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

Intracellular brain pH and indicator tissue perfusion were measured with a lipid-soluble, pH-sensitive fluorescent indicator in 10 rabbits who had either severe or moderate focal ischemia depending on whether the middle cerebral artery was occluded at its main trunk or bifurcation. Preocclusion tissue indicator perfusion was 50.1 ml/100 g/min and intracellular brain pH was 7.03. In severe focal ischemia, immediate postocclusion tissue perfusion was 12.7 ml/100 g/min and intracellular brain pH was 6.64. Four hours after occlusion, the perfusion was 5.2 ml/100 g/min and intracellular brain pH was 6.08. There was EEG and histological confirmation of infarction. In the moderate focal ischemia group, immediate postocclusion flow was 20.0 ml/100 g/min and intracellular brain pH was 6.92. At 3 h, postocclusion tissue perfusion was 22.6 ml/100 g/min and intracellular brain pH was 6.86. Therefore, for the first 3 h, this ischemic penumbra was stable. At the fourth hour, both cerebral tissue perfusion and intracellular brain pH worsened. This suggests that the ischemic penumbra is a dynamic state. The rabbit is a good experimental model for the production of both severe and moderate focal ischemia.
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PMID:Intracellular brain pH, indicator tissue perfusion, electroencephalography, and histology in severe and moderate focal cortical ischemia in the rabbit. 394 18

The effect of indomethacin on rCBF was studied in cats anesthetized with Nembutal either under resting conditions or with temporary middle cerebral artery (MCA) occlusion. RCBF was measured by the microsphere method. In control animals (n = 3), indomethacin (4 mg/kg, i.v.) significantly reduced rCBF by about 25% in both cortex (from 44 +/- 6 to 32 +/- 3 ml/100 g/min, p less than 0.001) and white matter (from 36 +/- 4 to 26 +/- 2 ml/100 g/min, p less than 0.001). After MCA occlusion rCBF was markedly decreased in the sylvian region ipsilateral to occlusion (ischemic core) (from 38 +/- 4 to 14 +/- 2 ml/100 g/min in cortex, 4 animals). Although pretreatment with indomethacin (4 mg/kg) (4 animals) 30 min prior to occlusion did not alter rCBF during ischemia, a marked enhancement of reactive hyperemia was observed in the ischemic core immediately upon reperfusion following 2 h occlusion (54 +/- 11 untreated vs 95 +/- 13 treated, p less than 0.05). In the delayed postischemic period, namely 2 h after recirculation, rCBF still remained to be higher in the animals treated with indomethacin (40 +/- 6 untreated vs 96 +/- 9 treated, p less than 0.001). Such an effect of indomethacin for ameliorating postischemic blood flow in both the immediate and delayed period was less prominent in the adjacent area (penumbra) ipsilateral to occlusion. In the contralateral hemisphere, indomethacin caused slight reduction in rCBF during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of indomethacin on rCBF during and after focal cerebral ischemia in the cat. 397 61

Interastrocytic gap junctions in the blood-brain barrier of the experimental penumbra area were studied in the cat caudate nucleus 1 h after ischemia. Transmission electron microscopy and freeze-fracture studies revealed only slight changes in gap junctions between astrocytes, indicating that these junctions are very resistant to hypoxia.
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PMID:Aspects of interastrocytic gap junctions in blood-brain barrier in the experimental penumbra area, revealed by transmission electron microscopy and freeze-fracture. 672 10

A photochemical method using the Rose Bengal dye as thrombogenic agent was employed to induce focal cerebral ischemia in frontoparietal cortex of rats. A transcerebral microdialysis probe was used to collect samples from ischemic cortical area. An increase in glutamate (6-fold) and in taurine (4-fold) within the first hour occurred. Neuropathological investigations demonstrate a reproducible damaged area surrounded by a thin peripheral area showing neuronal apoptotic phenomena. The method represents a reproducible model of focal cerebral ischemia with neuropathological aspects superimposable to those characteristic of thrombogenic stroke in man. This method could also be relevant in the study of neurotransmitters during the evolution of ischemia. Furthermore, the presence of apoptotic phenomena in the perilesional halo confirms an ischemic penumbra suggesting the significance of preclinical pharmacological trials.
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PMID:Aminoacid recovery via microdialysis and photoinduced focal cerebral ischemia in brain cortex of rats. 756 38

