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

The relationship between increase in water content in ischemic brain and levels of regional blood flow has been studied in 11 primates. Flows were recorded using the method of hydrogen (2-minute) clearance, from a total of 128 electrodes in cortex and white matter, and a gradation of ischemia was produced by middle cerebral occlusion transorbitally. The flows were reduced in the area of densest ischemia from control levels of 12.0 +/- 12.0 ml/100g/min to 7.0 +/- 5.4 ml/100g/min, with lesser decreases over the remainder of the ischemic hemisphere. Water content was measured in cortex and white matter, in regions topographically related to those of flow measurements, by densitometric assessment using precalibrated kerosene/bromobenzine columns. The average water content of cortex in regions remote from ischemia was 797.4 +/- 5.8 mg/gm and in white matter 708.5 +/- 8.2 mg/gm. Significant increases in water content (comparing corresponding regions of the two hemispheres) of up to 11.4 +/- 7.5 mg/gm were demonstrated in the most ischemic cortical areas. A gradient of water increase was evident in the ischemic hemisphere, increases water content being greatest in the opercular zone and least in the parasagittal area. Significant differences in white matter water content between the 2 hemispheres were demonstrated only in the most densely ischemic areas in the current experiments where ischemia was limited to 93 +/- 20 mins in the 11 animals without reperfusion. The relationship between ischemic density and water content increase showed that significant increases in water content occurred in regions where terminal flows had been below 20 ml/100g/min, indicating that accumulation of water in ischemic brain begins at flow values comparable to those associated with the failure of synaptic transmission, higher than those associated with failure of the ionic pump of the cell. Possible pathophysiological mechanisms are discussed.
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PMID:Ischemic brain edema following middle cerebral artery occlusion in baboons: relationship between regional cerebral water content and blood flow at 1 to 2 hours. 10 19

The autoregulatory capacity of areas of the cerebral circulation subjected to ischemia by acute middle cerebral occlusion has been assessed in experimental primates. Autoregulation was tested to a rise in blood pressure induced by aramine, and to a fall in blood pressure induced by exsanguination. Whole hemisphere autoregulation was substantially disturbed due to both increased blood pressure and lowered blood pressure, but fractionation of this response indicated that autoregulation to increased blood pressure was preserved in the parasagittal and intermediate zones of the hemisphere, and totally lost in the region of the sylvian opercula where middle cerebral occlusion had produced the most dense ischemia. In relation to reduced perfusion pressure, autoregulation was again widely impaired and assessment of the degree of impairment by areas indicated no significant difference between the areas of the sylvian opercula and the remainder of the lateral aspect of the hemisphere studied. Where the degree of ischemia in each individual electrode was assessed, however, it appeared that the degree of auto-regulatory loss to decreased perfusion pressure was dependent upon the intensity of ischemia, and autoregulation was partially preserved in electrodes whose immediate post-occulsion flow values were greater than 40% of basal flow. Retransfusion following exsanguination in animals with acute middle cerebral occlusion indicated that there was a linear relationship between the degreee of reperfusion achieved by retransfusion and the intensity of ischemia induced by exsanguination following middle cerebral occlusion. Thus there was some support for the no-reflow phenomenon in intensely ischemic areas.
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PMID:Autoregulation in acute focal ischemia. An experimental study. 82 33

Pharmacological inhibition of cell excitation during focal ischemia was studied in the rat middle cerebral artery occlusion model. The potent and selective N-methyl-D-aspartate antagonist CGS 19755, administered 5 minutes prior to or 5 minutes following permanent middle cerebral artery occlusion, caused a substantial decrease in infarct size, which was associated with reduction of postischemic cerebral glucose hypermetabolism. These data support a role for excitation-induced hypermetabolism in the pathogenesis of infarction following focal cerebrovascular occlusion.
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PMID:N-methyl-D-aspartate antagonist reduces stroke size and regional glucose metabolism. 216 36

