Brain Endothelial Cell-Derived Exosomes Induce Neuroplasticity in Rats with Ischemia/Reperfusion Injury

Gao, Beiyao; Zhou, Shao-Ting; Sun, Chengcheng; Cheng, Dandan; Zhang, Ye; Li, Xutong; Zhang, Li; Zhao, Jing; Xu, Dongsheng; Bai, Yulong

doi:10.1021/acschemneuro.0c00089

Cited by 32 publications

(22 citation statements)

References 46 publications

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“… 28 In the case of ischemia/hypoxia, exosomes derived from endothelial cells can suppress neuronal death, promote neural plasticity, and improve functional recovery. 29 In the current study, we found that exosomes released from IPASs were transmitted to neurons as shuttles carrying circSHOC2, which ameliorated ischemia-induced neuronal apoptosis, indicating that IPAS-EXO-mediated circSHOC2 transport may be sufficient to protect neurons from ischemia-induced damage.…”

Section: Discussionsupporting

confidence: 49%

Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis

Chen

Wang

Zhu

et al. 2020

Molecular Therapy - Nucleic Acids

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The aim of the present study was to investigate the neuroprotective roles and mechanisms of the circular RNA circSHOC2 in ischemic-preconditioned astrocyte-derived exosomes (IPAS-EXOs) against ischemic stroke. We established an ischemia model based on oxygen glucose deprivation (OGD) in vitro and isolated resultant exosomes from astrocytes. Neuronal viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assays and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling) staining, respectively. Autophagy-related proteins were analyzed by western blotting. We found that exosomes derived from IPAS-preconditioned medium (IPAS-CM) exerted neuroprotection. Furthermore, circSHOC2 expression was significantly upregulated in exosomes released from IPAS-CM. Overexpression of circSHOC2 in neurons yielded the same protective effects as those from IPAS-EXOs in vitro , and similar results were also observed in the middle cerebral artery occlusion (MCAO) mouse model. Mechanistically, circSHOC2 reduced neuronal apoptosis via regulating autophagy. Furthermore, circSHOC2 was found to sponge miR-7670-3p, which regulated SIRT1 expression. Transfection with an miR-7670-3p small interfering RNA (siRNA) (siRNA-7670-3p) and incubation with circSHOC2 extracellular vesicles attenuated ischemia-induced neuronal apoptosis in vivo and in vitro , while silencing of SIRT1 reversed the protective effects of exosomal circSHOC2 on hypoxic cerebral neurons. Taken together, our findings indicate that circSHOC2 in IPAS-EXOs suppressed neuronal apoptosis and ameliorated neuronal damage by regulating autophagy and acting on the miR-7670-3p/SIRT1 axis, which might contribute to a therapeutic strategy for ischemic stroke treatment.

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Section: Discussionsupporting

confidence: 49%

Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis

Chen

Wang

Zhu

et al. 2020

Molecular Therapy - Nucleic Acids

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“…In the past, most studies have focused on static parameters of gait (print area, maximal contact area, and stride length) (Domin et al, 2016;Fan et al, 2018;Hu et al, 2019). Few studies have focused on dynamic parameters (Gao et al, 2020). Our research highlights whole-body dynamic parameters (average speed, maximum variation, number of steps, swing) in gait analysis.…”

Section: Discussionmentioning

confidence: 89%

Cerebral Ischemia-Reperfusion Is Associated With Upregulation of Cofilin-1 in the Motor Cortex

Yin

Cheng

et al. 2021

Front. Cell Dev. Biol.

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Cerebral ischemia is one of the leading causes of death. Reperfusion is a critical stage after thrombolysis or thrombectomy, accompanied by oxidative stress, excitotoxicity, neuroinflammation, and defects in synapse structure. The process is closely related to the dephosphorylation of actin-binding proteins (e.g., cofilin-1) by specific phosphatases. Although studies of the molecular mechanisms of the actin cytoskeleton have been ongoing for decades, limited studies have directly investigated reperfusion-induced reorganization of actin-binding protein, and little is known about the gene expression of actin-binding proteins. The exact mechanism is still uncertain. The motor cortex is very important to save nerve function; therefore, we chose the penumbra to study the relationship between cerebral ischemia-reperfusion and actin-binding protein. After transient middle cerebral artery occlusion (MCAO) and reperfusion, we confirmed reperfusion and motor function deficit by cerebral blood flow and gait analysis. PCR was used to screen the high expression mRNAs in penumbra of the motor cortex. The high expression of cofilin in this region was confirmed by immunohistochemistry (IHC) and Western blot (WB). The change in cofilin-1 expression appears at the same time as gait imbalance, especially maximum variation and left front swing. It is suggested that cofilin-1 may partially affect motor cortex function. This result provides a potential mechanism for understanding cerebral ischemia-reperfusion.

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“…The cardioprotective effect was not observed when treated with EV depleted conditioned media. Increased axonal growth and upregulation of miRNA related to the regulation of Sema6A, Phosphatase and Tensin Homolog (PTEN), and RhoA was observed with rat cerebral EC-EVs in vitro (Zhang Y. et al, 2020). Vascular smooth muscle cells showed an increased vascular cell adhesion molecule 1 (VCAM1) expression and leukocyte adhesion when cultured with rat cerebral EC-EVs (Boyer et al, 2020).…”

Section: Biological Activities Of Ec-evsmentioning

confidence: 97%

“…Endothelial colony-forming cells (ECFC)-EVs inhibited apoptosis and reduced ischemic kidney injury in mice ( Vinas et al, 2018 ). Brain EC-EVs promoted motor function and Synapsin I expression in the cerebral artery occlusion model of rats ( Gao et al, 2020 ). EVs from HUVECs cultured in high glucose media restored wound healing of basal glucose cultured HUVECs compared to EVs from HUVECs cultured in basal media ( Saez et al, 2018 ).…”

Section: Endothelial Cell-evsmentioning

confidence: 99%

Extracellular Vesicles for the Treatment of Radiation Injuries

et al. 2021

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Normal tissue injury from accidental or therapeutic exposure to high-dose radiation can cause severe acute and delayed toxicities, which result in mortality and chronic morbidity. Exposure to single high-dose radiation leads to a multi-organ failure, known as acute radiation syndrome, which is caused by radiation-induced oxidative stress and DNA damage to tissue stem cells. The radiation exposure results in acute cell loss, cell cycle arrest, senescence, and early damage to bone marrow and intestine with high mortality from sepsis. There is an urgent need for developing medical countermeasures against radiation injury for normal tissue toxicity. In this review, we discuss the potential of applying secretory extracellular vesicles derived from mesenchymal stromal/stem cells, endothelial cells, and macrophages for promoting repair and regeneration of organs after radiation injury.

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Brain Endothelial Cell-Derived Exosomes Induce Neuroplasticity in Rats with Ischemia/Reperfusion Injury

Cited by 32 publications

References 46 publications

Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis

Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis

Cerebral Ischemia-Reperfusion Is Associated With Upregulation of Cofilin-1 in the Motor Cortex

Extracellular Vesicles for the Treatment of Radiation Injuries

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