Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In situ hybridization to mitochondrial ribosomal RNA (rRNA) has been used to study the distribution of mitochondria in paraffin-embedded autopsy brain tissue from two patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and other organs from one of the patients. Comparison of in situ hybridization and electron microscopic findings in an antemortem biopsy specimen of pylorus from the latter patient showed a close correspondence between the distribution of hybridization signal on light microscopy and of mitochondria in ultrathin sections. Strong hybridization signal was present over smooth muscle fibres of the muscularis externa, which contained abnormal accumulations of mitochondria on electron microscopy. Hybridization to sections of skeletal muscle confirmed previous reports of 'ragged-red' fibres in this disorder and of mitochondrial accumulations in the walls of intramuscular blood vessels. To try to elucidate the role of vessel wall accumulation of mitochondria in the genesis of the stroke-like lesions, the distribution of mitochondrial rRNA was assessed in sections of brain from both of the cases of MFLAS and several cases of atherothrombotic cerebrovascular disease. Blood vessels in and adjacent to the cerebral lesions of MELAS showed strong hybridization signal with the mitochondrial probes, as was also seen in infarcts of various ages in the control brains. Only weak signal was present in the walls of blood vessels distant from the lesions, in both MELAS and control brains. These findings suggest that mitochondria accumulate in vascular endothelium and tunica media as a normal response to cerebral infarction or ischaemia. The accumulation of mitochondria in the cerebral lesions of MELAS may, at least in part, be a reaction to the destructive effects of the underlying metabolic dysfunction.
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PMID:Assessment of the distribution of mitochondrial ribosomal RNA in melas and in thrombotic cerebral infarcts by in situ hybridization. 868 87

Encephalopathy associated with dengue fever is considered to be a rare condition in adults. We describe a patient with a primary dengue infection who, in the absence of overt signs of dengue shock syndrome, died due to progressive cerebral oedema. Autopsy findings demonstrated loss of integrity of cerebral vascular endothelium and involvement of complement activation.
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PMID:Fatal cerebral oedema associated with primary dengue infection. 966 54

Mouse adenovirus-type 1 (MAV-1) has recently been shown to cause a fatal hemorrhagic encephalopathy in certain strains of mice whereas other strains are resistant. Morbidity is associated with a productive infection of cerebrovascular endothelial cells, resulting in necrosis of the vasculature, infarction, hemorrhage and death within 4 - 6 days. Previous studies were not able to define a role for the innate or acquired immune response. In the current study we have addressed the effect of MAV-1 on chemokine and chemokine receptor expression in the central nervous system (CNS) and spleen of susceptible (C57BL/6) and resistant (BALB/c) strains of mice. Intra-peritoneal infection with MAV-1 in C57BL/6 animals resulted in early and prominent induction of IP-10/crg-2 in the spleen and CNS. Increased expression of MCP-1, MIP-1alpha, MIP-1beta and RANTES was also noted in the CNS of MAV-1-infected C57BL/6 animals commencing around 72 h post-infection. In contrast, chemokine expression in BALB/c animals was more restricted with prominent upregulation only of MIP-2 in the CNS. In situ hybridization identified the vascular endothelium and CNS glia as the principal site of IP-10/crg-2 production in the C57BL/6 animals. The chemokine receptors CCR1-5 were upregulated in the CNS of both strains of mice. These data show that productive infection of the CNS with MAV-1 leads to the upregulation of a characteristic pattern of chemokines and their receptors, which may point to a role for these factors in disease pathogenesis.
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PMID:Differential chemokine induction by the mouse adenovirus type-1 in the central nervous system of susceptible and resistant strains of mice. 1019 Jun 91

It is widely accepted that vascular mechanisms are involved in the genesis of many neurological disorders. In particular, blood-brain barrier (BBB) dysfunction has been related to the severity of Alzheimer's disease, encephalopathy due to meningitis, multiple sclerosis, HIV-associated encephalopathy, epilepsy, gliomas and metastatic brain tumors. The BBB may constitute an important therapeutic target to protect neurons after CNS diseases. Both in vivo and in vitro, the functional phenotype of vascular endothelium is dynamically responsive to circulating cytokines, growth factors and puslatile blood flow (shear stress). Shear stress can play a critical role in vascular homeostasis and pathophysiology; it is a major regulator of remodeling in developed blood vessels and in blood vessels affected by atherosclerotic lesions. The physiological fluid mechanic stimulus, shear stress, could be considered to be an important 'differentiative' stimulus capable of modulating endothelial phenotype in vivo. Endothelial cells undergo cell cycle arrest after exposure to physiological levels of shear stress. As for mature endothelial cells, in which flow mediated shear stress may play a role in the induction, progression and/or prevention of atherosclerosis by changing their function, stress may play a role in endothelial cell differentiation from hemopoietic stem cells and/or from embryonic stem cells. Stem cells may be used to repair vascular damage, including loss of EC, due to a variety of diseases (e.g. myocardial neovascularization by adult bone marrow derived angioblasts). In the brain, it was proposed that neuron-producing stem cells may be used to treat Alzheimer's disease, paralysis, etc. Surprisingly, very few investigators are exploring the use of endothelial precursors to revert or prevent cerebrovascular disease. This review summarizes the most recent data related to cerebral vasculature as a therapeutic target for neurological disorders and the role of shear stress in blood-brain barrier homeostasis and pathophysiology.
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PMID:The cerebral vasculature as a therapeutic target for neurological disorders and the role of shear stress in vascular homeostatis and pathophysiology. 1572 68

