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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of nicergoline on ischemic brain damages induced by bilateral carotid arterial ligation (BCAL) in ICR-strain mice and mongolian gerbils and lipid peroxide formation (LPOF) in normal brain homogenate of rats were compared with those of dihydroergotoxine (DHE). In mice, nicergoline (16 mg/kg, i.p.) significantly reduced the cumulative mortality rate after BCAL (from 80-83% in the control to 50-55%). In gerbils, nicergoline (32 mg/kg, i.p.) significantly prolonged the mean onset time of ischemic seizure following recirculation after the 30-min BCAL (from 45.8 min in the control to 94.9 min). DHE also showed protective effects in these animals. In the ischemic brain of mice, marked decreases of creatine-P, ATP, glucose and glycogen; a remarkable increase of lactate; and elevation of L/P ratio were observed 1 to 10 min after BCAL. Nicergoline (16 mg/kg, i.p.) slightly prevented these decreases and significantly suppressed the increase of lactate and the elevation of L/P ratio 2 min after BCAL. The inhibitory action of nicergoline (20-100 microM) on LPOF is more potent than those of alpha-tocopherol and DHE. These results suggest that nicergoline may have protective effects against ischemic brain damages due to its ameliorating action on cerebral energy metabolism and partially due to its inhibitory action of LPOF.
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PMID:[Pharmacological study of nicergoline. (II). Protective effect on ischemic brain damages in animals]. 375 14

The objective of this study was to evaluate changes in cortical energy metabolism in experimentally induced seizures in the primate. Cynamologus fascicularis monkeys were anesthetized, and a craniotomy was performed. Small samples from the motor cortex were removed for measurement of energy metabolites just prior to intravenous bicuculline infusion (0.6 mg/kg), 20 min after the onset of seizures, and 2 h after the second sample. Samples were also taken for electron microscopy. Results showed decreased phosphocreatine values 20 min after the onset of seizures, whereas ATP levels were normal. Two hours after the onset of seizures, phosphocreatine had returned to normal, but ATP levels were below normal. Examination of tissue by electron microscopy showed evidence of cell damage 2 h, 20 min after the onset of seizures. These findings are consistent with the concept that sustained seizures may lead to irreversible cell damage and that alterations in energy metabolism may contribute to the cell death.
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PMID:Status epilepticus-induced changes in primate cortical energy metabolism. 377 56

The substantia nigra pars reticulata (SNPR) has previously been shown to undergo tissue necrosis following status epilepticus induced by flurothyl in the rat. Even if the rat is ventilated, the SNPR develops necrosis if the epileptic period lasts more than 30 min. Rat brains were frozen in situ after 20 and 60 min of seizure activity and after 60 min of seizure activity followed by 60 min recovery. Labile energy metabolites were then analyzed in the SNPR and in the periaqueductal grey matter (PAG, control region). In the PAG, the metabolite changes during status epilepticus were similar to those reported for cerebral cortex and hippocampus. Measurements showed an unchanged ATP content and energy charge (97% and 98% of control, respectively) and an accumulation of lactate to 9.2 +/- 0.6 mumol/g in the 60-min group. In the PAG, all metabolites measured had returned to control values after 60 min of recovery. In the SNPR, the perturbation of the energy metabolites was much more pronounced during status epilepticus. The concentration of ATP decreased to 75 +/- 3%, the energy charge to 91% +/- 12% and the adenylate pool to 86.7 +/- 5.7% of control. Lactate accumulated to concentrations of 16.1 +/- 1.8 mumol/g and 24.9 +/- 2.3 mumol/g in the 20-min and 60-min groups, respectively. The concentration of lactate was still increased above control after 60 min recovery, whereas the concentration of ATP and the energy charge were lower than control. The findings demonstrate that sustained and intense neuronal activation can cause metabolic disturbance and thereby lead to necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic alterations underlying the development of hypermetabolic necrosis in the substantia nigra in status epilepticus. 380 59

