scholarly journals Resveratrol has an Overall Neuroprotective Role in Ischemic Stroke: A Meta-Analysis in Rodents

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianyang Liu ◽  
Jialin He ◽  
Yan Huang ◽  
Zhiping Hu

Background: Resveratrol, a natural polyphenolic phytoalexin, is broadly presented in dietary sources. Previous research has suggested its potential neuroprotective effects on ischemic stroke animal models. However, these results have been disputable. Here, we conducted a meta-analysis to comprehensively evaluate the effect of resveratrol treatment in ischemic stroke rodent models.Objective: To comprehensively evaluate the effect of resveratrol treatment in ischemic stroke rodent models.Methods: A literature search of the databases Pubmed, Embase, and Web of science identified 564 studies that were subjected to pre-defined inclusion criteria. 54 studies were included and analyzed using a random-effects model to calculate the standardized mean difference (SMD) with corresponding confidence interval (CI).Results: As compared with controls, resveratrol significantly decreased infarct volume (SMD −4.34; 95% CI −4.98 to −3.69; p < 0.001) and the neurobehavioral score (SMD −2.26; 95% CI −2.86 to −1.67; p < 0.001) in rodents with ischemic stroke. Quality assessment was performed using a 10-item checklist. Studies quality scores ranged from 3 to 8, with a mean value of 5.94. In the stratified analysis, a significant decrease of infarct volume and the neurobehavioral score was achieved in resveratrol sub-groups with a dosage of 20–50 mg/kg. In the meta-regression analysis, the impact of the delivery route on an outcome is the possible source of high heterogeneity.Conclusion: Generally, resveratrol treatment presented neuroprotective effects in ischemic stroke models. Furthermore, this study can direct future preclinical and clinical trials, with important implications for human health.

2020 ◽  
Vol 11 ◽  
Author(s):  
Yang Ye ◽  
Yu-Tian Zhu ◽  
Hong-Xuan Tong ◽  
Jing-Yan Han

Background: Recanalization with tissue plasminogen activator (tPA) is the only approved agent available for acute ischemic stroke. But delayed treatment of tPA may lead to lethal intracerebral hemorrhagic transformation (HT). Numerous studies have reported that immunomodulators have good efficacy on tPA-induced HT in ischemic stroke models. The benefits of immunomodulators on tPA-associated HT are not clearly defined. Here, we sought to conduct a systematic review and meta-analysis of preclinical studies to further evaluate the efficacy of immunomodulators.Methods: The PubMed, Web of Science, and Scopus electronic databases were searched for studies. Studies that reported the efficacy of immunomodulators on tPA-induced HT in animal models of stroke were included. Animals were divided into two groups: immunomodulators plus tPA (intervention group) or tPA alone (control group). The primary outcome was intracerebral hemorrhage, and the secondary outcomes included infarct volume and neurobehavioral score. Study quality was assessed by the checklist of CAMARADES. We used standardized mean difference (SMD) to assess the impact of interventions. Regression analysis and subgroup analysis were performed to identify potential sources of heterogeneity and evaluate the impact of the study characteristics. The evidence of publication bias was evaluated using trim and fill method and Egger’s test.Results: We identified 22 studies that met our inclusion criteria involving 516 animals and 42 different comparisons. The median quality checklist score was seven of a possible 10 (interquartile range, 6–8). Immunomodulators improved cerebral hemorrhage (1.31 SMD, 1.09–1.52); infarct volume (1.35 SMD, 0.95–1.76), and neurobehavioral outcome (0.9 SMD, 0.67–1.13) in experimental stroke. Regression analysis and subgroup analysis indicated that control of temperature and time of assessment were important factors that influencing the efficacy of immunomodulators.Conclusion: Our findings suggested that immunomodulators had a favorable effect on tPA-associated intracerebral hemorrhage, cerebral infarction, and neurobehavioral impairments in animal models of ischemic stroke.


Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 115
Author(s):  
Peter Shaw ◽  
Greg Raymond ◽  
Katherine S. Tzou ◽  
Siddhartha Baxi ◽  
Ravishankar Ram Mani ◽  
...  