Focal cerebral ischemia in the rat was induced by occlusion of the left middle cerebral artery. The temporal evolution of regional energy metabolism was studied over the 14 days consequent to the induction of ischemia in the frontal, cingulate, parietal, and occipital cortices as well as in the striatum. Regional concentrations of adenosine triphosphate (ATP), phosphocreatine, and lactate and, in addition, glucose and the cerebral/plasma glucose ratio (C/P) were measured in the hemispheres both ipsilateral and contralateral to the occlusion. Two hours after middle cerebral artery occlusion, the biochemical changes were severe in the striatum and moderate in cortical regions. Later on (at 24 and 48 h), an overall aggravated metabolic status was noted while lactate declined and glucose markedly increased. These latter biochemical changes likely indicate a marked inhibition of the rate of glucose utilization. At 48 h, the energy reserves (ATP, phosphocreatine) of parietal cortex no longer equaled those of other cortical regions, but abruptly fell to the levels found in the striatum without any increase in lactate level. Finally, at 7 and 14 days, the levels of the various metabolites in most cortical regions returned toward control values, although signs of a depressed glucose metabolism remained. However, in both striatum and parietal cortex, ATP and phosphocreatine concentrations, although higher than those observed at 48 h, remained significantly decreased. Our present biochemical study permits the classification of these selected brain regions into three categories. First there are those that are outside the area of infarction: the frontal, cingulate, and occipital cortices. These regions show little temporal evolution of brain energy metabolism but, notwithstanding, they are regions in which glucose use would appear to be greatly depressed. Second is a region considered to be the focus of infarction: the striatum. The caudate-putamen is a region with early and profound metabolic disturbances with no final restitution. Last is the region of metabolic penumbra--the parietal cortex, in which there is a time-related exacerbation of the consequences of middle cerebral occlusion in the rat.
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PMID:Temporal evolution of regional energy metabolism following focal cerebral ischemia in the rat. 339 11

A reduction in the apparent diffusion coefficient (ADC) of water measured by magnetic resonance imaging (MRI) has been shown to occur early after cerebrovascular occlusion. This change may be a useful indicator of brain tissue adversely affected by inadequate blood supply. The objective of this study was to test the hypothesis that loss of membrane ion homeostasis and depolarization can occur simultaneously with the drop in ADC. Also investigated was whether elevation of extracellular glutamate ([GLU]e) would occur before ADC changes. High-speed MRI of the trace of the diffusion tensor (15-second time resolution) was combined with simultaneous recording of the extracellular direct current (DC) potential and on-line [GLU]e from the striatum of the anesthetized rat. After a control period, data were acquired during remote middle cerebral artery occlusion for 60 minutes, followed by 30 minutes of reperfusion, and cardiac arrest-induced global ischemia. After either focal or global ischemia, the ADC was reduced by 10 to 25% before anoxic depolarization occurred. After either insult, the time for half the maximum change in ADC was significantly shorter than the corresponding DC potential parameter (P < 0.05). The [GLU]e remained at low levels during the entire period of varying ADC and DC potential and did not peak until much later after either ischemic insult. This study demonstrates that ADC changes can occur before membrane depolarization and that high [GLU]e has no involvement in the early rapid ADC decrease.
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PMID:The relationship between the apparent diffusion coefficient measured by magnetic resonance imaging, anoxic depolarization, and glutamate efflux during experimental cerebral ischemia. 1061 90

We examined the expression of IL-6 within the ischemic penumbra at various time points after transient (3 h) middle cerebral occlusion (MCA-O) in rats. The animals were killed at 1, 3, 7 or 14 days following operation. Coronal brain sections were processed for immunohistochemistry with antibodies against GFAP, OX 42, IL-6 and Nissl-staining. Glial activation within the penumbra started on day one after ischemia and persisted up to day 14. Expression of IL-6 was not present in sham-operated controls. One day after MCA-O there were several IL-6-positive cells in the penumbra. This expression of IL-6 increased on day 3 and remained elevated up to day 14. According to the shape of the IL-6-positive cells they seem to be microglia and neurons. The present results demonstrate a longlasting expression of IL-6 in the ischemic penumbra.
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PMID:Expression of IL-6 in the ischemic penumbra. 1079 Aug 64

A rat four-vessel cerebral occlusion model was used to examine the effects of D-lactate and oxamate, a lactate dehydrogenase inhibitor, on cortical window superfusate levels of amino acids, glucose and L-lactate. Superfusate levels of aspartate, glutamate, taurine, GABA and phosphoethanolamine rose during ischemia and then declined during reperfusion. Glycine and alanine levels tended to increase during reperfusion, whereas glutamine levels were lower. Serine levels were not altered. Glucose levels declined rapidly during ischemia and recovered during reperfusion. Lactate levels were sustained during ischemia and increased during reperfusion. Unlike L-lactate, which attenuated ischemia/reperfusion (I/R) evoked amino acid release (J.W. Phillis, D. Song, L.L. Guyot, M.H. O'Regan, Lactate reduces amino acid release and fuels recovery of function in the ischemic brain, Neurosci. Lett. 272 (1999) 195-198), topical application of D-lactate (20 mM), which is not used as an energy substrate, enhanced the I/R release of aspartate, glutamate, GABA and taurine into cortical superfusates, and also elevated L-lactate levels above those in the controls. Glucose levels were not altered. Oxamate (20 mM) application elevated the pre-ischemia levels of alanine, glycine and GABA and those of GABA during ischemia. Levels of all amino acids, with the exception of phosphoethanolamine, were elevated during reperfusion. Oxamate, an inhibitor of lactate dehydrogenases 1 and 5, did not alter the pattern of efflux of glucose and L-lactate. In the presence of oxamate, L-lactate (20 mM) failed to inhibit amino acid release. The failure of D-lactate to attenuate amino acid release confirms the inability of this isomer to act as a metabolic substrate. The oxamate data indicate that inhibition of lactate dehydrogenase is detrimental to the viability of cortical cells during I/R, even though extracellular lactate levels are elevated. The pre-ischemia increases in alanine and glycine are suggestive of elevations in pyruvate as a result of the block of its conversion to lactate, with transamination reactions converting pyruvate to form these amino acids. In summary, the results further substantiate the concept of a role for L-lactate as a cerebral energy substrate.
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PMID:Further studies on the effects of topical lactate on amino acid efflux from the ischemic rat cortex. 1136 47

