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CD200 signaling mediates the interactions of neurons and endothelia with circulating leukocytes in stroke

Award Number: R01NS129977
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: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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CD200 signaling mediates the interactions of neurons and endothelia with circulating leukocytes in stroke - PROJECT SUMMARY Immune responses are a fundamental pathophysiological process that significantly contribute to ischemic brain injury. Holding the immune response in check can alleviate the delayed injury seen in stroke and has considerable translational value. CD200 binds to its receptor, CD200R, that is expressed on immune cells. This forms an endogenous inhibitory signal and reduces the activation of immune cells. The traditional notion that the neuronal-microglial CD200-CD200R interaction is the key to suppressing deleterious immune activation has been increasingly questioned, as accumulating data has shown that the CD200R is expressed on peripheral immune cells but not on adult microglia. In this proposal we hypothesize that the CD200-CD200R signaling axis inhibits mobilization of peripheral immune cells after stroke, and that interruption of CD200-CD200R interaction will exacerbate both central (brain) and peripheral immune responses. We will specifically examine the CD200-CD200R axis from both ends, by manipulating either CD200 or the CD200R to determine the effects on peripheral immune cell activation and stroke injury. In Aim 1, we will use a bone marrow chimera mouse model generated from global CD200R knockout and GFP+ mice, to determine the contribution of peripheral vs. central (brain) CD200- CD200R signaling to stroke outcomes. Aim 2 will investigate the effect of endothelial CD200 signaling on peripheral leukocyte migration in the ischemic brain. Brain endothelial CD200 knockdown (by AAV-BR1-Cre virus) and lenti-CD200 virus (conjugated with endothelial specific promotor Cadherin 5) transfected mice will be used to examine the effects of down-/up-regulation of endothelial CD200 respectively on immune responses to stroke. Aim 3 will evaluate the role of neuronal CD200 signaling in post-stroke inflammation and stroke outcomes. Neuronal CD200 CKO mice (CD200fl/fl:Eno2-Cre) and lenti-CD200 virus on neuronal promotor Enolase 2 (Eno2) will be used. As CD200-CD200R signaling functions in various neuroinflammatory diseases, the proposed project will open up a new area of CD200-CD200R research not only in stroke, but also in other central nervous system disorders.


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: 2025 ( Subtotal = $561,996 )
2025	2025	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/23/2025	NON-COMPETING CONTINUATION	$561,996
														Subtotal = $561,996

Issue Date FY: 2024 ( Subtotal = $546,384 )
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/21/2024	NON-COMPETING CONTINUATION	$546,384
														Subtotal = $546,384

Issue Date FY: 2023 ( Subtotal = $561,996 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/25/2023	NEW	$561,996
														Subtotal = $561,996

Grand Total All Awards = $1,670,376

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CD200 signaling mediates the interactions of neurons and endothelia with circulating leukocytes in stroke

Award Number: R01NS129977

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: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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