# How do CNS fibroblasts regulate the response to neuroinflammation?

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $40,217

## Abstract

ABSTRACT
 Fibrosis, defined by the deposition of collagen I, is a devastating pathological event that occurs in many
organs including the heart, kidney, liver and lung in response to injury and inflammation. This fibrotic response
inhibits recovery inflammation and can even lead to organ failure. Despite the potential importance, very little is
known about whether there is a fibrotic response in the central nervous system (CNS) following
neuroinflammation that occurs in diseases such as multiple sclerosis, neuromyelitis optica, stroke and CNS
infections, and how this response affects repair and recovery. Using experimental autoimmune
encephalomyelitis (EAE), a mouse model of neuroinflammation, we have identified that a robust collagen I-
based fibrotic scar forms covering the neuroinflammatory lesion and we hypothesize that this fibrotic scar
inhibits the ability of reparative cells to enter the lesion. In preliminary studies using lineage tracing and single
cell sequencing, we have identified that this fibrotic scar is formed by the activation and proliferation of
fibroblasts. We have further generated methods to isolate and culture CNS fibroblasts providing an in vitro
model to study the proliferation, migration and collagen 1 production from these cells. In this proposal we aim
to determine whether the fibrotic scar is helpful or harmful for recovery following neuroinflammation and to
further study the mechanisms that regulate fibrotic scar formation. We will first determine whether inhibition of
fibrotic scar formation can lead to an increased recovery from EAE. We will then examine whether TGFβ and
PDGFR signaling pathways regulate fibrotic scar formation. We hypothesize that TGFβ signaling drives the
proliferation and collagen I production by the fibroblasts and that PDGFR signaling regulates the migration of
the fibroblasts to the lesion. Our goal is to determine whether modulating the fibrotic scar is a potential
therapeutic target to aid in recovery for patients with neuroinflammatory diseases.

## Key facts

- **NIH application ID:** 10841263
- **Project number:** 3R01NS119615-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Richard Daneman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $40,217
- **Award type:** 3
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841263

## Citation

> US National Institutes of Health, RePORTER application 10841263, How do CNS fibroblasts regulate the response to neuroinflammation? (3R01NS119615-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10841263. Licensed CC0.

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