Hypoperfusion and impaired blood flow in chronic spinal cord injury

Spinal cord injuries affect thousands of people every year, with approximately 18,000 new cases each year in the US alone, and the functional deficits from this condition last a lifetime. Currently, there are between 243,000 and 347,000 people living with chronic SCI in the US. Acute traumatic spinal cord injury (tSCI) is known to cause hypoperfusion of the injured area, which leads to ischemia and subsequently to hypotension and hypoxia in the affected tissue. However, less is known about blood flow alterations and tissue perfusion (i.e., blood flow in the microcirculation) within the spinal cord at the chronic stage. We hypothesize that after tSCI, spinal cord tissue caudal to the lesion site is chronically hypoperfused, and vascular response is altered within the microvasculature. Currently available techniques are not able to accurately examine the concurrent spinal tissue perfusion and vessel morphology in vivo. To visualize and quantify blood flow and vascular changes within the spinal cord after SCI, we propose to utilize a recently developed technique called ultrafast contrast-enhanced ultrasound (CEUS) imaging. CEUS imaging allows for the visualization of morphology and blood flow velocities within larger vessels (>100 microns), as well as in the smaller microvasculature (<100 microns), also known as tissue perfusion. We will examine vascular remodeling and hemodynamic changes in both grey matter (GM) and white matter (WM) at a chronic time point (8-10 weeks post-injury) in areas centered over the injury as well as caudal to the injury site. In addition, we will examine whether vascular reactivity is altered within these sites by exposure to acute intermittent hypoxia. Results obtained from the proposed work will significantly impact our knowledge of vascular remodeling and will help to identify specific portions of the vascular tree as targets for future repair strategies aimed at normalizing spinal blood flow and enhancing functional recovery after tSCI.

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