Exploring the Impact of Mitoquinone Supplementation on Glycan Profiles in a Repeated Mild Traumatic Brain Injury Mouse Model

Authors

• Mona Goli, Texas Tech University
• Akeem Sanni, Texas Tech University
• Sakshi Gautam, Texas Tech University
• Khalil Mallah, Medical University of South Carolina
• W. Brad Hubbard, University of KentuckyFollow
• Mohammad Reslan, American University of Beirut
• Muhammad Ali Haidar, American University of Beirut
• Karim Halabi, American University of Beirut
• Joseph Walker, Morehouse School of Medicine
• Stefania Mondello, University of Messina
• Firas Kobeissy, American University of BeirutFollow
• Yehia Mechref, Texas Tech UniversityFollow

Abstract

Traumatic brain injury (TBI) represents a significant cause of injury-related deaths and disabilities. Repeated exposure to mechanical impact can lead to metabolic and ionic imbalance, which can cause oxidative stress and worsen the cellular dysfunction initiated by the initial mild TBI (mTBI). Currently, no FDA-approved drug targets repeated mTBI (rmTBI) and its potential sequelae. Mitoquinone (MitoQ) is a mitochondrion-targeted drug that has proven beneficial in different brain-related diseases. We have previously demonstrated the neurotherapeutic effects of MitoQ at a 30-day chronic time point in a similar rmTBI mouse model, where we observed decreased neuroinflammation, enhanced behavioral outcomes, and diminished oxidation. Recently, alterations in glycans have been shown to modulate key roles in the nervous system. Their relevance has been recognized in several neurodegenerative disorders, including TBI, which indicated injury severity and pathobiology. In this study, we aimed to assess brain glycome profiles post MitoQ treatment in experimental rmTBI using liquid chromatography-tandem mass spectrometry. Our findings indicate that there is a correlation between the HexNAc₄Hex₅DeoxyHex₃ glycan profile and MitoQ administration at the acute phase, the levels of HexNAc₄Hex₄ glycan in the subacute phase of MitoQ treatment, and the HexNAc₄Hex₅ glycan profile at the chronic time point phase of MitoQ treatment. These data suggest that these three glycan profiles can be considered molecular signatures for MitoQ-associated neurotherapy. However, further research is required to validate and establish that these three glycan profiles are accurate and sensitive markers associated with TBI neuroprotection.

Document Type

Article

Publication Date

6-1-2025

Notes/Citation Information

Publisher Copyright: © The Author(s) 2025. Published by Mary Ann Liebert, Inc.

Digital Object Identifier (DOI)

10.1089/neur.2025.0054

Archival?

Archival

Repository Citation

Goli, Mona; Sanni, Akeem; Gautam, Sakshi; Mallah, Khalil; Hubbard, W. Brad; Reslan, Mohammad; Haidar, Muhammad Ali; Halabi, Karim; Walker, Joseph; Mondello, Stefania; Kobeissy, Firas; and Mechref, Yehia, "Exploring the Impact of Mitoquinone Supplementation on Glycan Profiles in a Repeated Mild Traumatic Brain Injury Mouse Model" (2025). Physiology Faculty Publications. 251.
https://uknowledge.uky.edu/physiology_facpub/251