Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


Dissertation.pdf (1.65 MB)

ETD Abstract Container

Abstract Header

EVALUATION OF BLOOD-BRAIN BARRIER INTEGRITY UNDER CUPRIZONE ADMINISTRATION

Shelestak, John Wesley
http://rave.ohiolink.edu/etdc/view?acc_num=kent1574351981114558

Abstract Details

2019, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
The blood-brain barrier is an extremely important protective mechanism for the central nervous system. The blood-brain barrier is often damaged in neurodegenerative diseases and understanding how the damage occurs is vital to understanding disease progression and for the development of new therapies. The cuprizone model of toxic demyelination is a common animal model used to study the effects of demyelination and remyelination in mice. It is a useful model because the demyelination is not caused by autoimmune assault, as is the case in many models. However, historically, the cuprizone model was believed to demyelination the brain without damage to the blood-brain barrier. This study sought to examine blood-brain barrier integrity throughout the administration of cuprizone to determine if blood-brain barrier disintegration occurs and at what time during administration. Mice were fed a 0.3% diet of cuprizone and timepoints across six weeks were analyzed for changes in blood-brain barrier permeability, changes in blood-brain barrier proteins, and immune activation of cell populations known to affect blood-brain barrier permeability. Blood-brain barrier hyperpermeability was observed to be highest early under cuprizone administration three days after beginning treatment. This permeability coincided with changes to tight junction protein expression as well as mast cell activation. It preceded, however, immune activation of CNS astrocytes and microglia as well as measurable changes in myelination. These findings indicate that the blood-brain barrier is affected by cuprizone administration and the timing of this effect coincides with mast cell activation and degranulation. This provides new timepoints at which to investigate early changes during cuprizone administration as well as new targets for treatment to prevent not only blood-brain barrier alterations, but also potentially the progression of the demyelination seen under cuprizone administration.
Robert Clements (Advisor)
Jennifer McDonough (Committee Member)
Ernest Freeman (Committee Member)
Derek Damron (Committee Member)
Mikhail Chebotar (Committee Member)
90 p.
Biology; Biomedical Research; Neurobiology
Blood-Brain Barrier; Cuprizone; Demyelination; Neurodegeneration; Neuroimmunology

Recommended Citations

Citations

  • Shelestak, J. W. (2019). EVALUATION OF BLOOD-BRAIN BARRIER INTEGRITY UNDER CUPRIZONE ADMINISTRATION [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1574351981114558

    APA Style (7th edition)

  • Shelestak, John. EVALUATION OF BLOOD-BRAIN BARRIER INTEGRITY UNDER CUPRIZONE ADMINISTRATION. 2019. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1574351981114558.

    MLA Style (8th edition)

  • Shelestak, John. "EVALUATION OF BLOOD-BRAIN BARRIER INTEGRITY UNDER CUPRIZONE ADMINISTRATION." Doctoral dissertation, Kent State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=kent1574351981114558

    Chicago Manual of Style (17th edition)

kent1574351981114558
393
© 2019, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.