Increase in oxidative stress biomarkers in dogs with ascending-descending myelomalacia following spinal cord injury.
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.
Center for Paralysis Research, Dept. of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, United States.
Andrew
A
Marquis
Dept. of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, United States.
Rebecca A
RA
Packer
Center for Paralysis Research, Dept. of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, United States.
Richard B
RB
Borgens
Center for Paralysis Research, Weldon School of Biomedical Engineering, School of Industrial Engineering, Purdue University, United States. Electronic address: bsd@purdue.edu.
Bradley S
BS
Duerstock
D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism; D003401:Creatine / Q000652:urine; D004285:Dogs; D005260:Female; D005978:Glutathione / Q000378:metabolism; D028421:Isoprostanes / Q000652:urine; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology; D013118:Spinal Cord Diseases / Q000209:etiology*; D013119:Spinal Cord Injuries / Q000150:complications* / Q000662:veterinary*
D015415:Biomarkers; D018821:CD18 Antigens; D028421:Isoprostanes; D005978:Glutathione; D003401:Creatine
8-Isoprostane; A–D myelomalacia; Canine; Secondary injury; Spinal cord trauma