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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemic stroke results from a reduction in cerebral blood flow to a focal region of the brain after the occlusion of an artery, causing damage to nervous tissue. There is a region of cerebral ischemic tissue (penumbra) surrounding an acute cerebral infarct that is dysfunctional but potentially viable. Restoration of perfusion in the penumbra may ameliorate the tissue damage. The identity and the role of growth factors that control the extent of tissue damage and its repair are poorly understood. Angiogenesis has been demonstrated to occur in brain tissues of patients surviving an acute ischemic stroke. In this paper we have investigated the status of a potent angiogenesis factor, vascular endothelial growth factor (VEGF), in patients after acute ischemic brain stroke. Western blotting and immunohistochemistry were used to determine protein expression, and in situ hybridization was used to quantify and localize mRNA synthesis. The expression of VEGF protein was increased in the penumbra compared with infarcted brain and contralateral hemisphere. Neurones, endothelial cells, and astrocytes in the penumbra in all patients studied had significant up-regulation of both VEGF165 and VEGF189 mRNA (p < 0.01, Wilcoxon Matched-Pairs Signed-Ranks Test) compared with infarcted tissue and the normal looking contralateral hemisphere that was used as a control. Immunohistochemistry demonstrated that kinase insert domain receptor was present in blood vessels within the infarct/penumbra and absent from the normal contralateral hemisphere. VEGF, which is important in angiogenesis, may also influence long term neuronal survival, and possibly its modulation may prove to be of therapeutic value for patients with ischemic stroke.
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PMID:Vascular endothelial growth factor and its receptor, KDR, in human brain tissue after ischemic stroke. 1021 94

C57Black/6 and SV129 mice are widely used for the production of transgenic mutants in molecular stroke research but the ischemic susceptibility of these strains is influenced by differences in vascular anatomy and the responsiveness to excitotoxins and vasodilatory stimuli. To differentiate between these opposing effects on infarct size, the vascular territory of the two strains was correlated with the hemodynamic, metabolic, and morphological consequences of permanent middle cerebral artery (MCA) occlusion. The vascular anatomy was studied by latex infusion, brain infarction by vital staining, the size of the ischemic penumbra by imaging of ATP and protein synthesis, and blood flow by laser-Doppler flowmetry. In C57Black/6 mice the MCA-supplied vascular territory and the size of brain infarcts were significantly larger than in SV129 mice but the size of the penumbra and the residual blood flow in the center of the MCA-supplying territory were similar in both strains. These findings suggest that differences in infarct size in C57Black/6 and SV129 mice are determined mainly by the vascular anatomy and not by differences in collateral vascular responsiveness or excitotoxicity.
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PMID:Regional metabolic disturbances and cerebrovascular anatomy after permanent middle cerebral artery occlusion in C57black/6 and SV129 mice. 1034 25

The ischaemic penumbra has been documented in the laboratory animal as a severely hypoperfused, non-functional, but still viable cortex surrounding the irreversibly damaged ischaemic core; with elapsing time, more penumbra gets recruited into the core, while tissue reperfusion is able to stop this deleterious process until a certain point in time. As saving the penumbra should improve clinical outcome, it should constitute the main target of acute stroke therapy. In a series of PET studies performed 5-18 h after stroke onset, we were able to (i) document, for the first time in man, the existence of tissue fulfilling operational criteria for penumbra in about one third of the cases; (ii) show that long-term neurological recovery is proportional to the volume of penumbra that eventually escapes infarction, and (iii) detect penumbral tissue as late as 16 h after symptom onset in occasional patients, suggesting the therapeutic window may be protracted in such cases. Mapping the penumbra in the individual patient with neuroimaging procedures should allow to formulate a pathophysiological diagnosis, and thus to design a rational management of the stroke patient and to improve the selection of candidates for therapeutic trials.
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PMID:Mapping the ischaemic penumbra with PET: implications for acute stroke treatment. 1039 5

