In vivo measures of brain metabolites with magnetic resonance spectroscopy as behavioural biomarkers post traumatic brain injury.

OBJECTIVES

Currently there are no biomarkers to predict chronic neurobehavioral and neurocognitive deficits following a traumatic brain injury (TBI). We measured brain metabolite using magnetic resonance spectroscopy in a rat model of TBI to determine their potential as biomarkers of neurobehavioral/neurocognitive outcomes after TBI.

METHODS

TBI or sham surgery was conducted in 11-12 weeks old Sprague Dawley (SD) rats. Rats underwent 1H-MRS at 1 week and 1 month following TBI. Behavioural evaluations were performed between 5 and 6 months post-TBI.

RESULTS

TBI rats showed significantly elevated myoinositol as well as sustained reductions in N-acetyl aspartate (NAA), gamma-aminobutyric acid (GABA), and glutamate levels compared to the sham operated rats. Behavioural assessments revealed cognitive impairment and depression-like behaviour in the TBI rats. We categorized TBI rats with (TBI+) and without (TBI-) behavioural impairment based on their performance relative to the sham rats on each assessment. TBI+ rats with cognitive impairment showed elevated myoinositol and decreased levels of glutathione (GSH), glutamate, and total choline, compared to the TBI- rats. Furthermore, TBI+ rats with depression-like behaviour demonstrated increased myoinositol and glutamate alongside decreased NAA, total choline and total creatine levels compared to the TBI- rats. Logistic regression analysis showed that certain MRS measures had good sensitivity and specificity to distinguish between the TBI+ and TBI- rats (AUC for ROC curve = 0.75-0.9, p < 0.05).

CONCLUSION

We identified specific early changes in brain metabolites that predict chronic behavioural impairments after TBI. These translational findings may help understand TBI pathophysiology and help to predict functional outcomes in the clinical settings.