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

Hypothermia was first applied therapeutically as a local anesthetic and later was used to achieve organ protection during procedures necessitating circulatory interruption. Profound whole-body hypothermia, typically carried out in conjunction with extracorporeal bypass, has long been employed during cardiac and neurosurgical operative procedures. More recently, studies in small-animal experimental models of cerebral ischemia have provided persuasive evidence that even small decreases in brain temperature confer striking protection against ischemic neuronal injury. By contrast, small elevations of brain temperature during ischemia accelerate and extend pathologic changes in the brain and promote early disruption of the blood-brain barrier. Hypothermia retards the rate of high-energy phosphate depletion during ischemia and promotes postischemic metabolic recovery. More importantly, mild intraischemic hypothermia markedly attenuates the release of glutamate into the brain's extracellular space and significantly diminishes the release of dopamine. Similarly, the inhibition of calcium-calmodulin-dependent protein kinase II triggered by normothermic ischemia is prevented by hypothermia, as is the ischemia-induced translocation and inhibition of the key regulatory enzyme protein kinase C. Hypothermia also appears to facilitate the resynthesis of ubiquitin following ischemia. Studies of potential clinical importance have shown that moderate hypothermia is capable of attenuating ischemic damage even if instituted early in the postischemic period. In the setting of focal cerebral ischemia, moderate brain hypothermia reduces the infarct size (particularly in the setting of reversible middle cerebral artery occlusion); conversely, hyperthermia markedly increases the infarct volume. These studies underscore the importance of monitoring and regulating the brain temperature during experimental studies of cerebral ischemia to insure a consistent pathologic outcome and to avoid the false attribution of "pharmacoprotection" to drugs that reduce the body temperature. The measurement of brain temperature is now practicable in neurosurgical patients requiring invasive monitoring, and human studies have shown that cortical and cerebroventricular temperatures may exceed systemic temperatures. Mild to moderate decreases in brain temperature are neuroprotective in cerebral ischemia, while mild elevations of brain temperature are markedly deleterious in the setting of ischemia or injury. It is anticipated that controlled clinical trials of therapeutic brain temperature modulation will be undertaken over the next several years.
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PMID:Therapeutic modulation of brain temperature: relevance to ischemic brain injury. 138 56

The effect of adrenalectomy has been investigated in a model of global cerebral ischemia. After bilateral carotid ligation the mortality rate was increased in adrenalectomized rats, and this effect was prevented by glucocorticoid pre-treatment. Adrenalectomy accelerated the appearance of the symptoms of cerebral ischemia, resulting in a moderate aggravation of brain edema and in a significant decrease in the concentration of high-energy phosphate esters. Our findings support the view that endogenous glucocorticoids may play a role in the amelioration of ischemic brain injuries in rats.
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PMID:Adrenalectomy aggravates ischemic brain edema in female Sprague-Dawley rats with carotid arteries ligated. 141 Apr 8

Tissue levels of inorganic phosphate (iP-) and lactate (lac) increase during cerebral ischemia and cortical spreading depression (SD). Since cell membranes become leaky during these insults, iP- and lac were expected to leak into the extracellular space (ECS). In order to find out whether this occurs or does not, a microdialysis (MD) fiber was implanted into the cortex of anesthetized rats and extracellular lactate (lac(e)) and extracellular iP- (iPe-) were determined during various insults. Extracellular lactate increased to about the same extent during ischemia and SD. In contrast, iPe- increased during ischemia but not during SD. Instead, iPe- started to rise after SD and reached its maximum about 45 min later. The distinct pattern of iPe- in comparison to lac(e) during the above mentioned insults points to a qualitative difference of the underlying mechanisms: whereas lac appears within the ECS at any stressful situation, elevation of iP- within the ECS indicates depletion of energy stores in parallel to the lack of control of ion homeostasis.
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PMID:Extracellular changes of inorganic phosphate are different during spreading depression and global cerebral ischemia of rats. 143 48

Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess cerebral high-energy phosphate metabolism and intracellular pH in normoglycemic and hyperglycemic sheep during hypothermic circulatory arrest. Two groups of sheep (n = 8 per group) were placed in a 4.7-T magnet and cooled to 15 degrees C using cardiopulmonary bypass. Spectra were acquired before and during circulatory arrest and during reperfusion and rewarming. Intracellular pH and adenosine triphosphate levels decreased during circulatory arrest. Compared with the normoglycemic animals, the hyperglycemic group was significantly more acidotic with the greatest difference observed during the first 20 minutes of reperfusion (6.40 +/- 0.08 versus 6.08 +/- 0.06; p < 0.001). Intracellular pH returned to baseline after 30 minutes of reperfusion in the normoglycemic group but did not reach baseline until 1 hour of reperfusion in the hyperglycemic animals. Adenosine triphosphate levels were significantly higher in the hyperglycemic group during circulatory arrest. Repletion of adenosine triphosphate during reperfusion was similar for both groups. These results support the hypothesis that hyperglycemia during cerebral ischemia drives anaerobic glycolysis and thus leads to increased lactate production and an increase [corrected] in the intracellular acidosis normally associated with ischemia.
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PMID:Hyperglycemia increases cerebral intracellular acidosis during circulatory arrest. 144 97

