Poster abstracts
Poster number 80 submitted by Samuel Houle
Sleep Fragmentation Stress Impairs Sleep Function and Dampens Neuroinflammation Acutely after Traumatic Brain Injury
Sam Houle (Neuroscience Graduate Program), Rebecca Boland (Neuroscience Graduate Program), Shannon Dobres (Department of Neuroscience, the Ohio State University), Grant Mannino Rachel Rowe (Integrative Physiology, University of Colorado Boulder), John Sheridan (College of Dentistry, the Ohio State University), Jonathan Godbout Niki Kokiko-Cochran (Institute for Behavioral Medicine Research, Chronic Brain Injury Program, the Ohio State University)
Abstract:
Studies show that environmental sleep fragmentation (SF) increases post-injury neuroinflammation at subacute and chronic timepoints. The injured brain is particularly vulnerable to secondary inflammation during the acute phase of recovery. Therefore, secondary immune stimuli during acute recovery from TBI may impair long term recovery. As SF is a common comorbidity of TBI, we hypothesized that 3 days of SF would worsen post-TBI outcome in clinically-relevant model of post-TBI stress. C57BL6/J mice received TBI or sham injury followed by 3 days of SF or control housing. Primary outcome measures included sleep behavior and neuroinflammatory gene and protein expression.
We found an overall increase in sleep in the dark phase due to SF alone, driven by increases in nREM sleep, suggesting compensatory sleep. Additionally, TBI increased brain infiltration of monocytes and granulocytes along with reactive microglia. This correlated with an increase in IL-6 and CXCL1 in the ipsilateral cortex. Contrary to expectations, post-TBI SF dampened gene expression of many genes that were increased by SF and TBI alone. Genes uniquely decreased by TBI-SF compared to TBI are related to microglia-mediated neuroinflammation (Tlr4, Aif1, Cd68, H2-d1) and the complement cascade (C1q, C3ar1, Itgam). These data point to a divergent immune response elicited by SF after TBI, which encompasses dampening of neuroinflammatory gene expression while increasing cytokine production, namely the pleiotropic cytokine IL-6. SF induced sleep alterations contribute to inflammatory responses post-TBI, further impairing recovery. Thus, the synergistic effects of post-injury stress have the potential to shift neuroimmune responses acutely, highlighting a potential critical period for therapeutic intervention.
Keywords: TBI, Inflammation, Sleep