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

Lukasz P Slomnicki,Scott R Whittemore,Michal Hetman,Darlene A Burke,Sujata Saraswat Ohri,Johnny R Morehouse,Scott A Myers,George Wei,Emily R Hodges,Christine D Yarberry,Simone Di Giovanni

doi:10.1371/journal.pone.0249981

Lukasz P Slomnicki, Scott R Whittemore + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0249981

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Journal: PloS one	Publication Date: Nov 23, 2021
Citations: 6	License type: CC BY 4.0

Affiliation: University of Louisville

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.

Highlights

Time of day affects the incidence of various acute pathologies including myocardial infarct (MI) and ischemic stroke [1]
Levels of selected clock pathway transcripts were analyzed at ZT1 and ZT12 in the intact spinal cord and the liver of naïve mice taken from the same cohort that was used for the spinal cord injury (SCI) study 1
Consistent with increasing BMAL1 transcription factors (TFs) activity during the rodent inactive period, expression of several BMAL1 target genes including Nr1d1, Nr1d2, Cry1, Per1, Per2, Per3, and Dbp was higher by 25–65% at ZT12

Summary

Introduction

Time of day affects the incidence of various acute pathologies including myocardial infarct (MI) and ischemic stroke [1]. The severity of those injuries may be influenced by the time of day at which they occur [2, 3]. Such effects stem from circadian rhythmicity of biological processes that determine the risk of a blood vessel occlusion and/or rupture and/or modify the tissue injury response [1]. In morning hours when the human active period begins, circadian maxima (acrophases) of blood pressure, sympathetic tone, and hemostasis may explain the higher occurrence and greater severity of MI and stroke seen at that time [1].

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