title: Biokinetic analysis of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in severe traumatic brain injury patient biofluids.
abstract: Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a neuron-specific enzyme that has been identified as a potential biomarker of traumatic brain injury (TBI). The study objectives were to determine UCH-L1 exposure and kinetic metrics, determine correlations between biofluids, and assess outcome correlations in severe TBI patients. Data were analyzed from a prospective, multicenter study of severe TBI (Glasgow Coma Scale [GCS] score ≤ 8). Cerebrospinal fluid (CSF) and serum data from samples taken every 6 h after injury were analyzed by enzyme-linked immunosorbent assay (ELISA). UCH-L1 CSF and serum data from 59 patients were used to determine biofluid correlations. Serum samples from 86 patients and CSF from 59 patients were used to determine outcome correlations. Exposure and kinetic metrics were evaluated acutely and up to 7 days post-injury and compared to mortality at 3 months. There were significant correlations between UCH-L1 CSF and serum median concentrations (r(s)=0.59, p<0.001), AUC (r(s)=0.3, p=0.027), Tmax (r(s)=0.68, p<0.001), and MRT (r(s)=0.65, p<0.001). Outcome analysis showed significant increases in median serum AUC (2016 versus 265 ng/mL*min, p=0.006), and Cmax (2 versus 0.4 ng/mL, p=0.003), and a shorter Tmax (8 versus 19 h, p=0.04) in those who died versus those who survived, respectively. In the first 24 h after injury, there was a statistically significant acute increase in CSF and serum median Cmax((0-24h)) in those who died. This study shows a significant correlation between UCH-L1 CSF and serum median concentrations and biokinetics in severe TBI patients, and relationships with clinical outcome were detected.
authors.affiliation: Virginia Commonwealth University, Pharmacotherapy & Outcomes Sciences and Neurosurgery, Richmond, Virginia 23298-0533, USA. gbrophy@vcu.edu
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Brophy
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
authors.forename: Linda
authors.initials: L
authors.lastname: Papa
authors.forename: Steven A
authors.initials: SA
authors.lastname: Robicsek
authors.forename: Andrea
authors.initials: A
authors.lastname: Gabrielli
authors.forename: Joseph
authors.initials: J
authors.lastname: Tepas
authors.forename: Andras
authors.initials: A
authors.lastname: Buki
authors.forename: Claudia
authors.initials: C
authors.lastname: Robertson
authors.forename: Frank C
authors.initials: FC
authors.lastname: Tortella
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D043222:Ubiquitin Thiolesterase / Q000097:blood* / Q000134:cerebrospinal fluid*; D055815:Young Adult
chemical_list: C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase