Eliprodil stimulates CNS myelination - New prospects for multiple sclerosis?

Objective: To examine the potential of eliprodil-a neuroprotective agent with a high affinity for sigma-receptors-to promote myelination in neuron-oligodendrocytes cocultures. Background: Remyelination is one of the major therapeutic issues in MS. Because neuronal integrity is required for CNS myelination, the authors postulated that neuroprotective molecules might favor myelination. Methods: Two experimental culture conditions were compared: standard medium Bottenstein and Sate ([B-S] medium) and a medium depleted of both thyroid hormones and progesterone (depleted [D] medium). Myelination was quantified by counting the number of myelinated internodes, identified immunocytochemically with an antimyelin basic protein(anti-MBP) antibody. Results: The authors first confirmed that in D medium myelination was reduced by a factor of 3.5 compared with cultures maintained in B-S medium. Under both culture conditions, addition of 10(-6) M eliprodil did not modify significantly the total number of either microtubule associated protein-2-positive neurons or MBP-positive oligodendrocytes. However, eliprodil induced a twofold (p < 0.01) increase in myelination when added do B-S medium, and a 4.7-fold (p < 0.0001) increase when added to D medium. Conclusions: Although the molecular mechanism mediating the effect; of the sigma-receptor agonist an myelination remains to be elucidated, these results strongly suggest that neuroprotective molecules may be of therapeutic interest in demyelinating diseases such as MS.