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Administration of thiazolidinediones for neuroprotection in ischemic stroke: a pre-clinical systematic review.

ABSTRACT: Thiazolidinediones (TZDs) may prevent or attenuate CNS injury arising from an ischemic event. We performed meta-analysis of experimental studies in which a TZD (either rosiglitazone or pioglitazone) was administered in a rodent model of focal or global cerebral ischemia. Infarct volume was the primary endpoint for analysis of drug efficacy, and neurological outcome was also assessed. We identified 31 studies through the use of PubMed and Embase, 22 of which met our pre-specified inclusion criteria and were analyzed with the Cochrane Review Manager software. Treatment with TZDs decreased infarct volume and improved neurological outcome regardless of study quality, dose timing, or ischemia model (transient or permanent). Rosiglitazone and pioglitazone were similarly effective in reducing infarct volume and protecting neurologic function. Importantly, the collective data suggest that pre-treatment with a TZD is not required for neuroprotection, although additional studies are clearly needed to define the breadth of the therapeutic window. The data warrant further studies into the potential acute use of TZDs for ischemic stroke therapy in the general population.

SUBMITTER: White AT

PROVIDER: S-EPMC2981074 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Administration of thiazolidinediones for neuroprotection in ischemic stroke: a pre-clinical systematic review.

White Amanda T AT Murphy Anne N AN

Journal of neurochemistry 20101007 4

Thiazolidinediones (TZDs) may prevent or attenuate CNS injury arising from an ischemic event. We performed meta-analysis of experimental studies in which a TZD (either rosiglitazone or pioglitazone) was administered in a rodent model of focal or global cerebral ischemia. Infarct volume was the primary endpoint for analysis of drug efficacy, and neurological outcome was also assessed. We identified 31 studies through the use of PubMed and Embase, 22 of which met our pre-specified inclusion criter ...[more]

PMID: 20964688

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Project description:BACKGROUND:Remote ischemic conditioning during cerebral ischemia (remote ischemic perconditioning, RIPerC) refers to the application of several cycles of brief ischemia and reperfusion (I/R) commonly to a limb, and it represents a new paradigm in neuroprotection with multiple mechanisms of action in ischemic stroke (IS) patients during acute phase. Some clinical trials just finished, and a few others are still ongoing; gather the current knowledge and pull it down to influence the present and future studies was the goal of this paper. METHODS:A systematic review of published research papers and/or registered clinical trials since 2000 was performed. RESULTS:Nineteen studies were identified and only four studies were completed. All of them have demonstrated that RIPerC is safe, feasible and well tolerated in IS patients. However, a high heterogeneity of clinical trial characteristics was observed: five (26.3%) randomized clinical trials (RCTs) included only thrombolytic-treated patients, three (15.8%) RCTs only thrombectomy-treated patients, and five (26.3%) RCTs required radiological confirmation of IS. Temporal inclusion criteria vary from 4 h to 48 h. Most of the clinical trials used 4 cycles of RIPerC in the upper non-affected limb. Interestingly, only three (16.7%) RCTs applied RIPerC during the transportation in the ambulance. Neuroimaging outputs were the main endpoints when endovascular therapy was applied; functional outcome is also the main endpoint in large-medium size studies. CONCLUSIONS:This review summarizes the completed and ongoing clinical trials on RIPerC in IS patients, where RIPerC has been used alone or in combination with recanalization therapies. Ongoing clinical trials will provide new information on the best RIPerC intervention strategy and potentially improve the functional outcome of IS patients; definition of new RIPerC strategies would ideally aim at enhancing tissue preservation, promoting neurological recovery, and stratify patients to improve treatment feasibility.

Project description:BackgroundStatin therapy is considered an effective measure for the prevention of ischemic stroke. Several recent studies have indicated that treatment with statins, prior to the onset of acute ischemic stroke, may also substantially reduce the severity of stroke and the degree of patient disability. The purpose of the present review is to systematically evaluate the effectiveness of statin pretreatment on functional outcome of acute ischemic stroke and to assess potential adverse events associated with statin use.MethodsRelevant articles on the role of statins in acute ischemic stroke were identified via MEDLINE/PubMed, EMBASE, CENTRAL, and by manual searches of the references of identified papers. Clinical studies (most were prospective cohort studies) assessing statin therapy for acute ischemic stroke were selected for the review. Only two randomized controlled clinical trials met the criteria to be included in the analysis. Clinical outcome was assessed based on the degree of disability determined with the modified Rankin Scale (mRS) and Barthel index (BI). The National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity. Recurrence of stroke in patients who had suffered from a previous stroke was analyzed with and without statin therapy. Incidence and severity of adverse reactions was reviewed. Because there were too many differences in study outcome measures, a quantitative analysis of data was deemed inappropriate. A qualitative summary of the data was consequently completed.ResultsThirteen reports were systematically reviewed to evaluate the efficacy and safety of statins in the pretreatment of acute ischemic stroke. Pretreatment with statins was found to reduce the recurrence of stroke and to result in more favorable outcomes for patients. The beneficial effects of prior statin therapy in acute ischemic stroke were shown to be especially profound in whites, diabetics, elderly patients with hypertension and other vascular diseases, and in patients with ideal low density lipoprotein (LDL) levels. There were few incidences of adverse reactions with statin pretreatment, most of which were not statistically significant.ConclusionsPretreatment with statins was associated with a favorable outcome in acute ischemic stroke, with few incidences of adverse reactions.