Introduction: Melanoma is a global disease that is predominant in Western countries. However, reliable data resources and comprehensive studies on the theragnostic efficiency of miRNAs in melanoma are scarce. Hence, a decisive study or comprehensive review is required to collate the evidence for profiling miRNAs as a theragnostic marker. This protocol details a comprehensive systematic review and meta-analysis on the impact of miRNAs on chemoresistance and their association with theragnosis in melanoma. Methods and analysis: The articles will be retrieved from online bibliographic databases, including Cochrane Review, EMBASE, MEDLINE, PubMed, Scopus, Science Direct, and Web of Science, with different permutations of ‘keywords’. To obtain full-text papers of relevant research, a stated search method will be used, along with selection criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Protocols 2015 (PRISMA-P) standards were used to create this study protocol. The hazard ratio (HR) with a 95% confidence interval will be analyzed using Comprehensive Meta-Analysis (CMA) software 3.0. (CI). The pooled effect size will be calculated using a random or fixed-effects meta-analysis model. Cochran’s Q test and the I2 statistic will be used to determine heterogeneity. Egger’s bias indicator test, Orwin’s and the classic fail-safe N tests, the Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill calculation will all be used to determine publication bias. The overall standard deviation will be evaluated using Z-statistics. Subgroup analyses will be performed according to the melanoma participants’ clinicopathological and biological characteristics and methodological factors if sufficient studies and retrieved data are identified and available. The source of heterogeneity will be assessed using a meta-regression analysis. A pairwise matrix could be developed using either a pairwise correlation or expression associations of miRNA with patients’ survival for the same studies.


2020 ◽  
Author(s):  
Nida Fatima ◽  
Maher Saqqur ◽  
Ashfaq Shuaib

Abstract Objectives: Leptomeningeal collaterals provide an alternate pathway to maintain cerebral blood flow in stroke to prevent ischemia, but their role in predicting outcome is still unclear. So, our study aims at assessing the significance of collateral blood flow (CBF) in acute stroke. Methods: Electronic databases were searched under different MeSH terms from Jan 2000 to Feb 2019. Studies were included if there was available data on good and poor CBF in acute ischemic stroke (AIS). The clinical outcomes included were modified rankin scale (mRS), recanalization, mortality, and symptomatic intracranial hemorrhage (sICH) at 90 days. Data was analyzed using random-effect model.Results: A total of 47 studies with 8,194 patients were included. Pooled meta-analysis revealed that there exist 2-fold higher likelihood of favorable clinical outcome (mRS≤2) at 90 days with good CBF compared with poor CBF (RR: 2.27; 95%CI: 1.94-2.65; p<0.00001) irrespective of the thrombolytic therapy [RR with IVT: 2.90; 95%CI: 2.14-3.94; p<0.00001, and RR with IAT/EVT: 1.99; 95% CI: 1.55-2.55; p<0.00001]. Moreover, there exists 1-fold higher probability of successful recanalization with good CBF (RR: 1.31; 95% CI: 1.15-1.49; p<0.00001). However, there was 54% and 64% lower risk of sICH and mortality respectively in patients with good CBF in AIS (p<0.00001).Conclusions: The relative risk of favorable clinical outcome is more in patients with good pretreatment CBF. This could be explained due to better chances of recanalization, combined with lesser risk of intracerebral hemorrhage in good CBF status.


2021 ◽  
pp. 174749302110473
Author(s):  
Jin Pyeong Jeon ◽  
Chih-Hao Chen ◽  
Fon-Yih Tsuang ◽  
Jianming Liu ◽  
Michael D Hill ◽  
...  

Background. The impact of renal impairment (RI) on the outcomes of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) was relatively limited and contradictory. We performed a systematic review and meta-analysis to investigate this. Aims. We registered a protocol on September 2020 and searched MEDLINE, EMBASE, and Google Scholar accordingly. RI was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Predefined outcomes included functional independence (defined as a modified Rankin Scale of 0, 1, or 2) at 3 months, successful reperfusion, mortality, and symptomatic intracerebral hemorrhage (sICH). Summary of review. Eleven studies involving 3453 patients were included. For the unadjusted outcomes, RI was associated with fewer functional independence (odds ratio (OR), 0.49; 95% confidence interval (CI), 0.39–0.62) and higher mortality (OR, 2.55; 95% CI, 2.03–3.21). RI was not associated with successful reperfusion (OR, 0.80; 95% CI 0.63–1.00) and sICH (OR, 1.41; 95% CI, 0.95–2.10). For the adjusted outcomes, results derived from a multivariate meta-analysis were consistent with the respective unadjusted outcomes: functional independence (OR, 0.59; 95% CI, 0.45–0.77), mortality (OR, 2.23, 95% CI, 1.45–3.43), and sICH (OR, 1.34; 95% CI, 0.85–2.10). Conclusions. We presented the first systematic review to demonstrate that RI is associated with fewer functional independence and higher mortality. Future EVT studies should publish complete renal eGFR data to facilitate prognostic studies and permit eGFR to be analyzed in a continuous variable. Systematic Review Registration: PROSPERO CRD42020191309


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Tyler P Behymer ◽  
Achala Vagal ◽  
Heidi Sucharew ◽  
Vineeth Yeluru ◽  
Arjun Minhas ◽  
...  

