title: Evaluation of endothelin-1 and MMPs-2, -9, -14 in cerebrospinal fluid as indirect indicators of blood-brain barrier dysfunction in chronic canine hypothyroidism.
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.
authors.affiliation: Department of Small Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, 225 Duck Pond Drive, Virginia Tech, Blacksburg, VA, 24061, United States. Electronic address: tepdvm@vt.edu.
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Pancotto
authors.affiliation: Department of Small Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, 225 Duck Pond Drive, Virginia Tech, Blacksburg, VA, 24061, United States.
authors.forename: John H
authors.initials: JH
authors.lastname: Rossmeisl
authors.affiliation: Department of Pathobiology, Virginia Maryland College of Veterinary Medicine, 225 Duck Pond Drive, Virginia Tech, Blacksburg, VA, 24061, United States.
authors.forename: William R
authors.initials: WR
authors.lastname: Huckle
authors.affiliation: Department of Small Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, 225 Duck Pond Drive, Virginia Tech, Blacksburg, VA, 24061, United States.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Inzana
authors.affiliation: Department of Pathobiology, Virginia Maryland College of Veterinary Medicine, 225 Duck Pond Drive, Virginia Tech, Blacksburg, VA, 24061, United States.
authors.forename: Kurt L
authors.initials: KL
authors.lastname: Zimmerman
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D002908:Chronic Disease; D004283:Dog Diseases / Q000503:physiopathology*; D004285:Dogs; D019332:Endothelin-1 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005260:Female; D007037:Hypothyroidism / Q000503:physiopathology / Q000662:veterinary*; D008666:Metalloendopeptidases / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D008666:Metalloendopeptidases
keywords: Blood–brain barrier; Canine; Hypothyroidism