31P NMR spectroscopy was used to assess the cerebral ischemia status in rats by measuring the relative levels of phosphate metabolites. Partial cerebral ischemia was induced in 49 rats by reversible occlusion of the carotid arteries. Rats were intubated and mechanically ventilated on a hypoxic gas mixture. Physiological parameters such as temperature and arterial pressure were strictly controlled during the experiments. 31P spectra were acquired at 7 T during basal observation, for 15-20 min after the induction of ischemia, and for 1 hr after reperfusion. Depletion and increase in PCr and Pi levels, respectively, were already observable in the collected spectra within few minutes after the onset of ischemia. No appreciable changes were found in the ATP levels.
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PMID:Partial cerebral ischemia assessed by "in vivo" 31P NMR spectroscopy in rats. 146 Oct 71

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

The present study was undertaken to elucidate the possible therapeutic effects of naftidrofuryl on energy metabolism of brain regions impaired for extended periods by microsphere embolism. Nine hundred microspheres (48 microns in diameter) were injected into the right internal carotid artery of rats, and changes in their behavior and energy metabolism of the cortex, striatum and hippocampus of both hemispheres were determined with and without naftidrofuryl treatment. Microsphere embolism induced increases in lactate, glucose and glycogen contents and decreases in ATP and creatine phosphate of these brain regions of the right hemisphere for up to 28 days after the operation, suggesting long-lasting cerebral ischemia or sustained damage to energy metabolism. These changes were gradually reversed with time after the operation. Microsphere-injected rats were treated twice a day with 15 mg/kg naftidrofuryl, and their behavioral and metabolic protection were determined on the 3rd, 5th and 28th days after the operation. Treatment of embolized animals with naftidrofuryl improved these variables appreciably on the 3rd and 28th days, but little on the 5th day. The improvement on the 3rd day was more evident in all brain regions monitored than that on the 28th day. The results suggest that naftidrofuryl exerts beneficial effects on the energy metabolism of brains damaged by microsphere embolism, the mechanism of which may be due to protection against the development of embolism-induced derangement.
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PMID:Beneficial effects of naftidrofuryl oxalate on brain regional energy metabolism after microsphere-induced cerebral embolism. 154 78

Two different techniques were utilized to identify the infiltration of polymorphonuclear leukocytes (PMN) into cerebral tissue following focal ischemia: histologic analysis and a modified myeloperoxidase (MPO) activity assay. Twenty-four hours after producing permanent cortical ischemia by occluding and severing the middle cerebral artery of male spontaneously hypertensive rats, contralateral hemiparalysis and sensory-motor deficits were observed due to cerebral infarction of the frontal and parietal cortex. In hematoxylin-and-eosin-stained histologic sections, PMN, predominantly neutrophils, were identified at various stages of diapedesis from deep cerebral and meningeal vessels at the periphery of the infarct, into brain parenchyma. When MPO activity in normal brain tissue was studied initially, it could not be demonstrated in normal tissues extracted from non-washed homogenates. However, if tissue was homogenized in phosphate buffer (i.e., washed), MPO activity was expressed upon extraction. Utilizing this modified assay, MPO activity was significantly increased only in the infarcted cortex compared to other normal areas of the brain. This was observed in non-perfused animals and after perfusion with isotonic saline to remove blood constituents from the vasculature prior to brain removal. The increased PMN infiltration and MPO activity were not observed in forebrain tissue of sham-operated control rats. Also, MPO activity was not increased in the ischemic cortex of MCAO rats perfused immediately after middle cerebral artery occlusion, indicating that blood was not trapped in the ischemic area. By using a leukocyte histochemical staining assay, activity of peroxidases was identified within vascular-adhering/infiltrating PMN in the infarcted cortex 24 hr after focal ischemia. An evaluation of several blood components indicated that increased MPO activity was selective for PMN. The observed increase of approximately 0.3 U MPO/g wet weight ischemic tissue vs. nonischemic cerebral tissues probably reflects the increased vascular adherance/infiltration of approximately 600,000 PMN/g wet weight infarcted cortex 24 hr after focal ischemia. This combined biochemical and histological study strongly suggests that PMN adhere within blood vessels and infiltrate into brain tissue injured by focal ischemia and that the associated inflammatory response might contribute to delayed progressive tissue damage in focal stroke. This modified MPO assay is a useful, quantitative index of PMN that can be utilized to elucidate the potential deleterious consequences of neutrophils infiltrating into the central nervous system after cerebral ischemia, trauma, or other pro-inflammatory stimuli.
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PMID:Polymorphonuclear leukocyte infiltration into cerebral focal ischemic tissue: myeloperoxidase activity assay and histologic verification. 165 59

Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting 32Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when 32Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury.
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PMID:Brain polyphosphoinositide metabolism during focal ischemia in rat cortex. 185 Aug 77

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


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