Abstract TP080: Extracellular vesicles derived from dysfunctional cerebral endothelial cells of rats with vascular dementia impair oligodendrocyte function and myelination

Background: Cerebral vascular damage and white matter demyelination are hallmarks of vascular dementia (VaD), a major contributor to cognitive decline. Oligodendrocyte progenitor cells (OPCs) and oligodendrocytes (OLs) interact with cerebral endothelial cells (CECs), but how they communicate in VaD is unclear. Extracellular vesicles (EVs) mediate intercellular signaling via their bioactive cargo. This study tested the hypothesis that CEC-derived EVs (CEC-EVs) in VaD impair OL function and myelination. Methods: A multiple microinfarct (MMI) model was used to induce VaD in rats. Endogenous CEC-EVs were tracked using CEC specific CD63 reporter mice (CEC-CD63, Slco1c1-CreERT2; CD63/GFPflox). Primary CECs isolated 7 days post-MMI (MMI-CECs) or from sham controls were cultured. The in vivo and in vitro blood–brain barrier (BBB) integrity was evaluated using albumin and fibrin staining, and FITC–dextran permeability assay, respectively. EVs were isolated from the cultured CECs by ultracentrifugation (MMI-CEC-EVs). Human OPCs (hOPCs) were treated with MMI-CEC-EVs or vehicle control, and RNA sequencing was performed to assess gene expression. Results: MMI significantly increased extravascular albumin and fibrin deposition in the corpus callosum and striatum (p