# Harnessing Corticospinal Axon Sprouting for Functional Recovery in Chronic Injury

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2020 · —

## Abstract

VA treats more than 26,000 people with spinal cord injury (SCI) and disorders each year, making the
department the largest health care system in the world providing spinal cord care. A better understanding of
axonal repair after central nervous system (CNS) injury is critical to the development of restorative treatment
for people with SCI, especially the chronically injured. The overarching goal of this proposal is to understand
how axonal sprouting, a form of endogenous repair mechanism in the CNS, can be enhanced and harnessed
to promote functional recovery in chronic SCI. An important premise of the proposed study is that axonal
sprouting from uninjured neurons represents an important and readily accessible form of axonal repair that will
likely generate near-term translational value as compared to the more challenging regeneration-promoting
strategies. Previous studies of axonal sprouting have focused on acute or subacute phases of SCI. The current
grant mechanism will encourage us to delve into the important biology of axonal sprouting with chronic injury.
This proposal builds upon our very recent published study on the impact of age on CNS axon regeneration and
our unpublished preliminary data on the effect of age and chronic injury in axonal repair. Using the mouse
corticospinal tract (CST) as the model system, we will test the hypothesis that sprouting can occur and
contribute to functional recovery in chronic SCI, and that this endogenous repair mechanism can be enhanced
through molecular intervention in the chronically injured CNS. We will use unilateral pyramidotomy injury model
that severs one side of the CST to study sprouting across the midline to the denervated side. We will assess
the level of CST axon sprouting in chronically injured mice, and identify effective molecular manipulations that
promote such sprouting in chronically injured mice. We will also combine sprouting-promoting strategies and
rehabilitative training to enhance functional recovery after a chronic spinal cord injury. Together, the proposed
studies will address the potential of axon sprouting as a potentially more accessible repair mechanism to
promote recovery of function in chronic SCI.

## Key facts

- **NIH application ID:** 9831580
- **Project number:** 5I01RX002483-02
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Binhai Zheng
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-11-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9831580

## Citation

> US National Institutes of Health, RePORTER application 9831580, Harnessing Corticospinal Axon Sprouting for Functional Recovery in Chronic Injury (5I01RX002483-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9831580. Licensed CC0.

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