匹罗卡品致癎大鼠海马γ-氨基丁酸能中间神经元生长抑素和微清蛋白mRNA表达研究

目的观察匹罗卡品致癎大鼠海马γ-氨基丁酸能中间神经元生长抑素（SS）mRNA和微清蛋白（PV）mRNA表达水平变化,拟从基因水平探讨其表达阳性叮一氨基丁酸能中间神经元在颞叶癫癎发生发展中的作用。方法建立匹罗卡品致癎大鼠模型,采用原位杂交法检测各观察时间点海马SSmRNA和PVmRNA表达阳性神经元数目。结果模型组大鼠海马各区吖．氨基丁酸能中间神经元SSmRNA表达水平均于出现癫癎持续状态后3d降低最为显著（均P=0．000）,随后逐渐升高;至发病后60d,海马CA3区SSmRNA表达水平高于对照组（t=1．021,P=0．005）,海马门区（t=3．211,P=0．009）和CA1区（t=1．902,JP=0．048）则仍低于对照组。模型组大鼠海马门区γ-氨基丁酸能中间神经元PVmRNA表达水平于出现癫癎持续状态后6h开始降低,至发病后60d降低最为显著（均P：0．000）;海马CA1区PVmRNA表达水平于发病后3d降低最为显著（均p=0．000）,随后逐渐升高但仍低于对照组（t=2．216,尸：0．048）;癫癎持续状态早期,海马CA3区PVmRNA表达水平无明显变化,至发病后7d逐渐升高且高于对照组（t=1．021,P=0．005）。结论γ-氨基丁酸能中间神经元SSmRNA和PVmRNA表达水平的下调可能在颞叶癫癎的发生中起重要作用,至慢性期γ-氨基丁酸能中间神经元SSmRNA和PVmRNA表达水平的恢复或上调可能与颞叶癫癎的发展或修复有关。γ-氨基丁酸能中间神经元数目的变化,部分是由于其标志物mRNA表达水平的调节所致,并非神经元数目变化的唯一因素。     

匹罗卡品致(癎)大鼠海马γ-氨基丁酸能中间神经元生长抑素和微清蛋白mRNA表达研究

目的 观察匹罗卡品致(癎)大鼠海马γ-氨基丁酸能中间神经元生长抑素(SS)mRNA和微清蛋白(PV)mRNA表达水平变化,拟从基因水平探讨其表达阳性γ-氮基丁酸能中间神经元在颞叶癫(癎)发生发展中的作用.方法 建立匹罗卡品致(癎)大鼠模型,采用原位杂交法检测各观察时间点海马SSmRNA和PVmRNA表达阳性神经元数目.结果 模型组大鼠海马各区γ-氨基丁酸能中间神经元SSmRNA表达水平均于出现癫(癎)持续状态后3d降低最为显著(均P=0.000),随后逐渐升高;至发病后60d,海马CA3区SSmRNA表达水平高于对照组(t=1.021,P=0.005),海马门区(t=3.211,P=0.009)和CA1区(t=1.902,P=0.048)则仍低于对照组.模型组大鼠海马门区γ-氨基丁酸能中间神经元PVmRNA表达水平于出现癫(癎)持续状态后6h开始降低,至发病后60d降低最为显著(均P=0.000);海马CA1区PVmRNA表达水平于发病后3d降低最为显著(均P=0.000),随后逐渐升高但仍低于对照组(江2.216,P=0.048);癫(癎)持续状态早期,海马CA3区PVmRNA表达水平无明显变化,至发病后7d逐渐升高且高于对照组(t=1.021,P=0.005).结论 γ-氨基丁酸能中间神经元SSmRNA和PVmRNA表达水平的下调可能在颞叶癫(癎)的发生中起重要作用,至慢性期γ-氨基丁酸能中间神经元SSmRNA和PVmRNA表达水平的恢复或上调可能与颞叶癫(癎)的发展或修复有关.γ-氨基丁酸能中间神经元数目的 变化,部分是由于其标志物mRNA表达水平的调节所致,并非神经元数目变化的唯一因素.     