The pathophysiology of ischaemia depends on the residual cerebral blood flow. As a result, it is different in global ischaemia, when compared with focal ischaemia, where the centre area is surrounded with an area called an ischaemic penumbra. Ischaemia results from a sudden failure in the oxygen and glucose supply. Oxidative phosphorylation fails, a major event that is responsible for all the other reactions. Anaerobic metabolism produces lactate and H+. Cell membrane ionic pumps are inactivated, which results in a breakdown of ionic homeostasis. Ca++ and Na+ penetrate into the cells, as K+ is released. The energy failure causes an extracellular accumulation of excitatory amino-acids, thus eliciting a hyperstimulation of the NMDA receptors. These receptors are hyperactivated as a result of the deterioration in the control systems with, especially, the blockade of the NMDA receptor by Mg++. As a consequence, there is a massive entry of Ca++ into the cell, including a series of enzymatic reactions involving phospholipases, proteases and endonucleases. Reperfusion will cause toxic lesions by producing free radicals, due to the action of arachidonic acid, xanthine oxidase and nitric oxide. The decrease in cell energetic supplies, as well as the overactivation of enzymes and the production of free radicals, result in cell death.
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PMID:[Cerebral ischemic cascade]. 767 74

Magnetic susceptibility contrast-enhanced and diffusion-weighted echo planar magnetic resonance (MR) imaging was performed using a cat model of acute regional cerebral ischemia induced by partial stenosis of the right middle cerebral artery (MCA). The imaging data were correlated with triphenyltetrazolium chloride (TTC)-stained histopathologic coronal brain sections to determine the prognostic efficacy of high-speed MR imaging techniques in differentiating mild, moderate, and severe cerebral hypoperfusion. Brains of animals without cortical injury on TTC staining were found to have a reduction in peak contrast enhancement of 32 +/- 6% (mean +/- SD) below control values with no significant change in the apparent diffusion coefficient (ADC), determined from the diffusion-weighted MR images. In cases where moderate ischemic injury was observed in the TTC-stained sections, a 10-20% drop in the ADC was found over the 6-h study period, accompanied by a much wider variation in peak contrast enhancement. Finally, where TTC staining showed severe ischemic brain damage, a 40-50% drop in ADC and a reduction in peak contrast enhancement effect of > 95% were observed as early as 1 h following MCA stenosis. The significant correlation between imaging observations and histologically confirmed cerebral ischemia indicates that magnetic susceptibility contrast-enhanced echo planar MR imaging is sensitive to slight reductions in cerebral perfusion that fall below the threshold for reliably detectable ischemia-induced alterations in ADC. First-pass perfusion-sensitive imaging may thus be diagnostically useful in differentiating severely hypoperfused permanently injured tissue from the mildly hypoperfused ischemic penumbra.
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PMID:High-speed MR imaging of ischemic brain injury following stenosis of the middle cerebral artery. 769 53

To ascertain the tempo of progression to irreversible injury in focal ischemia, we subjected halothane-anesthetized Sprague-Dawley rats to photochemically induced distal middle cerebral artery occlusion (dMCAO) combined with permanent ipsilateral and 1 h contralateral common carotid artery occlusions. Head temperature was maintained at 36 degrees C. At times centered at either 1.5 or 3 h post-dMCAO, the rate of local glucose metabolism (lCMRgl) was measured by 2-deoxyglucose autoradiography, and cytoskeletal proteolysis was assessed regionally by an immunoblotting procedure to detect spectrin breakdown products. At 1.5 h (n = 5), the cortical ischemic core was already severely hypometabolic (lCMRgl 15.5 +/- 10.8 mumol 100 g-1 min-1, mean +/- SD), whereas the cortical penumbral zone was hypermetabolic (69.0 +/- 9.7). (The lumped constant was verified to be unchanged by methylglucose studies). Neutral red pH studies at this time point showed that both the core and penumbral zones were equally acidotic. By 3 h post-dMCAO (n = 6), lCMRgl in the penumbral zone had fallen to low levels (15.4 +/- 2.2 mumol 100 g-1 min-1) equal to those of the ischemic core (16.7 +/- 4.5). Correspondingly, spectrin breakdown in the ischemic core was advanced at both 2 and 3.5 h post-dMCAO (36 +/- 18% and 33 +/- 18% of total spectrin, respectively), whereas in the penumbral zone spectrin breakdown was less extensive and more highly variable at both times (22 +/- 23% and 29 +/- 16%). We conclude that irreversible deterioration of the ischemic core, as evidenced by the onset of local cytoskeletal proteolysis, begins within 2 h of middle cerebral artery occlusion. In the ischemic penumbra, the transition from glucose hyper- to hypometabolism occurs by 3.5 h and is associated with a milder and more variable degree of spectrin breakdown.
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PMID:Local cerebral glucose utilization and cytoskeletal proteolysis as indices of evolving focal ischemic injury in core and penumbra. 771 97

