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

Previous studies in our laboratory have shown that L-carnitine suppresses seizures and alterations of brain energy metabolism in mice caused by hyperammonemia. The present study was done to exclude the effects of seizures on brain energy metabolism. When sublethal dose of ammonium acetate (12 mmol/kg b.wt.) was injected to mice, all mice survived without developing seizures, while clear increase of brain ammonia and alterations of brain energy metabolites were seen. In L-carnitine-treated animals, the levels of ammonia, AMP and lactate were lower and those of ATP and phosphocreatine were higher than in untreated animals. Treatment with D-carnitine also preserved the phosphocreatine level. This indicates that the improvement of brain energy metabolism by L-carnitine in hyperammonemia is not simply a result of the suppression of seizures, and that the "physiological" function of carnitine may not be the sole mechanism underlying this effect.
 ...
PMID:Effects of L and D-carnitine on brain energy metabolites in mice given sublethal doses of ammonium acetate. 851 63

Alterations in the energy state and glucose metabolism of hippocampal slices exposed to high extracellular K+ ([K+]o) were monitored using 31P and 13C NMR spectroscopy. Slices were perfused (37 degrees C) continuously within the NMR spectrometer and tissue viability and metabolic activity were maintained for at least 18 h. 31P spectra showed that upon exposure to 40 mM [K+]o, there was a rapid compromise in tissue energetics where, by 15 min of exposure, the ratio of phosphocreatine and of nucleoside triphosphates to inorganic phosphate (extra- and intracellular) decreased 30-50% relative to pre-exposure values. This was accompanied by a pH decrease of approximately 0.3 units in both the intra and extracellular environments. A lower but stable energy state was reached at approximately 15 min of exposure and full recovery was observed by 30 min following the removal of high [K+]o. Utilizing 13C NMR in the presence of [1-13C]glucose, an immediate and dramatic acceleration in tissue glycolysis was observed when slices were exposed to 40 mM [K+]o: the rates of both [1-13C]glucose consumption and [3-13C] acetate synthesis increased by approximately 20 fold. By 60 min following the removal of high-[K+]o, pre-exposure rates of tissue glycolysis were restored. The results indicated that the rapid and dramatic induction of energy production via glycolysis probably accounts for the ability of hippocampal slices to maintain viability and recuperate from brief but intense depolarizing conditions which are reminiscent of seizure states in vivo.
 ...
PMID:Energetics and glucose metabolism in hippocampal slices during depolarization: 31P and 13C NMR studies. 851 24

Ketosis is beneficial for seizure control, possibly through induction of cerebral acidosis. However, cerebral intracellular pH has not previously been measured in ketotic humans and the animal data are sparse. We describe a high-fat diet, avidly consumed by rats, that induced consistent and moderate ketosis. Adult male rats were fed either the high-fat ketogenic diet, a high-carbohydrate diet with the same protein content as the ketogenic diet, or regular laboratory chow. Five to 6 weeks later, the rats were anesthetized, paralyzed, and injected with neutral red; their brains were frozen in situ. Intracellular pH of the cerebral cortex and cerebral glucose, lactate, ATP, phosphocreatine, and gama-aminobutyric acid (GABA) levels were measured. Rats fed the ketogenic diet had > 10-fold increase in their plasma ketones, but we noted no significant differences in cerebral pH or in cerebral metabolites and GABA levels among the three groups. Therefore, the antiepileptic effect of the ketogenic diet probably is not mediated by cerebral acidosis or changes in total cerebral GABA levels.
 ...
PMID:Diet-induced ketosis does not cause cerebral acidosis. 859 84

