Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Metabolite Biomarkers for Early Ischemic Hypoxic Encephalopathy: An Experimental Study Using the NeoBase 2 MSMS Kit in a Rat Model

Yulia Shevtsova
,
Natalia Starodubtseva
,
Alisa Tokareva
,
Kirill Goryunov
,
Alsu Sadekova
,
Irina Vedikhina
,
Tatiana Ivanetz
ORCID logo ,
Oleg Ionov
,
Vladimir Frankevich
,
Egor Plotnikov
ORCID logo ,
Gennady Sukhikh
,
Dmitry Zorov
* ,
Denis Silachev
ORCID logo
Version 1 : Received: 4 December 2023 / Approved: 5 December 2023 / Online: 5 December 2023 (15:31:23 CET)

A peer-reviewed article of this Preprint also exists.

Shevtsova, Y.; Starodubtseva, N.; Tokareva, A.; Goryunov, K.; Sadekova, A.; Vedikhina, I.; Ivanetz, T.; Ionov, O.; Frankevich, V.; Plotnikov, E.; Sukhikh, G.; Zorov, D.; Silachev, D. Metabolite Biomarkers for Early Ischemic–Hypoxic Encephalopathy: An Experimental Study Using the NeoBase 2 MSMS Kit in a Rat Model. Int. J. Mol. Sci. 2024, 25, 2035. Shevtsova, Y.; Starodubtseva, N.; Tokareva, A.; Goryunov, K.; Sadekova, A.; Vedikhina, I.; Ivanetz, T.; Ionov, O.; Frankevich, V.; Plotnikov, E.; Sukhikh, G.; Zorov, D.; Silachev, D. Metabolite Biomarkers for Early Ischemic–Hypoxic Encephalopathy: An Experimental Study Using the NeoBase 2 MSMS Kit in a Rat Model. Int. J. Mol. Sci. 2024, 25, 2035.

Abstract

Hypoxic-ischemic encephalopathy (HIE) is one of the most common causes of childhood disability. Hypothermic therapy is currently the only approved neuroprotective approach. However, early diagnosis of HIE can be challenging, especially in the first hours after birth when the decision to treat with hypothermic therapy is critical. Differentiating HIE from other neonatal conditions, such as sepsis, further complicates the diagnosis. This study investigated the utility of a metabolomic-based approach using the NeoBase 2 MSMS kit to diagnose HIE using dry blood stains in a Rice-Vannucci model of HIE in rats. We evaluated the diagnostic accuracy of this method between 3 and 6 hours after the onset of HIE, including in the context of systemic inflammation and concomitant hypothermic therapy. Discriminant analysis revealed several metabolite patterns associated with HIE. A logistic regression model using glycine levels achieved high diagnostic accuracy with areas under the curve (AUC) of 0.94 at 3 hours and 0.96 at 6 hours after the onset of HIE. In addition, orthogonal partial least squares discriminant analysis, which included five metabolites, achieved 100% sensitivity and 80% specificity within 3 hours of HIE. These results highlight the significant potential of the NeoBase 2 MSMS kit for the early diagnosis of HIE and could improve patient management and outcomes in this serious illness.

Keywords

metabolomics; amino acids; diagnostics; neonatal asphyxia; liquid chromatography–mass spectrometry; newborn screening

Subject

Biology and Life Sciences, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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