title: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.|Division of Clinical Neurology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.|Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Mayer
authors.affiliation: Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.|Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Oevermann
authors.affiliation: Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.|Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Seuberlich
authors.affiliation: Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.|Division of Clinical Neurology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.|Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Vandevelde
authors.affiliation: Centre for Fish and Wildlife Health, Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Casanova-Nakayama
authors.affiliation: Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: S
authors.identifier: http://orcid.org/0000-0001-7224-2250
authors.initials: S
authors.lastname: Selimovic-Hamza
authors.affiliation: Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.|Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Bern, Switzerland.|Division of Small Animal Surgery, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Forterre
authors.affiliation: Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.|Division of Clinical Neurology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.|Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Henke
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D004283:Dog Diseases / Q000000981:diagnostic imaging* / Q000276:immunology; D004285:Dogs; D019332:Endothelin-1 / Q000276:immunology*; D005260:Female; D006408:Hematoma, Subdural / Q000000981:diagnostic imaging / Q000276:immunology / Q000662:veterinary*; D007150:Immunohistochemistry / Q000662:veterinary; D007405:Intervertebral Disc Displacement / Q000000981:diagnostic imaging / Q000276:immunology / Q000662:veterinary*; D008297:Male; D012720:Severity of Illness Index
chemical_list: D019332:Endothelin-1
keywords: Dog; IVD extrusion; Intramedullary hemorrhage; Myelomalacia