Fig. 9

A schematic representation illustrates the potential mechanisms through which exosomes secreted by neural stem cells (NSCs) contribute to the therapeutic effects of TBI. These exosomes, rich in bioactive molecules, can freely cross the BBB, suppress neuroinflammation and neuronal apoptosis, and enhance neuroregeneration and angiogenesis. In terms of neuroregeneration, NSCs release exosomes containing circAcbd6, which facilitates the differentiation of NSCs into cholinergic neurons via the miR-320-5p/oxysterol-binding protein–related protein 2 axis. Additionally, NSC-derived exosomes modulate immune responses by reducing inflammation, suppressing the expression of proinflammatory cytokines such as TNF-α, IL-1, and IL-6, and shifting microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Regarding anti-apoptotic effects, NSC-derived exosomes deliver miR-150-3p, a microRNA that effectively inhibits neuronal apoptosis. Furthermore, these exosomes enhance the expression of autophagy marker proteins LC3B and beclin-1, which contributes to reducing nerve cell apoptosis. Lastly, in promoting angiogenesis, NSC exosomes elevate VEGF expression, thereby accelerating the formation of new blood vessels. Figure adapted/reprinted from Zhong et al. [183] under a Creative Commons Attribution (CC BY) 4.0 license. © 2023 The Authors. Published by Stem Cell Research & Therapy. (https://creativecommons.org/licenses/by/4.0/)