Abstract
Traumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide. Although chronic disability is common after TBI, effective treatments remain elusive and chronic TBI pathophysiology is not well understood. Early after TBI, brain metabolism is disrupted due to unregulated ion release, mitochondrial damage, and interruption of molecular trafficking. This metabolic disruption causes at least part of the TBI pathology. However, it is not clear how persistent or pervasive metabolic injury is at later stages of injury. Using untargeted 1H-NMR metabolomics, we examined ex vivo hippocampus, striatum, thalamus, frontal cortex, and brainstem tissue in a rat lateral fluid percussion model of chronic brain injury. We found altered tissue concentrations of metabolites in the hippocampus and thalamus consistent with dysregulation of energy metabolism and excitatory neurotransmission. Furthermore, differential correlation analysis provided additional evidence of metabolic dysregulation, most notably in brainstem and frontal cortex, suggesting that metabolic consequences of injury are persistent and widespread. Interestingly, the patterns of network changes were region-specific. The individual metabolic signatures after injury in different structures of the brain at rest may reflect different compensatory mechanisms engaged to meet variable metabolic demands across brain regions.
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These studies received financial support from Cincinnati Children’s Hospital Medical Center as a Shared Facilities Discovery Award to NKE and JLM.
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McGuire, J.L., DePasquale, E.A.K., Watanabe, M. et al. Chronic Dysregulation of Cortical and Subcortical Metabolism After Experimental Traumatic Brain Injury. Mol Neurobiol 56, 2908–2921 (2019). https://doi.org/10.1007/s12035-018-1276-5
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DOI: https://doi.org/10.1007/s12035-018-1276-5