Recovery of neurological function despite immediate sleep disruption following diffuse brain injury in the mouse: clinical relevance to medically untreated concussion

Sleep. 2014 Apr 1;37(4):743-52. doi: 10.5665/sleep.3582.

Abstract

Study objective: We investigated the relationship between immediate disruption of posttraumatic sleep and functional outcome in the diffuse brain-injured mouse.

Design: Adult male C57BL/6 mice were subjected to moderate midline fluid percussion injury (n = 65; 1.4 atm; 6-10 min righting reflex time) or sham injury (n = 44). Cohorts received either intentional sleep disruption (minimally stressful gentle handling) or no sleep disruption for 6 h following injury. Following disruption, serum corticosterone levels (enzyme-linked immunosorbent assay) and posttraumatic sleep (noninvasive piezoelectric sleep cages) were measured. For 1-7 days postinjury, sensorimotor outcome was assessed by Rotarod and a modified Neurological Severity Score (NSS). Cognitive function was measured using Novel Object Recognition (NOR) and Morris water maze (MWM) in the first week postinjury.

Setting: Neurotrauma research laboratory.

Measurements and results: Disrupting posttraumatic sleep for 6 h did not affect serum corticosterone levels or functional outcome. In the hour following the first dark onset, sleep-disrupted mice exhibited a significant increase in sleep; however, this increase was not sustained and there was no rebound of lost sleep. Regardless of sleep disruption, mice showed a time-dependent improvement in Rotarod performance, with brain-injured mice having significantly shorter latencies on day 7 compared to sham. Further, brain-injured mice, regardless of sleep disruption, had significantly higher NSS scores postinjury compared with sham. Cognitive behavioral testing showed no group differences among any treatment group measured by MWM and NOR.

Conclusion: Short-duration disruption of posttraumatic sleep did not affect functional outcome, measured by motor and cognitive performance. These data raise uncertainty about posttraumatic sleep as a mechanism of recovery from diffuse brain injury.

Keywords: Behavior; TBI; concussion; diffuse; mild; mouse; sleep; sleep disruption.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries / complications
  • Brain Injuries / physiopathology*
  • Cognition / physiology*
  • Cognition Disorders / complications
  • Cognition Disorders / physiopathology*
  • Darkness
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Post-Concussion Syndrome / complications
  • Post-Concussion Syndrome / physiopathology*
  • Psychomotor Performance / physiology
  • Recovery of Function / physiology*
  • Rotarod Performance Test
  • Sleep / physiology*
  • Time Factors
  • Uncertainty