A型钾通道Kv4.1在戊四唑致痫大鼠海马区的表达

目的通过检测A型钾通道Kv4.1在戊四唑(PTZ)致痫大鼠海马CA1、CA3及齿状回区的表达变化,探讨A型钾通道在癫痫发病机制中的作用。方法 SD大鼠40只,随机分为正常组、致痫后1 h、24 h、72 h组。腹腔注射PTZ制备大鼠癫痫模型,应用免疫组化及Western Blot技术检测Kv4.1在各时间段海马CA1、CA3及齿状回区的蛋白表达情况。结果致痫组大鼠海马区Kv4.1蛋白表达水平在致痫后1 h、24 h、72 h三个时间段均明显高于正常组(P<0.05);各致痫组之间Kv4.1蛋白表达水平无明显差异(P>0.05)。结论大鼠癫痫模型海马区A型钾通道Kv4.1蛋白表达增多,Kv4.1的表达上调可能在癫痫的发生中起作用。     

脑缺血后大鼠海马CA1区神经元持续钠电流变化的研究

目的研究脑缺血后大鼠海马CA1区神经元持续钠电流的变化,探讨钠通道阻滞剂对缺血脑组织保护的机理。方法酶消化法急性分离SD大鼠(10~14d)海马CA1区神经元,全细胞膜片钳技术记录脑缺血对持续钠电流的影响。结果缺血3 min时持续钠电流增加到正常时的1.59±0.26倍(P﹤0.05),缺血5 min时增加到正常时的2.92±0.46倍(P﹤0.05)。结论脑缺血时钠通道开放,持续钠电流增加。     

去松果树对大鼠学习记忆及大脑皮质胆碱能纤维的影响

目的　探讨松果体功能减退致褪黑素 (MT)分泌减少对大鼠学习记忆及大脑皮质胆碱能纤维分布的影响。方法　将大鼠进行Y型迷宫测试 ,淘汰学习障碍的大鼠 ,将学习正常的大鼠随机分 2组 ,实验组手术摘除松果体 ,对照组给予假手术 ,饲养 40d后再行Y型迷宫测试 ,乙酰胆碱酯酶 (AChE)组织化学法测AChE。结果　实验组大鼠学习成绩由术前 (14.7± 5 .0 )次增加到术后(2 8.7± 2 .4)次 ,学习记忆能力明显低于术前自身及对照组 (13.8± 8.3)次 (P <0 .0 1) ,运动皮质、体感皮质第Ⅱ～Ⅳ层 ,海马CA1、CA2、CA3区辐状层、腔隙层、分子层和齿状回多形细胞层AChE阳性纤维密度明显低于对照组 (P <0 .0 1)。结论　大鼠松果体摘除可以引起大鼠学习记忆障碍及大脑皮质胆碱能纤维密度降低     

自发性癫痫大鼠脑内神经肽Y受体Y2R和Y5R的表达及分布

目的研究自发性癫痫大鼠(tremor rat,TRM)海马和颞叶皮质中神经肽Y(neuropeptide Y,NPY)Y2和Y5受体(Y2R和Y5R)的表达和分布。方法以TRM大鼠作为癫痫组,正常Wistar大鼠作为对照组,每组7只,以RT-PCR法检测Y2R和Y5R mRNA水平表达,Western Blot法检测其蛋白水平表达,免疫荧光法分析癫痫组和对照组大鼠海马CA1、CA3和齿状回(DG)区以及颞叶皮质中Y2R与Y5R的分布和定位。结果RT-PCR和Western Blot结果显示,与对照组大鼠相比较,癫痫组海马和颞叶皮质中Y2R mRNA相对表达水平(相对灰度值为海马:0.75±0.06 vs.0.51±0.07;颞叶皮质:0.70±0.05 vs.0.55±0.03)及蛋白相对表达水平(相对灰度值为海马:0.79±0.08 vs.0.42±0.05;颞叶皮质:0.72±0.05 vs.0.51±0.07)均显著上调(均P0.01),Y5R mRNA(相对灰度值为海马:0.52±0.10 vs.0.54±0.06;颞叶皮质:0.46±0.03 vs.0.42±0.04)及蛋白(相对灰度值为海马:0.28±0.06 vs.0.27±0.03;颞叶皮质:0.31±0.05 vs.0.27±0.07)表达均没有明显变化(均P0.05)。免疫荧光分析发现Y2R与Y5R在癫痫组大鼠海马CA1、CA3区神经元和DG区颗粒细胞以及颞叶皮质神经元中分布广泛且主要定位在细胞膜上。结论在TRM中Y2R表达在海马和颞叶皮质中均表达上调,但是Y5R的表达没有明显改变。     

慢性脑缺血老龄大鼠海马NMDA受体亚单位NR2B表达的特征

目的研究老龄大鼠慢性脑缺血后大脑海马中NR2B表达特征。方法应用免疫组化染色技术检测大鼠脑海马中CA1、CA3区和齿状回中NR2B的表达。结果缺血组海马CA1、CA3区和齿状回三处NR2B灰度值均低于对照组,差异具有统计学意义(P<0.05)。结论老龄大鼠海马结构内CA1、CA3区及齿状回内NR2B的表达明显减少。     

