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

Previously, using a middle cerebral artery occlusion model in Wistar rat, we showed autonomic disturbances similar to those seen clinically and observed striking neurochemical changes in cortical and subcortical sites at 5 days following stroke. The neurochemical changes may account for functional recovery and/or autonomic disturbances after focal ischemia. To understand the possible mechanisms and to facilitate future studies, it is necessary to define the time-courses of these changes. Using immunohistochemical staining with the peroxidase-antiperoxidase reaction, the changes in several neuropeptides over the peri-ischemic region and the ipsilateral central and basolateral nucleus of the amygdala were investigated at different times after middle cerebral artery occlusion. In the experimental group, neuropeptide Y immunoreactivity appeared to increase by 6 hours in the peri-ischemic region. Using image analysis to quantify the staining intensity, the change became statistically significant at 1 day, peaked around 3 days, and subsided at 10 days. There was a delayed increase in neuropeptide Y in the ipsilateral basolateral nucleus of the amygdala with a peak around 3 days. Immunoreactive staining for leucine-enkephalin, dynorphin, and neurotensin demonstrated an increase that was localized to the ipsilateral central nucleus of the amygdala with a peak around 3 days and a return to baseline levels by 10 days. The results support a specific time-course for each of the neuropeptides studied and indicate that a survival time of 3 days after focal ischemia is the critical period for examining the relationship between neuropeptide responses and neuronal or functional recovery.
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PMID:Time-course of neuropeptide changes in peri-ischemic zone and amygdala following focal ischemia in rats. 749 57

Reduced blood flow produced by bilateral carotid artery occlusion (BCAO) caused multiple histopathological alterations in the cerebral cortex of developing cats. BCAO was performed in the second postnatal week. At 1 and 2 months, global structural observations were made using magnetic resonance imaging (MRI). At 3 months, neuron and glial density, extent of myelination, blood vessel distribution, and the distribution of visual callosal projecting neurons (as visualized with the retrogradely transported tracer horseradish peroxidase) were assessed by light microscopy. MRI showed lateral ventricular dilatation at 1 month in five of eight subjects, with wide-ranging severity, although at 2 months only two animals still had enlarged ventricles. Histological observations at 3 months showed that neuron density in the motor cortex, but not the occipital cortex, of BACO animals was significantly lower than that in controls. BCAO animals had more dilated small vessels, again more evident in the motor cortex than in the occipital cortex. From frontal to occipital cortex, the corpus callosum was thinned and the subcortical white matter was reduced. Even with the reduction of white matter, the number of neurons in visual areas 17 and 18 contributing a callosal projection was much higher than normal. BCAO thus altered cerebral vascularization, caused neuronal death, and reduced myelinization over an area much greater than the direct area of carotid perfusion. The excess callosal projection in these animals suggests that neonatal ischemia interferes with the normal process of axon retraction during development.
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PMID:Consequences of reduced cerebral blood flow in brain development. I. Gross morphology, histology, and callosal connectivity. 750 62

The objective of this study was to determine the role of cyclosporin A (CsA) on cold-restraint-induced gastric lesions. Animals were subjected to 3 h immobilization at 4 degrees C in plastic restraining devices following a starvation period of 48 h. Gastric samples were obtained for the measurement of myeloperoxidase (MPO) activity, an index of number of peroxidase positive cells and thiobarbituric acid-reactive substances (TBARS; lipid peroxidation). Animals were pretreated with CsA which is a potent immunosuppressant and inhibits ischemia/reperfusion-induced polymorphonuclear leukocyte (PMN) infiltration. Cold-restraint administration significantly elevated the tissue MPO activity and TBARS formation. CsA pretreatment significantly reduced the severity of cold-restraint-induced gastric lesions while attenuating the elevated MPO measurements observed during cold-restraint administration. Animals rendered neutropenic with antineutrophil serum (ANS) exhibited significantly less gastric mucosal injury normally observed after cold-restraint stress. Neither CsA nor ANS treatment effected the elevated TBAR levels, indicating that PMNs are not involved in the lipid peroxidation process observed after cold-restraint stress. In conclusion, the results of this study indicate that CsA is capable of inhibiting cold-restraint-induced gastric mucosal injury and can attenuate the cold-restraint-induced increases in gastric MPO measurements. Our results also indicate that PMNs may be the important mediators of cold-restraint-induced gastric lesions.
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PMID:Cyclosporin A reduces the severity of cold-restraint-induced gastric lesions: role of leukocytes. 765 47

