Acute Post-Traumatic Sleep May Define Vulnerability to a Second Traumatic Brain Injury in Mice

Rachel K. Rowe, Jordan L. Harrison, Helena W. Morrison, Vignesh Subbian, Sean M. Murphy, Jonathan Lifshitz

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Chronic neurological impairments can manifest from repetitive traumatic brain injury (rTBI), particularly when subsequent injuries occur before the initial injury completely heals. Herein, we apply post-traumatic sleep as a physiological biomarker of vulnerability, hypothesizing that a second TBI during post-traumatic sleep worsens neurological and histological outcomes compared to one TBI or a second TBI after post-traumatic sleep subsides. Mice received sham or diffuse TBI by midline fluid percussion injury; brain-injured mice received one TBI or rTBIs at 3- or 9-h intervals. Over 40 h post-injury, injured mice slept more than shams. Functional assessments indicated lower latencies on rotarod and increased Neurological Severity Scores for mice with rTBIs within 3 h. Anxiety-like behaviors in the open field task were increased for mice with rTBIs at 3 h. Based on pixel density of silver accumulation, neuropathology was greater at 28 days post-injury (DPI) in rTBI groups than sham and single TBI. Cortical microglia morphology was quantified and mice receiving rTBI were de-ramified at 14 DPI compared to shams and mice receiving a single TBI, suggesting robust microglial response in rTBI groups. Orexin-A-positive cells were sustained in the lateral hypothalamus with no loss detected, indicating that loss of wake-promoting neurons did not contribute to post-traumatic sleep. Thus, duration of post-traumatic sleep is a period of vulnerability that results in exacerbated injury from rTBI. Monitoring individual post-traumatic sleep is a potential clinical tool for personalized TBI management, where regular sleep patterns may inform rehabilitative strategies and return-to-activity guidelines.

Original languageEnglish (US)
Pages (from-to)1318-1334
Number of pages17
JournalJournal of Neurotrauma
Issue number8
StatePublished - Apr 15 2019


  • concussion
  • inflammation
  • pathology
  • repetitive TBI
  • sleep

ASJC Scopus subject areas

  • Clinical Neurology


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