Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Astrocytic activation plays a major role in homeostatic maintenance of the central nervous system in response to neuronal damage. To assess the reactivity of astrocytes in transient cerebral ischemia of the gerbil, we studied the levels of glial fibrillary acidic protein (GFAP) and its mRNA. GFAP mRNA increased by 4 h after carotid artery occlusion, reached peak levels by 72 h with a 12-fold increase over control and then started declining as early as 96 h postischemia. An examination of the specific regions of the brain revealed an increase in GFAP mRNA associated with the forebrain, midbrain, hippocampus and striatum. GFAP mRNA in the non-ischemic cerebellum however, remained expressed at constitutively low levels. Immunoblot analysis with anti-GFAP antibodies demonstrated a 2- to 3-fold increase in the protein after 24 and 48 h of reperfusion. Pretreatment with pentobarbital and 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine (HWA 285), the drugs that have been shown to protect against ischemic damage, prevented the increase in GFAP mRNA in the cortex following ischemic injury. Forebrain ischemia also induced vimentin mRNA and protein quantities by 12 h of reperfusion in the cortex. The levels of c-fos and preproenkephalin mRNA increased rapidly within 1 h after ischemic injury, demonstrating a temporal difference in mRNA changes following ischemia. These results indicate that an increase in GFAP and vimentin, the two glial intermediate filament proteins in the area of the ischemic lesion may be associated with a glial response to injury.
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PMID:Transient ischemia stimulates glial fibrillary acid protein and vimentin gene expression in the gerbil neocortex, striatum and hippocampus. 131 93

Although unilateral clamping of the renal artery to induce chronic ischemia of the kidney tissue has been utilized in several animal species, the resultant morphologic, ultrastructural and immunologic changes have never been well characterized. Moreover, the pathogenesis of these changes, as well as their roles in causing or facilitating the development of chronic tubulointerstitial nephritis have not been known. To examine some of these issues, male Sprague-Dawley rats were subjected to unilateral stenosis of the left main renal artery for 28 days. Stenotic and contralateral kidneys of experimental animals and kidneys from sham-operated controls were subjected to: (1) light microscopic, electron microscopic and immunofluorescent studies; (2) morphometric quantitation of the structural changes; (3) staining for actin, epithelial membrane antigen, keratin, and vimentin by immunoperoxidase technique; (4) staining for complex glycoproteins by a panel of 13 lectins; and (5) phenotyping and quantitation of the interstitial inflammatory infiltrates by monoclonal antibodies, using immunoperoxidase technique. The results reveal that: (1) The ischemic kidney tissue displays marked tubulointerstitial damages including abundant interstitial chronic inflammatory infiltrates, with good preservation of glomerular structure, which is consistent with the standard criteria of chronic tubulointerstitial nephritis. (2) The antigenic profile of the ischemic tubular epithelium displayed marked alterations including a neo-expression of vimentin and keratin, as well as a loss of endogenous avidin binding activity, Ia antigen and several complex surface glycoproteins detectable by lectins. (3) Neither electron dense deposits nor immunoglobulins are detectable in the kidneys from experimental or control animals. (4) Tubulitis, defined as infiltration of tubular epithelium by inflammatory cells, was present in up to 42.2% of tubular cross sections of the ischemic kidneys. (5) The interstitial inflammatory infiltrates were composed of B lymphocytes, T helper lymphocytes, and macrophages whereas the T non-helper lymphocytes were scanty, a phenotypic pattern similar to that of several other experimental rat models of chronic tubulointerstitial nephritis. It is concluded that: (1) In the Sprague-Dawley rats, ischemia alone can cause a constellation of changes fulfilling the accepted features of chronic interstitial nephritis; (2) ischemia alters the antigenic profile of the tubular epithelium and thereby may initiate a cell mediated immune response, accounting for the observed tubulitis and interstitial inflammation; and (3) ischemia may well be the final common pathway for chronic tubulointerstitial nephritis of diverse etiologies.
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PMID:Experimental chronic renal ischemia: morphologic and immunologic studies. 138 Jan 4

