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

In focal ischaemia, the penumbra defines regions with blood flow below that needed to sustain electrical activity, but above that required to maintain cellular ionic gradients, and that lead in time to infarction. Among other terms used to describe regions surrounding the ischaemic core, "penumbra" is the only one based on a precise functional state of partially ischaemic tissue. The precarious balance between energy supply and demand that characterizes the penumbra and the proximity of the ischaemic core are the basis of a number of important features: (a) It is a time-limited condition, with a tendency to evolve towards infarction and to propagate to adjacent viable tissue; (b) "misery perfusion" is associated with increased oxygen extraction, acidosis, and high glucose utilization, but residual ATP; (c) recurrent spreading depression contributes to the deterioration of the penumbra, at least in animal models of stroke; (d) there is no sustained increase of extracellular glutamate; and (e) improvement of local perfusion and reduction of energy demand remain the most rational approaches to rescue the penumbra. By defining a window of opportunity for therapeutic intervention in stroke, the concept of ischaemic penumbra has enormously stimulated research in this field and led to a better understanding of the pathophysiology of cerebral ischaemia, with direct practical application for the surgical management of cerebrovascular disorders such as aneurysms.
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PMID:The ischaemic penumbra: twenty years on. 870 72

While case fatality rates in ischemic stroke tend to decline, the total number of strokes is expected to increase further in the future because of more people reaching a greater age. Acute ischemic stroke, usually caused by chronic arterial hypertension, in most cases is induced either by a sudden loss of perfusion pressure or by thromboembolism. Reduction of oxygen supply to brain tissue then leads to a cascade of biochemical reactions. Cell death finally occurs after massive Ca2+ influx into the cell and breakdown of the membranes. A rim of viable tissue called the penumbra often exists around a central necrotic core within the ischemic region. The tissue compartment may be brought back to function if perfusion is restored within a short time. Since some cytotoxic reactions within ischemic tissue are irreversible, current efforts in stroke therapy focus on measures to decrease cellular vulnerability. Restoring perfusion remains the first important therapeutic goal. A variety of compounds have been tested for cytoprotection, but none can yet be recommended for routine clinical use. General management of stroke patients in every case should be implemented for emergency assessment, since the first few hours after onset are crucial for the outcome.
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PMID:Acute ischemic stroke. 871 90

During focal cerebral ischemia, irreversible changes occur at the core of the lesion, whereas energy metabolism and ion homeostasis are preserved in the surrounding penumbra. Not all brain cells are killed at the start of a stroke; some are destroyed hours or days later, usually by toxins released during the early stages. Time is therefore the critical factor in treating acute ischemic stroke. Early management by the neurologist is associated to better functional outcome and shorter hospital stays. Patient evaluation and treatment must therefore take place as soon as possible.
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PMID:[Latency times and preadmission procedures]. 871 44

Changes in diffusion NMR imaging are believed to be based on intra/extracellular water homeostasis and will therefore reflect early disturbances of ion and water homeostasis after the onset of an ischemic event. Diffusion-weighted NMR imaging (DWI) thus has the potential to be a sensitive tool for the observation of stroke evolution. The present state of information extracted from diffusion-weighted NMR imaging for the understanding of cerebral focal ischemia in experimental research has been compiled in this review. The emphasis was set on three essential aspects of the technique in relation to focal ischemia. Firstly, the sensitivity of diffusion-weighted imaging for ischemic alterations is described. A comparison with conventional NMR imaging using relaxation time changes is included. Secondly, the comparison of the diffusion-weighted imaging with invasive techniques is discussed. Here, interpretation of the physiological, metabolic and hemodynamic alterations reflected in the observed diffusion changes is presented. The importance of regionally resolved information for a meaningful assignment of DWI changes to pathophysiological alterations is demonstrated for the differentiation between ischemic core and penumbra from DWI and quantitative diffusion coefficient data. The time dependence of correlations with physiological, biochemical and hemodynamic variables as a further important aspect is stressed. Thirdly, the potential of the technique for the assessment of development and effectiveness of new therapeutical strategies against stroke is demonstrated.
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PMID:Diffusion-weighted NMR imaging: application to experimental focal cerebral ischemia. 873 71

