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

Pilots of high-performance aircraft are subject to transient loss of consciousness due to cerebral ischemia resulting from sudden high gravitational stress. To assess the effects of gravitational stress-induced blackout on cerebral metabolism and electrical function, we developed an animal model in which global cerebral ischemia is produced repeatedly at short intervals. Rats were prepared by ligation of subclavian and external carotid arteries and the right carotid artery was cannulated bidirectionally to measure circle of Willis and systemic pressures. Ischemia was induced by inflation of an occluder about the left carotid artery. Interleaved 31P and 1H NMR spectra were acquired on a 4.7-T Biospec system simultaneously with EEG recordings. We report results from 20 experiments of 30-min duration in which rats were subject to 30 1-min ischemia:reflow cycles of 10I:50R, 20I:40R, 30I:30R, and 40I:20R [numbers are seconds of ischemia (I) and reflow (R) during each 1-min cycle]. During ischemia the graded delivery of the ischemic insult permitted direct correlations between 2- to 5- and 7- to 20-Hz EEG activity and progressive changes in pH, lactate, ATP, phosphocreatine (PCr) and Pi. The best correlations were found between EEG activity and pH and PCr; correlation coefficients ranged from 0.93 to 0.95. A loss of EEG activity was observed without significant sustained energy loss in all but the most severe cycle.
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PMID:Concomitant EEG, lactate, and phosphorus changes by 1H and 31P NMR spectroscopy during repeated brief cerebral ischemia. 779 37

Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive technique which has proved to be useful for monitoring various brain metabolites (N-acetyl-aspartate, choline, creatine-phosphocreatine, lactate). A total of 18 patients underwent a combined magnetic resonance imaging (MRI)/1H-MRS protocol in order to evaluate the distribution of the metabolites in the various stages of cerebral ischemia. Our results show a marked decrease of N-acetyl-aspartate and a large content of Lactate during the early phases, and a decrease in N-acetyl-aspartate, choline and creatine-phosphocreatine (Cr-PCr) during the chronic phase.
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PMID:Proton magnetic resonance spectroscopy in patients with ischemic stroke. 787 59

The effects of acetyl-L-carnitine (ALCAR) treatment on brain energy state recovery and lactic acid levels following 20 min ischemia and 2, 24 and 48 h reperfusion were investigated by 31P and 1H-NMR spectroscopy. Transient forebrain ischemia was induced by four-vessel occlusion method in fed 6-month-old Fischer rats. ALCAR or saline was administered by intraperitoneal route immediately after 20 min ischemia and again at 1, 4, 24 and 30 h during reperfusion. Twenty-min severe forebrain ischemia was associated with a marked decrease in phosphocreatine (PCr) and ATP levels and a corresponding increase in lactic acid, inorganic phosphate (Pi), AMP, creatine, glycerol 3-phosphate and alanine levels. Following reperfusion, a general tendency to restore pre-ischemic metabolite levels was observed. However, after 2 h reperfusion in saline-treated rats, lactic acid and Pi levels remained significantly higher, while ATP levels were still significantly lower than in non-ischemic controls. On the contrary, in ALCAR-treated animals a complete recovery of all metabolites including Pi and ATP was observed, while PCr levels were even more elevated compared with those in saline-treated rats. Furthermore lactic acid content was significantly lower than that in both saline-treated and non-ischemic control rats. It is concluded that a potential therapeutic role may be claimed for ALCAR in the treatment of cerebral ischemia through mechanisms that include faster recovery and improvement of brain energy production as well as a decreased lactic acid content during early post-ischemic reperfusion.
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PMID:Effect of acetyl-L-carnitine on recovery of brain phosphorus metabolites and lactic acid level during reperfusion after cerebral ischemia in the rat--study by 13P- and 1H-NMR spectroscopy. 803 36

The new non-NMDA (N-methyl-D-aspartate) receptor antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) has previously been shown to exert a neuroprotective effect in animal models of cerebral ischemia when administered in the post-ischemic phase. In this investigation the effect of NBQX on acidosis and energy recovery in early reperfusion after 10 min of transient forebrain ischemia with the 2-vessel occlusion model in the rat was studied with 31P NMR spectroscopy. In the intervention group the animals received a bolus dose of NBQX 30 mg.kg-1 i.v. at the start of reperfusion. 31P NMR spectroscopy was used to measure intracellular pH, ATP and phosphocreatine continuously in-vivo during, and after, the ischemic event. The recovery of high energy phosphates and pH was followed during 30 min of reperfusion. Pre-ischemic levels of phosphocreatine were reached after approximately 9-10 min in both groups. Although a slight improvement could be seen in the intervention group there was no significant difference in the rate of recovery between the two groups. ATP reached 90% of preischemic levels after about 8 min without significant difference between the two groups. With respect to the recovery of intracellular pH, no difference could be shown. Our results do not contradict previously published results, but suggest that the potential protective effect of NBQX is not mediated through improved recovery of energy metabolism in early reperfusion.
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PMID:NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) did not affect recovery of high energy phosphates and pH in early reperfusion in a rat model of transient forebrain ischemia. Or: an in vivo 31P NMR spectroscopy study. 817 53

