Evaluation of cerebrospinal fluid biomarkers of endothelial damage and basement membrane degradation as indirect indicators of blood-brain barrier dysfunction in chronic canine hypothyroidism

dc.contributor.authorPancotto, Theresa E.en
dc.contributor.committeechairRossmeisl, John H. Jr.en
dc.contributor.committeememberInzana, Karen D.en
dc.contributor.committeememberZimmerman, Kurt L.en
dc.contributor.committeememberHuckle, William R.en
dc.contributor.departmentVeterinary Medical Sciencesen
dc.date.accessioned2017-04-04T19:50:32Zen
dc.date.adate2011-05-16en
dc.date.available2017-04-04T19:50:32Zen
dc.date.issued2011-02-24en
dc.date.rdate2016-10-17en
dc.date.sdate2011-04-02en
dc.description.abstractA variety of neurologic illnesses including peripheral and cranial neuropathies, central vestibular disease, seizures and coma have been associated with hypothyroidism in dogs. Repeated studies have shown that there is loss of blood brain barrier (BBB) integrity in these animals. Current research has also shown the development cerebrospinal fluid abnormalities in neurologically normal hypothyroid dogs; a finding that is related to BBB degradation. This derangement may be secondary to atherosclerosis and vascular accidents. One possible mediator of vasospasm and ischemic brain injury is endothelin-1 (ET-1). Another group of mediators of vascular dysfunction that has been found in CSF of dogs with various other CNS diseases is matrix metalloproteinases (MMP). The purpose of this study was to assay molecular markers that may contribute to disruption in the blood brain barrier in chronically hypothyroid canines. We hypothesized that BBB disruption in hypothyroidism is mediated by ET-1 and MMPs, as evidenced by increased concentrations of these proteins in CSF compared to controls. Cerebrospinal fluid (CSF) previously collected from 9 control and 9 experimentally induced hypothyroid dogs was used. Administration of I-131 was used to create the experimental model. CSF from time points 0, 6, 12, and 18 months post-induction were evaluated using an ELISA kit for endothelin-1. CSF from each time point was also evaluated using gelatinase zymography to detect MMP-2,9, and 14. The endothelin assay was able to detect ET-1 in CSF as determined by a spike and recovery method. However, ET-1 was undetectable in CSF of control and hypothyroid dogs at all time points. Constitutively expressed MMP-2 was detectable in all dogs at all time points. No other MMPs were detectable in CSF. ET-1 and gelatinase MMP,-9, and -14 are not primary mediators of BBB damage in chronically hypothyroid dogs. They could be involved secondarily and may be better evaluated with different assays or in temporal association with the development of clinical signs of neurologic dysfunction. Additional research is needed to confirm this finding and to evaluate biomarkers of non-vascular components of the BBB.en
dc.description.degreeMaster of Scienceen
dc.identifier.otheretd-04022011-122741en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-04022011-122741/en
dc.identifier.urihttp://hdl.handle.net/10919/76955en
dc.language.isoen_USen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectmatrix metalloproteinaseen
dc.subjectcerebrospinal fluiden
dc.subjectdogen
dc.subjecthypothyroidismen
dc.subjectendothelinen
dc.titleEvaluation of cerebrospinal fluid biomarkers of endothelial damage and basement membrane degradation as indirect indicators of blood-brain barrier dysfunction in chronic canine hypothyroidismen
dc.typeThesisen
dc.type.dcmitypeTexten
thesis.degree.disciplineVeterinary Medical Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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