Astrocytic Extracellular Vesicles Regulated by Microglial Inflammatory Responses Improve Stroke Recovery

There are no effective treatments for post-stroke glial scar formation, which inhibits axonal outgrowth and functional recovery after stroke. We investigated whether astrocytic extracellular vesicles (AEVs) regulated by microglia modulate glial scars and improve stroke recovery. We found that peri-infarct glial scars comprised reactive astrocytes with proliferating C3d and decreased S100A10 expression in chronic stroke. In cultured astrocytes, microglia-conditioned media and treatment with P2Y(1) receptor antagonists increased and reduced the area of S100A10- and C3d-expressing reactive astrocytes, respectively, by suppressing mitogen-activated protein kinase/nuclear factor-kappa beta (NF-kappa B)/tumor necrosis factor-a (TNF-alpha)/interleukin-1 beta signaling after oxygen-glucose deprivation. Intracerebral administrations of AEVs enriched miR146a-5p, downregulated NF-kappa B, and suppressed TNF-alpha expressions, by transforming reactive astrocytes to those with S100A10 preponderance, causing functional recovery in rats subjected to middle cerebral artery occlusion. Modulating neuroinflammation in post-stroke glial scars could permit axonal outgrowth, thus providing a basis for stroke recovery with neuroprotective AEVs.

Automated summary

This study investigates whether astrocytic extracellular vesicles (AEVs) regulated by microglia can modulate glial scars and improve stroke recovery. The researchers found that the peri-infarct glial scars consisted of reactive astrocytes and that administering AEVs led to functional recovery in rats subjected to middle cerebral artery occlusion.