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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic Encephalopathy (HE) is a serious neuropsychiatric condition of both acute and chronic liver failure. Acute liver failure is characterized by rapid evolution of HE and by brain edema. Portal-Systemic encephalopathy (PSE) is particularly prevalent following treatment of portal hypertension or ascites by the TIPS procedure. Available evidence currently suggests that neurotransmission changes rather than brain energy failure are the primary cause of HE. Recent studies both in autopsied brain tissue from HE patients as well as in experimental animal models of HE reveal that liver failure results in altered expression of several genes coding for proteins having key roles in the control of neuronal excitability. Such alterations include decreased expression of the glutamate transporter GLT-1, and increased expression of monoamine oxidase (MAO-A isoform), the "peripheral-type" benzodiazepine receptor (PTBR) as well as constitutive neuronal nitric oxide synthase (nNOS). Such changes result in altered protein expression and in increased extracellular brain glutamate, increased degradation of monoamine neurotransmitters, increased synthesis of neurosteroids with inhibitory properties, and increased production of nitric oxide (respectively) in brain in chronic liver failure. In the case of GLT-1, PTBR, and nNOS, alterations in expression result from exposure to ammonia and/or manganese, two neurotoxic agents shown previously to be increased in brain in liver failure.
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PMID:Neurotransmitter dysfunction in hepatic encephalopathy: new approaches and new findings. 1172 89

Evidence from both clinical and experimental studies demonstrates that mild hypothermia prevents encephalopathy and brain edema in acute liver failure (ALF). As part of a series of studies to elucidate the mechanism(s) involved in this protective effect, groups of rats with ALF resulting from hepatic devascularization were maintained at either 37 degrees C (normothermic) or 35 C (hypothermic), and neurological status was monitored in relation to cerebrospinal fluid (CSF) concentrations of ammonia and lactate. CSF was removed via implanted cisterna magna catheters. Mild hypothermia resulted in a delay in onset of encephalopathy and prevention of brain edema, CSF concentrations of ammonia and lactate were concomitantly decreased. Blood ammonia concentrations, on the other hand, were not affected by hypothermia in ALF rats. These findings suggest that brain edema and encephalopathy in ALF are the consequence of ammonia-induced impairment of brain energy metabolism and open the way for magnetic resonance spectroscopic monitoring of cerebral function in ALF. Mild hypothermia could be beneficial in the prevention of severe encephalopathy and brain edema in patients with ALF awaiting liver transplantation.
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PMID:Mild hypothermia prevents cerebral edema and CSF lactate accumulation in acute liver failure. 1172 93

Cerebral edema and hepatic encephalopathy are major complications of acute liver failure. Brain herniation caused by increased intracranial pressure as a result of cell swelling is the major cause of death in this condition. Evidence available currently suggests that the rapid accumulation of ammonia by the brain is the major cause of the central nervous system complications of acute liver failure. Increased brain ammonia may cause cell swelling via the osmotic effects of an increase in astrocytic glutamine concentrations or by inhibition of glutamate removal from brain extracellular space. Acute liver failure results in altered expression of several genes in brain, some of which code for important proteins involved in CNS function such as the glucose (GLUT-1) and glutamate (GLT-1) transporters, the astrocytic structural protein glial fibrillary acidic protein (GFAP) the "peripheral-type" benzodiazepine receptor (PTBR) and the water channel protein, aquaporin IV. Loss of expression of GLT-1 results in increased extracellular brain glutamate in acute liver failure. Experimental acute liver failure also results in post-translational modifications of the serotonin and noradrenaline transporters resulting in increased extracellular concentrations of these monoamines. Therapeutic measures currently used to prevent and treat brain edema and encephalopathy in patients with acute liver failure include mild hypothermia and the ammonia-lowering agent L-ornithine-L-aspartate.
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PMID:Alterations in expression of genes coding for key astrocytic proteins in acute liver failure. 1174 25

