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)

Pentylenetetrazole was administered to Swiss-Albino mice, producing clonic-tonic seizures. Other groups were pretreated with one of the three anticonvulsants: phenytoin, clonazepam, or sodium valproate. Mice were sacrificed during the preseizure (1 minute) stage and at the onset of clonic-tonic seizures (2 minutes). Glucose, glycogen, ATP, and phosphocreatine were measured in layers of the parietal cortex and cerebellar vermis. Cortical metabolites were unchanged, or increased slightly, suggesting decreased utilization. In both cerebellar layers, glucose and glycogen were significantly decreased, and phosphocreatine was decreased in the molecular layer. These results indicate a regionally selective effect for pentylenetetrazole on cerebral energy metabolites. Pretreatment with anti-convulsants reduced the severity of the seizure, and eliminated the effect of pentylenetetrazole on glucose and glycogen.
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PMID:Pentylenetetrazole induced changes in cerebellar energy metabolism. 712 23

The protective effect of vinpocetine on experimental brain ischemia was studied in stroke-prone spontaneously hypertensive rats (SHRSP) with bilateral carotid artery occlusion (BCAO) and in Wistar-Kyoto rats (WKY) subjected to BCAO and hemorrhage (1% of body weight). In SHRSP with BCAO, intraperitoneal (i.p.) injection of vinpocetine (1 mg/kg) 10 min before BCAO significantly prolonged the time required for the onset of ischemic seizure from 65 +/- 13 min (mean +/- SEM) to 117 +/- 19 min. In WKY with BCAO and hemorrhage, vinpocetine (5 mg/kg, i.p.) reduced the lactate level in the cerebral cortex from 11.6 +/- 2.7 mmol/g to 5.9 +/- 1.2 mmol/g and elevated the concentration of ATP from 2.05 +/- 0.09 mmol/g to 2.25 +/- 0.03 mmol/g. These results suggest a protective effect of vinpocetine against brain ischemia.
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PMID:[Protective effect of vinpocetine on experimental brain ischemia]. 715 92

The objective of the present experiments was to study metabolic correlates to the localization of neuronal lesions during sustained seizures. To that end, status epilepticus was induced by i.v. administration of bicuculline in immobilized and artificially ventilated rats, since this model is known to cause neuronal cell damage in cerebral cortex and hippocampus but not in the cerebellum. After 20 or 120 min of continuous seizure activity, brain tissue was frozen in situ through the skull bone, and samples of cerebral cortex, hippocampus, and cerebellum were collected for analysis of glycolytic metabolites, phosphocreatine (PCr), ATP, ADP, AMP, and cyclic nucleotides. After 20 min of seizure activity, the two "vulnerable" structures (cerebral cortex and hippocampus) and the "resistant" one (cerebellum) showed similar changes in cerebral metabolic state, characterized by decreased tissue concentrations of PCr, ATP, and glycogen, and increased lactate concentrations and lactate/pyruvate ratios. In all structures, though, the adenylate energy charge remained close to control. At the end of a 2-h period of status epilepticus, a clear deterioration of the energy state was observed in the cerebral cortex and the hippocampus, but not in the cerebellum. The reduction in adenylate energy charge in the cortex and hippocampus was associated with a seemingly paradoxical decrease in tissue lactate levels and with failure of glycogen resynthesis (cerebral cortex). Experiments with infusion of glucose during the second hour of a 2-h period of status epilepticus verified that the deterioration of tissue energy state was partly due to reduced substrate supply; however, even in animals with adequate tissue glucose concentrations, the energy charge of the two structures was significantly lowered. The cyclic nucleotides (cAMP and cGMP) behaved differently. Thus, whereas cAMP concentrations were either close to control (hippocampus and cerebellum) or moderately increased (cerebral cortex), the cGMP concentrations remained markedly elevated throughout the seizure period, the largest change being observed in the cerebellum. It is concluded that although the localization of neuronal damage and perturbation of cerebral energy state seem to correlate, the results cannot be taken as evidence that cellular energy failure is the cause of the damage. Thus, it appears equally probable that the pathologically enhanced neuronal activity (and metabolic rate) underlies both the cell damage and the perturbed metabolic state. The observed changes in cyclic nucleotides do not appear to bear a causal relationship to the mechanisms of damage.
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PMID:Metabolic changes in cerebral cortex, hippocampus, and cerebellum during sustained bicuculline-induced seizures. 729 97

