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. 2020 Apr;245(8):740-747.
doi: 10.1177/1535370220919361. Epub 2020 Apr 16.

Normobaric intermittent hypoxic training regulates microglia phenotype and enhances phagocytic activity

Genell Tantingco  1 , Myoung-Gwi Ryou  1   2
Affiliations

Normobaric intermittent hypoxic training regulates microglia phenotype and enhances phagocytic activity

Genell Tantingco et al. Exp Biol Med (Maywood). 2020 Apr.

Abstract

The effects of intermittent hypoxic training or conditioning on many pathological conditions have been widely investigated. One of the pathological conditions dealt with intermittent hypoxic training is ischemic stroke. Well-known mechanisms of intermittent hypoxia-induced protection are related to increased energy metabolism and the enhanced antioxidant effects. In the last decades, the role of microglia in the progress of ischemic stroke-related brain damage has been focused. The dual-edge function of microglia indicates that the microglia-mediated inflammatory response is definitely beneficial in the early stage of ischemic stroke, but long-term activation of microglia is rather detrimental during the recovery process. The effect of IHT on microglia polarization is not investigated. This study focused on whether IHT regulates the polarization of microglia without dampening its classic phagocytic function. This study will provide pivotal information regarding the effects of IHT on the long-term effects on the recovery process from ischemic stroke.

Keywords: Microglia; inflammation; intermittent hypoxia training; ischemic stroke; oxygen–glucose deprivation; phagocytosis.

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Figures

Figure 1.
Figure 1.
IHT protects the microglia from the OGD and reoxygenation. (a, b) The Calcein-AM assay shows the protective effect of IHT against OGD and reoxygenation. (c) LDH assay supports that IHT protects the microglia by presenting that microglia exposed to the OGD and reoxygenation get stressed and increased LDH release into the culture media. *P < 0.05 vs. OGD/Reoxy. (A color version of this figure is available in the online journal.)
Figure 2.
Figure 2.
IHT derives microglia toward the anti-inflammatory M2 phenotype. (a) The characteristic of EOC20 cell is confirmed by detecting CD11b which is a microglia marker. CD206, M2 marker, is noticeably increased on the microglia treated with IHT. (b,c) Western blot data clearly show that CD206 protein content in the microglia is significantly increased by IHT compared to the microglia in the OGD and reoxygenation group. *P < 0.05 vs. OGD/Reoxy. (A color version of this figure is available in the online journal.)
Figure 3.
Figure 3.
Anti-inflammatory cytokines and toll-like receptor 2 content. (a) IHT increased the IL-4 contents compared to other groups including OGD and control. (b) IL-10 is not increased compared to the Normoxia but increased compared to the OGD group. (c,d) Toll-like receptor 2 is significantly increased in the OGD and reoxygenation group. #P < 0.05 vs. Normoxia *P < 0.05 vs. OGD/Reoxy.
Figure 4.
Figure 4.
Phagocytic activity of microglia enhanced by IHT. The phagocytic activity of microglia activated by OGD and reoxygenation is enhanced compared to the unstressed control group. IHT increases the phagocytic activity of microglia greater than the OGD–reoxygenation group. (A color version of this figure is available in the online journal.)
Figure 5.
Figure 5.
IHT reduced ROS generation from microglia. ROS generation in the OGD and reoxygenation activated-microglia was dampened by IHT. The bar graph represents a quantitative analysis of the H2DCFDA spectrophotometry assay. *P  < 0.05 vs. OGD/Reoxy. (A color version of this figure is available in the online journal.)
See this image and copyright information in PMC

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