Inflammation, Neurovascular Hemodynamics, and Sleep in Traumatic Brain Injury

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Veterans that experience traumatic brain injury often exhibit profound and debilitating sleep, impairments in their brain wave activity, and dysregulated brain vascular functions. Disturbed sleep can impair mood, the ability to work, cognition, relationships, and overall quality of life. Traumatic brain injury results in localized damage to the brain inducing long-term increased inflammation and impairments in cerebral blood flow. Evidence indicates that traumatic brain injury damage increases oxidative stress in the brain—a process known to induce inflammatory molecules in brain cells, such as glia and neurons, that alters brain vascular functions. Interestingly, growing evidence suggests that inflammation affects brain vascular functions and that vascular functions change during sleep, although the exact mechanism responsible for these effects are not well understood. The goal of this proposal is to determine how traumatic brain injury induces a major sleep regulatory inflammatory pathway affected by oxidative stress in dysregulating sleep, brain wave activity, and brain vascular functions. We hypothesize that traumatic brain injury drives oxidative stress to induce chronic brain inflammation impairing brain vascular functions to impair sleep and brain wave activity. We use molecular and cellular techniques, polysomnography, and vascular measurements in animal models for the aims of this project. Aim 1 determines how components of a major sleep regulatory inflammatory pathway that is induced by oxidative stress is activated in the brain by traumatic brain injury resulting in dysregulated sleep, brain wave activity and vascular functions. Aim 2 examines how this major sleep regulatory inflammatory pathway is activated by traumatic brain injury to induce both local and regional changes in brain vascular functioning and brain wave activity during sleep. Data obtained from this project will provide critical information to understand the relationship between inflammation and brain vascular functions on sleep and brain wave activity occurring from traumatic brain injury. Thus, the findings from this project will provide information about novel targets involved in sleep dysregulation which will lead to the future development of novel treatments for veterans with traumatic brain injury.