A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism
| Autor: | Teresa Macheda, Adam D. Bachstetter, Danielle N. Lyons, Hemendra J. Vekaria, Patrick G. Sullivan, David K. Powell, Ai-Ling Lin, Brian T. Gold, Vikas Bakshi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Bioenergetics Traumatic brain injury Mitochondrion Phosphocreatine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Concussion medicine Animals Choline Brain Concussion business.industry biomarkers Brain Original Articles medicine.disease arterial spin labeling magnetic resonance spectroscopy mitochondria Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry Cerebral blood flow Closed head injury concussion Neurology (clinical) Energy Metabolism business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurotrauma |
| ISSN: | 1557-9042 0897-7151 |
| DOI: | 10.1089/neu.2018.5663 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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