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Immune-Inflammatory, Metabolic, Oxidative, and Nitrosative Stress Biomarkers Predict Acute Ischemic Stroke and Short-Term Outcome

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Abstract

Immune-inflammatory, metabolic, oxidative, and nitrosative stress (IMO&NS) pathways and, consequently, neurotoxicity are involved in acute ischemic stroke (IS). The simultaneous assessment of multiple IMO&NS biomarkers may be useful to predict IS and its prognosis. The aim of this study was to identify the IMO&NS biomarkers, which predict short-term IS outcome. The study included 176 IS patients and 176 healthy controls. Modified Rankin scale (mRS) was applied within 8 h after IS (baseline) and 3 months later (endpoint). Blood samples were obtained within 24 h after hospital admission. IS was associated with increased white blood cell (WBC) counts, high sensitivity C-reactive protein (hsCRP), interleukin (IL-6), lipid hydroperoxides (LOOHs), nitric oxide metabolites (NOx), homocysteine, ferritin, erythrocyte sedimentation rate (ESR), glucose, insulin, and lowered iron, 25-hydroxyvitamin D [25(OH)D], total cholesterol, and high-density lipoprotein (HDL) cholesterol. We found that 89.4% of the IS patients may be correctly classified using the cumulative effects of male sex, systolic blood pressure (SBP), glucose, NOx, LOOH, 25(OH)D, IL-6, and WBC with sensitivity of 86.2% and specificity of 93.0%. Moreover, increased baseline disability (mRS ≥ 3) was associated with increased ferritin, IL-6, hsCRP, WBC, ESR, and glucose. We found that 25.0% of the variance in the 3-month endpoint (mRS) was explained by the regression on glucose, ESR, age (all positively), and HDL-cholesterol, and 25(OH)D (both negatively). These results show that the cumulative effects of IMO&NS biomarkers are associated with IS and predict a poor outcome at 3-month follow-up.

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The samples were consecutively and anonymously coded to guarantee the confidentiality.

Funding

This study was financed, in part, by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil (CAPES), Finance Code 001.

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Contributions

Conceptualization: DFA, ANCS, EMVR; Methodology: MFL, MCAM, NP, DFA, TF, FD, RMT, ERDA; Formal analysis and investigation: DFA, MM; Writing: DFA, ANCS, EMVR; Writing - review and editing: DFA, MM, EMVR; Supervision: MM; EMVR.

Corresponding author

Correspondence to Edna Maria Vissoci Reiche.

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The authors declare that they have no conflict of interest.

Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. The protocol was approved by the Institutional Research Ethic Committee of the State University of Londrina, Paraná State, Brazil (CAAE 0250.0.268.000-11).

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Written consent form was obtained from all individual participants included in the study.

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Alfieri, D.F., Lehmann, M.F., Flauzino, T. et al. Immune-Inflammatory, Metabolic, Oxidative, and Nitrosative Stress Biomarkers Predict Acute Ischemic Stroke and Short-Term Outcome. Neurotox Res 38, 330–343 (2020). https://doi.org/10.1007/s12640-020-00221-0

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  • DOI: https://doi.org/10.1007/s12640-020-00221-0

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