TY - JOUR T1 - Spinal cord injury in rats disrupts the circadian system JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0328-18.2018 SP - ENEURO.0328-18.2018 AU - Andrew D. Gaudet AU - Laura K. Fonken AU - Monica T. Ayala AU - Emily M. Bateman AU - Wolfgang E. Schleicher AU - Elana J. Smith AU - Heather M. D’Angelo AU - Steven F. Maier AU - Linda R. Watkins Y1 - 2018/12/03 UR - http://www.eneuro.org/content/early/2018/12/03/ENEURO.0328-18.2018.abstract N2 - Spinal cord injury (SCI) perturbs many physiological systems. The circadian system helps maintain homeostasis throughout the body by synchronizing physiological and behavioural functions to predictable daily events. Whether disruption of these coordinated daily rhythms contributes to SCI-associated pathology remains under-studied. Here, we hypothesized that SCI in rats would dysregulate several prominent circadian outputs including glucocorticoids, core temperature, activity, neuroinflammation, and circadian gene networks. Female and male Sprague-Dawley rats were subjected to clinically relevant thoracic (T-) 9 moderate contusion SCI (or laminectomy sham surgery). Diurnal measures – including rhythms of plasma corticosterone (CORT), body temperature and activity (using small implanted transmitters), and intraspinal circadian and inflammatory gene expression – were studied prior to and post-surgery. SCI caused overall increases and disrupted rhythms of the major rodent glucocorticoid, CORT. Pre-surgery and sham rats displayed expected rhythms in body temperature and activity, whereas rats with SCI had blunted daily rhythms in body temperature and activity. In parallel, SCI disrupted intraspinal rhythms of circadian clock gene expression. Circadian clock genes can act as transcriptional regulators of inflammatory pathways. Indeed, SCI rats also showed dysregulated rhythms in inflammatory gene expression in both the epicenter and distal spinal cord. Our data show that moderate SCI in rats causes wide-ranging diurnal rhythm dysfunction, which is severe at acute time points, and gradually recovers over time. Normalizing post-SCI diurnal rhythms could enhance recovery of homeostasis and quality-of-life.Significance Statement Spinal cord injury (SCI) can cause physiologic dysfunction throughout the body. Internal physiologic function is typically synchronized with the environment through the circadian system. Despite the crucial roles of the spinal cord and the circadian system in optimizing whole-body function, it remains unclear whether SCI alters diurnal rhythms. Here, we hypothesized that SCI would disrupt key circadian output and feedback mechanisms. Moderate SCI in rats caused widespread disruption of diurnal measures – including glucocorticoids, body temperature, locomotor activity, and intraspinal clock and inflammatory gene expression. We identify the circadian system as a novel potential target for SCI therapies. ER -