七叶皂苷钠对脑缺血再灌注损伤大鼠MG、iNOS表达的影响

目的观察七叶皂苷钠对大鼠脑缺血再灌注损伤后小胶质细胞(MG)及诱导型一氧化氮合酶(iNOS)表达的影响,探讨其脑保护作用的可能机制。方法将SD大鼠随机分为假手术组、对照组、七叶皂苷钠组。改良线栓法制备建立局灶性脑缺血-再灌注动物模型(MCAO模型),分别于手术后1d、3d、7d免疫组化法观察大鼠海马一区OX-42及iNOS的表达情况。结果对照组、七叶皂苷钠组3d时OX-42达峰,7d时明显降低;iNOS 1d达峰,3d明显下降,7d时接近正常。七叶皂苷钠组优于对照组(P<0.05)。结论七叶皂苷钠可能通过抑制小胶质细胞的活化和iNOS的表达,对大鼠脑缺血再灌注损伤发挥脑保护作用。     

环孢素A对大鼠急性脑缺血再灌注损伤后髓鞘保护作用机制研究

目的观察环孢素A(CsA)对脑缺血再灌注损伤后大鼠海马CA1区iNOS以及胼胝体区髓鞘碱性蛋白(MBP)表达的影响,探讨其对髓鞘保护作用的可能机制。方法将SD大鼠随机分为假手术组、模型组、环孢素A组。改良线栓法制备建立大脑中动脉闭塞(MCAO)模型,环孢素A组从手术后2h～2周,每天腹腔注射环孢素A(20mg/kg),模型组和假手术组每天腹腔注射等体积的生理盐水;分别于手术后1d、3d、7d、14d免疫组化观察大鼠海马一区iNOS以及胼胝体区MBP的表达情况,同时对大鼠胼胝体区髓鞘染色。结果模型组、环孢素组iNOS 1d达峰,3d时下降但仍高于正常,7d及14d时接近正常。胼胝体MBP阳性纤维1d即有减少,3d更为明显,7d有所恢复,14d仍低于正常,经检验环孢素A组好于模型组(P<0.05)。结论环孢素A可显著减少缺血再灌注损伤后脑组织中iNOS的表达,促进MBP的恢复,有一定的髓鞘保护作用。     

克罗卡林对急性脑缺血再灌注大鼠的脑保护作用

目的 探讨急性脑缺血再灌注后大鼠脑内小胶质细胞的活化及K-ATP通道开放剂克罗卡林(Cromakalin)的脑保护作用.方法 将72只SD大鼠,随机分为3组:A组为假手术组,B组为单纯缺血再灌注组,C组为克罗卡林干预组.应用改良Zea Longa线栓法制备大鼠大脑中动脉缺血再灌注(MCAO)模型,免疫组化染色检测OX42(小胶质细胞的标志)和诱导型一氧化氮合酶(iNOS)表达情况;应用特异性尼氏染色进行海马CA1区神经元计数.结果 A组各时间点海马 CA1区OX42,iNOS均有少量表达,B组OX42,iNOS随时间推移表达增多,72 h达高峰,7 d减少,与A组相比两者表达明显增多,差异有统计学意义(P<0.01).C组各时间点OX42、iNOS与B组相比表达明显减少,差异有统计学意义(P<0.01).结论 Cromakalin能明显抑制急性脑缺血再灌注后大鼠脑内OX42增殖,减少iNOS的表达,降低海马神经元的死亡程度,具有脑保护作用.     

大鼠脑缺血再灌注损伤中环孢素A作用的研究

目的:探讨环孢素A对脑缺血再灌注损伤的保护作用。方法:将108只大鼠分为假手术组、生理盐水对照组和环孢素A治疗组,参照Zealonga线栓法制备局灶性脑缺血再灌注模型,大鼠脑缺血2h再灌注22h和70h后,分别对各组各时间点大鼠进行行为学评分、细胞凋亡、脑TTC染色和脑超微结构观察,并对结果进行统计处理。结果:各时间点环孢素A治疗组与对照组相比,行为学评分优于对照组(P<0.05);环孢素A处理组脑梗死灶体积和细胞凋亡比例均比对照组明显减轻(P<0.05);环孢素A处理组脑超微结构的异常改变轻于对照组;假手术组各项观察指标则无明显异常改变。结论:免疫因素参与脑的缺血再灌注损伤,环孢素A对实验大鼠脑缺血再灌注损伤具有一定的保护作用。     

