暴发性肝损伤肝性脑病大鼠血浆及脑游离氨基酸变化的相关分析

本文测定了D-氨基半乳糖所致暴发性肝损伤肝性脑病大鼠血浆及脑勺浆游离氨基酸含量的变化,并作相应的相关分析。结果表明,正常大鼠血浆及脑内各种氨基酸含量间均无相关。肝性脑病大鼠血浆及脑勺浆多种氨基酸水平均有增高,脑内大多数氨基酸含量与血浆相应氨基酸的变化无相关关系,但一些与肝性脑病发生相关的氨基酸水平与其相应的血浆含量呈显著相关。提示肝性脑病的发生与血脑屏障氨基酸转运功能选择性改变有关。     

内毒素诱发肝硬化大鼠发生肝性脑病的实验研究

目的：观察外源性内毒素诱发肝硬化大鼠发生肝性脑病的可能性及可能机制。方法：采用腹腔内小剂量内毒素一次性注射（３００μｇ／１００ｇＢＷ）诱发肝硬化大鼠发生肝性脑病。结果：小剂量内毒素腹腔内注射可以诱发肝硬化大鼠发生肝性脑病。内毒素注射后,动物一般行为状态及脑电图皆有明显变化,与其他肝性脑病模型或肝性脑病病人类似。同时,血氨和胰高血糖素水平显著升高。血浆内毒素含量与血氨、血胰高血糖素含量之间及血氨与务     

内霉素诱发肝性脑病大鼠脑超微结构观察

目的：观察内毒素诱发肝硬化大鼠发生肝性脑病时血脑屏障超微结构变化。方法：用小剂量内毒素（３ ｍｇ／ｋｇＢＷ）一次性腹腔内注射诱发肝硬化大鼠发生肝性脑病。取部分大脑皮层组织制备超薄切片,在电子显微镜下观察其超微结构变化。结果：肝性脑病大鼠脑微血管明显扩张,内皮皱折增多,内皮下基底膜电子密度降低,甚至局部溶解消失。微血管周围星状胶质细胞突起及皮层内胶质细胞明显肿胀,细胞器成分减少,基质解聚。结论：内毒素诱发肝性脑病时,脑超微结构确有明显变化。这些变化提示,肝性脑病发生时,血脑屏障通透性增加;同时,脑胶质细胞呈现水肿。内毒素血症有可能是各种肝性脑病发生机制学说的共同基础。     

内毒素诱发肝性脑病大鼠脑超微结构观察

目的：观察内毒素诱发肝硬化大鼠发生肝性脑病时血脑屏障超微结构变化。方法：用小剂量内毒素（３ｍｇ／ｋｇＢＷ）一次性腹腔内注射诱发肝硬化大鼠发生肝性脑病。取部分大脑皮层组织制备超薄切片,在电子显微镜下观察其超微结构变化。结果：肝性脑病时血脑病大鼠脑微血管明显扩张。内皮皱折增多,内皮下基底膜电子密度降低。甚至局部溶解消失。微血管周围星状胶质细胞突起及皮层内胶质细胞明显肿胀。细胞器成分减少,基质解聚。结论     

暴发性肝衰竭血脑屏障通透性改变对肝性脑病发生发展的影响

采用硫代乙酰胺所致大鼠暴发性肝衰模型，以脑组织浸泡液中Ｅｖａｎｓ蓝含量为血脑屏障通透性指标。结果表明，在肝性脑病初期血脑屏障通透性就已增加，至脑病晚期则明显增加，并伴脑水肿发生，脑组织浸泡液中Ｅｖａｎｓ蓝含量与血浆内毒素呈正相关。以上结果提示，暴发性肝衰竭时，肝性脑病发生发展与内毒素所致血脑屏障通透性增加密切相关。     

脑干听觉诱发电们检测对亚临床肝性脑病的诊断价值

对无临床肝性脑病的30例非酒精性肝硬化患进行脑干听觉诱发电位（BAEP）检测。结果显示：肝硬化组60％BAEP异常，BAEP的Ⅰ、Ⅲ、Ⅴ波潜伏期及Ⅰ-Ⅴ、Ⅲ-Ⅴ波峰间其均比正常对照组明显延迟，提示肝化在发生临床肝性脑病前，脑干功能已有明显损害，存在亚临床肝性脑病。     

