# Intravital Imaging of Transplant Evoked Glia Repair in Stroke

> **NIH NIH R21** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2024 · $206,250

## Abstract

Ischemic stroke is a major healthcare burden and there is an important unmet need for new treatments that
can be applied beyond the narrow acute phase of injury after which ischemic tissue becomes infarcted. A
hallmark of natural wound responses after stroke is the formation of compartmentalized lesions that contain
non-neural cell cores that lack specialized glia cells that are fundamental to supporting neural circuits and
barrier functions. In organisms capable of neural regeneration such as zebrafish and the mammalian neonate,
immature glia cells readily repopulate lesion cores to effectively drive neural repair, but this competency is lost
in adult mammals. With the overall goal of promoting scar-free glia repair in stroke to transform lesion cores
into neural regeneration permissive environments, this project’s main objective is to use cutting-edge intravital
imaging methods to longitudinally track cell graft evoked changes in wound repair outcomes following cortical
strokes to identify critical graft parameters that lead to effective glia-repair. Our hypothesis is that multiple
intravital imaging modalities can be used to effectively track temporal changes in grafted cell number and
phenotype as well as quantify graft induced alterations to microvasculature density, perfusion, and permeability
in lesion cores. Grafting cells during the sub-acute injury phase to alter the nature of adult central nervous
system (CNS) wound healing and drive glia repair represents a novel and potentially transformative strategy
that would have broad impact for treatment of stroke and other CNS injuries. In the first aim, we will
longitudinally track differences in glia repair in cortical strokes directed by neural progenitor cells (NPC) and
immature astroglia grafts. Priming grafts into proliferating immature astrocytes prior to transplantation may
accelerate and better guide glia repair processes. Using two-photon microscopy (2PM) we will evaluate graft
cell number, density, and morphology and optical coherence tomography (OCT) to quantify graft induced
changes in vascular density and quantitative blood flow in and around stroke lesion cores. To evaluate return
of CNS barrier functions we will quantify the leakage of intravenous contrast agents using 2PM. In the second
aim, we evaluate the effect of post stroke grafting timepoint on glia repair outcomes. This project will provide
mechanistically validated, proof-of-principle evidence into how cell grafts, including immature astrocyte grafts,
can remodel lesion cores by directing angiogenesis and restoration of glia barriers. This project will advance
our understanding of cell transplantation and certify a toolkit for evaluating transplant functions in vivo that will
position us to pursue advanced stroke functional recovery studies in future work.

## Key facts

- **NIH application ID:** 10869970
- **Project number:** 5R21NS128821-02
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Timothy Mark O'Shea
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $206,250
- **Award type:** 5
- **Project period:** 2023-07-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869970

## Citation

> US National Institutes of Health, RePORTER application 10869970, Intravital Imaging of Transplant Evoked Glia Repair in Stroke (5R21NS128821-02). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/10869970. Licensed CC0.

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