丁苯酞氯化钠注射液对大鼠延髓缺血后微血管密度、NGF、BDNF表达的影响

目的探索丁苯酞氯化钠注射液对大鼠延髓缺血后脑微血管密度、神经生长因子(NGF)、脑源性神经生长因子(BDNF)表达的影响。方法将Wistar大鼠分为假手术组、丁苯酞氯化钠注射液治疗组(以下简称治疗组)、缺血对照组。采用电凝双侧椎动脉和结扎右侧颈总动脉的方法制造大鼠延髓缺血模型。分别给予治疗组和缺血对照组丁苯酞氯化钠注射液及等计量生理盐水腹腔注射。大鼠于相应时段灌注取材,每组标本分别采用单宁酸-氯化铁法染色微血管,免疫组织化学方法显示脑组织中的BDNF和NGF。光镜下观察脑组织中微血管密度、NGF和BDNF的变化,利用灰度值进行分析。结果微血管密度、NGF、BDNF灰度值治疗组均低于缺血对照组。结论NGF、BDNF水平与微血管密度密切相关;丁苯酞可上调大鼠缺血脑组织中NGF、BDNF的表达,减轻脑组织损伤。     

丁苯酞氯化钠注射液对大鼠延髓缺血后神经元凋亡、NGF、BDNF表达的影响

目的探索丁苯酞氯化钠注射液对大鼠延髓缺血后脑神经元凋亡、神经生长因子(NGF)、脑源性神经生长因子(BDNF)表达的影响。方法将Wistar大鼠分为假手术组、丁苯酞氯化钠注射液治疗组(以下简称治疗组)、缺血对照组。采用电凝双侧椎动脉和结扎右侧颈总动脉的方法制造大鼠延髓缺血模型。分别给予治疗组和缺血对照组丁苯酞氯化钠注射液及等计量生理盐水腹腔注射。大鼠于相应时段灌注取材,每组标本分别采用尼氏染色、Tunel染色,免疫组织化学方法显示脑组织中的神经元、凋亡神经元数量、BDNF和NGF。光镜下观察脑组织中神经元数量、神经元凋亡的数量。同时观察NGF和BDNF的变化,利用灰度值进行分析。结果神经元凋亡数量及NGF、BDNF灰度值治疗组均低于缺血对照组。结论 NGF、BDNF水平与神经元数量密切相关,丁苯酞可上调大鼠缺血脑组织中NGF、BDNF的表达,减轻脑组织损伤。     

依达拉奉和尼莫地平联合应用对脑缺血大鼠脑组织血管内皮生长因子表达的影响

目的 探讨依达拉奉与尼莫地平联合应用对脑缺血大鼠脑组织血管内皮生长因子(VEGF)表达的影响.方法 90只Wistar大鼠随机分为5组:正常对照组、脑缺血组、依达拉奉组、尼莫地平组和依达拉奉+尼莫地平组(依尼组),各组又分为缺血12 h、24 h、48 h亚组.用线栓法制作大鼠大脑中动脉堵塞(MCAO)脑缺血模型.制模后1 h,各药物干顶组分别注射依达拉奉3 mg/kg、尼莫地平2 mg/kg和依达拉奉+尼莫地平,正常对照组和脑缺血组大鼠分别腹腔注射生理盐水.各组大鼠分别于预定时间点处死,用逆转录-聚合酶链反应(RT-PCR)法检测脑组织VEGFmRNA水平.结果 各组缺血24 h、48 h亚组脑组织VEGF mRNA水平明显低于正常对照组(均P＜0.01),各药物干预组脑组织VEGF mRNA水平显著高于脑缺血组(均P＜0.01);依尼组脑组织VEGF mRNA水平又显著高于依达拉奉组和尼莫地平组(均P＜0.01).结论 依达拉奉和尼莫地平能上调缺血脑组织VEGF的表达水平,联合应用效果更好.     

依达拉奉对大鼠脑梗死溶栓治疗后MMP-9表达的影响

目的研究依达拉奉对大鼠脑梗死溶栓治疗后脑组织中MMP-9表达及血脑屏障的影响,探讨依达拉奉对脑梗死溶栓治疗后再灌注损伤的保护机制。方法采用SD大鼠自体血栓栓塞法制备大脑中动脉闭塞模型,并将SD大鼠随机分为假手术组、尿激酶溶栓治疗组(UK)、尿激酶+依达拉奉治疗组(UK+ED),12h后分别以免疫组织化学法和比色法对SD大鼠脑组织中MMP-9表达水平和伊文思蓝含量进行测定。结果与尿激酶溶栓治疗组相比,尿激酶+依达拉奉组SD大鼠缺血侧脑组织MMP-9表达水平和EB含量均显著降低,差异具有统计学意义(P值均<0.01)。结论依达拉奉可能通过下调MMP-9表达,减轻血脑屏障的破坏,减轻溶栓后脑缺血再灌注损伤。     

依达拉奉对大鼠延髓缺血后神经元凋亡微血管密度的影响

目的探索依达拉奉对大鼠延髓缺血后神经元数量及微血管密度的影响。方法将Wistar大鼠分为假手术组、实验组、缺血对照组。其中实验组及缺血对照组分别给予依达拉奉和生理盐水腹腔注射。标本采用单宁酸氯化铁染色、尼氏染色、Tunel染色,对延髓内微血管密度、神经元及凋亡、神经元计数进行观察。结果实验组中神经元、微血管密度(MVD)减少的程度及神经元凋亡数量均低于缺血对照组。结论依达拉奉在大鼠延髓缺血后具有明显保护作用。     

