Intermittent Hypoxia Elicits Prolonged Restoration of Motor Function in Human SCI

Principal Investigator: MITCHELL, GORDON S
Institution Receiving Award: WISCONSIN, UNIVERSITY OF, MADISON
Program: SCIRP
Proposal Number: SC090355
Award Number: W81XWH-10-1-0830
Funding Mechanism: Translational Research Partnership Award
Partnering Awards: SC090355P1, SC090355P2
Award Amount: $289,193.00


The goal of our study is to determine whether repeatedly breathing low oxygen levels for brief periods (termed intermittent hypoxia) will improve limb function after spinal cord injury. This idea stems from animal studies on respiration, in which investigators have shown that mild intermittent hypoxia improves breathing in spinally injured rats. These studies have shown that intermittent hypoxia induces spinal plasticity, strengthening neural connections and motor neuron function within the spinal cord. Exposure to mild intermittent hypoxia triggers a cascade of events, including increased production of key proteins and increased sensitivity of spinal cord circuitry necessary for improved breathing. In animal models, similar events occur in non-respiratory regions of the spinal cord, particularly in regions that control limb function. We propose to investigate whether daily, mild intermittent hypoxia can improve limb function in animal models and in persons with chronic spinal injury.

We initially hypothesize that daily exposure to intermittent hypoxia for 7 consecutive days will improve limb function in rats and in humans with chronic spinal injuries. First, we will compare limb function in spinally injured rats that receive mild intermittent hypoxia treatment with rats that did not. We will measure grip strength and locomotor abilities in both groups before treatment and for several months after treatment. We will also examine the spinal cords of these rats to look for the key proteins, which are indicators of spinal plasticity. We will use this information to guide the treatment protocols when we compare limb function in spinal-injured persons with and without intermittent hypoxia treatment.

Our second hypothesis is that combining intermittent hypoxia with locomotor training will further improve limb function after spinal injury. To test this idea, we will compare limb function in spinally injured rats that have received combined intermittent hypoxia and treadmill training with rats that only received intermittent hypoxia or locomotor training alone. We will examine key proteins in the spinal cords of these rats to determine whether the combination of hypoxia and training further alters these indicators of plasticity. We will also compare limb function in spinally injured humans who receive both intermittent hypoxia and locomotor treadmill training with those who receive either treatment alone. The ultimate goal of this research is to assess the potential of mild intermittent hypoxia as a therapeutic approach to stimulate recovery of limb function in human patients.