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

Acute perioperative anaemia may affect neurological injury from permanent focal ischaemic insults. We modelled the opposing effects of haemodilution (increasing cerebral blood flow, decreasing arterial oxygen content) on oxygen availability and uptake in the ischaemic penumbra. First, we validated a mathematical model of regional cerebral oxygen uptake by using published arterial oxygen content and cerebral blood flow values from normal rabbits with progressive anaemia. Then we applied the model to the problem of interest (i.e. the ischaemic penumbra of a focal embolic stroke). We re-analysed published experimental data giving the cerebral blood flow response to anaemia in the ischaemic penumbra. Penumbral extraction reserves were nearly exhausted at a haemoglobin concentration of approximately 10g 100ml-1. Oxygen uptake in the ischaemic penumbra decreased progressively when haemoglobin concentrations decreased to less than 10g 100ml-1. We conclude that, given the available clinical and experimental literature, and until a suitable randomized clinical study has been performed, a haemoglobin concentration of 10 g 100 ml-1 is the rational transfusion "trigger" for the acutely anaemic stroke patient.
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PMID:Effect of haemoglobin concentration on brain oxygenation in focal stroke: a mathematical modelling study. 938 54

This review focuses on the pathophysiological changes in acute cerebral ischemia, with special emphasis on disturbances of the cerebral blood flow (CBF) and the associated penumbra concept. Alternatively, the model of peri-infarct depolarization is demonstrated. Metabolic and molecular changes caused by cerebral ischemia and reperfusion are discussed, namely energy failure, release of glutamate with an excitatoric burst, calcium influx in neurons, generation of free radicals, activation of different proteases, disturbances of protein synthesis, induction of gene expression and apoptosis, loss of membrane integrity, edema formation and microvascular disturbances. In summary, the pathophysiological changes after focal cerebral ischemia and reperfusion are most adequately described by a network of interacting different mechanisms of tissue alterations. The simple concept of a cascade of ischemic effects which would be easy to block seems to be less applicable. A time window of approximately 6 h for the acute stroke therapy is postulated on the base of the above mentioned pathophysiological changes. The recently introduced treatment regimen with optimized basic treatment, recanalization using thrombolysis and neuroprotection by different agents is presented. Different modes of a possible intervention are discussed. Modern concepts of stroke therapy including stroke-unit care and thrombolysis with add-on neuroprotection seem to have potential for improving the outcome of acute stroke patients.
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PMID:[Acute cerebral infarct: physiopathology and modern therapeutic concepts]. 949 19

Stroke is one of the leading causes of death in the world. There are as yet no effective treatments for the ischemic cerebral lesion itself. Nevertheless, five potential therapeutic objectives can be identified. For cerebral infarction, the best treatment is prevention, including targeted preventive treatments for specific subsets of patients or individuals with different risk factors. Incidence rates and mortality rates of stroke have been successfully reduced in certain developed countries by adoption of a public health approach to the prevention and control of risk factors. To rescue the still viable but injured nerve cells, within the ischemic penumbra, effective therapy should be begun at the earliest possible time. Measures to halt or reverse programmed cell death, to enhance the intrinsic autoprotective and repair mechanisms, are under active study. The existence of down-regulated brain regions, where normal nerve cells have far less activities to perform due to interruption of information exchange with the infarct area, and the possibility to reactivate them are worthy of attention.
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PMID:A review of therapeutic potentials in ischemic stroke. 951 71

According to an epidemiological study of cerebrovascular disease carried out in China in 1986, the prevalence, incidence, and mortality rates were 159.93/100,000, 115.61/100,000, and 31.33/100,000, respectively. These figures were high compared to available epidemiological data for the rest of the world. This highlights the fact that, as in other countries, functional rehabilitation after stroke is an important medical and social need in China. Clinical experience shows that within a few hours to a few months after a stroke, a large proportion of patients spontaneously experience partial, or on occasion, complete recovery from neurologic symptoms. However, functional rehabilitation in medical care units is required because it assists in and accelerates the recovery of impaired function. Almitrine-raubasine has been used to improve functional rehabilitation after stroke for some time in China. By enriching the oxygen content of arterial blood, it brings more oxygen to the cerebral tissues and therefore promotes cerebral aerobic metabolism during ischemia. In the acute phase of stroke, positron emission tomography showed, in man, that almitrine-raubasine helps normalize the ischemic penumbra area, as shown by an improvement in the coupling between oxygenation and perfusion. Long after stroke, single photon emission computed tomography showed that almitrine-raubasine restores normal cerebral vasodilator response to acetazolamide. With a view to further documenting the clinical efficacy of almitrine-raubasine on the convalescent period of patients with cerebrovascular disease, a double-blind, placebo-controlled study is planned. One hundred patients with ischemic cerebrovascular disease in the territory of the carotid artery will be included 4-6 weeks after the acute onset. Two tablets daily of almitrine-raubasine or placebo will be prescribed for 3-6 months. Before treatment, there will be a 2-week washout period for all other drugs, except for antihypertensive and antidiabetic drugs. In addition to complete clinical monthly examinations, neurological functional deficit scores, Barthel index, Hasagawa Dementia scales, and CT scan are scheduled. The study results should confirm those reported in the scientific literature: although untreated patients may show spontaneous improvement, almitrine-raubasine should accelerate patients' functional rehabilitation.
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PMID:Stroke and functional rehabilitation: the Chinese experience. 951 72

