阿加曲班对大鼠脑出血后脑水肿作用的研究

目的探讨阿加曲班对大鼠脑出血模型脑水肿的作用。方法取雄性SD大鼠32只,体重300~350g,随机分为A、B、C、D,4组,每组8只。大鼠经立体定向分别向右侧尾状核区注入生理盐水60ul、无肝素自体血50ul+生理盐水10ul、生理盐水50ul+阿加曲班生理盐水溶液10ul、无肝素自体血50ul+阿加曲班生理盐水溶液10ul。实验大鼠于术后48小时断头处死,测定脑含水量,HE染色,观察脑组织学变化。结果D组脑组织含水量降低,与B组比较有明显差别(P<0.05);C组脑组织含水量与A组比较无明显差别(P>0.05);HE染色观察:B组可见血肿周围脑组织水肿,炎症细胞渗出,脑组织疏松;D组上述改变减轻;A、C两组未见明显病理学改变。结论阿加曲班可减轻大鼠脑出血后血肿周围脑组织脑水肿。     

经腹腔应用阿加曲班对脑出血后凝血酶神经毒性的抑制作用

目的:探讨经腹腔应用阿加曲班治疗脑出血（ICH）后凝血酶神经毒性损伤的可能性。方法:①研究阿加曲班对ICH及凝血酶注入后脑水肿、细胞损伤的影响。Wistar大鼠60只,随机分为假手术对照组（只进针不注血）;ICH组（50μL自体尾血注入右尾状核）;ICH+阿加曲班干预组(50μL自体尾血注入大鼠右侧尾状核,分别于术后3和12h经腹腔给予阿加曲班0.9mg·kg^-1,总量0.6mL);凝血酶组(10U·2μL^-1凝血酶注入大鼠右侧尾状核);凝血酶+阿加曲班干预组(10U·2μL^-1凝血酶注入大鼠右侧尾状核,分别于术后3和12h经腹腔给予阿加曲班0.9mg·kg^-1,总量为0.6mL)。各组均n=12,术后24h处死各组大鼠,每组中6只用于检测脑组织水含量,6只检测caspase-3免疫反应细胞及TUNEL阳性细胞数。②经腹腔注射阿加曲班对血肿容积的影响:建立胶原酶ICH大鼠模型组:注入Ⅰ型胶原酶+肝素;阿加曲班组:胶原酶ICH模型成功后3及12h分别经腹腔注入阿加曲班溶液0.9mg·kg^-1,每次注入液体量为0.6mL,测定两组大鼠脑组织血肿血红蛋白的含量(测定血红蛋白A₅₅₀值)以评价阿加曲班对血肿容量的影响。结果:自体血ICH及凝血酶模型大鼠在阿加曲班干预后,ICH组及凝血酶组的TUNEL阳性细胞数、caspase-3阳性细胞数明显下降（P<0.01或P<0.05）,脑组织水肿含量百分比明显降低（P<0.05）。胶原酶ICH血红蛋白A值为（0.45±0.12）,阿加曲班干预组为（0.46±0.09）,差异无统计学意义（P>0.05）。结论:ICH后3～12h经腹腔注入阿加曲班可减轻ICH后的脑水肿及细胞凋亡性损伤,且没有血肿增大的不良反应。     

水蛭素对抗脑出血后脑水肿作用机制的研究

目的探讨凝血酶在脑出血后脑水肿形成中的作用和水蛭素抗水肿的作用.方法健康wistar大鼠80只,随机分为4组,每组20只.A组生理盐水+生理盐水;B组生理盐水+水蛭素;C组血+生理盐水;D组血+水蛭素.采用立体定向注射方法,用微量注射器在右侧尾状核部位注入自体未凝血(C、D组)或等量生理盐水(A、B组)50μl,留置20min后同部位2次注射10μl生理盐水(A、C组)或等量水蛭素溶液(B、D组,浓度2u/μl).术后第3d断头取脑,测定脑水含量.结果 A、B组比较无明显差异外,其余各组间均有统计学意义(P＜0.05).结论凝血酶可以引起脑出血后脑组织水肿,水蛭素可以抑制凝血酶所引起的脑水肿,且水蛭素本身不对脑组织产生任何负面影响.     

