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

Author:

Shevtsova Yulia12,Starodubtseva Natalia13,Tokareva Alisa1,Goryunov Kirill1,Sadekova Alsu1,Vedikhina Irina1,Ivanetz Tatiana1ORCID,Ionov Oleg1,Frankevich Vladimir1,Plotnikov Egor12ORCID,Sukhikh Gennady1,Zorov Dmitry12ORCID,Silachev Denis12ORCID

Affiliation:

1. V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia

2. A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia

3. Moscow Institute of Physics and Technology, 141700 Moscow, Russia

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 use hypothermic therapy is critical. Distinguishing HIE from other neonatal conditions, such as sepsis, becomes a significant problem in diagnosis. This study explored the utility of a metabolomic-based approach employing 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 fidelity of this approach in a range between 3 and 6 h 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 fidelity with areas under the receiver operating characteristic curve of 0.94 at 3 h and 0.96 at 6 h 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 h 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.

Funder

Russian Science Foundation

Publisher

MDPI AG

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