γ-氨基丁酸转运体与癫痫

GABA转运体可以快速摄取突触间隙的GABA ,同时又可以通过逆转运释放GABA。因此 ,转运体可以调节细胞外的GABA浓度及作用时程。本文就GABA转运体的分类及在癫痫发病中的作用进行综述。     

谷氨酸转运体与癫痫关系的研究进展

谷氨酸转运体是一种位于神经元和神经胶质细胞膜上的糖蛋白 ,新近研究发现 ,癫痫及其敏感性的形成可能与致痫灶中谷氨酸天门冬氨酸转运体 (GLAST)、谷氨酸转运体 1(GLT - 1)和兴奋性氨基酸载体 1(EAAC1)的减少有关 ,这对于探讨癫痫反复发作机制具有重要意义。     

γ-氨基丁酸转运体与癫痫关系的研究进展

γ-氨基丁酸(GABA)是哺乳动物中枢神经系统中主要的抑制性神经递质,广泛分布于整个神经系统,临床上已经证明,许多中枢神经系统疾病,如偏头痛、焦虑症、抑郁症和癫痫等都与GABA介导的抑制性突触传递作用的降低有关。GABA转运体是降低突触间隙中GABA浓度的唯一途径,研究表明它与癫痫的关系密切,但目前对GABA转运体的研究报道不一,且存在较大的争议。本文就GABA转运体的结构,分类及与癫痫关系的最新进展作一综述。     

钾-氯离子协同转运体2与癫痫

钾-氯离子转运体2主要在中枢神经系统表达,具有神经元特异性。它主要调节细胞内Cl-的外向流量,使细胞内Cl-处于低浓度,从而促进快速的超极化的突触后抑制。KCC2在人类癫痫发病过程中具有一定的作用,在癫痫的神经元内,KCC2的表达减少,使GABA异常的兴奋,兴奋性神经递质与抑制性神经递质失衡,促进癫痫发生。     

自发性癫痫大鼠脑海马两种锌转运体表达的研究

目的 探讨反复癫痫发作后的自发性癫痫大鼠(SER)与正常Wistar大鼠脑海马锌转运体1和3的表达与癫痫的相关性,以及癫痫发作后脑海马内含锌神经元内锌稳态的改变情况.方法 应用Western blot和RT-PCR方法分析反复癫痫发作后的SER与正常Wistar大鼠脑海马锌转运体1和3表达情况.结果 SER反复癫痫发作后脑海马锌转运体1蛋白及mRNA表达均明显高于正常Wistar大鼠,差异有统计学意义(P<0.05);锌转运体3蛋白表达与正常Wistar大鼠相比无明显改变,差异无统计学意义(P>0.05).结论 反复癫痫发作后SER脑海马可能在神经元尤其突触后神经元内出现锌浓度增高现象,锌转运体1表达上调可通过降低神经元内Zn2+水平对抗癫痫发作引起的神经元损伤,从而起到保护神经元的作用.     

谷氨酸转运体与癫痫关系的研究进展

谷氨酸(Glutamate,Glu)作为哺乳动物中枢神经系统(Central nerve system,CNS)中最重要的兴奋性神经递质,对CNS发育和正常脑功能发挥起调节作用。Glu经突触前膜释放到突触间隙后,通过作用于谷氨酸受体发挥各种各样的生理功能,发挥作用后立即被位于神经胶质细胞和神经元胞浆     

谷氨酸转运体在全脑缺血性癫痫中作用的研究

目的比较三种谷氨酸转运体在全脑缺血性癫痫中的动态变化特征,为癫痫治疗提供有意义靶点.方法SD大鼠以胸部压迫8分钟造成全脑缺血性癫痫模型,分对照组、假手术组、全脑缺血无癫痫组和全脑缺血癫痫组.后两组又根据脑缺血后时间分为6h,24h,48h,72h,5d,7d组.应用免疫组化法研究谷氨酸转运体EAAT-1,EAAT-2,EAAT-3在海马CA1及皮质区表达;研究病理形态变化,同时测定大鼠脑电图改变.结果大鼠癫痫发生率为64%,全脑缺血癫痫大鼠神经损害较无癫痫组严重.与全脑缺血无癫痫大鼠比较,癫痫大鼠海马CA1及皮质区EAAT-2显著持续降低及EAAT-3表达明显升高.结论大鼠癫痫发生与脑缺血严重程度密切相关.海马CA1及皮层区EAAT-2、EAAT-3表达变化是抗癫痫治疗的作用靶点.     