Recent results have demonstrated that the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) reduces infarct size due to middle cerebral artery occlusion (MCAO), even when given after ischemia. The objective of the present study was to explore whether PBN influences recovery of energy metabolism. MCAO of 2-hr duration was induced in rats by an intraluminal filament technique. Brains were frozen in situ at the end of ischemia and after 1, 2, and 4 hr of recirculation. PBN was given 1 hr after recirculation. Neocortical focal and perifocal ("penumbra") areas were sampled for analyses of phosphocreatine (PCr), creatine, ATP, ADP, AMP, glycogen, glucose, and lactate. The penumbra showed a moderate-to-marked decrease and the focus showed a marked decrease in PCr and ATP concentrations, a decline in the sum of adenine nucleotides, near-depletion of glycogen, and an increase in lactate concentration after 2 hr of ischemia. Recirculation for 1 hr led to only a partial recovery of energy state, with little further improvement after 2 hr and signs of secondary deterioration after 4 hr, particularly in the focus. After 4 hr of recirculation, PBN-treated animals showed pronounced recovery of energy state, with ATP and lactate contents in both focus and penumbra approaching normal values. Although an effect of PBN on mitochondria cannot be excluded, the results suggest that PBN acts by preventing a gradual compromise of microcirculation. The results justify a reevaluation of current views on the pathophysiology of focal ischemic damage and suggest that a therapeutic window of many hours exists in stroke.
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PMID:N-tert-butyl-alpha-phenylnitrone improves recovery of brain energy state in rats following transient focal ischemia. 776 48

To determine which of two treatments for reducing ischemic injury after temporal focal ischemia is more effective, the effects of mild (33 degrees C) intraischemic hypothermia were compared with those of mannitol, the most commonly used neuroprotective agent. Four groups of Sprague-Dawley rats underwent 1 hour of endovascular middle cerebral artery occlusion followed by 23 hours of normothermic reperfusion. The four experimental groups were as follows: Group A, saline control; Group B, mannitol (25%, 1 g/kg); Group C, hypothermia; and Group D, hypothermia plus man-nitol. Laser-Doppler estimates of cortical blood flow showed that hypothermia did not affect blood flow during ischemia or reperfusion. Mannitol increased cortical blood flow during ischemia and reperfusion under both normothermic and hypothermic conditions (p < 0.05). Neurological deficit was significantly less severe in treated rats (Group B, p < 0.05; Group C or D, p < 0.01) than in controls (Group A). Infarct volume, measured on semiserial Nissl-stained sections, was significantly smaller in treated rats (p < 0.01) than in controls. Infarct volume was also significantly smaller in rats treated with hypothermia than in those treated with mannitol (Group C vs. Group B, p < 0.05); there was no difference between rats treated with mannitol and those treated with mannitol and hypothermia. All three treatments reduced infarct area in the ischemic penumbra; hypothermia with or without mannitol also reduced infarct area in the ischemic core. These results demonstrate that both mild intraischemic hypothermia and mannitol reduce infarct size and neurological deficit: hypothermia reduces infarct size more effectively than mannitol, and mannitol adds no significant protection to hypothermia, whereas hypothermia adds significant protection beyond that afforded by mannitol after brief focal ischemia followed by reperfusion in rats. The results suggest that mild intraischemic hypothermia alone, or in combination with mannitol, may be useful in avoiding ischemic injury from temporary vessel occlusion during cerebrovascular surgery.
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PMID:Use of mild intraischemic hypothermia versus mannitol to reduce infarct size after temporary middle cerebral artery occlusion in rats. 778 57

The cytokine tumor necrosis factor (TNF-alpha) is a pleotrophic polypeptide that plays a significant role in brain immune and inflammatory activities. TNF-alpha is produced in the brain in response to various pathological processes such as infectious agents [e.g., human immunodeficiency virus (HIV) and malaria], ischemia, and trauma. TNF-alpha mRNA is rapidly produced in response to brain ischemia within 1 h, reaches a peak at 6-12 h post ischemia, and subsides 1-2 days later. TNF-alpha mRNA expression corresponds in a temporal fashion to other cytokines such as interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (KC), and IL-1 and precedes the infiltration of inflammatory cells into the injured zone. TNF-alpha is present early in neuronal cells in and around the ischemic tissue (penumbra), yet at later time points, the peptide is found in macrophages in the infarcted tissue. TNF-alpha has been demonstrated to cause expression of proadhesive molecules on the endothelium, which results in leukocyte accumulation, adherence, and migration from capillaries into the brain. Furthermore, TNF-alpha activates glial cells, thereby regulating tissue remodeling, gliosis, and scar formation. Thus, evidence is emerging in support of a role for TNF-alpha in injury induced by infectious, immune, toxic, traumatic, and ischemic stimuli. TNF-alpha promotes inflammation by stimulation of capillary endothelial cell proinflammatory responses and thereby provides leukocyte adhesion and infiltration into the ischemic brain. The evidence generated so far suggests that agents that suppress TNF-alpha's production or actions will reduce leukocyte infiltration into ischemic brain regions and thereby diminish the extent of tissue loss.
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PMID:Cytokines, inflammation, and brain injury: role of tumor necrosis factor-alpha. 788 Jul 18


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