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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of hyperglycemia on the time course of changes in cerebral energy metabolite concentrations and intracellular pH were measured by nuclear magnetic resonance (NMR) spectroscopy in rats subjected to temporary complete brain ischemia. Interleaved 31P and 1H NMR spectra were obtained every 5 min before, during, and for 2 h after a 30-min bilateral carotid occlusion preceded by permanent occlusion of the basilar artery. The findings were compared with free fatty acid and excitatory amino acid levels as well as with cations and water content in funnel-frozen brain specimens. One hour before occlusion, nine rats received 50% glucose (12 ml/kg i.p.) and five received 7% saline (12 ml/kg i.p.). Before ischemia, there were no differences in cerebral metabolite levels or pH between hyperglycemic rats and controls. During the carotid occlusion, the lactate/N-acetylaspartate (Lac/NAA) peak ratio was higher (0.73-1.48 vs. 0.56-0.82; p less than 0.05) and pH was lower (less than 6.0 vs. 6.45 +/- 0.05; p less than 0.05) in the hyperglycemic rats than in the controls. Phosphocreatine and adenosine triphosphate were totally depleted in both groups. Within 5-15 min after the onset of reperfusion, the Lac/NAA peak ratio increased further in all rats; however, only in extremely hyperglycemic rats (serum glucose greater than 960 mg/dl) did the lactic acidosis progress rather than recover later during reperfusion. Total free fatty acid and excitatory amino acid levels, but not cation concentration or water content, in brain correlated with serum glucose levels during and after ischemia and with NMR findings after 2 h of reperfusion. Although profound hyperglycemia (serum glucose of 970-1,650 mg/dl) appears to be associated with progression of anaerobic glycolysis and failure of cerebral energy metabolism to recover after temporary complete brain ischemia and with postischemic excitotoxic and lipolytic reactions thought to participate in delayed cellular injury, severe hyperglycemia (490-720 mg/dl) was associated with recovery of energy metabolism.
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PMID:Effects of hyperglycemia on the time course of changes in energy metabolism and pH during global cerebral ischemia and reperfusion in rats: correlation of 1H and 31P NMR spectroscopy with fatty acid and excitatory amino acid levels. 156 39

Using in vivo 1H NMR spectroscopy (1H MRS) and biochemical analysis, the effects of hyperammonemia on cerebral function were studied in three rat models: acute liver ischemia (LIS), administration of urease (UREASE) and administration of methionine sulfoximine (MSO). By means of localization in three dimensions signals were obtained exclusively from the cerebral cortex. Specially developed lineshape correction and fitting methods were used to quantitate the MRS signals. The following concentration changes were observed; a decrease in glutamate and (phospho)choline for all the models; an increase in glutamine in the LIS and UREASE model but a decrease in the MSO model; a marked increase in lactate in the LIS and UREASE group; a tendency to a decrease in N-acetylaspartate in all the models. These changes agree well with the changes in the post-mortem biochemically determined cerebral cortex glutamine and glutamate concentrations. Estimated absolute 1H MRS metabolite concentrations agree well with those obtained by other techniques; cerebral cortex glutamate, however, is underestimated by about 35% by NMR. The present data support the hypothesis that hyperammonemia is associated with a decreased availability of glutamate for neurotransmission.
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PMID:The use of in vivo proton NMR to study the effects of hyperammonemia in the rat cerebral cortex. 167 7

Using proton and phosphorus magnetic resonance spectroscopy, we evaluated the metabolic effects of preischemic administration of the N-methyl-D-aspartate antagonist dextromethorphan (50 mg/kg i.p.) during global forebrain ischemia and subsequent reperfusion in rats. Dextromethorphan-treated animals (n = 10) showed less lactate formation during ischemia than untreated animals (n = 11, p less than 0.001). During reperfusion, the lactate level in the treated group was reduced (p less than 0.05). Tissue pH declined less in the treated group during ischemia (p less than 0.01). There was no difference in the phosphocreatine/inorganic phosphate peak height ratio between groups. During ischemia, the N-acetylaspartate resonance peaks decreased in both groups. Histologic damage assessed in the hippocampal CA1 region 7 days after the ischemic insult was more severe in the untreated group (p less than 0.05). There was a significant correlation between end-ischemic tissue pH and hippocampal damage (r = -0.73, p less than 0.05). In the dextromethorphan-treated animals, 90% of the rats survived compared with 47% of the untreated animals (p less than 0.05). These results support findings in previous studies that dextromethorphan attenuates ischemic damage.
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PMID:Effects of dextromethorphan on rat brain during ischemia and reperfusion assessed by magnetic resonance spectroscopy. 200 3