NMDA受体NR2A亚单位在凝血酶诱导的大鼠脑出血后脑损伤作用机制的研究

目的探讨N-甲基-D天冬氨酸受体(NMDA)受体NR2A亚单位在凝血酶诱导的大鼠脑出血后脑损伤中的作用机制。方法将健康雄性SD大鼠随机分为生理盐水对照组、凝血酶组、凝血酶+阿加曲班组,建立大鼠脑出血模型。造模后48h,采用伊文思蓝法检测血脑屏障(BBB)的通透性,干-湿重法测脑组织的含水量。采用Western-blot方法观察出血后各时间点(0h、0.5h、6h、24h、72h、120h)血肿周围脑组织NR2A分布及动态变化规律。结果 (1)阿加曲班可以明显改善大鼠脑出血BBB通透性(P<0.05),血肿周围脑水肿明显减轻(P<0.05)。(2)Western-blot结果显示,NR2A在6h时开始增加,72h达到高峰,在120h时基本恢复。阿加曲班可以明显减少NR2A在72h时的表达(P<0.05)。结论 (1)NR2A参与了凝血酶诱导的脑出血后脑损伤的病理生理过程。(2)凝血酶可能通过上调NR2A表达引起脑出血后脑组织的损伤。     

大鼠脑出血后血肿周围凝血酶与脑细胞凋亡和脑水肿的关系

目的 研究大鼠脑出血后血肿周围脑组织中凝血酶的变化及其与脑细胞凋亡和脑水肿的关系.方法 105只成年雄性SD大鼠随机均分为脑出血组、生理盐水组和正常对照组.每组再随机均分为7个时相,分别为6 h、12 h、24 h、48 h、3 d、5 d、7 d;用立体定向脑内注射法制备脑出血模型;用ELISA法检测脑组织中凝血酶-抗凝血酶复合物的含量;用流式细胞仪检测脑细胞的凋亡率;用干-湿重法检测脑组织的含水量;用透射电镜观察脑组织的形态学变化.结果 制备动物模型后,脑出血组各时相血肿周围脑组织中凝血酶含量、脑细胞凋亡率、脑组织含水量均明显高于生理盐水组和正常对照组;血肿周围脑组织中凝血酶-抗凝血酶复合物的含量与脑细胞凋亡率和脑组织含水量之间均呈正相关;电镜下,在脑出血组各时相脑组织切片中均可见大量的脑细胞凋亡和毛细血管周围大片组织间隙水肿,以及神经纤维脱髓鞘改变.结论 脑出血后,血肿周围脑组织中凝血酶含量明显升高,可导致脑细胞凋亡和脑水肿,凝血酶的含量与脑细胞凋亡率和脑组织含水量呈正相关;尽早清除血肿有望改善凝血酶引起的继发性脑损伤.     

大鼠脑出血后血肿周围凝血酶与脑细胞凋亡和脑水肿的关系

目的 研究大鼠脑出血后血肿周围脑组织中凝血酶的变化及其与脑细胞凋亡和脑水肿的关系.方法 105只成年雄性SD大鼠随机均分为脑出血组、生理盐水组和正常对照组.每组再随机均分为7个时相,分别为6 h、12 h、24 h、48 h、3 d、5 d、7 d;用立体定向脑内注射法制备脑出血模型;用ELISA法检测脑组织中凝血酶-抗凝血酶复合物的含量;用流式细胞仪检测脑细胞的凋亡率;用干-湿重法检测脑组织的含水量;用透射电镜观察脑组织的形态学变化.结果 制备动物模型后,脑出血组各时相血肿周围脑组织中凝血酶含量、脑细胞凋亡率、脑组织含水量均明显高于生理盐水组和正常对照组;血肿周围脑组织中凝血酶-抗凝血酶复合物的含量与脑细胞凋亡率和脑组织含水量之间均呈正相关;电镜下,在脑出血组各时相脑组织切片中均可见大量的脑细胞凋亡和毛细血管周围大片组织间隙水肿,以及神经纤维脱髓鞘改变.结论 脑出血后,血肿周围脑组织中凝血酶含量明显升高,可导致脑细胞凋亡和脑水肿,凝血酶的含量与脑细胞凋亡率和脑组织含水量呈正相关;尽早清除血肿有望改善凝血酶引起的继发性脑损伤.     

大鼠脑出血后血肿周围凝血酶与脑细胞凋亡和脑水肿的关系

目的 研究大鼠脑出血后血肿周围脑组织中凝血酶的变化及其与脑细胞凋亡和脑水肿的关系.方法 105只成年雄性SD大鼠随机均分为脑出血组、生理盐水组和正常对照组.每组再随机均分为7个时相,分别为6 h、12 h、24 h、48 h、3 d、5 d、7 d;用立体定向脑内注射法制备脑出血模型;用ELISA法检测脑组织中凝血酶-抗凝血酶复合物的含量;用流式细胞仪检测脑细胞的凋亡率;用干-湿重法检测脑组织的含水量;用透射电镜观察脑组织的形态学变化.结果 制备动物模型后,脑出血组各时相血肿周围脑组织中凝血酶含量、脑细胞凋亡率、脑组织含水量均明显高于生理盐水组和正常对照组;血肿周围脑组织中凝血酶-抗凝血酶复合物的含量与脑细胞凋亡率和脑组织含水量之间均呈正相关;电镜下,在脑出血组各时相脑组织切片中均可见大量的脑细胞凋亡和毛细血管周围大片组织间隙水肿,以及神经纤维脱髓鞘改变.结论 脑出血后,血肿周围脑组织中凝血酶含量明显升高,可导致脑细胞凋亡和脑水肿,凝血酶的含量与脑细胞凋亡率和脑组织含水量呈正相关;尽早清除血肿有望改善凝血酶引起的继发性脑损伤.     

