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Impairment of the cerebral vasculature during bacterial meningitis

Award Number: R15NS131921
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Impairment of the cerebral vasculature during bacterial meningitis - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2023	UNIVERSITY OF ALABAMA	801 UNIVERSITY BLVD	TUSCALOOSA	AL	35401	TUSCALOOSA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/23/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF ALABAMA	801 UNIVERSITY BLVD	TUSCALOOSA	AL	35401	TUSCALOOSA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/5/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $447,000 )
2023	2023	UNIVERSITY OF ALABAMA	301 ROSE ADMIN BLDG	TUSCALOOSA	AL	35487	TUSCALOOSA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/20/2023	NEW	$447,000
														Subtotal = $447,000

Grand Total All Awards = $447,000

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Impairment of the cerebral vasculature during bacterial meningitis

Award Number: R15NS131921

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/20/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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