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Metabolic-driven analytics of traumatic brain injury and neuroprotection by ethyl pyruvate

Authors :
Nikita Golovachev
Lorraine Siebold
Richard L. Sutton
Sima Ghavim
Neil G. Harris
Brenda Bartnik-Olson
Source :
Journal of Neuroinflammation, Vol 21, Iss 1, Pp 1-21 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract Background Research on traumatic brain injury (TBI) highlights the significance of counteracting its metabolic impact via exogenous fuels to support metabolism and diminish cellular damage. While ethyl pyruvate (EP) treatment shows promise in normalizing cellular metabolism and providing neuroprotection, there is a gap in understanding the precise metabolic pathways involved. Metabolomic analysis of the acute post-injury metabolic effects, with and without EP treatment, aims to deepen our knowledge by identifying and comparing the metabolite profiles, thereby illuminating the injury's effects and EP's therapeutic potential. Methods In the current study, an untargeted metabolomics approach was used to reveal brain metabolism changes in rats 24 h after a controlled cortical impact (CCI) injury, with or without EP treatment. Using principal component analysis (PCA), volcano plots, Random Forest and pathway analysis we differentiated the brain metabolomes of CCI and sham injured animals treated with saline (Veh) or EP, identifying key metabolites and pathways affected by injury. Additionally, the effect of EP on the non-injured brain was also explored. Results PCA showed a clear separation of the four study groups (sham-Veh, CCI-Veh, sham-EP, CCI-EP) based on injury. Following CCI injury (CCI-Veh), 109 metabolites belonging to the amino acid, carbohydrate, lipid, nucleotide, and xenobiotic families exhibited a twofold change at 24 h compared to the sham-Veh group, with 93 of these significantly increasing and 16 significantly decreasing (p

Details

Language :
English
ISSN :
17422094
Volume :
21
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Neuroinflammation
Publication Type :
Academic Journal
Accession number :
edsdoj.468e9481ba849cdadb33258747a77b4
Document Type :
article
Full Text :
https://doi.org/10.1186/s12974-024-03280-8