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

We hypothesized that ischemic insult to the lung allograft may render it more susceptible to rejection. Left canine single-lung allografts were subjected to usual periods of cold and warm ischemia (4 hours and 1 hour, respectively). Bronchoalveolar lavage and open lung biopsies were performed at 0, 1, 4, and 24 hours and 1 week after transplantation. Bronchoalveolar lavage fluid was examined for cellular phenotypes, lymphocyte lectin-mediated cytotoxicity, and natural killer cell cytotoxicity. Open lung biopsy specimens were examined for severity of injury/rejection and MHC class II expression. Within 1 to 4 hours of reimplantation, we observed marked influx of polymorphonuclear leukocytes and lymphocytes and an increase in lectin-mediated cytotoxicity (25.6% +/- 14.8% and 50.6% +/- 20.1% versus 5.4% +/- 7.5% preoperatively; p < 0.05). In addition, natural killer cell cytotoxicity increased from 10.2% +/- 13.5% before transplantation to 20.5% +/- 8.6% 4 hours after transplantation (p < 0.03). By 24 hours MHC class II expression became evident and continued to increase while subtle histologic evidence of rejection appeared by 1 week. We conclude that ischemia-reperfusion injury can alter the local bronchopulmonary milieu, thus rendering it more susceptible to the development of rejection.
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PMID:Early cellular events in the lung allograft. 144 89

Delayed neuronal death induced by transient forebrain ischemia in the rat hippocampus is preceded by a prominent microglial reaction which begins within minutes after the ischemic injury. In the present study we have examined the effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on microglial activation and neuronal survival. Using lectin histochemistry to detect microglia, we show that the systemic administration of MK-801 prior to ischemia prevents microglial activation, as well as delayed death of CA1 pyramidal neurons. The results demonstrate that early blockage of the glutamate cascade prevents microglial activation, and could suggest a role for microglia in mediating ischemic injury.
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PMID:MK-801 prevents microglial reaction in rat hippocampus after forebrain ischemia. 153

We have examined the distribution and time course of the microglial reaction in the rat dorsal hippocampus after 25-min transient forebrain ischemia (four-vessel occlusion model). Microglial cells were visualized in brain sections using lectin staining with the Griffonia simplicifolia B4-isolectin following intervals of reperfusion ranging from 20 min to 4 weeks. Increased staining of microglial cells was detected in the dentate hilus and area CA1 as early as 20 min after reperfusion. These same regions demonstrated more intense microglial staining after 24 h. The strongest microglial reaction was observed 4-6 days after reperfusion when reactive microglia were abundant throughout all laminae of CA1 and the dentate hilus. Following longer reperfusion intervals, the microglial reaction became less intense; however, it remained above normal levels until the end of the fourth week. At all time points examined, microglial reactivity in the CA3 pyramidal and dentate granule cell layers was considerably lower than that observed in CA1 and dentate hilus. Our results are consistent with the known serial pathological changes associated with cerebral ischemia, but, in addition, show that the examination of the microglial reaction provides an extremely sensitive indicator of subtle and morphologically nonapparent neuronal damage during the early stages of injury.
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PMID:The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia. 171 9

Warm ischemia is an important factor in early allograft dysfunction. To elucidate cellular events involved in such lung injury, we examined the effects of warm ischemia on the cytotoxic function of lymphocytes retrieved by bronchoalveolar lavage as compared with peripheral blood lymphocytes. Warm ischemia of the lung was induced in eight dogs by crossclamping left hilar structures for 1 hour. Bronchoalveolar cells from ischemia left and unaffected right lungs, as well as blood lymphocytes, were isolated before operation and 2 hours, 72 hours, and 7 days after operation. Lung and blood lymphocytes were assayed for natural killer and lectin-dependent cell-mediated cytotoxicity. Warm ischemia resulted in a significant impairment of natural killer activity within 2 hours of reperfusion (49% of preoperative control cytolysis, p less than 0.01). There was a significant increase in natural killer activity in bronchoalveolar lavage mononuclear cells 72 hours after reperfusion injury (178.4% of preoperative value, p less than 0.01). Interestingly, these functional alterations were not paralleled with changes seen in the peripheral blood lymphocytes or the opposite nonaffected lungs, where the natural killer activity appeared significantly depressed at 72 hours. Similarly, lectin-dependent cell-mediated cytotoxicity was noted to be increased in the bronchoalveolar lavage from the ischemic lung (179.5%, p less than 0.01) but decreased in the bronchoalveolar lavage from the nonaffected lung and peripheral blood lymphocytes at 72 hours after injury. We conclude that warm ischemia is associated with a functional alteration of the local lung immune cells. Such alteration is not observed in cells from the opposite lung or peripheral blood. The observed increase in nonspecific cytotoxicity of bronchoalveolar lymphocytes can be causative in the early damage seen in poorly preserved lung allografts.
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PMID:Warm ischemia induces alteration in lung immune cell functions. 203 96