脑干听觉诱发电位检测对亚临床肝性脑病的诊断价值

对无临床肝性脑病的 30例非酒精性肝硬化患者进行脑干听觉诱发电位 (BAEP)检测。结果显示 :肝硬化组 6 0 ?EP异常 ,BAEP的Ⅰ、Ⅲ、Ⅴ波潜伏期及Ⅰ—Ⅴ、Ⅲ—Ⅴ波峰间期均比正常对照组明显延迟 ,提示肝硬化在发生临床肝性脑病前 ,脑干功能已有明显损害 ,存在亚临床肝性脑病     

NO在脂多糖诱发的肝硬化大鼠肝性脑病中的作用

目的:探讨一氧化氮(NO)在LPS诱发的肝硬化大鼠肝性脑病中所起的作用。方法:采用复合因素复制肝硬化大鼠模型,于实验8周末开始分别用09%盐水、L-精氨酸(L-arg)和N-亚硝基L-精氨酸(LNNA)给大鼠灌胃2周。在处死大鼠前4h,腹腔内一次性注射LPS3mg/kg,以诱发大鼠肝性脑病。结果:L-arg组大鼠活动灵活且脑电图基本正常,LNNA组出现肝性脑病。L-arg组脑组织NO₂^-/NO₃^-含量明显高于LNNA组(P<0.05),脑组织组胺含量明显低于LNNA组(P<0.05)。脑组织中组胺含量与脑组织中NO₂^-/NO₃^-含量呈负相关。结论:NO能抑制LPS诱发肝硬化大鼠肝性脑病的发生。     

P300等诱发电位对亚临床肝性脑病早期诊断的意义

目的:观察事件相关电位P_(300)、体感诱发电位、视觉诱发电位和脑干听觉诱发电位在亚临床肝性脑病诊断中的意义。方法:50例亚临床肝性脑病患者进行了心理测验,并做了头颅CT和视觉诱发电位、体感诱发电位、脑干听觉诱发电位和事件相关电位检查,30例正常人做为对照组。结果:亚临床肝性脑病的心理测验,韦氏法智力低下率为76％,视觉诱发电位异常率为13％,脑干听觉诱发电位异常率为20％,体感诱发电位异常率为40％,事件相关电位异常率为71％,正常对照组四种诱发电位的正常率是100％。头颅CT结果与亚临床肝性脑病无关。结论:视觉诱发电位、体感诱发电位、脑干听觉诱发电位和事件相关电位在亚临床肝性脑病中是异常的。事件相关电位更为敏感,对亚临床肝性脑病的早期诊断有重要意义。     

纳洛酮治疗亚临床型肝性脑病疗效观察

目的探讨纳洛酮治疗亚临床型肝性脑病(SHE)的疗效。方法69例SHE按双盲法随机分为治疗组及对照组二组,分别给予纳洛酮0.4mg、0.9%氯化钠静脉推注,连用5-10天,用药前后分别作数字连接试验(NCT)、数字符号试验(DS)、脑干诱发电位(BAEP),并随访有否发性临床型肝性脑病。结果治疗组治疗后各项指标均较治疗前有明显改善,且随访无一例发生肝性脑病,对照组治疗前后各项指标改善不明显,且随诊有3例发生临床型肝性脑病。结论纳洛酮是一种对SHE治疗有效的药物。     

Regional distribution of metabotropic glutamate response in the rat brain using Xenopus oocytes

The regional distribution of metabotropic L-glutamate responses was investigated in Xenopus oocytes injected with poly(A)+-RNA from a rat brain which was separated into 3 parts: cerebrum, cerebellum and brainstem. Under voltage-clamp, oscillatory current responses were induced more in cerebellum or brainstem poly (A)+-RNA-injected oocytes, and less in cerebrum poly(A)+-RNA-injected oocytes. These results suggest that the metabotropic glutamate receptor is distributed mostly in cerebellum and brainstem.     

