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Therapeutic application of exosomes in ischaemic stroke.

ABSTRACT: Ischaemic stroke is a leading cause of long-term disability in the world, with limited effective treatments. Increasing evidence demonstrates that exosomes are involved in ischaemic pathology and exhibit restorative therapeutic effects by mediating cell-cell communication. The potential of exosome therapy for ischaemic stroke has been actively investigated in the past decade. In this review, we mainly discuss the current knowledge of therapeutic applications of exosomes from different cell types, different exosomal administration routes, and current advances of exosome tracking and targeting in ischaemic stroke. We also briefly summarised the pathology of ischaemic stroke, exosome biogenesis, exosome profile changes after stroke as well as registered clinical trials of exosome-based therapy.

SUBMITTER: Li Y

PROVIDER: S-EPMC8485240 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Therapeutic application of exosomes in ischaemic stroke.

Li Yongfang Y Tang Yaohui Y Yang Guo-Yuan GY

Stroke and vascular neurology 20210111 3

Ischaemic stroke is a leading cause of long-term disability in the world, with limited effective treatments. Increasing evidence demonstrates that exosomes are involved in ischaemic pathology and exhibit restorative therapeutic effects by mediating cell-cell communication. The potential of exosome therapy for ischaemic stroke has been actively investigated in the past decade. In this review, we mainly discuss the current knowledge of therapeutic applications of exosomes from different cell types ...[more]

PMID: 33431513

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Project description:BackgroundCerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue, which has potential neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries.ObjectivesTo assess the benefits and risks of cerebrolysin for treating acute ischaemic stroke.Search methodsIn May 2016 we searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian Databases. We also searched reference lists, ongoing trials registers and conference proceedings, and contacted the manufacturer of cerebrolysin, EVER Neuro Pharma GmbH (formerly Ebewe Pharma).Selection criteriaRandomised controlled trials (RCTs) comparing cerebrolysin, started within 48 hours of stroke onset and continued for any time, with placebo or no treatment in people with acute ischaemic stroke.Data collection and analysisTwo review authors independently applied inclusion criteria, assessed trial quality and risk of bias, and extracted data.Main resultsWe identified six RCTs (1501 participants) that met the inclusion criteria.We evaluated risk of bias and judged it to be unclear for generation of allocation sequence in four studies and low in two studies; unclear for allocation concealment in five studies and low in one study; high for incomplete outcome data (attrition bias) in five studies and unclear in one study; unclear for blinding; high for selective reporting in four studies and unclear in two; and high for other sources of bias in three studies and unclear in the rest. The manufacturer of cerebrolysin, pharmaceutical company EVER Neuro Pharma, supported three multi-centre studies, either totally, or providing cerebrolysin and placebo, randomisation codes, research grants, or statisticians.None of the included trials reported on poor functional outcome defined as death or dependence at the end of the follow-up period or early death (within two weeks of stroke onset).All-cause death: we extracted data from five trials (1417 participants). There was no difference in the number of deaths: 46/714 in cerebrolysin group versus 47/703 in placebo group; risk ratio (RR) 0.91 95% confidence interval (CI) 0.61 to 1.35 (5 trials, 1417 participants, moderate-quality evidence).Serious adverse events (SAEs): there was no significant difference in the total number of SAEs with cerebrolysin (RR 1.16, 95% CI 0.81 to 1.67). This comprised no difference in fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38) and an increase in the number of people with non-fatal SAEs (20/667 with cerebrolysin and 8/668 with placebo: RR 2.47, 95% CI 1.09 to 5.58, P = 0.03) (3 trials, 1335 participants, moderate-quality evidence).Total number of people with adverse events: three trials reported on this. There was no difference in the total number of people with adverse events: 308/667 in cerebrolysin group versus 307/668 in placebo group; RR 0.97 95% CI 0.86 to 1.09, random-effects model (3 trials, 1335 participants, moderate-quality evidence).Authors' conclusionsThe findings of this Cochrane Review do not demonstrate clinical benefits of cerebrolysin for treating acute ischaemic stroke. We found moderate-quality evidence of an increase in non-fatal SAEs with cerebrolysin use but not in total SAEs.

Project description:BackgroundMost ischaemic strokes are caused by a blood clot blocking an artery in the brain. Clot prevention with anticoagulants might improve outcomes if bleeding risks are low. This is an update of a Cochrane review first published in 1995, with recent updates in 2004 and 2008.ObjectivesTo assess the effectiveness and safety of early anticoagulation (within the first 14 days of onset) in people with acute presumed or confirmed ischaemic stroke.Search methodsWe searched the Cochrane Stroke Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR), the Database of Reviews of Effects (DARE) and the Health Technology Assessment Database (HTA) (The Cochrane Library 2014 Issue 6), MEDLINE (2008 to June 2014) and EMBASE (2008 to June 2014). In addition, we searched ongoing trials registries and reference lists of relevant papers. For previous versions of this review, we searched the register of the Antithrombotic Trialists' (ATT) Collaboration, consulted MedStrategy (1995), and contacted relevant drug companies.Selection criteriaRandomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in people with acute presumed or confirmed ischaemic stroke.Data collection and analysisTwo review authors independently selected trials for inclusion, assessed trial quality, and extracted the data.Main resultsWe included 24 trials involving 23,748 participants. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Over 90% of the evidence relates to the effects of anticoagulant therapy initiated within the first 48 hours of onset. Based on 11 trials (22,776 participants) there was no evidence that anticoagulant therapy started within the first 14 days of stroke onset reduced the odds of death from all causes (odds ratio (OR) 1.05; 95% confidence interval (CI) 0.98 to 1.12) at the end of follow-up. Similarly, based on eight trials (22,125 participants), there was no evidence that early anticoagulation reduced the odds of being dead or dependent at the end of follow-up (OR 0.99; 95% CI 0.93 to 1.04). Although early anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.76; 95% CI 0.65 to 0.88), it was also associated with an increase in symptomatic intracranial haemorrhages (OR 2.55; 95% CI 1.95 to 3.33). Similarly, early anticoagulation reduced the frequency of symptomatic pulmonary emboli (OR 0.60; 95% CI 0.44 to 0.81), but this benefit was offset by an increase in extracranial haemorrhages (OR 2.99; 95% CI 2.24 to 3.99).Authors' conclusionsSince the last version of the review, no new relevant studies have been published and so there is no additional information to change the conclusions. Early anticoagulant therapy is not associated with net short- or long-term benefit in people with acute ischaemic stroke. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis and pulmonary embolism, but increased bleeding risk. The data do not support the routine use of any of the currently available anticoagulants in acute ischaemic stroke.

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Therapeutic application of exosomes in ischaemic stroke.

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Therapeutic application of exosomes in ischaemic stroke.

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