The purpose of sleep continues to be debated. Prevailing hypotheses suggest a role in restoring energy balance, permitting synaptic reorganization, or cellular repair. With a traumatic brain injury, the mechanical forces and ensuing cellular signaling disrupt energy balance, initiate synaptic deafferentation followed by plasticity, and damage membranes, proteins and structural elements. Thus, acute post-traumatic sleep may mitigate injury-related damage. However, for the more than 1.4 million concussed individuals per year in the United States, prevailing folklore recommends that they should not be allowed to sleep or be awoken regularly, which is unsupported by medical evidence. Moreover, this sleep disturbance counteracts the natural repair processes of sleep that would be promoted by the ubiquitous inflammatory response after brain injury, as occurs with cytokine signaling upon infection. Surprisingly, the utility or detriment of acute post-traumatic sleep has yet to be explored. The current proposal tests the hypothesis that sleep is an immediate natural response to diffuse brain injury likely promoting recovery of the injured brain.
Aim 1 will correlate quantitative sleep parameters acutely following mild and moderate diffuse brain injury in the mouse to chronic physiological, behavioral and histopathological outcomes.
Aim 2 will explore the consequences of sleep disturbance on cognitive function, cytokine and glucocorticoid levels and histopathology across limbic and sleep structures. Post- traumatic sleep will be monitored by novel non-invasive technology validated for sleep- wake studies. This system employs custom-designed pressure sensors on the cage floor that continuously monitor for the motion associated with rhythmic breathing while animals are in a sleep posture. These experiments examine, for the first time, the effects of diffuse brain injury on sleep-wake patterns. Post-traumatic interventions to disrupt sleep may worsen or mitigate the behavioral and histopathological consequences of injury. Post-traumatic sleep may come to serve as an individualized biomarker to measure the severity of the initial injury and monitor the recovery process. For mild TBI, sleep itself could become a plausible behavioral intervention to mitigate the enduring neurological consequences of TBI.

Public Health Relevance

After a concussion, prevailing folklore recommends that individuals should not be allowed to sleep or be awoken regularly. Since sleep may be responsible for cellular repair and reorganization, post-injury sleep disturbance may delay or even prevent recovery. This proposal evaluates post-injury sleep in a mouse model of traumatic brain injury and the consequences, good or bad, of disturbing sleep shortly after injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21NS072611-02
Application #
8263023
Study Section
Brain Injury and Neurovascular Pathologies Study Section (BINP)
Program Officer
Hicks, Ramona R
Project Start
2011-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$189,375
Indirect Cost
$64,375
Name
University of Arizona
Department
None
Type
Schools of Medicine
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Harrison, Jordan L; Rowe, Rachel K; O'Hara, Bruce F et al. (2014) Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse. Exp Brain Res 232:2709-19
Rowe, Rachel K; Harrison, Jordan L; O'Hara, Bruce F et al. (2014) Recovery of neurological function despite immediate sleep disruption following diffuse brain injury in the mouse: clinical relevance to medically untreated concussion. Sleep 37:743-52
Rowe, Rachel K; Striz, Martin; Bachstetter, Adam D et al. (2014) Diffuse brain injury induces acute post-traumatic sleep. PLoS One 9:e82507
Rowe, Rachel K; Harrison, Jordan L; O'Hara, Bruce F et al. (2014) Diffuse brain injury does not affect chronic sleep patterns in the mouse. Brain Inj 28:504-10
Bachstetter, Adam D; Rowe, Rachel K; Kaneko, Machi et al. (2013) The p38? MAPK regulates microglial responsiveness to diffuse traumatic brain injury. J Neurosci 33:6143-53
Rowe, Rachel K; Harrison, Jordan L; Thomas, Theresa C et al. (2013) Using anesthetics and analgesics in experimental traumatic brain injury. Lab Anim (NY) 42:286-91