# Manipulation of metabolic pathways to enhance human macrophage phenotypes after ICH

> **NIH NIH R21** · YALE UNIVERSITY · 2022 · $251,250

## Abstract

Project Summary.
Intracerebral hemorrhage (ICH) is a devastating stroke subtype with high mortality and morbidity and no
effective treatment. We have shown in murine models of ICH that blood-derived macrophages initially
contribute to injury but over time are crucial to the resolution of inflammation and brain repair. This work
highlights the modulation of macrophage phenotype as an important potential therapeutic strategy. Emerging
data in murine cells has revealed that cellular metabolism is fundamentally linked to the inflammatory response
of the cell. However, studies on these mechanisms in human cells have been limited and the findings have not
been studied in the context of a complex neurological injury such as ICH. Determining whether the pathways
seen in rodents are relevant in patients is critical to the successful development of new therapies for the
treatment of ICH.
The overall goal of this proposal is to determine whether macrophage metabolism can be manipulated to
reduce proinflammatory cytokine production and enhance erthyrophagocytosis and growth factor production.
These functions of macrophages are critical to injury and recovery after ICH. In the proposed experiments, we
will (1) determine the effects of macrophage metabolic pathways on inflammatory and reparative phenotypes in
human cells after ICH-relevant stimuli, (2) determine the effects of important biological variables on the
manipulation of metabolic pathways in human macrophages, and (3) investigate whether pharmacological
manipulation of macrophage metabolism can modulate the inflammatory response in vivo in murine
experimental ICH.

## Key facts

- **NIH application ID:** 10308104
- **Project number:** 5R21NS108060-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** LAUREN H SANSING
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $251,250
- **Award type:** 5
- **Project period:** 2020-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10308104

## Citation

> US National Institutes of Health, RePORTER application 10308104, Manipulation of metabolic pathways to enhance human macrophage phenotypes after ICH (5R21NS108060-02). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10308104. Licensed CC0.

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