己酮可可碱预处理对癫痫发作大鼠海马损伤的影响

目的观察己酮可可碱(Ptx)预处理对癫痫发作大鼠海马损伤的影响。方法健康、成年雄性Wistar大鼠分为3组:对照组、癫痫组和Ptx预处理组。对照组腹腔注射生理盐水(127mg·kg~(-1));癫痫组和Ptx组大鼠用氯化锂-匹罗卡品(Li-Pc)诱发癫痫发作,先腹腔注射氯化锂(127mg·kg~(-1)),20h后背部皮下注射匹罗卡品(15mg·kg~(-1));Ptx组大鼠在匹罗卡品注射前30min通过腹腔给予Ptx(60mg·kg~(-1))。观察大鼠癫痫发作情况,利用Timm和Thionin染色分别观察海马苔藓纤维发芽(MSF)和神经元损伤情况。结果癫痫组大鼠在海马苔藓纤维发芽明显增多,并伴有海马神经元的损伤和脱失,Ptx预处理降低了Li-Pc诱发大鼠的癫痫发作率和癫痫发作程度,延长了其癫痫发作潜伏期,减轻了Li-Pc诱发大鼠海马的苔藓纤维出芽及神经元的损伤。结论 Ptx预处理缓解了Li-Pc诱发大鼠的癫痫发作和海马损伤,可能成为治疗癫痫的一种方法。     

粉防己碱和还原型谷胱甘肽治疗帕金森病大鼠模型的实验研究

目的 观察粉防己碱合用还原型谷胱甘肽对帕金森病(Parkinson's disease,PD)大鼠模型脑内多巴胺及代谢产物的影响并探讨其作用机制.方法 采用6-羟基多巴立体定向注射制作PD大鼠模型,将成功模型随机分为4组未治疗组(生理盐水)组,谷胱甘肽加粉防己碱(GSH Tet)组,谷胱甘肽(GSH)组,左旋多巴(L-dopa)组及正常对照组,分别腹腔注射上述药物共50 d,给药结束后观察大鼠旋转行为,测定各组大鼠脑纹状体单胺氧化酶B(MAO-B),高效液相色谱-电化学仪测定纹状体多巴胺(DA),高香草酸(HVA),3,4-二羟基苯乙酸(DOPAC)水平及DA的代谢率(HVA/DA).结果 ①GSH合用Tet能显著改善模型大鼠旋转行为[(7.72±2.05)r/min vs (12.39±3.20)r/min,P＜0.05].②GSH Tet组的DA、HVA、DOPAC含量明显高于其他对照组,且其DA,HVA含量与GSH组比较有统计学差异(P＜0.05).③GSH Tet组的HVA/DA(11.48±1.08)及MAO-B活性[(10.5±2.50)U/h/mgprot]明显低于其他治疗组,与GSH组比较均有统计学差异(P＜0.05).结论 粉防己碱合用还原型谷胱甘肽能增强对PD大鼠的神经保护作用.     

N-乙酰半胱氨酸通过介导m Calpain/TRPC6蛋白表达对癫痫大鼠学习认知功能的影响

目的探讨N-乙酰半胱氨酸对癫痫发作大鼠治疗后学习认知功能的影响及其机制。方法48只SD大鼠,随机分为对照组,癫痫组,N-乙酰半胱氨酸组(150mg·kg~(-1))和瞬时受体电位阳离子通道6 (TRPC6)抑制剂SKF96365组(0.06mg·kg~(-1)),每组12只。以匹罗卡品(300mg·kg~(-1))点燃大鼠癫痫发作,造模前7d,各组给对应剂量药物。观察匹罗卡品腹腔注射后0～180 min大鼠癫痫发作情况,癫痫发作3h后,给予7.5mg·kg~(-1)地西泮缓解癫痫发作。各组大鼠再继续给药观察7d,进行水迷宫测试,检测大鼠学习认知功能。水迷宫测试结束后取脑组织用于Nissl染色和Western Blot实验。结果行为学结果显示,匹罗卡品成功点燃大鼠癫痫发作,并造成大鼠认知功能损伤,而N-乙酰半胱氨酸与SKF96365能够缓解大鼠癫痫发作并改善大鼠认知功能损伤。与对照组相比,癫痫组中钙蛋白酶(mCalpain)蛋白和TRPC6蛋白表达显著升高,Nissl染色显示海马区神经元损伤。此外,癫痫组中,磷酸化的细胞外调节蛋白激酶(p-ERK)、磷酸化的环腺苷酸应答元件结合蛋白(p-CREB)和脑源性神经营养因子(BDNF)表达水平显著降低。然而,N-乙酰半胱氨酸的预给药和治疗能够降低mCalpain蛋白表达,抑制TRPC6蛋白表达,减少神经元凋亡,并增加p-ERK、p-CREB和BDNF蛋白表达。结论匹罗卡品能够点燃大鼠癫痫症状,并造成大鼠学习认知功能损伤,N-乙酰半胱氨酸通过抑制mCalpain蛋白表达,减少TRPC6激动,改善大鼠癫痫发作,此外,ERK/CREB/BDNF通路的激动与大鼠学习认知功能改善相关。     