The convulsant pentylenetetrazole was administered to the lower primate, the tree shrew. Shortly after the onset of seizures, the animals were killed using a microwave device at 25 Kw and 915 MHz. The energy metabolites glycogen, glucose, ATP, and phosphocreatine were measured in five layers of the cerebral cortex and three layers of the cerebellum. Results showed that, as compared with controls, seizing animals had decreased energy metabolites selective to certain layers. Glucose was decreased in all cortical layers, but only in the granular layer of the cerebellum. Phosphocreatine was decreased in the outer small pyramidal layer and the polymorphous layer of the cortex but was unchanged in the cerebellum. ATP was decreased only in the outer small polymorphous layer of the cortex. These changes are consistent with the concept that selective changes may occur during seizures and that these changes are localized to layers that contain pyramidal cells. Examination of whole cortex may mask more subtle regional changes.
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PMID:Pentylenetetrazole-induced changes in cerebral energy metabolism in Tupaia glis. 381 12

Rats with chronic electrode implants to region CA3 of the hippocampus were rapidly kindled by stimulation with a 10 s, 10 Hz train of biphasic square waves presented every 5 min, until generalized seizures developed (60-70 stimulations). The hippocampi were isolated from the brains of control animals (implanted but not stimulated), and experimental animals which had developed generalized seizures. Synaptic membranes (SM) were prepared. SM were incubated with [gamma-32P]ATP and the incorporation of 32P into proteins and glycoproteins isolated by affinity chromatography on concanavalin-A-agarose was investigated. There was no difference in the phosphorylation pattern of total SM proteins between groups. In contrast, the phosphorylation of a glycoprotein with an apparent molecular weight of 180,000 was decreased 20-40% in kindled animals. This result was replicated in three independent experiments. The results suggest that the phosphorylation of glycoprotein 180 may be related to neuroplastic events.
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PMID:Decreased phosphorylation of synaptic glycoproteins following hippocampal kindling. 382 74

A patient is presented who had therapy-resistant epileptic seizures from the 7th day of life. Examination at the age of 17 months revealed a mentally retarded boy with epileptic seizures, generalised myoclonic contractions, and abnormal ocular movements. A cerebral CT scan showed central and cortical atrophy. Lactate levels in serum, cerebrospinal fluid and urine were elevated, the pyruvate level was raised in serum. A quadriceps muscle biopsy revealed aspecific morphologic signs of a myopathy. Biochemical analysis showed decreased substrate oxidation rates in the mitochondria associated with low rates of ATP production. Total and free carnitine levels were decreased. Investigation of the respiratory chain revealed a defect in the proximal part of respiratory chain involving the region of coenzyme Q. Based on clinical and chemical data it is likely that the patient is suffering from a multi-system disorder.
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PMID:A mitochondrial encephalomyopathy: the first case with an established defect at the level of coenzyme Q. 395 32

Graded transient cerebral hemispheral ischemia was produced in nitrous oxide-anesthetized Wistar rats by a procedure combining unilateral common carotid artery occlusion; elevation of intracranial pressure to 40-45 mm Hg by infusion of mock cerebrospinal fluid; and maintenance of arterial blood pressure at 100-110 mm Hg by controlled hemorrhage. Cerebral perfusion pressure was thus reduced into the ischemic range ipsilateral to carotid occlusion but remained 55-70 mm Hg contralaterally. Regional cerebral blood flow, measured autoradiographically, fell by 85-90% in the ischemic dorsolateral and lateral neocortex, hippocampus and lateral striatum, but remained at 71% of control or higher contralaterally. Metabolite assay revealed a gradient of energy depletion, with profound reductions in ATP and phosphocreatine and marked elevations of lactate in lateral neocortex, lateral striatum, hippocampus and lateral thalamus. Importantly, dorsolateral neocortex proved to be a penumbral zone, with marked lactate elevation comparable to that of lateral cortex, yet only intermediate degrees of ATP and PCr reduction. Contralateral structures were metabolically unaffected apart from mild increases in lactate. The advantages of this focal ischemia model include the consistent topographic distribution of ischemia and its regional gradations of intensity; the avoidance of painstaking intracranial microsurgery and of systemic complications; preservation of intact energy state of the contralateral hemisphere; ease of reversibility of ischemia; and lack of seizures. The consistent metabolic penumbral zone is a unique feature of the model.
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PMID:Graded focal cerebral ischemia in the rat by unilateral carotid artery occlusion and elevated intracranial pressure: hemodynamic and biochemical characterization. 400 62

