Files and links (1)
PDFOpen Access (License Unspecified), Open Access
Dissertation
Grafting Embryonic Neural Progenitor Cells to Improve Sympathetic Regulation of Cardiac Function after Spinal Cord Injury
Doctor of Philosophy (Ph.D.), Drexel University
Aug 2022
DOI:
https://doi.org/10.17918/00001318
Abstract
Cardiac function is highly regulated by autonomic nervous system. A cervical or thoracic spinal cord injury (SCI) often disrupts supraspinal regulation of sympathetic input to the heart, leading to disordered cardiac function. To gain in-depth understanding of mechanisms underlying cardiac pathophysiology, we established a rat model of cardiac dysfunction by inducing a crush injury at the 2nd/3rd thoracic (T2/3) spinal cord. Using electrocardiogram (ECG) and blood pressure recordings, we examined cardiac function by spectral, pharmacological, and cardiac-behavioral tests. Notably, the injury decreased cardiac sympathetic and increased parasympathetic tone, resulting in imbalanced autonomic regulation of the heart. Autonomic dysreflexia and dobutamine test to increase cardiac stress triggered numerous arrhythmias in T2/3 injured rats. To develop a therapeutic strategy for SCI-induced cardiac disorders, we transplanted embryonic day 14 neural progenitor cells isolated from the raphe nuclei (RN-NPCs) or spinal cord (SC-NPCs), into the lesion site of the injured cord. Nine weeks post-grafting, spectral and pharmacological analyses revealed that grafting either RN- or SC-NPCs enhanced cardiac sympathetic tone. Consequently, the number of arrhythmias was dramatically reduced during dobutamine test in grafted groups. However, cell grafting neither restored resting hemodynamics nor improved arrhythmias during autonomic dysreflexia. In both grafted groups, cardiac parasympathetic tone remained high and the hormonal regulation of blood pressure via the renin angiotensin system was not decreased. Histological analysis revealed that grafted cells well-integrated with the host tissue and extended axons onto the caudal autonomic regions. Ultimately, transplanting NPCs reconstitutes sympathetic input to the heart and improves cardio-electric disorders after SCI.
Metrics
41 File views/ downloads
19 Record Views
Details
- Title
- Grafting Embryonic Neural Progenitor Cells to Improve Sympathetic Regulation of Cardiac Function after Spinal Cord Injury
- Creators
- Silvia Fernandes
- Contributors
- Shaoping Hou (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xvi, 150 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 991019104705604721