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)

Adenosine participates in the coupling of cerebral blood flow to oxygen consumption in the brain during such stimuli as hypoxia, ischemia, and seizures. It has been suggested that it also participates in the regulation of cerebral blood flow during somatosensory stimulation, a condition during which cerebral blood flow and oxygen consumption appear to be uncoupled. Interstitial adenosine was estimated by the microdialysis technique and cerebral blood flow was measured by hydrogen clearance in the hindlimb sensory-motor cortex during sciatic nerve stimulation. Cerebral blood flow increased from 102 to 188 ml min-1 100 g-1 (p less than 0.001) in the cortex contralateral to the stimulated leg without an associated increase in interstitial adenosine (baseline 0.624 microM, stimulation 0.583 microM). Infusion of the adenosine antagonist 8-sulfophenyltheophylline failed to block an increase in cerebral blood flow during central sciatic nerve stimulation, but decreased basal cerebral blood flow (69 ml min-1 100 g-1). These results suggest that adenosine does not mediate changes in cerebral blood flow during somatosensory stimulation, but may participate in the regulation of cerebral blood flow in the basal state.
J Cereb Blood Flow Metab 1992 Sep
PMID:Sciatic nerve stimulation does not increase endogenous adenosine production in sensory-motor cortex. 959 50

Extracellular levels of aspartate (ASP), glutamate (GLU), serine (SER), asparagine (ASN), glycine (GLY), threonine (THR), arginine (ARG), alanine (ALA), taurine (TAU), tyrosine (TYR), phenylalanine (PHE), isoleucine (ILEU), and leucine (LEU) were monitored by using intracerebral microdialysis in seven patients with medically intractable epilepsy, undergoing epilepsy surgery. In association with focal seizures, dramatic increases of the extracellular ASP, GLU, GLY, and SER concentrations were observed. The other amino acids analyzed, including TAU, showed small changes. The results support the hypothesis that ASP, GLU, GLY, and possibly SER, play an important role in the mechanism of seizure activity and seizure-related brain damage in the human epileptic focus.
J Cereb Blood Flow Metab 1992 Sep
PMID:Intracerebral microdialysis of extracellular amino acids in the human epileptic focus. 150 52

Focal cortical CBF and oxygenation were measured in rats during repetitive seizures to determine whether CBF is maintained above a critical level for adequate delivery of O2. Cerebral oxygenation was determined by measuring relative changes in the oxidation/reduction level of cytochrome aa3 and CBF was measured by the washout of H2. During early seizures, cortical CBF increased to 350% of control and cortical oxygenation also rose markedly. During later seizures, both the increases in CBF and in cortical oxygenation were attenuated progressively. This was accompanied also by attenuation of the associated increases in MABP. Cortical oxygenation decreased during a seizure if the increase in CBF failed to exceed 150-200% of control, defining the critical CBF value. Ventilating the rats on 97% O2 resulted in restoration of the seizure-associated increases in cortical oxygenation in 50% of the cases. The elevation of inspired O2 was effective only if CBF increased once again above 150-200% of control, confirming that the critical CBF lies within this range of values. We conclude that CBF must rise greater than 200% of control levels to provide sufficient O2 to meet the enhanced metabolic requirements of repetitive seizures.
J Cereb Blood Flow Metab 1991 Jan
PMID:Relative hypoperfusion in rat cerebral cortex during recurrent seizures. 184 66

Insulin, an endogenously produced circulating peptide that enters the brain, has been shown to reduce ischemic brain and spinal cord damage in several animal models. Because of its potential clinical use in humans, the present study was undertaken to test the hypotheses that (a) survival and regional ischemic brain necrosis are improved by insulin; (b) insulin requires concomitant hypoglycemia to exert its neuroprotective effect; (c) insulin is still neuroprotective with delayed administration after an episode of postischemic hypotension; and (d) insulin is beneficial after normoglycemic, as well as hyperglycemic ischemia. Rats were subjected to 10.5 min two-vessel occlusion forebrain ischemia followed by 30 min of hypotension to increase the infarction rate. Insulin administered concomitantly with glucose significantly reduced the seizure rate, as well as cortical and striatal neuronal necrosis below that seen in untreated animals. Neuroprotection was seen whether insulin was given before or after a 30-min episode of postischemic hypotension. Insulin reduced pan-necrosis in addition to selective neuronal necrosis: The infarction rate was reduced in the cerebral cortex, thalamus, and substantia nigra pars reticulata. Normoglycemic ischemia produced only selective neuronal necrosis, but a beneficial effect on structural damage was also seen. The results indicate that insulin acts directly on the brain, independent of hypoglycemia, to reduce ischemic brain necrosis. Possible direct CNS mechanisms of action include an effect on central insulin receptors mediating inhibitory neuromodulation, an effect on central neurotransmitters, or a growth factor effect of insulin.
J Cereb Blood Flow Metab 1991 Nov
PMID:Insulin attenuates ischemic brain damage independent of its hypoglycemic effect. 193 78

