Molecular abnormalities scale across three models of cerebral injury.

Overview

1. Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States
2. Department of Biomedical Engineering, Tufts University, Medford, MA, United States
3. Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States
4. Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, United States
5. Department of Computer Science, University of Cincinnati, Cincinnati, OH, United States
6. Department of Mechanical Engineering, University of Cincinnati, Cincinnati, OH, United States
7. Department of Kinesiology, Pennsylvania State University, State College, PA, United States
8. Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, United States

Abstract

Human studies have demonstrated that repetitive head acceleration events (HAEs) disrupt metabolic homeostasis, raising the question of whether similar biochemical cascades scale across diverse platforms, from human to rodent to cell, for other traumatic brain injuries (TBIs). This study analyzed molecular disruptions in (i) humans with repetitive HAEs, (ii) mice with singular blast-elicited HAE with loss of consciousness, and (iii) a human 3D in vitro model of blunt injury. Humans exhibited metabolic, protein glycation, and epigenetic regulation abnormalities, with 30 pre-season metabolites predicting post-season levels with 89% accuracy. In vivo and in vitro RNA sequencing studies revealed convergence in 211 genes, with 123 metabolic genes mirroring human results. Regression analysis reflected an unprecedented 86% information scaling between platforms, namely, cell culture data predicted 86% of the information in the murine data. Athlete data linked these pathways to HAEs and motor behavior, highlighting convergent molecular disruptions across TBI models in metabolic homeostasis required for neural information processing. This approach across three platforms has not been shown before for brain-related disorders.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• doi:10.17632/5tygm8sn24.1, at the source; found in “Transparency, rigor, and reproducibility summary”
• geo:GSE237013, at NCBI GEO; found in “Transparency, rigor, and reproducibility summary”

Other data links

• ncbi.nlm.nih.gov/geo, NCBI; found in “Data availability statement”

Data availability statement

All data generated and analyzed during this study are available within this article and its Supplementary Information. The in vitro mRNA sequencing dataset generated for this study has been deposited in the NCBI Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE237013 (https://ncbi.nlm.nih.gov/nucleotide/GSE237013) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE237013). The in vivo mRNA sequencing raw data are being deposited in the Open Data Commons for Traumatic Brain Injury (ODC-TBI), an NIH-supported repository for public data access. To ensure full accessibility of the data associated with the current manuscript, all applicable subject metadata, RNA sample information, and raw RNA sequencing data are also provided as a.csv file within the Supplementary Material.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 11 authors, 5 keywords, 1 funder, 80 references.

Cite

This paper

Liaudanskaya, V., Robson, M. J., Vike, N. L., Bari, S., O’Connell, C. J., Hoilett, O. S., Kaplan, D. L., Talavage, T. M., Nauman, E. A., Slobounov, S., & Breiter, H. C. (2026). Molecular abnormalities scale across three models of cerebral injury. Frontiers in molecular neuroscience, 19, 1844343. https://doi.org/10.3389/fnmol.2026.1844343

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