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J Neurotrauma. 2018 Oct 15;35(20):2435-2447. doi: 10.1089/neu.2018.5663. Epub 2018 Jul 2.

A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism.

Author information

1
1 Spinal Cord & Brain Injury Research Center, University of Kentucky , Lexington Kentucky.
2
2 Department of Neuroscience, University of Kentucky , Lexington Kentucky.
3
4 Sanders-Brown Center on Aging, University of Kentucky , Lexington Kentucky.
4
5 Department of Pharmacology and Nutritional Sciences, University of Kentucky , Lexington Kentucky.
5
3 Department of Biomedical Engineering, University of Kentucky , Lexington Kentucky.

Abstract

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 (1H 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.

KEYWORDS:

arterial spin labeling; biomarkers; concussion; magnetic resonance spectroscopy; mitochondria

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