Post-Injury Sleep Disruption Alters the Inflammatory Response to Traumatic Brain Injury
Abstract
Traumatic brain injury (TBI) is a serious concern in civilian and military populations. The frequency of brain injury in professional sports as well as the occurrence of neurodegenerative diseases such as Alzheimer’s disease (AD), chronic traumatic encephalopathy (CTE), and frontotemporal dementia (FTD) indicates that there are serious long-term consequences to even mild and/or repetitive brain injuries. Furthermore, modern military conflicts put Soldiers at risk for penetrating and blast-related brain injuries that often correlate with mental health decline, depression, and even increased risk for neurodegenerative disease. Although a TBI occurs in a matter of milliseconds, the biological consequences of a brain injury may last a lifetime. We propose that the brain’s stress response to an immune challenge is compromised following a single TBI. As a result, subsequent life stressors that further challenge the immune system worsen long-term recovery from TBI. Mounting evidence shows that chronic sleep/wake disruption is a significant stressor that promotes inflammation resulting in brain dysfunction and behavioral impairment. Thus, we predict that post-injury sleep disruption (SD) is a significant and understudied stressor that largely influences outcome through inflammatory pathways. The proposed studies will examine the effects of SD after TBI, including the development of AD-like brain pathology in an experimental model. We propose that SD after TBI impairs neuroendocrine (stress) signaling resulting in increased inflammation, impaired functional recovery (behavior), and enhanced neurodegenerative pathology reflecting key features of AD. To date, no studies have examined the effects of post-injury SD pertaining to development of AD-like pathological features. Thus the experiments included in this proposal will provide novel insight to the interrelationship between TBI, sleep/wake, stress, and AD. This project is particularly relevant to high-risk TBI populations such as military personnel where sleep/wake disruption is potentially enhanced following return to duty.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910732
Entities
People
- Olga Kokiko-cochran
Organizations
- Ohio State University
- United States Army