The Effect of Erythropoietin and Its Derivatives on Ischemic Stroke Therapy: A Comprehensive Review.
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ABSTRACT:
SUBMITTER: Ma Y
PROVIDER: S-EPMC8892214 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
The Effect of Erythropoietin and Its Derivatives on Ischemic Stroke Therapy: A Comprehensive Review.
Ma Yuanyuan Y Zhou Zhiyuan Z Yang Guo-Yuan GY Ding Jing J Wang Xin X
Frontiers in pharmacology 20220217
Numerous studies explored the therapeutic effects of erythropoietin (EPO) on neurodegenerative diseases. Few studies provided comprehensive and latest knowledge of EPO treatment for ischemic stroke. In the present review, we introduced the structure, expression, function of EPO, and its receptors in the central nervous system. Furthermore, we comprehensively discussed EPO treatment in pre-clinical studies, clinical trials, and its therapeutic mechanisms including suppressing inflammation. Finall ...[more]
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Project description:The German Multicenter EPO Stroke Trial, which investigated safety and efficacy of erythropoietin (EPO) treatment in ischemic stroke, was formally declared a negative study. Exploratory subgroup analysis, however, revealed that patients not receiving thrombolysis most likely benefited from EPO during clinical recovery, a result demonstrated in the findings of the Göttingen EPO Stroke Study. The present work investigated whether the positive signal on clinical outcome in this patient subgroup was mirrored by respective poststroke biomarker profiles. All patients of the German Multicenter EPO Stroke Trial nonqualifying for thrombolysis were included if they (a) were treated per protocol and (b) had at least two of the five follow-up blood samples for circulating damage markers drawn (n = 163). The glial markers S100B and glial fibrillary acid protein (GFAP) and the neuronal marker ubiquitin C-terminal hydrolase (UCH-L1) were measured by enzyme-linked immunosorbent assay in serum on d 1, 2, 3, 4 and 7 poststroke. All biomarkers increased poststroke. Overall, EPO-treated patients had significantly lower concentrations (area under the curve) over 7 d of observation, as reflected by the composite score of all three markers (Cronbach α = 0.811) and by UCH-L1. S100B and GFAP showed a similar tendency. To conclude, serum biomarker profiles, as an outcome measure of brain damage, corroborate an advantageous effect of EPO in ischemic stroke. In particular, reduction in the neuronal damage marker UCH-L1 may reflect neuroprotection by EPO.
| S-EPMC3321813 | biostudies-literature
Project description:The German Multicenter EPO Stroke Trial, which investigated safety and efficacy of erythropoietin (EPO) treatment in ischemic stroke, was formally declared a negative study. Exploratory subgroup analysis, however, revealed that patients not receiving thrombolysis most likely benefited from EPO during clinical recovery, a result demonstrated in the findings of the Göttingen EPO Stroke Study. The present work investigated whether the positive signal on clinical outcome in this patient subgroup was mirrored by respective poststroke biomarker profiles. All patients of the German Multicenter EPO Stroke Trial nonqualifying for thrombolysis were included if they (a) were treated per protocol and (b) had at least two of the five follow-up blood samples for circulating damage markers drawn (n = 163). The glial markers S100B and glial fibrillary acid protein (GFAP) and the neuronal marker ubiquitin C-terminal hydrolase (UCH-L1) were measured by enzyme-linked immunosorbent assay in serum on d 1, 2, 3, 4 and 7 poststroke. All biomarkers increased poststroke. Overall, EPO-treated patients had significantly lower concentrations (area under the curve) over 7 d of observation, as reflected by the composite score of all three markers (Cronbach α = 0.811) and by UCH-L1. S100B and GFAP showed a similar tendency. To conclude, serum biomarker profiles, as an outcome measure of brain damage, corroborate an advantageous effect of EPO in ischemic stroke. In particular, reduction in the neuronal damage marker UCH-L1 may reflect neuroprotection by EPO.
