Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microglial cell activation is a rapidly occurring cellular response to cerebral ischaemia. Microglia proliferate, are recruited to the site of lesion, upregulate the expression of several surface molecules including major histocompatibility complex class I and II antigens, complement receptor and the amyloid precursor protein (APP) as well as newly expressed cytokines, e.g. interleukin-1 and transforming growth factor beta 1. The ischaemia-induced production of APP may contribute to amyloid deposition in the aged brain under conditions of hypofusion. Ultrastructurally, microglia transform into phagocytes removing necrotic neurons but still respecting the integrity of eventually surviving neurons even in the close vicinity of necrotic neurons. Microglial activation starts within a few minutes after ischaemia and thus precedes the morphologically detectable neuronal damage. It additionally involves a transient generalized response within the first 24 hours post-ischaemia even at sites without eventual neuronal cell death. In functional terms, the microglial reaction appears to be a double-edged sword in ischaemia. Activated microglia may exert a cytotoxic effector function by releasing reactive oxygen species, nitric oxide, proteinases or inflammatory cytokines. All of these cytotoxic compounds may cause bystander damage following ischaemia. Pharmacological suppression of microglial activation after ischaemia has accordingly attenuated the extent of cell death and tissue damage. However, activated microglia support tissue repair by secreting factors such as transforming growth factor beta 1 which may limit tissue damage as well as suppress astroglial scar formation. In line with ultrastructural observations microglial activation in ischaemia is a strictly controlled event. By secreting cytokines and growth factors activated microglia most likely serve seemingly opposed functions in ischaemia, i.e. maintenance as well as removal of injured neurons. Post-ischaemic pharmacological modulation of microglial intervention in the cascade of events that lead to neuronal necrosis may help to improve the structural and functional outcome following CNS ischaemia.
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PMID:Reactive microglia in cerebral ischaemia: an early mediator of tissue damage? 749 96

Focal cerebral ischemia in the adult rat produces induction of 72-kDa heat shock protein (HSP-72) in neurons, glia and endothelial cells. Double antigen immunocytochemistry was carried out to find out whether microglial cells express HSP-72 following 1-h middle cerebral artery (MCA) occlusion. A monoclonal antibody against the CR3 complement receptor (OX-42) specific for microglia was used followed by a monoclonal antibody against HSP-72. Co-localization of these antibodies was seen in cells of the ipsilateral corpus callosum and striatum at 3 h following 1-h MCA occlusion, and in the ipsilateral striatal penumbra, corpus callosum and cortex at 8 h. Results demonstrate that stellate microglial cells show an early response to 1-h MCA occlusion by expressing inducible HSP-72, thus suggesting that microglial cells are sensitive to the ischemic insult.
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PMID:Early 72-kDa heat shock protein induction in microglial cells following focal ischemia in the rat brain. 771 11

In order to evaluate the involvement of inflammatory reactions following focal cerebral ischemia in the rat, we immunohistochemically visualized microglial cells and blood-borne leukocytes (neutrophils and monocytes) using various antibodies directed against immunomolecules expressed on these cells. Focal cerebral ischemia was produced by intraluminal occlusion of the right middle cerebral artery for 1 h. The brains were perfusion-fixed at 4 h, 1 day, 3 days, 7 days and 14 days after ischemia. Frozen brain sections were prepared and stained with monoclonal antibodies to complement receptor type 3 (OX42), major histocompatibility complex (MHC) class I and class II antigens (OX18 and OX6, respectively), a pan-macrophage/monocyte marker (ED1), intercellular adhesion molecule-1 (ICAM-1), LFA-1 alpha chain (CD11a) and beta chain (CD18), and T cells (CD5). In ischemic areas where infarction developed later, microglial cells were destroyed (beginning at 4 h), neutrophils migrated (1-3 days), and then monocytes/macrophages infiltrated and covered the entire lesions (3-14 days). The invading leukocytes expressed CD11 and CD18 adhesion molecules on their cell surface while ICAM-1 was expressed on endothelial cells. In surrounding areas, in contrast, there was a rapid activation of microglia showing morphological changes and upregulation of OX42 immunoreactivity (4 h-7 days), especially in the transitional rim of the infarct (7 days). ED1 and MHC antigens were expressed on both activated microglia and invading leukocytes. Thus, developing infarction was accompanied by accumulation of inflammatory cells of both intrinsic (microglia) and extrinsic (leukocytes) origins. Thus, results suggest that the relative importance of each source is determined by the time after ischemia and the site within the lesion, and that the expression of immunological molecules plays an important role in eliciting such inflammatory reactions.
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PMID:Progressive expression of immunomolecules on activated microglia and invading leukocytes following focal cerebral ischemia in the rat. 889 26

