胍丁胺对戊四氮诱导慢性癫癎大鼠的保护作用和海马星形胶质细胞表达的影响

目的:探讨不同剂量胍丁胺对戊四氮诱导的慢性癫癎大鼠模型的保护作用及对海马区星形胶质细胞表达的影响。方法:连续28 d腹腔注射戊四氮35 mg.kg-1建立大鼠慢性癫癎模型。不同剂量胍丁胺(20、40、80 mg.kg-1)进行干预。观察大鼠癫癎发作行为学及海马的形态学变化,检测海马星形胶质细胞的表达。结果:胍丁胺40、80 mg.kg-1可降低癫癎发作的日均等级评分,减少海马神经元丢失及星形胶质细胞增生。结论:胍丁胺40、80 mg.kg-1可抑制慢性癫癎大鼠发作,降低惊厥发作后海马星形胶质细胞的异常增生及神经元损伤。     

红藻氨酸诱发大鼠复杂部分性癫癎发作的海马神经元和星形胶质细胞反应及相互关系

目的:观察大鼠癫发作后海马内神经元与星形胶质细胞反应变化的时空效应及相互关系。方法:以红藻氨酸诱发的大鼠复杂部分性癫发作为模型,利用免疫组织化学法,在原位显示癫发作后153、0、60、901、20、180 min 6个时间点海马神经元Fos蛋白及星形胶质细胞内胶质原纤维酸性蛋白(GFAP)的表达变化、相互关系及分布规律。结果:致后15 min海马内GFAP表达开始增多,60 min达高峰。Fos阳性神经元在癫诱发后30 min开始出现,120 min达高峰。海马内GFAP阳性细胞与Fos阳性神经元分布规律基本一致。结论:在癫病理状态下,海马内星形胶质细胞的反应略早于神经元,两者之间分布呈平行关系,它们之间可能存在着复杂的信息通讯,以复合体的形式共同对各种病理生理刺激作出反应。     

红藻氨酸诱导癫(癎)发作大鼠海马星形胶质细胞C-FOS基因表达的研究

目的研究癫发作大鼠海马星形胶细胞C-FOS基因表达的变化,探讨其对癫发作的维持与复发的影响。方法将83只成年雄性SD大鼠随机分为实验组58只,对照组25只。实验组在海马CA3区注射红藻氨酸(Kainicacid,KA)建立癫模型,对照组在相同部位注射等量生理盐水。利用免疫组织化学双重染色技术,分别在癫发作后1h、3h、6h、12h和24h观察大鼠海马星形胶质细胞C-FOS基因的表达。结果与对照组大鼠比较,癫模型鼠海马CA1区CFAP/C-FOS双标记阳性细胞百分率于癫发作后1h(12.70±0.03)、3h(17.10±0.05)、6h(24.92±0.04)明显升高(P<0.01),在6h达到高峰,在12h下降,但是仍较对照组高(10.71±0.06;1.59±0.02,P<0.01),在24h下降至对照组水平(2.00±0.02;2.08±0.03,P>0.05)。结论KA诱导大鼠癫发作,导致海马星形胶质细胞C-FOS基因相对持续的高表达,从而激活星形胶质细胞,产生高致性的病理环境,可能是癫发作的维持以及复发的病理生理机制之一。     

抗癫癎药物致癎作用的临床观察

目的研究抗癫癎药物(AEDs)的致癎作用及对其的预防和治疗.方法总结32例AEDs致癫癎发作加重患者的临床资料.结果32例中以服用卡马西平最多(19.12%)、次之为巴比妥类药物(15%)、苯妥英钠(14.5%)、合并用药(14.29%)、苯二氮( )类(8.69%)、丙戊酸钠(2.78%).32例经停药并合理选择其他抗癫癎药物及减少药物剂量治疗,27例有效,5例无效.结论AEDs能致癫癎发作加重,应合理选择抗癫癎药物.     

