Mesenchymal stem cell-derived extracellular vesicles promote microglial M2 polarization after subarachnoid hemorrhage in rats and involve the AMPK/NF-κB signaling pathway

Han, Min; Cao, Ying; Guo, Xiaofan; Chu, Xili; Li, Tingting; Xue, Hao; Xin, Danqing; Yuan, Lin; Ke, Hongfei; Li, Gang; Wang, Zhen

doi:10.1016/j.biopha.2020.111048

Cited by 41 publications

(28 citation statements)

References 72 publications

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“…Nowadays, a rapidly developing field of stroke recovery studies indicates that traditional Chinese medicine (TCM), stem cells, and exosomes regulate the expression of various proteins and factors after stroke to reduce infract volume ( Larpthaveesarp et al, 2021 ). Meanwhile, stem cells could differentiate into glial cells to replace the necrotic cells and the exosomes contains various cargos, both of which have effects on ameliorating the motor functional recovery after stroke ( Han et al, 2021 ). TCM has been used in Eastern Asia for ischemic stroke treatment because of its function in preventing brain edema, neuronal apoptosis, and improving microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Challenges and Improvements of Novel Therapies for Ischemic Stroke

et al. 2021

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Stroke is the third most common disease all over the world, which is regarded as a hotspot in medical research because of its high mortality and morbidity. Stroke, especially ischemic stroke, causes severe neural cell death, and no effective therapy is currently available for neuroregeneration after stroke. Although many therapies have been shown to be effective in preclinical studies of ischemic stroke, almost none of them passed clinical trials, and the reasons for most failures have not been well identified. In this review, we focus on several novel methods, such as traditional Chinese medicine, stem cell therapy, and exosomes that have not been used for ischemic stroke till recent decades. We summarize the proposed basic mechanisms underlying these therapies and related clinical results, discussing advantages and current limitations for each therapy emphatically. Based on the limitations such as side effects, narrow therapeutic window, and less accumulation at the injury region, structure transformation and drug combination are subsequently applied, providing a deep understanding to develop effective treatment strategies for ischemic stroke in the near future.

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Section: Introductionmentioning

confidence: 99%

Challenges and Improvements of Novel Therapies for Ischemic Stroke

et al. 2021

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“…Accordingly, we demonstrate that APN promote phenotypic change of microglia from "classically" M1 activated to alternatively activated M2 states and enhances hematoma clearance, thereby reducing hydrocephalus by activation of PPARγ via AdipoR1 signaling. Emerging evidence has shown that the activation of AMPK promoted microglial M2 polarization, thereby inhibiting neuroin ammation after stroke [43][44][45]. Moreover, APN attenuated neuroin ammation after intracerebral hemorrhage through the AdipoR1-AMPK pathway [46].…”

Section: Discussionmentioning

confidence: 99%

Adiponectin ameliorates GMH-induced brain injury by regulating microglia M1/M2 polarization via AdipoR1/APPL1/AMPK/PPARγ signaling pathway in neonatal rats

Weng

Wei

et al. 2022

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Adiponectin (APN), a fat-derived plasma hormone, is a classic anti-inflammatory agent. Multiple studies have demonstrated the beneficial role of APN in acute brain injury, but the effect of APN in Germinal matrix hemorrhage (GMH) is unclear, and the underlying molecular mechanisms remain largely undefined. In the current study, we used a GMH rat model with rh-APN treatment, and we observed that APN demonstrated a protective effect on neurological function and an inhibitory effect on neuroinflammation after GMH. To further explore the underlying mechanisms of these effects, we found that the expression of Adiponectin receptor 1 (AdipoR1) primarily colocalized with microglia and neurons in brain. Moreover, AdiopR1, but not AdipoR2, were largely increased in GMH rats. Meanwhile, further investigation showed that APN treatment promoted AdipoR1/APPL1-mediated AMPK phosphorylation, and further increased peroxisome proliferator-activated receptor gamma (PPARγ) expression and induced microglial M2 polarization to reduce neuroinflammation and enhance hematoma resolution in GMH rats. Importantly, either knock down of AdipoR1, APPL1, or LKB1, or specific inhibition of AMPK/ PPARγ signaling in microglia abrogated the protective effect of APN after GMH in rats. In all, we propose that APN works as a potential therapeutic agent to ameliorate the inflammatory response following GMH by enhancing the M2 polarization of microglia via AdipoR1/APPL1/AMPK/PPARγ signaling pathway, ultimately attenuating inflammatory brain injury induced by hemorrhage.

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“…Various cellular targets, such as depletion of neutrophils or monocytes/macrophages, also downregulate inflammation [ 28 , 29 , 30 ]. Moreover, promoting microglial M2 polarization can afford neuroprotection after SAH [ 31 ]. Strategies aimed at promoting T-helper cells with anti-inflammatory roles, such Th2, Tregs opposed to Th1, and Th17, could be beneficial in reducing inflammation [ 32 , 33 , 34 ] and neuroprotective [ 33 , 34 ] via preventing BBB disruption [ 32 , 35 ], preserving endothelial function [ 35 ], and shifting microglia/macrophage response toward the M2 phenotype [ 36 ].…”

Section: Possible Novel Immune Pharmacological Approaches In Asahmentioning

confidence: 99%

“…Besides these, the role of immune checkpoint inhibitors may be evaluated to modulate inflammation after SAH [ 27 ]. Modulation of the inflammatory immune milieu by administering stem cell therapies [ 39 ] or stem-cell-derived extracellular vesicles [ 31 , 39 , 40 ] is another emerging frontier in this field that could be used to improve the post-SAH clinical outcome.…”

Section: Possible Novel Immune Pharmacological Approaches In Asahmentioning

confidence: 99%