Brain Endothelial CD200 Signaling Protects Brain Against Ischemic Damage

Authors

Afzal Misrani
Conelius Ngwa
Abdullah Al Mamun
Romana Sharmeen
Kanaka Valli Manyam
Rodney M Ritzel
Louise McCullough
Fudong Liu

Publication Date

2-1-2024

Journal

Brain Research Bulletin

Abstract

Ischemic stroke induced inflammatory responses contribute significantly to neuronal damage and stroke outcomes. CD200 ligand and its receptor, CD200R, constitute an endogenous inhibitory signaling that is being increasingly recognized in studies of neuroinflammation in various central nervous system disorders. CD200 is a type 1 membrane glycoprotein that is broadly expressed by endothelia and neurons in the brain. In the present study, we have examined the role of endothelial CD200 signaling in acute ischemic stroke. Endothelial CD200 conditional knock out (CKO) mice were generated by breeding CD200 gene floxed mice with Cdh5^Cre mice. The mice were subjected to a 60-min transient middle cerebral artery occlusion (MCAO). Flow cytometry, Immunohistochemical staining, and Western blotting were performed to assess the post-stroke inflammation; stroke outcomes (infarct volume and neurobehavioral deficits) were evaluated at 72 h after MCAO. We found CD200R was near-null expressed on microglia at 24 h after stoke. Endothelial CKO of CD200 had no impact on peripheral immune cell development. Immunohistochemical staining confirmed CD200 was expressed on CD200 floxed but not on CD200 CKO endothelia. CD200 CKO mice exhibited larger infarct size, worse neurological deficit scores (NDS), and more deficits in the adhesive removal when compared with control mice, 72 h after MCAO. Western blot results showed that endothelial CKO of CD200 did not change BBB protein expression. Together it suggests that endothelial CD200 signaling protects brains against ischemic injury through a mechanism not directly related to microglial activation.

Keywords

Endothelial CD200, Stroke, BBB, Neurological function