老龄和低龄大鼠脑出血后脑水肿的研究

目的对比研究老龄和低龄大鼠尾状核出血后血肿周围组织血-脑脊液屏障(BBB)破坏的时机和脑水肿的严重程度。方法将50μl自体动脉血注入老龄(16个月龄,n=28)和低龄(2个月龄,n=28)Wistar大鼠尾状核,30min和24h后进行MRI(T_2*WI、T_2WI、DWI)观察,同时对发病后6h、12h、24h血肿周围和对侧皮质脑组织对伊文氏蓝的通透性、脑组织含水量、神经功能障碍程度进行对比观察。结果发病6h后老龄和低龄大鼠均出现BBB的破坏,12h和24h时老龄纽破坏较低龄组更为严重;24h时老龄组脑组织含水量、神经功能缺损、T_2WI显示的病灶体积(包括血肿和水肿)均明显大干低龄组。结论老龄大鼠脑出血后神经功能损害、血肿周围组织水肿、BBB破坏均较低龄大鼠严重。     

脑出血后脑水肿经时变化机制的探讨

目的 研究脑出血(mtracerebral hemorrhage，ICH)后血肿周围脑水肿与血脑屏障(blood-brain barrier，BBB)随时间变化的机制，从而为预防脑水肿提供依据。方法90只大耳白兔随机分为3组。1组：在立体定向仪下将300μl生理盐水注入兔左侧基底节；2组：注入200μl自身动脉血与100μl生理盐水；3组：注入200μl自身动脉血与100μl水蛭素。每组每时相(6h、12h、24h、48h、72h)各6只兔。脑组织含水量采用干湿重法测量，血脑屏障的通透性测定采用伊文思兰法。结果动脉血组及水蛭素干预组血肿周围脑组织含水量均在48h达到高峰．此后逐步降低。动脉血组伊文思兰(EB)于24h到达高峰，水蛭素干预组伊文思兰(EB)于48h达高峰。结论脑出血后脑水肿是多种因素综合作用的结果。早期可能和血块凝缩、流体静力压有关；至中期时凝血酶是主导因素；后期则主要由于红细胞裂解物的损害。     

实验性脑出血大鼠脑水肿的动态变化

目的研究大鼠脑出血后脑水肿的动态变化。方法应用立体定向技术,用大鼠自体股动脉血液100μl缓慢注入大鼠尾状核,制成脑出血模型,动态观察脑水肿的时空变化。脑水肿的测定应用干/湿重法。结果脑出血血肿周围组织含水量与对照组间差别有显著性意义,出血侧脑组织含水量与出血对侧脑组织含水量间差别有显著性意义,以出血后24-72h最明显, 至脑出血后第7d大致恢复正常。24h出血侧基底节脑组织含水量为(77．80±0．53)％,出血对侧为(77．53±0．43)％;72h出血侧基底节为(79.42±0．89)％,出血对侧为(77．64±0．34)％;假手术组手术侧基底节为(76．86±0．88)％,手术对侧为(76．89± 0．87)％。结论脑出血后脑水肿的变化是导致疾病恶化的主要原因之一。     

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.     

Comparison of rates of infection of two methods of emergency ventricular drainage.

The rates of infection of two methods of external ventricular drainage in use at Atkinson Morley's Hospital--namely, (a) percutaneous drainage with Rickham reservoirs and (b) tunnelled ventriculostomies--were compared in this retrospective review. Percutaneous drainage of CSF with Rickham reservoirs was associated with a 27% rate of infection as identified by positive microbiological cultures; tunnelled ventriculostomy catheters had a 10% infection rate. The difference in the infection rate between the two methods was statistically significant (P < 0.015). Other variables examined, including the age and sex of the patients and the reasons for ventricular drainage, were not associated with an increased rate of infection. Most infections from either method were caused by a coagulase negative staphylococcus. The average duration of ventricular drainage before identification of positive cultures was 5.7 days for Rickham reservoirs and 6.0 days for ventriculostomies.