葡萄糖转运体1缺乏综合征研究进展

葡萄糖转运体1缺乏综合征是一种由于SLC2A1基因突变导致的罕见神经系统代谢性疾病,临床症状复杂多样,包括早发性癫痫、发育迟滞、运动障碍等,生酮饮食能够有效改善葡萄糖转运体1缺乏综合征患者的临床症状及预后,并且越早治疗,预后越好。文中从发病机制、临床表现、辅助检查及治疗4个方面对葡萄糖转运体1缺乏综合征进行综述,以提高广大临床医生对该病的认识,提高诊断能力,改善患者预后。     

与帕金森病相关的铁平衡调节

铁平衡对于机体的正常运转有重要作用,铁水平升高都可能会诱导氧化应激和自由基生成,从而与帕金森病等多种神经退行性变疾病的发病机制有关,因此,维持铁的平衡对于防治这些疾病至关重要。本文就年龄、性别对铁平衡的影响,以及铁的运输、储存形式和铁向细胞内、外转运的各种调节机制作一综述,通过阐述年龄增长可导致铁的累积,男性比女性更易引起铁水平的升高,控制铁的运输、储存及转运的多种蛋白可在分子水平从多方面对铁平衡产生影响,以期为寻找预防或阻延帕金森病等神经退行性疾病进程的治疗策略提供思路和依据。     

耐药性癫痫患者外周血铁调节转运体-1基因及蛋白表达的研究

目的通过检测耐药性癫痫(drug resistant epilepsy,DRE)患者外周血铁调节转运体-1(iron-regulated transporter 1,IREG1)基因及其蛋白的表达来探讨DRE的发病机制;并分析该项指标作为患者外周血标志物的临床价值。方法抽取32例DRE患者、30例抗癫痫药物(antiepileptic drugs,AEDs)控制良好患者及34例健康体检者的外周血。采用实时荧光定量PCR和蛋白免疫印迹方法测定外周血IREG1 mRNA及其蛋白的表达水平,对3组实验数据采用方差分析进行统计分析。结果在IREG1基因相对表达量方面,DRE组(1.326±0.102)显著高于AEDs控制良好组(1.001±0.051)(P=0.001);而AEDs控制良好组又显著高于正常组(0.643±0.012)(P=0.001)。在IREG1蛋白相对表达量方面,DRE组(2.092±0.020)显著高于AEDs控制良好组(1.779±0.084)(P=0.02);而AEDs控制良好组又显著高于正常组(1.399±0.083)(P=0.012)。结论 IREG1基因及其蛋白在DRE患者外周血中表达明显升高,提示其可能参与了DRE的发生与发展,或可作为预测DRE形成的耐药指标之一。     

药物难治性癫痫患者脑内多药耐药相关蛋白1表达的研究

目的 研究药物难治性癫痫患者脑内皮层多药耐药相关蛋白1（multidrug resistant-associated protein 1，MRP1）表达的情况。方法 选择12例药物难治性癫痫患者癫痫切除灶与12例正常对照脑组织标本．用逆转录聚合酶链反应（RT-PCR）、免疫组化及免疫蛋白印记（Western blot）方法，分析比较MRP1基因在各组的表达。结果 药物难治性癫痫患者组脑内MRP1的表达显著高于正常对照组（P〈0．01）。在癫痫病灶内广泛分布的MRP1免疫阳性细胞主要为毛细血管内皮细胞和星形胶质细胞。结论 脑内高表达的MRP1参与了难治性癫痫的耐药机制。     

Kinetic Properties of Hexokinase in Resected Temporal Lobes of Patients with Drug-Resistant Epilepsy