Disorders of ammonia metabolism including urea cycle enzymopathies, Reye Syndrome, and liver failure are associated with brain edema and severe neurological impairment. Excess blood-borne ammonia crosses the blood-brain barrier by diffusion as NH(3) where it interacts with various cellular processes involved in neurotransmission and brain energy metabolism. Ammonia exerts a potent effect on glutamate (AMPA) receptor-mediated neurotransmission. Ammonia also inhibits high affinity transport of glutamate by an action on astrocytic glutamate transporter expression, an action which results in increased extracellular concentrations of glutamate. Acute hyperammonemia directly activates the NMDA subclass of glutamate receptors resulting in increased intracellular Ca(2+) and increased synthesis of nitric oxide and cGMP. Chronic hyperammonemia, on the other hand, results in a loss of NMDA receptor sites. Activation of NMDA receptors in acute ammonia toxicity results in depletion of ATP in brain. Neuropathologic studies in experimental animals with congenital urea cycle disorders and severe hyperammonemia reveal evidence of neuronal cell death which is excitotoxic in nature. These findings suggest that overactivation of NMDA receptors is a significant feature of acute hyperammonemic syndromes and that antagonists of these receptors or of their signal transduction pathway enzymes such as nNOS could be beneficial in the treatment of the central nervous system manifestations (encephalopathy, brain edema) which are characteristic of hyperammonemic disorders.
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PMID:Glutamate transporter and receptor function in disorders of ammonia metabolism. 1175 22

A previously healthy, 29-year-old man developed generalized convulsion with disturbed consciousness 3 days after the flu-like symptoms. On the next day, his convulsion evolved into generalized status epilepticus (GSE) that was unresponsive to administration of various anticonvulsants. Then, intravenous anesthetic agents, including midazolam, propofol and vecuronium sodium, were continuously infused. During the following 9 days, despite of high-dose infusion of these anesthetic agents, his GSE could not be suppressed, and complex partial seizure with secondary generalization frequently occurred. The patient was comatose and mechanically ventilated, whereas the brainstem reflexes were preserved. Electroencephalogram revealed a diffuse slowing of the background activity and occasional focal spike and wave complexes with secondary generalization. Cerebrospinal fluid analysis showed pleocytosis and elevated protein concentration. Cranial CT scans obtained on day 8 demonstrated brain edema. On day 10, his GSE ceased with abolition of the brainstem reflexes, and he lapsed into brain death resulting from the progressive brain edema. Over the following six days, his systemic circulation gradually worsened, and he died on day 16. On postmortem examination, the brain was markedly edematous and showed the findings consistent with acute anoxic encephalopathy with extensive circulatory stasis. Mild gliosis was observed in the insular cortex, yet no evidence of inflammatory disease was found throughout the brain. This patient was characterized by acutely progressive severe brain edema without inflammatory changes, suggesting that his primary disease was acute toxic encephalopathy presumably induced by viral infection. His GSE was refractory and unresponsive to the intensive treatment with the intravenous anesthetic agents. This case epitomizes the difficulties in controlling refractory seizures in some patients with encephalopathy or encephalitis.
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PMID:[Acute edematous encephalopathy presenting with refractory generalized status epilepticus: an autopsy case]. 1176 16

Glial fibrillary acid protein (GFAP) is a major component of the glial filament network and alterations in expression of this protein in cultured astrocytes have been reported in response to acute ammonia exposure in vitro. In order to determine the effects of acute hyperammonemia in vivo on GFAP expression, brain extracts from rats with acute liver failure due to hepatic devascularization (portacaval anastomosis followed 24h later by hepatic artery ligation, HAL) were analyzed for GFAP mRNA using reverse transcription-polymerase chain reaction (RT-PCR) and appropriate oligonucleotide primers. GFAP protein was assayed by immunoblotting using a polyclonal antibody. Hepatic devascularization resulted in a significant 55-68% decrease (P<0.01) of GFAP mRNA and a concomitant loss of GFAP protein at precoma and coma stages of encephalopathy when brain water content was significantly increased and brain ammonia concentrations were in the millimolar range (1-5mM). Expression of a second glial filament protein S-100beta was unaffected by acute hyperammonemia. These findings suggest a role for GFAP in cell volume regulation and that loss of GFAP expression could contribute to the pathogenesis of brain edema in acute hyperammonemic syndromes.
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PMID:Loss of expression of glial fibrillary acidic protein in acute hyperammonemia. 1202 Jun 15

The mechanisms of action of hyperbaric oxygenation (HBO) in toxic hypoxic encephalopathy (THE) were studied using clinical psychopathological examinations, functional and laboratory tests in 268 patients with THE treated by a therapeutic complex including HBO and 75 patients with THE treated routinely (controls). The earliest possible addition of HBO to a complex of treatment of THE patients led to involution of signs of brain edema shown by computer tomography (CT) and improvement of its functional activity, while in patients exposed to HBO later the psychoorganic symptoms and CT signs of cerebral ischemia did not disappear. Detoxifying, neuroimmunomodulating, and neuroimmunostimulating effects of HBO in THE were demonstrated. Early HBO treatment decreased the dysfunction of various compartments of the brain characteristic of THE. The technology of HBO developed by the authors prevented the development of socially dysadapting psychoneurological disorders and reduced the mortality of THE patients.
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PMID:[Time course of toxic hypoxic encephalopathy during combined therapy including hyperbaric oxygenation]. 1222 91