马桑内酯点燃效应癫癎动物模型海马区星形胶质细胞的形态学研究

采用马桑内酯（coriarialactone，CL）肌注造成大鼠化学点燃效应癫动物模型并经光镜、电镜、突触素（synaptophysin）免疫组化方法对大鼠脑组织进行观察，发现，大鼠海马区星形胶质细胞有明显变性坏死。提示马桑内酯对星形胶质细胞有损伤性作用，星形胶质细胞的变性坏死可能在诱导癫发作中起重要作用。     

抗癫癎药物对癫癎发作后状态影响研究进展

癫癎发作后状态(PIS)是癫癎发作结束后患者的综合临床表现。PIS与癫癎患者持续的认知功能变化,抗癫癎药物(AEDs)的选择及长期保留率有关,并影响患者生活质量。新、老AEDs对PIS的冶疗效果至今未被明确阐述。目前,AEDs对PIS的疗效已被引起重视,并逐步纳入AEDs总体评价指标。本文对此进行综述。     

成人幕上脑胶质母细胞瘤术后癫癎发作的预防

目的探讨成人幕上脑胶质母细胞瘤（GBM）术后预防性应用抗癫癎药物对癫癎发作的影响。方法回顾性分析86例术前无癫癎发作的幕上GBM病例资料,根据病人术后预防性应用抗癫癎药物情况分为对照组（不使用抗癫癎药物）、研究1组（使用抗癫癎药物4周）和研究2组（使用抗癫癎药物24周）,统计术后癫癎发作情况和术后24周各组Karnofsky评分。结果术后4周内出现癫癎发作对照组5例（16．7％）,研究组1例（1．8％）,两组癫癎发作有显著性差异（P〈0．05）。术后5～24周新发癫癎发作对照组7例（23．3％）．研究1组7例（25．0％）,研究2组1例（3．6％）,研究2组新发癫癎发作屁著低于对照组和研究1组（P〈0．05）。研究2组术后24周Karnofsky评分为66．96±10．30,明显高于对照组和研究1组（P〈0．05）。结论预防性应用抗癫癎药物可减少GBM术后癫癎发作发病率,术后癫癎发作治疗困难且影响生活质量,术后预防性应用抗癫癎药物应当不少于24周。     

抑制胶质细胞增生对创伤性癫癎大鼠神经胶质细胞谷氨酸转运的影响

目的　探讨海马胶质细胞增生和谷氨酸转运异常在铁离子诱发创伤性癫大鼠发病机制中的作用,以及胶质细胞增生对谷氨酸转运体表达的影响。方法　36只SD大鼠随机分3组,A组单侧杏仁核内注射生理盐水,B组仅注射氯化铁,C组注射氯化铁后,静脉注射含7β羟基胆固醇的脂质包被微泡。动态观察大鼠脑电图和行为改变,并用免疫组化、免疫印迹方法观察鼠脑海马胶质纤维酸性蛋白(glialfibrillaryacidicprotein,GFAP)在注射氯化铁后15d的表达,同时应用逆转录聚合酶链反应(RT -PCR)检测双侧海马谷氨酸天门冬氨酸转运体(GLAST)、谷氨酸转运体1 (GLT1 )和兴奋性氨基酸载体1(EAAC1)mRNA的表达。结果　A组大鼠行为学和脑电图表现无明显改变;B组大鼠致成功92%,致潜伏期为( 6 .09±0 .37 )d;C组致比例降低到67%,致潜伏期延长至(10. 07±0. 56)d。致大鼠抽搐发作的同时记录到阵发的节律性的高幅棘波和尖波。B组大鼠双侧海马GFAP表达均比A组明显增高(P<0 05),C组双侧海马GFAP表达比B组低50% ~60%。与A组比较,B组大鼠双侧海马GLASTmRNA表达显著降低(P<0 .05),而EAAC1mRNA表达增高(P<0 .05);C组双侧海马GLASTmRNA表达与A组无明显差异,而GLT1和EAAC1均比A组明显增高(P<0. 05)。结论　胶质细胞的增生和GLAST的下调可能参与     

男性与癫癎

从癫癎发病及抗癫癎药物(AEDs)与男性激素、性功能、生殖、发育等问题的关系以及对男性癫癎病人性功能障碍的诊断及治疗等角度作一综述.     

