Noninvasive Urinary Biomarkers for Early Diagnosis of Mild Traumatic Brain Injury

The lack of an easily measured biomarker hampers mild traumatic brain injury (mTBI) diagnosis and limits the ability to monitor an objective feature in patients through recovery. Due to its ease of collection and mirroring of metabolism, urine is a useful source for biomarkers. Urine samples collected from mice at 1, 12, 24, 48, and 96 h following mild lateral fluid percussion injury were subjected to headspace gas chromatography coupled with mass spectrometry (GC-MS). Of the 68 urinary volatiles detected, three were both stable in the sham controls and significantly increased in the injured group. The potential biomarkers identified in the mouse model included a saturated ketone and two unsaturated ketones. Results with mice prompted a targeted search for ketones in concussed youth (aged 7-19 years). Leveraging bio-banked human urine samples, headspace GC-MS analyses were conducted with human urine collected 4.5-71 h following injury from 18 patients with mTBI and eight healthy controls. Of the three α,β-unsaturated ketones identified in human urine, one was found to be significantly increased following mTBI. Taken together, elevation of urinary ketones in mice and humans suggests acute perturbation of fatty acid metabolism immediately following injury. Thus, ketones could form the basis for an easily accessible human biomarker of mTBI and greatly improve diagnosis and monitoring of these injuries and potentially direct efforts for treatment of mTBI.