Immune-inflammatory, oxidative stress and biochemical biomarkers predict short-term acute ischemic stroke death

Reiche, Edna Maria Vissoci; Gelinksi, Jair Roberto; Alfieri, Daniela Frizon; Flauzino, Tamires; Lehmann, Márcio Francisco; Araújo, Maria Caroline Martins de; Lozovoy, Marcell Alysson Batisti; Simão, Andréa Name Colado; Almeida, Elaine Regina Delicato de; Maes, Michaël

doi:10.1007/s11011-019-00403-6

Cited by 37 publications

(50 citation statements)

References 90 publications

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“…Inflammatory factors can activate MMPs, disrupt BBB integrity and worsen brain damage (Rosell et al, 2008;Jickling et al, 2015). The cross-talk between oxidative stress and neuroinflammation in ischemic stroke has been extensively studied (Collino et al, 2006;Chehaibi et al, 2016;Reiche et al, 2019;Yang Q. et al, 2019;Zhou F. et al, 2019). ROS activates various inflammatory factors for inducing neural cell death, disrupting the integrity of the BBB and enlarging the infarct volume (Crack and Taylor, 2005;Chen H.S.…”

Section: Introductionmentioning

confidence: 99%

Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds

Chen

et al. 2020

Front. Physiol.

171

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Oxidative stress and inflammation are two critical pathological processes of cerebral ischemia-reperfusion injury. Myeloperoxidase (MPO) is a critical inflammatory enzyme and therapeutic target triggering both oxidative stress and neuroinflammation in the pathological process of cerebral ischemia-reperfusion injury. MPO is presented in infiltrated neutrophils, activated microglial cells, neurons, and astrocytes in the ischemic brain. Activation of MPO can catalyze the reaction of chloride and H 2 O 2 to produce HOCl. MPO also mediates oxidative stress by promoting the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), modulating the polarization and inflammation-related signaling pathways in microglia and neutrophils. MPO can be a therapeutic target for attenuating oxidative damage and neuroinflammation in ischemic stroke. Targeting MPO with inhibitors or gene deficiency significantly reduced brain infarction and improved neurological outcomes. This article discusses the important roles of MPO in mediating oxidative stress and neuroinflammation during cerebral ischemia-reperfusion injury and reviews the current understanding of the underlying mechanisms. Furthermore, we summarize the active compounds from medicinal herbs with potential as MPO inhibitors for anti-oxidative stress and anti-inflammation to attenuate cerebral ischemia-reperfusion injury, and as adjunct therapeutic agents for extending the window of thrombolytic treatment. We highlight that targeting MPO could be a promising strategy for alleviating ischemic brain injury, which merits further translational study.

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Section: Introductionmentioning

confidence: 99%

Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds

Chen

et al. 2020

Front. Physiol.

171

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“…IL-6 and TNF-α are potent pro-inflammatory cytokines that serve vital roles in the immune response during inflammation ( 19 ). IL-6 levels have been suggested as a potential biomarker that is associated with stroke outcomes ( 20 ), short-term acute ischemic stroke death ( 21 ) and post-stroke dementia ( 22 ). It has also been shown that the overexpression of TNF-α transcripts is an independent risk factor for the incidence of IS ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Promoter polymorphism of TNF‑α (rs1800629) is associated with ischemic stroke susceptibility in a southern Thai population

et al. 2021

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Stroke represents the leading cause of disability and mortality amongst the elderly worldwide. Multiple risk factors, including both genetic and non-genetic components, as well as their interactions, are proposed as etiological factors involved in the development of ischemic stroke (IS). Promoter polymorphisms of the IL-6-174G/C (rs1800795) and TNF-α-308G/A (rs1800629) genes have been considered as predictive risk factors of IS; however, these have not yet been evaluated in a Thai population. The aims of this study were to investigate the association of IL-6-174G/C and TNF-α-308G/A polymorphisms with IS. Genomic DNA from 200 patients with IS and 200 controls were genotyped for IL-6-174G/C and TNF-α-308G/A polymorphisms using TaqMan™ SNP genotyping and quantitative PCR-high resolution melting analysis, respectively. It was found that the TNF-α-308 A allele was significantly associated with an increased risk of IS development compared with the G allele [odds ratio (OR)=2.044; 95% CI=1.154-3.620; P=0.014]. Moreover, the IS risk was significantly higher in the presence of TNF-α-308 GA or AA genotypes compared with that in the presence of GG genotypes with a dominant inheritance (OR=1.971; 95% CI=1.080-3.599; P=0.027). However, there was no association between IL-6-174G/C and the risk of IS development. The interaction study demonstrated that IL-6-174 GG and TNF-α-308 GG genotypes enhanced IS susceptibility when combined with hypertension, hyperlipidemia and alcohol consumption. Hypertensive and hyperlipidemic subjects with the TNF-α-308 GA and AA genotypes were more likely to develop IS compared with those who did not have these two conditions and had the GG genotype. In a matched study design (1:1), the IL-6-174 GC genotype was associated with higher IL-6 levels in the control group. Collectively, the present results highlight the utility of the TNF-α-308G/A polymorphism as a predictive genetic risk factor for development of IS.

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“…The value of IL-6 to predict mortality after cerebral ischemia has also been studied before. Various studies support that increased baseline levels of IL-6 are associated with risk of death 3 months after the event [ 23 , 24 , 25 , 26 ]. Regarding long-term mortality, it has been revealed that IL-6 could also predict mortality both 1 year [ 27 ] and 2 years [ 28 ] after stroke.…”

Section: Discussionmentioning

confidence: 99%

Blood Biomarkers to Predict Long-Term Mortality after Ischemic Stroke

Ramiro

Abraira

Quintana

et al. 2021

Life

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Stroke is a major cause of disability and death globally, and prediction of mortality represents a crucial challenge. We aimed to identify blood biomarkers measured during acute ischemic stroke that could predict long-term mortality. Nine hundred and forty-one ischemic stroke patients were prospectively recruited in the Stroke-Chip study. Post-stroke mortality was evaluated during a median 4.8-year follow-up. A 14-biomarker panel was analyzed by immunoassays in blood samples obtained at hospital admission. Biomarkers were normalized and standardized using Z-scores. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with long-term mortality and mortality due to stroke. In the multivariate analysis, the independent predictors of long-term mortality were age, female sex, hypertension, glycemia, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Independent blood biomarkers predictive of long-term mortality were endostatin > quartile 2, tumor necrosis factor receptor-1 (TNF-R1) > quartile 2, and interleukin (IL)-6 > quartile 2. The risk of mortality when these three biomarkers were combined increased up to 69%. The addition of the biomarkers to clinical predictors improved the discrimination (integrative discriminative improvement (IDI) 0.022 (0.007–0.048), p < 0.001). Moreover, endostatin > quartile 3 was an independent predictor of mortality due to stroke. Altogether, endostatin, TNF-R1, and IL-6 circulating levels may aid in long-term mortality prediction after stroke.

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Immune-inflammatory, oxidative stress and biochemical biomarkers predict short-term acute ischemic stroke death

Cited by 37 publications

References 90 publications

Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds

Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds

Promoter polymorphism of TNF‑α (rs1800629) is associated with ischemic stroke susceptibility in a southern Thai population

Blood Biomarkers to Predict Long-Term Mortality after Ischemic Stroke

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