# How does the fibrotic scar regulate repair following neuroinflammation?

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $38,362

## Abstract

Project Summary
Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system in which the body’s immune
system attacks the myelin sheath that surrounds and insulates the axons of neurons. In many cases this myelin
is not repaired by oligodendrocyte lineage cells leading to long term disability. One hypothesis as to why myelin
is not repaired is that there is a physical barrier preventing oligodendrocyte lineage cells from interacting with
axons and repairing the damaged myelin. Following spinal cord injury, a scar forms around the site of trauma
and seals off the injured and inflamed tissue. The scar consists of an outer glial scar made up of reactive
astrocytes and an inner fibrotic scar made of extracellular matrix proteins. The glial scar has been studied
extensively as a potential therapeutic target for CNS trauma, but much less is known about the origins and role
of the fibrotic scar. In MS, the glial scar has also been characterized, and fibrosis in human tissue reported, but
the role of a fibrotic scar has not been investigated. To test for the presence of a fibrotic scar in neuroinflammatory
lesions, mice were induced with experimental autoimmune encephalomyelitis (EAE), which leads to the
formation of neuroinflammatory demyelinated lesions and is used as a mouse model of MS. An extensive fibrotic
scar was present in the lesioned tissue that remained for months following symptom onset and arose from the
proliferation of collagen-expressing fibroblasts. Nothing is known about the role this fibrotic scar plays in
repair following neuroinflammatory lesion formation and the signals that activate scar formation. The goal of this
project is to define the role of the fibrotic scar in repair following neuroinflammatory lesion formation and the
molecular mechanisms that cue its formation, with the hopes of identifying potential therapeutics to manipulate
the scar in vivo. The hypothesis to be tested is that the fibrotic scar that forms following EAE induction prevents
repair and forms through TGFβ pathway activation in fibrotic cells. First, the role of the scar in EAE repair in vivo
will be determined by preventing the fibrotic scar from forming through the ablation of dividing fibrotic cells
following EAE induction. To determine if TGFβ pathway activation is necessary for scar formation, a fibroblast-
specific Cre mouse line will be used to conditionally knockout key signaling TGFβ pathway genes prior
to scar formation. Additionally, to study how TGFβ signaling regulates the proliferation, collagen production
and migration of CNS fibroblasts, recombinant TGFβ and pathway inhibitors will be added to a primary, in vitro
cell model.

## Key facts

- **NIH application ID:** 9925652
- **Project number:** 5F31NS108651-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Cayce Elizabeth Dorrier
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,362
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925652

## Citation

> US National Institutes of Health, RePORTER application 9925652, How does the fibrotic scar regulate repair following neuroinflammation? (5F31NS108651-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9925652. Licensed CC0.

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