# Modulating the post-stroke inflammatory response to improve outcome in models of cerebral ischemia

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $518,800

## Abstract

Modulating the post-stroke inflammatory response to improve outcome in models of cerebral ischemia
ABSTRACT
inflammatory responses.
Stroke is a multiphasic process, with an initial ischemic phase followed by secondary progression of injury from
 Following ischemia, microglia and macrophages accumulate in the ischemic area and
produce inflammatory mediators and chemokines that initially recruit peripheral macrophages, neutrophils,
dendritic cells, and later T and B cells. This post-stroke inflammatory response is both beneficial and injurious,
as multiple and simultaneous immune pathways in distinct immune cell populations generate both beneficial
and maladaptive immune responses. Because the time window of intervention of thrombolytic strategies is
limited after onset of ischemia, and because attempts at neuroprotection after stroke have not shown positive
results, the post-stroke inflammatory response represents an attractive target for intervention to reduce brain
injury and accelerate functional recovery. The identification of specific immune pathways activated after stroke
that could be modulated therefore represents an opportunity to improve and accelerate recovery after stroke.
In previous studies, we have focused on the beneficial effects of inhibiting COX-2/PGE2 inflammatory signaling
through the myeloid PGE2 EP2 receptor. In these studies, we identified Triggering Receptor Expressed on
Myeloid cells-1, or TREM1, as highly regulated by inflammatory PGE2 EP2 signaling. TREM1 is an
inflammatory membrane receptor that is expressed only on myeloid lineage cells and is unique in its function
as an amplifier of maladaptive inflammatory responses. Our preliminary data suggest that this immune
signaling cascade enhances innate immune responses after cerebral ischemia days after stroke. Using a
combination of pharmacological and conditional knockout strategies to isolate the contribution of peripheral
immune cells to stroke, we propose to identify the mechanisms of action of TREM1 signaling after stroke and
test the hypothesis that inhibition of this pathway in the days after stroke will enhance brain repair and
accelerate recovery.

## Key facts

- **NIH application ID:** 9920227
- **Project number:** 5R01NS100180-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Katrin I. Andreasson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $518,800
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920227

## Citation

> US National Institutes of Health, RePORTER application 9920227, Modulating the post-stroke inflammatory response to improve outcome in models of cerebral ischemia (5R01NS100180-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9920227. Licensed CC0.

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