Localized in vivo proton magnetic resonance spectra obtained from diseased areas in 2 patients with chronic localized encephalitis (Rasmussen's syndrome) showed reduced resonance intensities from N-acetyl compounds, suggesting focally decreased N-acetylaspartate concentrations. One of the patients had epilepsia partialis continua secondary to the encephalitis. In this patient, the spectra demonstrated a high lactate resonance intensity (not seen in the normal, contralateral hemisphere) corresponding to an estimated local concentration of about 7.5 mM. We speculate that the observed decrease in the N-acetyl compound resonance may be a biochemical correlate of the neuronal loss characteristic of this disease. The results establish that excessive accumulation of lactate can occur in the human brain as a result of seizure activity even in the absence of ischemia. Thus, bioenergetic compromise may be 1 predisposing factor to the death of excitable cells in the epileptogenic area.
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PMID:A proton magnetic resonance spectroscopy study of focal epilepsy in humans. 211 99

This review has attempted to indicate areas of investigation that in vivo MRS methodology is particularly suited for and would answer important questions related to neonatal cerebral development or injury. There are several metabolites (PEth, PCr, NAA, taurine, glutamate) and lipids detectable by in vivo 31P or 1H MRS, which show substantial changes in concentration during ontogenesis. Do these biochemical markers correlate with major morphological changes, such as myelination? If they do, can this be used to quantitate abnormalities in brain development from congenital abnormalities or metabolic encephalopathies? In the neutral to mild acidic range (7.0 greater than pHi greater than 6.5) adult and neonatal brain appear to have similar intrinsic physicochemical buffering capacity. However, at the extremes of pHi induced by respiratory alkalosis or severe acidosis from partial ischemia, the possibility exists that the buffering capacities of adult and neonatal brain differ. Whether this is true requires further investigations using both neonates and adults, or perhaps more preferably, multiple measurements on a single species throughout its developmental period. Such studies are now feasible because multinuclear in vivo MRS can provide a large body of information from individual animals. A similar study design could prove useful for investigations of changes in cerebral resistance to hypoxia, ischemia, or asphyxia during development. The roles that blood pressure, glucose, temperature, or the administration of extrinsic buffers and drugs have on modulating the severity of and relationship between changes in blood flow, energy metabolites, or pHi, are all amenable to study using in vivo MRS. Furthermore, all of these variables can be measured simultaneously. The kinetics of brain acid and lactate homeostasis during chronic cerebral insults or following acute insults has not been thoroughly examined in either neonates or adult animals. There is evidence to suggest that following ischemia or seizures, brain acidosis resolves before brain lactosis. However, the clinical diagnostic significance of this post-insult uncoupling between pHi and lactate remains to be established. Finally, the application of in vivo MRS methodology to study the effects of trauma, drugs, environmental toxins, and other metabolic encephalopathies on neonatal cerebral perfusion and metabolism are virtually unexplored. Hopefully, the material presented here will prompt researchers to consider the application of in vivo MRS to new avenues of investigation.
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PMID:In vivo multinuclear magnetic resonance spectroscopy investigations of cerebral development and metabolic encephalopathy using neonatal animal models. 219 84

Proton nuclear magnetic resonance (NMR) spectroscopy of perchloric acid tissue extracts has been used to follow serial postischemic changes in the levels of metabolites in the hippocampus, cerebellum, frontal lobes, and parietal/occipital lobes in a rat model of short-duration (10 minutes) forebrain ischemia. Shortly (10 minutes, 1 hour) after the ischemic insult, the levels of the amino acids alanine and gamma-aminobutyric acid are elevated and that of glutamate is depressed in all regions except the cerebellum. The levels of these species return to control values by 24 hours postischemia. No changes are observed in the levels of aspartate or N-acetylaspartate. Greatly elevated levels of acetate 10 minutes postischemia, particularly in the hippocampus, may be due in part to metabolic degradation of fatty acids released due to membrane breakdown. Elevated levels of lactate persist for up to 7 days postischemia, suggesting that normal mitochondrial functioning is not fully restored following the ischemic insult.
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PMID:Nuclear magnetic resonance study of regional metabolism after forebrain ischemia in rats. 271 4

