• 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

    Modulation of ischemia- reperfusion injury in mammalian hibernators and non-hibernators: a comparative study

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Bhowmick_S_2017.pdf
    Size:
    14.45Mb
    Format:
    PDF
    Download
    Author
    Bhowmick, Saurav
    Chair
    Drew, Kelly L.
    Committee
    Kuhn, Thomas B.
    Duffy, Lawrence K.
    Oliver, Scott R.
    Keyword
    Cerebral ischemia
    Arctic ground squirrel
    Hibernation
    Metabolism
    Mammals
    Reperfusion injury
    Reperfusion (Physiology)
    Metadata
    Show full item record
    URI
    http://hdl.handle.net/11122/8112
    Abstract
    Events characterized by ischemia/reperfusion (I/R), such as stroke and cardiac arrest, are among the most frequent causes of debilitating neurological injury and death worldwide. During ischemia, the brain experiences oxygen and nutrition deprivation due to lack of blood flow, and tissue damage ensues. Arctic ground squirrel (AGS; Urocitellus parryii), a hibernating species has the innate ability to survive profound decreases in blood flow (ischemia) during torpor and return of blood flow (reperfusion) during intermittent euthermic periods without any neurological deficit. However, the mechanisms by which AGS tolerate the extreme fluctuations in blood flow remain unclear. The main focus of this thesis is to investigate the modulation of I/R injury in mammalian hibernators and non-hibernators. The first study validates the microperfusion approach for studying in vitro I/R injury (oxygen glucose deprivation, OGD) modeled in acute hippocampal slices and investigates the complex interactions of glutamate-mediated excitotoxicity with acidosis-mediated acidotoxicity to understand the role of acid-sensing ion channels (ASIC1a) and pH in mediating cellular injury during OGD. Using an ischemic tolerant animal model, AGS, the second and third studies explore if hibernation season or state influences tolerance to I/R injury and tests hypotheses regarding mechanisms involving nitric oxide and superoxide radicals in mediating cellular damage during cerebral I/R. Together, this dissertation demonstrates that when OGD is combined with acidosis as occurs in vivo, acidotoxicity mediated via ASIC1a occurs but low pH abolishes NMDAR mediated excitotoxicity. This dissertation also presents evidence that AGS tolerate OGD injury independent of hibernation season and state. At the tissue level, when tissue temperature is normalized to 36°C despite ATP depletion, ionic derangement, tissue acidosis, and excitatory neurotransmitter efflux, AGS hippocampus resists OGD injury. Finally, the dissertation shows that AGS resist brain injury caused by ONOO- generated from NO or O2•− during OGD while rat brain tissue succumbs to this mechanism of injury.
    Description
    Dissertation (Ph.D.) University of Alaska Fairbanks, 2017
    Date
    2017-12
    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.