Heparin-induced thrombocytopenia HIT is a potentially devastating complication of heparin therapy. The severe form of HIT has been associated with both venous and arterial thrombosis manifested by myocardial infarction, cerebrovascular occlusion, skin necrosis or limb ischemia. Several agents are now available as alternatives to heparin in patients with suspected HIT, including the thrombin specific inhibitors lepirudin and argatroban as well as the low molecular weight heparinoid known as danaparoid. When lacking these agents, here we report the use of plasmapheresis to create an artificial state of anticoagulation; exchanging patient's plasma with albumin rather than fresh frozen plasma, to allow the safe introduction of warfarin.
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PMID:Treating heparin-induced thrombocytopenia. The unconventional way! 1544 79

Animal models of cerebral infarction are crucial to understanding the mechanisms of neuronal survival following ischemic brain injury and to the development of therapeutic interventions for victims of all types of stroke. Rodents have been used extensively in such research. One rodent model of stroke utilizes either permanent or temporary occlusion of the middle cerebral artery (MCAO) to produce ischemia. Since the development of an endovascular method for this was published in 1989, MCAO has been applied commonly to the rat, and often paired with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining for stroke volume measurement. Meanwhile, advances in the ability to genetically alter mice have allowed exciting lines of research into ischemia. Because of technical demands and issues with survival, relatively few laboratories have investigated the MCAO method in the mouse. Our present work utilizes a mouse middle cerebral occlusion (MCAO) model of embolic stroke to study neuronal degeneration following temporary focal cerebral ischemia. C57Bl/6J mice were used to examine the exact effects of MCAO using Fluoro-Jade, a marker of neurodegeneration that allows observation of specific brain regions and cells destined to die. A time course of escalating neuronal degeneration from 10 min to 7 days following MCAO was established. Technical aspects of this popular method for transient focal ischemia as it applies to the mouse are discussed.
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PMID:Temporary focal ischemia in the mouse: technical aspects and patterns of Fluoro-Jade evident neurodegeneration. 1582 50

Heme oxygenase-2 (HO-2) has been suggested to be a cytoprotective enzyme in a variety of in vivo experimental models. HO-2, the constitutive isozyme, is enriched in neurons and, under normal conditions, accounts for nearly all of brain HO activity. HO-2 deletion (HO-2-/-) leads to increased neurotoxicity in cultured brain cells and increased damage following transient cerebral ischemia in mice. Moreover, pharmacologic inhibition of HO activity significantly augments focal ischemic damage in wildtype (WT) mice, but does not further exacerbate it in HO-2-/- mice. The HO system shares some similarities with nitric oxide synthase (NOS), notably their syntheses of carbon monoxide (CO) and nitric oxide (NO), respectively, which are diffusible gases with numerous biological actions, including neurotransmission and vasodilation. While deletion of HO-2 results in greater stroke damage, the pharmacologic inhibition of neuronal nitric oxide synthase (nNOS), or its gene deletion, confers neuroprotection in animal models of transient cerebral ischemia. To investigate the interactions, the outcome of focal cerebral ischemia-reperfusion in double knockout (HO-2-/- X nNOS-/-) mice lacking both genes was compared to control WT mice. Wildtype and double knockout male mice underwent intraluminal middle cerebral occlusion for 2 hours, followed by reperfusion for 22 hours. Outcomes in neurologic deficits and infarct size were determined. No difference was observed between WT and double knockout mice in the volume of infarction, neurologic signs, decrease in relative cerebral blood flow during ischemia, or core body temperature. The results suggest that the deleterious action of nNOS would counteract the role of HO-2 in neuroprotection.
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PMID:Stroke outcomes in mice lacking the genes for neuronal heme oxygenase-2 and nitric oxide synthase. 1618 Oct 97


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