# Mechanisms of inflammation in lipid-laden macrophages after spinal cord injury

> **NIH NIH F31** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $37,968

## Abstract

Abstract:
Spinal cord injury (SCI) patients face devastating physical consequences associated with failed neural
regeneration that severely impact their quality of life. One of these consequences include sustained
inflammation at the SCI lesion site which further damages spared tissue, is aversive to cellular regeneration
and prevents full functional recovery. Macrophages are one of the major classes of inflammatory immune cells
that persists long-term at the lesion site and may represent a driving force behind the chronic inflammation
observed after SCI. A subset of these cells with pro-inflammatory function are “foamy” macrophages. These
cells become lipid-laden due to excessive lipid uptake of myelin and cellular debris after injury and add to the
harmful inflammatory milieu of the chronic SCI wound. CD36 is a receptor that drives lipid uptake in
macrophages after SCI, and genetic deletion of this receptor has been shown to reduce lipid content and
improve locomotor recovery. However, the effect of macrophage lipid loading on surrounding neural cells has
not been specifically elucidated. Therefore, the first aim of this proposal will be to delineate the effect of foam
cell-mediated inflammation on neuronal and oligodendrocyte survival and function in vitro. These outcomes will
also be tested in vivo using a translationally relevant model of CD36 pharmacological inhibition. To understand
the intrinsic processes driving this macrophage phenotype, the second aim of this proposal will address foam
cell metabolism and its contribution to inflammation after SCI. Based on our preliminary data, we will test
whether metabolic dysfunction in foam cells enhances secretion of inflammatory cytokines. These studies will
evaluate my central hypothesis that excessive lipid uptake through receptors like CD36 produces harmful
effects in the surrounding neural tissue that prevents functional recovery; lipid accumulation causes these
effects through inducing metabolic dysregulation and driving foam cell inflammation. Together, this proposal
will examine the role of macrophage lipid uptake and inflammation after SCI and the metabolic mechanisms by
which foam cells contribute to cellular pathology after SCI, providing new mechanistic insight into potential
therapeutic targets to enhance functional and cellular recovery after injury.

## Key facts

- **NIH application ID:** 10318515
- **Project number:** 5F31NS115225-03
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Christine Bethany Ryan
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $37,968
- **Award type:** 5
- **Project period:** 2019-12-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318515

## Citation

> US National Institutes of Health, RePORTER application 10318515, Mechanisms of inflammation in lipid-laden macrophages after spinal cord injury (5F31NS115225-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10318515. Licensed CC0.

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