Dissertation
Impacts of epidural stimulation types on the recovery of function in combined bionic and biological SCI therapies
Doctor of Philosophy (Ph.D.), Drexel University
Apr 2024
DOI:
https://doi.org/10.17918/00010485
Abstract
Recovery of locomotor function is among the top goals of rehabilitation following spinal cord injury (SCI). Although recent clinical trials report promising therapies in recovering locomotion, there is currently no FDA-approved treatment. Preclinical studies have been used to guide and shape clinical trials, and work from our lab, and others, have demonstrated effective strategies to restore locomotor function after SCI in animals. We previously demonstrated that sustained expression of brain-derived neurotrophic factor (BDNF) during SCI therapy has been shown to induce spontaneous stepping in rats, but also it increases the prevalence of hyperreflexia after 3-4 weeks, causing functionally deleterious collapse in locomotion. To investigate this outcome and further improve BDNF-based rehabilitation, we explored combined rehabilitations using gene therapy (AAV5-BDNF), different epidural stimulation (ES) types, and robotic training for SCI in rats. Interneuronal circuits in the spinal cord which provide drives to motoneurons may be organized for modular muscle control and play roles in these outcomes. Electromyogram (EMG) recordings reflect the premotor network drives. Accordingly, we employed Independent Components Analysis (ICA) to uncover modular changes in synergies. We tested if types of ES therapy can better recover and maintain locomotion by preventing BDNF-associated hyperreflexia in the combined therapy. We hypothesized that the spatial synergies underlying motor modularity would be retained after SCI and different rehabilitation outcomes but that BDNF+ES treatment would selectively target the spinal central pattern generators, resulting in different utilization of these synergies, improving locomotion. Our data show that suprathreshold ES extends the therapeutic window of BDNF-induced plasticity to significantly improve assisted locomotion before any BDNF-driven collapse. ICA of EMGs revealed high post-SCI correlation values of the weighting matrices and synergy matching in all groups, supporting a conserved modular control of locomotion after SCI, even in collapse patterns. Altogether, the data suggest spatial synergies are conserved after complete SCI and combination therapy rehabilitation, regardless of collapse outcome, and that overexpression of BDNF needs to be tightly regulated in time.
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Details
- Title
- Impacts of epidural stimulation types on the recovery of function in combined bionic and biological SCI therapies
- Creators
- Andrey Borisyuk
- Contributors
- Marie-Pascale Côté (Advisor) - Drexel University, Neurobiology and Anatomy
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- ix, 126 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Other Identifier
- 991021876813104721