• Login
    View Item 
    •   Home
    • University of Alaska Fairbanks
    • UAF Graduate School
    • Chemistry and Biochemistry
    • View Item
    •   Home
    • University of Alaska Fairbanks
    • UAF Graduate School
    • Chemistry and Biochemistry
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Scholarworks@UACommunitiesPublication DateAuthorsTitlesSubjectsTypeThis CollectionPublication DateAuthorsTitlesSubjectsType

    My Account

    Login

    First Time Submitters, Register Here

    Register

    Statistics

    Display statistics

    Neuroprotection in hippocampal slices from the hibernating species Arctic ground squirrel, Spermophilus parryii

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Ross_Austin_8-2005.pdf
    Size:
    111.2Mb
    Format:
    PDF
    Download
    Author
    Ross, Austin Pfeiffer
    Metadata
    Show full item record
    URI
    http://hdl.handle.net/11122/4928
    Abstract
    Stroke is the third leading cause of death in the U.S. and the leading cause of adult onset disability worldwide. Despite tremendous efforts to find therapeutics, only one currently approved treatment for stroke exists which is indicated for use in less than 5% of stroke victims. During a stroke, the brain experiences oxygen and nutrient deprivation due to lack of blood flow (i.e., ischemia) and tissue destruction ensues. Hibernating Arctic ground squirrels (AGS), Spermophilus parryii, are able to survive profound decreases in blood flow and cerebral perfusion during torpor, and return of blood flow (i.e., reperfusion) during intermittent euthermic periods without neurological damage. Hibernating species are a natural model of tolerance to insults, such as ischemia, that would be injurious to non-hibernating species, and are a novel model for investigating much needed therapeutics for pathologies such as stroke. Tolerance to traumatic brain injury demonstrated in hibernating AGS in vivo could be due to tissue properties, circulating factors or hypothermia. To investigate mechanisms of tolerance in brain of hibernating animals, the current project established a chronic culture system for hippocampal slices from AGS at 37°C. By using this in vitro approach, tissue properties of AGS brain could be assessed without effects of circulating factors or the protective nature of hypothermia. This project determined whether an intrinsic tissue tolerance to oxygen and nutrient deprivation, an in vitro model of ischemia-reperfusion, persists in chronic AGS slice culture and addressed associated mechanisms. Here, for the first time, slices from hibernating AGS were shown to possess a persistent tolerance to oxygen and nutrient deprivation. Thus, intrinsic tissue properties in hippocampus of hibernating AGS confer tolerance to oxygen and nutrient deprivation in addition to hypothermia. Evidence in the literature supports that neuroprotective factors are present in serum and tissue of hibernating animals, and here a preliminary investigation suggests that factors in AGS serum may play a role in protection in brain of hibernating AGS. Finally, a model is proposed that incorporates these findings, which suggests that mimicking properties of tissue and serum from hibernating animals in non-hibernating species may yield success in developing efficacious stroke therapeutics.
    Description
    Dissertation (Ph.D.) University of Alaska Fairbanks, 2005
    Table of Contents
    Introduction -- Hibernating species are a natural model of tolerance in which to investigate neuroprotective mechanisms -- Investigation of protective mechanisms relevant to stroke is well warrented -- Etiology of ischemia -- Pathogenesis of ischemia -- The hippocampus is selectively vulnerable to ischemia -- Hibernation as a model of neuroprotection -- Hibernation as a model of neuroprotection -- Hibernation physiology -- Evidence of neuroprotection in hibernating animals -- Evidence of protective factors in tissue and serum of hibernating species -- Hypothermia occurs during hibernation and is a therapeutic strategy for stroke -- Hippocampal slice culture is an approach to investigate neuroprotection -- Establishing a chronic culture system for Arctic ground squirrel hippocampus -- Selection of euthermic controls -- Arctic ground squirrel hippocampus is selectively vulnerable -- Scope and aims of the project -- References -- Rationale and methods for hippocampal slice culture -- Tolerance to oxygen and nutrient deprivation and N-methyl-D-aspartate persists in cultured hippocampal slices from hibernating Arctic ground squirrel -- Potential for discovery of neuroprotective factors in serum and tissue isolated from hibernating species -- Conclusion -- Summary of findings -- Alternative explanation of tolerance to oxygen and nutrient deprivation and N-methyl-D-aspartate in Arctic ground squirrel slices -- Maintenance of energy balance can yield tolerance -- Evidence of maintenance of energy balance in hibernating animals -- Proposed model of tolerance in brain of hibernating animals -- What hibernating animals and ischemi preconditioning have in common -- What can be learned from hibernating animals regarding selective vulnerability -- What can be learned from hibernating animals regarding stroke therapeutics -- References -- Appendices.
    Date
    2005-08
    Type
    Dissertation
    Collections
    Chemistry and Biochemistry

    entitlement

     
    ABOUT US|HELP|BROWSE|ADVANCED SEARCH

    The University of Alaska is an affirmative action/equal opportunity employer, educational institution and provider and prohibits illegal discrimination against any individual.

    Learn more about UA’s notice of nondiscrimination.

    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.