We investigated whether the known neuroprotective effects of two selective glutamate receptor antagonists, the NMDA antagonist MK-801 and the AMPA antagonist NBQX, are reflected in the regional cerebral protein synthesis rates (CPSR) in rats with middle cerebral artery occlusion (MCAO). Rats treated with either saline, MK-801 (5 mg/kg i.p.) or NBQX (30 mg/kg i.p. x 3) were subjected to permanent MCAO. Regional CPSR and volumes of gray matter structures displaying normal CPSR were measured in coronal cryosections of the brain by quantitative autoradiography following an i.v. bolus injection of 35S-labelled L-methionine 2 h after occlusion. MCAO completely inhibited protein synthesis in the lateral part of striatum and part of the adjacent frontoparietal cortex corresponding to the ischemic focus. Surrounding this, a metabolic penumbra with approximately 50% reductions in CPSR was present. Treatment with MK-801 significantly increased the volume of tissue with normal CPSR in the ischemic hemisphere compared to controls, whereas this was not seen with NBQX treatment. The results suggest that MK-801 and NBQX have different effects on peri-infarct protein synthesis after MCAO. Since both compounds reduce infarct size, it is questionable that acute inhibition of protein synthesis in focal ischemia is of significant importance to the final outcome of a stroke lesion.
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PMID:Differential effect of NMDA and AMPA receptor blockade on protein synthesis in the rat infarct borderzone. 874 Nov 37

We prospectively tested the hypothesis that early recovery after ischemic stroke depends on the ultimate survival of functionally impaired, critically ischemic (i.e., "penumbral") tissue. From a series of 26 consecutive patients studied with positron emission tomography within 18 hours of first-ever stroke in the middle cerebral artery territory, all 11 survivors to the 2-month end point who exhibited increased oxygen extraction fraction were declared eligible. The positron emission tomographic images were compared to ultimate infarction defined by computed tomography performed during the chronic stage. The penumbra (operationally defined by increased oxygen extraction fraction and divided outcome despite uniformly reduced cerebral blood flow) was individually detected in 10 of the 11 patients; cerebral blood flow ranged from 7 to 17 ml/100 gm x min, consistent with that found in monkey studies. The volume of the penumbra that escaped infarction was highly correlated with neurological recovery (p < 0.04 to p < 0.0001, depending on the scale used). This longitudinal study is the first to characterize the penumbra in humans and to document one mechanism strongly influencing recovery; the surviving penumbra may offer opportunities for secondary perifocal neuronal reorganization. Therapeutic measures to prevent infarction of the penumbra (up to 16 hours in this series) may have reduced residual neurological impairment. Mapping the extent of the penumbra, according to prospective criteria, may allow one to predict each patient's potential for recovery, and to select the most appropriate candidates for therapeutic trials.
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PMID:Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra. 906 66

Cellular mechanisms, both destructive and protective, that are associated with cerebral ischemia are reviewed in this paper. Central to understanding the evolution of stroke are the concepts of ischemic core and surrounding penumbral region damage, delayed neuronal death, and neuronal rescue. The role of spreading depression in the evolution of subsequent ATP depletion, ion shifts, glutamate release, activation of glutamate receptors, intracellular Ca2+ changes, and generation of reactive oxygen species in the penumbra in relationship to neuronal and glial cell damage are discussed. We conclude that the most fruitful areas for future stroke research include traditional approaches as well as novel approaches. Traditional approaches include stroke prevention and examination of the effects of combinations of proven and promising effective therapeutic interventions. Novel approaches include delineating mechanisms whereby growth factors and compounds such as deprenyl and staurosporine afford neuroprotection, ultimately leading to direct manipulation of the signal transduction pathways that lead to neuronal dysfunction and death. This includes determining which genes are activated and repressed in specific response to hypoxia-ischemia and determining how such alterations in gene expression affect survival and function of neurons. We also suggest that advantage be taken of the blood-brain barrier compromise during stroke in designing neuroprotective therapies.
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PMID:Cellular mechanisms involved in brain ischemia. 878 4