Transient forebrain ischemia of 30 min duration was produced in anaesthetized rats by four-vessel occlusion. After survival periods of 3 h to three days brains were perfusion-fixed and sections through the mid-dorsal hippocampus were processed for conventional staining and immunohistochemical analysis. Neuronal damage in the hilus was manifested 3-8 h after ischemia; neurons in the CA1 and CA2 sector suffered delayed neuronal death after 48-72 h whereas the dentate gyrus and the CA3 sector were normal. Vasogenic edema formation was visualized using antibodies against rat serum-proteins, serum albumin and immunoglobulins. By 3 h after ischemia, only faint and diffuse serum-staining was detected. At 8 h survival, weak astrocytic-staining was present. After 24-72 h CA1-CA2 exhibited massive serum extravasation. The molecular layer of the dentate gyrus showed edema formation in the absence of granule cell damage. The glial reaction was studied using antibodies against glial fibrillary acidic protein, vimentin and S-100 protein. Glial fibrillary acidic protein and S-100 protein-staining increased in areas with either edema or neuronal damage. In contrast, changes in vimentin were only detected in areas with neuronal necrosis. The observations demonstrate that following 30 min of ischemia neuronal damage is accompanied by changes in blood-brain barrier function and reactive glial alterations. The dissociation between neuronal necrosis and astroglial hypertrophy and hyperplasia reflects differences in cellular responsiveness which constitute inherent features of postischemic hippocampal injury.
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PMID:Immunohistochemical study of glial reaction and serum-protein extravasation in relation to neuronal damage in rat hippocampus after ischemia. 170 95

Cytoskeletal proteins (i.e., cytokeratins, vimentin, actin, and desmin) are normally present in the placental chorionic villi and are related to the maintenance of the villous shape, and to the ability of the villi to contract and permit a normal blood flow. In areas of villitis of unestablished etiology, the normal reactivity of these proteins in the villous core around fetal stem vessels disappears, and an increased number of cytokeratin positive cells is identified. The vascular damage in stem villi with villitis could develop ischemia in the villous tree promoting cytotrophoblast proliferation. Increased numbers of these areas could be related with the appearance of abnormal pregnancies.
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PMID:Cytoskeletal proteins in chronic villitis of unestablished etiology. 171 12

Involvement of the IEGs in brain injury and ischemia is under intensive investigation (Gubits et al., 1993). There are several families of the IEGs. They include the fos, jun, and zinc finger genes that encode transcription factors. Products of the fos family (c-fos, fra-1, fra-2, and fos B) bind to members of the jun family (c-jun, jun B, jun D) via leucine zippers, and this dimer then binds to the AP-1 site (consensus sequence -TGACTCA-) in the promoter of target genes, which in turn regulate the expression of late response genes that produce long-term changes in cells. For example, c-fos may regulate the long-term expression of preproenkephalin, nerve growth factor, dynorphin, vasoactive intestinal polypeptide, tyrosine hydroxylase and other genes with AP-1 sites in their promoters (Curran and Morgan, 1987; Sheng and Greenberg, 1990). It is likely that the c-fos gene up-regulation observed in ischemic astrocytes leads to the changes observed in the expressions of hsp and cytoskeleton protein genes in this experimental model. This is supported by the findings of Sarid (1991) and Pennypacker et al. (1994) who have shown that AP-1 DNA binding activity in hippocampus recognized an AP-1 sequence from the promoter region of the GFAP which is a potential target gene. van de Klundert et al. (1992) also suggested the involvement of AP-1 in transcriptional regulation of vimentin. IEGs can be induced within minutes by extracellular stimuli including transmitters, peptides, and growth factors. In this study, we have shown that c-fos induction by ischemia was rapid and transient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gene expression in astrocytes during and after ischemia. 756 84

