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OBJECTIVE: This study examined concentrations of a novel \nbrain injury biomarker Ubiquitin C-terminal Hydrolase-L1 (UCH-\nL1) in CSF and serum of severe TBI patients and their \nassociation with clinical characteristics and outcome. METHODS: \nThis case-control study enrolled ninety-five severe TBI subjects \n(Glasgow Coma Score [GCS]=8). Using sensitive UCH-L1 sandwich \nELISA, we studied the temporal profile of CSF and serum UCH-L1 \nlevels over 7 days for severe TBI patients. RESULTS: Comparison \nof serum and CSF levels of UCH-L1 in TBI patients versus \ncontrols show robust and significant elevation of UCH-L1 in \nacute phase and over the 7 day study period. Serum and CSF UCH-\nL1 Receiver Operation Characteristics (ROC) curves further \nconfirm strong specificity and selectivity for diagnosing severe \nTBI versus controls, with area under the curve (AUC) values in \nserum and CSF statistically significant at all time points up to \n24 h(p < .001). The first 12 hour levels of both serum and CSF \nUCH-L1 in patients GCS 3-5 were also significantly higher than \nthose with GCS 6-8. Furthermore, UCH-L1 levels in CSF and serum \nappear to distinguish severe TBI survivors versus non-survivors \nwithin the study, with non-survivors having significantly higher \nand more persistent levels of serum and CSF UCH-L1. 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