# Multipronged approach to promote functional axonal regeneration in the spinal cord after injury

> **NIH NIH R01** · DREXEL UNIVERSITY · 2020 · $336,328

## Abstract

PROJECT SUMMARY
 The lack of successful regeneration after injury in the mature central nervous system is due to intrinsic and
environmental obstacles. Though progress in the field has been made, overcoming these barriers to result in
robust functional axon regeneration and recovery is still a significant challenge. We build upon preliminary data
and hypothesize that recurrent DREADD-mediated neuronal activation after injury is a means to enhance
functional axon regeneration. Additionally, we will test the hypothesis that neuronal activation increases axon
regeneration via both mTOR activation and increasing dynamic microtubules. We will these our hypotheses both
in vitro using adult dorsal root ganglion neuron cultures and in vivo using dorsal root crush, dorsal columns
spinal cord injury (SCI)/peripheral nerve graft (PNG), and incomplete cervical SCI/PNG models. In Aim 1, we
will elucidate how repeated, chemogenetic neuronal activation enhances axon regeneration. In Aim 2, we will
assess if neuronal activation – alone or in combination with manipulations that increase dynamic microtubules
and mTOR activation – promotes functional axon regeneration. Collectively, we will: 1) elucidate mechanisms
behind how neuronal activation enhances growth, potentially identifying new therapeutic targets; 2) determine
the extent to which neuronal activation enhances regeneration in different injury models (dorsal root crush, SCI);
3) determine if neuronal activation has disparate or similar effects in different populations of neurons (DRG vs.
CNS); 4) test whether meaningful axonal regeneration is facilitated using a unique, multi-faceted approach
that: a) uses chemogenetic neuronal activation – possibly along with further increasing dynamic microtubules
and/or mTOR activation – to enhance the axonal growth response; b) provides a more growth-permissive
environment after an injury (i.e. mitigation of the inhibitory matrix of the glial scar with chondroitinase;
transplantation of a PNG into an SCI cavity; chondroitinase digestion of plasticity-limiting perineuronal nets).
After the completion of these experiments, we will have identified novel therapeutic avenues to foster functional
repair after SCI.

## Key facts

- **NIH application ID:** 9916218
- **Project number:** 2R01NS085426-06A1
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Veronica Jean Tom
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,328
- **Award type:** 2
- **Project period:** 2014-05-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9916218

## Citation

> US National Institutes of Health, RePORTER application 9916218, Multipronged approach to promote functional axonal regeneration in the spinal cord after injury (2R01NS085426-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9916218. Licensed CC0.

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