# Stimulation-based strategies for forming new lesion-bridging circuitry and optimizing functional recovery after spinal cord injury

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $327,824

## Abstract

Abstract
Spinal cord Injury (SCI) leads to sensorimotor paralysis for which there is currently no cure. Our previous work
determined that optogenetic spinal stimulation, a relatively new method for stimulating the spinal cord, has robust
neuromodulating effects that significantly increases axonal growth, neuro-vasculature and importantly, functional
recovery in rats with sub-chronic cervical spinal injuries. However, recovery was less complete in rats with more
severe injuries. With the overarching goal of identifying effective therapeutics for spinal injuries of varying
magnitudes, the proposed study will further develop and optimize optogenetic spinal stimulation for the severely
hemi-contused spinal cord. More specifically, in Aim 1 we will identify if increasing the number of weekly
stimulation periods will promote significant recovery in rats with a severe cervical hemicontusion. We will increase
stimulation sessions from 1x/week to 2,3 and 4x/week and investigate the effects on forelimb functional recovery
of four behavioral tasks. In Aim 2, we will investigate the combinatorial effects of optogenetic spinal stimulation
and Intracellular Sigma Peptide (ISP) on functional recovery in rats after severe cervical hemicontusion. ISP
alleviates the inhibitory effects of chondroitin sulfate proteoglycans on axonal growth and new circuitry formation
after SCI. We hypothesize that combining this peptide with optogenetic stimulation will increase the critical
formation of new circuitry bridging the lesion site, helping to reconnect upstream neurons with downstream
targets that will translate into improved functional recovery. This will be further explored in Aim 3, where we will
identify the changes in circuitry that occur in response to optogenetic spinal stimulation alone or in combination
with ISP delivery. This will be assessed by looking at spinally-evoked forelimb muscle activity in combination
with the activity-sensitive viral vector CaMPARI2 to identify participating neurons, as well as additional tissue
analysis using immunohistochemistry and RNAScope. Overall, the proposed study will further develop and
optimize a new and powerful method for therapeutically stimulating the spinal cord and promoting significant
functional recovery within the sub-chronic, severe SCI community. The findings from circuitry analysis will also
provide important insights into future strategies for further improving functional recovery after SCI.

## Key facts

- **NIH application ID:** 10977595
- **Project number:** 1R01NS134713-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Sarah E. Mondello
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $327,824
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10977595

## Citation

> US National Institutes of Health, RePORTER application 10977595, Stimulation-based strategies for forming new lesion-bridging circuitry and optimizing functional recovery after spinal cord injury (1R01NS134713-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10977595. Licensed CC0.

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