Synergistic protective effect of FTY720 and Vitamin E against simulated cerebral ischemia in vitro

Abstract

The purpose of the present study was to explore the combination effect of FTY720 and Vitamin E on cerebral ischemia. Astrocytes were isolated from newborn Sprague-Dawley rats and were subjected to FTY720, Vitamin E, or combination of the two. The astrocyte cultures were then exposed to oxygen-glucose deprivation (OGD) to simulate an ischemic model in vitro. Cell viability, lactate dehydrogenase (LDH) leakage and cell apoptosis were detected following 12 h of exposure to OGD. In addition, the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, total antioxidant capacity, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, chemokine (C-X-C motif) ligand (CXCL)-10, heme oxygenase (HO)-1 and superoxide dismutase (SOD)-1 were measured. Pre-treatment with FTY720 or Vitamin E significantly elevated the cell viability and decreased LDH release and number of apoptotic cells. Combination treatment with FTY720 and Vitamin E demonstrated a synergistic protective effect on OGD-induced cell viability, toxicity and apoptosis. Pre-treatment with FTY720 markedly reduced the release of IL-1β, TNF-α, IL-6, ICAM-1, VCAM-1 and CXCL-10, and pre-treatment with Vitamin E increased the levels of antioxidant, HO-1 and SOD-1. However, pre-treatment with FTY720 combined with Vitamin E revealed a synergistic effect. Pre-treatment with FTY720 combined with Vitamin E exerts synergistic neuroprotective effects in the simulated cerebral ischemia in vitro.