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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regional cerebral ischemia was produced by common carotid artery occlusion in gerbils and by middle cerebral artery occlusion in dogs, cats, and squirrel monkeys. Anesthesia was induced with either pentobarbital or halothane and maintained for two to three hours after vessel occlusion. In acute studies, the effect of regional cerebral ischemia on cerebral concentrations of ATP, phosphocreatine, lactate, and pyruvate was determined at the end of this period in gerbils, cats, and squirrel monkeys. In chronic studies, the degree of neurological deficit and size of cerebral infarction were determined 48 hours after a two-hour to three-hour period of vessel occlusion in cats and squirrel monkeys and permanent occlusion in dogs. In gerbils, dogs, and cats, there were no differences in the metabolis, functional, or pathological effects of anesthesia with pentobarbital or halothane. However, in the squirrel monkey, in acute studies the metabolic alterations were significantly less with pentobarbital, and in chronic studies the frequency and magnitude of functional deficits and cerebral infarction were significantly less. We conclude that pentobarbital does provide a degree of protection during regional cerebral ischemia but that such effects are only consistently demonstrable in primates. In nonprimates, we assume that variability in the collateral circulation renders demonstration of significant differences difficult or impossible.
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PMID:Influence of anesthetics on metabolic, functional and pathological responses to regional cerebral ischemia. 80

Adult rhesus monkeys were subjected to complete cerebral ischemia for one hour and subsequent recirculation for up to 24 h. Animals with signs of functional recovery (e.g. spontaneous EEG activity) exhibited a partial replenishment of cellular energy sources (ATP, phosphocreatine) and a progressive normalization of cerebral lactate levels. Glucose and pyruvate concentrations showed a transient increase over control values during the early stages of postischemic recirculation. Monkeys without functional recovery lacked a significant resynthesis of energy-rich compounds; adenine nucleotides continued to decrease and lactate concentrations were higher than in animals subjected to ischemia without recirculation. Cerebral polysome profiles remained unaltered during the ischemic period but in all animals a marked disaggregation of polyribosomes with a concomitant increase in ribosomal subunits occurred after the onset of recirculation. In monkeys with indications of functional recovery these changes were reversible but a normal polysome profile was only observed after 24 h of recirculation. The results obtained indicate a postischemic depression of protein synthesis due to an inhibition of peptide chain initiation. After recirculation of the brain for 3-6 h there was evidence for an induction of enzymes involved in polyamine synthesis (ornithine decarboxylase and S-adenosylmethionine decarboxylase). No changes in the activity of these enzymes were observed at the end of the ischemic period, indicating that during complete cerebral ischemia not only the synthesis but also the catabolism of proteins is inhibited.
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PMID:Resuscitation of the monkey brain after one hour complete ischemia. III. Indications of metabolic recovery. 115 69

The effects of dichloroacetate (DCA) on brain lactate, intracellular pH (pHi), phosphocreatine (PCr), and ATP during 60 min of complete cerebral ischemia and 2 h of reperfusion were investigated in rats by in vivo 1H and 31P magnetic resonance spectroscopy; brain lactate, water content, cations, and amino acids were measured in vitro after reperfusion. DCA, 100 mg/kg, or saline was infused before or immediately after the ischemic period. Preischemic treatment with DCA did not affect brain lactate or pHi during ischemia, but reduced lactate and increased pHi after 30 min of reperfusion (p < 0.05 vs. controls) and facilitated the recovery of PCr and ATP during reperfusion. Postischemic DCA treatment also reduced brain lactate and increased pHi during reperfusion compared with controls (p < 0.05), but had little effect on PCr, ATP, or Pi during reperfusion. After 30 min of reperfusion, serum lactate was 67% lower in the postischemic DCA group than in controls (p < 0.05). The brain lactate level in vitro was 46% lower in the postischemic DCA group than in controls (p < 0.05). DCA did not affect water content or cation concentrations in either group, but it increased brain glutamate by 40% in the preischemic treatment group (p < 0.05). The potential therapeutic effects of DCA on brain injury after complete ischemia may be mediated by reduced excitotoxin release related to decreased lactic acidosis during reperfusion.
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PMID:Effect of dichloroacetate on recovery of brain lactate, phosphorus energy metabolites, and glutamate during reperfusion after complete cerebral ischemia in rats. 135 94