Cerebral malaria (CM) remains a deadly complication of Plasmodium falciparum infection, and children are at high risk of developing encephalopathy as a result of CM. This is probably a consequence of the activation of many of the inflammatory cytokines as well as the glial cells and the vascular endothelium in the brain. We have previously demonstrated that there is a striking reduction in cerebral blood flow by magnetic resonance imaging when mice are infected with Plasmodium berghei ANKA (PbA), and we now demonstrate a possible role for endothelin (ET-1) in the pathogenesis of CM. The brains of female C57BL/6 mice with PbA infection were examined at Day 5 for the expression of ET-1, endothelin converting enzyme (ECE), and the endothelin receptors A and B (ET(A) and ET(B)) by both reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR. ET-1 and ECE mRNA expression was markedly increased by RT-PCR in PbA-infected mice. Real-time quantitative PCR demonstrated a 3-fold increase in ET-1 (P < 0.05) and a significant increase in ET(A) and ET(B) expression (P < 0.05) in PbA-infected mice. Histopathology bof PbA-infected mice demonstrated a transformation in the morphology of microglial cells and clustering of these cells consistent with activation. Though the full impact of ET-1 on CM remains to be elucidated, these findings demonstrate that in the murine model, there is a significant increase in ET-1 and its components, which is associated with the vasculopathy and immunopathology of CM.
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PMID:Endothelin in a murine model of cerebral malaria. 1674 Oct 72

Inflammatory leukocytes infiltrate the CNS parenchyma in neuroinflammation. This involves cellular migration across various structures associated with the blood-brain barrier: the vascular endothelium, the glia limitans, and the perivascular space between them. Leukocytes accumulate spontaneously in the perivascular space in brains of transgenic (Tg) mice that overexpress CCL2 under control of a CNS-specific promoter. The Tg mice show no clinical symptoms, even though leukocytes have crossed the endothelial basement membrane. Pertussis toxin (PTx) given i.p. induced encephalopathy and weight loss in Tg mice. We used flow cytometry, ultra-small superparamagnetic iron oxide-enhanced magnetic resonance imaging, and immunofluorescent staining to show that encephalopathy involved leukocyte migration across the glia limitans into the brain parenchyma, identifying this as the critical step in inducing clinical symptoms. Metalloproteinase (MPs) enzymes are implicated in leukocyte infiltration in neuroinflammation. Unmanipulated Tg mice had elevated expression of tissue inhibitor of metalloproteinase-1, matrix metalloproteinase (MMP)-10, and -12 mRNA in the brain. PTx further induced expression of tissue inhibitor of metalloproteinase-1, metalloproteinase disintegrins-12, MMP-8, and -10 in brains of Tg mice. Levels of the microglial-associated MP MMP-15 were not affected in control or PTx-treated Tg mice. PTx also up-regulated expression of proinflammatory cytokines IL-1beta and TNF-alpha mRNA in Tg CNS. Weight loss and parenchymal infiltration, but not perivascular accumulation, were significantly inhibited by the broad-spectrum MP inhibitor BB-94/Batimastat. Our finding that MPs mediate PTx-induced parenchymal infiltration to the chemokine-overexpressing CNS has relevance for the pathogenesis of human diseases involving CNS inflammation, such as multiple sclerosis.
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PMID:Metalloproteinases control brain inflammation induced by pertussis toxin in mice overexpressing the chemokine CCL2 in the central nervous system. 1708 42