Introduction: Cryptogenic stroke is defined as not attributable to an identified source despite standard evaluation. The absence of small vessel or large artery disease in such evaluation suggests that cryptogenic stroke may be largely cardioembolic. We hypothesized that cryptogenic stroke would be similar to cardioembolic stroke in clinical and imaging characteristics. Methods: The Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) is a population-based study that tracks the regional incidence of stroke. A convenient subsample from the 2010 GCNKSS ischemic stroke cohort (N= 368) was selected for detailed neuroimaging analysis. The study physician subtyped cases based on clinical, radiographic and laboratory findings (carotid ultrasound, echocardiography, vascular imaging). Subtypes included cryptogenic, cardioembolic, large-vessel, small-vessel, undetermined, and other. Three radiologists performed imaging analysis including number of acute infarcts, location and white matter hyperintensity (WMH). Infarct volume was segmented using manual tracing. Results: Of 368 ischemic stroke cases with imaging data, subtypes were 26.4% cryptogenic, 16.3% large vessel, 15.5% small vessel, 24.7% cardioembolic, 5.4% undetermined, and 11.7% other. Compared to cardioembolic, cryptogenic stroke patients were younger, had less hypertension, higher alcohol use, smaller infarct volume and differed in location of stroke. Cryptogenic stroke had more clinical and radiological features in common with large and small-vessel stroke (Table). Undetermined and other had no significant differences to cryptogenic. Conclusion: Contrary to our hypothesis, cryptogenic stroke was different from cardioembolic stroke and appeared more similar to large vessel stroke in clinical and radiological characteristics. Further testing on a larger sample size to evaluate the impact of cardiac event monitoring on subtype distribution is needed.


2017 ◽  
Vol 38 (11) ◽  
pp. 1319-1328 ◽  
Author(s):  
Philipp P. Kohler ◽  
Cheryl Volling ◽  
Karen Green ◽  
Elizabeth M. Uleryk ◽  
Prakesh S. Shah ◽  
...  

BACKGROUNDMortality associated with infections caused by carbapenem-resistantEnterobacteriaceae(CRE) is higher than mortality due to carbapenem-sensitive pathogens.OBJECTIVETo examine the association between mortality from bacteremia caused by carbapenem-resistant (CRKP) and carbapenem-sensitiveKlebsiella pneumoniae(CSKP) and to assess the impact of appropriate initial antibiotic therapy (IAT) on mortality.DESIGNSystematic review and meta-analysisMETHODSWe searched MEDLINE, EMBASE, CINAHL, and Wiley Cochrane databases through August 31, 2016, for observational studies reporting mortality among adult patients with CRKP and CSKP bacteremia. Search terms were related toKlebsiella, carbapenem-resistance, and infection. Studies including fewer than 10 patients per group were excluded. A random-effects model and meta-regression were used to assess the relationship between carbapenem-resistance, appropriateness of IAT, and mortality.RESULTSMortality was higher in patients who had CRKP bacteremia than in patients with CSKP bacteremia (15 studies; 1,019 CRKP and 1,148 CSKP patients; unadjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.8–2.6; I2=0). Mortality was lower in patients with appropriate IAT than in those without appropriate IAT (7 studies; 658 patients; unadjusted OR, 0.5; 95% CI, 0.3–0.8; I2=36%). CRKP patients (11 studies; 1,326 patients; 8-year period) were consistently less likely to receive appropriate IAT (unadjusted OR, 0.5; 95% CI, 0.3–0.7; I2=43%). Our meta-regression analysis identified a significant association between the difference in appropriate IAT and mortality (OR per 10% difference in IAT, 1.3; 95% CI, 1.0–1.6).CONCLUSIONSAppropriateness of IAT is an important contributor to the observed difference in mortality between patients with CRKP bacteremia and patients with CSKP bacteremia.Infect Control Hosp Epidemiol2017;38:1319–1328


2020 ◽  
pp. 0271678X2096745
Author(s):  
Alicia Aliena-Valero ◽  
Júlia Baixauli-Martín ◽  
María Castelló-Ruiz ◽  
Germán Torregrosa ◽  
David Hervás ◽  
...  

Addition of uric acid (UA) to thrombolytic therapy, although safe, showed limited efficacy in improving patients’ stroke outcome, despite alleged neuroprotective effects of UA in preclinical research. This systematic review assessed the effects of UA on brain structural and functional outcomes in animal models of ischaemic stroke. We searched Medline, Embase and Web of Science to identify 16 and 14 eligible rodent studies for qualitative and quantitative synthesis, respectively. Range of evidence met 10 of a possible 13 STAIR criteria. Median (Q1, Q3) quality score was 7.5 (6, 10) on the CAMARADES 15-item checklist. For each outcome, we used standardised mean difference (SMD) as effect size and random-effects modelling. Meta-analysis showed that UA significantly reduced infarct size (SMD: −1.18; 95% CI [−1.47, −0.88]; p < 0.001), blood-brain barrier (BBB) impairment/oedema (SMD: −0.72; 95% CI [−0.97, −0.48]; p < 0.001) and neurofunctional deficit (SMD: −0.98; 95% CI [−1.32, −0.63]; p < 0.001). Overall, there was low to moderate between-study heterogeneity and sizeable publication bias. In conclusion, published rodent data suggest that UA improves outcome following ischaemic stroke by reducing infarct size, improving BBB integrity and ameliorating neurofunctional condition. Specific recommendations are given for further high-quality preclinical research required to better inform clinical research.