Properties of the cerebral glycolytic enzyme, hexokinase, were studied in biopsy samples of human temporal lobe, obtained during lobectomy for drug-resistant epilepsy and compared "blind" with contol biopsy samples of human cerebral cortex. No significant changes in the total activity or subcellular distribution of the enzyme were observed but the Km value for glucose was altered. The 17 control samples gave a normal mean value for Km (glucose) of 0.05 mM and the 14 epileptic samples gave a significantly higher mean value of 0.09 mM. The drugs used in previous treatment of the epilepsies were "scored" with respect to type and dose; analysis of these in relation to the kinetic results eliminated the possibility that the increase in Km value was an artifact due to the drugs. The observed change in enzyme kinetic properties is discussed in terms of potential interactions of small molecules with the isoenzymes of cerebral hexokinase.     

颞叶癫痈大鼠海马内Rnd1 mRNA及蛋白表达变化

目的：动态观察小分子GTPase Rho家族的Rnd1 mRNA及其蛋白在氯化锂-毛果芸香碱（匹罗卡品）致痫大鼠模型海马中的表达变化，探讨其在颞叶癫痫发生发展中的作用。方法：在氯化锂-毛果芸香碱颞叶癫痫模型中应用逆转录聚合酶链反应（RT—PCR）检测癫痫持续发作（SE）后各时间点海马内Rnd1 mRNA的表达变化，并运用免疫组织化学染色法及Neo—Timm染色法分别检测齿状回门区、CA1区及CA3区中该蛋白在不同时间点的表达变化及苔藓纤维出芽（MFS）情况。结果：实验发现模型组于SE后8h内即出现Rnd1表达上调，SE后约1d达高峰，7d左右回复至对照组水平，此后其mRNA表达水平与对照组相似；而免疫组化染色发现Rnd1蛋白表达从SE后8h内即开始上调，约3d达高峰，至7d虽略有回落，但仍高于对照组水平，且这种情况可一直持续至慢性期。结论：急性期海马齿状回门区Rnd1表达上调可能通过促进MFS的发生参与了颞叶癫痫的发生。     

Altered Expression of Synaptotagmin I In Temporal Lobe Tissue of Patients With Refractory Epilepsy

Synaptotagmin I is a key synaptic protein involved in both exocytosis and endocytosis. We aimed to investigate Synaptotagmin I expression in the anterior temporal neocortex of epilepsy patients, and to explore the possible role of Synaptotagmin I in refractory epilepsy. In the present study, 30 epilepsy patients were divided into refractory epilepsy and non-refractory epilepsy groups, another 15 histologically normal anterior temporal lobes from head trauma patients were used as control group. The results were compared among different groups. The findings were consistently observed using immunohistochemistry, immunofluorescence, and Western blotting technique. Synaptotagmin I was mainly expressed in the cytoplasm and cytomembrane of neurons. The expression of Synaptotagmin I in refractory epilepsy group was significantly higher than that in the control and non-refractory epilepsy groups. These findings provide new information in the epileptogenesis of refractory epilepsy, and suggest that Synaptotagmin I might be involved in human refractory epilepsy. Further studies will be required to elucidate the mechanism by which Synaptotagmin I plays role in refractory epilepsy. Zheng Xiao and Yun Gong contributed equally to this work.     

难治性癫痫大鼠脑内多药耐药相关蛋白1表达的研究

目的 研究杏仁核电刺激点燃的难治性癫痫大鼠脑内多药耐药相关蛋白1（multidrug resistant-associated protein 1 MRP1）表达的情况.方法 建立杏仁核电刺激点燃的难治性癫痫大鼠模型,用免疫组织化学及免疫蛋白印记（western blot）的方法,分析比较MRP1蛋白在癫痫模型组与正常对照组的表达.结果 药物难治性癫痫大鼠组脑内多药耐药相关蛋白的表达显著高于正常对照组（P〈0.01）.在癫痫大鼠脑内广泛分布的MRP1免疫阳性细胞主要为毛细血管内皮细胞和星形胶质细胞.结论 癫痫大鼠脑内高表达的MRP1参与了难治性癫痫的耐药机制.     