C-peptide, historically considered a biologically inactive peptide, has been shown to exert insulin-independent biological effects on a number of cells proving itself as a bioactive peptide with anti-inflammatory properties. Type 1 diabetic patients typically lack C-peptide, and are at increased risk of developing both micro- and macrovascular complications, which account for significant morbidity and mortality in this population. Inflammatory mechanisms play a pivotal role in vascular disease. Inflammation and hyperglycemia are major components in the development of vascular dysfunction in type 1 diabetes. The anti-inflammatory properties of C-peptide discovered to date are at the level of the vascular endothelium, and vascular smooth muscle cells exposed to a variety of insults. Additionally, C-peptide has shown anti-inflammatory properties in models of endotoxic shock and type 1 diabetes-associated encephalopathy. Given the anti-inflammatory properties of C-peptide, one may speculate dual hormone replacement therapy with both insulin and C-peptide in patients with type 1 diabetes may be warranted in the future to decrease morbidity and mortality in this population.
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PMID:Anti-inflammatory properties of C-Peptide. 2003 6

Blood-brain barrier (BBB) disruption occurs during human immunodeficiency virus encephalopathy, but the mechanisms involved are not understood. We studied how acute and ongoing exposure to human immunodeficiency virus 1 envelope gp120 alters BBB structure and permeability. Intravenous Evans blue, given before stereotaxic gp120 injection into the caudate putamen of rats, was rapidly extravasated. Gelatinolytic activity, studied by in situ zymography, was increased after gp120 administration and was localized within cerebral vessel walls. The gp120 increased the expression of matrix metalloproteinases (MMPs) 2 and 9. Laminin and claudin-5, key BBB components and targets of both MMPs, were greatly reduced upon gp120 administration. The gp120 increased lipid peroxidation in the vascular endothelium and in neurons. Prior administration of rSV40 vectors carrying the antioxidant enzymes Cu/Zn superoxide dismutase or glutathione peroxidase protected from gp120-induced BBB damage. N-methyl-D-aspartate receptor activation upregulated pro-MMP-9 and increased MMP-9 gelatinase activity, and memantine, an N-methyl-D-aspartate receptor blocker, mitigated gp120-induced BBB abnormalities. Using intra-caudate putamen SV(gp120) to test the effects of chronic exposure to expressed gp120, we determined that oxidant stress and increased BBB permeability occurred as in acute exposure. These data indicate that both direct administration and cellular expression of gp120 lead to disruption of the BBB by increasing MMPs and reducing vascular tight junction proteins via mechanisms involving reactive oxygen species generation and oxidant injury.
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PMID:HIV-1 gp120-induced injury to the blood-brain barrier: role of metalloproteinases 2 and 9 and relationship to oxidative stress. 2061 38

Encephalopathy due to reversible cerebral edema is an important cause of neurologic morbidity accompanying many disorders. Although controversy remains concerning the pathophysiologic trigger, the mechanism of this disorder ultimately depends on failure of the blood-brain barrier to maintain the compartmentalization of intravascular fluid. This failure of the blood-brain barrier depends primarily on the capillary hydrostatic pressure, under the influence of the systemic blood pressure, and on the integrity of the structures that make up the blood-brain barrier, most importantly the vascular endothelium, under the influence of various diseases and toxic medications. Although typical clinical contexts and presentations have been well defined, many patients have atypical features that pose a diagnostic challenge. Therefore, awareness of this clinical variability is important for prompt diagnosis. This review discusses the history and pathophysiology of posterior reversible encephalopathy syndrome and then addresses its clinical diagnosis and management.
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PMID:Posterior reversible encephalopathy syndrome: a review. 2159 Jun 25

Introduction. Posterior Reversible Encephalopathy Syndrome (PRES) is an increasingly recognized clinical and radiological entity with a wide spectrum of symptoms. Its mechanism depends on failure of the blood-brain barrier due to high systemic blood pressure (BP) and loss of integrity of vascular endothelium related with different triggers. Methods. We aim to report a case of PRES induced by arterial hypertension and very early systemic sclerosis (SSc) not previously known. Results. A 64-year-old female was admitted due to 1-week pulsating headache more prominent on frontal scalp, accompanied by phonophobia, photophobia, and facial flushing. Neurological exam revealed brisk deep tendon reflex. Brain magnetic resonance imaging (MRI) showed subcortical lesions mainly located in posterior regions. BP was monitored and episodic arterial hypertension was detected. In laboratory tests positive anti-topoisomerase I antibodies were detected. BP was controlled with angiotensin-converting-enzyme inhibitors and headache improved. In a new MRI a month later improvement of white matter lesions was observed. Capillaroscopy showed "active pattern," considered typical of SSc. Conclusion. In SSc anti-endothelial cell antibodies impair vascular endothelium and liberation of vasoconstrictors leads to BP increasing and disruption of blood-brain barrier autoregulation mechanisms. PRES can be the first manifestation of very early SSc and this entity should be considered even in absence of skin lesions or Raynaud phenomenon.
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PMID:Posterior reversible encephalopathy syndrome as presenting form of very early systemic sclerosis. 2580 77


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