Endothelin-1 Immunoreactivity and its Association with Intramedullary Hemorrhage and Myelomalacia in Naturally Occurring Disk Extrusion in Dogs

Abstract

BACKGROUND: The pathophysiology of ascending/descending myelomalacia (ADMM) after canine intervertebral disk (IVD) extrusion remains poorly understood. Vasoactive molecules might contribute. HYPOTHESIS/OBJECTIVES: To investigate the immunoreactivity of endothelin-1 (ET-1) in the uninjured and injured spinal cord of dogs and its potential association with intramedullary hemorrhage and extension of myelomalacia. ANIMALS: Eleven normal control and 34 dogs with thoracolumbar IVD extrusion. METHODS: Spinal cord tissue of dogs retrospectively selected from our histopathologic database was examined histologically at the level of the extrusion (center) and in segments remote from the center. Endothelin-1 immunoreactivity was examined immunohistochemically and by in situ hybridization. Associations between the immunoreactivity for ET-1 and the severity of intramedullary hemorrhage or the extension of myelomalacia were examined. RESULTS: Endothelin-1 was expressed by astrocytes, macrophages, and neurons and only rarely by endothelial cells in all dogs. At the center, ET-1 immunoreactivity was significantly higher in astrocytes (median score 4.02) and lower in neurons (3.21) than in control dogs (3.0 and 4.54) (P < .001; P = .004) irrespective of the grade of hemorrhage or myelomalacia. In both astrocytes and neurons, there was a higher ET-1 immunoreactivity in spinal cord regions remote from the center (4.58 and 4.15) than in the center itself (P = .013; P = .001). ET-1 mRNA was present in nearly all neurons with variable intensity, but not in astrocytes. CONCLUSION AND CLINICAL IMPORTANCE: Enhanced ET-1 immunoreactivity over multiple spinal cord segments after IVD extrusion might play a role in the pathogenesis of ADMM. More effective quantitative techniques are required