大剂量甲基强的松龙对缺血再灌注大鼠脑保护作用的研究

目的 探讨大剂量甲基强的松（MP）对缺血再灌注大鼠脑保护作用的机制。方法 采用大鼠全脑缺血再灌注模型,观察缺血前后应用大剂量MP对脑组织自由基和超氧化物歧化酶（SOD）含量的影响,同时做脑组织病理学观察。结果 MP治疗组脑组织丙二醛（MDA）水平较对照组（盐水组）明显降低（P＜0．01）,而SOD水平较对照组增高（P＜0．01）;脑组织超微结构观察发现MP可抑制再灌注中脑组织巨噬细胞浸润。结论 MP的脑保护作用与抑制作用自由基产生、减少抗氧化剂消耗以及抑制巨噬细胞浸润有关。     

β-七叶皂苷钠对大鼠局灶性脑缺血再灌注后AQP4蛋白表达的影响

目的探讨大鼠局灶性脑缺血再灌注脑组织缺血区AQP4蛋白的表达情况及β-七叶皂苷钠的治疗作用和可能机制。方法采用大鼠大脑中动脉闭塞法(MCAO)制作局灶性脑缺血再灌注模型。应用干-湿比重法、TTC染色、免疫组化SABC法分别测定脑含水量、脑梗死体积及水孔蛋白4(aquaporin4,AQP4)的表达。结果假手术组AQP4蛋白有轻微的表达,而模型组、治疗组缺血损伤后表达升高,脑含水量增高,梗死脑组织出现,给予β-七叶皂苷钠的治疗组AQP4蛋白的表达下降,脑含水量明显降低,脑梗死体积减少,且β-七叶皂苷钠中高剂量组明显优于低剂量组(P<0.05)。结论脑缺血再灌注脑组织缺血区AQP4蛋白表达的上调与脑水肿的发生发展与有密切的关系,而β-七叶皂苷钠有抑制脑水肿发生的作用。     

局灶性脑缺血后脑内髓过氧化物酶活性观察

目的　探讨局灶性脑缺血后脑组织髓过氧化物酶（ＭＰＯ） 活性的测定方法,以及与缺血性损害的关系。方法　采用新型小鼠大脑中动脉线栓模型,检测不同缺血时间组梗塞体积及ＭＰＯ活性。结果　缺血１ ｈ 后再灌注２３ ｈ 组（ｔＭＣＡＯ）缺血灶体积明显小于缺血２４ ｈ 组（ｐＭＣＡＯ）;ＭＰＯ活性在各缺血组缺血侧明显高于对照侧和对照组（ Ｐ＜ ０－０５）,ｐＭＣＡＯ 组缺血侧基底节区ＭＰＯ 活性显著高于ｔＭＣＡＯ 组（ Ｐ＜ ０－０５） ,而两组缺血皮质区ＭＰＯ 活性则无显著差异。结论　本研究建立了局灶性脑缺血的ＭＰＯ活性测定方法,证明ＭＰＯ活性与缺血损伤间具有一定关系。     

甲烯土霉素在脑缺血动物实验中的治疗作用

目的探讨实验性脑缺血嗜中性粒细胞（ＮＣ）的浸润规律及甲烯土霉素（ＭＣ）对其影响。方法采用线栓法制成大脑中动脉脑缺血模型，测定脑组织中髓过氧化物酶（ＭＰＯ）活性，并观察神经病学评分及脑组织病理学改变。结果脑缺血及再灌组局灶性缺血脑组织有ＭＰＯ活性、ＮＣ浸润。ＭＣ能有效地降低局灶性缺血脑组织ＭＰＯ活性，减少ＮＣ浸润数量，减轻脑组织缺血坏死程度，改善缺血后神经功能损害。结论局灶性缺血脑组织中有ＮＣ浸润，后者参与脑缺血损伤的病理生理过程，ＭＣ可通过减轻ＮＣ介导的脑损伤而发挥重要的脑保护作用。     

