Affordable Access

deepdyve-link
Publisher Website

Sleep Disruption Exacerbates and Prolongs the Inflammatory Response to Traumatic Brain Injury.

Authors
  • Tapp, Zoe M1
  • Kumar, Julia E1
  • Witcher, Kristina G1
  • Atluri, Ravitej R1
  • Velasquez, John A1
  • O'Neil, Shane M1
  • Dziabis, Julia E1
  • Bray, Chelsea E1
  • Sheridan, John F2, 3
  • Godbout, Jonathan P1, 3, 4
  • Kokiko-Cochran, Olga N1, 3, 4
  • 1 Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
  • 2 Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, Ohio, USA.
  • 3 Neurological Institute, Institute for Behavioral Medicine Research (IBMR), The Ohio State University, Columbus, Ohio, USA.
  • 4 Chronic Brain Injury Program, The Ohio State University, Columbus, Ohio, USA.
Type
Published Article
Journal
Journal of Neurotrauma
Publisher
Mary Ann Liebert
Publication Date
Aug 15, 2020
Volume
37
Issue
16
Pages
1829–1843
Identifiers
DOI: 10.1089/neu.2020.7010
PMID: 32164485
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Traumatic brain injury (TBI) alters stress responses, which may influence neuroinflammation and behavioral outcome. Sleep disruption (SD) is an understudied post-injury environmental stressor that directly engages stress-immune pathways. Thus, we predicted that maladaptive changes in the hypothalamic-pituitary-adrenal (HPA) axis after TBI compromise the neuroendocrine response to SD and exacerbate neuroinflammation. To test this, we induced lateral fluid percussion TBI or sham injury in female and male C57BL/6 mice aged 8-10 weeks that were then left undisturbed or exposed to 3 days of transient SD. At 3 days post-injury (DPI) plasma corticosterone (CORT) was reduced in TBI compared with sham mice, indicating altered HPA-mediated stress response to SD. This response was associated with approach-avoid conflict behavior and exaggerated cortical neuroinflammation. Post-injury SD specifically enhanced neutrophil trafficking to the injured brain in conjunction with dysregulated aquaporin-4 (AQP4) polarization. Delayed and persistent effects of post-injury SD were determined 4 days after SD concluded at 7 DPI. SD prolonged anxiety-like behavior regardless of injury and was associated with increased cortical Iba1 labeling in both sham and TBI mice. Strikingly, TBI SD mice displayed an increased number of CD45+ cells near the site of injury, enhanced cortical glial fibrillary acidic protein (GFAP) immunolabeling, and persistent expression of Trem2 and Tlr4 7 DPI compared with TBI mice. These results support the hypothesis that post-injury SD alters stress-immune pathways and inflammatory outcomes after TBI. These data provide new insight to the dynamic interplay between TBI, stress, and inflammation.

Report this publication

Statistics

Seen <100 times