KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Neurochemical Investigation of Locally Induced Epilepsy and Subsequent Oxidative Damage Using Microdialysis Sampling

    Thumbnail
    View/Open
    Furness_ku_0099D_15131_DATA_1.pdf (2.904Mb)
    Issue Date
    2017-05-31
    Author
    Furness, Amanda Marie
    Publisher
    University of Kansas
    Format
    198 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Chemistry
    Rights
    Copyright held by the author.
    Metadata
    Show full item record
    Abstract
    The goal of this research was to develop and understand an anesthetized, multiple-seizure rat model for local epilepsy. Local seizures are not as well understood as global seizures due to their specificity and unpredictability. Furthermore, patients are diagnosed with epilepsy after experiencing two or more unprovoked seizures. In this model, two separate seizure episodes were induced by locally administering the epileptic agent 3-mercaptopropionic acid through a microdialysis probe to the CA1 region of the hippocampus. Upon development of the model, attenuation in glutamate release was observed in the second seizure stimulation. To investigate neurochemical and biochemical pathways which may be responsible for the glutamate diminution, the perfusion fluid was spiked with either glucose, lactate, or dihydrokainic acid. Additionally, as it is well known that high levels of extracellular glutamate can result in excitotoxicity, neuronal staining was performed to determine the neuronal viability after the induction of the first seizure. It was determined that the attenuation in glutamate release in the second seizure episode was primarily due to a combination of mitochondrial starvation and cell damage. The local seizure model was then used to correlate local seizure induction to oxidative damage. Glutathione (GSH) and malondialdehyde (MDA) were selected as biomarkers of oxidative stress. Intracellular levels GSH were up regulated and down regulated in hopes of modifying the amount of seizure induced oxidative damage. There was no statistically significant change in MDA formation with changing GSH levels; however, GSH did appear to serve as a release modifier of the redox cycle. Extracellular GSH increased significantly during the seizure induction and returned to basal after the seizure ended. This increase in extracellular GSH concentration can be accounted for by astrocytes and glial cells releasing GSH to counteract reactive oxygen species produced during the seizure. Additional experiments need to be done in order to make further conclusions; however, it is evident that there is a correlation between seizures and oxidative stress. Finally, Appendix I describes a small in vitro pharmacokinetic project using microdialysis sampling to measure plasma protein binding values of commercially available drugs with the ultimate goal of applying the technique for in vivo studies.
    URI
    http://hdl.handle.net/1808/26936
    Collections
    • Dissertations [3958]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps