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To investigate the safety and efficacy of breathing low oxygen (acute intermittent hypoxia, AIH) as a pretreatment to enhance the functional benefits of transcutaneous spinal neuromodulation (TSN) on walking training (WALK+TSN) in people with chronic, motor-incomplete spinal cord injury (iSCI). Double-blind, placebo-controlled multisite randomized clinical trial. Spaulding Rehabilitation Hospital; Boston, MA and Shirley Ryan AbilityLab; Chicago, IL. We plan to enroll 60 adults (18-70 yrs.) with chronic (>1 yr. post injury) iSCI who are ambulatory. All participants will receive two weeks of high intensity (8, 60min sessions) walking practice (WALK) before randomly receiving either two weeks (8 sessions) of AIH (15 episodes; 90s at 10% O2, 60s intervals of room air) pretreatment to WALK+TSN, SHAM (15 episodes; 90s at 21% O2, with 60s intervals of room air) pretreatment to WALK+TSN, or AIH pretreatment to WALK+NoTSN. The primary outcome of this study is walking speed which we will quantify using the change in 10-meter walk test time relative to baseline as the primary endpoint. The timed up-and-go test, six-minute walk test, as well as measures of pain, spasticity, autonomic dysreflexia, cognition, and bladder and bowel function will be secondary outcomes. We will record these measures at baseline, after WALK, and after the combinatorial treatments, and at 1-week, 4-weeks, and 8-weeks follow-up. We hypothesize that AIH pretreatment to WALK+TSN safely increases potency and efficacy of training-related walking improvements in people with chronic iSCI more than either alone. We also predict dose-dependent associations between a single day of AIH pretreatment and the long-term effects of daily AIH pretreatment. Functional walking remains a significant goal for many persons with iSCI. Prior studies show daily AIH promotes rapid spinal plasticity and augments the benefits of other therapies that enhance walking ability in individuals with chronic iSCI. The outcomes from this study will offer new insight into the potential enduring benefits of AIH pretreatment for TSN training to boost walking recovery in people with chronic iSCI. Gad & Edgerton: SpineX. [ABSTRACT FROM AUTHOR]

Primates are an important and unique animal resource. We have developed a nonhuman primate model of spinal cord injury (SCI) to expand our knowledge of normal primate motor function, to assess the impact of disease and injury on sensory and motor function, and to test candidate therapies before they are applied to human patients. The lesion model consists of a lateral spinal cord hemisection at the C7 spinal level with subsequent examination of behavioral, electrophysiological, and anatomical outcomes. Results to date have revealed significant neuroanatomical and functional differences between rodents and primates that impact the development of candidate therapies. Moreover, these findings suggest the importance of testing some therapeutic approaches in nonhuman primates prior to the use of invasive approaches in human clinical trials. Our primate model is intended to: 1) lend greater positive predictive value to human translatable therapies, 2) develop appropriate methods for human translation, 3) lead to basic discoveries that might not be identified in rodent models and are relevant to human translation, and 4) identify new avenues of basic research to "reverse-translate" important questions back to rodent models. [ABSTRACT FROM AUTHOR]

The lumbosacral spinal cord of mammals contains the neural circuitry capable of generating full weight-bearing locomotion of the hind limbs without any supraspinal input. One or more interventions, for example, pharmacological, epidural stimulation, and/or locomotor training, however, are necessary to gain access to and modulate the properties of this circuitry and to facilitate recovery of full weight-bearing locomotion after spinal cord injury. [ABSTRACT FROM AUTHOR]