Date of Award

5-2014

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Biomedical Sciences

Track

Cancer and Developmental Biology

Research Advisor

Erin Schuetz, Ph.D

Committee

Rennolds Ostrom, Ph.D. Radhakrishna Rao, Ph.D.

Keywords

Pgp, BCRP, central nervous system, bloodbrain barrier, blood-CSF barrier, arachnoid

Abstract

The central nervous system (CNS) includes the brain and spinal cord, where both possess a blood to brain and a blood to cerebrospinal fluid (CSF) barrier. The blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) regulate the passage of many molecules to maintain and protect these sensitive organs from harmful xenobiotics (i.e. drugs, pollutants, etc.) or physiologic changes (i.e. glucose, ion, or water composition). These barriers also express ABC transporters, including P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP), which are known to contribute to efflux of endogenous toxins and therapeutics from the CNS. Pgp and BCRP expression and activity are a crucial determinant of drug efficacy in the CNS and have been studied using global transporter knockout mouse models. Since the CNS compartment and location of transporters is unique at each barrier site, a global knockout model does not address questions of how each barrier site contributes to ineffectiveness of drugs getting into the CNS. This unique composition also makes developing therapeutic strategies more difficult. In order to look at each barrier independently, we have attempted to generate conditional knockout mouse models of each transporter and in each barrier site. Our BBB and BCSFB models will provide insight into the biology of drug movement within the CNS while considering each barrier site’s contribution.

DOI

10.21007/etd.cghs.2014.0280

Comments

One year embargo expired May 2015

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