Extracellular vesicles derived from different brain tissue cells: A potential therapeutic measure for hypoxic-ischemic brain injury in immature brains.

Neonatal hypoxic-ischemic encephalopathy and neonatal acute ischemic stroke are common causes of hypoxic-ischemic brain injury (HIBI) in the neonatal period, which may lead to permanent neurological sequelae. It is difficult to distinguish the two in the early stage. As a timely brain protection measure, hypothermia is still the standard treatment, but its efficacy in the treatment of immature brain injury is still controversial. The underlying pathophysiological mechanisms and effective treatment strategies of neonatal hypoxic-ischemic brain damage (HIBD) have been an active area of research. Extracellular vesicles (EVs), a class of nanoscale membranous structures, play a critical role in intercellular communication by facilitating the transfer of bioactive molecules or engaging in receptor-mediated interactions. Recent studies have demonstrated that various cell types within brain tissue, including neurons, astrocytes, microglia, endothelial cells, and stem cells, secrete substantial amounts of EVs. These vesicles carry diverse cargo, such as microRNAs, DNA, and proteins, which exert regulatory effects on recipient cells within the brain, thereby mediating neuroprotective effects. These effects include enhancing synaptic plasticity, modulating neuroinflammation, promoting angiogenesis, and regulating cellular autophagy, collectively contributing to neuroprotection. This review aims to summarize the functional characteristics of EVs derived from different cell types within the brain and to highlight recent advancements in this field. By providing insights into the role of EVs in HIBI, it seeks to provide novel insights and references for understanding the pathogenesis of neonatal HIBI and exploring innovative therapeutic approaches.