Keratan sulfate expression is associated with activation of a subpopulation of microglia/macrophages in Wallerian degeneration

Wallerian degeneration is a fundamental process of axonal degeneration distal to the injury site. Although axonal degeneration itself is accomplished in a few days, the subsequent process of removing debris, including myelin debris, in the central nervous system takes more time. Since this debris is a potent inhibitor of axonal regeneration, the removal process is critical for functional recovery after neuronal injuries. Although it is known that microglia/macrophages are involved in this process, the underlying mechanisms are not fully understood. Here, we found that keratan sulfate (KS) expression was induced far from the injury site after spinal cord injury. A hemilateral section of the spinal cord at the third cervical level induced KS expression in a restricted area of the ipsilateral column at the first lumbar level 1 week after injury. This localized KS expression lasted for at least 1 month after injury. The KS signal was merged with a portion of Iba1-positive cells, suggesting that a subpopulation of microglia/macrophages expressed KS. KS-positive cells expressed CD68 and CD86, but not CD206 or arginase 1, suggesting that these microglia/macrophages were in an activated state probably polarized to M1. Our study has explored for the first time the relation between KS expression and activation of microglia/macrophages in Wallerian degeneration.