We have previously developed a reproducible model of transient forebrain ischaemia in rats by bilateral carotid artery occlusion combined with temporary increase of ICP. With this model, reversibility of the energy metabolism and intracellular pH (pHi) was investigated by 31P-MRS during 120 min of recirculation in three groups of, respectively, 30, 60, and 120 min of ischaemia. With the induction of ischaemia, ATP and phosphocreatine (PCr) disappeared, and measurement of pHi showed severe acidosis in all rats. In the 30 min ischaemia group, both energy metabolism and pHi recovered almost completely. In the 60 min ischaemia group, ATP recovered to 74% of control values, but pHi showed full recovery. In the 120 min ischaemia group, ATP recovered to about 50% of control values, and recovery of pHi was variable. Showing logarithmical changes during recirculation in ATP and PCr, the rate of metabolic recovery was fast during 60 min of recirculation, but it decreased and reached plateau thereafter in all groups. Recovery of pHi was affected by ATP levels, and was precipitously accelerated as ATP levels exceeded 50% of pre-ischaemic values. These results suggest that prolongation of the duration of ischaemia limits the restoration of the energy state, and the quality of pHi recovery after cerebral ischaemia is affected by the degree of ATP recovery during 60 min of recirculation.
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PMID:Reversibility of energy metabolism and intracellular pH after cerebral ischaemia evaluated by 31P-MRS. 136 56

To ascertain the alterations in cerebral oxidative and energy metabolism that occur during hypothermic circulatory arrest, nitrous oxide-anesthetized, paralyzed, and artificially ventilated newborn dogs were surface cooled to 18-20 degrees C, after which their hearts were arrested with KCl. At 10, 30, 60, and 105 min of circulatory arrest, their brains were prepared by in situ freezing for the regional analysis of glycolytic intermediates and high-energy phosphate reserves. Hypothermia alone was associated with optimal preservation of labile metabolites in brain, even in caudal brainstem and cerebellum, compared with barbiturate-anesthetized littermates. After onset of hypothermic circulatory arrest, glucose decreased progressively in cerebral cortex, caudate nucleus, hippocampus, and subcortical white matter to negligible levels by 30 min. Pyruvate increased transiently (+50%) at 10 min, whereas lactate increased and plateaued (10-11 mmol/kg) at 30 min. The disproportionate increases in pyruvate and lactate resulted in a progressive rise in the lactate/pyruvate ratio. Phosphocreatine fell precipitously to < 0.5 mmol/kg in all structures, with a preservation of ATP for the first 10 min of cerebral ischemia. Thereafter, ATP decreased to < 0.1 mmol/kg in cerebral cortex and between 0.1 and 0.2 mmol/kg in caudate nucleus, hippocampus, and white matter. Total adenine nucleotides (ATP+ADP+AMP) were partially depleted by 30 min in the gray matter structures but were unchanged from control for 60 min in white matter. The findings showed a direct correlation between preservation of cerebral energy stores during hypothermic circulatory arrest and the selective resistance of subcortical white matter to ischemic damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebral oxidative metabolism during hypothermia and circulatory arrest in newborn dogs. 148 Apr 56

Proton magnetic resonance spectroscopy (MRS) with the depth resolved surface coil spectroscopy technique and the 1331-2662 water suppression method was used to examine two cerebral ischemia patients and 10 normal volunteers. In all cases, N-acetyl-aspartate, creatine, phosphocreatine, and residual lipid were clearly observed. No lactic acid peak was observed in normal volunteers, but a large lactic acid peak appeared in the early stage of cerebral ischemia. This MRS abnormality was observed before abnormalities appeared in conventional imaging such as computed tomographic scanning and magnetic resonance imaging.
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PMID:Clinical application of proton magnetic resonance spectroscopy to cerebral ischemia. 172 Feb 15

We measured the parameter lambda, which is the ratio of the distribution spaces of 2-deoxy-D-glucose (DG) and glucose in the brain, in a model of focal cerebral ischemia in the cat. lambda is the parameter in the lumped constant of the [14C]DG technique most susceptible to changes in ischemia. Cats were subjected to occlusion of the middle cerebral artery for a period of 2 h. During the last 60 min of occlusion, [14C]DG was infused in a programmed fashion so as to obtain a stable arterial blood [14C]DG concentration. The brain was funnel-frozen to preserve tissue metabolites and the frozen brain was sampled regionally (4 to 7-mg samples) for local concentrations of glucose, ATP, phosphocreatine (PCr), and lactate. In a separate series of cats, the infusion of [14C]DG was started after 2 h of occlusion and 3 h of recirculation. In both series, lambda declined slightly for increased levels of tissue glucose and increased appreciably as tissue glucose decreased. A similar relationship was observed between lambda and ATP and PCr, although the correlation was not as clear. Since lambda, and hence the lumped constant, increases in ischemia as well as in postischemic tissue, it is important to measure tissue glucose concentration if quantitative values of local cerebral glucose metabolism are desired in this condition.
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PMID:Effect of ischemia and reperfusion on lambda of the lumped constant of the [14C]deoxyglucose technique. 172 44

