UCH-L1 is a Poor Serum Biomarker of Murine Traumatic Brain Injury After Polytrauma.

Abstract

BACKGROUND:

Several serum biomarkers have been studied to diagnose incidence and severity of traumatic brain injury (TBI), but a reliable biomarker in TBI has yet to be identified. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) has been proposed as a biomarker in clinical and preclinical studies, largely in the setting of isolated TBI or concussion. The aim of this study was to evaluate the performance of UCH-L1 as a serum biomarker in the setting of polytrauma and TBI.

METHODS:

Multiple variations of murine TBI and polytrauma models were used to evaluate serum biomarkers. The different models included TBI with and without hemorrhagic shock and resuscitation, isolated extremity vascular ligation, extremity ischemia/reperfusion, and blunt tail injury. Blood was drawn at intervals after injury, and serum levels of neuron-specific enolase, UCH-L1, creatine kinase, and syndecan-1 were evaluated by enzyme-linked immunosorbent assay.

RESULTS:

UCH-L1 levels were not significantly different between TBI, tail injury, and sham TBI. By contrast, neuron-specific enolase levels were increased in TBI mice compared with tail injury and sham TBI mice. UCH-L1 levels increased regardless of TBI status at 30 min and 4 h after hemorrhagic shock and resuscitation. In mice that underwent femoral artery cannulation followed by hemorrhagic shock/resuscitation, UCH-L1 levels were significantly elevated compared with shock sham mice at 4 h (3158 ± 2168 pg/mL, 4 h shock versus 0 ± 0 pg/mL, 4 h shock sham; P < 0.01) and at 24 h (3253 ± 2954 pg/mL, 24 h shock versus 324 ± 482 pg/mL, 24 h shock sham; P = 0.03). No differences were observed in UCH-L1 levels between the sham shock and the arterial ligation, vein ligation, or extremity ischemia/reperfusion groups at any time point. Similar to UCH-L1, creatine kinase was elevated only after shock compared with sham mice at 4, 24, and 72 h after injury.

CONCLUSIONS:

Our study demonstrates that UCH-L1 is not a specific marker for TBI but is elevated in models that induce central and peripheral nerve ischemia. Given the increase in UCH-L1 levels observed after hemorrhagic shock, we propose that UCH-L1 may be a useful adjunct in quantifying severity of shock or global ischemia rather than as a specific marker of TBI.

• Authors: Mackenzie C Morris, Aron Bercz, Grace M Niziolek, Farzaan Kassam, Rose Veile, Lou Ann Friend, Timothy A Pritts, Amy T Makley, Michael D Goodman
• Journal: The Journal of surgical research (J Surg Res) Vol. 244 Pg. 63-68 (12 2019) ISSN: 1095-8673 [Electronic] United States
• PMID: 31279265 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Ubiquitin carboxyl-Terminal Hydrolase L-1, mouse
• Ubiquitin Thiolesterase

Topics

• Animals
• Biomarkers (blood)
• Brain Injuries, Traumatic (blood, diagnosis, etiology)
• Disease Models, Animal
• Glasgow Coma Scale
• Humans
• Male
• Mice
• Multiple Trauma (blood, complications)
• Severity of Illness Index
• Shock, Hemorrhagic (blood, diagnosis, etiology)
• Ubiquitin Thiolesterase (blood)