A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism
Open accessAbstract
Metabolic uncoupling has been well-characterized during the first minutes-to-days after a traumatic brain injury (TBI), yet mitochondrial bioenergetics during the weeks-to-months after a brain injury is poorly defined, particularly after a mild TBI. We hypothesized that a closed head injury (CHI) would be associated with deficits in mitochondrial bioenergetics at one month after the injury. A significant decrease in state-III (adenosine triphosphate production) and state-V (complex-I) driven mitochondrial respiration was found at one month post-injury in adult C57Bl/6J mice. Isolation of synaptic mitochondria demonstrated that the deficit in state-III and state-V was primarily neuronal. Injured mice had a temporally consistent deficit in memory recall at one month post-injury. Using proton magnetic resonance spectroscopy ( 1 H MRS) at 7-Tesla, we found significant decreases in phosphocreatine, N-Acetylaspartic acid, and total choline. We also found regional variations in cerebral blood flow, including both hypo- and hyperperfusion, as measured by a pseudocontinuous arterial spin labeling MR sequence. Our results highlight a chronic deficit in mitochondrial bioenergetics associated with a CHI that may lead toward a novel approach for neurorestoration after a mild TBI. MRS provides a potential biomarker for assessing the efficacy of candidate treatments targeted at improving mitochondrial bioenergetics.
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Female mice showed greater deficits in bioenergetic markers such as phosphocreatine and N-acetylaspartate following mild TBI, compared with male mice.
“female mice showed greater deficits in bioenergetic markers such as phosphocreatine and N -acetylaspartate following mild TBI, compared with male mice.”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [129]
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Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know
Gupte, R. P., Brooks, W. M., Vukas, R. R., Pierce, J. D., & Harris, J. L. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.6171 · Cited by 533 · see citing works
- Authors
- Lyons, D. N., Vekaria, H., Macheda, T., Bakshi, V., Powell, D. K., Gold, B. T., Lin, A.-L., Sullivan, P. G., & Bachstetter, A. D.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Bachstetter, Adam D.
- ORCID
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2018-10
- Volume
- 35
- Issue
- 20
- Pages
- 2435-2447
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- PMC
- PMC6196750
- OpenAlex
- W2806143103
- Cited by
- 55
- References
- 60
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 9 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 7 · 2018: 2
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neurotrauma (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX003405)
- University of Kentucky
- National Institutes of Health (GM110787)
- National Institute on Aging (R00AG044445, R01AG054459)
- National Institute of General Medical Sciences (P30GM110787)
- Topics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mild traumatic brain injury, closed head injury, mitochondrial bioenergetics, metabolic uncoupling, synaptic mitochondria, ATP production, memory impairment, phosphocreatine, N-acetylaspartate, choline, cerebral blood flow, arterial spin labeling, 1H NMR, neurorestoration, biomarkers, mice
- MeSH terms
- Animals, Brain, Brain Concussion, Energy Metabolism, Mice, Inbred C57BL, Mitochondria, Mice
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