# Arachnoid barrier breakdown in bacterial meningitis

> **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2021 · $66,390

## Abstract

Project Summary
 The central nervous system (CNS) is protected by two major barrier systems, the blood brain-barrier (BBB)
and the blood-cerebrospinal fluid barrier (B-CSFB). These essential barrier systems each have unique cellular
properties that tightly regulate the molecules and cells that can enter (or exit) the brain and the cerebrospinal
fluid (CSF). CNS barriers are also vulnerable to breakdown in a variety of diseases, causing or exacerbating
CNS pathology. The breakdown of the B-CSFB at the level of the meninges, a trilayered structure that surrounds
the brain and spinal cord, is poorly understood.
 The critical B-CSFB structures of the meninges is the arachnoid barrier, a tight junction containing epithelial-
like layer that segregates the outer meningeal dura and periphery from the inner leptomeninges and CSF. Unlike
the BBB and other parts of the B-CSFB, there is very little known about the susceptibility of the arachnoid barrier
to breakdown during disease. Here, I utilize Group B Streptococcus (GBS), a model of acute bacterial meningitis,
in order to identify the cellular and molecular mechanisms of arachnoid barrier breakdown. I will leverage the
combined knowledge of the Siegenthaler lab (experts in CNS vasculature and the BBB) as well as the Doran
Lab (leaders in studying bacteria-host interactions during meningitis) in order to test the hypothesis that bacterial
meningitis disrupts cellular barrier properties by driving Snail1-dependent Epithelial to Mesenchyme Transition
(EMT), loss of tight and adherens junctions, and impaired functional barrier integrity. Furthermore, I will elucidate
if GBS directly binds primary arachnoid barrier cells or if GBS exerts its effects through inflammatory cytokines.
 Completion of this work will substantially advance the field of CNS barrier systems by providing new tools
to study arachnoid barrier function and a novel understanding of how the arachnoid barrier breaks down in
disease. I will also generate a comprehensive model of arachnoid barrier cellular properties that can be
investigated for breakdown in other diseases that involve the meninges. This new knowledge about the
arachnoid barrier has the potential to be exploited to design new ways to limit crossing of molecules and cells at
the arachnoid barrier to treat disease and will provide novel in vitro and in vivo approaches for understanding
the B-CSFB during homeostasis and disease. Finally, the proposed goals of this fellowship will give me the
conceptual, technical, and professional training necessary to develop myself as an independent researcher
investigating the impact of CNS barriers on CNS health and neurological diseases.

## Key facts

- **NIH application ID:** 10285828
- **Project number:** 1F32NS122999-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Julia Derk
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 1
- **Project period:** 2021-08-15 → 2023-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285828

## Citation

> US National Institutes of Health, RePORTER application 10285828, Arachnoid barrier breakdown in bacterial meningitis (1F32NS122999-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10285828. Licensed CC0.

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