依达拉奉对大鼠延髓缺血后神经元神经胶质细胞及微血管的影响

目的探索依达拉奉对大鼠延髓缺血后神经元、神经胶质细胞及微血管的影响。方法将Wistar大鼠分为假手术组、实验组、缺血对照组。其中实验组及缺血对照组,分别给予依达拉奉和生理盐水腹腔注射。标本采用HE染色、单宁酸氯化铁染色,对延髓内微血管密度、神经元计数、神经胶质细胞计数进行观察。结果实验组中神经元数量、微血管密度(MVD)减少的程度及神经胶质细胞增加的程度低于缺血对照组。结论在大鼠延髓缺血后依达拉奉治疗具有明显保护作用。     

NGF、BDNF在脑梗死及糖尿病合并脑梗死大鼠脑中的表达

目的探讨神经生长因子(nerve growth factorNGF)、脑源性神经营养因子(brain-derived neu— rotropic factor,BDNF)在大鼠单纯性脑梗死时脑中的表达情况及糖尿病对它的影响。方法将SD大鼠分成对照组、单纯脑梗死组和糖尿病合并脑梗死组,采用线栓法制作大脑中动脉闭塞(MCAO)模型,2％链脲佐菌素按60mg／ kg腹腔注射制作糖尿病模型,用免疫组化SABC方法检测脑组织NGF、BDNF蛋白表达。结果正常脑组织有少量NGF、BDNF的表达。局灶性脑缺血后24h,NGF、BDNF在梗死的缺血边缘区均有表达上调,其中单纯脑梗死比糖尿病合并脑梗死的NGF、BDNF表达更为明显。NGF、BDNF表达见于缺血边缘区神经元及胶质细胞的胞浆。结论 NGF、BDNF在脑梗死时表达上调是机体对缺血性损伤的内源性代偿机制。糖尿病合并脑梗死时NGF、BD- NF表达上调的不明显,NGF、BDNF表达不足可能与糖尿病加重梗死有关。     

依达拉奉预处理对大鼠脑缺血-再灌注损伤的保护机制

目的探讨依达拉奉预处理对大鼠局灶性脑缺血-再灌注损伤的保护机制。方法将36只SD大鼠随机分为假手术组、缺血-再灌注组和依达拉奉组。依达拉奉组术前给予60 mg/(kg.d)的依达拉奉灌胃,共3 d。采用大脑中动脉线栓法制备大鼠缺血-再灌注损伤模型。比较各组神经功能缺损评分、脑梗死体积、血清神经元特异性烯醇化酶(NSE)含量及脑组织白介素-1β(IL-1β)和肿瘤坏死因子(TNF-α)含量。结果与缺血-再灌注组比较,依达拉奉组的神经功能缺损评分显著下降,脑梗死灶体积显著缩小,血清NSE含量明显降低(均P<0.01);脑组织IL-1β和TNF-α含量显著降低(P<0.05～0.01)。结论依达拉奉预处理可减少大鼠脑缺血-再灌注损伤后脑组织IL-1β和TNF-α表达,保护脑组织。     

电针对MCAO大鼠皮层神经营养因子表达的影响

目的　应用免疫组织化学法观察电针对缺血皮层神经元脑源性神经营养因子 (BDNF)和神经生长因子 (NGF)表达的影响。方法　实验分缺血组和缺血 电针组 ,大脑中动脉线栓 (MCAO)造成局灶性缺血 75 m in,缺血 电针组在缺血后立即给予电针 1h。在缺血再灌不同时间分别处死 ,然后进行免疫组织化学染色。结果　 BD-NF和 NGF主要在缺血灶周围的皮层表达。在再灌后 8h内缺血 电针组 BDNF和 NGF免疫阳性细胞的表达高于缺血组 (P<0 .0 1)。结论　电针能够提高 NGF和 BDNF在缺血灶周围皮层的表达 ,这种高表达可能对脑缺血具有保护作用。     

神经生长因子联合康复训练对脑梗死大鼠神经行为学及脑源性神经营养因子、Bax表达的影响

目的 研究神经生长因子(NGF)联合康复训练对脑梗死大鼠神经行为学及脑源性神经营养因子(BDNF)和促凋亡蛋白Bax表达的影响.方法 将72只SD大鼠随机分为对照组、NGF组、康复训练组及NGF联合康复训练治疗组(联合治疗组),每组又分为脑梗死后7d、14 d、21 d 3个亚组.采用线栓法制作脑梗死大鼠模型,NGF组制模后即予腹腔注射鼠NGF 20 μg/(kg·d);康复训练组制模后72 h给予平衡木、转棒、网屏训练;联合治疗组同时给予NGF和康复训练.各组分别于相应时间点进行神经行为学评分,采用免疫组化染色检测脑组织BDNF、Bax的表达,逆转录-PCR法检测BDNF mRNA、BaxmRNA的表达.结果 与对照组相比,NGF组、康复训练组及联合治疗组各时间点亚组的神经行为学评分均明显降低,脑组织BDNF、BDNFmRNA表达明显升高,Bax及Bax mRNA表达明显降低(均P＜0.05).与联合治疗组比较,NGF组、康复训练组各时间点亚组的神经行为学评分均明显升高,脑组织BDNF、BDNF mRNA水平明显降低,Bax、Bax mRNA表达水平明显增高(均P＜0.05).结论 NGF联合康复训练能上调BDNF、下调Bax的表达,而显著改善脑梗死大鼠的神经功能恢复.     

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.