Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury*

Abstract

Objective Ubiquitin C-terminal hydrolase (UCH-L1), also called neuronal-specific protein gene product (PGP 9.3), is highly abundant in neurons. To assess the reliability of UCH-L1 as a potential biomarker for traumatic brain injury (TBI) this study compared cerebrospinal fluid (CSF) levels of UCH-L1 from adult patients with severe TBI to uninjured controls; and examined the relationship between levels with severity of injury, complications and functional outcome. Design This study was designed as prospective case control study. Patients This study enrolled 66 patients, 41 with severe TBI, defined by a Glasgow coma scale (GCS) score of ≤8, who underwent intraventricular intracranial pressure monitoring and 25 controls without TBI requiring CSF drainage for other medical reasons. Setting Two hospital system level I trauma centers. Measurements and Main Results Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, 120, 144, and 168 hrs following TBI and analyzed for UCH-L1. Injury severity was assessed by the GCS score, Marshall Classification on computed tomography and a complicated postinjury course. Mortality was assessed at 6 wks and long-term outcome was assessed using the Glasgow outcome score 6 months after injury. TBI patients had significantly elevated CSF levels of UCH-L1 at each time point after injury compared to uninjured controls. Overall mean levels of UCH-L1 in TBI patients was 44.2 ng/mL (±7.9) compared with 2.7 ng/mL (±0.7) in controls (p <.001). There were significantly higher levels of UCH-L1 in patients with a lower GCS score at 24 hrs, in those with postinjury complications, in those with 6-wk mortality, and in those with a poor 6-month dichotomized Glasgow outcome score. Conclusions These data suggest that this novel biomarker has the potential to determine injury severity in TBI patients. Further studies are needed to validate these findings in a larger sample.

Mind the gaps—advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions

“…141 The neuron-specific protein UCH-L1 (ubiquitin carboxyl-terminal hydrolase isozyme L1) was first linked to neurodegenerative pathology through its involvement in PD, 142 and its presence in serum was later identified as a biomarker for severe TBI. [143][144][145] Serum levels of UCH-L1 may have diagnostic utility in concussion, 146 but recent evidence suggests a lack of correlation between elevated serum levels and subconcussive hits. 147 The clinical utility of UCH-L1 in paediatric populations warrants further study.…”

Biomarkers for the Diagnosis, Prognosis, and Evaluation of Treatment Efficacy for Traumatic Brain Injury

“…To test this possibility, Papa et al 39 carried out a prospective study to determine the CSF levels of ubiquitin C-terminal hydrolase in patients who had severe brain injury and in uninjured controls. They found that ubiquitin C-terminal hydrolase levels were significantly increased in the CSF of brain-injured patients, and that the magnitude of this increase correlated with mortality, post-injury complications, and outcome tested 6 months post-discharge.…”

Therapy Development for Diffuse Axonal Injury

“…Using a systems biologybased approach to select top down candidate markers, ubiquitin C-terminal hydrolase L1 (UCH-L1) has been demonstrated in both CSF and serum of both animals and humans after TBI. 135,[144][145][146][147][148][149][150][151][152] This biomarker is associated with the occurrence of neuronal cell death, particularly in association with large contusional lesions. Likewise, glial fibrillary acidic protein (GFAP) and its breakdown products may be important companion biomarkers for distinguishing focal and diffuse pathologies in TBI.…”