The relationship between the saccharide chain on the endothelial cell surface and the permeability of intracerebral blood vessels has been studied. In the present study, wheat germ agglutinin (WGA) was perfused into capillaries in the area postrema of the normal Mongolian gerbil, where the blood brain barrier (BBB) is known to lack, and into intracerebral blood vessels, the BBB of which had been destroyed by experimentally induced brain ischemia. The light microscopic features of the sections from WGA-perfused brain tissues of the normal gerbil revealed that most of the blood vessels, including capillaries in the brain parenchyma, showed positive findings (the reaction induced a very distinct staining of the vascular wall) from which the course and structure of the fine vessels could be determined. The reaction to WGA on the diaphragma fenestra (DF) in capillaries in the area postrema was relatively weak, and DF without the reaction were occasionally revealed by electron microscopy. The gerbil, in which cerebral ischemia had been induced, also showed partial defect of the reaction with WGA on the luminal side of the endothelial cells. The results of the present experiment suggest some degree of correlation between the saccharide chains, including the specific monosaccharide of WGA, on the endothelial cell surface and permeability. It was considered that lectin can be used as an index for morphological observations, suggesting an alteration in function of the endothelial cell membrane. In addition, the perfusion method in this experiment suggested the possibility of distinguishing pinocytotic vesicles from pits of cell membranes.
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PMID:Experimental study of WGA binding on the endothelial cell surface in cerebral ischemia. 298 Jan 3

The beta-amyloid precursor protein (APP) bears characteristics of an acute-phase protein and therefore is likely to be involved in the glial response to brain injury. In the brain, APP is rapidly synthesized by activated glial cells in response to comparatively mild neuronal lesions, e.g., a remote peripheral nerve injury. Perfusion deficits in the brain result largely in neuronal necrosis and are a common condition in elderly patients. This neuronal necrosis is accompanied by a pronounced reaction of astrocytes and microglia, which can also be observed in animal models. We have therefore studied in the rat, immunocytochemically, the induction of APP after 30 min of global ischemia caused by four-vessel occlusion. The postischemic brain injuries were examined at survival times from 12 h to 7 days. From day 3 onward, APP immunoreactivity was strongly induced in the CA1 and CA4 regions of the rat dorsal hippocampus as well as in the dorsolateral striatum. In these areas, the majority of APP-immunoreactive cells were reactive glial fibrillary acidic protein (GFAP)-positive astrocytes, as shown by double-immunofluorescence labeling for GFAP and APP. Additionally, small ramified cells, most likely activated microglia, expressed APP immunoreactivity. In contrast, in the parietal cortex, APP immunoreactivity occurred focally in clusters of activated microglia rather than in astrocytes, as demonstrated by double-immunofluorescence labeling for APP and the microglia-binding lectin Griffonia simplicifolia isolectin B4. In conclusion, following global ischemia, APP is induced in reactive glial cells with spatial differences in the distribution pattern of APP induction in astrocytes and microglia.
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PMID:Glial expression of the beta-amyloid precursor protein (APP) in global ischemia. 779 Apr 14

