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)

The hamster neurotropic (HNT) strain of measles virus causes non-inflammatory encephalopathy in Balb/c mice, associated with neurodegeneration in hippocampal CA1 and CA3 regions. This loss of pyramidal cells can be prevented by twice daily systemic treatment with 1 mg/kg dizocilpine (5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate; MK-801) for 7 days. By varying the MK-801 treatment protocol, we now found that drug administration during the last 4 days prior to sacrifice (i.e. days 4-7 post inoculation, p.i.) is essential for neuroprotection. In contrast, MK-801 treatment during the first days (days 0-4 p.i.) did not prevent the neuronal necrosis. These data suggest that the concentration of an excitotoxic factor in the mouse brain increases after virus inoculation, reaching toxic levels by days 4-5 p.i. This novel 'subacute' mouse model of neurodegeneration therefore constitutes an attractive tool for mechanistic and interventional studies in excitotoxicity research.
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PMID:Measles virus-induced hippocampal neurodegeneration in the mouse: a novel, subacute model for testing neuroprotective agents. 836 21

Both clinical and epidemiological studies of the effects of exposure to toluene have shown that long-term exposure may result in chronic toxic encephalopathy, where one of the major symptoms is memory deficits. We have attempted to identify the structural basis of the toxic effects of toluene in the hippocampus, a region of the brain known to be involved in learning and memory processes and well suited for stereological analysis. Rats were exposed to 1500 ppm of toluene, six hours per day, five days per week for six months. This was followed by a four-month-period without exposure prior to sacrifice. The total number of neurons in each of the five subdivisions of hippocampus of six exposed and six control rats was estimated with the optical fractionator. A statistically significant neuron loss of 16% was found in regio inferior (CA3 and CA2) of the exposed rats.
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PMID:Neuronal loss in hippocampus in rats exposed to toluene. 885 32

The effect of sepsis on cellular calcium homeostasis in the central nervous system (CNS) was investigated using hippocampal slices of rats in which sepsis was induced by cecal ligation and puncture (CLP). Hippocampal slices were prepared from septic or sham-operated rats at 24 h after abdominal surgery. The basal intracellular calcium ([Ca2+]i) and its response to oxygen-glucose deprivation in hippocampal slices were measured for assessing cellular calcium homeostasis using fura-2 fluorescent imaging technique. The levels of [Ca2+]i were estimated by the fluorescence ratio (R340/380). Twenty-four hours after CLP, spontaneous movement was reduced and plasma lactate was increased in the septic rats in comparison with the sham-operated rats in which laparotomy was performed without CLP. Basal level of R340/380 in the CA4 ara (.72 +/- .07) was significantly higher (p < .001) in the septic group than that in the sham-operated group (.55 +/- (.06). The fluorescence ratio of septic vs. sham-operated in other hippocampal regions were .55 +/- .09 vs. .48 +/- .06 in CA1 (not significant) and .65 +/- .10 vs. .59 +/- .08 (not significant) in CA3, respectively. Increase in [Ca2+]i due to oxygen-glucose deprivation was significant in CA1 and CA3 of the septic group and in all hippocampal regions of sham-operated group. However, it was not significantly increased in CA4 of the septic group. These results suggest that regional deregulation of cellular calcium occurs in the CNS following CLP. Cellular calcium deregulation may be one of the pathogeneses occurred in clinically observed septic encephalopathy.
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PMID:Regionally different elevation of intracellular free calcium in hippocampus of septic rat brain. 890 48

Cerebral hypoxia-ischemia causes encephalopathy and neurologic disabilities in newborns by unclear mechanisms. We tested the hypothesis that hypoxia-ischemia causes brain damage in newborns that is system-preferential and related to regional oxidative metabolism. One-week-old piglets were subjected to 30 minutes of hypoxia and then seven minutes of airway occlusion, producing asphyxic cardiac arrest, followed by cardiopulmonary resuscitation and four-day recovery. Brain injury in hypoxic-ischemia piglets (n = 6) compared to controls (n = 5) was analyzed by hematoxylin-eosin, Nissl, and silver staining, relationships between regional vulnerability and oxidative metabolism were evaluated by cytochrome oxidase histochemistry. Profile counting-based estimates showed that 13% and 27% of neurons in layers II/III and layers of somatosensory cortex had ischemic cytopathology, respectively; CA1 neuronal perikarya appeared undamaged, and < 10% of CA3 and CA4 neurons were injured; and neuronal damage was 79% in putamen, 17% in caudate, but nucleus accumbens was undamaged. Injury was found preferentially in primary sensory neocortices (particularly somatosensory cortex), basal ganglia (predominantly putamen, subthalamic nucleus, and substantia nigra reticulata), ventral thalamus, geniculate nuclei, and tectal nuclei. In sham piglets, vulnerable region generally had higher cytochrome oxidase levels than less vulnerable areas. Postischemic alterations in cytochrome oxidase were regional and laminar, with reductions (31-66%) occurring in vulnerable regions and increases (20%) in less vulnerable areas. We conclude that neonatal hypoxia-ischemia causes highly organized, system-preferential and topographic encephalopathy, targeting regions that function in sensorimotor integration and movement control. This distribution of neonatal encephalopathy is dictated possibly by regional function, mitochondrial activity, and connectivity.
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PMID:Primary sensory and forebrain motor systems in the newborn brain are preferentially damaged by hypoxia-ischemia. 898 85

