# Single cell RNA-seq characterization of CNS myeloid cells after ischemic preconditioning

> **NIH NIH R03** · UNIVERSITY OF WASHINGTON · 2020 · $155,500

## Abstract

PROJECT SUMMARY
Stroke is the 5th leading cause of death in the United States and the number one leading cause of long-
term disability in adults. Progress in the development of effective pharmacotherapies for acute stroke
has been limited and centered on neuronal preservation despite extensive and robust data implicating
glial cells, including microglia, in the pathophysiology of ischemic injury. Ischemic preconditioning (IPC)
is a brief period of ischemia that confers robust neuroprotection against subsequent ischemic events.
Elucidating cellular and molecular mediators of IPC is considered a critical challenge in stroke research
with promising therapeutic applications. Research by our group and others has implicated innate
immune signaling pathways as being critical for IPC-mediated neuroprotection, and we have
specifically identified a requirement for these innate immune pathways in microglia. Research from
other groups have suggested possible roles for infiltrating peripheral immune cells in supporting IPC-
mediated protection in the central nervous system (CNS), however individual immune cell contributions
are not well understood. Furthermore, a growing body of data suggest differential responses to injury
between white and grey matter microglia. In this study we will collect single cell RNA sequencing
(scRNA-seq) data from the myeloid cells of the cortex after animals have been exposed to an IPC
stimulus, prolonged cerebral ischemia (stroke), or both. We will use this dataset to identify differential
clusters of cells based on gene expression profiles in these different experimental paradigms to
determine neuroimmune and peripheral immune cell responses to IPC and cerebral ischemia, and how
the latter is modulated to a neuroprotective milieu by a prior IPC stimulus. Additionally, we will perform
these experiments in a white matter model of ischemia/reperfusion injury to elucidate differential
responses between white matter and grey matter injury after prolonged cerebral ischemia. Gathering
data on white matter predominant tracts is important due to the large volume of white matter impacted
in human stroke patients compared to in vivo mouse models, which are grey matter predominant. These
studies will help us better understand the contribution of immune cells to ischemia/reperfusion injury
and identify potential cellular and molecular targets for therapeutic intervention in stroke patients.

## Key facts

- **NIH application ID:** 10041730
- **Project number:** 1R03NS118105-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** JONATHAN R WEINSTEIN
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,500
- **Award type:** 1
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041730

## Citation

> US National Institutes of Health, RePORTER application 10041730, Single cell RNA-seq characterization of CNS myeloid cells after ischemic preconditioning (1R03NS118105-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10041730. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*