Project description:Background: In recent years pre-clinical stroke research has shown increased interest in the development of biomaterial-based therapies to promote tissue repair and functional recovery. Such strategies utilize biomaterials as structural support for tissue regeneration or as delivery vehicles for therapeutic agents. While a range of biomaterials have been tested in stroke models, currently no overview is available for evaluating the benefit of these approaches. We therefore performed a systematic review and meta-analysis of studies investigating the use of biomaterials for the treatment of stroke in experimental animal models. Methods: Studies were identified by searching electronic databases (PubMed, Web of Science) and reference lists of relevant review articles. Studies reporting lesion volume and/or neurological score were included. Standardized mean difference (SMD) and 95% confidence intervals were calculated using DerSimonian and Laird random effects. Study quality and risk of bias was assessed using the CAMARADES checklist. Publication bias was visualized by funnel plots followed by trim and fill analysis of missing publications. Results: A total of 66 publications were included in the systematic review, of which 44 (86 comparisons) were assessed in the meta-analysis. Overall, biomaterial-based interventions improved both lesion volume (SMD: -2.98, 95% CI: -3.48, -2.48) and neurological score (SMD: -2.3, 95% CI: -2.85, -1.76). The median score on the CAMARADES checklist was 5.5/10 (IQR 4.25-6). Funnel plots of lesion volume and neurological score data revealed pronounced asymmetry and publication bias. Additionally, trim and fill analysis estimated 19 "missing" studies for the lesion volume outcome adjusting the effect size to -1.91 (95% CI: -2.44, -1.38). Conclusions: Biomaterials including scaffolds and particles exerted a positive effect on histological and neurological outcomes in pre-clinical stroke models. However, heterogeneity in the field, publication bias and study quality scores which may be another source of bias call for standardization of outcome measures and improved study reporting.

Project description:BackgroundPredictors of recurrent ischemic stroke are less well known in patients with a recent ischemic stroke than in patients with transient ischemic attack (TIA). We identified clinical and radiological factors for predicting recurrent ischemic stroke in patients with recent ischemic stroke.MethodsA systematic search in PubMed, Embase, Cochrane Library, and CINAHL was performed with the terms "ischemic stroke," "predictors/determinants," and "recurrence." Quality assessment of the articles was performed and the level of evidence was graded for the articles included for the meta-analysis. Pooled risk ratios (RR) and heterogeneity (I2) were calculated using inverse variance random effects models.ResultsTen articles with high-quality results were identified for meta-analysis. Past medical history of stroke or TIA was a predictor of recurrent ischemic stroke (pooled RR 2.5, 95% CI 2.1-3.1). Small vessel strokes were associated with a lower risk of recurrence than large vessel strokes (pooled RR 0.3, 95% CI 0.1-0.7). Patients with stroke of an undetermined cause had a lower risk of recurrence than patients with large artery atherosclerosis (pooled RR 0.5, 95% CI 0.2-1.1). We found no studies using CT or ultrasound for the prediction of recurrent ischemic stroke. The following MRI findings were predictors of recurrent ischemic stroke: multiple lesions (pooled RR 1.7, 95% CI 1.5-2.0), multiple stage lesions (pooled RR 4.1, 95% CI 3.1-5.5), multiple territory lesions (pooled RR 2.9, 95% CI 2.0-4.2), chronic infarcts (pooled RR 1.5, 95% CI 1.2-1.9), and isolated cortical lesions (pooled RR 2.2, 95% CI 1.5-3.2).ConclusionsIn patients with a recent ischemic stroke, a history of stroke or TIA and the subtype large artery atherosclerosis are associated with an increased risk of recurrent ischemic stroke. Predictors evaluated with MRI include multiple ischemic changes and isolated cortical lesions. Predictors of recurrent ischemic stroke concerning CT or ultrasound have not been published.

Dataset Information

Administration of thiazolidinediones for neuroprotection in ischemic stroke: a pre-clinical systematic review.

Publications

Administration of thiazolidinediones for neuroprotection in ischemic stroke: a pre-clinical systematic review.

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