低氧预处理对大鼠脑缺血再灌注后梗死体积和血脑屏障通透性的影响

目的　探讨低氧预处理对大鼠脑缺血再灌注损伤的保护作用。方法　将SD大鼠分为 3组 ,即假手术组、缺血再灌注组、缺氧预处理 +缺血再灌注组。连续吸入 8%O2 +92 %N2 3h作缺氧预处理 ,12h后再经插线左大脑中动脉栓塞 (MCAO)制作缺血再灌注模型 ,到相应时间点后观察缺氧预处理对MCAO大鼠的行为、脑含水量、血脑屏障通透性和脑梗死体积的影响。结果与缺血再灌注组相比 ,缺氧预处理组大鼠的行为明显改善 ,脑伊文思蓝 (EB)含量、脑含水量 (P <0 0 5 ) ,脑梗死体积缩小。结论　低氧预处理降低缺血再灌注脑组织血脑屏障通透性 ,抑制脑水肿 ,缩小梗死体积 ,对缺血再灌注损伤具有保护作用     

亚低温治疗大鼠缺血性脑水肿研究

目的研究亚低温对延迟时间窗再灌注的局灶脑缺血大鼠缺血性脑水肿的治疗作用。方法 SD雄性大鼠96只,线栓法制作大脑中动脉闭塞模型后随机分为缺血3 h组、缺血6 h组、缺血9 h组(每组各30只),分别在造模3 h、6 h和9 h后拔出线栓,使大脑中动脉再灌注。各缺血组按照再灌注后是否给予亚低温治疗及亚低温持续时间分为常温、亚低温3 h和亚低温5 h三个亚组,每个亚组有10只大鼠。另设假手术组6只。缺血组大鼠在再灌注24 h后处死取脑,假手术组在术后24 h处死取脑,干-湿重法测定各组缺血侧脑组织含水量并进行比较。结果与假手术组比较,缺血组缺血侧脑组织含水量明显增高。缺血3 h组中3 h亚低温和5 h亚低温亚组的缺血侧脑组织含水量与缺血3 h常温组比较,差异有统计学意义(79.39%±2.44%vs82.16%±1.50%,P0.05;79.20%±1.55%vs 82.16%±1.50%,P0.05)。其余各缺血组中经过亚低温治疗的大鼠与常温亚组的脑组织含水量无统计学差异。结论亚低温可减轻缺血早期(3 h)再灌注的脑组织水肿,保护缺血脑组织,而对晚期(6 h和9 h)再灌注的缺血性脑水肿无论亚低温时间长短均无明显保护作用。     

bFGF对脑缺血再灌注大鼠ICAM-1表达及脑组织含水量的影响

目的探讨bFGF对局灶性缺血再灌注大鼠脑组织含水量及脑组织ICAM-1水平的影响。方法SD大鼠48只,随机分为假手术组（n=16）、缺血再灌注组（n=16）和bFGF组（n=16）。应用线栓法制作大鼠局灶性脑缺血再灌注模型,大脑中动脉阻塞1h再灌注损伤24h,bFGF组伤后即刻一次性经腹腔注射bFGF（10g／kg）,假手术组和损伤组以相同方法给予0．9％的生理盐水。采用干湿法检测各组大鼠脑组织含水量,采用伊文思蓝（evansblue,EB）法检测脑毛细血管通透性,采用免疫组化法检测大鼠脑组织ICAM-1水平。结果与假手术组比较,缺血再灌注组脑含水量、脑皮质EB含量及ICAM-1表达显著增加（P〈0．05）,与缺血再灌注组比较,bFGF组脑含水量、脑皮质EB含量及ICAM-1表达较模型组显著性降低（P〈0．05）。结论ICMA-1表达增加是脑缺血再灌注后脑水肿形成和缺血性损伤的重要原因之一,减少ICAM-1表达和脑组织含水量推测是bFGF脑保护作用机制之一。     

