神经颗粒素在海人酸诱发癫(疒间)大鼠皮质及海马中表达的研究

目的探讨海人酸(KA)诱发癫疒间后不同时间大鼠皮质及海马各区神经颗粒素的表达及意义。方法将52只SD大鼠随机分为癫疒间诱发组(KA组)和正常对照组。运用免疫荧光染色共聚焦显微镜观察大鼠制模成功后6 h、12 h、18 h、24 h、48 h 5个时点皮质及海马各区神经颗粒素表达的变化;蛋白质免疫印记(W estern B lot)技术对皮质及海马神经颗粒素作选择性半定量分析,并进行比较。结果与正常对照组相比,KA组制模18 h大鼠皮质神经颗粒素表达开始减少(P<0.05),24 h为最低(P<0.01),48 h恢复正常;制模12 h海马齿状回神经颗粒素明显下降(P<0.05),18 h最低(P<0.01),48 h恢复正常;海马CA1区制模后神经颗粒素持续下降,48 h时与正常对照组比较差异有显著性(P<0.05);CA3区未见显著变化。W estern B lot实验印证了这一结果。结论KA诱发的复杂部分性癫疒间发作急性期能引起大鼠皮质及海马神经颗粒素表达减少,在各脑区的变化不同,且有可恢复的趋势,可能与癫疒间发作后引起大脑神经元突触可塑性改变有关。     

实验性癫痫大鼠发作后海马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)诱导的实验性癫疒间(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致疒间早期(6～12 h)2种亚单位mRNA表达水平广泛下降,至1 d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,3 d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疒间组(P<0.05～0.01).结论 致疒间鼠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亚单位的抗疒间药提供新途径.     

癫大鼠血清、海马组织中神经元特异性烯醇化酶和S-100β蛋白的变化及其临床意义

目的探讨红藻氨酸(KA)诱导癫疒间大鼠血清及海马组织中神经元特异性烯醇化酶(NSE)和S100β蛋白(S100β)的变化及其临床意义。方法180只Wistar大鼠随机分为对照组、KA组和卡马西平(CBZ)组,后两组再按癫疒间发作后1h、4h、12h、24h、48h和72h不同时点分为6个亚组。以放射免疫法(RIA)和酶联免疫吸附试验(ELISA)分别测定大鼠血清和海马匀浆液中NSE和S100β的变化。结果癫疒间发作72h内,血清和海马匀浆液中NSE和S100β的含量是一个动态变化过程,且呈同步变化的趋势,在12h时均达到峰值。在4～48h时,KA组和CBZ组的二者含量均明显高于对照组(P<0.05～0.01)。结论癫疒间发作后NSE和S100β的含量升高,二者可作为癫疒间发作后脑组织损伤的一个参考指标。     

迷走神经刺激对癫癎大鼠行为及脑电图的影响

目的 :观察颈部迷走神经干电刺激对癫大鼠行为及额叶、海马、杏仁核脑区放电的影响 ,为迷走神经刺激 (VagusNerveStimulation ,VNS)抑机制研究提供理论依据。方法 :利用脑立体定位手段 ,将电极埋入大鼠脑部双侧额叶皮质、海马和杏仁核 ,记录VNS前后由红藻氨酸 (KA)诱发复杂部分性癫大鼠脑电变化并观察动物行为的改变。结果 :VNS后大鼠癫强直 阵挛发作次数明显减少 ,首次发作潜伏期延长 ,癫发作平均持续时间缩短 ;VNS尤其对杏仁核放电有明显的抑制作用。结论 :VNS能有效抑制KA诱发的复杂部分性癫发作 ,并且杏仁核可能是抑作用的关键核团     

氯化锂-匹罗卡品致(疒间)大鼠脑髓鞘转录因子的表达及其意义

目的探讨氯化锂-匹罗卡品致疒间大鼠脑髓鞘转录因子1(MyT1)的表达及其意义.方法给SD大鼠先后腹腔注射氯化锂、匹罗卡品,制成癫疒间动物模型;用免疫荧光组化法检测癫疒间大鼠癫疒间发作后不同时间大脑皮质和海马CA1区MyT1阳性细胞数.结果与对照组相比,癫疒间后1 d组大鼠海马CA1区MyT1阳性细胞数显著减少(P＜0.05),癫疒间后其他各时间组大鼠脑皮质和海马CA1区MyT1阳性细胞数均有明显的增加,其中癫疒间后7 d组MyT1阳性细胞数最多(P＜0.01,P＜0.05).结论氯化锂-匹罗卡品致疒间大鼠早期大脑MyT1表达增加,并有时程性变化.     

