Oligodeoxynucleotide IMT504: Effects on remyelination in the corpus callosum and cerebral cortex after experimental demyelination

Demyelination is a pathological process characterized by myelin loss around axons, whereas remyelination restores myelin and function. Multiple sclerosis is an inflammatory demyelinating disease in which remyelination frequently fails. IMT504 (IMT) is a 24-nucleotide non-CpG oligodeoxynucleotide containing two PyNTTTTGT motifs with immunomodulatory and regenerative effects. Based on previous findings in a cuprizone (CPZ)-induced demyelination model, in which IMT was administered for five days before CPZ withdrawal and improved neuroinflammation and remyelination in the corpus callosum (CC), we evaluated a second treatment scheme in which IMT was administered subcutaneously for five days after CPZ withdrawal. Rats were sacrificed at 0 (T0), 5 (T5), and 10 (T10) days after CPZ withdrawal. Oligodendroglial and microglial populations were evaluated in the CC and cerebral cortex (Ctx) by immunohistochemistry. At T5, CPZ-treated rats showed an increase of PDGFRα+ oligodendrocyte (OL) precursor cells (OPCs) and a decrease of mature MAG+ OL in the CC. Phagocytic Iba1/CD68+ microglia increased following demyelination, whereas IMT reduced this response. In the Ctx, IMT did not modify OPC or mature OL populations but increased MAG+ fluorescence intensity compared with saline-treated animals. IMT also induced significant changes in microglial morphological complexity. These findings suggest that IMT modulates the microglial response and may promote remyelination following demyelination.