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

• Published in: Journal of neurotrauma Vol. 35; no. 20; pp. 2435 - 2447
• Main Authors: Lyons, Danielle N., Vekaria, Hemendra, Macheda, Teresa, Bakshi, Vikas, Powell, David K., Gold, Brian T., Lin, Ai-Ling, Sullivan, Patrick G., Bachstetter, Adam D.
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 15.10.2018; Mary Ann Liebert, Inc., publishers
• Subjects: Adenosine triphosphate; Aging; Animals; Bioenergetics; Blood flow; Brain - metabolism; Brain - pathology; Brain Concussion - metabolism; Brain Concussion - pathology; Brain research; Cerebral blood flow; Choline; Data analysis; Electron transport; Energy Metabolism - physiology; Experiments; Females; Head injuries; Laboratory animals; Magnetic resonance spectroscopy; Medical imaging; Metabolism; Mice; Mice, Inbred C57BL; Mitochondria; Mitochondria - metabolism; Mitochondria - pathology; N-Acetylaspartate; Original; Phosphocreatine; R&D; Research & development; Spin labeling; Surgery; Traumatic brain injury; United States > US; Lexington Kentucky; magnetic resonance spectroscopy; concussion; biomarkers; mitochondria; arterial spin labeling
• ISSN: 0897-7151; 1557-9042; 1557-9042
• DOI: 10.1089/neu.2018.5663

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 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.