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Determination and Implications of Physicochemical Properties of the Brain

Guy, Yifat (2011) Determination and Implications of Physicochemical Properties of the Brain. Doctoral Dissertation, University of Pittsburgh.

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    Abstract

    Electroosmotic flow is a bulk fluid flow that influences solute transport through capillary conduits and porous material under the influence of an electric field. The magnitude of electroosmotic flow is proportional to the zeta-potential of the capillary or porous material. A porous material such as living tissue would need to have an appreciable zeta-potential to create electroosmotic flow in the interstitial space. Transporting solutes in and out of tissue by virtue of electroosmotic flow in principle has advantages such as avoiding pressure effects and sample dilution that accompany micropush-pull and microdialysis approaches. In order to assess the viability of this approach, it is necessary to know the zeta-potential in the tissue of interest. To address this, a method and apparatus was developed to measure the zeta-potential and tortuosity in tissue slices. The method was applied to organotypic hippocampal slice cultures. The apparatus was improved on in order to provide feedback control to maintain a constant electric field through the tissue culture. The zeta-potential of the organotypic tissue culture is -22 ± 0.8 mV and the tortuosity is 2.24 ± 0.10. With a zeta-potential of -22 mV, low electric fields applied to the brain will create electroosmotic flow. Electroosmotic flow can be directed to transport extracellular fluid from brain tissue into a conduit such as a sampling capillary. Furthermore, electroosmotic flow can be used in the opposite way to eject fluid and solutes from a capillary or pipette into brain tissue. The electroosmotic effect may be important in the widely used solute delivery method of iontophoresis. In iontophoresis, solutes are ejected into tissue via an applied current. Once in the tissue, solute transport is affected by the electroosmotic flow in the tissue and thus depends on the tissue zeta-potential. The dependence of solute transport on zeta-potential is illustrated using a set of poly(acrylamide-co-acrylic acid) hydrogels. A method of measuring the thickness of organotypic tissue cultures has also been developed. Characterization of zeta-potential and tortuosity provides the fundamentals for understanding electroosmotic flow through the extracellular space of brain tissue.


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    Item Type: University of Pittsburgh ETD
    Title: Determination and Implications of Physicochemical Properties of the Brain
    Status: Unpublished
    Abstract: Electroosmotic flow is a bulk fluid flow that influences solute transport through capillary conduits and porous material under the influence of an electric field. The magnitude of electroosmotic flow is proportional to the zeta-potential of the capillary or porous material. A porous material such as living tissue would need to have an appreciable zeta-potential to create electroosmotic flow in the interstitial space. Transporting solutes in and out of tissue by virtue of electroosmotic flow in principle has advantages such as avoiding pressure effects and sample dilution that accompany micropush-pull and microdialysis approaches. In order to assess the viability of this approach, it is necessary to know the zeta-potential in the tissue of interest. To address this, a method and apparatus was developed to measure the zeta-potential and tortuosity in tissue slices. The method was applied to organotypic hippocampal slice cultures. The apparatus was improved on in order to provide feedback control to maintain a constant electric field through the tissue culture. The zeta-potential of the organotypic tissue culture is -22 ± 0.8 mV and the tortuosity is 2.24 ± 0.10. With a zeta-potential of -22 mV, low electric fields applied to the brain will create electroosmotic flow. Electroosmotic flow can be directed to transport extracellular fluid from brain tissue into a conduit such as a sampling capillary. Furthermore, electroosmotic flow can be used in the opposite way to eject fluid and solutes from a capillary or pipette into brain tissue. The electroosmotic effect may be important in the widely used solute delivery method of iontophoresis. In iontophoresis, solutes are ejected into tissue via an applied current. Once in the tissue, solute transport is affected by the electroosmotic flow in the tissue and thus depends on the tissue zeta-potential. The dependence of solute transport on zeta-potential is illustrated using a set of poly(acrylamide-co-acrylic acid) hydrogels. A method of measuring the thickness of organotypic tissue cultures has also been developed. Characterization of zeta-potential and tortuosity provides the fundamentals for understanding electroosmotic flow through the extracellular space of brain tissue.
    Date: 21 July 2011
    Date Type: Completion
    Defense Date: 08 December 2010
    Approval Date: 21 July 2011
    Submission Date: 01 December 2010
    Release Date: 21 July 2011
    Access Restriction: No restriction; Release the ETD for access worldwide immediately.
    Patent pending: Yes
    Institution: University of Pittsburgh
    Thesis Type: Doctoral Dissertation
    Refereed: Yes
    Degree: PhD - Doctor of Philosophy
    URN: etd-12012010-153952
    Uncontrolled Keywords: tortuosity; Zeta-potential; organotypical hippocampal slice cultures; electroosmosis; electroosmotic sampling; brain; iontophoresis
    Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
    Date Deposited: 09 Oct 2012 16:20
    Last Modified: 10 Oct 2012 01:15
    Other ID: etd-12012010-153952

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