We previously demonstrated markedly inhibited brain mitochondrial respiration only in cats that (a) were hyperglycemic at anoxia and (b) had neurologic signs, i.e., fasciculations in tongue or facial muscles or focal seizures following reoxygenation. However, since the relationship between time of onset of mitochondrial dysfunction and neurologic signs was unclear, in the present study we killed postanoxic cats immediately when signs first appeared. Cerebrocortical homogenates and isolated brain mitochondria only from symptomatic cats showed markedly inhibited substrate-, ADP-, and uncoupler-stimulated respiration rates. Cytochrome oxidase activity and cytochrome aa3 concentrations were also markedly reduced in these mitochondria. Since brain mitochondrial function was impaired when neurologic signs first appeared, mitochondrial alterations are an important early organellar change correlated with development of neurologic deterioration following anoxia.
J Cereb Blood Flow Metab 1990 May
PMID:Delayed onset of neurologic deterioration following anoxia/ischemia coincides with appearance of impaired brain mitochondrial respiration and decreased cytochrome oxidase activity. 215

Transient cerebral ischemia in normoglycemic animals is followed by a decrease in glucose utilization, reflecting a postischemic cerebral metabolic depression and a reduction in the activity of the pyruvate dehydrogenase complex (PDHC). Preischemic hyperglycemia, which aggravates ischemic brain damage and invariably causes seizure, is known to further reduce cerebral metabolic rate. To investigate whether these effects are accompanied by changes in PDHC activity, the postischemic cerebral cortical activity of this enzyme was investigated in rats with preischemic hyperglycemia (plasma glucose 20-25 mM). The results were compared with those obtained in normoglycemic animals (plasma glucose 5-10 mM). The activated portion of PDHC and total PDHC activity were measured in neocortical samples as the rate of decarboxylation of [14C]pyruvate in crude brain mitochondrial homogenates after 5 min, 15 min, 1 h, 6 h, and 18 h of recirculation following 15 min of incomplete cerebral ischemia. In normoglycemic animals the fraction of activated PDHC, which rises abruptly during ischemia, was reduced to 19-25% during recirculation compared with 30% in sham-operated controls. In hyperglycemic rats the fraction of activated PDHC was higher during the first 15 min of recirculation. However, after 1 and 6 h of recirculation, the fraction was reduced to values similar to those measured in normoglycemic animals. Fifteen of 26 rats experienced early (1-4 h post ischemia) seizures in the recovery period. The PDHC activity appeared unchanged prior to these early postischemic seizures. We conclude that the accentuated depression of postischemic metabolic rate observed in hyperglycemic animals is not coupled to a corresponding postischemic depression of PDHC.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1990 Jul
PMID:Preischemic hyperglycemia and postischemic alteration of rat brain pyruvate dehydrogenase activity. 234 83

Status epilepticus of greater than 30-min duration in rats gives rise to a conspicuous lesion in the substantia nigra pars reticulata (SNPR) and globus pallidus (GP). The objective of the present study was to explore whether the lesion, which encompasses necrosis of both neurons and glial cells, is related to intra- and extracellular acidosis. Using the flurothyl model previously described to produce seizures, we assessed regional pH values with the autoradiographic 5,5-dimethyl[2-14C]oxazolidine-2,4-dione technique. Regional pH values were assessed in animals with continuous seizures for 20 and 60 min, as well as in those allowed to recover for 30 and 120 min after seizure periods of 20 or 60 min. In additional animals, changes in extracellular fluid pH (pHe) were measured with ion-selective microelectrodes, and extracellular fluid (ECF) volume was calculated from the diffusion profile for electrophoretically administered tetramethylammonium. In structures such as the neocortex and the hippocampus, which show intense metabolic activation during seizures, status epilepticus of 20- and 60-min duration was accompanied by a reduction of the "composite" tissue pH (pHt) of 0.2-0.3 unit. Recovery of pHt was observed upon termination of seizures. In SNPR and in GP, the acidosis was marked to excessive after 20 and 60 min of seizures (delta pHt approximately 0.6 after 60 min).(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1989 Dec
PMID:Seizure-induced damage to substantia nigra and globus pallidus is accompanied by pronounced intra- and extracellular acidosis. 258 76

