Glycosidase-Mediated Cell Surface Remodeling as a Therapeutic Strategy for Spinal Cord Injury

This hypothesis paper revisits a largely unexplored therapeutic strategy for spinal cord injury: the use of glycosidases, particularly neuraminidases, to transiently remodel neuronal cell surfaces and promote regeneration. We present preliminary experimental observations showing that embryonic rat hippocampal neurons treated with neuraminidase lose cell-cell contacts and adopt spheroid morphology within 4 hours. Upon enzyme removal, neurons re-extend processes and establish new contacts by 12 hours — supporting an "adhesion reset" mechanism. The concept, originally developed circa 2002, is re-examined in light of recent advances: the discovery that Neu3 sialidase activation is essential for peripheral axon regeneration (2014), and the demonstration that neuraminidase inhibitors can promote functional recovery after brain injury (2024). We propose that glycosidase-based treatment may complement current approaches including chondroitinase ABC, anti-Nogo-A antibodies, and stem cell transplantation. The preliminary data are qualitative and limited to embryonic neurons in vitro. This paper is intended to place the hypothesis on record and invite systematic investigation by groups with appropriate resources.