Extracellular vesicles derived from M2 microglia reduce ischemic brain injury through microRNA-135a-5p/TXNIP/NLRP3 axis

The Emerging Role of Extracellular Vesicle Derived From Neurons/Neurogliocytes in Central Nervous System Diseases: Novel Insights Into Ischemic Stroke

“…For example, in traumatic brain injury, Li et al (2019) illustrated that neuronal EVs enriched with miR-21-5p can suppress neuronal autophagy induced by scratch injury, directly targeting the Rab11a 3′UTR region to reduce its translation, thus attenuating trauma-induced, autophagy-mediated nerve injury in vitro . Likewise, Liu et al (2021a) found that M2 type microglia derived EVs could transfer miR-135a-5p into neurons to suppress the expression of thioredoxin-interacting protein, which in turn suppresses the activation of the nod-like receptor protein 3 inflammasome, thereby inhibiting neuronal autophagy induced by ischemia. To date, a vast number of studies have assessed the interaction between neuron/glial cell-EVs and autophagy in CNS diseases ( Li et al, 2019 ; Pei et al, 2019 ; Guo et al, 2020 ; Pei et al, 2020 ; Zang et al, 2020 ; Liu et al, 2021a ).…”

“…Likewise, Liu et al (2021a) found that M2 type microglia derived EVs could transfer miR-135a-5p into neurons to suppress the expression of thioredoxin-interacting protein, which in turn suppresses the activation of the nod-like receptor protein 3 inflammasome, thereby inhibiting neuronal autophagy induced by ischemia. To date, a vast number of studies have assessed the interaction between neuron/glial cell-EVs and autophagy in CNS diseases ( Li et al, 2019 ; Pei et al, 2019 ; Guo et al, 2020 ; Pei et al, 2020 ; Zang et al, 2020 ; Liu et al, 2021a ). The characteristics of these studies are summarized in Table 2 .…”

“…The process was repeated until no further studies would be obtained. A total of 29 studies were identified in this section ( Frühbeis et al, 2013 ; Fröhlich et al, 2014 ; Guitart et al, 2016 ; Xin et al, 2017 ; Xu et al, 2017 ; Hira et al, 2018 ; Yang et al, 2018 ; Song et al, 2019a ; Song et al, 2019b ; Pei et al, 2019 ; Tian et al, 2019 ; Xu et al, 2019 ; Chen et al, 2020b ; Bu et al, 2020 ; Frühbeis et al, 2020 ; Huang et al, 2020 ; Pei et al, 2020 ; Wu et al, 2020 ; Xie et al, 2020 ; Zang et al, 2020 ; Liu et al, 2021a ; Yang et al, 2021a ; Zhang et al, 2021a ; Li et al, 2021b ; Liu et al, 2021b ; Zhang et al, 2021b ; Chiang et al, 2021 ; Du et al, 2021 ; Raffaele et al, 2021 ), conducted from 2016 to 2021. The most extensively adopted species and associated stroke models are mice and middle cerebral artery occlusion, respectively.…”

“…The most extensively adopted species and associated stroke models are mice and middle cerebral artery occlusion, respectively. Among these 29 publications, 10 focused on microglia-EVs ( Yang et al, 2018 ; Song et al, 2019a ; Tian et al, 2019 ; Xie et al, 2020 ; Zang et al, 2020 ; Liu et al, 2021a ; Zhang et al, 2021a ; Li et al, 2021b ; Zhang et al, 2021b ; Raffaele et al, 2021 ), 11 focused on astrocyte-EVs ( Guitart et al, 2016 ; Xin et al, 2017 ; Hira et al, 2018 ; Pei et al, 2019 ; Xu et al, 2019 ; Chen et al, 2020b ; Bu et al, 2020 ; Pei et al, 2020 ; Wu et al, 2020 ; Liu et al, 2021b ; Du et al, 2021 ), 3 focused on oligodendrocytes ( Frühbeis et al, 2013 ; Fröhlich et al, 2014 ; Frühbeis et al, 2020 ) and 5 focused on neuron-EVs ( Xu et al, 2017 ; Song et al, 2019b ; Huang et al, 2020 ; Yang et al, 2021a ; Chiang et al, 2021 ), demonstrating that it is sufficient to suggest that EVs derived from neurons/glial cells play an important role in regulating the progress and prognosis of ischemic stroke.…”

“…For example, M2 microglial EVs can reduce glial scar formation by repressing the expression of astrocyte proliferation gene signal transducer and activator of transcription 3 and glial fibrillary acidic protein. Similarly, M2 microglial EVs can also reduce neuronal autophagy and apoptosis, which further inhibits ischemic brain injury ( Song et al, 2019a ; Liu et al, 2021a ). EVs secreted by microglial cell lines also play a significant role in the treatment of stroke.…”