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

  • Edna Maria Vissoci ReicheEmail author
  • Jair Roberto Gelinksi
  • Daniela Frizon Alfieri
  • Tamires Flauzino
  • Marcio Francisco Lehmann
  • Maria Caroline Martins de Araújo
  • Marcell Alysson Batisti Lozovoy
  • Andrea Name Colado Simão
  • Elaine Regina Delicato de Almeida
  • Michael Maes
Original Article
  • 36 Downloads

Abstract

The aim of the study was to define new immune-inflammatory, oxidative stress and biochemical biomarkers, which predict mortality within a period of 3 months after acute ischemic stroke (AIS). We recruited 176 healthy volunteers and 145 AIS patients, categorized as AIS survivors and non-survivors, and measured interleukin (IL)-6, high sensitivity C-reactive protein (hsCRP), ferritin, iron, total serum protein (TSP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), 25 hydroxyvitamin D [25(OH)D], lipid hydroperoxides (CL-LOOH), insulin, glucose and high-density lipoprotein (HDL)-cholesterol. In patients, these biomarkers were measured within 24 h after AIS onset. We also computed two composite scores reflecting inflammatory indices, namely INFLAM index1 (sum of z scores of hsCRP+IL-6 + ferritin+ESR + WBC) and INFLAM index2 (z INFLAM index1 – z 25(OH)D – z iron + z TSP). Three months after AIS, non-survivors (n = 54) showed higher baseline levels of IL-6, hsCRP, ferritin and glucose and lower levels of HDL-cholesterol and 25(OH)D than survivors (n = 91). Non-survivors showed higher baseline ESR and lowered TSP than controls, while survivors occupied an intermediate position. Death after AIS was best predicted by increased IL-6, glucose, ferritin and CL-LOOH and lowered 25(OH)D levels. The area under the receiver operating curves computed on the INFLAM index1 and 2 scores were 0.851 and 0.870, respectively. In conclusion, activation of peripheral immune-inflammatory, oxidative and biochemical pathways is critically associated with mortality after AIS. Our results may contribute to identify new biomarker sets, which may predict post-stroke death, as well as suggest that IL-6 trans-signaling coupled with redox imbalances may be possible new targets in the prevention of short-term outcome AIS death.

Keywords

Ischemic stroke Mortality Inflammation IL-6 Oxidative stress Biomarkers 

Notes

Acknowledgments

Thanks to the Institutional Program for Scientific Initiation Scholarship (PIBIC) of the National Council for Scientific and Technological Development (CNPq); Clinical and Laboratory Pathophysiology Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil; and Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil.

Authors’ contributions

Study concept and design: EMVR and ANCS; acquisition of data: JRG, DFA, TF, MFL, MCMA; analysis and interpretation of data: EMVR, ANCS, MM; drafting of the manuscript: EMVR and MM; statistical analysis: MM; study supervision: EMVR, ERDA.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Edna Maria Vissoci Reiche
    • 1
    Email author
  • Jair Roberto Gelinksi
    • 2
  • Daniela Frizon Alfieri
    • 3
  • Tamires Flauzino
    • 3
  • Marcio Francisco Lehmann
    • 4
  • Maria Caroline Martins de Araújo
    • 5
  • Marcell Alysson Batisti Lozovoy
    • 1
  • Andrea Name Colado Simão
    • 1
  • Elaine Regina Delicato de Almeida
    • 1
  • Michael Maes
    • 6
    • 7
    • 8
  1. 1.Department of Pathology, Clinical Analysis, and Toxicology, Health Sciences CenterLondrina State UniversityLondrinaBrazil
  2. 2.Clinical and Laboratory Pathophysiology Postgraduate Program, Health Sciences CenterState University of LondrinaLondrinaBrazil
  3. 3.Health Sciences Postgraduate Program, Health Sciences CenterState University of LondrinaLondrinaBrazil
  4. 4.Department of Clinical Surgery, Health Sciences Center, and Neurosurgery Service of the University HospitalState University of LondrinaLondrinaBrazil
  5. 5.Neurology Postgraduate Program, Health Sciences CenterState University of LondrinaLondrinaBrazil
  6. 6.IMPACT Strategic Research Centre, School of MedicineDeakin UniversityGeelongAustralia
  7. 7.Department of Psychiatry, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  8. 8.Department of PsychiatryMedical University PlovdivPlovdivBulgaria

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