Repetitive Brain Injury of Juvenile Mice Impairs Environmental Enrichment-Induced Modulation of REM Sleep in Adulthood

Neuroscience. 2018 Apr 1;375:74-83. doi: 10.1016/j.neuroscience.2018.01.064. Epub 2018 Feb 10.


Traumatic brain injuries (TBIs) are a common and costly ongoing public health concern. Injuries that occur during childhood development can have particularly profound and long-lasting effects. One common consequence and potential mediator of negative outcomes of TBI is sleep disruption which occurs in a substantial proportion of TBI patients. These individuals report greater incidences of insomnia and sleep fragmentation combined with a greater overall sleep requirement meaning that many patients are chronically sleep-deprived. We sought to develop an animal model of developmental TBI-induced sleep dysfunction. Specifically, we tested the hypothesis that early (postnatal day 21), repeated closed head injuries in Swiss-Webster mice, would impair basal and homeostatic sleep responses in adulthood. Further, we asked whether environmental enrichment (EE), a manipulation that improves functional recovery following TBI and has been shown to alter sleep physiology, would prevent TBI-induced sleep dysfunction and alter sleep-modulatory peptide expression. In contrast to our hypothesis, the mild, repeated head injury that we used did not significantly alter basal or homeostatic sleep responses in mice housed in standard laboratory conditions. Sham-injured mice housed in enriched environments exhibited enhanced rapid eye movement (REM) sleep and expression of the REM-promoting peptide pro-melanin-concentrating hormone, an effect that was not apparent in TBI mice housed in enriched environments. Thus, TBI blocked the REM-enhancing effects of EE. This work has important implications for the management and rehabilitation of the TBI patient population.

Keywords: REM sleep; environmental enrichment; mild traumatic brain injury; neurodegeneration; non-REM sleep; orexin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / growth & development
  • Brain / pathology
  • Brain / physiopathology
  • Brain Injuries, Traumatic / pathology
  • Brain Injuries, Traumatic / physiopathology*
  • Brain Injuries, Traumatic / rehabilitation
  • Disease Models, Animal
  • Environment*
  • Homeostasis / physiology
  • Housing, Animal*
  • Hypothalamic Hormones / metabolism
  • Male
  • Mice
  • Motor Activity / physiology
  • Orexins / metabolism
  • Protein Precursors / metabolism
  • Random Allocation
  • Sleep Wake Disorders / pathology
  • Sleep Wake Disorders / physiopathology
  • Sleep, REM* / physiology


  • Hypothalamic Hormones
  • Orexins
  • Protein Precursors
  • melanin-concentrating hormone precursors