The role of astrocytes in the development of hepatic encephalopathy

Thioacetamide (TAA), a hepatotoxin used to ascertain the role of astrocytes in hepatic encephalopathy, was administered to prepare four experimental groups of rats. (The TAA1D, TAA1.5D, TAA2D, and TAA2.5D group rats were perfusion fixated with formalin at 1, 1.5, 2, and 2.5 days, respectively, after initial administration of TAA. In addition, TAA was readministered to the TAA2D and TAA2.5D rats 24 h after the first dose.) Abnormalities of higher brain function and equilibrium that progressed with time were apparent in the rats receiving TAA. On the other hand, innate reflexes (e.g. pupillary reflex) were similar to those in the normal control group. Astrocyte cell areas in the hippocampus, neocortex, hypothalamus, cerebellum, and basal ganglia (striatum) from the TAA rats were significantly larger than in corresponding sites from the normal rats (maximum in TAA1D and TAA1.5D groups). However, there were no differences with respect to the midbrain. Any morphological difference was not observed in neurons between the hepatic encephalopathy and normal rats. Administration of TAA caused hepatic tissue injury that progressed over time. Surprisingly, encephalopathy was apparent even when hepatic injury was mild. These findings suggest that abnormalities in astrocytes, which precede any abnormal change in neurons, play a role in the development of hepatic encephalopathy.     

Extracorporeal treatment in fulminant hepatic failure: pathophysiologic considerations

Fulminant hepatic failure is a life-threatening clinical syndrome following severe hepatic injury leading to cerebral edema and brainstem herniation. Excessive mortality can be currently reduced only by timely orthotopic liver transplantation. Due to the shortage of donor organs, a considerable proportion of patients develop irreversible neurological damage, multiorgan failure or death while waiting for transplantation. Consequently, alternatives to orthotopic liver transplantation and methods of stabilizing patients on the waiting list including extracorporeal detoxification treatment are currently investigated. Recent advances in the pathophysiology of cerebral edema have challenged some of the traditional assumptions on which many blood detoxification systems are based. This article aims to integrate pathophysiology of hepatic encephalopathy and cerebral edema into a proposed future concept of liver support.     

Acute exposure to sarin increases blood brain barrier permeability and induces neuropathological changes in the rat brain: dose-response relationships

We hypothesize that a single exposure to an LD(50) dose of sarin induces widespread early neuropathological changes in the adult brain. In this study, we evaluated the early changes in the adult brain after a single exposure to different doses of sarin. Adult male rats were exposed to sarin by a single intramuscular injection at doses of 1, 0.5, 0.1 and 0.01 x LD(50). Twenty-four hours after the treatment, both sarin-treated and vehicle-treated (controls) animals were analyzed for: (i) plasma butyrylcholinesterase (BChE) activity; (ii) brain acetylcholinesterase (AChE) activity, (iii) m2 muscarinic acetylcholine receptor (m2 mAChR) ligand binding; (iv) blood brain barrier (BBB) permeability using [H(3)]hexamethonium iodide uptake assay and immunostaining for endothelial barrier antigen (EBA); and (v) histopathological changes in the brain using H&E staining, and microtubule-associated protein (MAP-2) and glial fibrillary acidic protein immunostaining. In animals treated with 1 x LD(50) sarin, the significant changes include a decreased plasma BChE, a decreased AChE in the cerebrum, brainstem, midbrain and the cerebellum, a decreased m2 mAChR ligand binding in the cerebrum, an increased BBB permeability in the cerebrum, brainstem, midbrain and the cerebellum associated with a decreased EBA expression, a diffuse neuronal cell death and a decreased MAP-2 expression in the cerebral cortex and the hippocampus, and degeneration of Purkinje neurons in the cerebellum. Animals treated with 0.5 x LD(50) sarin however exhibited only a few alterations, which include decreased plasma BChE, an increased BBB permeability in the midbrain and the brain stem but without a decrease in EBA expression, and degeneration of Purkinje neurons in the cerebellum. In contrast, animals treated with 0.1 and 0.01 x LD(50) did not exhibit any of the above changes. However, m2 mAChR ligand binding in the brainstem was increased after exposure to all doses of the sarin.Collectively, the above results indicate that, the early brain damage after acute exposure to sarin is clearly dose-dependent, and that exposure to 1 x LD(50) sarin induces detrimental changes in many regions of the adult rat brain as early as 24 hours after the exposure. The early neuropathological changes observed after a single dose of 1 x LD(50) sarin could lead to a profound long-term neurodegenerative changes in many regions of the brain, and resulting behavioral abnormalities.     