The protective effect of nilvadipine, a Ca2+ antagonist, on cerebral ischemia was investigated in spontaneously hypertensive rats. The 12-week-old animals were treated for 7 days with either nilvadipine or vehicle using osmotic pumps implanted subcutaneously. Group 1 animals (n = 10) received the vehicle, and Group 2 (n = 10) and 3 animals (n = 10) received 1 and 3 mg/kg/day nilvadipine, respectively. The left middle cerebral artery was occluded under halothane anesthesia on the 6th day of treatment, and neuropathological outcomes were quantified 24 hours later. The systolic blood pressure measured before occlusion decreased to 137 +/- 9 mmHg (Group 2) and 130 +/- 9 mmHg (Group 3), compared to 189 +/- 12 mmHg for Group 1 (p < 0.05). The percentage infarct volumes in Groups 1-3 were 39 +/- 3%, 37 +/- 2%, and 34 +/- 3%, respectively (p < 0.05, Groups 1 vs. 3). Therefore, nilvadipine decreased the infarct size dose-dependently. Nilvadipine has a protective effect against cerebral ischemia in rats with chronic hypertension. Neuropathological findings suggest that nilvadipine may act at the ischemic penumbra. Nilvadipine may have the additional benefit of reducing the consequences of a possible later stroke in patients with hypertension (one of the risk factors for stroke).
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PMID:Protective effect of nilvadipine on focal cerebral ischemia in spontaneously hypertensive rats. 886 50

The aim of the study was to compare the first-passage profiles of dysprosium diethylenetriamine penta-acetic acid bis(methylamide) (DTPA BMA) and the superparamagnetic iron oxide particles NSR 0430 in regions with severe and moderate cerebral ischemia. In seven rats subjected to middle cerebral artery occlusion, two dynamic MR perfusion imaging series were acquired after intravenous bolus injections of .5 mmol/kg dysprosium DTPA BMA and .06 mmolFe/kg iron oxide particles, respectively. The doses were chosen to obtain similar maximum signal change in normally perfused brain. The first-passage profiles were compared in a region of interest (ROI) in the core area with severe ischemia and in a ROI in the penumbra area of moderate ischemia. The results were compared both as the calculated mean signal intensity versus time curves for all seven rats and statistically for an estimated mean transit time (MTT) after gamma variate fitting of the calculated concentration versus time curves. The first-passage profiles for the two contrast agents were similar, both in the core area of severe ischemia and in the penumbra area of moderate ischemia. In this rat stroke model, dysprosium DTPA BMA and the superparamagnetic iron oxide particles NSR 0430 were found to be equally efficacious for the diagnosis of the perfusion deficit, but if safe for human investigations, iron oxide particles would have an advantage as equal susceptibility effect may be achieved with smaller injection volumes.
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PMID:Comparison of dysprosium DTPA BMA and superparamagnetic iron oxide particles as susceptibility contrast agents for perfusion imaging of regional cerebral ischemia in the rat. 889 8

Reliable, simple and safe criteria are needed for the early prediction of short-term outcome in patients with acute ischemic stroke. The aim of our study was to evaluate, in terms of their individual and combined power, the prognostic value of a few widely available clinical and instrumental variables obtained during the acute phase. The study involved 351 consecutive patients who were examined within 48 hours of their first ischemic stroke. Eight variables were chosen: age, initial level of consciousness, limb paresis, arterial blood pressure, glycemia, the results of electrocardiography and electroencephalography, and the infarct size revealed by computed tomography. Mortality and disability were evaluated on Day 30, when the variables that significantly correlated with disability were the severity of limb paresis, electroencephalographic abnormalities, infarct size and (less significantly) the level of consciousness and hyperglycemia. There was no statistical correlation with blood pressure. Logistic analysis confirmed only infarct size, the severity of limb paresis and electroencephalographic abnormalities as independent variables. The variables that significantly correlated with early death were the severity of limb paresis, infarct size, electrocardiographic abnormalities, the level of consciousness, electroencephalographic abnormalities and hyperglycemia. More intriguingly, logistic analysis confirmed only the electroencephalographic and electrocardiographic abnormalities as independent variables. The predictive prognostic value of limb paresis, infarct size, the level of consciousness and hyperglycemia is well known, but we would like to stress the fact that only a few independent variables are predictive of early death (electroencephalographic and electrocardiographic abnormalities) and poor recovery (infarct size, the severity of limb paresis, electroencephalographic abnormalities). The prognostic value of electroencephalography may express the potential involvement of dynamic non-structural phenomena, such as penumbra ischemica and diaschisis.
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PMID:Value of early variables as predictors of short-term outcome in patients with acute focal cerebral ischemia. 893 27


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