# Spinal Neuromodulation to Promote Physiologic and Molecular Plasticity in theInjured Spinal Cord

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2024 · $455,365

## Abstract

Abstract
There is growing interest in the use of electrical stimulation to promote the recovery of sensorimotor and
autonomic function after neural injury. Previous research from our lab and others has demonstrated that
stimulation of spinal lumbar segments activates central pattern generators, which, in turn, facilitates standing
and walking. However, while there is extensive animal, pre-clinical, and clinical data examining the impact of
lumbar stimulation, studies that apply neuromodulation to the cervical spinal cord for upper limb are very limited.
Here, we propose that fundamental blind spots exist in the field of neuromodulation for upper limb, including
where to stimulate anatomically, how to dose and, especially, mechanisms of action. The Horner lab has
developed a clinically relevant rat model of cervical spinal cord injury and engineered a self-contained epidural
stimulation device that can be deployed in freely behaving rats to stimulate sensorimotor circuitry from multiple
surfaces of the spinal cord. Hence, we are well positioned to test critically important hypotheses on the role of
cervical stimulation in the restoration of upper limb function. We present exciting preliminary data demonstrating
that epidural stimulation of the cervical spinal cord improves forelimb function. The rationale for the proposed
research is that the site of epidural stimulation provides unique access to motor circuitry. We hypothesize that
ventral positioning of electrodes (VSS) will provide access to stimulate motor circuitry at the site of
lesion that are inaccessible from the more common dorsal approach (DSS). Further, we propose that
VSS will produce novel mechanisms of function plasticity that can amplify recovery when combined with
DSS. To test this hypothesis, we propose the following aims: Aim 1: Determine acute molecular and physiological
mechanisms of VSS when applied to subacute cervical spinal cord injury. Aim 2: Establish the functional impact
of site of stimulation and rehabilitative training on recovery from early chronic cervical spinal cord injury. Aim 3:
Establish the synergistic effects of combined VSS and DSS after cervical spinal cord injury. These studies will
explore an exciting new approach to promote neural recovery of the upper limb, an area of research that has
had limited investigation, but remains a primary concern for the patient. Our approach will rigorously establish
the physiological and functional effects of the site of stimulation on the molecular and physiological mechanisms
of upper limb plasticity.

## Key facts

- **NIH application ID:** 10932286
- **Project number:** 5R01NS132123-02
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** Philip J Horner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $455,365
- **Award type:** 5
- **Project period:** 2023-09-20 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932286

## Citation

> US National Institutes of Health, RePORTER application 10932286, Spinal Neuromodulation to Promote Physiologic and Molecular Plasticity in theInjured Spinal Cord (5R01NS132123-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10932286. Licensed CC0.

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