Sodium ferulate attenuates ischaemic stroke by mediating the upregulation of thrombospondin-4 expression and combined treatment with bone marrow mesenchymal stem cells

Abstract

Ischaemic stroke is one of the major diseases affecting human health, involving complex and diverse pathological mechanisms, including inflammatory response, oxidative stress and angiogenesis. Sodium ferulate (SF) exerts a protective effect on cerebral ischaemia/reperfusion and when combined with bone marrow mesenchymal stem cells (BMSCs), has a considerable therapeutic effect on brain injury in rats. Here, we speculate that SF also exerts cerebroprotective effects. In this study, we found that after SF intervention, thrombospondin 4 (TSP4) protein expression increased in oxygen glucose deprivation/restoration (OGD/R)–treated human brain microvascular endothelial cells (HBMECs). In addition, the transfection of sh-TPS4 reversed the inhibitory effects of SF on inflammatory infiltration, oxidative stress and apoptosis and promoted effects on cell migration and angiogenesis. BMSCs have strong proliferation ability and multi-directional differentiation potential and alleviate brain injury. We found that compared with wild-type BMSCs, the TSP4-modified BMSCs had a more considerable effect that alleviated OGD/R-induced cell injury. Furthermore, SF combined with TSP4-modified BMSCs promoted the repair of damaged OGD/R-treated HBMECs by activating the PI3K/AKT/mTOR pathway. In the rat middle cerebral artery occlusion (MCAO) model, the therapeutic effect of SF combined with BMSCs on brain injury in rats was better than that of SF alone, and the therapeutic effect of the TSP4-modified BMSCs was better than that of the wild-type BMSCs. In conclusion, our results showed that SF upregulated TSP4 expression and combined with BMSCs to promote repair of damaged OGD/R-treated HBMECs and improve ischaemic stroke in rats.