For many after spinal cord injury (SCI) there is immobilization, muscle atrophy, bone loss, fracture risk during transferring (or falls), and the risk of secondary complications, and increase in attendance care and cost. It is important to develop multi dimensional rehabilitation strategies for people after SCI to enhance functional recovery towards walking, and enhance an increase in muscle and bone to potentially prepare the injured nervous system in the event of a cure. Locomotor training (Stand retraining and step re training) an activity-based rehabilitative approach generates muscle activity and provides weight bearing and joint contact kinetics, even in individuals who are unable to stand or step independently. Cross-sectional animal and human SCI studies have demonstrated that locomotor training (LT) (stand retraining and step retraining using body weight support treadmill training) has improved the capacity to stand independently and walk at faster speeds. Neuromuscular stimulation (NMS) or electrical stimulation (ES) training is a rehabilitative approach that generates muscle activity, alternating leg extension and flexion even in individuals who are unable to stand or step independently. NMS studies for individuals after SCI have shown improvements in bone density and muscle strength after cycling and resistance training. The main purpose of this study is to address whether stand retraining and NMS compared to stand retraining alone or NMS alone will increase neural and musculoskeletal gains and provide a greater functional recovery towards independent standing.

This project will be completed at two sites: Kessler Foundation Research Center (the grant PI site) and Frazier Rehabilitation Institute, University of Louisville, Kentucky.

There will be three groups in this study. Each group will receive 1.25 hr of intervention per session, for a total of 60 sessions (3 - 4 x week, 15- 20 weeks). Participants in Group 1 will receive 1hr of ES while lying down in the chair followed by 15 min of overground training. Group 2 will receive standing retraining using BWS followed by 15 minutes of overground training. Group 3 will receive standing retraining with ES, followed by 15 min of overground training. Participants will complete the study after 20 weeks of training. The participant will be able to miss 8 consecutive training sessions before being dropped from the study.

PRIMARY AIMS

Specific Aim 1: To examine the effectiveness of standing retraining with ES for alterations in muscle volume (MV) and BMD in the lower limb:

Hypothesis 1.1. SRT with ES compared to SRT alone or ES alone will increase muscle volume(MV) and muscle cross sectional area(MCSA) and potential muscle torque(PMT) at hip, knee and ankle joints (compared to baseline).

Hypothesis 1.2. SRT with ES compared to SRT alone or ES alone will increase absolute BMD in the lower limbs(compared to baseline) Hypothesis 1.3. SRT with ES compared to SRT alone or ES alone will increase markers for bone formation and a decrease in markers for bone resorption commensurate with the observed increase in BMD (compared to baseline) SECONDARY AIMS Specific Aim 2 To examine the effectiveness of standing with ES for improvements in functional outcome and alterations in EMG in lower limb.

Hypothesis 2.1. SRT with ES compared with SRT alone or ES alone will improve functional performance(as measured by standing time on the treadmill and overground) Hypothesis 2.2. SRT with ES compared to SRT alone and ES alone will experience a greater increase in the electromyography (EMG) amplitude for all leg muscles examined (compared to baseline) during standing.

Hypothesis 2.3. LT with ES compared to SRT alone and ES alone will experience significantly greater cardiac output (CO) and/or stroke volume SV (compared to baseline).

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Inclusion Criteria:

• Must be between 18 and 58 years old with a neurological SCI level between the C6-T10 level and an impairment grade A, B, or C, according to the American Spinal Injury Association (ASIA) Impairment scale.
• Must have a spinal cord injury that is greater than 6 month or less than 2 years post injury
• Must have score less than 3 on the Modified Ashworth Scale.
• Must be able to tolerate electrical stimulation and must show visible muscle contraction to electrical stimulus
• Must be wheelchair reliant for more than 75% of the time

Exclusion Criteria:

• Bone density measurement (as recorded by the researcher) for knee at or below 0.5755 gm/cm2
• Weigh more than 225 Ibs.
• Taller than 6 feet 3 inches
• Post -menopausal, pregnant or a lactating woman.