Background
Cerebral infarction ranks as the second leading cause of disability and death globally, and inflammatory response of glial cells is the main cause of brain damage during cerebral infarction.
Methods
Studies have shown that mesenchymal stem cells (MSCs) can secrete exosomes and contribute to cerebral disease. Here, we would explore the function of MSC-derived exosome in cerebral infarction.
Results
Microarray indicated a decrease of miR-542-3p and an increase of Toll-Like Receptor 4 (TLR4) in middle cerebral artery occlusion (MCAO) mice comparing with sham mice. And luciferase and RIP analysis indicated a binding of miR-542-3p and TLR4. Then, we injected AAV9-miR-542-3p into paracele of sham or MCAO mice. Functional analysis showed that AAV9-miR-542-3p inhibited infarction area and the number of degenerating neurons and suppressed inflammatory factors’ expression and inflammatory cell infiltration. As well, transfection of miR-542-3p mimics into HA1800 cells underwent oxygen and glucose deprivation (OGD). Similarly, overexpression of miR-542-3p alleviated OGD induced cell apoptosis, ROS, and activation of inflammation response. Moreover, miR-542-3p could be packaged into MSCs and secreted into HA1800 cells. The extractive exosome-miR-21-3p treatment relieved MCAO- or OGD-induced cerebral injury and inflammation through targeting TLR4.
Conclusion
These results confirmed that MSC-derived exosome miR-542-3p prevented ischemia-induced glial cell inflammatory response via inhibiting TLR4. These results suggest possible therapeutic strategies for using exosome delivery of miR-542-3p to cure cerebral ischemic injury.
Microglia are the resident immune cells in the central nervous system and play an essential role in brain homeostasis and neuroprotection in brain diseases. Exosomes are crucial in intercellular communication by transporting bioactive miRNAs. Thus, this study aimed to investigate the function of microglial exosome in the presence of ischemic injury and related mechanism. Oxygen-glucose deprivation (OGD)-treated neurons and transient middle cerebral artery occlusion (TMCAO)-treated mice were applied in this study. Western blotting, RT-PCR, RNA-seq, luciferase reporter assay, transmission electron microscope, nanoparticle tracking analysis, immunohistochemistry, TUNEL and LDH assays, and behavioral assay were applied in mechanistic and functional studies. The results demonstrated that exosomes derived from microglia in M2 phenotype (BV2-Exo) were internalized by neurons and attenuated neuronal apoptosis in response to ischemic injury
in vitro
and
in vivo
. BV2-Exo also decreased infarct volume and behavioral deficits in ischemic mice. Exosomal miRNA-137 was upregulated in BV2-Exo and participated in the partial neuroprotective effect of BV2-Exo. Furthermore, Notch1 was a directly targeting gene of exosomal miRNA-137. In conclusion, these results suggest that BV2-Exo alleviates ischemia-reperfusion brain injury through transporting exosomal miRNA-137. This study provides novel insight into microglial exosomes-based therapies for the treatment of ischemic brain injury.
Objective. In this paper, we retrospectively reviewed the difference in clinical effectiveness of shock wave therapy and electroacupuncture therapy on knee osteoarthritis. Methods. A total of 128 treatment cases of knee osteoarthritis patients were extracted from the medical record system of Shenzhen Longhua District Central Hospital during the period from January 1, 2018, to January 30, 2020. The cases were divided into three groups for different treatments: shock wave group (
n
=
54
), electroacupuncture group (
n
=
41
), and control group (
n
=
33
). The shock wave group was given shock wave therapy combined basis clinical treatment; meanwhile, the electroacupuncture group was given electroacupuncture on the basis of actual clinical treatment. The control group was given conventional topical nonsteroidal anti-inflammatory drugs (Voltaren). Osteoarthritis index scale, NRS scale, and WHOQOL-BREF were observed before treatment, after 2 weeks, and 4 weeks after treatment. Results. This study found that the osteoarthritis index scale and NRS scale of the shock wave group and the electroacupuncture group were lower than those before treatment; it had significant difference (
P
<
0.001
). In WHOQOL-BREF, the shock wave group and the electroacupuncture group improved significantly four weeks after treatment (
P
<
0.001
), which was statistically different from the conventional group (
P
=
0.04
). Conclusion. Physical and rehabilitation medicine treatment (shock wave therapy) and traditional medical treatment (electroacupuncture) have better clinical effects on knee osteoarthritis, compared with conventional treatment. Shock wave and electric acupuncture have no apparent adverse reaction, suggesting that the treatment is safe and effective.
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