Faculty, Staff and Student Publications

Language

English

Publication Date

1-1-2026

Journal

Brain Research Bulletin

DOI

10.1016/j.brainresbull.2025.111686

PMID

41397547

Abstract

The immune responses to ischemic stroke are subjected to endogenous inhibitory pathways that delimitate the post-stroke inflammation. Among them, the interaction between CD200 and its receptor (CD200R) is increasingly recognized for its role in regulating neuroinflammation across various central nervous system (CNS) disorders. In the present study, we have examined the role of central (brain) vs. peripheral CD200R signaling in acute ischemic stroke using aged bone marrow chimeric (BMC) mice (16-19 months old). These chimeras were generated by transplanting bone marrow from CD200R knockout (KO), green fluorescent protein (GFP), or wild-type (WT) donor mice into irradiated recipient mice, and then subjected to a 45-min transient middle cerebral artery occlusion (MCAO). At three days post-stroke, flow cytometry, ELISA, and immunohistochemistry (IHC) were used to assess immune responses. Infarct volumes and neurobehavioral deficits were also evaluated. We found that T cell infiltration into the brain was significantly greater in KO-to-GFP (central CD200R signaling) compared to GFP-to-KO (peripheral CD200R signaling) mice. KO-to-GFP mice also exhibited significantly higher levels of pro-inflammatory cytokines IL-1β and TNF-α in the ischemic brain than GFP-to-KO chimeras. Correspondingly, KO-to-GFP mice showed significantly larger brain infarct volumes and worse neurobehavior deficits compared to GFP-to-KO chimeras. Together, these findings indicate that the peripheral (not the central) CD200R signaling plays a critical role in controlling post-stroke immune responses and delineating ischemic injury.

Keywords

Animals, Mice, Signal Transduction, Mice, Knockout, Orexin Receptors, Male, Stroke, Infarction, Middle Cerebral Artery, Mice, Inbred C57BL, Inflammation, Aging, Ischemic Stroke, Neuroinflammatory Diseases, Brain, Antigens, CD, Aging, Bone marrow chimeras, CD200, CD200R, Ischemic stroke, Lymphocytes, Neuroinflammation

Published Open-Access

yes

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