Intracellular high energy phosphates (HEP) were monitored in rat hippocampal slices in vitro by 31P-NMR during continuous superfusion, no flow and reperfusion in order to model the changes which occur during cerebral ischemia and reperfusion in vivo. With continuous superfusion, stable intracellular HEP resonance signals were observed for over 4 h. When superfusion was stopped, there were rapid decreases in pH and phosphocreatine levels followed by slower loss of ATP. These changes are similar to those observed during cerebral ischemia in vivo by 31P-NMR. Upon reperfusion, the pH returned to normal, but the extent of HEP recovery depended on the length of time superfusion was halted. Following a 10 min ischemic period HEP levels returned to greater than 90% of preischemic values, while following a 16 min ischemic period there was only 60% recovery. Superfusion with low calcium, high magnesium medium significantly improved the recovery of HEP following 16 min of ischemia to 80% of preischemic levels. These data support the hypothesis that calcium influx during and following ischemia can disrupt energy metabolism in the hippocampus, and that magnesium can have a protective action on cellular energy status, perhaps by further blocking calcium influx.
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PMID:31P-NMR study of transient ischemia in rat hippocampal slices in vitro. 825 25

We used 31P magnetic resonance spectroscopy (MRS) to investigate changes in brain intracellular [Mg2+] following human focal cerebral ischemia. Mean brain pMg (where pMg = -log[Mg2+]) was significantly lower in the ischemic focus of all stroke patients (pMg = 3.34 +/- 0.28, n = 45, p < 0.01) when compared with normal controls (pMg = 3.50 +/- 0.08, n = 25). Ischemic brain pMg was also significantly reduced when the pH of the stroke region was acidotic (pH < 6.90, pMg = 3.07 +/- 0.44, n = 11, p < 0.01) and when the phosphocreatine index (PCrI = PCr/[PCr+Pi (inorganic phosphate)]) was reduced (PCrI < 0.47, pMg = 3.12 +/- 0.42, n = 13, p < 0.01). Mean brain pMg was significantly reduced at days 0 to 1 (acute) poststroke (pMg = 3.32 +/- 0.28, n = 26, p < 0.01) and at days 2 to 3 (subacute) poststroke (pMg = 3.38 +/- 0.28, n = 21, p = 0.03). There was also a significant (p < 0.01) correlation between decreased pMg and increased relative signal intensity of Pi (normalized by total phosphate signal, Pi/TP) for all stroke groups studied. During the temporal evolution of stroke, pH returned to normal levels by days 2 to 3, and pMg returned to normal by days 4 to 10 (subacute). PCrI and Pi/TP returned toward normal levels after 10 days (chronic), at a time when ischemic brain pH had become significantly alkalotic (pH = 7.10 +/- 0.24, n = 15, p < 0.01). Elevation of ischemic brain [Mg2+] is temporally linked to the acidotic phase of human stroke as well as the breakdown of energy metabolism. These acute changes in [Mg2+] may contribute to, or be a marker for, cellular injury.
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PMID:Acute elevation and recovery of intracellular [Mg2+] following human focal cerebral ischemia. 835 Oct 15

The effect of benidipine on experimental cerebral ischemia was investigated in rats subjected to occlusion of the bilateral common carotid arteries. Benidipine (30 micrograms/kg, i.p.) improved neurological symptoms such as ataxia, convulsion and loss of righting reflex, and prolonged survival time after occlusion of the bilateral common carotid arteries. In the nicardipine (100 micrograms/kg, i.p.)-treated group, a similar effect was observed, whereas nifedipine (100, 300 micrograms/kg, i.p.) and verapamil (300 micrograms/kg, i.p.) did not show any beneficial effect in this model. Furthermore, pretreatment with benidipine (30 micrograms/kg, i.p.) suppressed the increase in cerebral water content 3 h after the occlusion. Nicardipine (100 micrograms/kg, i.p.) showed a tendency to reduce the increase in cerebral water content, though the effect was not statistically significant. Nifedipine (100 micrograms/kg, i.p.) produced no improvement. After occlusion of the bilateral common carotid arteries, depletion of adenosine triphosphate (ATP) and phosphocreatine (CP) and an accumulation of lactate occurred in a time-dependent manner. Prophylactic administration of benidipine (30 micrograms/kg, i.p.), 20 min before occlusion, attenuated the depletion of ATP and CP and the accumulation of lactate 3h after the occlusion. Furthermore, post-treatment with benidipine 30 min after occlusion also suppressed these metabolic disorders. In conclusion, the beneficial effects of benidipine in this severe cerebral ischemia model show that the compound has advantages over nicardipine, nifedipine and verapamil. Thus, these results suggest that benidipine may be useful in the treatment of acute ischemic cerebral damage.
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PMID:Effect of benidipine hydrochloride (KW-3049), on cerebral ischemia induced by bilateral occlusion of the common carotid arteries in rats. 836 94

