Transplanting Neural Progenitor Cells Improves Neural Regulation But Not Hormonal Reliance of Cardiovascular Function Following Spinal Cord Injury.

High-level spinal cord injury (SCI) often reduces neural regulation of cardiovascular function. During the chronic phase, humoral regulation via the renin-angiotensin system (RAS) is enhanced to compensatorily maintaining blood pressure. It was recently shown that transplanting early-stage neurons into the injured cord mitigates cardiovascular disorders. However, the mechanisms underlying this recovery remain largely unknown. Here, we employed various pharmacological interventions to elucidate whether this strategic transplantation affects the imbalance of neuroendocrine regulation of hemodynamics and the role of specific serotonergic and catecholaminergic components. Female rats received a complete crush at the fourth thoracic spinal cord. Embryonic neural progenitor cells (NPCs) harvested from the raphe nuclei or the spinal cord were transplanted into the lesion. Naive rats or injury alone served as controls. After 8-9 weeks, radio-telemetric recordings demonstrated that both implants decreased tachycardia at rest and diminished the frequency or severity of autonomic dysreflexia (AD). Pharmacological interventions demonstrated that both NPC grafts partially restored neural regulation of blood pressure without normalizing the aberrant RAS hyperactivity. Subsequently, specific neural mechanisms were explored through intrathecal administration of the 5-HT_2A antagonist ketanserin, the 5-HT_1A antagonist WAY100635, or the α1-adrenoreceptor antagonist prazosin. It revealed that graft-derived serotonergic signaling was involved in the restoration of the resting heart rate via 5-HT_2A receptors but did not attenuate AD. In addition, catecholaminergic mechanisms remained critical for blood pressure maintenance after SCI. Ultimately, the results provide insight into understanding the mechanistic nuances associated with cell therapy for SCI-induced cardiovascular dysfunction.