Systemic progesterone administration results in a partial reversal of the age‐associated decline in CNS remyelination following toxin‐induced demyelination in male rats

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Abstract
In order to establish the effects of systemically administered progesterone on central nervous system (CNS) remyelination, a toxin-induced model of CNS demyelination was used in which the rate of remyelination is age-dependent. The rapid remyelination in young adult rats allowed an assessment of potential adverse effects of progesterone while the slow remyelination in older adult rats allowed an assessment of its potentially beneficial effects. There was no significant difference in the rate of remyelination between young control and treated animals. However, a modest but significant increase in the extent of oligodendrocyte remyelination in response to progesterone (and a comparable significant decrease in the proportion of axons that remained demyelinated) was observed in older rats 5 weeks after lesion induction. We also found a significant increase in the proportion of Schwann cell remyelinated axons between 3 and 5 weeks after lesion induction that was not apparent in the control animals. These results indicate that progesterone does not inhibit CNS remyelination and that it has a positive modulating effect on oligodendrocyte remyelination in circumstances where it is occurring sub-optimally.