Cerebral infarction was produced in rats by internal carotid injection of 35 mu plastic microspheres. Electroencephalograms were recorded through the scalp and from the thalamus. Regional concentration of endogenous brain ATP was studied by the histochemical bioluminescent method. Following embolization, a specific pattern of seizure propagation is noted. Spike activity appears first in the contralateral hemisphere, then the contralateral thalamus, infarcted thalamus, and finally the cortex. The results of these present experiments suggest that seizure activity following an evolving focal ischemic injury in the brain appears in the face of lowered ATP content.
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PMID:Seizure propagation and ATP depletion in the rat stroke model. 735 65

Decreased brain ATP and phosphocreatine (PCr) concentrations and intracellular pH were compared in hypoxic 4-, 10-11, and 24-25-day-old rats. Surface coil 31P-nuclear magnetic resonance (NMR) spectra were acquired in vivo every minute before, during, and after 7 min of breathing 4% O2. At all ages PCr decreased rapidly. At the two younger ages, the nucleoside triphosphate signal was still 80-85% of pre-hypoxic values, indicating 20-30% decrease in ATP, when PCr was almost fully depleted. At 24-25 days, PCr initially decreased 40-50% with an ATP loss of about 30%. Then, PCr and ATP decreased simultaneously. The decrease in brain pH was greatest at 24-25 days. More electrocortical seizure activity during hypoxia was seen at 10-11 days than at other ages. Seizure activity was seen only when ATP was less than 20% depleted and was not associated with more rapid decreases in ATP or PCr. At all ages, loss of electrocortical activity occurred when ATP was about 30% depleted. Brain creatine kinase catalyzed flux, measured by the NMR saturation transfer experiment before the hypoxic period, was 4-fold higher at 24-25 days than at 4- or 10-11 days. In conclusion, the temporally coupled depletion of PCr and ATP during hypoxia, which is characteristic of the mature brain, is seen only after the maturational increase in brain CK activity.
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PMID:Phosphocreatine and ATP regulation in the hypoxic developing rat brain. 760 Jun 67

Na+,K(+)-ATPase (the sodium pump) is a ubiquitous enzyme that consumes ATP to maintain an adequate neuronal transmembrane electrical potential necessary for brain function and to dissipate ionic transients. Reductions in sodium pump function augment the sensitivity of neurons to glutamate, increasing excitability and neuronal damage in vitro. Temporal lobe epilepsy (TLE) is one disease characterized by hyperexcitability and marked hippocampal neuronal losses that could depend in part, on impaired sodium pump capacity secondary to changes in sodium pump levels and/or insufficient ATP supply. To assess whether abnormalities in the sodium pump occur in this disease, we used [3H]ouabain to determine the density of Na+,K(+)-ATPase for each anatomic region of hippocampus by in vitro autoradiography. Tissues were surgically obtained from epileptic patients with hippocampal sclerosis and compared with specimens from patients with seizures originating from temporal lobe tumors and autopsy controls. Changes in cellular population arising from neuronal losses or gliosis were assessed by protein densities derived from quantitative computerized densitometry of Coomassie-stained tissue sections. We estimated regional differences in capacity for ATP generation by determining cytochrome c oxidase (CO) activity. Principal neurons of hippocampus exhibit high levels of sodium pump enzyme. Both epilepsy groups exhibited slight but significant increases in sodium pump density/unit mass of protein in the dentate molecular layer, CA2, and subiculum as compared with autopsy controls. Greater hilar sodium pump density was also observed in sclerotic hippocampi. In contrast, CO activity was reduced in both epilepsy types throughout hippocampus. Results suggest that although sodium pump protein in surviving neurons appears to be upregulated in epilepsy, sodium pump capacity may be limited by the reduced levels of CO activity. Functional reduction in sodium pump capacity may be an important factor in hyperexcitability and neuronal death.
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PMID:Regional distributions of hippocampal Na+,K(+)-ATPase, cytochrome oxidase, and total protein in temporal lobe epilepsy. 760 16

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid, and pyrimidines bases were determined in cerebrospinal fluid (CSF) of 52 children after simple febrile seizures and in a control group of 63 children. There was no statistically significant difference between the two groups for any of these metabolites, suggesting that simple febrile seizures (SFS) neither significantly disturb the metabolism of nucleotides, nucleosides, or bases nor significantly deplete neuron adenosine ATP levels. Therefore, they do not appear to constitute a threat of neuronal damage.
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PMID:Cerebrospinal fluid purine metabolites and pyrimidine bases after brief febrile convulsions. 761 24