Basal Temporal Subdural Electrodes in the Evaluation of Patients with Intractable Epilepsy

In evaluation of patients with complex partial seizures who are candidates for surgical treatment, exact definition of the epileptogenic focus is essential for a good surgical outcome. We report a new technique which permits detailed mapping of the epileptogenic activity in the basal temporal lobe and the convexity of the temporal lobe. The technique consists of placement of at least 16 basal temporal electrodes and an additional 64 electrodes covering the temporal convexity. This extensive coverage permits accurate definition of the limits of the epileptogenic focus and also of adjacent functional areas and therefore allows more significant determination than have previous techniques of the ideal extent of the surgical resection. This accuracy cannot be achieved with depth electrodes or the limited coverage provided by previously reported epidural or subdural electrode techniques.     

前颞叶切除术对癫痫患者临床记忆商的影响

目的探讨前颞叶切除术前后癫痫患者临床记忆力的变化。方法58例颞叶癫痫患者均经前颞叶切除手术治疗,其中左侧手术者27例,右侧手术者31例。在手术治疗前后对其记忆商(MQ)进行测定,并比较分析手术预后、术前MQ与术后MQ的关系。结果51例预后EngleⅠ-Ⅱ级,其中术后MQ改善16例(31.4%),无变化30例,下降5例;7例预后Ⅲ-Ⅳ级,其中术后MQ无变化1例,下降6例;两组术后MQ改善率相差显著(P<0.01)。右侧手术者术后MQ评分均值显著高于术前(P<0.01),但左侧手术者手术前后MQ评分均值没有显著差异(P>0.05)。右侧手术组术后MQ改善率(35.5%,11/31)明显高于左侧手术组(18.5%,5/27)。术前MQ障碍者术后MQ改善率(38.5%,10/26)明显高于术前MQ优秀(0.0%,0/5)和中等者(22.2%,6/27)。结论经受了右侧前颞叶手术切除的癫痫病人术后MQ有明显改善,左侧手术者则无明显变化;颞叶癫痫患者的手术预后和术前MQ是影响其术后MQ变化的重要因素。     

铁离子致创伤后癫痫大鼠模型海马胶质纤维酸性蛋白的动态表达

目的:观察创伤后癫痫大鼠模型海马区胶质纤维酸性蛋白的动态表达,探讨反应性胶质细胞增生在创伤后癫痫发病机制中的作用。方法:应用铁离子颅内注射制作创伤后癫痫模型,采用免疫荧光法染色观察海马各区胶质纤维酸性蛋白的表达。结果:7～15d胶质纤维酸性蛋白反应达高峰,注射侧海马CAl区锥体细胞层神经元大量脱失,30d胶质纤维酸性蛋白仍维持较高水平。结论:反应性胶质细胞增生可能与神经无异常放电环路形成有关,最终诱发创伤后癫痫,并成为慢性复发性癫痫的重要病理学基础。     

Memory Tests Distinguish Between Patients with Focal Temporal and Extratemporal Lobe Epilepsy

We examined the ability of preoperative memory performance to distinguish between patients who had been diagnosed as having left (LTLE, n = 31), right (RTLE, n = 37), and extra-(ETLE, n = 17) temporal lobe focal epilepsy. All patients eventually underwent surgical resections. Analyses indicated that the ETLE group performed better than the RTLE group on nonverbal memory measures and better than the LTLE group on verbal memory measures. Discriminant function analyses indicated that use of a combination of measures that assess different aspects of memory were of significant value in distinguishing between patients with focal TLE and ETLE. This approach, as compared the use of single measures, improved classification rates of all three groups. The best single predictor of group membership, an index of verbal learning, yielded a 47% overall correct classification rate, with sensitivities ranging from 25 to 59%, and performed at worse than chance levels in classifying RTLE patients. A multivariate approach, which included an index of verbal and nonverbal learning, incidental nonverbal memory, and consolidation of organized and rote verbal material, yielded a 65% correct classification rate, with sensitivities ranging from 57 to 75%. This compares favorably with other noninvasive techniques for lateralizing epileptogenic lesions.     

The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.