Dissertation
Grafting embryonic neural progenitor/stem cells to improve neuronal regulation of cardiovascular function after spinal cord injury
Doctor of Philosophy (Ph.D.), Drexel University
May 2022
DOI:
https://doi.org/10.17918/00001386
Abstract
High-level SCI often results in cardiovascular dysfunction. It was recently demonstrated that transplantation of embryonic raphe nuclei-derived neural progenitor/stem cells (RN-NPCs) into a transected spinal cord may reestablish serotonergic regulation of sympathetic activity for hemodynamic recovery. However, this strategy is hindered by several limitations, such as poor cell survival and integration. Using a spinal cord crush injury rat model, in the present study, we transplanted embryonic day 14 (E14) RN-NPCs into the lesion site and evaluated cardiovascular recovery. Grafting E14 spinal cord-derived NPCs or injury alone served as two controls. Eight weeks after cellular grafting, cardiovascular parameters and responses were recorded by a telemetric system. Histological analysis revealed well-survived grafts and remarkable integration with host tissues in the lesion site. Numerous graft-derived serotonergic axons topographically projected to the caudal autonomic regions. As a result, grafting RN-NPCs decreased SCI-induced tachycardia at rest, and attenuated both spontaneously occurring and colorectal distention (CRD)-induced autonomic dysreflexia. Subsequent blockade of 5-HT2A receptors in the spinal cord with Ketanserin eliminated the recovery of heart rate in RN-NPC grafted rats but not in injury only or SC-NPC controls, while it did not affect the severity of autonomic dysreflexia. It indicates that improvement of resting hemodynamics is mediated at least partially through central graft-derived serotonergic mechanisms. In addition, pharmacological interventions showed that hormonal regulation of basal blood pressure was increased whereas neural regulation was decreased after SCI, and RN-NPC grafts enhanced neuronal/hormonal balance of the cardiovascular system. Ultimately, transplantation of RN-NPCs reconstitutes neuronal, particularly serotonergic, regulation of sympathetic activity improving cardiovascular function following SCI.
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Details
- Title
- Grafting embryonic neural progenitor/stem cells to improve neuronal regulation of cardiovascular function after spinal cord injury
- Creators
- Cameron Terrissa Trueblood
- Contributors
- Shaoping Hou (Advisor)Itzhak Fischer (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiv, 131 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 991017495593004721