Increase in oxidative stress biomarkers in dogs with ascending–descending myelomalacia following spinal cord injury

Abstract Multiple biochemical and immunohistochemical tests were performed to elucidate the role of oxidative stress during ascending–descending (A–D) myelomalacia by comparing dogs with this progressive terminal condition to dogs with chronic, focal spinal cord injuries (SCIs) and controls without SCI. Dogs with A–D myelomalacia exhibited increased biochemical markers for oxidative stress, including 8-isoprostane F2α and acrolein, as well as decreased endogenous glutathione with greatest changes occurring at the lesion center. Inflammation, as evident by the concentration of CD18 + phagocytes and hemorrhagic necrosis, was also exacerbated in the lesion of A–D myelomalacic spinal cord compared to focal SCI. The greatest differences in oxidative stress occurred at the lesion center and diminished distally in both spinal cords with A–D myelomalacia and focal SCIs. The spatial progression and time course of A–D myelomalacia are consistent with the development of secondary injury post-SCI. Ascending–descending myelomalacia is proposed as a clinical model that may further the understanding of the role of oxidative stress during secondary injury. Our results indicate that the pathology of A–D myelomalacia is also similar to subacute progressive ascending myelopathy in humans, which is characterized by recurrent neurodegeneration of spinal cord post-injury.