Single-cell multiome analysis reveals that intranasally-delivered elovanoids (ELV34 or its precursor) after ischemic stroke reduce disease-associated microglia and reactive astrocyte states while upregulating homeostatic microglia signatures and genes involved in synaptic organization.
ELV treatment reduced disease-associated microglia (DAM) marker expression after ischemic stroke.
ELV treatment decreased reactive astrocyte markers while upregulating genes involved in synaptic organization.
ELV reduced the abundance of oligodendrocytes and oligodendrocyte precursor cells (OPCs) expressing immune markers after ischemic stroke.
Intranasal delivery of ELV34 or its precursor reduced the loss of neuronal markers after ischemic stroke.
ELV induced a broad phenotype shift from pro-inflammatory states across multiple glial cell types in response to ischemic stroke damage.
This research suggests that a class of lipid molecules called elovanoids (ELVs), when delivered through the nose after a stroke, can shift the brain's immune and support cells away from harmful inflammatory states toward more protective, normal-functioning states. Using a cutting-edge technique called single-cell multiome analysis—which simultaneously measures gene activity in thousands of individual brain cells—the researchers found that ELV treatment reduced the activity of genes associated with harmful microglia (the brain's immune cells) and reactive astrocytes (support cells that become overactivated after injury), while boosting genes that help maintain healthy brain cell connections. Specifically, after a stroke, microglia typically turn on genes like Spp1 and Clec7a that drive inflammation, and astrocytes activate genes like Gfap and Lcn2 that reflect a reactive, potentially damaging state. This research suggests that intranasal ELV treatment suppresses these inflammatory programs across multiple brain cell types—including microglia, astrocytes, oligodendrocytes, and their precursor cells—and instead promotes gene activity linked to synapse maintenance and normal brain function. Neurons, which are the primary cells that die during stroke, also showed less loss of their identifying markers when ELV was administered. These findings matter because stroke remains a leading cause of death and disability, and current treatment options are very limited. This research suggests that elovanoids could potentially protect the brain after stroke not just by targeting one cell type, but by broadly reshaping the inflammatory environment across the entire brain's cellular ecosystem, preserving the connections between surviving neurons and reducing the collateral damage caused by the brain's own immune response.
Ji J, Bhattacharjee S, Giles B, Belayev L, Bazan N. (2026). Single-cell multiome landscape reveals elovanoid-mediated suppression of inflammatory glial states and induction of homeostatic signaling after ischemic stroke.. Experimental neurology. https://doi.org/10.1016/j.expneurol.2026.115998