托吡酯对戊四氮致癫癎大鼠海马AQP4表达水平的影响

目的探讨托吡酯对戊四氮致癫癎大鼠海马AQP4表达水平的影响。方法将30只Wistar大鼠随机分为戊四氮致癫癎组、托吡酯干预组和正常对照组，每组各10只；癫癎模型点燃后在不同时相点灌注取材，通过HE染色观察大鼠海马神经元的变化，并应用免疫组化法检测大鼠海马AQP4表达水平。结果HE染色显示托吡酯干预组神经元变性和坏死较戊四氮致癫癎组明显减轻；免疫组化显示戊四氮致癫癎组在致癫癎后12hAQP4的表达显著增强，致癫癎后24h达高峰，托吡酯干预组在致癫癎后12h～36h各时相点AQP4表达水平均分别低于戊四氮致癫癎组相应时间点（P〈0．05）。结论托吡酯通过下调大鼠海马AQP4的表达可能参与了对大鼠海马神经元的保护过程。     

Results of barbiturate antiepileptic drug discontinuation on antipsychotic medication dose in individuals with intellectual disability

Five individuals with intellectual disability prescribed both a barbiturate antiepileptic drug (AED) and an antipsychotic medication were identified in a public residential facility. It was hypothesized that antipsychotic medication was prescribed at doses higher than necessary as a result of inadvertent barbiturate AED behavioural side‐effects thought to be part of the underlying psychiatric or behavioural condition. To test this hypothesis, barbiturate AEDs were gradually reduced, and replaced with either carbamazepine or valproic acid, and antipsychotic medication was gradually reduced as well. Challenging behaviours, such as physical aggression, self‐injurious behaviour and property destruction, were measured with a frequency count or partial interval recording, and retrospectively analysed for time periods of ≈60 days before phenobarbital reduction, after phenobarbital discontinuation and after the lowest antipsychotic medication dose. Challenging behaviour collectively decreased by 81.5% after barbiturate discontinuation, mean antipsychotic medication dose significantly decreased from 146 mg day^–1 (SD = 98) to 106 mg day^–1 (SD = 88) chlorpromazine equivalence, and antipsychotic medication was discontinued in the cases of two individuals. Compared to the prebarbiturate AED reduction period, challenging behaviour collectively decreased by 96.3% after the lowest antipsychotic medication dose, which confirmed that reduced antipsychotic medication was not achieved at the expense of behaviour deterioration. The data supported the hypothesis that discontinuation of barbiturate AEDs results in decreased challenging behaviour and less antipsychotic medication.     

育龄期女性癫痫患者抗癫痫药物使用的情况

目的探讨育龄期女性癫痫患者的抗癫痫药物使用情况。方法回顾性分析478例育龄期女性患者的药物使用情况。结果 478例患者中,332例患者使用单药治疗,其中133例(40.06%)使用拉莫三嗪,62例(18.67%)使用卡马西平,60例(18.07%)使用丙戊酸钠。96例(20.08%)两药联用,其中36例(32.73%)使用拉莫三嗪+丙戊酸钠。24例(5.02%)使用≥3种药物治疗。26例(5.44%)使用其他药物治疗。结论育龄期女性癫痫患者主要采用单药治疗,以拉莫三嗪为主。单药治疗效果不佳的患者中,以两药联用多见,以拉莫三嗪+丙戊酸钠为主。     

抗癫痫药物对大鼠记忆和学习功能影响的研究

目的探讨抗癫痫药物对大鼠认知功能的影响。方法健康雄性性成熟SD大鼠70只,随机分为正常对照组(NS组)、癫痫对照组(PTZ组)、卡马西平(CBZ)组、苯妥英钠(PHT)组、丙戊酸钠(VPA)组、妥泰(TPM)组及拉莫三嗪(LTG)组,每组10只。除NS组外其他6组用PTZ点燃。抗癫痫治疗2周后用Morris水迷宫测试认知功能。采用方差分析进行统计学处理。结果PTZ组学习成绩提高快(P<0.05,P<0.01)。卡马西平组、丙戊酸钠组、拉莫三嗪组测试成绩捉高很快(P<0.01),优于NS组。苯妥英钠组测试成绩提高较慢(P<0.05),与NS组比较无明显差异。妥泰组测试成绩提高慢,各次、各天之间差异无显著性(P>0.05),较NS组差。在寻找平台象限和在平台象限逗留时间的测试中,妥泰寻找时间最长,逗留时间最短,两项成绩均低于其他组(P<0.05,P<0.01);其他各组之间差异无显著性。结论PHT可能损害大鼠的学习、判断功能,TPM还可损害大鼠的记忆功能。     

