Damage Mechanisms to Oligodendrocytes and White Matter in Central Nervous System Injury: The Australian Context

Traumatic brain injury (TBI) and spinal cord injury (SCI) present a significant contribution to the global disease burden. White matter tracts are susceptible to both the physical forces of trauma and cascades of pathological secondary degeneration. Oligodendrocytes, the myelinating cells of the central nervous system (CNS), and their precursors are particularly vulnerable cell populations and their disruption results in a loss of white matter, dysmyelination, and poor myelin repair. White matter aberrations in TBI and SCI can be visualized in vivo using a number of magnetic resonance imaging (MRI)-based modalities. Recent advances in diffusion MRI allow researchers to investigate subtle abnormalities in white matter microstructure and connectivity, resting state networks, and metabolic perturbations associated with injury. Damage to oligodendroglia underlies white matter aberrations and occurs as a result of glutamate excitotoxicity, intracellular calcium ion (Ca²⁺) overload, and oxidative damage to lipids, proteins, and DNA. Structural changes to myelin include myelin decompaction, loosening of myelin lamellae, and disruption to the node of Ranvier complex. Neuronal and functional loss accompany dysmyelination together with an increase in astro- and microgliosis. Remyelination is often partial, and more work is needed to understand deficits in remyelination post-injury to develop strategies to both protect and repair myelin and thereby preserve function. This review covers disruptions to oligodendrocyte function and white matter tract structure in the context of TBI and SCI, with an emphasis on Australian contributions in recognition of the International Neurotrauma Symposium held in Melbourne, Australia in 2020.