# Modulating a critical inhibitory proteoglycan receptor to promote functional recovery after stroke

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2022 · $351,455

## Abstract

Stroke is one of the leading causes of death and disability worldwide and places a heavy burden on the
economy in our society. Current treatment strategies for stroke primarily focus on reducing the size of ischemic
damage and on rescuing dying cells early after occurrence. Treatments, such as the use of thrombolytic
agents, are often limited by a narrow therapeutic time window. However, the regeneration of the brain after
damage is still active days, or even weeks after stroke occurs, which might provide a second window for
treatment. Our preliminary data suggests that systemic in vivo delivery of a peptide that blocks a specific receptor
mediated inhibitory action of sulphated proteoglycans in the glial scar in stroke animals 24 hours after stroke or 7 days
after stroke both improve their functional recovery. We hypothesize that the CSPG signaling pathway is involved
in the regulation of neuroregeneration and axonal sprouting after stroke and that modulating the CSPG
signaling pathway will lead to better functional outcome in stroke recovery. We will test this hypothesis in both
young and aged mice in the proximal transient middle cerebral artery occlusion (MCAo) animal model. Towards
this goal, we have developed a proposal that consists of three specific aims. In specific aim 1 and 2, we will
investigate the role of the CSPGs signaling pathway in functional recovery in young or aged stroke animals. In
specific aim 3, we will examine the mechanisms of neurorepair in stroke animals by combination of genetic and
pharmacological modulation with inducible cell type specific RPTPσ knockout or ISP peptide treatment. Two
main mechanisms of neurorepair including neurogenesis and axonal sprouting in stroke will be analyzed in
genetically and pharmacologically modulated stroke animals. Together, the comprehensive analysis of
molecular, cellular and behavioral measurements in stroke animals will generate data that will provide insights
on the precise role of CSPG signaling in the process of injury-induced neurorepair. The data gained will be
directly applicable to developing novel therapeutic interventions in treating cerebral ischemia through the
manipulation of the cellular microenvironment in the CNS. We anticipate that the resources and results
generated from our study will open new avenues in neuroregeneration research and lead to the identification of
molecular therapeutic targets.

## Key facts

- **NIH application ID:** 10380110
- **Project number:** 5R01NS107365-04
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Yu Luo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $351,455
- **Award type:** 5
- **Project period:** 2019-04-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380110

## Citation

> US National Institutes of Health, RePORTER application 10380110, Modulating a critical inhibitory proteoglycan receptor to promote functional recovery after stroke (5R01NS107365-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10380110. Licensed CC0.

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