Oligodendrocyte-protection and remyelination post-spinal cord injuries: A review

In the past four decades, the main focus of investigators in the field of spinal cord regeneration has been to devise therapeutic measures that enhance neural regeneration. More recently, emphasis has been placed on enhancing remyelination and providing oligodendrocyte-protection after a spinal cord injury (SCI). Demyelination post-SCI is part of the cascading secondary injury that takes place immediately after the primary insult; therefore, therapeutic measures are needed to reduce oligodendrocyte death and/or enhance remyelination during the acute stage, preserving neurological functions that would be lost otherwise. In this review a thorough investigation of the oligodendrocyte-protective and remyelinative molecular therapies available to date is provided. The advent of new biomaterials shown to promote remyelination post-SCI is discussed mainly in the context of a combinatorial approach where the biomaterial also provides drug delivery capabilities. The aim of these molecular and biomaterial-based therapies is twofold: (1) oligodendrocyte-protective therapy, which involves protecting already existing oligodendrocytes from undergoing apoptosis/necrosis; and (2) inductive remyelination, which involves harnessing the remyelinative capabilities of endogenous oligodendrocyte precursor cells (OPCs) at the lesion site by providing a suitable environment for their migration, survival, proliferation and differentiation. From the evidence reported in the literature, we conclude that the use of a combinatorial approach including biomaterials and molecular therapies would provide advantages such as: (1) sustained release of the therapeutic molecule, (2) local delivery at the lesion site, and (3) an environment at the site of injury that promotes OPC migration, differentiation and remyelination.

► An overview of the pathophysiology that occurs during a spinal cord injury (SCI), and specifically the onset of demyelination is presented to provide the readers with the appropriate background.
► A comprehensive study of all the molecular therapies that target remyelination and/or promote oligodendrocyte-protection post-SCI has been carried out.
► A review of all the biomaterials used in spinal cord regeneration that have shown positive effects on remyelination have been presented.
► Examples of drug delivery systems used in spinal cord regeneration that could potentially be used in enhancing remyelination have been explored.
► An expert opinion is promoted in the review, which encourages the use of a combinatorial approach using molecular therapies and drug delivery systems to target remyelination and oligodendrocyte-protection post-SCI.