TY - JOUR
T1 - Novel Metabolites as Potential Indicators of Ischemic Infarction Volume
T2 - a Pilot Study
AU - Sidorov, Evgeny V.
AU - Bejar, Cynthia
AU - Xu, Chao
AU - Ray, Bappaditya
AU - Gordon, David
AU - Chainakul, Juliane
AU - Sanghera, Dharambir K.
N1 - Funding Information:
This work was supported by the NIH (R01DK082766) and a Presbyterian Health Foundation Grant.
Funding Information:
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 Information:
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.
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - Acute ischemic stroke
KW - Biomarkers
KW - Infarction volume
KW - Metabolites
KW - Metabolomics
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U2 - 10.1007/s12975-020-00876-z
DO - 10.1007/s12975-020-00876-z
M3 - Article
C2 - 33215346
AN - SCOPUS:85096303223
SN - 1868-4483
VL - 12
SP - 778
EP - 784
JO - Translational Stroke Research
JF - Translational Stroke Research
IS - 5
ER -