N-methyl-d-aspartate (NMDA) receptors represent a major subtype of excitatory amino acid receptors in the mammalian brain. In addition to their physiological role, NMDA receptors have been linked to the occurrence of nerve cell death in several neurodegenerative diseases. The hamster neurotropic (HNT) strain of measles virus causes non-inflammatory encephalopathy in mice. This is associated with neuronal loss in areas CA1 and CA3 of the hippocampus. Systemic treatment with the non-competitive NMDA receptor antagonist 5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate (MK-801) prevented this cellular necrosis. Thus, a virus may have indirect neurodegenerative effects in the brain due to activation of NMDA receptors.
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PMID:NMDA-Receptor Antagonist Prevents Measles Virus-induced Neurodegeneration. 1210 70

The industrial use of bismuth is increasing. In medicine, bismuth compounds have long been used in the treatment of gastrointestinal disorders, recently in combination with antibiotics for the treatment of Helicobacter pylori-associated peptic ulcers. Bismuth-induced encephalopathy is a known side-effect. One of the symptoms of bismuth encephalopathy is ataxia, suggesting possible cerebellar involvement. The introduction of autometallography (AMG) for tracing BiS/BiSe nanocrystals has provided histochemical evidence supporting the cerebellum being involved in bismuth encephalopathy, but the effect of bismuth on the neuron number in the cerebellum has never been evaluated. In vitro studies have indicated that CA1 neurons may be targets for bismuth intoxication, but results have been conflicting. Recently, the loss of dorsal root ganglion cells was reported after moderate bismuth exposure. This raises the question whether the use of another neurotoxic stimulus, such as hypoxia, amplifies the toxic effects of bismuth. Despite AMG-detectable bismuth accumulations, stereological examinations revealed no statistically significant decrease in the number of Purkinje, CA1 or CA3 neurons or in the volume of the cerebellar granule layer. Surprisingly, intermittent hypoxia led to a statistically significant loss of Purkinje cells without affecting the hippocampus. Bismuth neither ameliorated nor exacerbated the hypoxic effects on the cerebellum.
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PMID:Influence of bismuth on the number of neurons in cerebellum and hippocampus of normal and hypoxia-exposed mouse brain: a stereological study. 1601 41

Here we report an autopsy case of hypoglycemic encephalopathy with prolonged coma. Laboratory data obtained when the patient lapsed into a coma showed that she had a low level of serum glucose (27 mg/dL). Although the level of glucose returned to within the normal range rapidly after glucose infusion, the patient remained in a coma for 22 months. It was presumed that the state of hypoglycemia persisted for about 4 h. There was no evidence of hypotension or hypoxia. Magnetic resonance imaging was performed 3 h after glucose administration; diffusion-weighted images revealed hyperintensity in the cerebral white matter and in the boundary zone between the middle and posterior cerebral arteries. Post-mortem examination revealed superficial laminar necrosis throughout the cerebral cortex. Neuronal necrosis was also found in the hippocampus and dentate gyrus, although the CA3 region appeared normal. In addition to these lesions, which are consistent with hypoglycemia-induced brain damage, the cerebral white matter exhibited severe loss of myelin and axons with reactive astrocytosis and macrophage infiltration. Old infarcts were also present in the bilateral occipital lobes. Since the cerebral blood flow is reported to be decreased during severe hypoglycemia, the present findings suggest that white matter lesions and boundary-zone infarctions may develop primarily in uncomplicated hypoglycemia.
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PMID:Hypoglycemic encephalopathy with extensive lesions in the cerebral white matter. 1670 47