Heterogeneous effects of antiepileptic drugs in an in vitro epilepsy model – a functional multineuron calcium imaging study

Epilepsy is a chronic brain disease characterised by recurrent seizures. Many studies of this disease have focused on local neuronal activity, such as local field potentials in the brain. In addition, several recent studies have elucidated the collective behavior of individual neurons in a neuronal network that emits epileptic activity. However, little is known about the effects of antiepileptic drugs on neuronal networks during seizure‐like events (SLEs) at single‐cell resolution. Using functional multineuron Ca²⁺ imaging (fMCI), we monitored the activities of multiple neurons in the rat hippocampal CA1 region on treatment with the proconvulsant bicuculline under Mg²⁺‐free conditions. Bicuculline induced recurrent synchronous Ca²⁺ influx, and the events were correlated with SLEs. Other proconvulsants, such as 4‐aminopyridine, pentetrazol, and pilocarpine, also induced synchronous Ca²⁺ influx. We found that the antiepileptic drugs phenytoin, flupirtine, and ethosuximide, which have different mechanisms of action, exerted heterogeneous effects on bicuculline‐induced synchronous Ca²⁺ influx. Phenytoin and flupirtine significantly decreased the peak, the amount of Ca²⁺ influx and the duration of synchronous events in parallel with the duration of SLEs, whereas they did not abolish the synchronous events themselves. Ethosuximide increased the duration of synchronous Ca²⁺ influx and SLEs. Furthermore, the magnitude of the inhibitory effect of phenytoin on the peak synchronous Ca²⁺ influx level differed according to the peak amplitude of the synchronous event in each individual cell. Evaluation of the collective behavior of individual neurons by fMCI seems to be a powerful tool for elucidating the profiles of antiepileptic drugs.     

Double-blind study of milacemide in hospitalized therapy-resistant patients with epilepsy

Milacemide, 2-N-pentylaminoacetamide, a glycine prodrug, which readily crosses the blood-brain barrier, has been tested for antiepileptic efficacy and tolerability in 30 patients compared in a double-blind design with 30 patients treated with placebo. All patients continued to receive, without alteration, their previous partly effective medication. All patients presented an average of at least 10 seizures a month during the 6 months preceding the trial with no more than 50% fluctuation. The ratio of seizure frequency in the trial period over the seizure frequency in the baseline period (RSF) was calculated. In the milacemide group, 9 of 29 patients had an RSF less than 0.7 as opposed to 2 of 29 in the placebo group. Although no firm proof of therapeutic efficacy, this and the dramatic improvement of a patient with myoclonus epilepsy indicates that further studies are warranted. This opinion is strengthened if one considers the subgroup of patients aged less than or equal to 25 years in which a statistically significant reduction in seizure frequency was observed with milacemide treatment. The drug was well tolerated.     

Opinion of Belgian neurologists on antiepileptic drug treatment in 2006: Belgian study on epilepsy treatment (BESET‐2)

Objectives – (i) To describe the medical treatment of epilepsy in Belgium in 2006, (ii) to detect the presence or absence of consensus in epilepsy treatment and (iii) to analyze the evolution of the neurologists’ opinion between 2003 and 2006. Materials and methods – In December 2006, 100 neurologists were interviewed with a structured questionnaire, based on ordinal four‐point scales. The questionnaire contained questions on treatment choices in adult patients with epilepsy. The results of this survey were compared with results of a previous one done in 2003. Results – Initial monotherapy was the preferred treatment strategy. Valproate was first choice in idiopathic generalized epilepsy. Carbamazepine and oxcarbazepine were first choice in focal epilepsy with partial seizures. Valproate was also first choice in focal epilepsy with secondarily generalized seizures. New antiepileptic drugs were recommended in second line. However, in special treatment situations, they were considered first‐line, e.g. lamotrigine in case of women in childbearing age. In comparison with 2003, there was a trend of using earlier the new antiepileptic drugs. Conclusions – In end 2006, carbamazepine, valproate and oxcarbazepine were considered to be first choice drugs, whereas other newer drugs, like lamotrigine, levetiracetam and topiramate were predominantly prescribed in second line.