【摘 要】
：
Extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs) have previously been shown to protect against brain injury caused by hypoxia-ischemia (HI). The neuroprotective effects have been found to relate to the anti-inflammatory effects of EVs. H
【机 构】
：
Department of Physiology,School of Basic Medical Sciences,Cheeloo College of Medicine,Shandong Unive
论文部分内容阅读
Extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs) have previously been shown to protect against brain injury caused by hypoxia-ischemia (HI). The neuroprotective effects have been found to relate to the anti-inflammatory effects of EVs. However, the underlying mechanisms have not previously been determined. In this study, we induced oxygen-glucose deprivation in BV-2 cells (a microglia cell line), which mimics HI in vitro, and found that treatment with MSCs-EVs increased the cell viability. The treatment was also found to reduce the expression of pro-inflammatory cytokines, induce the polarization of microglia towards the M2 phenotype, and suppress the phosphorylation of selective signal transducer and activator of transcription 3 (STAT3) in the microglia. These results were also obtained in vivo using neonatal mice with induced HI. We investigated the potential role of miR-21a-5p in mediating these effects, as it is the most highly expressed miRNA in MSCs-EVs and interacts with the STAT3 pathway. We found that treatment with MSCs-EVs increased the levels of miR-21a-5p in BV-2 cells, which had been lowered following oxygen-glucose deprivation. When the level of miR-21a-5p in the MSCs-EVs was reduced, the effects on microglial polarization and STAT3 phosphorylation were reduced, for both the in vitro and in vivo HI models. These results indicate that MSCs-EVs attenuate HI brain injury in neonatal mice by shuttling miR-21a-5p, which induces microglial M2 polarization by targeting STAT3.
其他文献
Amyotrophic lateral sclerosis (ALS) is associated with proteostasis collapse: ALS is an unrelenting neurodegenerative disease that is characterized by the loss of motor neurons in the brain and spinal cord, resulting in the progressive atrophy, and eventu
Previous studies on the mechanisms of peripheral nerve injury (PNI) have mainly focused on the pathophysiological changes within a single injury site. However, recent studies have indicated that within the central nervous system, PNI can lead to changes i
In the 1950s to 1970s, the research on Parkinson\'s disease (PD) and its treatment had mainly been focused on the Nigro-striatal dopamine (DA) neurons as the major site of degeneration in this disease. It contributed to the search for drugs that restore
Degeneration of retinal ganglion cells (RGCs) is one of the hallmarks of common optic neuropathies (Weinreb et al., 2014). Glaucoma, the most common optic neuropathy, is characterized by degeneration of RGCs. Acute angle-closure glaucoma is a serious ocul
Traumatic brain injury (TBI) remains a major cause of disability among young adults in both civilian and military settings contributing to a high burden on healthcare systems (Badhiwala et al., 2019). Sequel of TBI, even mild injuries, include motor and s
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by the homozygous mutation or deletion of the survival motor neuron 1 (SMN1) gene. A second copy, SMN2, is similar to SMN1, but produces only ～10％ SMN protein because of a single-point mutati
Tendon pathology is characterized by damage to the tendon structural integrity with disruption of collagen fibers (Nourissat et al., 2015). Acute tendon injuries show a macroscopic discontinuity, ranging from partial to complete tendon rupture. They invol
Bradykinin (BK) is an active component of the kallikrein-kinin system that has been shown to have cardioprotective and neuroprotective effects. We previously showed that BK postconditioning strongly protects rat hippocampal neurons upon restoration of spo
Pericytes, as the mural cells surrounding the microvasculature, play a critical role in the regulation of microcirculation; however, how these cells respond to ischemic stroke remains unclear. To determine the temporal alterations in pericytes after ische
Extracellular aggregation of amyloid-beta (Aβ) and intracellular tau tangles are two major pathogenic hallmarks and critical factors of Alzheimer\'s disease. A linear interaction between Aβ and tau protein has been characterized in several models. Aβ in