Current methods of experimental infarct size measurement require tissue analysis several hours after the ischemic event. Electron microscopy identifies irreversibly injured myocytes early after ischemia, but cannot be used to measure myocardial infarct size. Horseradish peroxidase (HRP), a tracer protein that permeates the disrupted sarcolemma of injured myocytes, was used to determine infarct size. New Zealand White rabbits (n = 15) were subjected to 30 min coronary artery occlusion and 24 h reperfusion. Prior to euthanasia, HRP was administered intravenously. The hearts were excised, perfused with triphenyl tetrazolium chloride (TTC), and perfusion fixed. A frozen section was cut from left ventricular slices, and the brown HRP reaction product was developed with 3,3'-diaminobenzidine tetrahydrochloride and H2O2. The areas delineated by intramyocyte HRP (as a percent of the left ventricle) closely correlated with infarct size determined by conventional hematoxylin-eosin (H&E) stain and TTC (means +/- S.E.M.): 29.5 +/- 3.0% vs 27.6 +/- 2.9% vs 28.6 +/- 2.6%, respectively. The coefficient of correlation between HRP and H&E was 0.94. This method was tested for early infarct detection in rabbits subjected to 30 min coronary occlusion followed by intravenous injection of HRP and sacrifice. HRP-delineated infarcts measured 21.4 +/- 3.7% of the left ventricle, and electron microscopic examination from ischemic and non-ischemic areas was used to confirm that cells containing HRP were irreversibly injured. Thus, HRP can be used to accurately measure myocardial infarct size in experimental coronary artery occlusion and reperfusion in infarcts as early as 30 min after coronary occlusion or following 24 h of reperfusion.
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PMID:Early detection and measurement of experimental myocardial infarcts with horseradish peroxidase. 768 52

Neutrophil adherence and/or aggregation has been implicated in ischemia reperfusion injuries. We examined the role of P-selectin in PMN-mediated injury after reperfusion of the rabbit ear. The ear was partially amputated, and then reattached leaving the central artery and vein intact. To induce ischemia the central artery was then occluded. Treatment was at reperfusion with either saline or one of two murine P-selectin mAbs, designated PB1.3 and PNB1.6 mAb PB1.3 cross-reacts with rabbit P-selectin and prevents histamine-induced leukocyte rolling, whereas PNB1.6 does not. Using a peroxidase-antiperoxidase system P-selectin was detected in the ischemic ear, but not in the nonischemic ear. Ear volume increased to 5.3 times baseline in the saline-treated animals (n = 8), 6.6 times baseline in the nonblocking mAb PNB1.6-treated animals (n = 2), and 3.7 times baseline in the blocking mAb PB1.3-treated animals (n = 8). Estimated tissue necrosis of the combined saline- and PNB1.6-treated animals was 46 vs. 2.7% for the mAb PB1.3-treated animals. We conclude that: (a) P-selectin is expressed in ischemia reperfusion; (b) P-selectin participates in PMN-endothelial cell interactions in ischemia reperfusion; and (c) inhibiting P-selectin adhesion significantly reduces reperfusion injury.
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PMID:Anti-P-selectin monoclonal antibody attenuates reperfusion injury to the rabbit ear. 769 90

