One important therapeutic goal during CNS injury from
trauma or
demyelinating diseases such as
multiple sclerosis is to develop methods to promote remyelination. We tested the hypothesis that spontaneous remyelination in the toxic nonimmune model of
lysolecithin-induced
demyelination can be enhanced by manipulating the inflammatory response. In PBS-treated SJL/J mice, the number of remyelinating axons per square millimeter of lesion area increased significantly 3 and 5 weeks after
lysolecithin injection in the spinal cord. However,
methylprednisolone or a
monoclonal antibody (mAb),
SCH94.03, developed for its ability to promote remyelination in the Theiler's virus murine model of
demyelination, further increased the number of remyelinating axons per lesion area at 3 weeks by
a factor of 2.6 and 1.9, respectively, but did not increase the ratio of myelin sheath thickness to axon diameter or the number of cells incorporating tritiated
thymidine in the lesion. After 3 weeks, the number of remyelinating axons in the
methylprednisolone or mAb
SCH94.03 treatment groups was similar to the spontaneous remyelination in the 5 week PBS control-treated group, indicating that these treatments promoted remyelination by increasing its rate rather than its extent. To address a mechanism for promoting remyelination, through an effect on scavenger function, we assessed morphometrically the number of macrophages in lesions after
methylprednisolone and mAb
SCH94.03 treatment.
Methylprednisolone reduced the number of macrophages, but
SCH94.03 did not, although both enhanced remyelination. This study supports the hypothesis that even in toxic nonprimary immune
demyelination, manipulating the inflammatory response is a benefit in myelin repair.