Analysis of structural and molecular events associated with adult rat optic chiasm and nerves demyelination and remyelination: possible role for 3rd ventricle proliferating cells.

Multiple sclerosis frequently affects the optic apparatus, particularly optic chiasm and nerves. Here, we have reported the structural and molecular characteristics of remyelination in the adult rat optic chiasm and nerves. Moreover, considering the proximity of optic chiasm and 3rd ventricle, we have tried to determine if proliferating cells residing in 3rd ventricle region are able to migrate in response to experimental demyelination of the optic chiasm. Following local demyelination by lysolecithin, remyelination pattern in longitude of optic chiasm and proximal nerves was investigated using myelin staining and marker genes expression. Furthermore, cell tracing was carried out using BrdU labeling of proliferating cells prior to gliotoxin injection. Morphometric analysis revealed that demyelination was considerable on days 7 and 14 and an incomplete remyelination occurred on day 28 post-lesion. Interestingly, myelin repair was more evident in the caudal part of chiasm, compared to rostral part and proximal optic nerves. Following chiasm and nerve demyelination, trains of BrdU+ cells were seen near the 3rd ventricle which subsequently moved to lesion site. Nestin was significantly up-regulated in 3rd ventricle surroundings. At the lesion site, Nogo-A gene expression was significantly decreased on days 7 and 14 post lesion, while Olig2, nestin, and GFAP expression was increased on day 7. The changes were then reversed by the time. Myelin repair in optic chiasm seems to be mediated by endogenous progenitors and stem cells. Adult 3rd ventricle proliferating cells may play a role in this context by mobilization into the demyelinated chiasm.