In previous studies, we have used histological methods to characterize cellular changes, and validated the use of the myeloperoxidase (MPO) activity assay to quantitate increased neutrophil infiltration in ischemic stroke. We also identified increased leukotriene B4 (LTB4) binding sites as a potential marker for neutrophil infiltration into focal ischemic tissue. However, these studies were conducted at only one time-point, 24 h after ischemia. In the present study, we examined the full time-course of MPO activity and LTB4 receptor binding following middle cerebral artery occlusion (MCAO) made permanently (PMCAO) or transiently (160 min followed by reperfusion; TMCAO) in spontaneously hypertensive rats, and compared the results to previously characterized histologic changes in these models. Ischemic and contralateral (control) cortical tissue samples were assayed for MPO (U/g wet wt) and [3H]LTB4 receptor binding (fmol/mg protein). Following PMCAO, MPO activity significantly increased as early as 12 h and continued to increase over the next 5 d (p < 0.05). Following TMCAO, MPO activity was significantly elevated already after only 6 h of reperfusion and also continued to increase over the next 5 d of reperfusion (p < 0.05). LTB4 receptor binding and MPO activity were highly correlated during periods when both measures increased together (i.e., 0.5-5 d; p <0.01). However, by 15 d post-MCAO, LTB4 receptor binding remained elevated after MPO activity levels had returned to normal. This persistent LTB4 binding was associated with the significant gliosis that was characterized previously to persist in these models. The time-course of increased MPO activity and initially increased LTB4 binding post-MCAO correspond very well to our previous histological data that characterized the time-course for leukocyte infiltration under these conditions. Therefore, the increased MPO activity over time was associated with initial neutrophil and later mononuclear cell infiltration into ischemic tissue in these models. In addition, the present studies utilized histochemical analysis to demonstrate peroxidase activity in macrophages within the cerebral infarct following MCAO, thus validating that MPO activity originates from the later infiltrating mononuclear cells in addition to the early infiltrating neutrophils that had been previously characterized in the same manner. TMCAO produces a significantly larger and earlier increase in ischemic cortex MPO activity and a similar later increase in MPO activity compared to PMCAO treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Time-related changes in myeloperoxidase activity and leukotriene B4 receptor binding reflect leukocyte influx in cerebral focal stroke. 775 44

Brief transient ischemia causes a delayed neuronal death of pyramidal neurons in the CA1 area of hippocampus after a period of hyperexcitability. We have previously shown that the hyperexcitability is due to an increase in an N-methyl-D-aspartate (NMDA) component of the response. In the present study, we recorded intracellularly from pyramidal neurons in CA1 and find that there is little change in membrane potential or input resistance at this point in time. The dramatic increase in the NMDA component of the synaptic response is a result of a significant reduction in the ability of Mg2+ to induce a normal voltage-dependent blockade of the response. In spite of the relatively normal membrane properties, there is at this time a significant reduction in the amplitude of the population excitatory potential and a near total loss of long-term potentiation. In contrast, post-tetanic potentiation is unchanged in magnitude and character. These observations suggest more severe damage to the neuron than indicated by the membrane potential and resistance. When single neurons were injected with horseradish peroxidase and visualized after the electrophysiological recording, we found extensive beading of the dendrites in both the apical and basal regions, presumably reflecting a disproportionate damage to the dendritic areas, which are the primary sites of the excitatory amino acid synapses onto the neuron. These observations are consistent with the hypothesis that transient ischemia causes a fundamental change in the NMDA-activated ion channel such that Mg2+ is no longer able to block the response, resulting in increased entry of calcium into synaptic regions, which causes dendritic damage that progresses to neuronal cell death.
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PMID:Functional and morphological changes induced by transient in vivo ischemia. 795 41

