Neuroprotective effect of the recombinant human leukemia inhibitory factor in mice with an experimental cuprizone model of multiple sclerosis: possible mechanisms

Abstract

Aim. To investigate the effects of the rhLIF recombinant human leukemia inhibitory factor on the structural and functional changes in the central nervous system in the cuprizone-induced experimental model of multiple sclerosis in mice and to evaluate the involvement of the brain macrophages, T-lymphocytes and antioxidant enzymes in the observed rhLIF effects. Methods. Young 129/Sv mice were fed with the cuprizone neurotoxin daily for three weeks. rhLIF was injected daily (50 μg/kg) after seven days of the cuprizone treatment. We used histology, flow cytometry, spectrophotometric and functional methods. Results. The cuprizone treatment resulted in an increase in the number of the brain and spinal cord neurons with destructive changes, the brain macrophages, CD3+-cells and the content of malondialdehyde; it changes the behavior of animals, decreases the brain superoxide dismutase and glutathione peroxidase activities. The rhLIF injection partially or completely restored the cuprizone-changed parameters. The effect of rhLIF was preserved during two months after the experiment completion. Conclusions. The neuroprotective effect of rhLIF is connected with a decrease in the cuprizone-induced changes in the number of the brain T-cells and macrophages and the activity of antioxidant enzymes.