# Converting the glial scar to neurons repairs the injured neural circuits for functional recovery following spinal cord injury

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $356,623

## Abstract

ABSTRACT
The cellular basis of the central nervous system (CNS) consists of neurons and glial cells. Although
glial cells massively outnumber neurons in the CNS across species, only neurons are specially
endowed with the ability to communicate precisely and rapidly with other cells at distant sites in the
body. Unfortunately, unlike glial cells, the adult spinal cord is incapable of generating new neurons. In
addition, the axons also fail to regenerate after the damage, even their neuron somas are survived.
Thus, after the adult spinal cord injury (SCI), the irreversible loss of neurons and disruption of axons
lead a permanent functional deficit. The intrinsic reduced regenerative capacity of adult neurons and
the extrinsic inhibitory glial scar formation cause the regeneration failure after spinal cord injury. An
ideal spinal repair strategy should 1) replenish neurons for circuit reconstruction, 2) modulate the
inhibitory glial scar, to allow resident neural regeneration, and 3) establish new functional neural circuits
for electrical and chemical signal conduction. Our recent study has confirmed that the spinal cord fails
to generate new mature neurons after injury. The critical stem cell factor SOX2 was discovered to be
the key modulator of endogenous reprogramming. We demonstrated that our SOX2-mediated
reprogramming strategy successfully converted the NG2 glia into a great number of new neurons in the
lesioned spinal cord, and simultaneously reduced the astrocytic glial scar. Furthermore, the converted
neurons were able to make synaptic connections to the resident neurons in various areas of the CNS,
indicating the integration of the converted neurons into the h(1, 2)post neural circuits. Importantly, it
also promoted forelimb functional recovery. Surprisingly, our pilot study demonstrated a robust
corticospinal axonal regeneration after SCI. Together, we hypothesized that our reprogramming
strategy significantly modulates the inhibitory glial scar and activates pro-regenerative factors,
allowing for axonal regeneration, which will restore the signal transduction in the injured spinal
cord. We aim to characterize the alteration of the glial scar and pyramidal neurons during the
reprogramming process and relate it to axonal outgrowth and circuitry establishment. The
finding from this proposal is expected to sharpen our understanding of the reprogramming-mediated
axonal regeneration and neural circuits reorganization for the development of an optimized
reprogramming strategy to treat SCI.

## Key facts

- **NIH application ID:** 10802755
- **Project number:** 1R01NS131489-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Wei Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $356,623
- **Award type:** 1
- **Project period:** 2024-04-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802755

## Citation

> US National Institutes of Health, RePORTER application 10802755, Converting the glial scar to neurons repairs the injured neural circuits for functional recovery following spinal cord injury (1R01NS131489-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10802755. Licensed CC0.

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