# The Influence of Arc on Remapping, Network Repair, and Functional Recovery After Stroke

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2022 · $46,752

## Abstract

PROJECT SUMMARY/ABSTRACT
 Although some stroke survivors experience spontaneous recovery in the weeks to months following
stroke, it is often incomplete. This critical period after stroke, when brain plasticity is heightened, provides a
window of opportunity to enhance recovery. However, the precise mechanisms underlying this post-stroke
plasticity will need to be better understood before therapeutic interventions can be developed to take advantage
of this critical period of recovery. Some of the mechanisms involved in brain repair appear to recapitulate
mechanisms involved in developmental plasticity. Exploiting similar processes that enhance plasticity, the Lee
lab has recently demonstrated that recovery after stroke in adult mice can be enhanced by focal sensory
deprivation, targeted to peri-infarct cortex. Enhanced recovery was mediated by activity-regulated cytoskeleton-
associated protein (Arc) – a protein with critical roles in synaptic plasticity. Furthermore, remapping and
functional recovery following stroke were absent in Arc knockout mice. Previous studies have shown that Arc
overexpression can reopen developmental plasticity in adult visual cortex, raising the possibility of therapeutic
intervention for enhancing post-stroke plasticity and repair.
 The Lee lab has also demonstrated that focal ischemia leads to disruption of functional connectivity (FC)
in several brain networks. Here, FC was assessed using optical intrinsic signal imaging (OIS), relying on a
neurovascular signal (intrinsic hemoglobin contrast) as a readout for remapping. Therefore, the true assessment
of neuronal circuit repair was not determined. Using a wide-field fluorescent imaging system in combination with
mice with genetically encoded calcium indicators (GECI), I have collected preliminary data demonstrating
neuronal remapping after focal stroke. Furthermore, using FC analyses to examine resting state spontaneous
activity, I have shown rapid changes in global brain networks following stroke. It is likely that complete recovery
from stroke requires not only local thalamocortical circuit repair, but reintegration of this repaired local circuit into
larger brain networks, as well as the temporal coordination of these two processes.
The two specific aims of the project are therefore as follows:
Aim 1: To determine the relationship between neuronal circuit repair, reintegration of repaired circuits into global
brain networks, and behavioral recovery after stroke.
Aim 2: To determine the effects of Arc on spatially directing neuronal circuit repair and reintegrating remapped
circuits into brain networks, enhancing functional recovery.

## Key facts

- **NIH application ID:** 10389115
- **Project number:** 1F31NS122499-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Ryan Bowen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389115

## Citation

> US National Institutes of Health, RePORTER application 10389115, The Influence of Arc on Remapping, Network Repair, and Functional Recovery After Stroke (1F31NS122499-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10389115. Licensed CC0.

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