The aim of this study was to characterize the microglial and astroglial reactions to degeneration of (a) hippocampal CA1 pyramidal cells and dentate hilar neurons induced by cerebral ischemia and (b) CA3 pyramidal cells and dentate hilar neurons induced by intraventricular injections of kainic acid (KA). The microglial reactions to ischemia, as monitored by histochemical staining for the enzyme nucleoside diphosphatase (NDPase) and immunohistochemical staining for the complement type 3 receptor (CR3), could be divided into (1) initial and generalized, but transient, reactions which also included areas devoid of subsequent neural degeneration and (2) protracted, degeneration-specific reactions in the areas with neural degeneration. Due to more widespread hippocampal involvement a similar distinction was not possible after KA lesions. After both ischemia and KA application the protracted degeneration-specific reactions were characterized by increased NDPase/CR3 reactivity and prominent morphological changes. In the dentate hilus, reactive microglial cells clustered around the degenerating hilar neurons. In stratum radiatum of CA1, reactive microglial cells transformed into either (1) "rod cells," aligned along the postischemic, degenerating pyramidal cell dendrites, followed by subsequent transformation into ameboid-like cells, or (2) "bushy" cells, in response to degeneration of Schaffer collaterals induced by KA lesioning of CA3 pyramidal cells. Within stratum radiatum of the KA-lesioned CA3, where both dendrites and axons were degenerating, the microglial cells developed into stellate cells with thickened, retracted processes and plump cell bodies. These cells were supplemented by rounded macrophage-like cells. Astroglial reactions, monitored by immunohistochemical staining for the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin (VIM), and the normal plasma constituent immunoglobulin G (IgG), showed an initial and generalized astroglial immunoreactivity for IgG, which paralleled the initial and transient microglial reactions, while the reactive changes in GFAP and VIM immunohistochemistry paralleled the protracted, degeneration-specific reactions with regard to timing, strength, and distribution. In the KA-lesioned CA3, the most prominent finding was a prompt loss of astroglial GFAP immunoreactivity corresponding to the degenerating pyramidal cell layer and the adjacent mossy fiber layer. The results strongly indicate that stimuli other than neural degeneration initiated the activation of both microglial and astroglial cells, which then upon further activation by actual neuronal damage and degeneration adjust according to which neuronal structures were undergoing degeneration.
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PMID:Microglial and astroglial reactions to ischemic and kainic acid-induced lesions of the adult rat hippocampus. 768 70

This study investigated astroglial responses after focal cerebral ischemia in the rat cortex induced by photothrombosis. Astrocyte activation was studied at various time points by immunocytochemistry for glial fibrillary acidic protein (GFAP) and vimentin (VIM). We found a dual astrocytic response to focal ischemia: In the border zone of the infarct, GFAP-positive astrocytes were present within 2 days and persisted for 10 weeks. These astrocytes additionally expressed VIM. Remote from the ischemic lesion, cortical astrocytes of the entire ipsilateral hemisphere transiently expressed GFAP, but not VIM, beginning on day 3 after photothrombosis. This response had disappeared on day 14. By recording DC potentials, five to seven spreading depressions (SD) could be detected on the cortical surface during the first 2 h after photothrombosis. Treatment with MK801, a non-competitive NMDA-receptor antagonist, completely abolished SD and remote ipsilateral astrocytic activation, while the reaction in the border zone of the infarct remained unchanged. Functionally, persistent astrocytosis around the infarct might be induced by leukocyte-derived cytokines, while NMDA-receptor-mediated SD might cause remote responses.
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PMID:Astroglial responses in photochemically induced focal ischemia of the rat cortex. 854 65

Reactive astrocytes influence not only the severity of brain injury, but also the capacity of brain to reshape itself with learning. Mechanisms responsible for astrogliosis remain unknown but might be best studied in vitro, where improved access and visualization permit application of modern molecular and cellular techniques. We have begun to explore whether gliosis might be studied in hippocampal organotypic cultures (HOTCs), where potential cell-to-cell interactions are preserved and the advantages of an in vitro preparation are still realized. Following HOTC exposure to N-methyl-D-aspartate (NMDA), dose-dependent changes occurred in the optical density (OD) values for the astrocytic immunohistochemical [immunostaining (IS)] markers glial fibrillary acidic protein (GFAP) and vimentin. Exposure of HOTCs to NMDA (10 microM) caused selective death in the CA1 hippocampal region and the dentate gyrus. It also significantly increased GFAP IS and vimentin IS OD values in these regions. Increased GFAP IS and vimentin IS OD values were also seen in CA3, a hippocampal region that displayed no cell death. Light microscopic examination revealed hypertrophied GFAP and vimentin IS cells, characteristic of reactive astrocytes. Cellular proliferation, as assessed by proliferating cell nuclear antigen IS, was also significantly increased in all three of these hippocampal regions. In contrast, exposure of HOTCs to a noninjurious level of NMDA (1 microM) caused only minor changes in GFAP IS and vimentin IS OD values but a significantly reduced cellular proliferation in all HOTC regions. These results show that reactive astrocytosis from excitotoxic injury of HOTC parallels changes seen in vivo after global ischemia. Furthermore, since resting astroglia within HOTCs are also similar to their counterparts in vivo, HOTCs may be used to examine mechanisms by which these cells are transformed into reactive species within tissue that resembles intact brain.
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PMID:Reactive astrocytosis from excitotoxic injury in hippocampal organ culture parallels that seen in vivo. 897 84

