Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured simultaneously the oxidative metabolic activity, monitored as the tissue fluorescence attribute to intramitochondrial NADH, the extracellular potassium level with ion-selective microelectrodes, and the focal extracellular electrical potential, of one site in intact cerebral cortex of cats. When the cerebral was stimulated by trains of repeated electric pulses applied either directly to its surface or to an afferent pathway, the corrected cortical fluorescence (F-R) declined indicating oxidation of NADH, the activity of extracellular potassium [K+]o increased, and the extracellular potential (Vec) shifted in the negative direction. When mild to moderate stimuli not exceeding 10-15 sec in duration were used, a 3-fold correlation was found between these three variables. The regression of F-R over either Vec, or over log [K+]o had a positive ordinal intercept. The results are in agreement with earlier suggestions 4,24,25,43,45,46 that (a) much but not all the oxidative metabolic response of cortex to electrical stimulation is expended in restoring disturbed ion balance; and (b) that sustained shifts of potential (SP) in response to repetitive electrical stimulation are generated by glia cells depolarized by excess potassium. The magnitude of SP shifts associated with a given elevation of [k+]o are smaller in cerebral cortex than in spinal cord48,49. The correlation of F-R with [K+]o breaks down when pathologic processes of either seizure activity or spreading depression set in. During paroxysmal activity [K+]o tends to remain confined below 10-12 mM, a level observed in non-convulsing cortex as well, but oxidation of NADH progresses beyond that seen in non-convulsing cortex as well, but oxidation of NADH progresses beyond that seen in non-convulsing tissue. This observation is hard to reconcile with the suggestion that excess potassium is a factor in the generation of seizures, at least of the type observed in this study. When [K+]o levels exceeded 10-12 mM, spreading depression invariably followed at least under the unanesthetized condition in these experiments. During spreading depression [K+]o levels rose to exceed 30 mM, sometimes 80 mM. NADH was oxidized during spreading depression to a level comparable to that seen in seizures. The observations are compatible with the suggestion13 that spreading depression occurs whenever the release of potassium into extracellular fluid is overloading its clearance therefrom.
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PMID:Responses of electrical potential, potassium levels, and oxidative metabolic activity of the cerebral neocortex of cats. 16 65

Reviewed is the author's investigation of potassium in extracellular fluid of cerebral neocortex and spinal cord determined with ion-selective microelectrodes, and of oxidative metabolism monitored by fluorometric determination of intramitochondrial NADH in intact cortex. When gray matter is excited by afferent input, or by direct electrical stimulation, the logarithm of the rise of extracellular potassium concentration ([K+]0), the sustained shift of electrical potential, and the response of oxidative metabolism are linearly correlated. However, during seizures and during spreading depression, the correlation is broken, suggesting that the demand for oxidative energy exceeds that corresponding to the elevation of [K+]0. There exists a critical concentration of [K+]0 at which spreading depression inevitably erupts (12 mM for cat cerveau isole), but no such critical level could be detected for seizures. The rate of clearance of excess potassium from extracellular fluid is slower for high concentrations than for low; this rate is further slowed by the administration of phenobarbital, and possibly also of diphenylhydantoin. Changes of membrane potential of glia cells in the mammalian spinal cord can adequately be described by the Nernst equation.
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PMID:Potassium, neuroglia, and oxidative metabolism in central gray matter. 17 18

Post-tetanic potentiation (PTP) of monosynaptic reflex was estimated in spinal cords in the drug-free state after the administration of a convulsant dose of penicillin and after the administration of phenytoin. There was no apparent correlation between the degree of depression of PTP and the efficacy of controlling seizure activity by phenytoin. Extracellular potassium levels were measured with ion-selective microelectrodes. The post-stimulation clearing of [K+]0 was not accelerated by phenytoin, and frequently it was slowed. Post-stimulus undershooting of [K+]0 was diminished. Oxidation of NADH in cortex and of cytochrome a, a3 in spinal cord were measured by optical methods. Stimulus-evoked transient oxidation responses evoked by electrical stimulation were depressed by phenytoin. It is concluded that systemic administration of phenytoin in therapeutic doses does not stimulate Na+-K+-activated membrane ATPase in cortex and spinal cord. Unlike other depressants, phenytoin did not cause a reduction of "resting" redox levels of respiratory enzymes. The local regulation of blood flow remained unaltered after phenytoin administration. Phenytoin caused a moderate but consistent depression of the stimulus-evoked responses of potassium activity, electric potential, and oxidative enzymes, consistent with diminished outflow of potassium from cells, owing either to lesser activation of cells or to a lesser exchange of ions.
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PMID:Phenytoin, electric, ionic, and metabolic responses in cortex and spinal cord. 19 41

