Evaluation of endothelin-1 and MMPs-2, -9, -14 in cerebrospinal fluid as indirect indicators of blood-brain barrier dysfunction in chronic canine hypothyroidism

Res Vet Sci. 2016 Apr:105:115-20. doi: 10.1016/j.rvsc.2016.01.021. Epub 2016 Jan 27.

Abstract

Chronic canine hypothyroidism is associated with blood-brain barrier (BBB) disruption. We hypothesized that this change is mediated by endothelin-1(ET-1) and matrix metalloproteinases (MMP) -2, -9, and -14, as evidenced by increased concentrations of these proteins in cerebrospinal fluid (CSF) compared to controls. CSF from 18 dogs, 9 controls and 9 with experimentally induced hypothyroidism was collected before and 6, 12, and 18 months after induction of hypothyroidism. Concentrations of ET-1 using an ELISA kit, and for MMP-2, -9, and -14 using gelatinase zymography were measured in CSF. ET-1 was undetectable in CSF of control and hypothyroid dogs at all time-points. Constitutively expressed MMP-2 was detectable in CSF samples in all dogs at all time-points. No other MMPs were detectable in CSF. No differences in CSF concentrations of ET-1 and MMP-2, 9, and 14 were found between hypothyroid and euthyroid dogs. Therefore, ET-1 and MMP-2, 9, and 14 are unlikely to be primary mediators of BBB damage in chronically hypothyroid dogs.

Keywords: Blood–brain barrier; Canine; Hypothyroidism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / physiopathology*
  • Chronic Disease
  • Dog Diseases / physiopathology*
  • Dogs
  • Endothelin-1 / metabolism*
  • Enzyme-Linked Immunosorbent Assay / veterinary
  • Female
  • Hypothyroidism / physiopathology
  • Hypothyroidism / veterinary*
  • Metalloendopeptidases / metabolism*

Substances

  • Endothelin-1
  • Metalloendopeptidases