头孢曲松钠对脑缺血再灌注大鼠脑损伤和谷氨酸转运体-1表达的影响

目的 研究头抱曲松钠对脑缺血再灌注损伤大鼠的神经损害程度、脑组织水肿以及谷氨酸转运体-1(GLT-1)表达的影响.方法 线栓法阻塞大鼠大脑中动脉,并于缺血后2h进行再灌注,造成脑缺血再灌注损伤,大鼠分为假手术组(S组)、脑缺血再灌注组(M组)、头孢曲松钠组(C组)3组,C组于造模后6h给予头孢曲松钠200mg/(kg·d),共5d.脑缺血再灌注ld、3d、5d时进行大鼠神经行为学评分和脑组织含水量测定,RT-PCR检测GLT-1 mRNA表达.结果 M组、C组较S组大鼠神经行为学评分降低,脑组织含水量增加,GLT-1 mRNA表达相对量减少;M组上述改变在缺血再灌注3d时最明显,5d时有所减轻.在同一实验时间点,C组较M组大鼠神经行为学评分明显升高,脑组织含水量明显减少,GLT-1 mRNA表达量明显增加(P<0.01),且C组GLT-1 mRNA表达相对量随时间延长逐渐增加(P<0.05).结论 脑缺血再灌注损伤中,头孢曲松钠可能通过上调GLT-1 mRNA的表达来减轻脑缺血损伤和再灌注后脑水肿,从而发挥神经保护作用.     

丁苯酞对慢性脑缺血大鼠海马iNOS及MG表达的影响

目的观察丁苯酞对慢性脑缺血大鼠海马区诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、小胶质细胞(microglia,MG)表达的影响,探讨丁苯酞脑保护作用机制。方法 48只雄性SD大鼠随机分为4组:正常大鼠组为A组,假模型组为B组,模型组为C组,丁苯酞干预组为D组。行双侧大鼠颈总动脉永久结扎的方法制作大鼠慢性脑缺血模型。丁苯酞干预组在慢性脑缺血模型成功后给予丁苯酞软胶囊0.2g·kg~(-1)治疗12周,采用Y迷宫测定各组大鼠学习记忆能力,免疫组化染色测定iNOS及OX42(小胶质细胞的标志)表达,特异性尼氏染色方法测定海马CA1区神经元。结果 A、B组大鼠学习记忆能力正常,海马区iNOS、OX42少量表达,神经元数目正常。C、D组大鼠学习记忆能力下降,海马区iNOS、OX42表达增多,神经元数目减少。与C组相比,D组大鼠学习记忆能力明显增加(P0.01),海马区iNOS、OX42表达减少(P0.01),神经元数目增加(P0.01)。结论丁苯酞可减少慢性脑缺血大鼠海马区iNOS、OX42表达,减少MG的过度激活,减少海马区神经元坏死,提高大鼠的学习记忆能力,具有脑保护作用。     

缺血后海马高迁移率族蛋白与星形胶质纤维酸蛋白表达及相关性

目的研究大鼠局灶性脑缺血再灌注星形胶质纤维酸蛋白(GFAP)与高迁移率族蛋白(HMGB1)在海马CA1区表达变化,探讨二者之间的关系。方法采用大脑中动脉栓塞2h制备SD大鼠脑缺血模型,60只雄性SD大鼠随机分为假手术组、缺血再灌注组,按1d、3d、7d、14d、28d时间点再分5个亚组,各时间点处死取脑,用免疫组化和荧光双标结合共聚焦扫描的方法来检测高迁移率族蛋白和星形胶质纤维酸蛋白在脑内海马CA1区表达变化。结果不同时间点缺血再灌注组GFAP、HMGB1表达均高于同时期的假手术组(P<0.05)。缺血再灌注组星形胶质细胞1d、3d、7d逐渐激活增生,7d达到高峰,14d开始下降;HMGB1在1d、3d、7d、14d是表达增加,14d达高峰,28d下降(与前一时间点比较P<0.05)。缺血再灌注组GFAP和HMGB1表达具有相关性(P<0.05),存在HMGB1和GFAP共定位细胞。结论脑缺血再灌注后,海马CA1区HMGB1增加与星形胶质细胞激活成正相关,过度表达的HMGB1和增殖的星形胶质细胞可能与缺血再灌注后神经元的迟发性损伤有关。     