实验性癫癎大鼠发作后海马γ-氨基丁酸B受体亚单位的表达及其激动剂的影响

目的观察海人酸(KA)诱导的实验性癫癎(EP)大鼠发作后海马γ-氨基丁酸B受体(GABABR)亚单位mRNA表达及其激动剂巴氯芬的影响。方法运用原位杂交法检测各实验组大鼠EP发作后及巴氯芬干预后海马区GABABR亚单位GAR1a及GAR2 mRNA表达。结果KA致癎早期(6~12h)2种亚单位mRNA表达水平广泛下降,至1d仍明显低于对照组(均P<0.05),但齿状回(DG)区mRNA表达开始回升,3d后表达水平已明显高于对照组(P<0.05),而CA1与CA3区表达仍维持低水平(均P<0.05),但其表达水平渐向对照组水平恢复。巴氯芬干预后亚单位表达明显下降的时间点延迟,且表达水平明显高于非干预的致癎组(P<0.05~0.01)。结论致癎鼠2种亚单位表达下降后又上调为颞叶EP的内源性自我保护机制;巴氯芬促进2种亚单位表达,增强GABA抑制作用,有利于控制EP,为筛选针对GABABR亚单位的抗癎药提供新途径。     

颞叶癫癎的病理

简明介绍颞叶癫癎的病理改变,重点介绍内侧颞叶硬化和双重病理改变,强调致癎灶、异常灶和病理灶之间的关系是揭示致癎原理的关键.     

神经干细胞向γ-氨基丁酸能神经元的诱导分化

目的探索海马神经干细胞在特定条件下分化成γ-氨基丁酸能神经元的情况,为颞叶癫痫的细胞替代学治疗奠定基础。方法新生大鼠海马组织中的神经干细胞在体外增殖后,加入特定的细胞因子进行诱导,使其向γ-氨基丁酸能神经元分化,对分化的细胞进行神经元烯醇化酶（NSE）、微管相关蛋白（MAP-2）、γ-氨基丁酸（GABA）、胶质纤维酸性蛋白（GFAP）和半乳糖脑苷脂酶（GalC）免疫荧光染色鉴定,判断其分化成γ-氨基丁酸能神经元的情况。结果海马神经干细胞诱导贴壁后即发生分化,其中几乎全部分化成神经元（γ-氨基丁酸能神经元）,只有极少的胶质细胞和少突胶质细胞形成。结论从海马神经干细胞中几乎可以完全诱导形成γ-氨基丁酸能神经元,这为颞叶癫痫的细胞替代学治疗奠定了基础。     

低频电刺激丘脑底核对癫(癎)大鼠海马谷氨酸和γ-氨基丁酸表达的影响

目的 探讨低频电刺激(LFS)丘脑底核对癫(癎)大鼠海马谷氨酸(Glu)及γ-氨基丁酸(GABA)表达的影响.方法 用30只大鼠制备杏仁核电刺激点燃模型,同时在丘脑底核埋置刺激电极;制模成功的大鼠随机分为LFS组及对照组;两组大鼠每日点燃1次,共10 d;LFS组大鼠每次点燃前予以LFS丘脑底核.观察10 d后两组大鼠癫(癎)发作程度和持续时间,应用免疫组化法测定大鼠海马Glu、GABA阳性细胞数及灰度值.结果 与对照组比较,LFS组癫(癎)发作的Racine评分明显降低,癫(癎)发作持续时间明显缩短;海马GABA阳性细胞数明显增多、灰度值降低;Glu阳性细胞数明显减少,灰度值明显增加(均P＜0.05＝.结论 LFS丘脑底核能有效抑制大鼠杏仁核点燃发作,其作用机制可能是改变了脑内Glu、GABA的表达.     

