Single-cell multiome landscape reveals elovanoid-mediated suppression of inflammatory glial states and induction of homeostatic signaling after ischemic stroke.
TL;DR
ELV induced a phenotype shift from pro-inflammatory microglia, astrocytes, oligodendrocytes, oligodendrocytes, and OPCs in response to ischemic stroke damage, and upregulated gene pathways promoting synaptic integrity, reducing immune cell activation and neuronal loss.
Abstract
Ischemic stroke is a leading cause of death and disability. Administration of the lipid mediators elovanoids (ELVs) is protective in human neuronal-glia cultures and in experimental ischemic stroke. We now report using a single-cell multiome approach that intranasally-delivered (IN) ELV34 or its precursor reduced the loss of neuronal markers and upregulated homeostatic microglia signatures after stroke. Thus, ELV reduces disease-associated microglia (expressing Spp1, Gpnmb, Lgals3, Clec7a) and the expression of neuroinflammatory signaling genes. In astrocytes, ELV decreased reactive astrocytes (expressing Gfap, Vim, Nes, Lcn2) and upregulated genes involved in synaptic organization. Also, ELV reduced abundance of oligodendrocytes and OPCs expressing immune markers. ELV induced a phenotype shift from pro-inflammatory microglia, astrocytes, oligodendrocytes, and OPCs in response to ischemic stroke damage. ELV upregulated gene pathways promoting synaptic integrity, reducing immune cell activation and neuronal loss.