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dc.contributor.authorSmart, Dee Dee Kay
dc.date.accessioned2021-05-02T18:17:20Z
dc.date.available2021-05-02T18:17:20Z
dc.date.issued2002
dc.identifier.urien
dc.identifier.urihttp://hdl.handle.net/10675.2/623990
dc.description.abstractThe restricted permeability properties of cerebral microvascular endothelium are considered to reflect the pal!city, or near complete absence, of transcytotic· vesicles (caveolae) as well as the presence of complex tight junctions. Although cerebral microvasculature lacks caveolae, caveolin-1, the principle structural and functional component of caveolae, is detected predominantly in association with endothelia throughout the adult brain. In this study, I have investigated the expression of caveolin-1 within the microvasculature of the rat neocortex using imrnunolocalization, imrnunoblot, and subcellular fractionation methodologies. Although caveolin-1 immunoreactivity was displayed principally by differentiating astroglial and neuronal cells at early developmental timepoints, caveolin- I immunoreactivity in the adult neocortex distributed predominantly to the microvascular endothelium. The change in the cellular distribution of caveolin-1 immunoreactivity was accompanied by a dramatic change in the detergentsolubility characte~ of the caveolin-·1·, protein. Because these morphological and biochemical changes in caveolin-1 expression and character paralleled the developmental maturation of interendothelial junctions, I pursued studies to determine if caveolin-1 associated with the junctional domain in forming and adult microvascular endothelia. The detergent-i11solubility character of caveoiin-1 in adult cerebral microvasculature was not altered by increased detergent solubilization, depolymerization of the actin or the microtubule cytoskeleton, or disruption of intercellular adhesions. Depletion of membrane cholesterol with saponin, however, increased the solubility of caveolin suggesting that caveolin-1 was localized within cholesterol-enriched microdomains. Both caveolin-1 and occludin revealed an enrichment in isolated junctional domain fractions. Caveolin-1 within the junctional domain fraction resolved as a 150-200 kDa protein complex, although a direct interaction with occludin was not apparent. Taken together, these data suggest that caveolin-1 expression in cerebral microvascular endothelium is associated with the formation and function of the junctional domain in cerebral microvasculatureen_US
dc.language.isoen_USen_US
dc.publisherAugusta Universityen_US
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en_US
dc.subjectcaveolin-1en_US
dc.subjectblood-brain barrieren_US
dc.subjecttight junctionsen_US
dc.titleCaveolin-1 in the cerebral microvasculature: identification and characterization within junctional domains and implications for a role in blood-brain barrier permeabilityen_US
dc.typeDissertationen_US
dc.contributor.departmentMedical College of Georgiaen_US
dc.description.advisorCameron, Richard
dc.description.committeeCameron, Patricia
dc.description.committeeGoldenring, Jim
dc.description.committeeHess, David
dc.description.committeeSmith, Silvia
dc.description.degreeDoctor of Philosophyen_US
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refterms.dateFOA2021-05-02T18:17:21Z


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