脂肪源性γ-氨基丁酸能神经元移植治疗帕金森病大鼠的疗效观察

目的 研究脂肪来源的间充质干细胞诱导为γ-氨基丁酸(GABA)能神经元的方法 ,探讨GABA能神经元移植治疗帕金森病模型大鼠的疗效. 方法 取大鼠脂肪组织.利用本单位自行配制的神经干细胞培养基诱导分化为神经干细胞,利用GABA能神经元定向诱导培养基对神经干细胞进行二次定向诱导,并对其进行特异性鉴定.将诱导成功的神经干细胞、GABA能神经元分别移植入帕金森病大鼠模型的丘脑底核,在移植后2周、4周、8周观察大鼠行为学变化情况.结果 体外扩增的脂肪间充质干细胞经过神经干细胞培养基培养后,细胞定向诱导并表达巢蛋白、神经元烯醇化酶(NSE)等神经干细胞标志.经GABA能神经元定向分化培养基二次诱导后,免疫荧光鉴定细胞GAD65阳性.立体定向移植细胞4周后,神经干细胞组与GABA能神经元组的大鼠行为学均得到改善,且GABA能神经元组的疗效更加显著. 结论 脂防来源的间充质干细胞可诱导分化为GABA能神经元,将其移植人大鼠的丘脑底核可以明显改善帕金森病大鼠的运动功能.     

海马神经元癫癎样放电模型中神经元凋亡的研究

目的通过检测体外海马神经元癫癎样放电后的细胞凋亡,旨在探讨颞叶癫癎病人海马神经元丢失的机制.方法首先制备Sombati神经元癫癎样放电模型,然后采用Tunel标记、荧光染色以及流式细胞技术对模型中的凋亡神经元作了定性和定量检祆测.结果发现神经元癫癎样放电后出现细胞凋亡,且随着放电时间的延长,凋亡细胞增加.结论反复癫癎样放电导致神经元凋亡,其发生可能与癫癎样放电的兴奋性毒性有关.     

小儿颞叶癫癎的临床表现及脑电图分析

目的 探讨小儿颞叶癫癎的临床特征及脑电图特点.方法 收集16例颞叶癫癎患儿,对其发作的临床特点及脑电图资料进行分析,对比难治性癫癎的脑电图变化规律.结果 患儿的癫癎发作形式主要表现为单纯部分性发作、复杂部分性发作、继发全面性发作.单纯部分发作频率高而持续时间短,复杂部分发作持续时间长但发作频率低并常见发作后朦胧状态.颞叶癫癎的脑电图特点:背景正常者约占62.5%(10/16);背景异常约占37.5%(6/16);异常放电及部位:颞叶棘波或慢波放电,表现为单侧或双侧同步或不同步放电.结论 小儿颞叶癫癎是一组部分性症状性癫癎综合征,多表现为复杂部分发作,临床发作及同步脑电图特点可为临床诊治提供帮助.     

神经干细胞移植治疗颞叶癫癎的可行性研究进展

神经干细胞移植治疗颞叶癫癎的研究近年来已在国内外广泛开展,并取得了一定的研究成果.本文从神经干细胞移植到大脑一定部位后癫癎模型动物的行为学、电生理、形态学改变等方面综述神经干细胞移植治疗颞叶癫癎的研究进展,以总结其可行性.     

A study of the relationship between the seizure focus and 1H-MRS in temporal lobe epilepsy and frontal lobe epilepsy

Several studies of temporal lobe epilepsy (TLE) patients have investigated the relationship between the seizure focus and 1H magnetic resonance spectroscopy (1H-MRS). There have also been a few reports in other types of partial epilepsy. We examined the relationship between the seizure focus and the reduction in N-acetylaspartate: creatine (NAA : Cr) ratio using 1H-MRS in both TLE and frontal lobe epilepsy (FLE) patients. We studied 21 patients with unilateral TLE and seven patients with unilateral FLE. We used a 1.5 Tesla magnetic resonance unit (Signa Horizon; General Electric). Approximately 15 x 15 x 20 mm3 voxel of interest (VOI) was placed over the anterior portion of the bilateral hippocampus in the TLE patients, and the anterodorsal position of bilateral frontal lobe in the FLE patients. The seizure focus was identified by interictal scalp electro-encephalogram (EEG). In the TLE patients the NAA : Cr ratios were reduced in the seizure focus, while in the FLE patients they were not always reduced in the seizure focus. In the TLE patients the coincidence rate between the seizure focus and the reduction in the NAA:Cr ratio was 90% (19 of 21 patients), while in the FLE patients the coincidence rate was only 57% (four of seven patients).     