还原型谷胱甘肽对黑质多巴胺能细胞保护作用的实验研究

目的　观察还原型谷胱甘肽 (GSH)对帕金森病 (PD)大鼠模型的保护性治疗作用 ,并探讨其作用机制。方法　应用 6 羟基多巴制作PD大鼠模型 ,随机分为 4组 :模型组 ,GSH组 ,左旋多巴 (L dopa)组 ,GSH并L dopa组 ,并设正常组 ,给药结束后行电镜观察 ,并测定各组其余大鼠黑质区谷胱甘肽过氧化物酶 (GSH Px)、丙二醛 (MDA)、活性氧 (ROS)及线粒体呼吸链酶复合体Ⅰ水平 ,测定尾状核头部多巴胺 (DA)、高香草酸 (HVA)及单胺氧化酶 B(MAO B)水平。结果　①GSH组旋转行为无明显变化 ,但GSH并L dopa组可使大鼠旋转行为明显改善 ;②GSH能减轻黑质区氧化应激损伤 ;③GSH能增强黑质呼吸链酶复合体Ⅰ活性 ;④GSH组对MAO B活性及DA、HVA含量和DA/HVA比值均无明显影响 ;⑤电镜下发现模型组存在大量中、晚期凋亡细胞 ,而GSH组以早、中期凋亡为主。结论　①GSH能减轻PD模型大鼠黑质区氧化应激损伤 ,并对线粒体呼吸链具有一定保护作用 ;②GSH与L dopa合用 ,既可有效改善症状 ,又对残存DA能神经元具有保护性治疗作用。     

人羊膜上皮细胞移植治疗帕金森病鼠的研究

目的 观察人羊膜上皮细胞在帕金森病鼠移植后的存活情况,以及它对帕金森病鼠旋转行为的改善作用.方法 采用6-羟多巴胺立体定向纹状体注射制作帕金森病鼠模型;51只大鼠随机分三组:人羊膜上皮细胞移植组、假手术PBS对照组以及空白模型对照组.制模成功后第5周用人特异性抗体Nestin和Vimentin检测人羊膜细胞的存活情况,第10周切片观察黑质部TH阳性神经元的变化情况,高效液相色谱--电化学仪测定纹状体多巴胺(DA),高香草酸(HVA),3,4-二羟基苯乙酸(DOPAC)等浓度以及脑脊液DA的含量.结果 人羊膜上皮细胞帕金森病鼠侧脑室内移植可以存活达10周;移植组大鼠旋转数较对照组明显降低(P≤0.01);黑质部TH阳性神经元数量较对照组升高(P≤0.01),纹状体区DA、HVA和DOPAC含量较PBS对照组明显升高(P＜0.01～0.05),移植组脑脊液DA含量较PBS对照组也显著增加(P＜0.01).结论 人羊膜上皮细胞侧脑室移植可以改善帕金森病鼠的旋转行为,其机制可能与其增加纹状体区多巴胺等递质水平有关.     

经皮三叉神经慢性电刺激对癫痫大鼠的癫痫行为和海马炎性反应抑制作用

目的观察经皮三叉神经电刺激(TNS)处理对匹罗卡品诱发的癫痫大鼠的行为、海马区细胞因子IL-1β和TNF-α及小胶质细胞活化的影响,探讨经皮三叉神经电刺激对实验性癫痫的治疗作用及其可能炎性机制。方法选择健康雄性大鼠,设正常对照组和实验组,实验组建立匹罗卡品癫痫持续状态模型6 h后,再分成单纯匹罗卡品模型组(pilo组)和经皮三叉神经电刺激组(TNS组),分别给予假刺激和电刺激4 w后,再次进行匹罗卡品致痫,观察大鼠癫痫行为,用酶联免疫吸附(Elisa)的方法检测大鼠海马组织IL-1β、TNF-α的蛋白含量,免疫组化的方法观察小胶质细胞活化情况。结果 (1)经皮三叉神经电刺激后再次匹罗卡品致痫TNS组大鼠较pilo组发作严重程度减轻,持续时间较短,死亡率降低(P<0.05,P<0.01);(2)TNS组大鼠海马IL-1β和TNF-α含量较pilo组显著降低(P<0.05);(3)TNS组活性小胶质细胞的数量较pilo组在各时间点均明显减少(P<0.05)。结论在实验性癫痫中,经皮三叉神经电刺激有显著的抗癫痫作用,提高了癫痫发作的阈值,其机制可能与其下调炎性因子IL-1β和TNF-α及减轻小胶质细胞的活化有关。     