环孢素A对大鼠脑缺血再灌注后IL-1β表达的影响

目的探讨环孢素A对大鼠脑缺血再灌注损伤后的脑保护作用及其对IL-1β表达的影响.方法将72只大鼠分为假手术组、生理盐水对照组和环孢素A治疗组,参照Zealonga线栓法制备局灶性脑缺血再灌注模型,大鼠脑缺血2 h再灌注22 h和70 h后,分别对各组各时间点大鼠进行脑TTC染色评价脑梗死体积、采用RT-PCR和放免法分别对缺血区皮层IL-1β基因表达和蛋白表达进行测定.结果各时间点环孢素A治疗组与生理盐水对照组相比,环孢素A治疗组脑梗死灶体积比对照组明显减小(P＜0.05);环孢素A可有效降低大鼠局灶性脑缺血再灌后脑组织中IL-1β基因和蛋白的表达(P＜0.01);与上述两组相比,假手术组各项观察指标则无明显异常.结论IL-1β参与脑缺血再灌注损伤,环孢素A对大鼠脑缺血再灌注损伤有明显的保护作用,环孢素A的脑保护机制可能与抑制缺血区内IL-1β的表达有关.     

重复经颅磁刺激对大鼠海马、齿状回胶质纤维酸性蛋白、Ⅲ型补体受体表达的影响

目的观察重复经颅磁刺激(rTMS)对大鼠海屿、齿状间星形胶质细胞和小胶质细胞标记物胶质纤维酸性蛋白(GFAP)、Ⅲ型补体受体(OX-42)表达的影响。方法每日1次给予大鼠1Hz、100mT的TMS 10 min,共14d,观察大鼠行为的变化;14d后采用免疫组化ABC法检测其海马、齿状间GFAP、OX-42的表达,并与对照组比较。结果rTMS组、对照组大鼠海马、齿状MGFAP、OX-42阳性表达物在形态、数量等方面差异无显著性。结论本实验条件下的rTMS不会造成大鼠中枢神经系统明显损伤。     

经侧脑室注射脂多糖诱导大鼠黑质部位小胶质细胞激活及多巴胺能神经元损伤的研究

目的观察经脑室注射脂多糖(LPS)后大鼠的黑质部小胶质细胞激活及多巴胺(DA)能神经元的变化,探讨脑内炎性反应在黑质DA能神经元慢性变性过程中的作用。方法健康雄性SD大鼠30只,随机分为生理盐水(NS)对照组和LPS组,分别向大鼠右侧脑室注射20μL NS或50μg LPS,40周后用免疫组织化学方法检测大鼠黑质小胶质细胞是否激活、激活的程度(OX-42及OX-6抗体水平),以及酪氨酸羟化酶(TH)阳性神经元的形态和数量。以Fluoro-Jade B(FJB)染色法检测黑质部位神经元变性情况。结果 (1)NS对照组大鼠黑质部位OX-42阳性小胶质细胞呈静息状态,染色浅。LPS组大鼠黑质部OX-42阳性小胶质细胞呈部分激活状态,染色深。两组大鼠黑质部位均未发现OX-6阳性小胶质细胞。(2)NS对照组大鼠黑质部位有大量深染的TH阳性神经元。LPS组大鼠黑质部位TH阳性染色神经元数目(99.11±20.31)比NS对照组(189.52±12.12)减少47.7%(P<0.01)。(3)两组大鼠黑质部位均未见FJB阳性染色神经元。结论经侧脑室单次注射LPS可能造成大鼠黑质部位小胶质细胞长期慢性激活及DA能神经元慢性迟发性功能性损伤。     

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.