A reproducible model of thread occlusion of the middle cerebral artery (MCA) was established in C57 Black/6J mice by matching the diameter of the thread to the weight of the animals. For this purpose, threads of different diameter (80 to 260 microns) were inserted into the MCA of animals of different weights (18 to 33 g), and the success of vascular occlusion was evaluated by imaging the ischemic territory on serial brain sections with carbon black. Successful occlusion of the MCA resulted in a linear relationship between body weight and thread diameter (r = 0.46, P < 0.01), allowing precise selection of the appropriate thread size. Laser-Doppler measurements of CBF, neurological scoring, and 2,3,5-triphenyltetrazolium chloride staining confirmed that matching of animal weight and suture diameter produced consistent cerebral infarction. Three hours after MCA occlusion, imaging of ATP, tissue pH, and cerebral protein synthesis allowed differentiation between the central infarct core, in which ATP was depleted, and a peripheral penumbra with reduced protein synthesis and tissue acidosis but preserved ATP content. Perfusion deficits and ischemic tissue alterations could also be detected by perfusion- and diffusion-weighted magnetic resonance imaging, demonstrating the feasibility of dynamic evaluations of infarct evolution. The use of multiparametric imaging techniques in this improved MCA occlusion model opens the way for advanced pathophysiological studies of stroke in gene-manipulated animals.
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PMID:A reproducible model of middle cerebral artery occlusion in mice: hemodynamic, biochemical, and magnetic resonance imaging. 953 1

A prerequisite for the successful treatment of acute ischaemic stroke is the existence of viable tissue that is morphologically intact but functionally impaired due to a flow decrease below a certain threshold. At this stage, tissue at risk of infarction can be identified only by functional imaging. This penumbral tissue can be classified as having a critical flow decrease with preservation of oxygen consumption and therefore increased oxygen extraction. Such 'misery-perfused' tissue has been observed consistently in the first few hours following ischaemic stroke but usually develops into necrosed tissue at follow-up observations. Several studies have indicated that penumbral tissue can be identified up to 17 h or even 48 h after stroke in the border zones of ischaemic tissue and that this condition is occasionally reversible without resulting in permanent infarction. Positron emission tomography studies of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2) and cerebral metabolic rate of glucose (CMRglc) can be used to demonstrate the effect of treatment on functional variables within tissue showing perfusional disturbances. Such studies have shown the value of these markers of ischaemia, which also correlate with clinical efficacy. However, when therapeutic strategies, such as thrombolysis, do not permit arterial blood sampling, quantitative determinations of CBF and CMRO2 are not feasible. In such cases relative indices, such as those for CBF, must be applied. Such qualitative assessments of perfusion, which were calibrated in an independent cohort of patients with acute stroke, were used to demonstrate the effect of early systemic treatment of acute ischaemia with recombinant tissue plasminogen activator. By applying operationally defined thresholds for tissue viability and the penumbra, and co-registering these tissue compartments to infarcted and non-infarcted tissue on late magnetic resonance imaging, the proportions of at-risk tissue salvaged from infarction could be revealed in individual patients. In the future, functional imaging modalities that could eventually include tracers for neuronal integrity could be used to select patients for thrombolytic therapy. In some instances such techniques may permit the extension of the critical time period for inclusion of patients to aggressive stroke management strategies.
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PMID:Quantitative neuroimaging for the evaluation of the effect of stroke treatment. 957 23