Astrocytes cope more readily with hypoxic insults than do neurons. We hypothesized that astrocytes can upregulate their glycolytic capacity, allowing anaerobic glycolysis to provide sufficient ATP for cell survival as well as for carrying out critical functions such as taking up glutamate. To test this hypothesis, astrocytes were subjected to hypoxia for 5 hr. Lactate dehydrogenase (LDH) and pyruvate kinase activities increased 3- to 4-fold. Examination of LDH isoenzyme patterns determined that it was the anaerobic isoenzymes that were upregulated. To determine whether increase in enzyme activity translates into increased glycolytic capacity, astrocytes were subjected to varying time periods of hypoxia, and glucose uptake was measured under conditions where astrocytes were forced to consume more ATP. This demonstrated that 8 hr of hypoxia resulted in a doubling of glycolytic capacity. We suggest that how quickly astrocytes upregulate glycolytic capacity may determine whether or not neurons within the stroke penumbra survive.
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PMID:Astrocytes respond to hypoxia by increasing glycolytic capacity. 1039 3

Proton magnetic resonance spectroscopy (1H MRS) permits the acquisition of the signal arising from several brain metabolites. At long echo-time (TE) 1H MRS can detect N-acetyl-aspartate containing compounds, choline containing compounds, creatine + phosphocreatine and lactate. At short TE, lipids, tryglicerides, alanine, glutamate, glutamine, GABA, scyllo-inositol, glucose, myo-inositol, carnosine and histydine are visible. 1H MRS can be performed with single-voxel, multivoxel, single slice and multislice techniques. With single voxel 1H MRS it is possible to measure metabolites relaxation time, which allows the measurement of metabolite concentrations. This technique can be useful in the study of focal lesions in the central nervous system (CNS) such as epilepsy (pre-surgical identification of epileptic focus), brain tumors (evaluation of recurrence and radiation necrosis), stroke, multiple sclerosis, etc. Single slice and multislice 1H MRS imaging (1H MRSI) can be performed only at long TE and permits the mapping of the brain metabolites distribution which makes them particularly useful in studying diffuse diseases and heterogeneous lesions of the CNS. 1H MRS can also be useful in the evaluation of 'ischemic penumbra' of stroke; developmental (myelin and neuronal dysgenesis); head trauma (evaluation of cerebral damage not visible with MRI); degenerative disorders (identification of microscopic pathology not visible with MRI); and metabolic diseases (metabolic disturbances with specific metabolic patterns).
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PMID:Proton MRS in neurological disorders. 1040 93

Brain injury following transient or permanent focal cerebral ischaemia (stroke) develops from a complex series of pathophysiological events that evolve in time and space. In this article, the relevance of excitotoxicity, peri-infarct depolarizations, inflammation and apoptosis to delayed mechanisms of damage within the peri-infarct zone or ischaemic penumbra are discussed. While focusing on potentially new avenues of treatment, the issue of why many clinical stroke trials have so far proved disappointing is addressed. This article provides a framework that can be used to generate testable hypotheses and treatment strategies that are linked to the appearance of specific pathophysiological events within the ischaemic brain.
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PMID:Pathobiology of ischaemic stroke: an integrated view. 1044 Dec 99

As the brain attack message is disseminated throughout our medical community and the awareness of the public increases, neurosurgeons will have the opportunity to treat patients with stroke at a much earlier time in the evolution of the process than we have been accustomed. Are the relatively unimpressive results of acute surgical intervention in patients operated on later in the course of the disease applicable to those who seek medical attention early, within the first few hours of ictus? There is little firm data. However, there is an overwhelming amount of anecdotal and experimental evidence supporting the potential for ultra-early intervention, which frequently should be surgical. New surgical techniques may improve safety and feasibility of emergent operations. In the coming years, diagnostic techniques such as perfusion/diffusion magnetic resonance imaging will allow the clinician to determine who may benefit from intervention. These determinations will be made on physiological data, addressing the issues of tissue viability and degree of compromise of the blood-brain barrier. In the future, the window of opportunity for intervention will not be solely a function of time from ictus or a qualitative impression based on collateral circulation as extrapolated from angiography, transcranial Doppler, or magnetic resonance angiography. These new magnetic resonance imaging techniques, which are beginning to be tested clinically or are still in the developmental stages, will provide the functional data now provided by positron emission tomography and xenon computed tomography, but with improved sensitivity, specificity, and logistical ease. Neurosurgeons have been leaders in stroke care and have provided some of the most important experimental rationale for the brain attack concept. These contributions include demonstration of the ischemic penumbra, the importance of time and potential collateral circulation as factors determining viability of ischemic tissue, and the value of early revascularization and many neuroprotective maneuvers in preserving brain tissue after arterial occlusion. There is every reason to preserve and to enhance the role of the neurosurgeon as a "stroke expert" and as a leading member of the brain attack team. Early access to patients with stroke will offer us the opportunity to test clinically, in a rigorous fashion, the value of surgical revascularization procedures (open or endovascular) and medical maneuvers that we have developed clinically and tested in the laboratory. We have shown, as we did with the bypass study, that neurosurgeons know how to perform these trials and abide by their results, even when they are not to our liking.
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PMID:Stroke: indications for emergent surgical intervention. 1046 8

