Penetrating Ballistic Brain Injury Produces Acute Alterations in Sleep and Circadian-Related Genes in the Rodent Cortex: A Preliminary Study

Andrea Mountney, Jennifer Blaze, Zhaoyu Wang, Michelle Umali, William Jesse Flerlage, Jacqueline Dougherty, Yongchao Ge, Deborah Shear, Fatemeh Haghighi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Traumatic brain injury (TBI) affects millions of Americans each year, with extremely high prevalence in the Veteran community, and sleep disturbance is one of the most commonly reported symptoms. Reduction in the quality and amount of sleep can negatively impact recovery and result in a wide range of behavioral and physiological symptoms, such as impaired cognition, mood and anxiety disorders, and cardiovascular effects. Thus, to improve long-term patient outcomes and develop novel treatments, it is essential to understand the molecular mechanisms involved in sleep disturbance following TBI. In this effort, we performed transcriptional profiling in an established rodent model of penetrating ballistic brain injury (PBBI) in conjunction with continuous sleep/wake EEG/EMG recording of the first 24 h after injury. Rats subjected to PBBI showed profound differences in sleep architecture. Injured animals spent significantly more time in slow wave sleep and less time in REM sleep compared to sham control animals. To identify PBBI-related transcriptional differences, we then performed transcriptome-wide gene expression profiling at 24 h post-injury, which identified a vast array of immune- related genes differentially expressed in the injured cortex as well as sleep-related genes. Further, transcriptional changes associated with total time spent in various sleep stages were identified. Such molecular changes may underlie the pathology and symptoms that emerge following TBI, including neurodegeneration, sleep disturbance, and mood disorders.

Original languageEnglish
Article number745330
JournalFrontiers in Neurology
Volume12
DOIs
StatePublished - 21 Oct 2021
Externally publishedYes

Keywords

  • circadian
  • gene expression
  • prefrontal cortex
  • sleep
  • traumatic brain injury

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