难治性颞叶癫(癎)的手术治疗

目的 探讨难治性颞叶癫(癎)的手术疗效.方法 回顾性分析2003年7月至2007年2月我科手术治疗的72例难治性颞叶癫(癎)患者临床资料.结果 按我国谭氏标准,满意:59例;显著改善:2例;良好:3例;效差:2例;无改善:5例;死亡:1例.结论 手术治疗难治性颞叶癫(癎)疗效确切可靠,在有条件的医院可推广.     

Psychopathology and temporal lobe epilepsy in adolescents

Although high rates of psychopathology in children and adolescents suffering from temporal lobe epilepsy (TLE) have been reported in the literature, the subject remains controversial. In this investigation we made a psychiatric study of 26 adolescents with TLE using a detailed structure interview and rigorous diagnostic criteria. These were compared to 26 matched controls suffering from chronic bronchial asthma (BA). In neither group was there a high rate of specific psychiatric illness, although many adolescents in both samples showed moderate to severe depression. We conclude that TLE may not be a specific cause of psychopathology in adolescence, and that the depression might result from the suffering involved in chronic illness.     

Magnetic resonance imaging and temporal lobe epilepsy

Surgical treatment is a well established option for patients with medically refractory temporal lobe epilepsy. Magnetic resonance imaging (MRI) has revolutionized the evaluation of these patients. New techniques can identify structural, metabolic and functional abnormalities associated with the epileptogenic zone. Mesial temporal sclerosis is the most common pathological finding and presents as hippocampal atrophy, which can be detected by visual inspection in most cases. Volumetric analysis of medial temporal structures offers the advantage of detecting bilateral abnormalities. Magnetic resonance spectroscopy can detect metabolic abnormalities associated with the epileptogenic focus. Functional MRI allows for the non-invasive evaluation of cognitive function, allowing for the localization of the neuroanatomic substrate of motor, sensory and cognitive functions. Intraoperative MRI-based image guided systems are a useful adjunct in the surgical treatment of this epileptic syndrome.     

Effectiveness and tolerance of clobazam in temporal lobe epilepsy

Introduction — The main objective of this retrospective study was the further exploration of the loss of efficiency of the clobazam therapy (CLOB tolerance) in resistant temporal lobe epilepsy (TLE). Material and methods — For up to 42 months we closely followed the state of 55 TLE patients placed on CLOB as an add-on therapy. Also, we sought for a connection between CLOB tolerance and clinical characteristics. Results — by the end of the 1st month 71% of the patients were seizure-free; 20% improved; 3% relapsed totally and 6% did not respond at all. After 24 months 15% were seizure-free, 11 % maintained the original improved state, 36% relapsed totally and 32% partially — which remained unchanged thereafter. Long-term efficiency was in inverse proportion to the pretreatment interictal spike activity. No significant cross-tolerance was noted between CLOB and clonazepam. Conclusion — Although the problem of CLOB tolerance is hardly overestimated, the use of CLOB in the treatment of TLE deserves consideration - despite the possibilities new drugs offer.     

