Review Of The Pathogenesis And Treatment Of Acute Spinal Cord Injury And Investigation Into The Use Of Urine 3-Hpma As A Novel Biomarker Of Secondary Injury After Acute Spinal Cord Injury In The Dog

Acute spinal cord injury (ASCI) has two pathophysiological stages of injury: the primary injury and the secondary injury cascade. Primary injury includes the initial or mechanical insult to the spinal cord. Secondary injury is a cascade of biochemical events that propagates damage of adjacent, healthy tissue increasing the overall volume of spinal cord tissue that is affected. Acrolein is a toxic byproduct of lipid peroxidation produced during secondary injury. A metabolite of acrolein-glutathione adduct found in urine, 3-HPMA, has recently been shown to increase after spinal cord injury in a rat model. The aim of our study was to apply this urine 3-HPMA assay to dogs to indirectly quantify acrolein levels resulting from ASCI due to intervertebral disc herniation (IVDH). Urine was collected from ten client-owned dogs with ASCI upon presentation to PUVTH and analyzed for the acrolein metabolite, 3-HPMA per gram of creatinine. These concentrations were compared with urinary 3-HPMA levels from 10 healthy, control dogs. Mean urine 3-HPMA of ASCI dogs with IVDH (8.52 μmol 3-HPMA/g Cre) was significantly higher than the mean from control dogs (3.28 μmol 3-HPMA/g Cre). Therefore, urine 3-HPMA is higher in dogs after ASCI due to IVDH therefore supporting an important role of lipid peroxidation in canine ASCI. This study supports the use of urine 3-HPMA in future clinical trials to measure the effect of therapeutic intervention targeted at reducing acrolein concentration after ASCI