In 14 patients operated upon for focal cerebral seizures under local anesthesia, cortical electrical activity was compared with the levels of nicotinamide adenine dinucleotide (NADH) observed fluorometrically. NADH levels fell 3 to 15% in response to 5-second intervals of cortical stimulation in 42 of 70 observations. Although a rough correlation was seen between the quantity of current delivered (milliamperes X seconds) and the NADH decrease, this varied from case to case. The presence of cortical afterdischarge often, but not invariably, corresponded to a greater percentage of change in the NADH levels. Averaging the NADH response to sporadic interictal epileptiform discharges failed to demonstrate concomitant NADH reductions. A similar lack of change was seen in four patients in whom low frequency spike foci were induced by topically applied penicillin in cortex destined for excision. Preliminary studies of the topography of spread of NADH change after cortical stimulation indicate that this is usually asymmetrical in human epileptogenic cortex. Under experimental conditions in cats, it seemed possible to differentiate primary from projected epileptiform activity, in that the projected activity had little or no concomitant fall in the NADH level after the electrographic spike. Pathological examination of the excised sites of NADH recording showed, with one exception, fibrous astrocytic transformation of the central cortex layers.
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PMID:Fluorometric monitoring of NADH levels in cerebral cortex: preliminary observations in human epilepsy. 21 33

Changes in cortical extracellular potassium activity ([K+]0), NADH fluorescence, and oxygen consumption were studied in anesthetized cats during pentylenetetrazol seizures. The effects of partial ischemia induced by either hypotension or intermittent carotid artery occlusion on these parameters were investigated. Nonischemic seizures were characterized by gradual generalized decreases in cortical NADH fluorescence and increases in O2 consumption, along with rapid increases in [K+]0, which then usually fell slightly as the ictal discharge continued. Ischemic seizures, on the other hand, were accompanied by complex changes in NADH fluorescence, by smaller delayed maximal increases in O2 consumption that lasted beyond the end of ictal activity, and by more sustained increases in [K+]0. The decay of [K+]0 after the termination of seizures in both nonischemic and moderately ischemic animals was not a monoexponential function: plots of ln delta [K+]0 versus time showed an initial linear decline (of slope M1) that rather abruptly slowed (to slope M2) after 2 to 5 sec and then often increased to the original rate. Both M1 and M2 were proportionately decreased by ischemia. In addition, the rate of [K+]0 removal could be slowed by acute ischemia induced either during or after the end of ictal activity. The initial rate of postictal [K+]0 removal (M1) was found to be linearly and inversely related to the level of cortical NADH fluorescence at the time of seizure termination. The results of this study suggest that an O2-dependent transport mechanism plays a major role in the removal of [K+]0 during and following the termination of generalized pentylenetetrazol seizures in the cat.
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PMID:Effects of ischemia on the removal of extracellular potassium in cat cortex during pentylenetetrazol seizures. 22 67

The effect of sodium cyanate (25, 50, 75, and 100 mg/kg body weight i.p. daily for 10 days) upon cerebral metabolism and the EEG of Wistar rats was studied. This treatment resulted in a dose-related carbamylation of hemoglobin and left shift in the oxygen dissociation curve. Animals receiving the highest dose of cyanate developed a significant systemic metabolic acidosis. In brain there was dose-dependent decrease in phosphocreatine, TCO2 and cytoplasmic NADH/NAD+ ratio, reflecting the calculated drop in intracellular pH. Glucose levels were elevated despite a normal calculated energy charge, which suggests a balanced slowing of the energy-producing and energy-utilizing systems. The higher doses of cyanate produced spontaneous seizure activity on the EEG.
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PMID:Effects of high-dose cyanate upon cerebral energy metabolism of the rat. 120 41