The inorganic phosphate (Pi) NMR peak in brain has an irregular shape, which suggests that it represents more than a single homogeneous pool of Pi. To test the ability of the Marquardt-Levenberg (M-L) nonlinear curve fit algorithm software (Peak-Fit) to separate multiple peaks, locate peak centers, and estimate peak heights, we studied simulated Pi spectra with defined peak centers, areas, and signal-to-noise (S/N) ratios ranging from infinity to 5.8. As the S/N ratio decreased below 15, the M-L algorithm located peak centers accurately when they were detected; however, small peaks tended to grow smaller and disappear, whereas the amplitudes of larger peaks increased. We developed an in vitro three-compartment model containing a mixture of Pi buffer, phosphocreatine, phosphate diester, and phosphate monoester (PME), portions of which were adjusted to three different pHs before addition of agar. Weighed samples of each buffered gel together with phospholipid extract and bone chips were placed in an NMR tube and covered with mineral oil. Following baseline correction, it was possible to separate the Pi peaks arising from the three compartments with different pH values if each peak made up 10-35% of total Pi area. In vivo, we identified the plasma compartment by intraarterial infusion of Pi. It was assumed that intracellular compartments contained high-energy phosphates and took up glucose. Based on these assumptions we subjected the brains to complete ischemia and observed that Pi compartments at pH 6.82, 6.92, 7.03, and 7.13 increased markedly in amplitude. If the brain cells took up and phosphorylated 2-deoxyglucose (2-DG), 2-DG-6-phosphate (2-DG-6-P) would appear in the PME portion of the spectrum ionized according to pH. Four 2-DG-6-P peaks with calculated pH values of 6.86, 6.94, 7.04, and 7.15 did appear in the spectrum, thereby confirming that the four larger Pi peaks represented intracellular spaces.
 ...
PMID:NMR studies of Pi-containing extracellular and cytoplasmic compartments in brain. 863 89

Proton magnetic resonance spectra include signals from N-acetylaspartate, creatine + phosphocreatine, and choline-containing compounds. Abnormalities in these signals can be used in the assessment of patients with intractable epilepsy. In particular, they provide a means of identifying metabolic abnormalities within the temporal lobes, detecting bilateral and diffuse pathology, and aiding lateralization of the seizure focus. The pathology demonstrated on MRS can also be related to cognitive dysfunction.
 ...
PMID:N-acetylaspartate and epilepsy. 875 Mar 36

The present experiments were undertaken to study how preischemic hyperglycemia, which is known to exaggerate ischemic damage and to trigger delayed postischemic seizures affects the bioenergetic state and the intracellular pH (pHi) of brain tissue at early (6 h) and late (18 h) recirculation times. To that end, normo- and hyperglycemic rats were subjected to 10 min of forebrain ischemia, and neocortical tissue was frozen in situ for analyses of labile energy metabolites. Animals with preischemic hyperglycemia failed to show a postischemic reduction of the phosphorylation state of the adenine nucleotide pool, or a rise in tissue lactate content, nor did they show a change in tissue redox state. However, the hyperglycemia led to a rise in phosphocreatine (PCr) content after 6 h of recirculation. Calculations of intracellular pH (pHi) from the creatine kinase (CK) equilibrium showed a rise in pHi above normal, a finding which was supported by a limited number of 5,5-dimethyl[2-14C]oxazolidine-2,4-dione (DMO) measurements. The preischemic hyperglycemia also blunted the postischemic rise in tissue glycogen content, which is usually observed in normoglycemic rats. The results thus fail to reveal that the hyperglycemia-triggered, massive exaggeration of ischemic brain damage, which is heralded by generalized seizures after 18-24 h of recirculation, is preceded by mitochondrial dysfunction of a degree which affects the bioenergetic state or the redox potential of the tissue. However, the results suggest that the hyperglycemia enhances and/or prolongs the postischemic alkalosis. It is discussed whether the rise in pH contributes to the mitochondrial dysfunction which subsequently develops.
 ...
PMID:Changes in labile energy metabolites, redox state and intracellular pH in postischemic brain of normo- and hyperglycemic rats. 883 45

