Destabilization of Hypothalamic Sleep/Wake Neuronal System in the Experimental SCI

Project: Research project

Project Details



Spinal cord injury (SCI) produces dramatic, life-long, impairment of multiple basic physiological processes, including the regulation of sleep. Chronic sleep disturbances are hypothesized to initiate wide-ranging co-morbidities in the able-bodied population. It is well regarded that the physiological consequence of insufficient sleep includes elevated stress, increased levels of inflammatory markers, diminished protein synthesis, reduced wound healing, increased pain sensitivity, elevated risk for obesity/type II diabetes, and results in cognitive impairment. As such, the post-injury clinical picture of SCI patients may be exacerbated by diminished sleep efficiency.

In the present proposal we will use an animal model of high thoracic (spinal level T3) SCI with the overarching aim to elucidate the neural mechanisms responsible for reduced sleep efficiency after T3-SCI. Specifically, we will experimentally develop our hypotheses that (1) EEG analysis will quantify sleep quality and reveal that SCI animals display more frequent arousals during sleep periods leading to reduced sleep efficiency compared to surgical controls; (2) chronic T3-SCI interrupts the functioning of the neural systems that regulate sleep and wakefulness. We predict that SCI rats will have reduced expression of markers for active neurons in the region of the brain that is responsible for promoting sleep (the ventrolateral preoptic nucleus; VLPO) when compared to surgical controls. We further predict that analysis of the VLPO region of SCI rats will reveal higher levels of the neurotransmitters norepinephrine and serotonin compared to surgical controls. Release of these neurotransmitters acts to inhibit sleep by reducing activity in the VLPO.

The current project will validate our ability to quantify sleep disturbances in our experimental model of SCI. Indeed, while descriptive reports have revealed sleep disturbances in experimental models of SCI, to date, no study of the neural mechanisms responsible for the observed sleep disorders have been conducted. This research will begin to establish that reduced sleep efficiency is a critical secondary pathology of SCI and will provide insights into the complex neural sleep/wake mechanisms altered by SCI. Ultimately, the model that will be developed in this project may be used toward understanding diminished sleep quality in human SCI and provide immediate understanding regarding the influence of sleep upon post-SCI co-morbidities in the clinical setting.

Effective start/end date1/1/0912/31/09


  • U.S. Department of Defense: $147,941.00


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