The disappearance of high-energy phosphates (HEPs) in the rat brain during global ischemia induced by cardiac arrest is slowed down significantly by dihydropyridine Ca antagonists (DCAs) compared to controls. Two mechanisms might account for this effect: increased HEP production via anaerobic glycolysis or decreased HEP consumption. In order to obtain more insight into the underlying mechanisms of ATP preservation we have studied in the rat the effect of the DCAs isradipine, darodipine and nimodipine on the cerebral steady-state levels of HEPs and lactate as well as the intracellular pH value during global ischemia using combined 31P/1H magnetic resonance spectroscopy. We have found that the ATP preservation in DCA-treated animals is not associated with significantly higher postischemic lactate levels (lactate/N-acetylaspartate 0.97 +/- 0.08 for isradipine at a dose of 2.5 mg/kg i.p.) or lower pH values (6.40 +/- 0.03) as compared to control rats (lactate/N-acetylaspartate 0.94 +/- 0.13, pH = 6.49 +/- 0.03). This is in contrast to hyperglycemic rats, in which similar preservation of ATP levels during ischemia was observed; however, at the expense of a larger drop in brain pH (6.22 +/- 0.09) and a concomitant increase in cerebral lactate (lactate/N-acetylaspartate = 1.40 +/- 0.09). These results strongly favor reduced ATP consumption to be the cause for the protective effect of DCAs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dihydropyridine calcium antagonists reduce the consumption of high-energy phosphates in the rat brain. A study using combined 31P/1H magnetic resonance spectroscopy and 31P saturation transfer. 281 Jan 19

In vivo 1H NMR spectral editing techniques were used to monitor cerebral lactate production during remotely controlled temporary forebrain ischemia in rats. The lactate/N-acetylaspartate (NAA) ratio correlated with survival after ischemia and subsequent reperfusion. The lactate/NAA ratio that predicted death after ischemia in rats was estimated to be approximately 1.3.
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PMID:Measurement of lactate accumulation by in vivo proton NMR spectroscopy during global cerebral ischemia in rats. 368 64

High-resolution proton magnetic resonance (MR) spectroscopy was performed on perchlorate extracts of tumors (24 cases) or peritumoral vermis (five cases) obtained at surgery. Fifteen tumors were typical cerebellar astrocytomas and nine were posterior fossa primitive neuroectodermal tumors/medulloblastomas. Spectra obtained from the five samples of peritumoral vermis revealed a pattern of metabolites similar to that reported for cerebellar tissue, but concentrations of most metabolites were low, perhaps due to dilution from peritumoral edema. The astrocytomas were characterized by high levels of valine, alanine, and choline, an increase in the choline:N-acetylaspartate (NAA) ratio, and a shift from glutamate to glutamine. Elevations in lactate, pyruvate, and glucose were the result of ischemia during sampling. The primitive neuroectodermal tumors/medulloblastomas were distinguished from astrocytomas by a greater increase in the choline:NAA ratio, a smaller decrease in the glutamate:glutamine ratio, and a relative increase in glycine, taurine, and inositol levels. These metabolic patterns may be of value diagnostically as in vivo MR spectroscopy achieves higher resolution.
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PMID:High-resolution 1H-magnetic resonance spectroscopy of pediatric posterior fossa tumors in vitro. 791 30

The suitability of two-dimensional (2D) proton spectroscopy for monitoring, in vivo, the changes in levels of brain metabolites induced by cerebral ischemia was investigated in an experimental model of 30-min reversible ischemia induced by four-vessel occlusion in the rat. The resulting data were compared with those obtained by one-dimensional (1D) proton and phosphorus spectroscopy. Phosphorus spectra obtained during ischemia showed significant drops in levels of phosphocreatine (-73%), beta-ATP (-60%), and intracellular pH (to 6.30) and an increase in inorganic phosphate level (905%). 1D and 2D proton spectra showed decreases in the N-acetylaspartate/creatine-phosphocreatine ratio that were not significantly different [-21% (1D) and -32% (2D)]. Similarly, the increases in lactate/creatine-phosphocreatine ratio were not significantly different [2,546% (1D) and 3,020% (2D)]. 2D spectroscopy also indicated a decrease in aspartate (-66%) and an increase in the inositol-choline derivative (+124%) pools during ischemia and an increase in alanine pool (+516%) during reperfusion. The glutamate-glutamine pool and taurine content did not change significantly during ischemia but decreased during reperfusion. The glucose level transiently decreased (-67%) during ischemia and increased immediately after (+261%). The levels of all the metabolites investigated returned to control values within 175 min after ischemia. 2D spectroscopy seems to be a reliable method of monitoring the changes in levels of cerebral compounds known to be involved in ischemia.
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PMID:A one-dimensional (proton and phosphorus) and two-dimensional (proton) in vivo NMR spectroscopic study of reversible global cerebral ischemia. 863 74


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