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Fellowship for Annabel McAtee: Elucidating the role of the dura mater in the post-stroke B cell response

Award Number: F30NS141486
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/24/2025
PERIOD OF PERFORMANCE END DATE: 08/23/2028

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Fellowship for Annabel McAtee: Elucidating the role of the dura mater in the post-stroke B cell response - After ischemic stroke, B cells play both detrimental and beneficial roles in injury and/or functional recovery depending on responding subset and timing of activation. There is interest in developing novel immune- modulating therapies for stroke patients, but clinical trials have had limited success, partly because key factors that determine which subsets are helpful or harmful remain to be elucidated. Recent discoveries show that the dura mater plays an active role in the immune environment of the brain in health and disease. Further, the dura was recently shown to be a hub of B cell development from immature to mature antibody-secreting populations. However, the roles of dura-localized B cells after stroke are unknown. The overall objective of this proposal is to determine if, after stroke, B cells in the dura form antibody-secreting subsets that travel to the brain and worsen functional recovery. This project will address a key gap in knowledge on the unique properties of immune cells in this novel niche and may allow for the development of therapies that differentially target these cells without affecting other populations. The central hypothesis is that, after stroke, dura-localized B cells mature into plasma cells, travel to the brain through the arachnoid and pia mater, and release CNS antigen-specific antibodies that impede functional recovery. To test this hypothesis, a mouse model of transient middle cerebral artery occlusion (tMCAo) in aged male and female mice (>16 mos., n=12-18/sex), combined with B cell depletion methods will be used. Aim 1 hypothesis is that dura B cells are exposed to more inflammatory cytokines compared to cervical lymph node B cells, leading to a robust development of B cell activation and maturation that is stronger than lymph node activation. This aim will achieve a full characterization of dura B cells at 3 days, 10 days, and 7 weeks following stroke using 1) flow cytometry, 2) histology, and 3) single cell B cell receptor sequencing. Aim 2 hypothesis is that ischemic stroke induces maturation of dura-localized B cells that travel through the pia/arachnoid to the brain to worsen functional outcome. This aim includes a series of selective B cell depletion assays in human (h)CD20-expressing mice with dura versus systemic population depletion via Rituximab for 7 weeks. Motor and cognitive testing (rotarod, Y maze) will be assessed every week and B cell depletion by niche will be confirmed. The expected outcome is an increased understanding of the role of dura-localized B cells in post-stroke recovery, leading to eventual development of effective immunotherapies. The trainee will gain experience with a number of experimental techniques and statistical analyses, and will be well positioned for a career as a neurosurgeon-scientist.


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 = $43,714 )
2026	2026	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	8/26/2026	NON-COMPETING CONTINUATION	$43,714
														Subtotal = $43,714

Issue Date FY: 2025 ( Subtotal = $43,138 )
2025	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	7/31/2025	NEW	$0
2025	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/31/2025	NEW	$43,138
														Subtotal = $43,138

Grand Total All Awards = $86,852

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Fellowship for Annabel McAtee: Elucidating the role of the dura mater in the post-stroke B cell response

Award Number: F30NS141486

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/24/2025

PERIOD OF PERFORMANCE END DATE: 08/23/2028

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