The energy state and the levels of metabolites involved in the phospholipid turnover during and following a transient cerebral ischemia have been evaluated with the aids of 31P and 1H nuclear magnetic resonance spectroscopy. Ischemia was induced by electrocoagulation of vertebral arteries in combination with transient occlusion of both common carotid arteries. After 10-min ischemia, the brain energy charge and the levels of high-energy phosphates were reduced, whereas lactic acid levels had undergone an 8-fold increase. Sixty minutes after cerebral blood flow recovery, brain energy charge and levels of high-energy phosphates returned to basal values, whereas lactic acid levels remained persistingly elevated; an increase in phosphocreatine was also observed. At this same time, glycerolphosphorylcholine levels were found to be significantly reduced.
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PMID:Transient cerebral ischemia in the rat: a study by nuclear magnetic resonance spectroscopy. 175 21

In vivo NMR (nuclear magnetic resonance) spectroscopy allows for non-invasive measurement of the intracellular pH and the concentration of different metabolites in defined areas of the brain. Phosphocreatine, ATP and lactic acid are of prime interest in ischaemia research. Moreover, a distinction can be made between glycolysis and the oxidative breakdown of glucose after administering C-13-labelled glucose. Finally, spectroscopy of fluorine-containing inert gases such as Freon-23 allows for measuring cerebral blood flow and for directly relating the metabolic alterations to the changes in cerebral blood flow. Given the non-invasive character of NMR spectroscopy all metabolic process occurring throughout one experiment can for the first time be followed up. Thus metabolic alterations during ischaemia can directly be correlated with post-ischaemic recovery processes. It has been shown with the cerebral ischaemia model in the cat that recovery after circulatory failure rather depends on post-ischaemic changes such as the recirculation rate or the speed of high-energy phosphate formation than on the speed of energy metabolism breakdown or acidosis occurring during ischaemia. The future of nuclear magnetic resonance spectroscopy in experimental ischaemia research certainly lies in the therapeutic range. As the exact extent of ischaemic damage can be determined in each experiment it is possible for the first time to define the effect of a drug substance on metabolic dysfunction in each individual experiment. This method is not only expected to reduce the number of laboratory animals but also to dramatically improve statistical variability compared to group comparisons.
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PMID:[Studies of experimental cerebral ischemia with NMR spectroscopy]. 185 98

We superimposed extreme hypercapnia (arterial Pco2 400-450 mmHg) immediately before and during incomplete cerebral ischemia to distinguish the role of intracellular pH (pHi) and bicarbonate [( HCO3-]i) in postischemic metabolic and electrophysiological recovery. Incomplete global ischemia was produced in seven anesthetized dogs by 30 min of intracranial hypertension followed by 4 h of reperfusion. ATP, phosphocreatine (PCr), and pHi were measured with 31P magnetic resonance spectroscopy, and [HCO3-]i was calculated from the Henderson-Hasselbalch equation using the measured pHi and sagittal sinus Pco2. Cerebral blood flow was reduced to 7 +/- 1 ml.min-1.100 g-1 (+/- SE) during ischemia with extreme hypercapnia, and pHi decreased to 5.72 +/- 0.09. During normocapnic reperfusion, pHi rapidly returned to near baseline values by 14 min. [HCO3-]i fell from 12.1 +/- 0.9 to 6.0 +/- 1.2 mM by the midpoint of ischemia and recovered by 30 min of reperfusion. ATP, PCr, and O2 consumption also recovered rapidly and completely. Somatosensory-evoked potentials (SEP) recovered to 43 +/- 10% of control amplitude. These results are in marked contrast to the poor metabolic and SEP recovery previously observed in hyperglycemic dogs in which pHi decreased to the same range as with hypercapnic ischemia, but in which [HCO3-]i was much lower (1.1 +/- 0.5 mM). Therefore, [HCO3-]i depletion during hyperglycemic ischemia may be a more important factor in recovery than end-ischemic pHi per se. We speculate that higher [HCO3-]i may improve glial cell buffering capacity or decrease iron availability for hydroxyl radical production.
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PMID:Bicarbonate conservation during incomplete cerebral ischemia with superimposed hypercapnia. 190 5


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