Journal
JOURNAL OF NEUROTRAUMA
Volume 35, Issue 20, Pages 2435-2447Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2018.5663
Keywords
arterial spin labeling; biomarkers; concussion; magnetic resonance spectroscopy; mitochondria
Funding
- Kentucky Spinal and Head Injury Trust trainee fellowship
- National Institutes of Health [R00 AG044445, P30 GM110787]
- University of Kentucky
- United States Department of Veterans Affairs Biomedical Laboratory Research and Development Program [I01BX003405]
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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 (H-1 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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