We investigated the temporal course of microglia activation in different brain regions after permanent middle cerebral artery (MCA) occlusion in mice and compared this microglia response with the appearance of apoptotic cells, Microglia activation and morphological changes of microglial cells were visualized using an immunohistochemical method with a polyclonal antibody recognizing the mouse CR3 complement receptor. Cells showing morphological and biochemical features of apoptosis were identified using the terminal deoxynucleotidyl transferase nick end-labeling (TUNEL) method and light microscopy. As early as 30 min after onset of MCA occlusion activated microglia with hypertrophic cell bodies and stout processes were detected in the periphery of the ischemic lesion as identified by diffusion-weighted magnetic resonance imaging. A wider distribution and a progressive increase in the number of activated microglia was found with increasing time. Only few TUNEL-positive cells with apoptotic features were observed within the lesion area at 6 h after onset of cerebral ischemia. From 12 h after MCA occlusion onward a tremendous increase in the number of TUNEL-positive cells was found. Within the thalamus from 24 h onward microglia cells with few processes, irregular morphology and fragmented appearance were detected. Microglia activation in the thalamus progressed up to 4 weeks after MCA occlusion, but had declined after 90 days. Neuronal degeneration in the thalamus as determined by anti-neuronal nuclei immunohistochemistry progressed from 6 days after MCA occlusion onward. Only a few TUNEL-positive cells were found in the thalamus. In summary, microglia activation both in the primary cortical lesion area and in the secondarily affected thalamus preceded the manifestation of tissue injury. These observations encourage further studies on the role of microglia in focal cerebral ischemia.
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PMID:Time course of microglia activation and apoptosis in various brain regions after permanent focal cerebral ischemia in mice. 970 33

The mechanisms that contribute to inflammatory damage following ischemic stroke are poorly characterized, but studies indicate a role for both complement and P-selectin. In this study, we show that compared with wild-type mice, C3-deficient mice showed significant improvement in survival, neurological deficit, and infarct size at 24 h after middle cerebral artery occlusion and reperfusion. Furthermore, P-selectin protein expression was undetectable in the cerebral microvasculature of C3-deficient mice following reperfusion, and there was reduced neutrophil influx, reduced microthrombus formation, and increased blood flow postreperfusion in C3-deficient mice. We further investigated the use of a novel complement inhibitory protein in a therapeutic paradigm. Complement receptor 2 (CR2)-Crry inhibits complement activation at the C3 stage and targets to sites of complement activation. Treatment of normal mice with CR2-Crry at 30 min postreperfusion resulted in a similar level of protection to that seen in C3-deficient mice in all of the above-measured parameters. The data demonstrate an important role for complement in cerebrovascular thrombosis, inflammation, and injury following ischemic stroke. P-selectin expression in the cerebrovasculature, which is also implicated in cerebral ischemia and reperfusion injury, was shown to be distal to and dependent on complement activation. Data also show that a CR2-targeted approach of complement inhibition provides appropriate bioavailability in cerebral injury to enable complement inhibition at a dose that does not significantly affect systemic levels of serum complement activity, a potential benefit for stroke patients where immunosuppression would be undesirable due to significantly increased susceptibility to lung infection.
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PMID:Complement-dependent P-selectin expression and injury following ischemic stroke. 1708 45