Promoting axonal myelination for improving neurological recovery in spinal cord injury

Abstract

Spinal cord injury (SCI) remains a major challenge to neurological research. Progress in both basic and clinical research has shown that neurons and oligodendrocytes are equally susceptible to such injury. In injuries secondary to direct injury to the spinal cord, oligodendrocytes appear to be highly vulnerable to various harmful factors and eventually undergo apoptosis. Due to the loss of myelinating cells, axonal demyelination is likely to affect the neural function of surviving axons. Recently, improved understanding of the pathological changes ongoing in oligodendrocytes following injury has shown that the death of these cells plays a vital role in the demyelination of axons. Because the demise of oligodendrocytes and subsequent axonal demyelination impair the conductive capacity of surviving axons, it seems reasonable to expect that reducing oligodendrocyte death and improving axonal myelination holds potential for the treatment of SCI. In the clinical setting, such therapy may help these patients, including those with complete functional injury and those with white matter preservation. Accordingly, it appears reasonable that improving axonal myelination and the conductive capacity of surviving axons will be of great benefit in patients with mild to moderate injury of the spinal cord. We here present a review of the pathophysiology and mechanisms of oligodendrocyte death and axonal demyelination that follow injury to the spinal cord, and discuss the potential for treating them. Because cell transplantation has recently become a promising strategy for replacing lost oligodendrocytes and improving axonal myelination in SCI, we also discuss the significance of cell transplantation as a novel approach to treating SCI.