家族性颞叶癫痫的临床与脑电图特征分析

目的探讨家族性颞叶癫痫(FTLE)的临床和脑电图(EEG)特点。方法收集6个 FTLE的家系资料,通过详细的调查,建立较完善的家系谱,并对受累者的临床资料、EEG进行分析总结。结果6个家系共78名家族成员,其中受累者20例,每个家系2-6例受累者不等,2代发病居多。发病年龄0．5-27岁,平均(13．7±10．5)岁。平均发作频率(6．7±8．9)次/月。表现为复杂部分性发作13 例次(76．5％),继发全身强直一阵挛性发作12例次(70．6％),单纯部分性发作4例次(23．5％),强直发作和全身强直一阵挛性发作各1例次;无法分类3例。20例受累者中3例出现复杂视幻觉,1例出现听幻觉。受累者中13例进行发作间期EEG检查,仅1例示颞叶局灶痫性放电(7．7％),2例痫性异常放电, 余未见明显异常;10例进行MRI检查,仅1例示右额颞发育异常(10．0％)。18例受累者疗效观察,3例发作自然缓解,另15例接受抗癫痫药物(AEDs)治疗,14例有效(4例发作控制),仅1例无效。结论 FTLE家庭受累者临床症状呈多样性,发作间期EEG大部分未见局灶异常放电,MRI检查未见异常。 FTLE的正确诊断主要依据患者临床发作特征和家系谱,AEDs治疗疗效良好。     

颞叶癫痫手术时的皮质脑电描记

报告1980年10月至1992年6月间,在皮质脑电描记下手术治疗颞叶癫痫55例,前颞叶切除50例.杏仁核海马切除5例。皮质脑电描记结果说明颞叶癫痫的痫灶绝大多数来源于颞叶外侧皮质和颞叶内侧结构。术中皮质脑电描记可提供痫灶的精确部位和范围。     

Prognostic factors in anterior temporal lobe resections for mesial temporal lobe epilepsy: multivariate analysis

PURPOSE: Even though there have been several studies on the prognostic factors of temporal lobe epilepsy (TLE) after lobectomy, no studies have been performed for homogeneous mesial TLE. Furthermore, most studies on the predictors of outcome of epileptic surgery were based on univariate analyses and did not consider modern epileptic surgery investigation modalities such as brain magnetic resonance imaging (MRI) and positron emission tomography (PET). We attempted to identify the prognostic factors in anterior temporal lobectomy (ATL) for mesial TLE with multivariate analysis. METHODS: Ninety-three patients with mesial TLE (54 men and 39 women, mean age at surgery, 28.3 +/- 8.2 years) were included in the study. The primary outcome variable was the status of patients in the second postoperative year, classified as either seizure free (except aura), or not seizure free. Clinical, electroencephalographic, MRI, PET, Wada test, and pathological data were considered. RESULTS: Seventy-eight (84.0%) patients had remission of seizures. With univariate analysis, age at surgery (p < 0.001), epilepsy duration before surgery (p = 0.04), and ipsilateral hippocampal sclerosis on MRI (p = 0.02) were found to be significant. By using multivariate analysis, age at surgery (p = 0.001) and ipsilateral hippocampal sclerosis on MRI (p = 0.03) were found to be the most significant prognostic factors. CONCLUSIONS: Age at surgery and hippocampal sclerosis are independent prognostic factors for ATL in mesial TLE. These findings suggest that mesial TLE may be a progressive disorder, and surgical outcome is better when early ATL is performed.     

Contralateral temporal hypometabolism on positron emission tomography in temporal lobe epilepsy

Introduction — No detailed case studies report lateralised hypometabolism on positron emission tomography (PET) contralateral to the epileptogenic focus in temporal lobe epilepsy (TLE). Material and methods — We performed ¹⁸F fluorodeoxyglucose (FDG) PET in two intractable TLE patients. Results — One had right temporal interictal spikes on electroencephalography (EEG) and a right medial temporal lobe lesion on magnetic resonance imaging (MRI). FDG-PET showed decreased uptake in the left temporal lobe. Right temporal ictal onset, with bilateral interictal epileptiform activity, occurred on intracranial EEG. He is seizure free after right temporal lobectomy and ganglioglioma resection. The second had right temporal lobe interictal and ictal EEG activity. MRI demonstrated right anteriomedial temporal increased T2 signal. Neuropsychology revealed bilateral cognitive dysfunction. FDG-PET showed left anterior temporal and lateral frontal hypometabolism. He is seizure free after right temporal lobectomy. Conclusion — These findings suggest that regional uptake asymmetry on FDG-PET may be give misleading lateralising information in TLE.