# Inflammatory Mediators and Mechanisms of Cerebral Aneurysm Formation and Rupture

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $377,438

## Abstract

PROJECT SUMMARY/ABSTRACT
Cerebral aneurysms affect up to 5% of the population. When cerebral aneurysms rupture, they cause
devastating subarachnoid hemorrhage with greater than 50% mortality. Currently, the only treatments that
prevent rupture are prophylactic cranial or endovascular surgery which are risky. A gap in knowledge persists
about the pathophysiology of aneurysm formation, growth, and rupture. The long-term goal is to improve
understanding of the mediators and mechanisms of cerebral aneurysm formation and rupture, and thereby
identify therapeutic targets for the development of novel therapies. Our laboratory studies this problem from
two different approaches: 1) improve aneurysm endovascular devices to achieve complete aneurysm healing,
and 2) improve our understanding of what causes aneurysms to develop and grow. We recently found
chemokine (C-X-C motif) ligand 1 (CXCL1) antagonism achieves both: we found CXCL1 antagonism
significantly inhibits mouse cerebral aneurysm formation (13.3 versus 66.7%; P =0.0078), and in mouse carotid
aneurysms treated with coiling, CXCL1 antagonism, significantly improves intrasaccular aneurysm coil
occlusion and healing (preliminary data). Improving our understanding of the mechanisms is intriguing because
this could translate to treating patients' aneurysms with coiling, and supplementing with a drug that facilitates
intrasaccular aneurysm healing and by a separate mechanism inhibits further cerebral aneurysm growth. Our
central hypothesis: CXCL1 antagonism promotes intrasaccular aneurysm occlusion and healing with coiling
and protects against cerebral aneurysm formation by modulating the macrophage and neutrophil-mediated
site-specific inflammatory response. We will test our central hypothesis with the following aims in this Early
Established Investigator application: 1) Demonstrate CXCL1 is necessary for aneurysm rupture. CXCL1
antagonism improves aneurysm healing; 2) Demonstrate IL17 induces CXCL1-mediated aneurysm formation
and rupture and CXCL1 inhibition of aneurysm coil healing; and 3) Demonstrate infiltrating macrophages and
neutrophils mediate CXCL1-induced aneurysm formation and rupture and CXCL1 inhibition of aneurysm coil
healing. The proposal is conceptually innovative in that we will propose a novel link between IL17, CXCL1,
neutrophils and macrophages and precisely define their roles as mediators in cerebral aneurysm formation and
rupture. Furthermore, the proposed studies are the first to investigate a mediator that both promotes
intrasaccular aneurysm healing and protects against cerebral aneurysm growth and rupture. The significance
of this work is the potential identification of novel targets with direct translational benefit.

## Key facts

- **NIH application ID:** 9887928
- **Project number:** 1R01NS110710-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Brian Lim Hoh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,438
- **Award type:** 1
- **Project period:** 2020-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9887928

## Citation

> US National Institutes of Health, RePORTER application 9887928, Inflammatory Mediators and Mechanisms of Cerebral Aneurysm Formation and Rupture (1R01NS110710-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9887928. Licensed CC0.

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