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

Ischemic stroke is the most common life-threatening neurological disease and has limited therapeutic options. One component of ischemic neuronal death is inflammation. Here we show that doxycycline and minocycline, which are broad-spectrum antibiotics and have antiinflammatory effects independent of their antimicrobial activity, protect hippocampal neurons against global ischemia in gerbils. Minocycline increased the survival of CA1 pyramidal neurons from 10.5% to 77% when the treatment was started 12 h before ischemia and to 71% when the treatment was started 30 min after ischemia. The survival with corresponding pre- and posttreatment with doxycycline was 57% and 47%, respectively. Minocycline prevented completely the ischemia-induced activation of microglia and the appearance of NADPH-diaphorase reactive cells, but did not affect induction of glial acidic fibrillary protein, a marker of astrogliosis. Minocycline treatment for 4 days resulted in a 70% reduction in mRNA induction of interleukin-1beta-converting enzyme, a caspase that is induced in microglia after ischemia. Likewise, expression of inducible nitric oxide synthase mRNA was attenuated by 30% in minocycline-treated animals. Our results suggest that lipid-soluble tetracyclines, doxycycline and minocycline, inhibit inflammation and are neuroprotective against ischemic stroke, even when administered after the insult. Tetracycline derivatives may have a potential use also as antiischemic compounds in humans.
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PMID:Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. 986 Oct 45

Epidemiological investigations have shown a linear positive correlation between the risk of haemorrhagic stroke and level of alcohol consumption. Ischaemic stroke shows a weaker relationship, which is J-shaped, suggesting that regular light-to-moderate alcohol consumption may carry a decreased risk. Case reports and case-control studies indicate that heavy recent drinking, but not heavy former drinking, increases the risk for both types of stroke. Larger amounts of alcohol are needed to trigger aneurysmal subarachnoid haemorrhage than spontaneous intracerebral haemorrhage. The increased risk caused by recent heavy drinking may be partly due to elevated systolic blood pressure, but alcohol may also provoke cerebral arterial vasospasm, as observed in animal experiments. Alcohol-induced fluctuation in haemostatic and fibrinolytic factors has not been proved to precipitate alcohol-related strokes, but may contribute to both an increase and a decrease of the risk. Subtypes of ischaemic stroke associate differently with alcohol consumption. A recent series of patients with ischaemic brain infarction showed that of the victims having a high and medium risk for cardiogenic embolism, 50% and 45% were intoxicated, respectively. This suggests that cardiogenic embolism is a significant mechanism leading to ischaemic stroke during heavy drinking of alcohol.
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PMID:Mechanisms of alcohol-related strokes. 994 94

Primary care providers play an instrumental role in both coordinating prevention efforts and facilitating emergency care for patients with signs and symptoms of acute ischemic stroke. Acute Ischemic stroke, also known as brain attack, is the third leading cause of death and the leading cause of adult disability in the United States. Acute ischemic stroke is currently considered a medical emergency that can respond to early treatment. In addition, primary and secondary prevention activities have proved effective. This article reviews the current literature regarding the types of stroke as well as specific information about prevention, signs and symptoms, and management. Guidelines for assessment and emergency care for patients with acute ischemic stroke are also provided.
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PMID:Acute ischemic stroke. 1004 79

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

Ischemic stroke is associated with altered systemic immune responses both early after the onset and in the recovery phase. Interleukin (IL)-10, a Th2 related cytokine, has multiple effects on different cell types, including T and B lymphocytes, monocytes, neutrophils and mast cells. IL-4 is another Th2 cytokine that inhibits the synthesis of pro-inflammatory cytokines by Th1 clones. We used enzyme-linked immunospot assays to detect and enumerate blood mononuclear cells (MNC) secreting IL-10 and IL-4 spontaneously as well as after stimulation with myelin basic protein (MBP), considered to be an autoantigen of possible pathogenic importance in, for example, multiple sclerosis, to evaluate the involvement of anti-inflammatory cytokines in ischemic stroke. All patients with ischemic stroke and cerebral hemorrhage had strongly elevated numbers of IL-10 secreting blood MNC compared with healthy individuals. Numbers of MBP-reactive IL-10 secreting blood MNC were also elevated in a proportion of the patients with stroke and hemorrhage. Levels of IL-4 secreting blood MNC did not differ in ischemic stroke versus healthy individuals. The anti-inflammatory IL-10 could play a pivotal role in ischemic stroke as well as cerebral hemorrhage.
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PMID:High levels of IL-10 secreting cells are present in blood in cerebrovascular diseases. 1036 96

