Mesenchymal stem cells-derived IL-6 activates AMPK/mTOR signaling to inhibit the proliferation of reactive astrocytes induced by hypoxic-ischemic brain damage.

In this study, we investigated the therapeutic effects of MSCs on astrocyte proliferation in neonatal rats subjected to HIBD. A HIBD model was established in Sprague Dawley (SD) rats, and MSCs were administered by intracerebroventricular injection 5 days after HIBD. Rat primary astrocytes were cultured, subjected to oxygen glucose deprivation (OGD) injury and then immediately co-cultured with MSCs in vitro. Immunofluorescence staining, Cell Counting Kit (CCK)-8, flow cytometry, Ca2+ imaging, enzyme-linked immunosorbent assay (ELISA), western blotting, and co-immunoprecipitation (Co-IP) were performed. We found that MSCs transplantation not only promoted the recovery of learning and memory function in HIBD rats but also significantly reduced the number of Ki67+/glial fibrillary acidic protein (GFAP)+ cells in the hippocampi 7-14 days after HIBD. In addition to increasing IL-6 expression in both the hippocampi of HIBD rats and astrocyte culture medium, MSCs treatment in vitro significantly increased the expression levels of glycoprotein (gp) 130 and phosphorylated AMP-activated protein kinase α (p-AMPKα) and decreased the expression levels of p-mammalian target of rapamycin (mTOR) and its downstream targets. Furthermore, MSCs treatment induced a protein-protein interaction between gp130 and p-AMPKα. Suppression of IL-6 expression in MSCs reversed the above regulatory functions of MSCs in hippocampal astrocytes. The utilization of rapamycin further confirmed that mTOR par...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research