# Impairment of the cerebral vasculature during bacterial meningitis

> **NIH NIH R15** · UNIVERSITY OF ALABAMA IN TUSCALOOSA · 2023 · $447,000

## Abstract

Project Summary
Bacterial meningitis is a serious life-threatening infection of the central nervous system (CNS) that
occurs when bacteria are able to cross highly specialized brain endothelial cells (BECs) and enter the
brain. While modern medical intervention has transformed bacterial meningitis from a uniformly fatal
disease, many survivors exhibit permanent neurological damage. One major complication during
bacterial meningitis is stroke. The CNS is protected by the blood-brain barrier (BBB) and meningeal
blood-cerebrospinal fluid barrier (mBCSFB), that are comprised of BECs and make up the blood
vessels in the brain. When compared with peripheral endothelial cells, BECs exhibit unique properties
that contribute to barrier function and support proper brain homeostasis. However, during bacterial
meningitis, BECs fail to protect the brain. The goal of this study is to use the most state-of-the-art
human stem-cell modeling techniques to assess how BECs fail to maintain their unique properties
and protect the brain during bacterial meningitis. In Aim 1 we will explore how Group B Streptococcus
(GBS) alters the cellular uptake pathways endocytosis and pinocytosis that is shut off in healthy
BECs, and how this contributes to GBS invasion of BECs and progression to meningitis. In Aim 2, we
have discovered that GBS can disrupt the efflux transporter P-glycoprotein (Pgp), we will discover the
host cell signaling that contributes to Pgp disruption and identify the GBS factor responsible. Synergy
between aims exists because both interrogate unique properties of BECs and how they fail during
disease. Our aims will determine mechanisms of BEC failure during infection yet have implications in
many neurological disorders and may uncover avenues for novel therapeutic interventions.

## Key facts

- **NIH application ID:** 10795568
- **Project number:** 1R15NS131921-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA IN TUSCALOOSA
- **Principal Investigator:** Robert Nathan Correll
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $447,000
- **Award type:** 1
- **Project period:** 2023-09-20 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795568

## Citation

> US National Institutes of Health, RePORTER application 10795568, Impairment of the cerebral vasculature during bacterial meningitis (1R15NS131921-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10795568. Licensed CC0.

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