We report the clinical, electroencephalographic, neurophysiologic, and neuroimaging findings in eight children with infant-onset progressive myoclonus epilepsy, all of whom had muscle biopsies performed as as part of the diagnostic evaluation. Each child had myoclonic seizures, generalized tonic-clonic seizures, and neurologic regression or marked developmental delay. Four children died before 3 years of age. Electroencephalograms in seven children showed an abnormally slow background with bilateral multifocal paroxysmal discharges but no burst suppression pattern or photoparoxysmal response. Muscle biopsy specimens were submitted for histopathology and respiratory-chain enzyme studies. Nonspecific abnormalities on light microscopy or electron microscopy were found in seven samples, including increased subsarcolemmal deposits of mitochondria or morphologic mitochondrial changes, but no ragged-red fibers were seen. Respiratory-chain enzyme studies were performed on five samples and in three children (all of whom had a history of elevated lactate in serum or cerebrospinal fluid), there were low levels of rotenone-sensitive reduced nicotinamide adenine dinucleotide (NADH) cytochrome c reductase characteristic of a defect in the complex I part of the respiratory-chain pathway. This study has shown that infant-onset progressive myoclonus epilepsy can be distinguished from other myoclonic epilepsy syndromes of infancy by clinical and electrographic features. Furthermore, respiratory-chain enzyme defects are a relatively common cause of infant-onset progressive myoclonus epilepsy. The absence of ragged-red fibers on muscle histopathology does not preclude a mitochondrial enzyme abnormality.
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PMID:Infant-onset progressive myoclonus epilepsy. 2198 53

A 24-year-old male had a deficiency of the complex I (NADH coenzyme-Q-reductase) of the mitochondrial respiratory chain, which clinically presented as a mitochondrial encephalomyopathy, with lactic acidosis and stroke-like episodes (MELAS syndrome). The encephalopathic episodes were preceded by migraine and were characterized by focal deficit signs, motor partial seizures and hypodense areas in the CT scan. An echocardiographic diagnosis of hypertrophic cardiomyopathy without intracavitary thrombi was made. It is suggested that hypertrophic cardiomyopathy is caused by the mitochondrial abnormalities that have been reported in the myocardium, and that migraine and cerebral infarctions are associated with abnormalities in the mitochondria from the endothelium and smooth muscle fibres of the cerebral small arteries and arterioles.
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PMID:[Complex I (NADH coenzyme-Q-reductase) deficiency, MELAS syndrome and hypertrophic cardiomyopathy]. 190 55

Influx of calcium ion (Ca++) into the neurons has recently been implicated in the generation of seizure activity. Utilizing indo-1, a fluorescent Ca++ indicator, changes in cytosolic free calcium ([Ca++]i), NAD/NADH redox state and hemodynamics were simultaneously measured in vivo from the cat cortex during bicuculline-induced seizure activity. A ratio of indo-1-Ca++ fluorescence at 400 and 506 nm during ultraviolet excitation (340 nm) was utilized as a measure of changes in [Ca++]i. Alterations in the NAD/NADH redox state and local cortical blood volume (1CBV) were assessed at 464 nm and 340 nm, respectively. Local cortical blood flow (1CBF) was calculated from 1CBV and mean transit time determined from cortical hemodilution curves. Electroencephalogram (EEG) was monitored from the same cortical region as the optical measurements. The [Ca++]i signal ratio started to increase 19 +/- 2 sec prior to the onset of seizure activity on the EEG and remained elevated until the activity was suppressed by an intravenous administration of diazepam (2 mg/kg). The early increase in [Ca++]i is presumably due to a synaptic Ca++ entry associated with facilitated excitatory neurotransmission. The NAD/NADH redox state became oxidized during the seizure activity and started to recover as the EEG activity was suppressed. The 1CBV and 1CBF increased by 17 +/- 8% and 68 +/- 16%, respectively, 10 min into the seizure activity. This study provides direct in vivo evidence suggesting a possible role of calcium entry into the neurons in the epileptogenesis.
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PMID:Alterations in cytosolic free calcium in the cat cortex during bicuculline-induced epilepsy. 232 63

We describe a 16-year-old Japanese girl with a mitochondrial encephalomyopathy who presented with progressive dementia, limb weakness and atrophy, episodic vomiting, generalized convulsions, myoclonic seizures, and hypertrophic cardiomyopathy. CT scan revealed transient focal low density areas in her occipital and parietal lobes, and cerebellar atrophy. The clinical features were consistent with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Microscopically, most of muscle fibers in the skeletal muscles and heart were occupied by markedly increased mitochondria. Polarographic studies on mitochondria isolated from postmortem heart muscle showed severe impairment of oxidation of NADH-linked substrates in contrast to normal succinate oxidation. The rotenone-sensitive NADH-coenzyme Q reductase activity was markedly decreased in heart, skeletal muscle and liver mitochondria. The biochemical investigations have led to the identification of a defect of complex I in the respiratory chain. Reported cases of a defect of complex I have revealed pure myopathy, encephalopathy or encephalomyopathy. The reason for a varied clinical expression of a single defect remains to be clarified.
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PMID:A mitochondrial encephalomyopathy with cardiomyopathy. A case revealing a defect of complex I in the respiratory chain. 310 81


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