# Neuronal and Astrocytic Interaction in Recovery after Stroke

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $334,520

## Abstract

Project Description
Stroke is the primary cause of long-term disability. However, no effective treatment is available for the majority
of stroke patients. Interestingly, a process of self-repair and recovery starts to occur days following stroke.
Mounting evidence suggests that axonal plasticity is a critical aspect of this process, as it is essential for
establishing new neural connections to compensate for the stroke-induced functional loss. However, after
injury, this regrowth and remodeling in the adult mammalian central nervous system (CNS) is limited. The
weak intrinsic growth capacity in neurons and the inhibitory factors from extrinsic glial environments are among
the major causes that limit regeneration. This potential for regrowth has emerged as an alternative and
potentially more tractable target in stroke research. Indeed, emerging data suggest that Ras-related C3
botulinum toxin substrate 1 (Rac1), a Rho GTPase, plays a central role in axonal regeneration in the injured
brain, specifically by stimulating neuronal intrinsic growth and counteracting the growth inhibitory signaling that
leads to growth cone collapse. The overall goal of this proposal is to define the functional role of Rac1 in
neurite regeneration after stroke and uncover its underlying neuronal and astrocytic specific mechanisms. We
showed that pharmacological inhibition of Rac1, starting one week after stroke, results in decreased functional
recovery as well as reduced axonal density while post-stroke over-expression of Rac1 improves brain
functional recovery. Furthermore, Rac1 inhibition decreases activation of intrinsic pro-regenerative molecules
in mice after stroke and reduced axonal density in neuronal culture following oxygen-glucose deprivation. In
contrast, inhibition of Rac1 increases glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycan
(CSPG), both of which are major astrocytic inhibitory signals after ischemia. Finally, aging leads to a decline in
the levels/activities of proteins involved in the Rac1 pathway in the brain, and we aim to test if activating this
pathway in young and aging brains could enhance neurite regeneration and improve post-stroke functional
recovery. We will use a combination of pharmacological tools, diffusion tensor imaging, inducible knockout
mice and viral transduction systems to over-expression Rac1 in vivo. These studies represent the first steps in
understanding the endogenous pathways that promote brain axonal regeneration and subsequently recovery
following stroke.

## Key facts

- **NIH application ID:** 9973176
- **Project number:** 5R01NS099628-05
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Jun Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,520
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973176

## Citation

> US National Institutes of Health, RePORTER application 9973176, Neuronal and Astrocytic Interaction in Recovery after Stroke (5R01NS099628-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9973176. Licensed CC0.

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