"Oxygen Deprivation as a Potential Adjuvant to Spinal Cord Injury Rehabilitation"

Randy Trumbower, PhD - Assistant Professor, Department of Rehabilitation Medicine, Emory University

Spinal cord injury (SCI) leads to disrupted connections within and between the brain and spinal cord, causing life-long paralysis. However, most injuries are not complete, leaving at least some spared neural pathways to the motor neurons that initiate and coordinate movement. Consequently, neural plasticity contributes to spontaneous recovery of motor function following SCI. Although injury-induced plasticity in spared spinal synaptic pathways enables partial spontaneous recovery, the extent of this repair is slow, variable, and limited. Thus, there is an overwhelming need for new clinical approaches that induce/enhance plasticity and improve motor function in persons with SCI.

Acute intermittent hypoxia (AIH) induces spinal plasticity, repairing synapses on motor neurons. Considerable progress has been made towards an understanding of cellular mechanisms giving rise to AIH-induced respiratory plasticity. Repetitive breathing bouts of AIH enhance the expression of key proteins for AIH-induced respiratory plasticity within respiratory motor neurons. Key steps in this regenerative process include episodic release of serotonin near respiratory motor neurons, thereby increasing local protein synthesis, which includes brain derived neurotrophic factor (BDNF). AIH may increase the expression of these same proteins in non-respiratory motor neurons; serotonergic neurons innervate motor neurons at multiple spinal levels, including both respiratory and non-respiratory motor nuclei. Thus, our working hypothesis is that similar, serotonin-dependent endogenous mechanisms enhance BDNF expression, thereby improving motor function in both respiratory and non-respiratory motor neurons within the spinal cord.

Since the neural system controlling breathing is similar to limb control in many details (eg. alpha-motor neurons, volitional and automatic control), it would not be surprising if AIH improves limb motor function after spinal injury. Indeed, exciting results from my collaborating laboratories demonstrate that AIH facilitates non-respiratory motor output in spinally injured rats and humans. Daily breathing exposures of AIH (5 min episodes, 5 min intervals, 7 consecutive days) completely restored lost forelimb function in a horizontal ladder-walking task in spinal-injured rats, and this effect lasted more than 3 weeks post-treatment (G. Muir laboratory; Mitchell et al. 2009). With shorter hypoxic episodes (1-1.5 min, 1 min intervals, 15 episodes), a single-day exposure of AIH increased maximum ankle torque generation and EMG activation for up to 3 hours in persons with incomplete SCI (Trumbower et al. 2011). Although these findings are striking, much work needs to be done to determine the clinical feasibility of AIH as a neuroregenerative tool to elicit long-term improvement of limb function (i.e., walking, grasping, etc.) after spinal injury. Thus, the ultimate goal of our future work is to assess the potential of AIH as an adjuvant to SCI rehabilitation.

The IBB Breakfast Club seminar series was started with the spirit of the Institute's interdisciplinary mission in mind. The goal of the seminar series is to highlight research taking place throughout the institute to enable the IBB community to further collaborative opportunities and interdisciplinary research. Faculty are often asked to speak at other universities and conferences, but rarely present at their home institution, this seminar series is an attempt to close that gap. The IBB Breakfast Club is open to anyone in the bio-community.