Proliferation and dedifferentiation of tubular cells are the hallmark of early regeneration after renal ischemic injury. Vimentin, a class III intermediate filament expressed only in mesenchymal cells of mature mammals, was shown to be transiently expressed in post-ischemic renal tubular epithelial cells. Vimentin re-expression was interpreted as a marker of cellular dedifferentiation, but its role in tubular regeneration after renal ischemia has also been hypothesized. This role was evaluated in mice bearing a null mutation of the vimentin gene. Expression of vimentin, proliferating cell nuclear antigen (a marker of cellular proliferation), and villin (a marker of differentiated brush-border membranes) was studied in wild-type (Vim+/+), heterozygous (Vim+/-), and homozygous (Vim-/-) mice subjected to transient ischemia of the left kidney. As expected, vimentin was detected by immunohistochemistry at the basal pole of proximal tubular cells from post-ischemic kidney in Vim+/+ and Vim+/- mice from day 2 to day 28. The expression of the reporter gene beta-galactosidase in Vim+/- and Vim-/- mice confirmed the tubular origin of vimentin. No compensatory expression of keratin could be demonstrated in Vim-/- mice. The intensity of proliferating cell nuclear antigen labeling and the pattern of villin expression were comparable in Vim-/-, Vim+/- and Vim+/+ mice at any time of the study. After 60 days, the structure of post-ischemic kidneys in Vim-/- mice was indistinguishable from that of normal non-operated kidneys in Vim+/+ mice. In conclusion, 1) the pattern of post-ischemic proximal tubular cell proliferation, differentiation, and tubular organization was not impaired in mice lacking vimentin and 2) these results suggest that the transient tubular expression of vimentin is not instrumental in tubular regeneration after renal ischemic injury.
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PMID:Normal tubular regeneration and differentiation of the post-ischemic kidney in mice lacking vimentin. 909 92

A case of atypical decubital fibroplasia of the right forearm arising in a 25-year-old male with melorheostosis is presented. The diagnosis of melorheostosis involving the right-sided bones was made by radiographical studies, and the patient has been obliged to use crutches due to the contracture and limited range of motion of the right leg. Two painless masses occurred in the subcutis of the posterior aspect of the right forearm over the excrescences of the underlying ulna due to melorheostotic deformity. Grossly, ill-defined firm masses, which measured 3 x 6 x 1.5 cm and 4 x 5 x 1 cm, respectively, were white and intermingled with yellow fatty tissue. Histologically, the lesions consisted of a proliferation of plump fibroblastic cells with abundant collagenous stroma. Vascular proliferation and occasional eosinophilic degeneration of the collagen fibers were also seen. The gross and histological features were those of atypical decubital fibroplasia (ischemic fasciitis). Immunohistochemically, the plump fibroblastic cells were positive for vimentin, but negative for desmin, muscle specific actin, and alpha-smooth muscle actin. Chondroid metaplasia was focally noted and round-shaped cells within this area were positive for S-100 protein. This lesion seemed to be a fibroblastic response against the long-standing, intermittent ischemia of the subcutaneous tissue between the bony excrescences due to melorheostosis and the weight-bearing forces of the crutch.
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PMID:Atypical decubital fibroplasia in a young patient with melorheostosis. 958 81


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