人羊膜上皮细胞侧脑室移植对帕金森病大鼠模型行为、多巴胺能神经元、神经递质影响的实验研究

目的 观察人羊膜上皮细胞(HAECs)移植入帕金森病(PD)大鼠模型侧脑室后的存活及分化情况,及其对PD大鼠模型旋转行为、纹状体区多巴胺及其代谢产物的影响.方法 采用6-羟多巴立体定向脑内注射制作PD大鼠模型,将制模成功大鼠随机分成3组:人羊膜上皮细胞移植组(HAECs组)、磷酸缓冲组(PBS组)和帕金森组(PD组),1w后腹腔注射阿朴吗啡观察各组大鼠旋转行为的变化,连续观察10w,HAECs组5w后用人特异性抗体Nestin和Vimentin检测人羊膜细胞的存活情况,10w后酪氨酸羟化酶(TH)染色观察各组PD大鼠模型黑质部TH阳性神经元的变化情况及HAECs的分化情况,高效液相色谱--电化学仪测定纹状体多巴胺(DA)、高香草酸(HVA)、3,4-二羟基苯乙酸(DOPAC)等神经递质的水平.结果 HAECs在PD大鼠侧脑室内移植可以长期存活达10w,并且可以分化为DA能神经元,HAECs组大鼠旋转数较PBS组及PD组明显降低(P<0.01),黑质部TH阳性神经元数量较PD组及PBS组升高(P<0.01),HAECs组大鼠纹状体区DA及其代谢产物DOPAC、HVA含量较PBS组明显升高(P<0.05).结论 人羊膜上皮细胞移植入PD大鼠侧脑室可以改善PD大鼠的旋转行为,其机制可能与增加纹状体区DA等神经递质有关.     

内源性MAO-B抑制因子-靛红预防MPTP对多巴胺神经递质的耗竭作用

研究内源性单胺氧化酶B抑制因子-靛红(2,3-吲哚醌,isatin)对MPTP引起的小鼠纹状体DA含量降低的影响.用高效液相色谱配电化学检测器测定纹状体DA,DOPAC和HVA水平.MPTP 30 mg/kg ip使纹状体DA,DOPAC和HVA含量与各自对照组比较显著降低(P＜0.01),预先靛红(200mg/kg@d,×4 d,ig)几乎完全抑制了上述效应,并减少了MPTP对DA更新率的升高,说明靛红有预防MPTP对中枢DA能神经元的毒性.     

星形胶质细胞在帕金森大鼠中的作用机制研究

目的观察移植星形胶质细胞后的PD大鼠行为学改变和单胺类神经递质含量的时空变化及相互关系,旨在分析星形胶质细胞在帕金森大鼠中的作用机制。方法偏侧两点法建立PD模型大鼠后,将星形胶质细胞移入PD大鼠纹状体中,2 w后对比PD组,观察行为学改变,检测单胺类神经递质(DA、DOPAC、HVA)含量变化。结果 PD+T2As组的行为学从第4周开始较PD组有显著改善(P 0. 01),单胺类神经递质(DA、DOPAC、HVA)含量与PD组比较第2周无明显区别(P0. 05),从第3周开始显著高于PD组(P 0. 01)。结论星形胶质细胞在一定程度上保护了受损的DA能神经细胞,对PD大鼠的黑质-纹状体通路具有修复作用。     

甲硫氨酸维B_1对创伤性癫痫大鼠的治疗机制研究

目的探讨甲硫氨酸维B_1(MVB_1)对创伤性癫痫(PTE)的治疗机制。方法将15只雄性SD大鼠随机分为假手术组、癫痫组和癫痫MVB1治疗组,Morris水迷宫方法观察各组大鼠学习和记忆行为变化,检测各组大鼠血清和海马组织中超氧化物歧化酶(SOD)、丙二醛(MDA)和还原性谷胱甘肽(GSH)浓度变化。结果癫痫组大鼠5d的逃避潜伏期显著延长,站台穿越次数显著降低,目标象限时间显著缩短,血清及海马组织SOD和GSH水平显著降低,MDA水平显著增加。癫痫大鼠MVB1处理后,5d的逃避潜伏期均显著缩短,站台穿越次数显著增加,目标象限时间显著延长,血清及海马组织SOD和GSH水平显著增加,MDA水平显著降低。结论 MVB1可改善PTE大鼠的学习记忆功能,可通过提高SOD和GSH浓度,降低MDA浓度来抑制脂质过氧化和减轻自由基损伤,为MVB1临床治疗癫痫提供了新的理论依据。     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

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.     

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.     

Summary of legislation of 1935 of interest to the department of Mental Hygiene

Psychiatric Quarterly -