Carnitine (beta-hydroxy-gamma-trimethylammonium butyrate) is widely distributed in the body including the nervous system. Its physiological function, viz. a carrier of long-chain fatty acids through the inner mitochondrial membrane, has been well established. In this review, mainly based on our experiments, we discuss the possibility that carnitine may have effects other than the "physiological" function and that it may be a potent protector of the brain. When mice were exposed to ammonia (intraperitoneal injection of ammonium acetate), they developed seizures and concentrations of brain energy metabolites were altered; ATP and phosphocreatine decreased while ADP, AMP, pyruvate and lactate increased. The seizures and changes in brain energy metabolites were clearly suppressed when the mice were pre-treated with carnitine. Furthermore, changes in energy metabolites in the brain caused by severe ischemia (decapitation) were also suppressed by carnitine. Since D-carnitine showed similar effects as those of L-carnitine, the effects seem due to function(s) of carnitine yet to be defined. Intrinsic substances including carnitine appear to deserve further studies for possible use in protecting the brain.
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PMID:Protection of the brain by carnitine. 774 96

1. K channels are a diverse and ubiquitous class of proteins that regulate a number of biological functions. 2. Ligands for the study of a variety of K channels are available. These include "openers" and antagonists for the ATP sensitive K channel and peptide toxins such as apamin and charybdotoxin that block other subtypes. 3. Antagonists of the ATP sensitive K channel are useful in the treatment of type II diabetes while "openers" of this channel are being tested in asthma and cardiovascular disease. 4. Intracerebroventricular administration of K channel "openers" block experimentally induced seizures in rodents through a hyperpolarization of neurons. K channel openers may also be useful in the treatment of neurodegenerative diseases, pain and cerebral ischemia. 5. A key to the development of psychopharmacological agents to modify brain K channel function is CNS selectivity. The promise of the ATP sensitive K channel openers suggests a bright future for this mechanism.
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PMID:ATP sensitive potassium channels: potential drug targets in neuropsychopharmacology. 784 82

The effects of ATP (5-500 microM) were evaluated on the proliferation rate of cultured astrocytes by measuring 3H-thymidine incorporation and by flow cytometric analysis of the cell cycle. Determinations after 16 hours showed that ATP present in the culture medium for the whole period caused a dose-dependent reduction of cell proliferation, while if the exposure to ATP was limited to the first 8 hours, the proliferation was increased (always in a dose-dependent manner). A time course study of 3H-thymidine incorporation showed that, in the presence of ATP, 3H-thymidine was incorporated at a slower rate than in controls; the replacement of the culture medium with an ATP-free fresh medium, at the 8th hour, was followed by a 3H-thymidine incorporation occurring at such a fast rate to overshoot the control values. High performance liquid chromatography (HPLC) analysis, carried out to identify purine compounds present in the culture medium during cell exposure to ATP, indicated that more than 95% of the added ATP was metabolized within 1 hr. Conversely, an increase of purine metabolites was measured, this accumulation being greater at the highest concentrations of added ATP. The presence of high levels of extracellular ATP catabolites suggested that these compounds may act on the regulation of cell replication via the different purine receptors. This hypothesis was tested and confirmed by using agonists and antagonists selective for the P1 and the P2 sites. One hundred microM 2methylthio-ATP (2MeSATP), a P2Y agonist metabolized as fast as ATP, reproduced effects very similar to the ATP-induced ones. On the other hand, the nonhydrolisable ATP analogue, adenosine 5'-(beta, gamma-imido)-triphosphate (AMP-PNP) at 100 microM, induced a mitogenic effect as well as the A2 site stimulation. On the contrary, the activation of A1 receptors by 5 microM R-phenyl-isopropyladenosine (R-PIA) inhibited astrocyte proliferation; moreover, 100 nM 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1 site antagonist, reversed the ATP-induced inhibition of cell proliferation. These results indicate that exogenous ATP, as a consequence of its rapid extracellular breakdown, exerts a dual influence on astrocyte proliferation by the involvement of both P1 and P2Y receptors. These findings might be relevant to such pathological conditions of the central nervous system (CNS), as seizures, hypoxia or ischemia, in which great amounts of purines released in the brain can influence a reactive astrocyte proliferative response to injury.
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PMID:Effects of exogenous ATP and related analogues on the proliferation rate of dissociated primary cultures of rat astrocytes. 789 91


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