Ubiquitin carboxy-terminal hydrolase-l1 as a serum neurotrauma biomarker for exposure to occupational low-level blast

Abstract

Repeated exposure to low-level blast is a characteristic of a few select occupations and there is concern that such occupational exposures present risk for traumatic brain injury. These occupations include specialized military and law enforcement units that employ controlled detonation of explosive charges for the purpose of tactical entry into secured structures. The concern for negative effects from blast exposure is based on rates of operator self-reported headache, sleep disturbance, working memory impairment, and other concussion-like symptoms. A challenge in research on this topic has been the need for improved assessment tools to empirically evaluate the risk associated with repeated exposure to blast overpressure levels commonly considered to be too low in magnitude to cause acute injury. Evaluation of serum-based neurotrauma biomarkers provides an objective measure that is logistically feasible for use in field training environments. Among candidate biomarkers, ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) has some empirical support and was evaluated in this study. We used daily blood draws to examine acute change in UCH-L1 among 108 healthy military personnel who were exposed to repeated low-level blast across a 2-week period. These research volunteers also wore pressure sensors to record blast exposures, wrist actigraphs to monitor sleep patterns, and completed daily behavioral assessments of symptomology, postural stability, and neurocognitive function. UCH-L1 levels were elevated as a function of participating in the 2-week training with explosives, but the correlation of UCH-L1 elevation and blast magnitude was weak and inconsistent. Also, UCH-L1 elevations did not correlate with deficits in behavioral measures. These results provide some support for including UCH-L1 as a measure of central nervous system effects from exposure to low-level blast. However, the weak relation observed suggests that additional indicators of blast effect are needed.

Keywords: biomarker; blast; breacher; military; neurotrauma.

Figure 1

Representation of training schedule and days of blast exposure across a 2-week period for each of the three study sites. Training days are labeled with serial Session numbers, with Sites 1 and 3 showing 10 Sessions and Site 2 showing 9 Sessions. Sessions with blast exposure are indicated by a jagged line surrounding the Session serial number. Group-level blast was recorded in 7 of 10 Sessions at Site 1, 7 of 9 Sessions at Site 2, and 4 of 10 Sessions at Site 3.

Figure 2

Normalized UCH-L1 concentrations (relative to individual baseline) for each Session of the study at each of the three sites. Error bars represent standard error. For two of the three sites, there is a Session in the series that shows a high UCH-L1 level that differs from the next highest Session. [Site 2 Session 8 vs. Session 9, t(21) = 2.10, p = 0.048; Site 3 Session 9 vs. Session 3, t(31) = 2.55, p = 0.016]. Site 1 did not show a single Session that clearly met criterion, with pairwise comparisons of Site 1 Sessions with the greatest UCH-L1 concentrations showing no difference (p values >0.05). Session 8 was used to represent post-blast exposure UCH-L1 concentrations for Site 1. Arrows indicate Sessions selected for comparison to baseline (Session 1).

Figure 3

The percentage of participants showing increase in normalized UCH-L1 from the previous day for each Session at each of the three sites. Session 8 for Sites 1 and 2 and Session 9 for Site 3 show that 40% or more of the subjects showed an increase in UCH-L1. Arrows indicate Sessions selected for comparison to baseline (Session 1). No data are shown for Session 1 in this figure because there was no prior timepoint available to assess daily increase in UCH-L1.

Figure 4

Scatterplot of individuals’ normalized UCH-L1 from the Session that was compared to baseline in the primary analysis (Session 8 for Sites 1 and 2, Session 9 for Site 3) expressed as a function of the greatest peak overpressure recorded for that individual on that day. The line represents simple linear regression.

Figure 5

Mean blast magnitude [peak pressure (psi)] recorded for each Session for each site. Error bars are standard error. Data are not included for Session 2 at Site 3 due to the use of alternate recording equipment in that Session. The arrow indicates the unique Session selected for focused analysis of greatest blast magnitude on UCH-L1 concentration.

Figure 6

Mean normalized UCH-L1 for baseline and the Session with the final blast exposure in the 2-week training protocol for each site (i.e., Session 9). Error bars are standard error.

Figure 7

Mean postural sway (standard deviation from center of gravity) for baseline and post-blast comparison Sessions, shown for test conditions with eyes open on each of two surfaces. Greater degree of postural sway corresponds to worse performance. Left panel is baseline and the post-blast Session with the greatest UCH-L1 increase (Session 8 for Sites 1 and 2, Session 9 for Site 3). Right panel is baseline and the final post-blast Session (Session 9). All three sites are combined. Error bars are standard error.