A型钾通道Kv1.4在致痫大鼠海马区的表达

目的 通过检测A型钾通道Kv1.4在戊四唑(PTZ)致痈大鼠海马CA1、CA3及齿状同区的表达变化,探讨A型钾通道与癫痫发病的关系.方法 SD大鼠40只,随机分为对照组、致痫后1h、24h、72h组,每组各10只.腹腔注射PTZ制备大鼠癫痫模型,应用免疫组化及Western Blot技术检测Kv1.4在各时间段海马CA1、CA3及齿状回区的蛋白表达.结果 致痫组大鼠海马区Kv1.4蛋白水平在致痫后1h、24h、72h 3个时间段均明显低于正常组(P<0.05);各致痫组之间Kv1.4蛋白水平均无明显差异(P>0.05).结论 (1)A型钾通道Kv1.4在SD大鼠海马中广泛分布.表达丰富,以轴突处最为明显.(2)大鼠癫痫模型海马区A型钾通道Kv1.4蛋白表达减少,提示Kv1.4的表达下调可能与癫痫的发病相关.     

雌孕激素对鼠脑皮层及海马N-甲基-D-天冬氨酸受体亚单位1 mRNA表达的影响

目的　探讨雌、孕激素对中枢神经系统作用的分子机制。方法　采用原位杂交技术 ,研究雌、孕激素对大鼠大脑皮层、海马N 甲基 D 天冬氨酸受体亚单位 1(NMDAR1)mRNA表达的影响。结果　给予雌二醇后大鼠顶叶大脑皮层及海马CA1、CA3 及齿状回NMDAR1mRNA水平显著高于生理盐水对照组 ;给予孕酮后大脑皮层及海马各区NMDAR1mRNA水平与生理盐水对照组比较 ,差异无显著性意义。结论　雌激素上调脑组织内NMDAR1mRNA水平 ,使惊厥易患性增加 ,此可能是雌激素致癫痫作用的分子机制之一。而孕激素的抗癫痫作用与调节NMDAR1mRNA的表达没有明显关系     

急性脑缺血大鼠海马和齿状回神经元β-NGF与NGFRs基因表达变化对其生存影响的研究

目的探讨急性脑缺血时大鼠海马各区及齿状回神经元β-神经生长因子(β-nervegrowthfactor,β-NGF)及其受体trkA2和p75NGFR基因表达变化对神经元生存的影响。方法采用mRNA原位杂交、免疫组织化学染色和原位细胞凋亡检测等方法,分别观察各缺血组和对照组大鼠海马各区及齿状回神经元上述3种基因表达的变化和神经元凋亡状况。结果正常大鼠海马和齿状回神经元均表达β-NGF、trkA2和p75NGFRmRNA及蛋白,无神经元凋亡。急性脑缺血后,海马CA1、CA2和CA3区均出现大量凋亡的神经元,其密度均明显高于同组CA4区及齿状回(P<0.01)。缺血组海马CA1、CA2和CA3区神经元β-NGF、trkA2和p75NGFRmRNA及蛋白的表达水平均低于对照组的对应区域(P<0.05或P<0.01),它们的表达水平彼此间均呈正相关(r=0.213～0.835,P<0.05～P<0.0001),并均与对应区域的凋亡神经元密度呈负相关(r=?0.551～?0.823,P<0.0001)。缺血组CA4区及齿状回神经元β-NGF及其受体的表达无显著变化,且与凋亡无相关关系。结论β-NGF以自分泌和(或)旁分泌方式发挥神经元保护作用,β-NGF可能对其两种受体的表达具有正性诱导作用,缺血引起的β-NGF及其两种受体表达减少可能是导致对缺血敏感的海马CA1、CA2和CA3区神经元凋亡的重要因素。     

颞叶内侧癫痫患者海马区胶质细胞中GFAP、GLAST和GLT-1的表达

目的研究胶质纤维酸性蛋白(GFAP)及谷氨酸-胱氨酸转运体(GLAST)、神经胶质谷氨酸转运体(GLT-1)在颞叶癫痫患者海马区的表达情况。方法取40例难治性颞叶内侧癫痫患者在手术中切除的海马组织,根据在光镜下观察到的神经元丢失情况,分为海马硬化组(A组)23例和海马非硬化组(B组)17例,通过免疫组化法检测两组GFAP、GLAST、GLT-1的表达情况。结果A组GFAP的表达与B组比较,总海马区域、CA1区、CA2区、齿状回表达增加(P<0.01)。A组GLAST的表达与B组比较,海马总区域、齿状回差异无显著性(P>0.05)、CA1区减少(P<0.05)、CA2区则增加(P<0.05)。A组GLT-1的表达与B组比较,总海马区域、CA1区减少(P<0.01)、CA2区增加(P<0.01),齿状回差异无显著性(P>0.05)。结论颞叶内侧癫痫患者海马各区GFAP表达增加,GLAST、GLT-1在海马CA1区减少、CA2区表达增加,提示癫痫发作后海马区谷氨酸转运体重新分布可能是难治性癫痫发病机制之一。     

慢性脑缺血老龄大鼠海马中突触素的表达特征

目的 研究老龄大鼠慢性脑缺血后大脑海马中突触素表达特征.方法 应用免疫组化染色技术检测大鼠脑海马中CA1区、CA3区和齿状回中突触素的表达.结果 缺血组海马CA1区、CA3区和齿状回三处突触素灰度值均低于对照组,差异有统计学意义(P<0.05.结论 老龄大鼠海马结构内CA1区、CA3区及齿状回内突触素和NR2B的表达明显减少.     

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.     

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.     

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.     

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.     

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.     

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.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.