可能导致这两种蛋白的聚集,同时Aβ的毒性作用可能对脑梗死后CA1区神经元的迟发性死亡起着一定的作用。     

脑缺血大鼠再灌注后脑皮质中PC1mRNA及蛋白质的表达

背景：前蛋白转化酶（Proprotein convertases,PCs)是神经肽的加工酶,前蛋白转化酶1（Proprotein convertase 1,PC1) 是PCs家族中的一员, PC1加工许多神经肽及肽类激素,已有研究表明PC1对应激高度敏感,但尚不明确脑缺血后PC1的变化。 目的: 观察局灶性脑缺血后大鼠脑皮层内PC1mRNA 及PC1的经时表达变化。 设计：完全随机设计,对照实验研究。 地点和材料：美国俄勒冈州波特兰Robert S. Dow 神经生物研究室, Legacy 临床研究与技术中心,所有动物实验均遵照国家健康指南中实验室动物养护及使用制度,雄性健康Sprague–Dawley 大鼠 (250 g--300 g) 购自美国Wilmington的Charles River实验室。 干预: 用大脑中动脉阻塞(MCAO)的方法建立短暂性局灶性脑缺血模型,用原位杂交及免疫组化双标法分析假手术对照组大鼠及100分钟MCAO后再灌注4小时、8小时、16小时及24小时大鼠脑皮层内PC1mRNA及PC1表达的变化。 主要观察指标: 100分钟MCAO后再灌注4小时、8小时、16小时及24小时大鼠缺血脑皮层、非缺血脑皮层内及假手术对照大鼠脑皮层内PC1mRNA及PC1表达的变化。 结果: 假手术对照大鼠及100分钟MCAO后再灌注4小时、8小时、16小时及24小时大鼠缺血侧及非缺血侧脑皮层表达PC1mRNA的细胞数分别是每高倍镜视野35.6 ±4.3及36.2±3.6,29.6±5.1及36.1 ±4.1,30.1±4.6及35.8±4.3,28.2 ±4.9及35.9 ±5.2,18.2±5.3及35.6±4.9,而表达PC1的细胞数分别是每高倍镜视野28.2 ±3.3及28.8±4.1,17.8±4.2及29.1±3.6,17.6±4.6及28.7±3.6,18.1±3.9及29.3 ±4.5,22.3±3.2及29.0±4.1。缺血侧脑皮层PC1mRNA及PC1的表达在再灌注4小时、8小时及16小时逐渐下降,在再灌注24小时时下降最显著,缺血侧脑皮层PC1表达水平在再灌注24小时较再灌注4小时、8小时及16小时增高,而此时PC1mRNA表达水平仍低。 结论: 局灶性短暂脑缺血可影响大鼠缺血脑皮层内PC1mRNA及PC1的表达,缺血性应激可调节PC1。     

CGRP和NGF对脑局部缺血再灌注大鼠脑组织神经元凋亡及PKCmRNA表达的调节作用

目的研究大鼠脑缺血再灌注后蛋白激酶C信使RNA(PKCmRNA)的表达,探讨降钙素基因相关肽(CGRP)和神经生长因子(NGF)对脑组织缺血再灌注的保护作用及机制。方法采用颈动脉负压分流法制作大鼠脑缺血再灌注模型,采用TUNEL法、原位杂交方法及显微图像分析检测海马及皮质内神经元凋亡和PKCmRNA的表达。结果大鼠缺血再灌注海马及顶叶皮质内神经元凋亡数及PKCmRNA反应产物较正常组增多(P<0.05),而注射CGRP或NGF后神经元凋亡数及PKCmRNA反应产物明显低于缺血再灌注组(P<0.01),二者联合应用效果更加显著(P<0.05)。结论CGRP和NGF抑制缺血神经元凋亡,参与PKCmRNA的调节,二者对缺血神经元有协同修复作用。     

白细胞介素8单克隆抗体对大鼠脑缺血再灌注损伤的保护作用

脑缺血再灌注损伤与炎症反应关系密切,白细胞介素8(IL8)作为一种中性粒细胞趋化因子,在脑缺血后炎症损伤中有重要作用[1]。我们设想IL8单克隆抗体(简称IL8单抗)可能对脑缺血再灌注损伤具有保护作用,在建立脑缺血再灌注模型基础上,侧脑室注射IL8单抗,通过观察脑梗死表1各组大鼠脑梗死灶体积及TUNEL、Bcl2及Bax阳性细胞数分组鼠数梗死灶体积(mm3)TUNELBcl2Bax生理盐水对照组6210.26±25.5845.82±7.0322.97±5.6470.16±8.54IL8单抗0.5μg组6207.25±28.5944.92±7.1124.46±6.3868.26±8.43IL8单抗1μg组6166.29±31.7338.87±7.1…     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Effects of NMD A- and AMPA-Receptor Antagonists on Different Forms of Epileptiform Activity in Rat Temporal Cortex Slices

