# Development and function of the meninges arachnoid barrier

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $401,072

## Abstract

Project Summary
 The central nervous system (CNS) is protected by two barrier systems, the blood brain-barrier (BBB) and the
blood-cerebrospinal fluid barrier (B-CSFB). These barrier systems have unique cellular properties that regulate
the molecules and cells that can enter or exit the CNS and the CSF. CNS barriers are essential for development
and health but breakdown in a variety of diseases, causing or exacerbating CNS pathology. A detailed under-
standing of CNS barriers is also essential for efficient drug delivery to the brain and spinal cord. The development
and function of the B-CSFB at the level of the meninges, a trilayered structure that surrounds the CNS, is poorly
understood. This is despite evidence implicating meninges-located barriers in perinatal and adult diseases as
an early site of immune cell activation and entry in neuroinflammation. One of two barrier structures in the me-
ninges is the arachnoid barrier layer, which segregates the outer meningeal dura and its non-barrier vasculature,
from the CSF and cell types in the subarachnoid space. Unlike the BBB and other parts of the B-CSFB, nothing
is known about mechanisms of arachnoid barrier cell specification, timing of layer maturation or acquisition of
functional properties. Further, only a few studies have looked at arachnoid barrier dysfunction in CNS diseases
and so far, no studies have tested if an immature arachnoid barrier has enhanced vulnerability to breakdown.
 We have combined our knowledge of CNS vascular and BBB development with our unique expertise in the
meninges to develop new tools to study the arachnoid barrier. Experiments proposed here build upon our initial
discoveries to identify mechanisms that underlie arachnoid barrier layer development, investigate arachnoid bar-
rier maturation and function, and measure its response in insult. To do this we will: 1) utilize in vivo and culture
models to uncover the molecular mechanisms of arachnoid barrier cell specification, 2) use our new model where
we perturb arachnoid barrier formation prenatally to determine its role in establishing separate meninges immune
cell and vascular compartments and in protecting the fetal brain in an animal model of maternal infection 3)
identify the cellular and molecular mechanisms of arachnoid barrier breakdown in bacterial meningitis. Comple-
tion of this work will substantially advance the field of CNS barrier systems. It will provide the first model of
arachnoid barrier development including the cellular and molecular mechanisms and the timing of emergence of
barrier properties. It will provide important information about the function of the arachnoid barrier. Experiments
proposed here focus on the prenatal brain however findings will set the stage for future studies in postnatal and
adult function. Third, it will provide the most detailed analysis to date of arachnoid barrier response to CNS insult,
paving the way for future studies in other CNS diseases. In the long term, th...

## Key facts

- **NIH application ID:** 10620852
- **Project number:** 5R01NS098273-07
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Julie Siegenthaler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $401,072
- **Award type:** 5
- **Project period:** 2016-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10620852

## Citation

> US National Institutes of Health, RePORTER application 10620852, Development and function of the meninges arachnoid barrier (5R01NS098273-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10620852. Licensed CC0.

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