Acute liver failure (ALF) results in alterations of energy metabolites and of glucose-derived amino acid neurotransmitters in brain. However, the dynamics of changes in glucose metabolism remain unclear. The present study was undertaken using (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy to determine the rates of incorporation of glucose into amino acids and lactate via cell-specific pathways in relation to the severity of encephalopathy and brain edema in rats with ALF because of hepatic devascularization. Early (precoma) stages of encephalopathy were accompanied by significant 2- to 4.5-fold (P <.001) increases of total brain glutamine and lactate concentrations. More severe (coma) stages of encephalopathy and brain edema led to a further significant increase in brain lactate but no such increase in glutamine. Furthermore, (13)C isotopomer analysis showed a selective increase of de novo synthesis of lactate from [1-(13)C]glucose resulting in 2.5-fold increased fractional (13)C enrichments in lactate at coma stages. [2-(13)C]glutamine, synthesized through the astrocytic enzyme pyruvate carboxylase, increased 10-fold at precoma stages but showed no further increase at coma stages of encephalopathy. (13)C-label incorporation into [4-(13)C]glutamate, synthesized mainly through neuronal pyruvate dehydrogenase, was selectively reduced at coma stages, whereas brain GABA synthesis was unchanged at all time points. In conclusion, increased brain lactate synthesis and impaired glucose oxidative pathways rather than intracellular glutamine accumulation are the major cause of brain edema in ALF. Future NMR spectroscopic studies using stable isotopes and real-time measurements of metabolic rates could be valuable in the elucidation of the cerebral metabolic consequences of ALF in humans.
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PMID:Selective increase of brain lactate synthesis in experimental acute liver failure: results of a [H-C] nuclear magnetic resonance study. 1254 Jul 93

During influenza epidemics in Japan, the number of children with acute encephalopathies and encephalitis has recently increased. Although the pathophysiologies remain unclear, there is usually brain edema with evidence of damage to the blood-brain-barrier (BBB). We investigated the glial reaction and apoptosis in brains of eight such cases comprising two of acute necrotizing encephalopathy and six of influenza encephalopathy, and compared the results with those in five control brains. Apoptosis, evidenced by chromatin condensation and fragmentation in hematoxylin sections, in situ end labeling of fragmented DNA (TUNEL) and DNA laddering, was observed in neurons and glial cells in four brains with influenza encephalopathy. In the TUNEL-positive brains, the increase in microglia was greater than in the TUNEL-negative brains. Immunoreactivity for active-caspase 3, demonstrated by immunohistochemistry, and the overexpression of a caspase-cleaved fragment of poly(ADP-ribose) polymerase, demonstrated by Western blotting, indicated that activation of caspase 3 is involved in the apoptotic pathway in the brains of influenza encephalopathy cases. Apoptosis or specific pathological processes that cause apoptosis may give rise to aggravated encephalopathy.
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PMID:Apoptosis and microglial activation in influenza encephalopathy. 1255 9

The pathogenesis of influenza encephalopathy or encephalitis is poorly understood. This review summarizes our recent studies of the roles played by inflammatory cytokines, inducible nitric oxide synthase (iNOS), adhesion molecules and mini-plasmin in influenza encephalitis. After the intranasal infection of newborn mice with the non-neurotropic strain of influenza A virus (IAV) Aichi/2/68/H3N2, encephalitis and severe brain edema were observed within 3-5 days. IAV-RNA and abnormalities in the blood-brain barrier permeability were detected in association with an increase in the mRNA expressions of endothelin-1, iNOS, and tumor necrosis factor-alpha. Furthermore, the accumulation in the brain capillaries of mini-plasmin, which proteolytically induces the viral envelope fusion activity and allows the virus to enter the cells, changes the brain from non-susceptible to susceptible to non-neurotropic IAV multiplication. The accumulation of mini-plasmin was markedly greater in newborn mice with an impaired mitochondrial fatty acid metabolism. These inflammatory mediators and the accumulation of mini-plasmin in the brain may play an important role in the onset and progression of LAV encephalitis.
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PMID:Pathologic mechanisms of influenza encephalitis with an abnormal expression of inflammatory cytokines and accumulation of mini-plasmin. 1263 May 63


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