We have studied the microglial reaction that accompanies cortical infarction induced by middle cerebral artery occlusion (MCAO). Lectin histochemistry with the B4-isolectin from Griffonia simplicifolia as well as immunocytochemistry with a panel of monoclonal antibodies directed against major histocompatibility complex (MHC) and lymphocytic antigens were performed. Principal attention was focused on neocortical and thalamic regions, representative of primary and secondary ischemic damage, respectively. With the lectin procedure, activated microglial cells were abundant in the neocortex 24 hours after MCAO. In contrast, microglial activation in the thalamus was not apparent until day 2 after MCAO. On day 5, MHC class II antigen was expressed by reactive microglia in fiber tracts traversing the striatum, but was absent from activated microglia in the primary cortical infarction area. MHC class I and lymphocytic antigens were expressed differentially on microglia with class I antigens appearing early and lymphocytic antigens appearing late in the time course after focal ischemia. The findings are compatible with previous studies during global ischemia and confirm the early activation and the progressive nature of immunomolecule expression on activated microglia after an ischemic insult. In addition to neocortical and thalamic sites, our results showed an early microglial activation to be present also in forebrain regions outside of the middle cerebral artery (MCA) territory, such as the contralateral cortex and hippocampus. A unilateral microglial reaction was also detectable after long-term survival (> or = 4 weeks) in the pyramidal tracts, as well as in the corticospinal tracts at cervical but not lumbar spinal cord levels. Ischemia-induced neuronal damage, as evaluated by Nissl staining, was found only in cortical and thalamic regions. We conclude that the demonstration of reactive microglia indicates not only imminent ischemic neuronal damage within MCA territory but can also delineate extra-focal disturbances, possibly reflecting subtle and transitory changes in neuronal activity.
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PMID:Characterization of microglial reaction after middle cerebral artery occlusion in rat brain. 843 4

The morphological and histochemical changes in the rat brain, resulting from global cerebral ischemia due to cardiac arrest and cessation of respiratory function, connected with the disturbances of blood-brain barrier mechanisms inclined us to perform a series of studies on the localization of specific sugar residues in the membrane glycoprotein chains, using lectin techniques. Chosen lectins, represented by synthetic plant glycoproteins which are specifically bound to particular sugar residues located on the cell surfaces, made it possible to localize the following sugar residues: beta-D-galactose (using Ricinus communis agg.-RCA-1); beta-D-galactosyl (Ricinus communis agglutinin <RCA-1>), N-acetyl-glucosaminyl and N-acetyl-neuraminic acid (Wheat germ agglutinin WGA), N-acetyl-glucosaminyl (Helix pomatia agglutinin <HPA> and Dolichos biflorus agglutinin<DB A>), N-acetyl and N-glycol-neuraminic acid (Limax flavus agglutinin <LFA>), alpha-D-galactosyl and D-galactosyl neuraminic acid (Peanut agglutinin <PNA>), alpha-D-galactosyl and alpha-D-mannosyl (Concanavalin A <Con A>), alpha-D-galactosyl and alpha-D-galactopyranoside (Bandeirea simplicifolia agglutinin A <BSA>). In the presented paper changes in the localization of examined glycoconjugates found both in the vascular network as well as in other morphological elements of the brain (neurons, glial cells and neuropil), resulting from 10 min cardiac arrest, connected with global cerebral ischemia are characterized. In the group of control animals the strongest reaction of the vessels was obtained with RCA-1 and BSA, weaker with WGA and the weakest with DBA and LFA. Experimental rats, examined at different time following resuscitation showed significant changes in the histochemical reaction with use of different lectins. Sugar residues revealed by BSA disappeared from the brain vessels already 3 h following clinical death reappearing at 3 and 14 days after ischemia and regaining the picture described in control animals one year later. Additionally the experimental animals were characterized by a remarkably weaker reaction with WGA while location and intensity of RCA-1 receptors in the brain blood vessels remained unchanged or even increased. Additionally in the group of rats which survived 3 days after ischemia, the number of vascular receptors revealed by DBA also increased. The neuropil was characterized by a strong affinity to the sugar residues recognized by DBA, HPA, BSA, PNA, and LFA. As a rule it was stronger in the white structures of the brain than in the gray ones. Starting from the 24 h of postresuscitation till the end of the observation (1 year) staining reaction of neuropil with the above mentioned lectins was reduced. From the group of glycoconjugates used the strongest reaction in parenchymal brain cellular elements concerned those sugar residues which are identified Con A and HPA. In a group of experimental animals staining reaction with Con A was decreased whereas that with HPA was remarkably increased in all animals which survived ischemia. Additionally, BSA-recognized residues not detectable in normal conditions appeared in the neurons and glial cells of hippocampus and subiculum. The presented results indicate deep histochemical and probably functional changes taking place in endothelial cells as well as in other cellular elements of the brain and in neuropil of animals which survived clinical death. The abnormalities appearing in the early postischemic stage persisted for the long observation time indicating an active and progressing process leading to postischemic encephalopathy.
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PMID:Lectin histochemistry in the rats brain in experimental postresuscitation syndrome. (Early and late changes). 879 96