Amino acid disturbances in experimental hepatic coma rats

In our previous paper (1), we discussed the in-vitro adsorption spectrum of plasma amino acids by coated charcoal hemoperfusion. We now describe the general amino acid disturbances in plasma, CSF and cerebrum in the galactosamine induced hepatic coma model in rats. All aromatic amino acids (AAA) increased significantly in the three compartments studied. Branched chain amino acids (BCAA) were either elevated to a much lesser extent or remained unchanged. The molar ratio of BCAA:AAA was consequently reduced. This is similar to findings in fulminant hepatic failure in human and other animal models. Most of the 20 amino acids analyzed were increased significantly in the plasma. Increases of amino acids were minimal in the brain tissue studied, i.e. the cerebrum.     

Subclinical hepatic encephalopathy: relationship between neuropsychological deficits and standard laboratory tests assessing hepatic status.

A multivariate analysis of the relationship between biochemical measures of hepatic function and neuropsychological assessments of specific cognitive domains was performed on data obtained from 74 patients with chronic liver disease and subclinical hepatic encephalopathy. Biochemical tests of hepatic protein synthesis correlated significantly with measures of impaired language efficiency, perceptual speed, and psychomotor efficiency. Biochemical indices of impaired processing of nitrogenous compounds correlated with visuopractic deficits. Hepatic blood flow indices correlated with language inefficiency. Interestingly, biochemical measures of hepatic injury did not demonstrate a significant association with any neuropsychological parameter assessed. These results suggest that subclinical hepatic encephalopathy is the consequence of a multifactorial hepatic dysfunction, and that acute hepatic injury, as assessed by elevation of aminotransferases, does not appear to be involved in the pathogenesis of subclinical hepatic encephalopathy.     

Louping-ill encephalomyelitis in the sheep: II. Distribution of virus and lesions in nervous tissue

Louping-ill virus was demonstrated consistently, by both virus isolation and immunofluorescence, in nervous tissue from moribund sheep. In only one case was virus detected in cerebrospinal fluid. Viral antigen was observed only in neuronal cytoplams. The distributions of virus and nerve cell damage corresponded. The highest concentrations of virus were found in the brainstem and spinal cord, where neuron necrosis was also most apparent. The cerebellum was less uniformly affected. Lesions in the cerebrum were predominantly inflammatory, and virus was detected less frequently and in smaller amounts. There were slight pathological changes in surviving animals, but virus could not be demonstrated in nervous tissue.     

Identification of cells responsible for synthesis of sulphated glycosaminoglycans in schistosome-induced hepatic granulomas

Sulphated glycosaminoglycans were isolated from schistosome-induced hepatic granuloma and from the pericellular, intracellular and extracellular compartments of two murine cell lines derived from granulomas: the primary cell line GR, and the permanent cell line GRX, established spontaneously from GR. The glycosaminoglycans composition in the whole granuloma was similar to that observed in the intracellular and extracellular compartments of GR cells. This result suggests that GR cells may be the major cell population involved in the synthesis and accumulation of glycosaminoglycans in the granulomas, and play an important role in the process of hepatic fibrosis. The conversion of the primary cell line GR into the established GRX cells did not modify the ratios that prevail among different glycosaminoglycans of the cell surface. However, it decreased the synthesis and secretion of glycosaminoglycans, reduced the proportion of iduronic acid units in the chondroitin sulphate, and increased the proportion of heparan sulphate in intracellular and extracellular pools. These characteristics of the GRX cells are similar to those observed in long-term cultures of smooth-muscle cells. In agreement with the general phenomenon of progressive de-differentiation during in-vitro culture of primary cell lines, these data indicate that the connective tissue cells of liver may belong to the myofibroblastic cell lineage.