| S-EPMC3321813 | biostudies-literature
Project description:Ischemic stroke is the most common stroke, caused by occlusion of cerebral vessels and leading causes of disability. Erythropoietin (EPO) has non-hematopoietic effects as a neuroprotectant after ischemic event. This study aimed to learn the serum level of EPO in acute ischemic stroke. This cross-sectional study of ischemic stroke patients with onset < 24 h and consecutive sampling was used to collect the data from medical records review, physical examinations, head CT, 24-h EPO, 24-h and seventh-day NIHSS. A total of 47 patients consisting of 59.6% women, with a median age of 53 years old (21-70). The median 24 h EPO level was 808.6 pg/mL (134.2-2988.9). The relationship between 24 h-EPO and 24-h NIHSS were not significant (r = 0.101; p = 0.250), nor to 7th day NIHSS (r = - 0.0174; p = 0.121) and to delta NIHSS (r = 0.186; p = 0.106). The relationship of blood collection time (hour) and EPO was significant (r = - 0.260; p = 0.039). There was a statistically significant difference between serum EPO levels in ischemic stroke patients with lacunar stroke compared to non-lacunar stroke (288.5 vs. 855.4 ng/mL; p = 0.021). There was a relationship between the time of collection of blood and the level of EPO and also there was difference EPO level in lacunar stroke subtype compared with non-lacunar. The relationship between EPO and NIHSS lost significance after analysis. There is a need for a future study comparing each stroke risk factor and the same blood collection time.
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Project description:Background: This study investigates the relationship between sleep patterns and ischemic stroke beyond the predominant focus on obstructive sleep apnea. Through a systematic review of the existing literature, we aim to elucidate the connections between insomnia, sleep duration, cardiovascular factors, and ischemic stroke onset. Methods: We searched databases, including MEDLINE, SciELO, Scopus, and Science Direct, using an adapted PICO framework. Using a search strategy with MeSH words, keywords, and expressions related to insomnia and stroke, we included clinical trials and analytical observational epidemiological studies, comprising cohort, case-control, and cross-sectional studies. Results: Following the initial search, we identified 984 records, with 779 titles and abstracts screened for eligibility after removing duplicates. From these, 63 full-text articles, including 5 in the data synthesis, were reviewed. Our findings highlight a significant correlation between poor sleep quality, extreme sleep durations, and a heightened risk of ischemic stroke, along with established cardiovascular risk factors, such as hypertension, hyperlipidemia, obesity, and diabetes. Conclusions: This systematic review offers a comprehensive analysis of ischemic stroke prevalence and its association with cardiovascular factors, such as hypertension, hyperlipidemia, obesity, and diabetes. It suggests that poor sleep quality and extreme sleep durations, particularly long ones, are linked to a heightened risk of ischemic stroke.
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Project description:The complement system is an essential part of innate immunity, typically conferring protection via eliminating pathogens and accumulating debris. However, the defensive function of the complement system can exacerbate immune, inflammatory, and degenerative responses in various pathological conditions. Cumulative evidence indicates that the complement system plays a critical role in the pathogenesis of ischemic brain injury, as the depletion of certain complement components or the inhibition of complement activation could reduce ischemic brain injury. Although multiple candidates modulating or inhibiting complement activation show massive potential for the treatment of ischemic stroke, the clinical availability of complement inhibitors remains limited. The complement system is also involved in neural plasticity and neurogenesis during cerebral ischemia. Thus, unexpected side effects could be induced if the systemic complement system is inhibited. In this review, we highlighted the recent concepts and discoveries of the roles of different kinds of complement components, such as C3a, C5a, and their receptors, in both normal brain physiology and the pathophysiology of brain ischemia. In addition, we comprehensively reviewed the current development of complement-targeted therapy for ischemic stroke and discussed the challenges of bringing these therapies into the clinic. The design of future experiments was also discussed to better characterize the role of complement in both tissue injury and recovery after cerebral ischemia. More studies are needed to elucidate the molecular and cellular mechanisms of how complement components exert their functions in different stages of ischemic stroke to optimize the intervention of targeting the complement system.
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Project description:Since the realization that erythropoietin (EPO) molecules have 'neuroprotective' properties, they have been investigated as treatments for acute ischemic stroke (AIS), but not systematically. The results of the 2009 clinical trial showed that EPO was ineffective as a stroke treatment, and moreover, increased mortality when combined with tissue plasminogen activator. Currently, CEPO, an EPO analog, is entering into a safety, tolerability and pharmacokinetic clinical trial for the treatment of AIS.This review covers translational and clinical studies carried out over the period 1998 - 2010.The primary aim of this article is to review the information available regarding the pharmacological and biological characteristics of EPO molecules. Second, based upon the translational research with EPO molecules in preclinical stroke models, a recommendation is made regarding the continued development of EPO molecules as an option to treat AIS.EPO, CEPO and helix B peptide EPO analogs have significant neuroprotective activity is preclinical stroke models. However, given the detrimental effect of EPO in a recent clinical trial, preclinical safety studies of EPO molecules in embolic stroke models that parallel acute ischemic stroke in humans are warrented.
