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Novel Metabolites as Potential Indicators of Ischemic Infarction Volume: a Pilot Study

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Abstract

Metabolomics may identify biomarkers for acute ischemic stroke (AIS). Previously, circulating metabolites were compared in AIS and healthy controls without accounting for stroke size. The goal of this study was to identify metabolites that associate with the volume of AIS. We prospectively analyzed 1554 serum metabolites in the acute (72 h) and chronic (3–6 months) stages of 60 ischemic stroke patients. We calculated infarct volume using diffusion-weighted images with MR segmentation software and associated the volume with stage-specific metabolites, acute-to-chronic stage changes, and multiple mixed regression in metabolite concentrations using multivariate regression analysis. We used the two-stage Benjamini and Hochberg (TSBH) procedure for multiple testing. Four unknown metabolites at the acute stage significantly associated with infarct volume: X24541, X24577, X24581, and X2482 (all p < 0.01). Nine metabolites at the chronic stage are significantly associated with infarct volume: indolpropinate, alpha ketoglutaramate, picolinate, X16087, X24637, X24576, X24577, X24582, X24581 (all p < 0.048). Infarct volume is also associated with significant changes in serum concentrations of twenty-seven metabolites, with p values from 0.01 to 1.48 × 10−7, and on five metabolites using mixed regression model. This prospective pilot study identified several metabolites associated with the volume of ischemic infarction. Confirmation of these findings on a larger dataset would help characterize putative pathways underlying the size of ischemic infarction and facilitate the identification of biomarkers or therapeutic targets.

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All data are available on request.

References

  1. Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics-2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139–596.

    Article  Google Scholar 

  2. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46–e110.

    Article  Google Scholar 

  3. Albers GW, Goyal M, Jahan R, Bonafe A, Diener HC, Levy EI, et al. Ischemic core and hypoperfusion volumes predict infarct size in SWIFT PRIME. Ann Neurol. 2016;79(1):76–89.

    Article  Google Scholar 

  4. Sidorov E, Sanghera DK, Vanamala JKP. Biomarker for ischemic stroke using metabolome: a clinician perspective. J Stroke. 2019;21(1):31–41.

    Article  Google Scholar 

  5. Santucci JA, Ross SR, Greenert JC, et al. Radiological estimation of intracranial blood volume and occurrence of hydrocephalus determines stress-induced hyperglycemia after aneurysmal subarachnoid hemorrhage. Transl Stroke Res. 2018. https://doi.org/10.1007/s12975-018-0646-7.

  6. National Institute of Neurological D, Stroke rt PASSG. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581–7.

    Article  Google Scholar 

  7. LaCombe DM, Gordon DL, Issenberg SB, Vega A, Brocato C, Siegel M, et al. Stroke on the mend. JEMS. 2000;25(10):32–41.

    CAS  PubMed  Google Scholar 

  8. del Zoppo GJ, Poeck K, Pessin MS, Wolpert SM, Furlan AJ, Ferbert A, et al. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol. 1992;32(1):78–86.

    Article  Google Scholar 

  9. Pessin MS, Del Zoppo GJ, Estol CJ. Thrombolytic agents in the treatment of stroke. Clin Neuropharmacol. 1990;13(4):271–89.

    Article  CAS  Google Scholar 

  10. Long T, Hicks M, Yu HC, Biggs WH, Kirkness EF, Menni C, et al. Whole-genome sequencing identifies common-to-rare variants associated with human blood metabolites. Nat Genet. 2017;49(4):568–78.

    Article  CAS  Google Scholar 

  11. Dehaven CD, Evans AM, Dai H, Lawton KA. Organization of GC/MS and LC/MS metabolomics data into chemical libraries. J Cheminform. 2010;2(1):9.

    Article  Google Scholar 

  12. Costa C, Maraschin M, Rocha M. An R package for the integrated analysis of metabolomics and spectral data. Comput Methods Prog Biomed. 2016;129:117–24.

    Article  Google Scholar 

  13. Chong J, Yamamoto M, **a J. MetaboAnalystR 2.0: from raw spectra to biological insights. Metabolites. 2019;9(3):57.

  14. Allison PD. Multiple regression : a primer. Thousand Oaks: Pine Forge Press; 1999.

    Google Scholar 

  15. Bendheim PE, Poeggeler B, Neria E, Ziv V, Pappolla MA, Chain DG. Development of indole-3-propionic acid (OXIGON) for Alzheimer’s disease. J Mol Neurosci. 2002;19(1–2):213–7.

    Article  CAS  Google Scholar 

  16. Liu M, Zhou K, Li H, Dong X, Tan G, Chai Y, et al. Potential of serum metabolites for diagnosing post-stroke cognitive impairment. Mol BioSyst. 2015;11(12):3287–96.

    Article  CAS  Google Scholar 

  17. Sundaram B, Aggarwal A, Sandhir R. Chromium picolinate attenuates hyperglycemia-induced oxidative stress in streptozotocin-induced diabetic rats. J Trace Elem Med Biol. 2013;27(2):117–21.

    Article  CAS  Google Scholar 

  18. Cheng S, Shah SH, Corwin EJ, et al. Potential impact and study considerations of metabolomics in cardiovascular health and disease: a scientific statement from the American Heart Association. Circ Cardiovasc Genet. 2017;10(2):e1–e13.

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Acknowledgments

This work was supported by the NIH (R01DK082766) and a Presbyterian Health Foundation Grant. The authors thank Rebecka Bourn, PhD, for writing assistance (U54GM104938). Authors thank the participants of MISS and are grateful for their contribution in this study.

Funding

This work was supported by the NIH (R01DK082766) and a Presbyterian Health Foundation Grant.

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Authors and Affiliations

  1. Department of Neurology, University of Oklahoma Health Sciences Center (OUHSC), 920 S.L.Young Blvd #2040, Oklahoma City, OK, 73014, USA

    Evgeny V. Sidorov, David Gordon & Juliane Chainakul

  2. Oklahoma Center for Neuroscience, OUHSC, Oklahoma City, OK, USA

    Evgeny V. Sidorov, David Gordon & Dharambir K. Sanghera

  3. Department of Pediatrics, College of Medicine, OUHSC, 940 Stanton Y Blvd, BMSB 317D, Oklahoma City, OK, 73104, USA

    Cynthia Bejar & Dharambir K. Sanghera

  4. Biostatistics and Epidemiology, OUHSC, Oklahoma City, OK, USA

    Chao Xu

  5. Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Oklahoma City, OK, USA

    Bappaditya Ray

  6. Pharmaceutical Sciences, OUHSC, Oklahoma City, OK, USA

    Dharambir K. Sanghera

Authors
  1. Evgeny V. Sidorov
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  2. Cynthia Bejar
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  3. Chao Xu
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  4. Bappaditya Ray
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  5. David Gordon
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  6. Juliane Chainakul
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  7. Dharambir K. Sanghera
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Corresponding authors

Correspondence to Evgeny V. Sidorov or Dharambir K. Sanghera.

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The authors declare that they have no conflict of interest.

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Study was approved by local IRB office.

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Obtained from all participants.

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Obtained from all participants.

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R package MetaboAnalystR.

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Sidorov, E.V., Bejar, C., Xu, C. et al. Novel Metabolites as Potential Indicators of Ischemic Infarction Volume: a Pilot Study. Transl. Stroke Res. 12, 778–784 (2021). https://doi.org/10.1007/s12975-020-00876-z

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  • DOI: https://doi.org/10.1007/s12975-020-00876-z

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