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)

Three to 12 h of mild hypothermia (HT) starting after hypoxia-ischemia is neuroprotective in piglets that are anesthetized during HT. Newborn infants suffering from neonatal encephalopathy often ventilate spontaneously and are not necessarily sedated. We aimed to test whether mild posthypoxic HT lasting 24 h was neuroprotective if the animals were not sedated. Thirty-nine piglets (median weight 1.6 kg, range 0.8-2.2 kg; median age 24 h, range 7-48 h) were anesthetized and ventilated and subjected to a 45-min hypoxic (FiO(2) approximately 6%) global insult (n = 36) or sham hypoxia (n = 3). On reoxygenation, 18 were maintained normothermic (NT, 39.0 degrees C) for 72 h, and 21 were cooled from 39 (NT) to 35 degrees C (HT) for the first 24 h before NT was resumed (18 experimental, three sham hypoxia). Cardiovascular parameters and intermittent EEG were documented throughout. The brain was perfusion fixed for neuropathology and five main areas examined using light microscopy. The insult severity (duration in minutes of EEG amplitude < 7 microV) was similar in the NT and HT groups, mean +/- SD (28 +/- 7.2 versus 27 +/- 8.6 min), as was the mean FiO(2) (5.9 +/- 0.7 versus 5.8 +/- 0.8%) during the insult. Six NT and seven HT piglets developed posthypoxic seizures that lasted 29 and 30% of the time, respectively. The distribution and degree of injury (0.0-4.0, normal-maximal damage) within the brain (hippocampus, cortex/white matter, cerebellum, basal ganglia, thalamus) were similar in the NT and HT groups (overall score, mean +/- SD, 2.3 +/- 1.5 versus 2.4 +/- 1.3) as was the EEG background amplitude at 3 h (13 +/- 3.5 versus 10 +/- 3.3 microV). The HT animals shivered and were more active. The sham control group (n = 3) shivered but had normal physiology and neuropathology. Plasma cortisol was significantly higher in the HT group during the HT period, 766 +/- 277 versus 244 +/- 144 microM at 24 h. Mild postinsult HT for 24 h was not neuroprotective in unsedated piglets and did not reduce the number of animals that developed posthypoxic seizures. Cortisol reached 3 times the NT value at the end of HT. We speculate that the stress of shivering and feeling cold interfered with the previously shown neuroprotective effect of HT. Research on the appropriateness of sedation during clinical HT is urgent.
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PMID:Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective. 1151 29

Glutamate transporters are essential for maintaining the extracellular levels of glutamate at synaptic clefts and are regulated developmentally in a subtype-specific manner. We investigated chronological changes of immunoreactivities for glial glutamate transporters GLAST and GLT-1 and a neuronal glutamate transporter, EAAC1, in postnatal 7-day-old rat neocortices and hippocampi at 12, 24, 48 and 72 h after hypoxia-ischemia. Glutamate transporter subtypes are differentially expressed in the ischemic core and the boundary area of the neonatal rat brain with hypoxia-ischemia. Expressions of these glutamate transporters decreased in the ischemic core at 12 h, then immunoreactivities for GLAST and GLT-1 were recovered at the hippocampus. This was accompanied by a GFAP-positive gliosis at 72 h, whereas these immunoreactivities were reduced at the neocortex in the ischemic core. Glial glutamate transporters, especially GLAST, were noted in some astrocytes appearing as apoptosis as well as shrunken pyramidal neurons mainly in the boundary area of the neocortex. Increased perikaryal expression of EAAC1 was associated with that of MAP2 at the border of the boundary area. These temporal and regional expressions of glutamate transporters may contribute towards understanding the excitotoxic cell death mechanism in hypoxic-ischemic encephalopathy during the perinatal period.
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PMID:Altered expressions of glutamate transporter subtypes in rat model of neonatal cerebral hypoxia-ischemia. 1174 17

The interrelationship between inflammation and ischemia is complex and poorly understood in the developing nervous system. In the preterm newborn, maternal infection may predispose to white matter injury and may be associated with cytokine elevation. In the term infant, few studies exist linking elevation of cytokines with encephalopathy and poor neurodevelopmental outcome. This review discusses the interplay among inflammatory cytokines, neonatal encephalopathy, and neuroimaging parameters.
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PMID:Neonatal encephalopathy in the term infant: neuroimaging and inflammatory cytokines. 1192 82

