Critical role for scavenger receptor CD36 in microparticle-mediated neuroinflammation in a murine model of decompression sickness

Blood-borne microparticles (MPs) play a role in several forms of brain injury, but how they interact with the vasculature and contribute to neuroinflammation is unknown. The scavenger receptor CD36 is expressed across various cell types and regulates inflammation, vascular function, and innate immunity. We hypothesized that CD36 mediates MPs-induced neuroinflammatory responses in a murine model of decompression sickness (DCS). Wild-type mice subjected to decompression and naïve mice injected with MPs from decompressed mice exhibited a 2.2 ± 0.5-fold elevation in perivascular MPs deposition, 2.8 ± 0.6-fold elevation of inflammatory MPs in blood and 2.4 ± 0.4-fold in cervical lymph nodes, 2.7 ± 0.6-fold increase in neutrophil activation, 2.0 ± 0.3-fold increased glymphatic flow, 3.1 ± 0.4-fold increased leakage of six megadalton dextran at the blood-brain barrier, and a doubling of inflammatory proteins in brain. These events failed to occur in CD36 knockout mice and those conditionally deficient in endothelial CD36 (FLOX). We conclude that inflammatory MPs interact with endothelial CD36 to mediate neuroinflammatory responses and vascular injury in DCS.<b>NEW & NOTEWORTHY</b> Elevated glymphatic flow, glial cell activation, increased circulating microparticles (MPs), and neutrophil activation due to decompression have been well documented in animal models. This report shows that filamentous (F)-actin expressing MPs produced postdecompression interact with endothelial CD36 driving a feed-forward neuroinflammatory cycle and inducing vascular injury.