Microglia-Astroglia-Neuron network following stroke: Novel insight into extracellular vesicles communication

Stroke is one of the leading causes of death and disability worldwide, with ischemic stroke accounting for the majority of cases. Intercellular communication is critical to its prognostic impact, and extracellular vesicles (EVs) are an emerging important mechanism. EVs are increasingly recognized as key mediators of crosstalk between neurons and glial cells, affecting processes such as neuroinflammation, oxidative stress and tissue repair. More previous studies have focused on signaling and information exchange between the two types of cells. This paper reviews the EVs-mediated triad interaction between neurons, astrocytes and microglia after stroke based on the spatiotemporal entanglement of them. Not only the intercellular crosstalk of EVs of microglial, astrocytic, or neuronal origins is explored in detail, the cargoes carried by EVs and their mechanisms of action are resolved, but also the overlapping parts in the EVs-mediated cellular communication mechanisms are analyzed, such as the NF-κB signaling pathway and miR-124 which play an important and complex role in a variety of intercellular communications. On this basis, EVs were revealed to have potential as biomarkers and therapeutic carriers. The aim of this paper is to contribute to our deeper understanding of stroke pathophysiology and to inspire new possible therapeutic strategies.