Neuroserpin is an axonally secreted serine protease inhibitor expressed in the nervous system that protects neurons from ischemia-induced apoptosis. Mutant neuroserpin forms have been found polymerized in inclusion bodies in a familial autosomal encephalopathy causing dementia, or associated with epilepsy. Regulation of neuroserpin expression is mostly unknown. Here we demonstrate that neuroserpin mRNA and the RNA-binding protein HuD are co-expressed in the rat central nervous system, and that HuD binds neuroserpin mRNA in vitro with high affinity. Gel-shift, supershift and T1 RNase assays revealed three HuD-binding sequences in the 3'-untranslated region (3'-UTR) of neuroserpin mRNA. They are AU-rich and 20, 51 and 19 nt in length. HuD binding to neuroserpin mRNA was also demonstrated in extracts of PC12 pheochromocytoma cells. Additionally, ectopic expression of increasing amounts of HuD in these cells results in the accumulation of neuroserpin 3'-UTR mRNA. Furthermore, stably transfected PC12 cells over-expressing HuD contain increased levels of both neuroserpin mRNAs (3.0 and 1.6 kb) and protein. Our results indicate that HuD stabilizes neuroserpin mRNA by binding to specific AU-rich sequences in its 3'-UTR, which prolongs the mRNA lifetime and increases protein level.
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PMID:HuD binds to three AU-rich sequences in the 3'-UTR of neuroserpin mRNA and promotes the accumulation of neuroserpin mRNA and protein. 1200 Aug 40

Hypoxia-ischemia leads to an acute depletion of high-energy phosphates in neonatal brain. After reperfusion, energy status is restored, but may show progressive secondary failure, associated with neuronal loss, brain damage, or death. Oxidants are produced on reperfusion. We investigated whether a biphasic energy failure develops in cultured neurons after oxidant exposure, and whether the degree of primary disturbance correlates with later ATP synthesis and mode of cell death. Embryonic rat cortical neurons were exposed to varying doses of hydrogen peroxide for 60 min and incubated for 12, 24, or 48 h. Adenine nucleotides and the incorporation of [(14)C]adenine into adenine nucleotides were quantified. Apoptosis was evaluated by DNA electrophoresis and in situ end-labeling. A mild insult (10-50 microM) caused no ATP depletion or change in subsequent growth or energy metabolism, whereas an intermediate insult (100 microM) caused acute ATP depletion (49 +/- 12% of control). This recovered to 91 +/- 28% by 12 h, but then declined to 61 +/- 18% at 24 h. A severe insult (1 mM) depleted ATP to 15 +/- 3% of control, with no recovery. Moderate ATP depletion was associated with apoptotic cell death, whereas a severe insult caused acute necrosis. Transient oxidant exposure of embryonal cortical neurons causes a biphasic energy depletion followed by apoptosis in analogy with asphyxiated brains. This model may prove useful for the study of pathogenesis and treatment of hypoxic-ischemic encephalopathy.
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PMID:Biphasic ATP depletion caused by transient oxidative exposure is associated with apoptotic cell death in rat embryonal cortical neurons. 1208 45

The perinatal age window is characterized by vulnerability to age-specific patterns of injury. Hypoxia/ischemia occurs in a number of settings both in term and preterm neonates, yet the patterns of response appear dependent upon the age of the infant. In the preterm neonate, hypoxic/ischemic insults result in selective white matter injury, termed periventricular leukomalacia (PVL), with little or no cortical pathology. However, in term babies, hypoxic encephalopathy is the most common cause of seizures, and also can result in cortical infarction. Extracellular glutamate accumulates in the setting of hypoxia/ischemia, and excess activation of glutamate receptors has been implicated in hypoxic/ischemic cellular death. Glutamate receptors are developmentally regulated in both neuronal and glial cells within the brain. Using rodent models, we have shown that hypoxia/ischemia results in selective white matter injury in postnatal day (P) seven rat pups, while hypoxia causes seizures in P10-12 rats, but not at younger or older ages. We have further demonstrated that antagonists of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor subtype block white matter injury at P7 and seizures at P10. We have shown that AMPA receptors are relatively overexpressed in oligodendrocytes (OLs) within white matter at P7 and in neurons in cortex and hippocampus at P10. Hence maturational patterns of glutamate receptor expression correlate with age-specific regional susceptibility to injury to hypoxia/ischemia. While glutamate receptor blockade represents a rational strategy in the treatment of perinatal hypoxic/ischemic brain injury, it is unclear what role variations in their expression play in normal development and plasticity. Further investigation of patterns of glutamate receptor subunit expression in human brain and in experimental animal models is necessary to determine potential age specific strategies as well as adverse effects.
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PMID:The role of glutamate receptor maturation in perinatal seizures and brain injury. 1217 72