高张盐水在局灶性脑缺血再灌注损伤中的作用及其机制

目的 研究高张盐水对大鼠局灶性脑缺血再灌注损伤后脑含水量、肿瘤坏死因子-α(TNF-α)含量以及脑细胞凋亡的影响,探讨高张盐水在脑缺血再灌注损伤中的作用和机制. 方法 健康SD雄性大鼠96只按随机数字表法分为4组,即假手术组(P组)、单纯缺血再灌注组(IR组)、7.5%高张盐水组(HS-A组)、4.2%高张盐水组(HS-B组),每组各24只.采用线栓法制作大脑中动脉缺血模型,再灌注前经股静脉分别给予7.5%NaCl(HS-A组)或4.2%NaCl(HS-B组),P组和IR组不给任何药.检查再灌注前,再灌注后30 min、60 min、90 min时的血清Na+浓度.再灌注22 h后,对大鼠进行神经功能缺陷评分,然后断头取脑检测左右两侧脑含水量;取缺血侧前脑皮质测TNF-α含量;取梗死灶周围脑组织,用TUNEL法检测神经元凋亡情况. 结果输入高张盐水后,HS-A组和HS-B组大鼠血清Na+浓度明显升高,HS-A组持续到再灌注后90min,HS-B组在再灌注60min后基本恢复正常.IR组大鼠两侧脑含水量较假手术组增加,缺血侧增加更明显,比较差异有统计学意义(P<0.05).HS-A组和HS-B组大鼠两侧脑含水量较IR组相比明显减少,并以缺血侧减少更明显,比较差异有统计学意义(P<0.05);同IR组相比,HS-A组和HS-B组大鼠脑组织TNF-α含量明显降低,凋亡细胞计数明显下降,神经缺陷评分也明显下降,比较差异均有统计学意义(P<0.05).结论 高张盐水可减少缺血再灌注后脑含水量和脑组织TNF-α含量,减轻脑细胞凋亡,改善缺血再灌注损伤后神经功能.     

脑复康对大鼠局灶性脑缺血引起的脑水肿及神经功能变化的影响

目的探讨脑复康(吡拉西坦)对局灶性脑缺血引起的脑水肿及神经学行为的影响.方法阻断大鼠一侧大脑中动脉造成局灶性脑缺血模型.分别通过舌下静脉输注不同剂量的脑复康注射液及甘露醇注射液,观察各组动物在阻断大脑中动脉24h后,动物神经功能、脑梗塞体积及脑组织含水量的变化,并与假手术组及对照组进行比较分析.结果阻断大鼠一侧大脑中动脉引起了动物神经功能的明显变化及阻断侧大脑半球的严重水肿.脑复康注射液剂量依赖性地降低动物的脑梗塞体积及阻断侧大脑半球的含水量,改善其神经功能,1000 mg/kg脑复康注射液的降低脑水含量及脑梗塞体积、改善神经功能的作用与同剂量的甘露醇效果相当.结论较大(250 mg/kg以上)剂量的脑复康注射液对局灶性缺血的脑组织有明显的保护作用.     

rt-PA与尿激酶溶栓治疗对MMP-9和血-脑屏障通透性的影响

目的 探讨重组组织型纤溶酶原激活物和尿激酶溶栓治疗对缺血-再灌注大鼠脑组织基质金属蛋白酶-9 表达水平和血-脑屏障通透性的影响.方法 采用自体血栓塞大脑中动脉制备大脑中动脉闭塞模型,于缺血-再灌注后6 h 静脉注射重组组织型纤溶酶原激活物或尿激酶,分别检测大鼠脑组织基质金属蛋白酶-9 表达水平、血-脑屏障通透性、梗死灶体积及脑组织含水量.结果 缺血-再灌注后24 h,缺血组大鼠脑组织基质金属蛋白酶-9 表达水平(0.16 ± 0.01)、伊文蓝浓度[(5774.00 ± 1659.70)ng/g]明显升高(t = 19.687,P = 0.000;t = 15.170,P = 0.000),梗死灶体积[(32.43 ± 9.93)%]扩大(t = 7.993,P =0.000);经重组组织型纤溶酶原激活物或尿激酶溶栓治疗后,溶栓治疗组大鼠脑组织基质金属蛋白酶-9表达水平[(0.23 ± 0.03)、(0.23 ± 0.02)]进一步升高(t = 21.194,P = 0.000;t = 30.486,P = 0.000),梗死灶体积[(15.51 ± 8.80)%、(17.06 ± 9.73)%]明显缩小(t = 3.928,P = 0.011;t = 1.393,P = 0.022).其余各项参数组间差异无统计学意义(均P > 0.05).结论 重组组织型纤溶酶原激活物和尿激酶溶栓治疗可显著提高基质金属蛋白酶-9表达水平,进而导致血-脑屏障通透性增加.     

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.