Activated microglia may contribute to the progression of neuronal injury after a wide range of CNS insults. In this study, we used two complementary methods to evaluate acute changes in the morphology and regional distribution of microglia induced by a focal hypoxic-ischemic insult in 7-d-old (P7) rats. To elicit injury, P7 rats underwent right carotid ligation followed by 3 h of 8% O2 exposure; rats were killed 10 min to 5 d later (n > or = 3/group). A histochemical assay using Griffonia simplicifolia B4-isolectin enabled detection of both resting and activated microglia in tissue sections; vascular cells were also reactive. Activated microglia were also identified immunocytochemically using a macrophage-specific MAb, ED-1. In normal P7-12 brain, lectin, and ED-1 immunoreactive-activated microglia were concentrated in white matter; lectin-positive resting, ramified microglia were also detected throughout the gray and white matter. Subtle morphologic evidence of microglial activation was noted 10 min posthypoxia-ischemia in the lesioned right cerebral hemisphere; activated microglia began to accumulate within the next 4 h. Accumulation of lectin-positive activated microglia peaked at 2-4 d posthypoxia-ischemia. ED-1 immunoreactive-microglia were first noted 4 h after hypoxic-ischemic injury in the lesioned right hemisphere, and there was a corresponding increase in accumulation over the first 48 h posthypoxia-ischemia. In the left hemisphere, contralateral to the ligation, no increase in activated microglia were detected with either method. In brain sections where no neuronal injury was evident, activated microglia did not accumulate. These data demonstrate that perinatal hypoxic-ischemic brain injury induced rapid accumulation of activated microglia in hypoxic-ischemic forebrain.
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PMID:Hypoxic-ischemic brain injury induces an acute microglial reaction in perinatal rats. 882 84

Although transforming growth factor-beta (TGF-beta) is known to be multifunctional in many physiological systems, its role in the brain is undergoing elucidation. The situation is made more complex by the presence of multiple isoforms, which may be differentially regulated and have various activities in each particular cell type. Because neurons are dependent on neurotrophic factors for survival, we utilized a rat model of transient forebrain ischemia (TFI) to test the hypothesis that TGF-beta isoforms are important in the hippocampal response to injury. Northern blot analysis demonstrated a differential and temporal alteration in TGF-beta isoform expression following TFI. In-situ hybridization experiments revealed that at day 1 following TFI, there was a strong neuronal increase in the TGF beta-1 transcript but a reciprocal decrease in TGF-beta 2 and -beta 3 transcript levels. Immunohistochemical analysis of all three TGF-beta s demonstrated at day 1 following TFI a loss of the immunoreactive proteins in the vulnerable CA-1 hippocampal neurons, but protein preservation in the CA-2-4 neurons which are more resistant to the ischemic insult. At 3-5 days following TFI, significant extraneuronal changes in TGF-beta isoform expression were also detected. Double-staining experiments with antibody to glial fibrillary acidic protein (GFAP) as a marker for astrocytes, and lectin isolectin B4 Griffonia simplicifolia for microglia, demonstrated increased expression of all TGF-beta isoforms in astrocytes but not microglia. Taken together, these results suggest that the TGF-beta peptides in neurons and astrocytes are important endogenous mediators in the CNS response to ischemic injury.
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PMID:Differential neuronal and astrocytic expression of transforming growth factor beta isoforms in rat hippocampus following transient forebrain ischemia. 884 7


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