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

Stroke is a heterogeneous disease, but about 85% of strokes are as a result of cerebral ischaemia due to arterial occlusion. It seems logical to assume that, as in myocardial infarction, treatment designed to dissolve clots should be helpful. We now have a substantial amount of data on the use of aspirin, heparin and thrombolytic drugs in the treatment of acute ischaemic stroke. Aspirin 300 mg daily has a modest effect in reducing mortality and handicap when used within 48 hours of stroke onset. The beneficial effects of low dose, medium dose subcutaneous unfractionated heparin, and various low molecular weight heparins in reducing early recurrent ischaemic stroke seem to be outweighed by haemorrhagic side effects. Streptokinase used within six hours of stroke onset results in excess mortality with some reduction in handicap in survivors, while in carefully selected patients recombinant tissue plasminogen activator (r-TPA) may be less hazardous. At the moment it is unclear which stroke patients will benefit from the use of r-TPA, and the use of criteria, as outlined by the NINDS group, means that only a very small proportion of stroke victims are suitable for thrombolytic therapy. Further research is necessary, while the concept of a 'Brain Attack' with appropriate urgency being used in the assessment of possible stroke needs development.
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PMID:Reperfusion therapy for stroke. 1086 20

Ischaemic penumbra is defined as the area of brain tissue that maintains some blood flow following ischaemic accident. This zone may be rescued by both neuroprotection and arterial revascularization. Early thrombolysis has been used with encouraging results since 1995 in several trials testing both streptokinase and recombinant tissue plasminogen activator (r-TPA): the r-TPA results are definitely more positive than those of streptokinase, despite an increased incidence of symptomatic haemorrhagic transformation, r-TPA significantly reducing death or dependency at the end of follow-up. Despite the fact that some experimental periods of application of these therapeutic strategies demonstrated real cost-effective benefits, only 1% of patients reaching hospital in time for thrombolysis are currently treated. This is because the profile of patients at risk of haemorrhagic transformation, which is definitely the most feared side-effect of thrombolysis in stroke, is yet to be clearly defined. Extended computerized tomography (CT) signs of the index stroke have been repeatedly indicated as reliable predictors of haemorrhagic transformation even if currently there are significant discrepancies in the criteria adopted by different researchers to define early CT signs. Based on experimental ischaemia, strategies for protecting the basal lamina during thrombolysis are suggested: neuroprotection is the second approach to stroke therapy; pharmacological reperfusion and brain protection are probably mutually dependent.
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PMID:Treatment of cerebrovascular diseases: state of the art and perspectives. 1181 86

In Italy (130,000 new strokes in the general population per year) ischemic stroke is the third cause of death, after cardiovascular disease and neoplastic disease with a prevalence of 6.5%. Different physicians are involved in the emergent evaluation and treatment of the acute ischemic stroke. As other acute events, the initial evaluation must be addressed to assess the patient's airway and breath-ing and cardiocirculatory conditions. The neurological examination must not be exhaustive and it should be completed in 5-10 minutes and a particular attention should be given to clinical findings leading to the suspect of an intracranial hemorrhages. A plain CT scan of the brain is the most important initial diagnostic study. Emergency therapy must be mainly directed to the correction of hypovolemia, hypoxia and the treatment of severe hypertension, hypoglycemia, intracranial hypertension and seizures. The goal is to achieve and to maintain an adequate cerebral perfusion by lowering the intracranial pressure (treating the cerebral oedema) and by increasing the mean arterial pressure, with an appropriate volemic expansion and/or with inotropic or vasopressor drugs. The thrombolytic therapy with intravenous recombinant tessutal plasminogen activator (r-TPA) when not specifically contraindicated, is recommended within 3 hours of onset of ischemic stroke. The benefit of intravenous r-TPA for acute ischemic stroke beyond 3 hours from the onset has never been proved.
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PMID:Stroke patients, what to do and what to avoid. 1202 99

YM872, an AMPA receptor antagonist, was administered together with t-PA to investigate the effects of coadministration on neuroprotection in a rat embolic stroke model, when administered 2 h after embolism. T-PA or YM872 alone decreased infarct volume and improved the neurological deficit score. Coadministration of YM872 and t-PA resulted in a further decrease in infarct volume and improvement of the neurological score as compared with single administration of t-PA. These data demonstrate that coadministration of YM872 and t-PA produces more potent neuroprotective effects than when t-PA is administered alone.
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PMID:Neuroprotective effects of YM872 coadministered with t-PA in a rat embolic stroke model. 1248 Jan 71

Neuroserpin is a member of the serine proteinase inhibitor (serpin) gene family that reacts preferentially with tissue-type plasminogen activator (tPA) and is primarily localized to neurons in regions of the brain where tPA is also found. Outside of the central nervous system (CNS) tPA is predominantly found in the blood where its primary function is as a thrombolytic enzyme. However, tPA is also expressed within the CNS where it has a very different function, promoting events associated not only with synaptic plasticity but also with cell death in a number of settings, such as cerebral ischemia and seizures. Neuroserpin is released from neurons in response to neuronal depolarization and plays an important role in the development of synaptic plasticity. Following the onset of cerebral ischemia there is an increase in both tPA activity and neuroserpin expression in the area surrounding the necrotic core (ischemic penumbra), and treatment with neuroserpin following ischemic stroke or overexpression of the neuroserpin gene results in a significant decrease in the volume of the ischemic area as well as in the number of apoptotic cells. TPA activity and neuroserpin expression are also increased in specific areas of the brain by seizures, and treatment with neuroserpin slows the progression of seizure activity throughout the CNS and results in significant neuronal survival in the hippocampus. Mutations in human neuroserpin result in a form of autosomal dominant inherited dementia which is characterized by the presence of intraneuronal inclusion bodies and is known as Familial Encephalopathy with Neuroserpin Inclusion Bodies.
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PMID:Neuroserpin: a selective inhibitor of tissue-type plasminogen activator in the central nervous system. 1498 20

Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation. It is now accepted that inflammation and related events, such as activation of NF-kappaB, are key components in the initiation and progression of epithelial cancer and in particular in the neoplastic transformation of keratinocytes and skin carcinogenesis. Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis. In parp-1(-/-) mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced. In addition, epidermis of parp-1(-/-) mice did not show increased proliferation rates after treatment with carcinogen. Deregulated NF-kappaB is a hallmark for tumorigenesis together with the concomitant release of early inflammatory mediators. In the absence of PARP-1, NF-kappaB activation and induction kappaB-target genes did not take place during the promotion of tumor development. These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-kappaB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.
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PMID:Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia. 1507 72

Presented are the clinical data of 18 consecutive patients who were treated by IV recombinant tissue plasminogen activator (r-TPA) for suspected vertebrobasilar (VB) acute ischemia within 7 hours. The mean delay for treatment was 5 +/- 3.6 hours. Mean baseline NIH Stroke Scale score was 17 +/- 4. At 3 months, 10 patients were independent (modified Rankin Scale [mRS] score = 0 to 2), whereas 8 patients showed a poor outcome (mRs = 3 to 6). IV r-TPA in VB ischemia in a 7-hour window may be safe and efficient.
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PMID:Intravenous r-TPA in vertebrobasilar acute infarcts. 1515 94

The management of acute ischemic stroke has not made significant strides since the introduction of recombinant tissue plasminogen activator (r-TPA) two decades ago. The use of other therapies, such as heparin, aspirin, dipyridamole, and/or clopidogrel, have only moderately aided in the treatment of this ischemic disease. Therefore, major medical innovative approaches are critically needed. Because of the side effects associated with r-TPA (specifically bleeding) and its limited 3-h therapeutic window, new studies using current developments encountered in the molecular biology of ischemia are being incorporated into the potential therapy of ischemic stroke. A review of the major advances in the field, including glutamate receptor blockade, magnesium infusion, inflammation blockade, apoptosis inhibition, and other therapies, is introduced with special emphasis on the molecular findings recognized as targets for a better and more effective treatment. As new therapies are being considered, the time of administration is becoming a central point of study for the application of novel therapeutic initiatives.
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PMID:Molecular mechanisms in the pathogenesis and treatment of acute ischemic stroke. 1612 32

Clomethiazole has been marketed for several years as a sedative/antiepileptic. Astra is now developing it for the potential treatment of stroke. An NDA is expected to be filed in 1999/2000. A North American phase III trial for large stroke has commenced. This will include 1200 patients. Two other smaller scale phase III studies with clomethiazole have also commenced in North America for intracerebral hemorrhage (n=200) and safety in combination with TPA (n=100 to 200) (Genentech). A large-scale phase III trial has been completed in which clomethiazole was evaluated for its ability to reduce nerve damage in acute cerebrovascular ischemia. The multicenter, international trial, called CLASS (Clomethiazole Acute Stroke Study), analyzed 1360 patients and found no significant treatment effect. However, a subgroup of patients who presented with large stroke, experienced a significant benefit. Of these (n=545), 41% treated patients were functionally independent after 90 days, compared to 30% patients on placebo. Clomethiazole reduced functional disability and brain damage in the marmoset permanent MCAO model. Clomethiazole is thought to act through a GABAergic pathway, whereby it augments GABA's depressive effect on the CNS, giving the drug both hypnotic and neuroprotectant properties.
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PMID:Clomethiazole (Astra Arcus AB). 1616 Sep 52

Several studies have stressed the involvement of inflammation in the pathophysiology of acute brain ischemia, but the role of immunoinflammatory activation in diabetic stroke patients has not yet been fully evaluated. The aim of our study was to evaluate immunoinflammatory activation of acute phase of stroke in relation to time of symptoms onset, diabetic state and diagnostic subtype. We enrolled 60 patients (32 diabetics; 28 non- diabetics) with acute ischemic stroke and 123 subjects without acute ischemic stroke, and measured levels of IL-1beta, TNF-alpha IL-6, IL-10, E-selectin, P-selectin, sICAM-1, sVCAM-1, VWF, 24-72 h and 7-10 days after stroke onset; TPA, PAI-1 plasma levels at 24-72h. Our stroke patients exhibited significantly higher plasma levels of cytokines, selectins, adhesion molecules and PAI-1, and diabetic stroke patients exhibited higher plasma levels of PAI-1 in comparison with non-diabetic ones. Lacunar strokes in comparison with those non-lacunar exhibited significantly lower levels of TNF-alpha and IL1-beta P-selectin and ICAM-1. Moreover, diabetic patients with lacunar strokes exhibited a minor grade of immunoinflammatory activation of the acute phase at 24-72h and 7-10 days after stroke onset. The minor grade of immunoinflammatory activation of patients with lacunar strokes, particularly diabetic ones, could be related to the minor extension of the infarct size, owing to the typical microvascular disease of diabetic subjects which could also explain the reported better outcome of this subtype of ischemic stroke.
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PMID:Immunoinflammatory activation during the acute phase of lacunar and non-lacunar ischemic stroke: association with time of onset and diabetic state. 1702 49


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