Ischaemic stroke is a rare occurrence in children and in a proportion of cases the aetiology remains unknown. We have investigated the role of thrombophilia in the aetiology of this condition. Of 50 cases identified at two centres, 37 were available for detailed haematological analysis. No cases were identified with deficiencies of antithrombin, protein C or protein S. One case had elevated IgG anticardiolipin antibodies at low titre. The prevalence of the prothrombin 20210 G-->A mutation, factor V Leiden (FVL) mutation and the C677T mutation in the MTHFR gene was compared in cases to that observed in random unselected cord blood controls. The odds ratio for stroke was not significantly increased in carriers of the prothrombin mutation (OR 1.2; 95% CI 0.1-10.7), FVL (OR 2.5; 95% CI 0.5-13.5), or the C677T mutation (OR 1.7; 95% CI 0.6-4.5). Our findings suggest that thrombophilia may not play a significant role in the aetiology of stroke in children, although a large prospective study is required to investigate this area further.
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PMID:Factor V Leiden, prothrombin 20210G-->A and the MTHFR C677T mutations in childhood stroke. 1036 38

Ischemic stroke, myocardial infarction and peripheral arterial disease are different clinical manifestations commonly due to the same underlying disease, i.e. atherosclerosis with subsequent thrombosis/embolism (atherothrombosis). Many clinical trials of secondary prevention after stroke or TIA have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of subsequent vascular events. Aspirin and triclopidine have been shown to be effective in placebo-controlled studies for the composite outcome of stroke, myocardial infarction, or vascular death. Contrasting with these benefits, there were potentially serious, though rare, adverse effects. These considerations certainly justify the development of new antiplatelet agents. Clopidogrel is a new ADP-receptor antagonist, with a greater activity in animal models of thrombosis. CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events) was a randomized, blinded, international trial designed to assess the relative efficacy of clopidogrel and aspirin in reducing the risk of the outcome cluster of ischemic stroke, myocardial infarction, or vascular death, as well as to assess their relative safety. 19,185 patients were recruited. The intention-to-treat analysis showed that the relative risk reduction was 8.7% (95% CI 0.3-16.5, p = 0.043) in favor of clopidogrel from an overall annual event rate of ischemic stroke, myocardial infarction, or vascular death, ranging from 5.83% in the aspirin group to 5.33% in the clopidogrel group. The percentage of adverse events reported was higher in the aspirin group for all categories except rash, diarrhea, and abnormal liver function. It seems likely that clopidogrel will replace ticlopidine for stroke prevention, because of its better safety profile, and comparable efficacy. Clopidogrel probably will not replace aspirin as the first line therapy for many clinicians because of its higher cost and lack of widespread experience. However, other clinicians have already decided that they will use clopidogrel as first choice, because of the significant advantage over aspirin demonstrated in the CAPRIE study.
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PMID:Clopidogrel for cerebrovascular prevention. 1047 7