The objective of the present work was to study cerebral energy metabolism at threshold levels of hypoxia, i.e., degrees of hypoxia that abolish cerebral electrical activity, in the "normal" and in the epileptic brain. Seizures were induced by intravenous bicuculline and cerebral oxygen availability was reduced by a combination of lowered PO2 and reduced blood pressure to give a transformation of the burst suppression pattern to either one with single spikes or overt EEG flattening. Nonepileptic control animals were exposed to degrees of hypoxia that gave either a markedly depressed EEG pattern with sparse slow waves or EEG flattening. Epileptic and nonepileptic groups proved comparable in terms of calculated oxygen availability and cerebral oxygen consumption at the threshold of "transmission failure." At levels of hypoxia that markedly attenuated or completely abolished seizure discharge, the cerebral metabolic changes were more marked than in comparable nonepileptic animals. These changes comprised an imminent severe perturbation of cerebral cortical phosphorylation potential, a pronounced lactic acidosis with a precipitous redox change, and a marked accumulation of ammonia. The more labile energy balance of the epileptic brain may indicate that the "seizure state" either increases cellular energy demands in spite of the electrical silence or reduces the efficiency of ATP production at the prevailing oxygen availability. It is conceivable that energy failure elicited by complicating hypoxia can aggravate or precipitate brain cell damage in epilepsy.
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PMID:Influence of reduced oxygen availability on cerebral metabolic changes during bicuculline-induced seizures in rats. 403 Sep 21

The effects of prolonged bicuculline-induced seizures on cerebral blood flow and metabolism were determined in paralyzed, mechanically ventilated neonatal dogs. Transient changes occurring early in the course of status epilepticus included significant arterial hypertension, hypocarbia, elevation of plasma norepinephrine levels, and decline in brain glucose concentration. Cerebral blood flow remained elevated throughout the 45 minutes of seizure. Determination of cerebral metabolite values by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy and by in vitro enzymatic analysis of frozen brain samples showed significant decreases in the level of phosphocreatine and relatively less change in ATP values. Progressive intracellular acidosis occurred, coincident with elevation of brain lactate concentrations. We conclude that the physiological and metabolic alterations that occur during prolonged seizures are not uniform, but change with time. Any hypothesis advanced to explain the mechanism of neuronal injury during prolonged seizures must take into account these temporally related changes.
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PMID:31P NMR study of cerebral metabolism during prolonged seizures in the neonatal dog. 403 47

The cerebral blood flow is lower in spontaneously hypertensive rats than in normotensive anaesthetized and mechanically ventilated rats during bicuculline-induced seizures, presumably due to the increase in vascular resistance in the hypertensive rats. This study investigates whether the hypertensive rats develop more severe derangement of the cerebral energy metabolites than normotensive rats because of the reduced cerebral blood flow. After 20 min of continuous seizure activity both normotensive and hypertensive rats had significantly decreased levels of phosphocreatine, ATP and glycogen as well as increased lactate and lactate/pyruvate ratio within the parietal cortex compared to controls. The metabolic disturbances were somewhat less pronounced in the hypertensive rats than in the normotensive rats. Thus, ADP was significantly increased in normotensive rats only and the lactate/pyruvate ratio was higher in the normotensive rats. We conclude that spontaneously hypertensive rats are not more prone than normotensive rats to derangement of cerebral energy metabolites during short term bicuculline-induced seizures and that insufficient blood flow is not the primary cause of the metabolic alterations.
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PMID:Cerebral energy metabolism during bicuculline-induced status epilepticus in spontaneously hypertensive rats. 406 Nov 12


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