# Elucidating Serotonergic Mechanisms Regulating Cardiovascular Recovery After Grafting Embryonic Raphe Neurons into the Injured Rat Spinal Cord

> **NIH NIH F31** · DREXEL UNIVERSITY · 2021 · $36,459

## Abstract

PROJECT SUMMARY/ABSTRACT
 Spinal cord injury (SCI) at the 6th thoracic level (T6) or above often results in the loss of supraspinal
regulation over cardiovascular function. This dysfunction manifests as abnormal resting hemodynamics and the
development of orthostatic hypotension and autonomic dysreflexia (AD). Collectively, these irregularities mark
cardiovascular dysfunction as one of the leading causes of morbidity and mortality among the population.
Although there are current pharmacological and preventative measures in place to mitigate these issues, they
lack long-term efficacy and do not address the underlying loss of supraspinal connectivity. Recently, we
discovered grafting raphe nuclei-derived neural progenitors/stem cells (RN-NPCs) after SCI partially restores
hemodynamic regulation. More specifically, we found that the graft restores connectivity between raphe nuclei
cell populations and sympathetic preganglionic neurons in the spinal cord. Moreover, silencing serotonergic
receptor 5HT2A resulted in the loss of functional recovery. Therefore, we hypothesize that functional recovery
after grafting is centrally mediated through supraspinal and intraspinal serotonergic mechanisms. In Aim 1, we
will graft RN-NPCs into rats sustaining a T4 crush injury and measure cardiovascular output including resting
hemodynamics, and AD frequency and severity. Subsequently, we will reinjury the rats above the transplant site
and reevaluate all hemodynamic parameters. This will determine if functional restoration is contingent on
supraspinal connectivity with the graft. In Aim 2, we will employ chemogenetic techniques to silence serotonergic
neurons of the host caudal raphe nuclei after RN-NPC grafting to identify if supraspinal serotonergic regulation
of cardiovascular function has been reestablished. In Aim 3, we will use the same chemogenetic tools to silence
graft-derived serotonergic neurons, elucidating if these neurons facilitate hemodynamic restoration. We will also
administer serotonergic and noradrenergic receptor antagonists to examine which spinal receptors are involved
in reestablishing cardiovascular regulation. Collectively, these results will provide guidance for potential clinical
translation to mitigate hemodynamic dysfunction after SCI.

## Key facts

- **NIH application ID:** 10231367
- **Project number:** 1F31NS122245-01
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Cameron T Trueblood
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,459
- **Award type:** 1
- **Project period:** 2021-07-01 → 2022-03-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231367

## Citation

> US National Institutes of Health, RePORTER application 10231367, Elucidating Serotonergic Mechanisms Regulating Cardiovascular Recovery After Grafting Embryonic Raphe Neurons into the Injured Rat Spinal Cord (1F31NS122245-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10231367. Licensed CC0.

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