Bone marrow mesenchymal stem cells promote remyelination in spinal cord by driving oligodendrocyte progenitor cell differentiation via TNFα/RelB-Hes1 pathway: a rat model study of 2,5-hexanedione-induced neurotoxicity

Abstract Background N -hexane, with its metabolite 2,5-hexanedine (HD), is an industrial hazardous material. Chronic hexane exposure causes segmental demyelination in the peripheral nerves, and high-dose intoxication may also affect central nervous system. Demyelinating conditions are difficult to treat stem cell therapy using bone marrow mesenchymal cells (BMSCs) a promising novel strategy. Our previous study found that BMSCs promoted motor function recovery rats modeling neurotoxicity. This work aimed explore underlying mechanisms focused on changes spinal cord. Methods Sprague Dawley were intoxicated HD (400 mg/kg/day, i.p, for 5 weeks). A bolus of (5 × 10 7 cells/kg) was injected via tail vein. Demyelination remyelination cord before after BMSC treatment examined microscopically. Cultured oligodendrocyte progenitor (OPCs) incubated ± BMSC-derived conditional medium (BMSC-CM). OPC differentiation studied by immunostaining morphometric analysis. The expressional Hes1, transcription factor negatively regulating OPC-differentiation, studied. upstream Notch1 TNFα/RelB pathways studied, some key signaling molecules measured. correlation between neurotrophin NGF TNFα investigated. Statistical significance evaluated one-way ANOVA performed SPSS 13.0. Results demyelinating damage evidenced electron microscopy, LFB staining NG2/MBP immunohistochemistry. In vitro cultured OPCs showed more incubation BMSC-CM. Hes1 expression be significantly increased decreased or change found, however, independent activation, but dependent signaling. increase TNFα, RelB expression, have opposite effect. Addition recombinant overexpression similarly caused upregulation expression. secretion activation receptor important suppression production OPCs. Conclusions findings demonstrated promote HD-exposed TNFα/RelB-Hes1 pathway, providing insights evaluating further exploring therapeutical effect neurodegenerative disease.