Short chain fatty acids reduces OPCs loss by inhibiting activation of astrocytes via SGK1/IL-6 signaling pathway

Short chain fatty acids (SCFAs) are known to be actively involved in neurological disease, but their roles in hypoxic-ischemic brain injury (HIBI) is unclear. This study established a rat model of HIBI, then measured the changes in IL-6 and NLRP3, proliferation and apoptosis indicators of oligodendrocyte precursor cells (OPCs). The mechanism of SCFAs on astrocytes were also investigated. To further explore the mechanism, astrocytes were treated with hypoxia in vitro and OPCs were treated with IL-6. The results showed that SCFAs significantly alleviated the activation of astrocyte and loss of OPCs induced by HIBI. SCFAs pretreatment was associated with the following: (1) downregulation of NLRP3, IL-6, CCL2, and IP-10; (2) was no effect on proliferation of OPCs; (3) amelioration of the abnormal expression of Bax and Bcl-2; and (4) regulation of IL-6 expression via SGK1 related pathway in astrocytes. Our findings revealed that SCFAs alleviated loss of OPCs through regulating the astrocytes activation by SGK1/IL-6 signaling pathway.