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Dissertation
Cell transplantation combined with exercise improves cardio-electric conduction after spinal cord injury
Doctor of Philosophy (Ph.D.), Drexel University
Apr 2025
DOI:
https://doi.org/10.17918/00010931
Abstract
Cardiovascular function is tightly regulated by the autonomic nervous system, which maintains blood pressure and heart rate under normal physiological conditions. High-level spinal cord injury (SCI) disrupts supraspinal control of sympathetic activity, resulting in impaired hemodynamics, autonomic imbalance, and increased susceptibility to cardiac conduction disorders. Current treatment options are limited to symptom management, with no available therapies to restore central autonomic control. We previously demonstrated that transplantation of raphe nucleus-derived neuronal progenitor cells (RN-NPCs) partially restores sympathetic pathways and improves cardiovascular function after SCI. However, single-modality interventions have proven insufficient for full functional recovery. Here, we investigated a combinatorial therapeutic strategy pairing RN-NPC transplantation with long-term exercise rehabilitation. Using a T2/3 crush SCI model in rats, we implemented passive hindlimb cycling (PHLC) for 5 or 10 weeks. Cardiovascular function was assessed via telemetric blood pressure and electrocardiogram (ECG) recordings. Long-term PHLC improved autonomic balance by reducing elevated parasympathetic tone and significantly attenuated severe cardiac arrhythmias including atrioventricular block, sinus pause, and premature ventricular contractions during colorectal distension-induced autonomic dysreflexia and dobutamine-induced cardiac stress. To assess the efficacy of a combined approach, RN-NPCs were transplanted acutely post-injury, followed by 10 weeks of PHLC. Pseudorabies virus (PRV) injected into the epicardial space transsynaptically labeled neurons in both the graft and brainstem, confirming reestablishment of supraspinal pathways. Histological analysis revealed enhanced host-graft integration and axonal projections into caudal autonomic regions. Although both PHLC alone and in combination with RN-NPCs improved autonomic regulation and reduced arrhythmias, neither intervention significantly altered resting or stress-induced hemodynamic measures. These findings support the use of integrative therapies targeting multiple mechanisms as a promising strategy for treating cardiac conduction disorders following high-level SCI.
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Details
- Title
- Cell transplantation combined with exercise improves cardio-electric conduction after spinal cord injury
- Creators
- Marissa Ann Cusimano
- Contributors
- Shaoping Hou (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 134 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Other Identifier
- 991022052538904721