The protective effects of cyproheptadine (Cyp), an antiserotonin-antihistaminic agent with calcium channel blocker activity, on myocardial reperfusion injury in isolated Langendorff heart of rats were studied. After a low perfusion [0.17 ml.min-1, standard Krebs-Henseleit (K-H) buffer without glucose, gassed with 95% O2 + 5% CO2] of 60 min followed by a normal K-H buffer perfusion of 20 min, an extensive and severe myocardial injury appeared: a release of lactate dehydrogenase (LDH) and creatine kinase (CK), a decrease of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) activities, and an increase of malondialdehyde (MDA) content. Serious inhibition of cardiac functions and appearance of arrhythmia, even asystole, were also elicited in the injured hearts. Cyp (2.5 and 5 mumol.L-1) effectively antagonized the damage. The results suggested that the protective effects of Cyp on the ischemia-reperfusion injury may be related to its actions of blocking the calcium channel, scavenging the oxygen free radicals, protecting the antioxygen free radical enzymes, and inhibiting the lipid peroxidation in the myocardium.
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PMID:[Protective effects of cyproheptadine on myocardial reperfusion injury in isolated rat hearts]. 797 81

It is well known that reperfusion damage of ischemic myocardium may be attributed to alterations in the antioxidant defense system against free radical aggression. In addition, the degree of myocardial damage may depend on the duration and severity of ischemia that precedes reperfusion. We carried out serial ischemic experiments (10, 30, 60 and 120 min) in ex-vivo rat hearts followed by 30 min reperfusion and we assayed the glutathione-dependent enzymatic activities (selenium-dependent glutathione-peroxidase: GSH-Px; selenium-independent glutathione peroxidase: GST-Px; glutathione-transferase: GST and glutathione-reductase: GS-SG-Red), Catalase activity (CAT) and non-proteic thiol compounds (NP-SH) at the end of reperfusion. We found a significant reduction of NP-SH, GSH-Px and CAT in ischemic/reperfused hearts from 30 min on, while GST activity was increased. In addition, we observed the appearance of a selenium-independent glutathione peroxidase activity (GST-Px) belonging to the GST system. In conclusion, we found the longer the duration of ischemia the greater the inbalance between the myocardial antioxidant system especially the GST activation, suggesting in particular for GST-Px, a role in the control of the damage against oxygen toxicity during ischemia/reperfusion.
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PMID:Myocardial antioxidant defense mechanisms: time related changes after reperfusion of the ischemic rat heart. 801 40

The progression from ischemic injury to pannecrosis that occurs in the rat brain several hours after occluding a large artery may be partly attributable to a worsening of the circulation through the microvessels. The objective of this study was to quantitate selected structural changes involving astrocytes and endothelial cells within an area of focal brain ischemia created by the occlusion of a middle cerebral artery. The magnitude of these structural changes was correlated with alterations in the patency to a circulating macromolecule through the microvessels (< or = 15 mu in diameter) located within the territory of the occluded artery. One hundred eighty-five adult male Wistar rats had the right middle cerebral artery occluded after threading a nylon monofilament through the external carotid artery. Experiments were terminated by either cardiovascular perfusion or decapitation and immersion fixation at intervals ranging between 30 minutes and 7 days after the arterial occlusion. Randomly selected animals from each experimental subgroup were injected intravenously with horseradish peroxidase (molecular weight 44 kd) approximately 20 minutes before death. The progressive decline in the area fraction comprised by the vessels filled with horseradish peroxidase was preceded at 30 to 60 minutes by an increase in the surface area occupied (on a cross-section of a microvessel) by endothelial cells (both nucleus and cytoplasm). This was followed by an increase of 23.7% in the mean diameter of astrocytes nuclei and a decrease of approximately 35% in lumenal surface of the microvessels. These observations suggest that the occlusion of a large cerebral artery causes prompt swelling of endothelial cells and astrocytes; both of these early biological responses may interfere with erythrocyte circulation and oxygen delivery, which (after the arterial occlusion) are entirely dependent on the circulation provided by the collateral arterial connections. Through its interference with microvascular patency and oxygen delivery, cell swelling may influence the rate at which neurons become necrotic. In this model of brain infarct the number of necrotic neurons peaks approximately 72 hours after middle cerebral artery occlusion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Brain microvessels: factors altering their patency after the occlusion of a middle cerebral artery (Wistar rat). 808 52


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