Previous studies have shown that global cerebral ischemia induced by decapitation leads to the stimulated hydrolysis of poly-phosphoinositides. In this study, the decapitation model was used to further examine the temporal events related to metabolism of Ins(1,4,5)P3 and the release of diacylglycerols (DGs) and free fatty acids (FFAs) in the mouse brain. Since lithium administration is known to inhibit inositol monophosphatase activity in brain, the effects of acute lithium injection on Ins(1,4,5)P3 metabolism were also examined. Cerebral ischemia induced by decapitation of C57 Bl/6J mice resulted in transient increases of Ins(1,4,5)P3, Ins(1,4)P2 and Ins(4)P which peaked at 35, 65 and 125 s, respectively. The level of Ins(1)P, however, was not altered. Mice administered lithium by intraperitoneal injection (8 meq/kg for 4 h) gave rise to a 40- and 4-fold increase in levels of Ins(1)P, Ins(4)P, respectively, a 20% increase in levels of Ins(1,4)P2 but no apparent changes in the levels of Ins(1,4,5)P3. Decapitation also induced an increase in the levels of DGs and FFAs. Unlike the transient appearance of Ins(1,4,5)P3, however, DG levels increased steadily for 2 min and then reached a plateau whereas the FFAs showed a lag time of 35 s prior to a biphasic increase. During the initial 2 min after decapitation, there was a preferential increase in the DG species containing 18:0 and 20:4. Lithium administration did not alter the decapitation-induced release of DG and FFA. As expected, decapitation gave rise to a rapid decrease in the levels of phosphocreatine and ATP and the decline in ATP was marked by a transient appearance of ADP and a concomitant increase in AMP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolism of inositol 1,4,5-trisphosphate in mouse brain due to decapitation ischemic insult: effects of acute lithium administration and temporal relationship to diacylglycerols, free fatty acids and energy metabolites. 849 Jul 17

Ischemia-induced changes in 31P NMR relaxation were examined in 16 piglets. NMR spectra were acquired under control conditions and during complete cerebral ischemia induced via cardiac arrest. Changes in T1 were assessed directly in six animals during control conditions and after 30-45 min of complete ischemia when changes in brain Pi levels had reached a plateau. The T1 for Pi did not change, i.e., 2.3 +/- 0.5 s during control conditions versus 2.4 +/- 1.0 s during ischemia. To evaluate phosphocreatine and ATP, two types of spectra, with a long (25-s) or short (1-s) interpulse delay time, were collected during the first 10 min of ischemia (n = 10). Both types of spectra showed the same time course of changes in phosphocreatine and ATP levels, implying that the T1 relaxation times do not change during ischemia. There were no changes in the linewidths of phosphocreatine, ATP, or Pi during ischemia, implying that the T2* values remain constant. Our results suggest that the 31P T1 and T2* for phosphocreatine, Pi, and ATP do not change during ischemia, and therefore changes in 31P NMR peak intensity accurately reflect changes in metabolite concentrations.
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PMID:31P NMR relaxation does not affect the quantitation of changes in phosphocreatine, inorganic phosphate, and ATP measured in vivo during complete ischemia in swine brain. 851 60

Cerebral ischaemia causes activation of ornithine decarboxylase followed by accumulation of putrescine, and these biochemical phenomena have been thought to contribute to the development of neuronal damage. We have used a transgenic mouse line overexpressing the human ornithine decarboxylase gene in their neurons with constitutively high putrescine to study the possible role of putrescine in development of neuronal damage in forebrain ischaemia. An incomplete forebrain ischaemia model was developed in which common carotid arteries were bilaterally occluded and reduction of blood pressure caused by orthostatic reaction was used as a way of decreasing cerebral circulation. Cerebral high-energy metabolites, intracellular pH and lactate were monitored by means of 31P and 1H nuclear magnetic resonance spectroscopy respectively. Incomplete ischaemia for 15 min resulted in severe energy failure, as indicated by an increase in the inorganic phosphate/phosphocreatine ratio, intracellular acidification from a pH of approximately 7.1 to approximately 6.5 and an increase in lactate concentration from < 1 to approximately 10 mmol/kg in both syngenic and transgenic mice. Following deocclusion, recovery of energy metabolites intracellular pH and lactate were identical in both animal groups. Ornithine decarboxylase activity rose 9- and 3-fold in syngenic and transgenic mice respectively 6 h after ischaemia, which was approximately 50-fold greater than the basal level in syngenic mice. In situ hybridization experiments revealed induction of transcription factors c-Fos and zif-268 in the hippocampus, throughout the cerebral cortex and striatum 1-3 h after ischaemia. Messenger RNA of heat shock protein 70 was induced in dentate gyrus and CA3 and CA4 subfields of the hippocampus 1 h after ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebral energy metabolism and immediate early gene induction following severe incomplete ischaemia in transgenic mice overexpressing the human ornithine decarboxylase gene: evidence that putrescine is not neurotoxic in vivo. 852 57


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