We examined the expression of protein kinase C isoforms in infarcted tissue, penumbra and contralateral brain tissue from 10 patients who died between 1-52 days after ischaemic stroke. Ten patients aged 61-89 years were used in the study. Tissue samples were assayed for protein kinase C activity using a non-radioactive method, and specific isoforms expression determined by Western blotting and staining with anti-PKC polyclonal antibodies. There was a 2-24 fold increase in PKC gamma in the ischaemic penumbra of nine out of 10 patients compared to contralateral tissue. In infarcted tissue expression of PKC gamma was not significantly changed in any of 10 samples but the beta I isoform increased in eight and the beta II in nine patients. There was no significant change in expression in PKC alpha or in infarct or penumbra. Differences in total PKC activity were not specific in seven out of eight patients and it is difficult to estimate their significance. In conclusion after ischaemia there was an altered expression of PKC isoforms with an increase of PKC gamma in the surviving penumbra and beta I and beta II in the infarcted core.
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PMID:Protein kinase C expression and activity in the human brain after ischaemic stroke. 958 83

In stroke penumbra perfusion depends passively on hemodynamics. So far hemodynamic effects of low molecular weight hydroxyethylstarch (HES) has not been investigated. Ten stroke patients received hypervolemic HES therapy. Cardiac output and heart rate were monitored using the bioimpedance method, blood pressure by conventional measurement. The Scandinavian Stroke Scale assessed clinical outcome. Circadian cardiac output changes were measured in 20 controls. Patients' cardiac output increased after the loading dose (5.3 +/- 1.4 l min(-1) to 6.5 +/- 1.7 l min(-1), p < 0.01), fluctuating then between 5 and 7 l min(-1) without nocturnal decrease. Beside an initial increase, the heart rate showed, like blood pressure, no remarkable changes. The Scandinavian Stroke Scale score did not change significantly. The controls showed a circadian cardiac output fluctuation (2.00 am, 5.3 +/- 0.3 l min(-1); 8.30 am, 8.1 +/- 0.6 l min(-1). Our patients showed a hemodynamic and clinical stabilization under therapy with low molecular weight HES. The physiological nocturnal decrease of cardiac output and blood, which might cause clinical deterioration in stroke patients, was avoided.
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PMID:Hemodynamics of stroke patients under therapy with low molecular weight hydroxyethyl starch. 958 84

Multiple metabolic processes have been identified within the critically perfused ischaemic penumbra on the margins of cerebral infarcts. Intervention in many of these processes has been neuroprotective, notably blockade of glutamate receptors such as the N-methyl D-aspartate (NMDA) receptor. Magnesium may act as a neuroprotective agent through vascular effects (increasing regional cerebral blood flow to ischaemic tissue, anticonstrictor effects against vascular mediators, vasodilatation of the cerebral circulation) or neuronal effects. Neuronal effects include block of the NMDA receptor ion channel, calcium antagonism at voltage-gated channels, enhanced buffering of intracellular calcium ions, and enhanced regeneration of adenosine triphosphate. Magnesium infusions of sulphate or chloride salts are significantly neuroprotective in standard animal focal cerebral ischaemia models, with benefits being evident at serum concentrations attainable in humans. Mg systemic infusion causes rises in cerebrospinal fluid and brain magnesium concentrations. Magnesium is also neuroprotective in other models of cerebral ischaemia. Three clinical trials in acute stroke have involved just over 100 patients. No adverse effects have been observed, and trends favouring magnesium treatment have been seen. A large multicentre clinical trial testing the efficacy of magnesium sulphate is underway, and should report within 4 years.
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PMID:New experimental and clinical data on the efficacy of pharmacological magnesium infusions in cerebral infarcts. 959 48

Apoptosis and programmed cell death have attracted major scientific interest during the last few years. Apoptosis can be differentiated from necrosis by means of morphological, biochemical, molecular and pharmacological parameters. Several molecular pathways leading to apoptosis have been elucidated over the last few years. Apoptosis is not only important for physiological cell turnover, but also plays a role in many pathological processes. Recently, a number of laboratories have found evidence of apoptotic cell death in cerebral ischemia in animal models. Quantitatively, apoptosis seems to be important in the border zone of the infarction, the so-called penumbra. Since parts of the apoptotic cascade can be inhibited, pharmacological treatment seems feasible. The so-called caspase inhibitors are promising therapeutic agents for the treatment of acute stroke and may be administered with other neuroprotective medications in humans in the near future.
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PMID:[Apoptosis and ischemic infarct]. 967 68


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