We performed proton magnetic resonance spectroscopic imaging of the temporal lobes between, during, and soon after nonconvulsive seizures in 20 patients with documented temporal lobe epilepsy, 5 patients with primary generalized epilepsy, and 2 patients with secondary generalized epilepsy. Our objective was to determine whether there were metabolic changes observable by magnetic resonance spectroscopic imaging during seizures and whether these changes were specific for focal or generalized nonconvulsive seizures. We found a significant increase in lactate to creatine plus phosphocreatine (lactate/creatine) values, reflecting an imbalance in energy supply and demand or an adaptation in response to ictal neuronal discharges, during and soon after complex partial seizures, but not during or soon after absence seizures associated with generalized epilepsy. In patients with temporal lobe epilepsy, the N-acetylaspartate resonance relative to creatine plus phosphocreatine was low in one or both temporal lobes, indicating neuronal loss or damage. This was not observed in patients with primary generalized epilepsy. The regions with abnormal lactate/creatine and N-acetylaspartate/creatine values corresponded to the epileptogenic focus as defined by clinical-electroencephalographic investigation. There was no change in the N-acetylaspartate/creatine values in the temporal lobes between the interictal, ictal, or postictal states. We conclude that (1) partial seizures are associated with abnormally high lactate levels, but absence seizures are not, and (2) no short-term changes of N-acetylaspartate occur during or soon after complex partial seizures or absence seizures. These findings may be related to the lack of postictal confusion in patients with absence seizures, as well as with the more benign course of primary generalized epilepsy with nonconvulsive attacks.
 ...
PMID:Proton magnetic resonance spectroscopic imaging for discrimination of absence and complex partial seizures. 900 68

When ddY mice were pretreated with L-carnitine (5, 10 or 20 mmol/kg), clonic as well as tonic seizures induced by pentylenetetrazol (PTZ) were dose-dependently suppressed. A time/response study (PTZ was injected 1, 5, 15 or 30 min after L-carnitine) showed that the anticonvulsive effects were apparent when the interval between L-carnitine and PTZ administration was 15-30 min. Saline containing 43% sucrose prolonged the latency to the first clonic seizure but was less effective than 20 mmol/kg L-carnitine and did not suppress clonic or tonic seizures. Alterations in brain energy metabolites caused by PTZ including increase of lactate and decrease of ATP and phosphocreatine were also suppressed by L-carnitine. L-carnitine was more potent than D-carnitine in prolonging the latency to the first clonic seizure and in decreasing the frequency of clonic as well as tonic seizures. The anticonvulsive effects of L-carnitine in PTZ-induced seizures may be unrelated to the transport of long-chain acyl CoA since they were not interfered with by D-carnitine.
 ...
PMID:Suppression of pentylenetetrazol-induced seizures by carnitine in mice. 910 73

Brain creatine kinase (CK) catalyzed phosphorus fluxes between phosphocreatine (PCr) and ATP and changes in reactant concentrations were measured using [31P] nuclear magnetic resonance spectroscopy ([31P]NMR) before and during pentylenetetrazole-induced seizures in 7 and 21 day old rats. The CK rate constants measured before seizures were three times higher in the older than in the younger rats. The rate constants increased 60% during seizures in the older rats but did not change or decreased in the younger. Small decreases in PCr were seen during seizures at both ages. A small decrease in ATP was seen at 7 days but not at 21 days.
 ...
PMID:Brain creatine kinase reaction rates and reactant concentrations during seizures in developing rats. 916 86

Mitochondrial and cytosolic creatine kinase (CK) isozymes are active in cells with high and variable ATP metabolic rates. beta-Guanidinopropionic acid (GPA), a competitive inhibitor of creatine transport, was used to study the hypothesis that the creatine-CK-phosphocreatine (PCr) system is important in regulating brain ATP metabolism. The CK-catalyzed reaction rate and reactant concentrations were measured in vivo with 31P nuclear magnetic resonance spectroscopy during energy deficit (hypoxia) or high-energy turnover (seizures) states in urethane-anesthetized mice fed GPA, creatine, or standard chow (controls). Brain phosphagen (i.e., cellular energy reserves) or PCr plus phosphorylated GPA (GPAP) concentrations were equal. The phosphagen-to-NTP ratio was lower than in controls. In vivo CK reaction rate decreased fourfold, whereas ex vivo CK activity that was biochemically measured was doubled. During seizures, CK-catalyzed fluxes increased only in GPA-fed mice. Phosphagen increased in GPA-fed mice, whereas PCr decreased in controls. Survival was higher and brain phosphagen and ATP losses were less for hypoxic GPA-fed mice than for controls. In contrast to mice fed GPA, hypoxic survival and CK reactant concentrations during hypoxia and seizures were the same in creatine-fed mice and controls. Thus GPA, GPAP, or adaptive changes in ATP metabolism stabilize brain ATP and enhance survival during hypoxia in mice.
 ...
PMID:In vivo brain phosphocreatine and ATP regulation in mice fed a creatine analog. 917 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>