Discovering novel plasma biomarkers for ischemic stroke: Lipidomic and metabolomic analyses in an aged mouse model.

Autor:	Becktel DA; Department of Immunobiology, College of Medicine, University of Arizona, Tucson, Arizona, USA., Frye JB; Department of Immunobiology, College of Medicine, University of Arizona, Tucson, Arizona, USA., Le EH; Department of Immunobiology, College of Medicine, University of Arizona, Tucson, Arizona, USA., Whitman SA; Department of Immunobiology, College of Medicine, University of Arizona, Tucson, Arizona, USA., Schnellmann RG; Department of Pharmacology and Toxicology, R. Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona, USA; Coit Center for Longevity and Neurotherapeutics, R. Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona, USA; BIO5 Institute, College of Medicine, University of Arizona, Tucson, Arizona, USA., Morrison HW; College of Nursing, University of Arizona, Tucson, Arizona, USA., Doyle KP; Department of Immunobiology, College of Medicine, University of Arizona, Tucson, Arizona, USA; BIO5 Institute, College of Medicine, University of Arizona, Tucson, Arizona, USA; Department of Neurology, College of Medicine, University of Arizona, Tucson, Arizona, USA; Arizona Center on Aging, University of Arizona, Tucson, Arizona, USA; Department of Psychology, College of Science, University of Arizona, Tucson, Arizona, USA; Department of Neurosurgery, College of Medicine, University of Arizona, Tucson, Arizona, USA. Electronic address: doylekr@arizona.edu.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2024 Sep; Vol. 65 (9), pp. 100614. Date of Electronic Publication: 2024 Aug 02.
DOI:	10.1016/j.jlr.2024.100614
Abstrakt:	Ischemic stroke remains a leading cause of mortality and long-term disability worldwide, necessitating efforts to identify biomarkers for diagnosis, prognosis, and treatment monitoring. The present study aimed to identify novel plasma biomarkers of neurodegeneration and inflammation in a mouse model of stroke induced by distal middle cerebral artery occlusion. Using targeted lipidomic and global untargeted metabolomic profiling of plasma collected from aged male mice 24 h after stroke and weekly thereafter for 7 weeks, we discovered distinct acute and chronic signatures. In the acute phase, we observed elevations in myelin-associated lipids, including sphingomyelin (SM) and hexosylceramide (HCER) lipid species, indicating brain lipid catabolism. In the chronic phase, we identified 12-hydroxyeicosatetraenoic acid (12-HETE) as a putative biomarker of prolonged inflammation, consistent with our previous observation of a biphasic pro-inflammatory response to ischemia in the mouse brain. These results provide insight into the metabolic alterations detectable in the plasma after stroke and highlight the potential of myelin degradation products and arachidonic acid derivatives as biomarkers of neurodegeneration and inflammation, respectively. These discoveries lay the groundwork for further validation in human studies and may improve stroke management strategies. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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