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Project description:Radiation therapy is widely used for the treatment of residual and recurrent pituitary adenomas and proved to effectively control tumor growth. However, it is suggested that this treatment might result in an increased risk of ischemic stroke. This review aims to evaluate the radiotherapy-related risk of stroke in pituitary adenoma patients. PubMed and Embase databases were systematically searched for current literature on ischemic stroke risk after radiotherapy in pituitary adenoma, in accordance with the PRISMA statement. Two authors independently selected eligible studies and extracted data. The New Castle Ottawa-scale was used for quality assessment. Out of 264 publications, 11 studies were selected, including 4394 irradiated patients. Incidence of ischemic stroke ranged from 0 to 11.6% (mean 6.7%). While one large, long term follow-up study showed a threefold increased risk of stroke after radiation therapy, another nationwide study of high quality found no significant difference in stroke risk after irradiation. Four studies, which applied stereotactic radiosurgery (SRS) or Gamma-knife surgery (GKS), found no ischemic strokes. Included studies described different radiation techniques and regimens and different lengths of follow-up. In conclusion, complications of cerebral ischemia after radiotherapy for pituitary adenoma are infrequently reported. Moreover, after correction for several confounders, no significant difference in ischemic stroke rate between irradiated and non-irradiated patients could be identified.
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Project description:The utility of intravenous tissue plasminogen activator (IV t-PA) in improving the clinical outcomes after acute ischemic stroke has been well demonstrated in past clinical trials. Though multiple initial small series of endovascular stroke therapy had shown good outcomes as compared to IV t-PA, a similar beneficial effect had not been translated in multiple randomized clinical trials of endovascular stroke therapy. Over the same time, there have been parallel advances in imaging technology and better understanding and utility of the imaging in therapy of acute stroke. In this review, we will discuss the evolution of endovascular stroke therapy followed by a discussion of the key factors that have to be considered during endovascular stroke therapy and directions for future endovascular stroke trials.
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Project description:ObjectiveTo consolidate the evidence from randomized trials for the use of endovascular therapy (ET) in patients with acute ischemic stroke.MethodsWe searched major databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus) from their inception to February 12, 2013, for randomized trials evaluating the efficacy of ET compared with standard of care for acute ischemic stroke. Pooled absolute and relative risk estimates were synthesized by using a random-effects model. Heterogeneity was assessed by using Q statistic and I(2) statistic. Subset analysis was performed for patients with severe stroke (National Institutes of Health Stroke Scale score ≥20). The study was conducted from January 15, 2013 to April 30, 2013.ResultsOf the 1252 retrieved articles, 5 randomized trials enrolling 1197 patients with acute ischemic stroke were included. Seven hundred eleven patients received ET, and 486 received intravenous (IV) tissue plasminogen activator. There was no significant improvement in any of the outcomes in patients receiving ET compared with those receiving IV thrombolysis. On subgroup analysis, ET was found to have better outcomes in patients with severe stroke (National Institutes of Health Stroke Scale score ≥20), showing a dose-response gradient and improving excellent, good, and fair outcomes by an additional 4%, 7%, and 13%, respectively, compared with IV thrombolysis.ConclusionOverall, ET is not superior to IV thrombolysis for acute ischemic strokes (level B recommendation). However, ET showed promise and improved outcomes in patients with severe strokes, but the evidence is limited due to sample size. There is a need for further trials evaluating the role of ET in this high-risk group.
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Project description:Brain ischemic stroke is one of the most common causes of death and disability, currently has no efficient therapeutic strategy in clinic. Due to irreversible functional neurons loss and neural tissue injury, stem cell transplantation may be the most promising treatment approach. Neural stem cells (NSCs) as the special type of stem cells only exist in the nervous system, can differentiate into neurons, astrocytes, and oligodendrocytes, and have the abilities to compensate insufficient endogenous nerve cells and improve the inflammatory microenvironment of cell survival. In this review, we focused on the important role of NSCs therapy for brain ischemic stroke, mainly introduced the methods of optimizing the therapeutic efficacy of NSC transplantation, such as transfection and overexpression of specific genes, pretreatment of NSCs with inflammatory factors, and co-transplantation with cytokines. Next, we discussed the potential problems of NSC transplantation which seriously limited their rapid clinical transformation and application. Finally, we expected a new research topic in the field of stem cell research. Based on the bystander effect, exosomes derived from NSCs can overcome many of the risks and difficulties associated with cell therapy. Thus, as natural seed resource of nervous system, NSCs-based cell-free treatment is a newly therapy strategy, will play more important role in treating ischemic stroke in the future.
| S-EPMC6828598 | biostudies-literature