During recent years it has been demonstrated that activated leukocytes may play a role in disturbances of flow in microcirculation, such disturbances leading to the enlargement of the necrosis zone and area of ischaemic penumbra. Astrocytes, microglial and endothelium cells are also active in the evolution of ischaemic changes in brain. The above cells are producing cytokines, which upregulate the expression of adhesion molecules being responsible for accumulation of inflammatory cells in injured brain. Very significant is also the secretion of neurotoxic substances such as free radicals, nitric oxide or proteolytic enzymes by leukocytes and glial cells. Pre-stroke infection may increase activation of leukocytes and enhance inflammatory process in ischaemic focus. This paper discusses also the results of a treatment of the experimental brain stroke using therapy which reduces inflammatory and immunological response.
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PMID:[Inflammatory changes and immunological disturbances in stroke]. 1046 35

What happens to the ischemic penumbra--defined as a territory of critically reduced blood flow in the close neighborhood of an ischemic core--determines outcome after stroke. Currently the pathophysiology of the penumbra is studied predominantly in rat models with occlusion of the middle cerebral artery. Here we propose two other rat models with distinct advantages. One produces a large territory of critical flow reduction in the cortex of one hemisphere without presence of an infarct core: this model is suited to study mediator mechanisms that may transform the penumbra into necrotic tissue. It is produced by occluding one carotid artery and in addition reducing arterial pressure to 50 mm Hg using the hypobaric hypotension technique. Cortical flow is assessed by laser Doppler scanning. The second mode involves the photochemical occlusion of two adjacent cortical veins and goes along with a rather widespread reduction of cortical flow and the development of small infarcts of 2-5 mm3 infarct volume. Like the first model it is suited to administer mediators causing the infarct to grow in size, and thereby to evaluate the pathophysiologic significance of individual mediator mechanisms. In addition the model can be used to study specific therapeutic approaches.
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PMID:Modelling of the ischemic penumbra. 1049 39

Extracellular lactate concentration rises following ischaemic stroke in both the infarcted area and in the surrounding ischaemic penumbra. We investigated the effect of lactate accumulation on glucose metabolism in cortical slices from guinea pigs initially by varying superfusion medium to tissue volumes. Stable intracellular K+ concentrations indicated that a decrease in media/ tissue volume did not impair viability of the tissue, but 13C NMR demonstrated that lactate accumulation in the superfusion medium reduced glucose oxidation with inhibition of glial metabolism via pyruvate carboxylase. The concentration of lactate which had accumulated when significant inhibition was observed was approximately 0.85 mM. In independent experiments we found that superfusion of brain slices with lactate at this concentration (even using a 'high-volume' of superfusion fluid) decreased oxygen consumption by 40 +/- 3%. K(-)-induced depolarisation partially reversed this effect. These results suggest that even low extracellular lactate concentrations may depress metabolic rates in inactive and poorly perfused brain tissue in vivo through inhibition of glial metabolism of glucose.
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PMID:Lactate-induced inhibition of glucose catabolism in guinea pig cortical brain slices. 1051 1


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