脑内局部给药建立颞叶癫疒间模型的研究

目的研究脑内局部给药建立颞叶癫疒间(EP)模型的方法。方法通过立体定向技术向大鼠海马局部注射海人酸(KA)4μg/kg,观察注射后大鼠的行为学、脑电图和病理学改变。结果KA注入海马后大鼠表现为凝视、湿狗样抖动、咀嚼运动、点头、肢体阵挛等;随后出现阵发性旋转、向上窜跳、四肢抽搐,反复间歇性发作,约10h后发作停止。以后每周约自发性发作1～3次,主要为Ⅱ～Ⅳ级发作。EEG记录到大脑皮质丛集放电,棘波或尖波持续发放。光镜下KA致疒间鼠海马结构的CA1区和CA3区锥体细胞变性及坏死,实验侧CA3区神经元丢失尤为明显。结论大鼠脑内局部注射KA可成功建立颞叶EP模型,其行为症状、电生理及海马病理改变类似人颞叶EP,是很好的研究颞叶EP的工具。     

海藻氨酸致癎大鼠中海马谷氨酸转运体功能的研究

目的　研究海藻氨酸(KA)致疒间大鼠海马谷氨酸转运体(GluTs)功能的变化,进一步探讨GluTs 参与癫疒间发生的机制。方法　60只Wistar大鼠随机分为KA组和对照组,每组再按点燃后4h、24h、48h、5 d、7d不同时点随机分为5个亚组,分别测定不同时点海马突触颗粒和海马组织切片对3H L 谷氨酸的摄取 量,观察GluTs于点燃后不同时点的活性。结果　KA组点燃后海马突触颗粒GluTs功能在各时点均降低(均 P<0.01),海马组织切片GluTs功能在点燃后初期上升而后下降(P<0.05)。结论　KA可引起海马GluTs 功能的变化,其可能与癫疒间的发生及易感性的形成有关。     

癫大鼠海马区囊泡锚定蛋白Ⅰ的表达及突触超微结构的改变

目的观察大鼠癫发作后海马区囊泡锚定蛋白Ⅰ(synapsinⅠ)的表达和突触超微结构的变化,探讨突触功能、形态可塑性与癫的关系。方法用锂匹罗卡品制作癫疒间大鼠模型,应用免疫组化法观察致疒间后急性期、静止期和慢性期synapsinⅠ在海马的表达;应用电镜和图像处理软件观察海马突触超微结构。结果癫疒间组大鼠海马区synapsinⅠ的表达于致疒间后3h减弱;6h和12h达高峰,与对照组比较差异有显著性(P<0.05～0.01);24h恢复正常并持续到60d。致疒间后3h突触后致密物质厚度(PSD)和突触数密度(Nv)无显著改变;6hPSD增高,Nv降低;7d、30dPSD恢复正常,Nv增高。结论synapsinⅠ的高表达和PSD的增高可能与急性期癫疒间持续状态的维持有关;synapsinⅠ的正常表达和PSD的正常可能是静止期内癫疒间不发作的原因之一;慢性期Nv的增加是自发性发作出现的物质基础。     

癫痫发作大鼠海马神经元凋亡与caspase-3 mRNA表达的研究

目的 :研究癫大鼠海马神经元凋亡与caspase 3mRNA表达的关系。方法 :采用大鼠红藻氨酸 (KA)致模型 ,以原位末端标记 (TUNEL)检测癫后不同时间海马神经元凋亡 ;RT PCR检测caspase 3mRNA的表达。结果 :KA致后 1d ,海马CA1、CA3及CA4区开始出现凋亡细胞 ,3d时明显增多 ,7d时最多。KA致后 6h ,海马组织caspase 3mRNA表达显著增高 ,1、3、7d仍持续高水平表达。结论 :癫大鼠海马神经元凋亡与caspase 3mRNA的表达密切相关 ,caspase 3在神经元凋亡过程中起着重要的作用     

强直电刺激大鼠海马、中部颞叶新皮质诱发癫癎模型中电振荡与癫癎发生的关系研究(英文)

在急性、慢性在体大鼠及离体脑片癫疒间 模型上观察 EEG、深部电图、神经元网络及单个神经元的电活动 ,研究中枢同步化电振荡行为在癫疒间发生中的重要作用。实验结果表明 :离体脑片 ( n=40 )上强直电刺激海马 Schaeffer侧枝 ,32 .5% CA1神经元全细胞记录呈现 3～ 1 0 0 Hz膜电位振荡 ,这种电振荡能促进细胞外场电位癫疒间 活动形式的转化。急性癫疒间 模型上 ( n=1 0 ,in vivo) ,反复强直电刺激海马或中部颞叶新皮质可诱发海马区 4～ 7Hz和中部颞叶新皮质 2 0 Hz( n=1 1 )深部电图电振荡。慢性强直电刺激大鼠背侧海马 ( n=1 2 )或中部颞叶新皮质 ( n=1 1 ) ,7～ 8d后出现这些脑区和 EEG电振荡活动的频率及幅度的增加。巨大 EEG节律性电振荡活动成为电图和癫疒间 行为性发作的先兆。说明过度激活海马 -内嗅皮质 -颞叶新皮质产生的同步化电振荡可能是颞叶癫疒间发生的重要原因之一。     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

Sense of coherence as a predictor of subjective state of health: results of 4 years of follow-up of adults

A number of cross-sectional population studies have shown that a strong sense of coherence (SOC) is associated with various aspects of good perceived health. The association does not seem to be entirely attributable to underlying associations of SOC with other variables, such as age or level of education. OBJECTIVE: The aim of the study reported here was to determine whether SOC predicted subjective state of health. METHODS: The study was carried out as a two-way panel mail survey of 1976 individuals with 4 years interval for two collections of data. The statistical method used was multivariate cumulative logistic modeling. Age, initial subjective state of health, initial occupational training level, and initial degree of social integration were included as potential explanatory variables. RESULTS: A strong SOC predicted good health in women and men. CONCLUSIONS: SOC can be interpreted as an autonomous internal resource contributing to a favorable development of subjective state of health. SOC data should, however, be regarded as complementary to and not a substitute for information already known to be associated with increased risk of future ill health.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.