Ischaemic stroke accounts for 70-85% of stroke incidence worldwide, causing substantial morbidity and mortality. Antiplatelet agents and carotid endarterectomy are effective in stroke prevention but active therapy for acute stroke is limited at present. Treatments investigated to date include thrombolysis and antiplatelet agents, both of which have been shown to modify the effects of stroke and provide a small long-term benefit in selected patients, and anticoagulation with heparin derivatives and oral agents. The value of unfractionated heparin (UFH) in modifying the acute effects of stroke has never been clearly established, and the risk of intracranial bleeding has limited its clinical application. However, disability and death following stroke stem from both the acute cerebral event and the secondary development of venous thromboembolism (VTE). Antithrombotic therapy may therefore, in principle, provide the dual benefit of retarding ongoing cerebral thrombosis and preventing secondary VTE. Low-molecular-weight heparins (LMWHs) and one heparinoid may have an improved ratio of antithrombotic action to haemorrhagic effect compared with UFH. Recent trials with these agents demonstrated a significant reduction in deep vein thrombosis and pulmonary embolism. Evidence has also emerged of improved long-term outcomes in terms of combined rates of death and residual disability, but data from different studies are conflicting. The potential role of LMWHs and heparinoids in acute stroke remains to be clarified.
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PMID:Anticoagulation in acute ischaemic stroke: deep vein thrombosis prevention and long-term stroke outcomes. 1049 41

Ischaemic stroke is a leading cause of death and long-lasting disability. Several neuroprotective drugs have been developed that have the potential to limit ischaemic brain damage and improve outcome for patients. While promising results with these drugs have been achieved in animal stroke models, all Phase III trials conducted so far indicate that these drugs have failed to live up to their promise. Despite the limits of animal models, which cannot mimic the clinical situation, the disappointing results of neuroprotective trials might largely be due to methodological problems. Future trials with neuroprotective drugs should be performed in stroke (care) units, after sufficient information regarding therapeutic time window, dosage, duration of therapy and safety has been gathered from pilot studies, and a better selection of target patients has been made. Much of this information can now be obtained by techniques that visualize the penumbra, such as combined diffusion-weighted and perfusion MRI. Consideration should also be given to clinical trials with well-designed combinations of treatments.
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PMID:Clinical trials with neuroprotective drugs in acute ischaemic stroke: are we doing the right thing? 1083 91

Ischemic stroke is a rare event in childhood. In approximately one third of cases no obvious underlying cause or disorder can be detected. We investigated the importance of genetic risk factors of venous thromboembolism in childhood or stroke in adulthood as risk factors for spontaneous ischemic stroke in children. One hundred forty-eight Caucasian infants and children (aged 0.5 to 16 years) with stroke and 296 age-matched controls from the same geographic areas as the patients were analyzed for increased lipoprotein (a) [Lp(a)] levels >30 mg/dL; for the presence of the factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, and the TT677 genotype of methylenetetrahydrofolate reductase (MTHFR); and deficiencies of protein C, protein S, and antithrombin. The following frequencies (patients v controls), odds ratios (ORs), and confidence intervals (CIs) of single risk factors were found: Lp(a) >30 mg/dL (26.4% v 4.7%; OR/CI, 7.2/3.8 to 13.8; P <.0001), FV G1691A (20.2% v 4%; OR/CI, 6/2.97 to 12.1; P <.0001), protein C deficiency (6% v 0.67%; OR/CI, 9.5/2 to 44.6; P =.001), PT G20210A (6% v 1.3%; OR/CI, 4.7/1.4 to 15.6; P =.01), and the MTHFR TT677 genotype (23.6% v 10.4%; OR/CI, 2.4/1.53 to 4.5; P <.0001). A combination of the heterozygous FV G1691A mutation with increased Lp(a) (n = 11) or the MTHFR TT677 genotype (n = 5) was found in 10. 8% of cases, but only 0.3% of controls (OR/CI, 35.75/4.7 to 272; P <. 0001). Increased Lp (a) levels, the FV G1691A mutation, protein C deficiency, the prothrombin G20210A variant, and the MTHFR TT677 are important risk factors for spontaneous ischemic stroke in childhood.
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PMID:Lipoprotein (a) and genetic polymorphisms of clotting factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of spontaneous ischemic stroke in childhood. 1057 79


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