Perinatal hypoxia-ischemia remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. White matter injuries in newborn infants have long-term effects on physical, visual, motor, sensory, cognitive and social development in human infants. There is no known cure for neonatal hypoxic ischemic encephalopathy (NHIE). Activated protein C has potent anticoagulant activity due to its ability to inactivate factor Va and VIIIa. APC is the first effective biological therapy approved for the treatment of severe sepsis. Although APC is well defined as a physiological anticoagulant, emerging data suggest that it also has cytoprotective, anti-inflammatory and antiapoptotic properties. APC has been shown to provide neuroprotection in ischemic brain and spinal cord injury. Here, we propose that APC, which modulates many of these processes, may represent a promising therapeutic agent for NHIE. Seven days old Wistar Albino rat pups have been used in the study (n=42). Experimental groups in the study were: sham-operated group, APC treated group, and vehicle treated group. In hypoxia-ischemia groups, the left common carotid artery was ligated permanently on the seventh postnatal day. Two hours after the procedure, hypoxia (92% nitrogen and 8% oxygen) was applied for 2.5 h. APC were injected (intraperitoneally; i.p.) as a single dose immediately after the hypoxia period. Brain nitrite levels, neuronal cell death, and apoptosis were evaluated in both hemispheres 72 h after the hypoxic-ischemic insult. Histopathological evaluation demonstrated that APC significantly diminished the number of "apoptotic cells" in the hippocampal CA1, CA2, CA3 and gyrus dentatus regions in both hemispheres. APC treatment significantly reduced "apoptotic cell death" in both hemispheres, when compared with vehicle treated group. APC significantly preserved the number of neurons CA1, CA3 regions of the hippocampus, when compared with vehicle treated group. Our results showed that hypoxic-ischemic injury caused a significant increase in NO production. The APC-treated animals were reduced brain nitrite levels in carotid ligated hemispheres. To our knowledge, this is the first study that demonstrates a protective effect of the APC against hypoxia-ischemia in the developing brain.
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PMID:Effects of activated protein C on neonatal hypoxic ischemic brain injury. 1842 Jan 81

Activation of the Smad signalling pathway has been implicated in the pathological process of diabetic associated complications. The current study was designed to see whether Smad signalling was activated in the hippocampus of streptozotocin-induced diabetic rats. Compared with vehicle-treated controls, immunoblot analysis of hippocampal extracts showed that phosphorylated Smad2 was upregulated at 8 weeks post streptozotocin induction (p<0.01), and phosphorylated Smad3 protein was upregulated at 4 and 8 weeks post streptozotocin induction (p<0.01) in streptozotocin-induced diabetic rats. In addition, immunofluorescence labelling assay showed that the percentage of pSmad2 immunoreactive astrocytes increased significantly in CA1, CA3 and dentate gyrus region (p<0.01), and pSmad3 immunoreactive astrocytes increased significantly in CA1 region (p<0.01) and in CA3 and dentate gyrus region (p<0.05) of the hippocampus in diabetic rats. These data indicate that Smad signalling is enhanced in hippocampal astrocytes of diabetic rats, and may thereby represent a clue to explore its exact role in the development of diabetic encephalopathy.
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PMID:Increased expression of phosphorylated Smad2 and Smad3 in the hippocampus of streptozotocin-induced diabetic rats. 1983 80

Sepsis occurs in 14-37 percent of patients admitted to intensive care units and sepsis associated encephalopathy (SAE) is its severe complication. In an attempt to provide insight into the question how sepsis and SAE contributes cerebral dysfunction, apoptotic cell death was investigated in hippocampal formation, centers of adult neurogenesis and main autonomic centers which are known to regulate heart rate, respiration and other visceral activities, in cecal ligation and puncture (CLP) rat model of sepsis. Vital parameters and electrophysiological changes were monitored for the confirmation of sepsis and SAE, respectively. Apoptotic cell death was evaluated by TUNEL staining, Caspase-3 immunohistochemistry and transmission electron microscope (TEM). Significantly higher number of TUNEL positive apoptotic cells in the median preoptic nucleus, subventricular zone, dentate gyrus and CA1 and CA3 regions of the hippocampal formation were observed in CLP group and Caspase-3 immunohistochemistry and TEM findings were in line with these results, suggesting that the apoptotic cell death would bare a major role in the pathogenesis of the SAE.
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PMID:Sepsis induces apoptotic cell death in different regions of the brain in a rat model of sepsis. 2087 44


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