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NMR metabolomic study of blood plasma in ischemic and ischemically preconditioned rats: an increased level of ketone bodies and decreased content of glycolytic products 24 h after global cerebral ischemia

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Abstract

Cardiac arrest is one of the leading causes of death among adults in older age. Understanding mechanisms how organism responds to ischemia at global level is essential for the prevention and ischemic patient’s treatment. In this study, we used a global cerebral ischemia induced by four-vessel occlusion as an established animal model for ischemic stroke to investigate metabolic changes after 24 h reperfusion, when transitions occur due to the onset of delayed neuronal death. We also focused on the endogenous phenomenon known as ischemic tolerance by the pre-ischemic treatment. The experiments were carried out on blood plasma samples as easily available and metabolically reflecting the overall changes in injured organism. Our results imply that disturbed glycolysis pathway, as a consequence of ischemic injury, leads to the increased level of ketone bodies (acetone, acetoacetate and β-hydroxybutyrate) along with increased utilization of triacylglycerols in plasma of ischemic and ischemically preconditioned rats. Complementary to, a decreased level of glycolytic intermediates (lactate, pyruvate, acetate) with increased level of glucose was found in ischemic and preconditioned animals. The protective effect of ischemic preconditioning on metabolome recovery was demonstrated by significantly increased level of creatine compared to ischemic, non-preconditioned rats. We also document that acetoacetate, pyruvate, lactate, and leucine have the best discriminatory power between ischemic and control plasma. Conclusively, our results provide evidence that NMR spectra analysis can identify specific group of metabolites present in plasma with the capability for discrimination between individual groups of animals. In addition, an excellent feasibility for the statistical discrimination among ischemic, preconditioned, and control rats can be applied regardless of native or deproteinated plasma and also regardless of noesy or cpmg NMR acquisition.

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Acknowledgments

This work was supported by the project “Biomedical Center Martin” ITMS code 26220220187, the project is co-financed from EU sources, Slovak Research and Development Agency (APVV) grant number APVV 15/0107, Slovak Scientific Grant Agency grant number VEGA 128/16, and “Identification of Novel Markers in Diagnostic panel of Neurological Diseases” code: 26220220114. This work was also supported by the project “ Center of Translational Medicine,” ITMS: 26220220021, co-funded from EU sources and European Regional Development Fund.

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Authors and Affiliations

  1. Division of Neuroscience, Biomedical Center BioMed, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4, 036 01, Martin, Slovakia

    Eva Baranovicova & Jan Lehotsky

  2. Bioinformatic Unit, Biomedical Center BioMed, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4, 036 01, Martin, Slovakia

    Marian Grendar

  3. Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4, 036 01, Martin, Slovakia

    Dagmar Kalenska, Anna Tomascova & Jan Lehotsky

  4. Department of Clinical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava and University Hospital Martin, Kollarova 2, 036 59, Martin, Slovakia

    Daniel Cierny

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  1. Eva Baranovicova
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Correspondence to Jan Lehotsky.

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Baranovicova, E., Grendar, M., Kalenska, D. et al. NMR metabolomic study of blood plasma in ischemic and ischemically preconditioned rats: an increased level of ketone bodies and decreased content of glycolytic products 24 h after global cerebral ischemia. J Physiol Biochem 74, 417–429 (2018). https://doi.org/10.1007/s13105-018-0632-2

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