Advanced Restoration Therapies in Spinal Cord Injury 0186 - FY 08 - 09

Principal Investigator: John McDonald

Evidence suggests that functional electrical stimulation (FES) can improve certain functions in the central nervous system (CNS) following injury or disease. Using FES-based therapies in spinal cord injured patients in our clinic, we have observed neurological, physical, and functional improvements. We wish to study this effect further to optimize the benefits of FES ergometry. Many studies now demonstrate that electrical stimulation can promote numerous aspects of regeneration following CNS injury, including axon myelination. We and others have shown that remyelination following SCI is one rational and effective approach to promoting recovery of function following experimental SCI. However, very few research groups are testing similar FES parameters in cell culture, animal models of SCI and in patients as part of one study. By systematically measuring the impact of FES on remyelination and functional recovery in these three settings, we hope to advance our understanding of how FES promotes regeneration.

Objective/Hypothesis

We will expand the studies begun in FY07, year 1 of our funding, and will continue to test the hypothesis that patterned neural activity induced by FES enhances recovery of function in the injured spinal cord in animal models and patients with paralysis. In addition, indices of remyelination will be measured in cell culture, animal models, and humans to test whether remyelination correlates with recovery of function.

Study Design

SA1: [FY08][FY09] We will continue a randomized, controlled, single-blinded trial in 24 subjects with SCI following an A (FES assisted)-B (non-FES assisted) type protocol regimen of the upper extremities. Neurological and functional outcome measures will be assessed.

SA 2: [FY08] Preservation of topography and function in sensorimotor cortex measured by fMRI-derived metrics and transcranial magnetic stimulation (TMS)-derived metrics will be correlated with ASIA scores in spinal cord injured subjects. [FY09] Advanced MRI techniques will be used to correlate conventional ASIA scores with myelin integrity of the spinal cord in SCI patients with stabilizing paramagnetic hardware in place.

SA3: [FY08] We will perform short term FES in rats with complete transection SCI using peroneal nerve stimulation and we will assess subsequent long-term oligodendrocyte differentiation and myelination in vivo and following cell culture ex vivo [FY09] FES will be applied to rats with a clinically relevant contusion spinal cord injury and recovery of myelination and function will be measured.

SA4: [FY08][FY09] We will determine if brief exposure of mixed neural cultures to electrical field stimulation alters cell signaling and promotes myelination.