Glutamate decarboxylase (GAD) activity was determined in caudoputamen (CP), substantia nigra (SN), and cerebral cortex (CCX) after 19-22 h of recirculation following 10 min of transient ischemia in hyperglycemic rats, i.e., under the conditions when previously a pronounced nerve cell damage was demonstrated in both CP and SN. The present results demonstrate a decrease of GAD activity in SN by 30% and in CP by 22% and no change in CCX. No statistically significant change in GAD activity could be detected in SN, CP, or CCX 1,4, and 7 days following 10 min of ischemia in normoglycemic animals. The decrease of GAD activity in SN at the time preceding the onset of postischemic seizures suggests that there may be an imbalance between augmented excitatory and decreased inhibitory transmission in SN. We tentatively conclude that this may increase the probability of generalized seizures in the postischemic period following ischemia in hyperglycemic animals.
J Cereb Blood Flow Metab 1989 Dec
PMID:Decrease of glutamate decarboxylase activity in substantia nigra and caudoputamen following transient hyperglycemic ischemia in the rat. 258 79

The objective of the present study was to explore metabolic correlates to the appearance of postischemic seizures and the enhancement of brain damage observed in subjects that are made hyperglycemic prior to the induction of ischemia. To that end, transient forebrain ischemia of 10-min duration was induced in normo- and hyperglycemic rats, with subsequent measurements of local CMRglc (LCMRglc) after 3, 6, 12, and 18 h of recirculation. We posed the questions of whether postischemic depression of LCMRglc is exaggerated by preischemic hyperglycemia and whether there are signs of localized increases in LCMRglc in hyperglycemic rats, reflecting subclinical seizure activity. The results confirmed the presence of a long-lasting postischemic depression of LCMRglc in normoglycemic rats. This depression was partially but not tightly related to the degree of reduction of local CBF during ischemia. The depression was most pronounced in neocortical areas and in the hippocampus, but notably it was less pronounced in the densely ischemic caudoputamen. Little or no reduction of LCMRglc was observed in moderately or mildly ischemic structures such as the hypothalamus, red nucleus, and cerebellum. Preischemic hyperglycemia markedly accentuated the postischemic depression of LCMRglc. For example, although the subjects quickly regained wakefulness and motility, they had LCMRglc values in neocortical areas that remained below 50% of control. Corresponding but quantitatively less pronounced reductions in LCMRglc were observed in other areas. Notably, preischemic hyperglycemia reduced postischemic LCMRglc also in areas that showed only moderate to mild reductions in CBF during the ischemia. The results thus demonstrate that preischemic hyperglycemia has pronounced metabolic effects in the postischemic recovery period. The data provide no indication that postischemic seizures, which develop after a recovery period of approximately 24 h, are preceded by the appearance of hypermetabolic "seizure" foci.
J Cereb Blood Flow Metab 1989 Aug
PMID:Preischemic hyperglycemia enhances postischemic depression of cerebral metabolic rate. 273 14

In this study, the cerebral hemisphere content of calcium as well as selected parameters of oxidative metabolism and electrophysiological function were assessed in normoglycemic and hyperglycemic rats that were exposed to ischemia produced by electrocautery of the vertebral arteries and reversible occlusion of the carotid arteries. In hyperglycemic animals, 0.5 h of ischemia was associated with large accumulations of lactate (27 mmol/kg), whereas normoglycemic animals showed lesser lactate accumulation (17 mmol/kg). At this sampling time (0.5 h of ischemia), both groups of ischemic animals showed tissue calcium contents that were unchanged from preischemic control levels. In normoglycemic animals, release of the carotid clamps and recirculation for 1.5-24 h was associated with normalization of lactate, ATP and phosphocreatine, clinical behavior, and EEG. During this 24 h of recirculation, cerebral calcium levels showed no changes. Hyperglycemic ischemic animals recirculated for 1.5-24 h showed a persistent lactic acidosis, depressed ATP and phosphocreatine, gross EEG abnormalities, seizures, and a high mortality rate. Again, during this 24 h period, cerebral calcium content showed no changes from preischemic control or from the matched saline-treated group. These data suggest that significant accumulation of calcium in brain tissue is not an early event in ischemic-hyperglycemic brain damage, and thus does not provide support for a role of calcium in the production of this form of ischemic damage.
J Cereb Blood Flow Metab 1989 Oct
PMID:Influence of lactate accumulation on calcium content of ischemic and postischemic brain. 277 33


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