2015 ◽  
Vol 35 (11) ◽  
pp. 1783-1789 ◽  
Author(s):  
Junxiang Yin ◽  
Pengcheng Han ◽  
Zhiwei Tang ◽  
Qingwei Liu ◽  
Jiong Shi

Stroke is one of the leading causes of death. Growing evidence indicates that ketone bodies have beneficial effects in treating stroke, but their underlying mechanism remains unclear. Our previous study showed ketone bodies reduced reactive oxygen species by using NADH as an electron donor, thus increasing the NAD+/NADH ratio. In this study, we investigated whether mitochondrial NAD+-dependent Sirtuin 3 (SIRT3) could mediate the neuroprotective effects of ketone bodies after ischemic stroke. We injected mice with either normal saline or ketones (beta-hydroxybutyrate and acetoacetate) at 30 minutes after ischemia induced by transient middle cerebral artery (MCA) occlusion. We found that ketone treatment enhanced mitochondria function, reduced oxidative stress, and therefore reduced infarct volume. This led to improved neurologic function after ischemia, including the neurologic score and the performance in Rotarod and open field tests. We further showed that ketones' effects were achieved by upregulating NAD+-dependent SIRT3 and its downstream substrates forkhead box O3a (FoxO3a) and superoxide dismutase 2 (SOD2) in the penumbra region since knocking down SIRT3 in vitro diminished ketones' beneficial effects. These results provide us a foundation to develop novel therapeutics targeting this SIRT3-FoxO3a-SOD2 pathway.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3993-3993
Author(s):  
Lisa K Lütkhoff ◽  
Manuela Albisetti ◽  
Timothy J. Bernard ◽  
Mariana Bonduel ◽  
Leonardo R. Brandao ◽  
...  

Abstract Abstract 3993 Poster Board III-929 Background The incidence of stroke in children is estimated at about 2.6 per 100,000 per year. Risk factors include congenital heart malformations, trauma, hemolytic anemias, collagen tissue diseases, inborn metabolic disorders, and infectious diseases. Apart from acquired thrombophilic risk factors, such as the presence of antiphospholipid antibodies, inherited thrombophilias (IT) have been found to be associated with stroke in infants and children. However, results of single studies on the risk of stroke onset associated with IT have been contradictory or inconclusive, mainly due to lack of statistical power. The aim of this study was to estimate the impact of thrombophilia (IT) on risk of childhood stroke via meta-analysis of published observational studies. Methods and Results A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted using key words in combination both as MeSH terms and text words. Citations were independently screened by two authors and those meeting the a priori defined inclusion criteria were retained. Data on year of publication, study design, country of origin, number of patients/controls, ethnicity, stroke type (arterial ischemic stroke [AIS]; cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed-effects and random-effects models. Twenty-one of 185 references found met inclusion criteria. 1698 patients (AIS: 1291; CSVT: 407) and 2913 controls aged neonate to 18 years were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with stroke onset was demonstrated for each IT trait evaluated, with no difference found between AIS (table) and CSVT. Summary ORs/CIs (random-effects model) for AIS & CSVT cohorts were as follows: Protein C-deficiency (8.76/4.53-16.96), FV G1691A (3.34/2.66-4.26), FII G20210A (2.50/1.67-3.74), MTHFR T677T (1.61/1.21-2.14), antiphospholipid antibodies (5.84/3.06-11.18), elevated lipoprotein (a) (6.24/4.51-8.64), and combined ITs (8.85/3.32-23.57). Carrier rates reported for antithrombin- or protein S deficiency among patients were 1.5% and 1.6% as compared with 0.06% (p<0.001) and 0.4% (p=0.003) in healthy controls. Conclusions The present meta-analysis indicates that IT serve as risk factors for incident stroke. However, the impact of IT upon outcome and recurrence risk needs to be further investigated. Disclosures: Manco-Johnson: Baxter BioScience: Honoraria; Bayer HealthCare: Honoraria; CSL Behring: Honoraria; NovoNordisk: Honoraria; Octapharma: Honoraria. Off Label Use: Enoxaparin (LMWH) is used off-label in children to prevent symptomatic thromboembolism.


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