# Characterization of Chronic Contusive Spinal Cord Injury and Promotion of Corticospinal Tract Regeneration

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2021 · —

## Abstract

Characterization of Chronic Contusive Spinal Cord Injury and Promotion of
 Corticospinal Tract Regeneration
Summary
Chronic spinal cord injury (SCI) is a post-injury stage when the injury is stable with little additional
change. Although the vast majority of SCI are chronic, there are few studies to characterize the chronic
injury at histological, cellular, and molecular level in clinical relevant animal models. There are even
fewer studies for development of therapeutic treatment of chronic SCI, especially for promotion of
supraspinal motor axonal regeneration, including the corticospinal tract (CST) system that is the most
important voluntary motor control system in humans. Therefore, we propose to use a chronic clinical
relevant moderate bilateral lower cervical contusion model for characterization it at cellular and molecular
levels and development of new therapies for improvement of skilled hand function.
There are three Specific Aims in this proposal. Aim 1 is to identify cellular mechanisms associated
with chronic contusive SCI, to guide discovery of new molecular mechanisms to promote
regeneration. We will develop a moderate chronic bilateral lower (C6) cervical contusion model since
the majority of SCI patients (65%) are quadriplegic, with loss of hand function that is critical for
independence and quality of life. The injured rats survive for up to 12 months to a chronic stage of SCI
for characterization of glial scar, extra cellular molecules (ECM) and axonal state. Aim 2 is to identify
transcriptional mechanisms associated with chronic contusive SCI, to guide discovery of new
molecular mechanisms to promote regeneration. We will use a newly developed technique
developed in our lab, Cre-dependent Ribotag vectors, to isolate mRNA specific from chronically injured
CST neurons for characterization of their transcriptome using RNAseq. We then compare this
transcriptome to intact and sub-acutely injured CST neurons (we already have these datasets) and
chronically injured CST neurons that regenerate into neural progenitor cell (NPC) graft to identify key
molecular pathways related to cellular/axonal growth that are disrupted, We can therapeutically target
these molecular pathways in Aim 3 and future studies. Aim 3 is to test candidate mechanisms to
promote recovery of chronically injured CST neurons and promote axonal regeneration after
chronic SCI. We will first perform in vitro screen for the potential candidate targets identified in Aim2 to
promote neurite growth of postnatal cortical neurons and adult dorsal root ganglion (DRG) neurons. We
then test these candidate genes to promote regeneration of chronically injured CST in combination with
NPC transplants that serve as a permissive cellular substrate. Findings of this work will substantially
extend our knowledge of chronic SCI and develop potential treatment for chronic SCI.

## Key facts

- **NIH application ID:** 10046295
- **Project number:** 5I01BX003892-03
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Pengzhe Lu
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046295

## Citation

> US National Institutes of Health, RePORTER application 10046295, Characterization of Chronic Contusive Spinal Cord Injury and Promotion of Corticospinal Tract Regeneration (5I01BX003892-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10046295. Licensed CC0.

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