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

J Vet Intern Med. 2016 Jul;30(4):1099-111. doi: 10.1111/jvim.14364. Epub 2016 Jun 29.

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.

Keywords: Dog; IVD extrusion; Intramedullary hemorrhage; Myelomalacia.

MeSH terms

  • Animals
  • Case-Control Studies
  • Dog Diseases / diagnostic imaging*
  • Dog Diseases / immunology
  • Dogs
  • Endothelin-1 / immunology*
  • Female
  • Hematoma, Subdural / diagnostic imaging
  • Hematoma, Subdural / immunology
  • Hematoma, Subdural / veterinary*
  • Immunohistochemistry / veterinary
  • Intervertebral Disc Displacement / diagnostic imaging
  • Intervertebral Disc Displacement / immunology
  • Intervertebral Disc Displacement / veterinary*
  • Male
  • Severity of Illness Index

Substances

  • Endothelin-1

Associated data

  • GENBANK/AB115087.1