HUMAN GLYMPHATIC FUNCTION IN EXTREME ENVIRONMENTS
Abstract
Maintaining optimal neurological health is key for ensuring warfighter resilience and readiness, particularly those personnel exposed to multiple potential stressors that impact brain homeostasis and long-term neurological health. Recent studies have pointed to the importance of optimal clearance and function of the brains recently-discovered glymphatic system for clearance of metabolic byproducts, inflammatory and immune-mediated molecules, and other solutes, in addition to playing a key role in brain immune and inflammatory responses to injury. A number of warfighter-related conditions, including sleep deprivation and concussive/subconcussive head injury, have been shown to significantly impact glymphatic function and resulting brain health.In addition to changing in response to the stressors described above, it has been hypothesized that changes in cerebral blood flow and molecular signaling in response to exercise, hypo/hyperoxia, hypo/hypercarbia, and immersion can have a significant impact on glymphatic function in undersea divers, submariners, and warfighters working in extreme environments or high stress exposures. Understanding how these mission-related stimuli affect glymphaticfunction will be key for maintaining and optimizing operator health and resilience. However, to date, there have been no studies assessing the effects of mission-relevant environmental stressors on glymphatic function.Specific Aims: We propose a coordinated, multi-institution program to assess glymphatic function in response to Navy diver-relevant exposures (hypoxia, hyperoxia, hypercapnia and deep-diving field exposures) in human participants and parallel studies in murine models. This proposal specifies the human research to be led by Dr. Dawn Kernagis in collaboration with Dr. Rachael Seidler at the University of Florida. The concurrent animal research and assessment of both murine and human blood markers will be led in a separately funded effort by Dr. Stephen Thom, as outlined in his ONR proposal Glymphatic Function in Extreme Environments.Aim 1: Assess glymphatic, CSF, and cerebral blood flow characteristics in response to operationally-relevant stressors (hypoxia, hyperoxia, hypercapnia) in human subjects by MRI and photoacoustic, near-infrared, and fluorescence imaging.Aim 2: Evaluate changes in peripheral blood neutrophil activation, sub-populations of MPs, and protein markers for neuronal integrity and function in human subjects and in mice (collected in a separate, parallel effort by Dr. Stephen Thom) concurrently with glymphatic function in Aim 1.Aim 3: Conduct field-based assessment of deep cervical lymphatic outflow (a non-invasive, indirect measure of glymphatic function), cerebral blood flow, and associated peripheral markers of glymphatic function in deep divers conducting extended profile, immersed, mandatory decompression dives.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 08, 2020
- Source ID
- N000142012463
Entities
People
- Dawn Kernagis
Organizations
- Florida Institute for Human and Machine Cognition
- Office of Naval Research
- United States Navy