Limited changes in locomotor recovery and unaffected white matter sparing after spinal cord contusion at different times of day

Abstract

The circadian gene expression rhythmicity drives diurnal oscillations of physiological processes that may determine the injury response. While outcomes of various acute injuries are affected by the time of day at which the original insult occurred, such influences on recovery after spinal cord injury (SCI) are unknown. We report that mice receiving moderate, T9 contusive SCI at ZT0 (zeitgeber time 0, time of lights on) and ZT12 (time of lights off) showed similar hindlimb function recovery in the Basso mouse scale (BMS) over a 6 week post-injury period. In an independent study, no significant differences in BMS were observed after SCI at ZT18 vs. ZT6. However, the ladder walking test revealed modestly improved performance for ZT18 vs. ZT6 mice at week 6 after injury. Consistent with those minor effects on functional recovery, terminal histological analysis revealed no significant differences in white matter sparing at the injury epicenter. Likewise, blood-spinal cord barrier disruption and neuroinflammation appeared similar when analyzed at 1 week post injury at ZT6 or ZT18. Therefore, locomotor recovery after thoracic contusive SCI is not substantively modulated by the time of day at which the neurotrauma occurred.

Effects of dim light at night in C57BL/6J mice on recovery after spinal cord injury

“…If anything, we observed a small but statistically significant improvement in dLAN mice at 28 dpo, which is in contrast to dLAN results in other models of CNS injury (Fonken et al, 2019;Weil et al, 2020). Although-to our knowledge-no previous study has specifically tested effects of dLAN on SCI, a pair of recent studies has examined related circadian interventions (Slomnicki et al, 2020(Slomnicki et al, , 2021. Slomnicki et al (2020) investigated post-SCI recovery and neuroprotection in mice lacking Bmal1-a core circadian clock component (Bunger et al, 2000;Bell-Pedersen et al, 2005)-and found a beneficial effect.…”

“…In addition to uncovering a potential role for Bmal1 in enhancing the neuroinflammatory response after SCI, these findings also illustrate the fact that disruptions to the circadian clock— depending on the specific experimental context—are not intrinsically harmful. In another study, the same group examined how time of injury effects post-SCI recovery and found little to no effect (Slomnicki et al, 2021), in contrast with previous work demonstrating that the neuroimmune system is more reactive during the light phase (Weil et al, 2009; Wang et al, 2020). Notably, like our study, this work used C57BL/6J mice, which, as we discuss below, may be important.…”

“…If anything, we observed a small but statistically significant improvement in dLAN mice at 28 dpo, which is in contrast to dLAN results in other models of CNS injury (Fonken et al, 2019; Weil et al, 2020). Although—to our knowledge—no previous study has specifically tested effects of dLAN on SCI, a pair of recent studies has examined related circadian interventions (Slomnicki et al, 2020, 2021). Slomnicki et al .…”

“…Circadian disruption and suboptimal lighting is common in hospital settings (Tamburri et al, 2004;Gazendam et al, 2013;Oldham et al, 2016). Circadian disruption and dLAN also worsens outcomes in preclinical models of neurological disorders (Fonken et al, 2019;Weil et al, 2020;Hetman et al, 2022), yet few studies have addressed whether clock-related disruption exacerbates recovery after SCI (Slomnicki et al, 2020(Slomnicki et al, , 2021. To test this possibility, we subjected C57BL/6J mice raised in standard LD conditions (12 h light (150 lux); 12 h dark) to SCI or sham surgeries and then subsequently housed them in LD or dLAN (12 h 150 lux light (150 lux); 12 hr dim light (15 lux)) conditions (Fig.…”