Fulminant hepatic failure (FHF) is an acute and eventually fatal illness, caused by a severe hepatocyte damage with massive necrosis. Its hallmarks are hepatic encephalopathy and a prolonged prothrombin time (< 40%). FHF is currently defined as hyperacute (encephalopathy appearing within 7 days of the onset of jaundice), acute (encephalopathy appearing between 8 and 28 days) or subacute (encephalopathy appearing between 5 and 12 weeks). FHF can be caused by viruses, drugs, toxins, and miscellaneous conditions such as Wilson's disease, Budd-Chiari syndrome, ischemia and others. However, a single most common etiology is still not defined. Factors that are valuable in assessing the likelihood of spontaneous recovery are age, etiology, degree of encephalopathy, prothrombin time and serum bilirubin. The management is based in the early treatment of infections, hemodynamic abnormalities, cerebral edema, and other associated conditions. Liver transplant has emerged as the most important advance in the therapy of FHF, with a survival rate that ranges between 60 and 80%. The use of hepatic support systems, extracorporeal liver support and auxiliary liver transplantation are innovative therapies.
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PMID:[Fulminant hepatic failure]. 1219 94

FROM AN EPIDEMIOLOGICAL POINT OF VIEW: With the aging of the population and increased indications for angioplasty or anticoagulant therapy, the incidence of cholesterol crystal embolism is going to increase. FROM A CLINICAL POINT OF VIEW: A systemic disease related to multiorgan distal ischemia, cholesterol crystal embolism has multiple facets. Rapidly progressive renal failure, malignant hypertension in the elderly, mesenteric ischemia, acute pulmonary edema, cutaneous ischemia or encephalopathy symptomatology may reveal cholesterol crystal embolism. THE IMPORTANCE OF DIAGNOSIS: The occurrence of such symptoms in poly-vascular patients, notably following exposure to inductive factors such as arterial catheterism, anticoagulant therapy or cardiac or vascular surgery is highly suggestive of the diagnosis. The lack of its knowledge can lead to inappropriate anticoagulant therapy and useless arteriography, which may even prolong or worsen cholesterol crystal embolism.
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PMID:[Cholesterol crystal embolism disease, diagnostic criteria]. 1223 76

Following critical hypoxia-ischemia during labor and delivery, there is a window of therapeutic opportunity during hypoxic-ischemic encephalopathy. Meta-analysis of three randomized trials of prophylactic barbiturate therapy for neonatal hypoxic-ischemic encephalopathy showed no significant effect on death or disability. One randomized trial of allopurinol showed short-term benefits but was too small to test death or disability. No adequate trials of dexamethasone, calcium channel blockers, or magnesium sulphate have yet been completed, but pilot studies in infants have shown the cardiovascular risks of magnesium sulphate and calcium channel blockers. There is considerable evidence from animal studies that posthypoxic mild hypothermia reduces brain injury. One small randomized trial of mild hypothermia found no adverse effects but was too small to examine death or disability. One large randomized trial of selective head cooling has finished recruitment and a number of large trials of systemic mild hypothermia are ongoing. As time is critical with post-hypoxic interventions, the delay involved in obtaining informed parental consent for such trials might obscure a clinically important therapeutic effect.
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PMID:Clinical trials of treatments after perinatal asphyxia. 1243 31

Experimental studies demonstrate an alkaline shift in brain intracellular pH (pH(i)) after hypoxia-ischemia (HI). In infants with neonatal encephalopathy after HI, our aims were to assess (1) brain pH(i) during the first 2 weeks after birth in infants categorized according to magnetic resonance imaging (MRI) during the first 2 weeks after birth and at more than 3 months of age, and neurodevelopmental outcome at 1 year; (2) the relationship between brain pH(i) and lactate/creatine; and (3) duration of alkaline brain pH(i). Seventy-eight term infants with neonatal encephalopathy were studied using MR techniques. One hundred and fifty-one studies were performed throughout the first year including 56 studies of 50 infants during the first 2 weeks after birth. pH(i) was calculated using phosphorus-31 MR spectroscopy and lactate/creatine was measured using proton MRS. The mean (standard deviation [SD]) brain pH(i) during the first 2 weeks after birth in infants with severely abnormal versus normal MRI was 7.24 (SD, 0.17) versus 7.04 (SD, 0.05; p < 0.001); in infants who subsequently developed cerebral atrophy versus those who did not: 7.23 (SD, 0.17) versus 7.06 (SD, 0.06; p < 0.05); in infants who died or had a severe neurodevelopmental impairment versus normal outcome: 7.28 (SD, 0.15) versus 7.11 (SD, 0.09; p < 0.05). Brain alkalosis was associated with increased brain lactate/creatine (p < 0.001). pH(i) remained more alkaline in the severe outcome group up to 20 weeks after birth (p < 0.05).
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PMID:Brain alkaline intracellular pH after neonatal encephalopathy. 1244 26


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