Brain Aging and Traumatic Brain Injury: Novel Neuroimaging Biomarkers
Janna Harris, PhD
Traumatic brain injury (TBI) is a major public health concern, with 1.7 million cases reported annually in the United States. TBI has a disproportionately high impact on adults aged 65 and over, who are more likely to be hospitalized and have higher mortality and poorer outcomes than younger adults. However the mechanisms responsible for this discrepancy remain poorly understood. In the present work, we sought to explore the biological mechanisms that make the aged brain more vulnerable to an acquired injury.
Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive neuroimaging approach to measure neurochemicals (biomarkers). 1H-MRS biomarkers reflect specific aspects of brain function and/or pathology, for example neuronal mitochondrial status (N-acetylaspartate), oxidative stress (glutathione and ascorbate), neurotransmission (glutamate, aspartate, GABA), and inflammation (inositol and choline). We used 1H-MRS to compare the neurochemical profile of young adult and aged brains in an animal model (3 month vs. 21 month F344 rats) before and after experimental TBI. Longitudinal brain imaging and behavioral testing allowed us to track the metabolic and behavioral effects of TBI over time in the same subjects.
Biomarker changes observed in the aging brain suggested altered baseline conditions including increased glial populations (inositol), altered neurotransmitter balance (aspartate, glutamate), and increased oxidative stress (ascorbate) that may enhance the vulnerability of the aged brain to TBI. 1H-MRS biomarkers measured after TBI also revealed enhanced metabolic disturbances in the aged brain, particularly in markers of bioenergetic status (glucose, glutamate, phosphocreatine). Aged rats also had significantly worse functional outcomes after TBI compared with younger adults.
Together these results support the utility of 1H-MRS for quantifying the involvement of injurious molecular and cellular mechanisms in brain aging and injury. These mechanism-specific biomarkers represent a promising approach for elucidating mechanisms of TBI and for translating treatments from pre-clinical to clinical trials.