Icariin ameliorates the cuprizone-induced acute brain demyelination and modulates the number of oligodendrocytes, microglia and astrocytes in the brain of C57BL/6J mice

Abstract

This study aimed at testing the hypothesis that treatment with icariin (ICA, a type of flavonoid) could mitigate the cuprizone (CPZ)-induced acute demyelination in the brain of mice and the potential mechanisms. Female C57BL/6J mice were fed continually with regular rodent chow or the chow supplemented with CPZ (0.2 % w/w) for six weeks to induce acute demyelination. The CPZ-fed mice were treated with vehicle or ICA at 12.5 or 25 mg/kg beginning at three weeks post CPZ feeding daily for three weeks. Their brain tissue sections were stained with oil red O, luxol-fast blue (LFB) and immunohistochemistry to characterize the levels of brain demyelination, myelin basic protein (MBP) and brain-derived neurotrophic factor (BDNF) and the numbers of oligodendrocytes (Ols), oligodendrocyte progenitor cells (OPCs), microglia and astrocytes in mice. Compared with the healthy controls, CPZ feeding caused the brain demyelination by increasing NG2+ OPCs, but decreased oil red O and LFB staining, MBP level and GST-pi+ Ols in the brain corpus callosum region of mice. Furthermore, CPZ feeding decreased the number of BDNF+ cells in the brain cortex and hippocampus regions, but increased microglia in the brain corpus callosum, cortex and caudate putamen, and astrocytes in the corpus callosum regions of mice. Treatment with ICA significantly mitigated or abrogated the toxic demyelination of CPZ by preserving MBP and BDNF proteins and modulating the numbers of Ols, OPCs, microglia and astrocytes in the brain of mice. ICA treatment significantly ameliorated the CPZ-mediated demyelination and modulated the number of Ols, microglia and astrocytes in the brain of mice.