Summary: Lowering extracellular magnesium induces different patterns of epileptiform activity in rat hippocampus and entorhinal cortex. Short recurrent epileptiform discharges in the hippocampus are stable over time, whereas seizurelike events (SLEs) in the entorhinal cortex, the subiculum, and the neighboring neocortex develop into late recurrent discharges which are not blocked by clinically employed antiepileptic drugs. We tested the sensitivity of the different epileptiform discharge patterns to. /V-methyl-D-aspartate (NMDA)- and non-NMDA-receptor antagonists. As NMDA-receptor antagonist we used dextrorphan, ket-amine, and 2-aminophosphonovalerate (2APV); as α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist we employed the quinoxaline derivative glutamate 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The findings show that the different patterns of epileptiform activity, including the late recurrent discharges, are sensitive to all NMDA-receptor antagonists. However, when dextrorphan was employed to suppress seizure-like events, later recurrent discharges did not develop during the remaining time course of the experiment. CNQX reversibly suppressed recurrent discharges in the hippocampus and SLEs in the entorhinal cortex. However, late recurrent discharges become insensitive to CNQX, even at a high concentration of 60 μM m. This finding suggests a prominent role for NMDA receptors in the generation of late recurrent discharges.     

The influence of comorbid depression on seizure severity

PURPOSE: To determine the relation between depressive symptoms and seizure severity among people with epilepsy. METHODS: A postal questionnaire was used to survey a nationwide community sample about seizures and depression. The Seizure Severity Questionnaire (SSQ) assessed the severity and bothersomeness of seizure components. The Centers for Epidemiological Studies-Depression scale categorized levels of depression. RESULTS: Respondents categorized as having current severe (SEV, n = 166), mild-moderate (MOD, n = 74), or no depression (NO, n = 443) differed significantly in SSQ scores (all p < 0.0001). People with SEV or MOD reported significantly worse problems than did those with NO depression for overall seizure recovery (mean, 5.3, 4.9, 4.5, respectively); overall severity (5.0, 4.5, 4.2); and overall seizure bother (5.3, 4.8, 4.4) (all p < 0.005). Cognitive, emotional, and physical aspects of seizure recovery also were rated worse among people with SEV than with NO depression (all p < 0.05). Symptoms of depression were significantly correlated with higher levels of all components of generalized tonic-clonic seizure severity (r = 0.33-0.48; all p < 0.0001), and partial seizures (r = 0.31-0.38; all p < 0.01). CONCLUSIONS: Clinically depressed people with epilepsy reported higher levels of perceived severity and bother from seizures, as well as greater problems with overall seizure recovery than did nondepressed people experiencing similar types of seizures. The pervasive influence of depressive symptoms on reports of seizure activity suggests that people with epilepsy should be screened for depression. These data highlight the importance of detecting and treating depression among people with epilepsy.     

Une phénoménologie de la dépendance à l'alcool. Une expérience primordiale de la « nostrité »

The phenomenological approach to alcoholism interestingly focuses on specific dynamics of interpersonal relationships displaying the founding of the Self from a primary “us” and its original basis in the human feast. Priorities for treatment intervention recommend to involve social setting and relationships of the patients, reaching their active participation to a motivational and long term group treatment, underlying the specific therapeutic effect of world exchanges. Biopsychosocial determination of alcoholism could be primarily based on components of interpersonal relationships. Regarding social background, drinking is one of the most famous supports for the achievement of the feast, a founding marker of present time. Taking an existential point of view, the feast appears as the heart of mankind because it presents a primary “us”, a plural state which indicates the beginning and founding of the Self from the others. During the feast, we regularly have to reach our Self from the “us” while avoiding two main dangers, drunkenness, an increase in the dizziness of upright verticality, and addiction, an opposite vertical surrender to alcohol and falling into in the alcoholic relapse, both situations imply a spatial domination and the disappearance of others. Treatment programs of alcohol addicts need to integrate the necessity of reaching the existential basic trust from the support of a group to the appropriation of the community which can be defined as an original “usness”.