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Issue 5, 2019
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Exosomes from LPS-stimulated macrophages induce neuroprotection and functional improvement after ischemic stroke by modulating microglial polarization

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Abstract

Inflammation occurs throughout the progression of cerebral ischemia/reperfusion and mediates myriads of pathological events following an ischemic insult. After ischemic stroke, inflammation was significantly triggered and microglia were activated to phenotypes (M1) typically releasing pro-inflammatory mediators, thus inducing neuron apoptosis and exacerbating brain injury. Therefore, shifting the polarization of microglia from the detrimental pro-inflammatory M1 phenotype to the beneficial anti-inflammatory M2 phenotype seems a promising therapeutic strategy in ischemic stroke. In this study we aimed to investigate the effects of exosomes (Ex) secreted from the lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cell line (LPS-Ex) on inducing neuroprotection and functional improvement after ischemic stroke by enhancing microglial M2 polarization. The results showed that LPS-Ex treatment exhibited more potent anti-inflammatory and neuroprotective effects in vitro; furthermore it significantly reduced the brain infarct volume and improved neurological function in a rat model of transient focal cerebral ischemia. The beneficial effects of LPS-Ex in ischemic stroke were associated with enhancing microglial polarization from the M1 phenotype to the M2 phenotype and inhibiting inflammation response. In conclusion, LPS-Ex protected against cerebral ischemia by skewing the microglial functional polarity from M1 toward an anti-inflammatory M2 phenotype. It may serve as a novel therapeutic strategy for neuroprotection and functional recovery upon ischemic stroke onset.

Graphical abstract: Exosomes from LPS-stimulated macrophages induce neuroprotection and functional improvement after ischemic stroke by modulating microglial polarization

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Publication details

The article was received on 10 Nov 2018, accepted on 23 Feb 2019 and first published on 02 Mar 2019


Article type: Paper
DOI: 10.1039/C8BM01449C
Citation: Biomater. Sci., 2019,7, 2037-2049

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    Exosomes from LPS-stimulated macrophages induce neuroprotection and functional improvement after ischemic stroke by modulating microglial polarization

    Y. Zheng, R. He, P. Wang, Y. Shi, L. Zhao and J. Liang, Biomater. Sci., 2019, 7, 2037
    DOI: 10.1039/C8BM01449C

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