Experimental Neurology | March 13, 2021

O’Brien WT, Pham L, Brady RD, Bain J, Yamakawa GR, Sun M, Mychasiuk R, O’Brien TJ, Monif M, Shultz SR and McDonald SJ

Exp Neurol. 2021 Mar 13;341:113698

DOI: 10.1016/j.expneurol.2021.113698

Abstract

There is a widely recognized need for blood biomarkers to assist clinical decisions surrounding mild traumatic brain injury (mTBI). Serum neurofilament light (NfL), an indicator of neuroaxonal damage, is one such candidate, with early mTBI clinical investigations demonstrating significant promise. To facilitate the translation of pre-clinical mTBI findings, clinically relevant outcomes should be integrated into animal studies wherever possible. Despite this, the temporal profile and potential utility of NfL as a blood biomarker in pre-clinical mTBI is poorly understood. Here, we quantified serum NfL at 2-h, 1-, 3-, 7- and 14-days following mTBI in rats and compared these to pre-injury levels. We also investigated cumulative effects of repeat-mTBI by delivering 0, 1 or 5 mTBIs separated by 24 h. Sensorimotor performance was evaluated with the beam task at 1- and 4-h after mTBI, and serum was collected 1-day after the final procedure. We found that serum NfL levels were substantially elevated at all acute and sub-acute time-points after a single-mTBI, peaked at 1-day, and remained elevated 14-days post-injury. An mTBI dose-dependent effect on serum NfL levels was also observed, with substantially higher NfL levels found at 1-day post repeat-mTBI when compared to single-mTBI and sham-injured rats. Furthermore, NfL levels were found to be greatest in rats with the highest degree of sensorimotor impairment. In conclusion, these findings have described the temporal profile of serum NfL elevations following a single-mTBI in rats, and indicate a profile with some similarities and differences to that seen in the clinical condition. Moreover, we found that serum NfL levels were potentiated by repeat-mTBI, and that this biomarker may have utility as an indicator of injury severity. As such, future pre-clinical TBI studies may benefit from incorporating measures of serum NfL as an objective injury outcome.