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Dern Masters Thesis Submit 5.pdf (2.64 MB)

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Evaluation of the Effects of Therapeutic Digital Hypothermia on Lamellar Signaling in Sepsis Related Laminitis

Dern, Kathryn V
http://rave.ohiolink.edu/etdc/view?acc_num=osu1492639420006617

Abstract Details

2017, Master of Science, Ohio State University, Comparative and Veterinary Medicine.
Laminitis is a debilitating, often fatal disease of the equine foot which, specifically, refers to the loss of integrity of the digital lamellae, commonly termed the suspensory apparatus of the distal phalanx. Causes of laminitis can be separated into three broad categories: sepsis related laminitis, equine metabolic syndrome associated laminitis, and supporting limb laminitis. Although the anamneses of patients afflicted by these disparate types of laminitis can be varied, many similarities can be drawn between the ultrastructural changes seen in the lamellar tissue of the affected animals: namely, stretching of the lamellar basal and parabasal epithelial cells, loss of hemidesmosomal integrity in the basal epithelial cells, and lengthening of the secondary epidermal lamellae. Recent investigations into the pathogenesis of sepsis related laminitis have implicated inflammatory signaling as a causative agent for the lamellar damage seen in acute sepsis related laminitis, and, more importantly, these investigations have discovered a decrease in lamellar inflammatory signaling with the institution of therapeutic digital hypothermia. Therapeutic digital hypothermia is the only therapy demonstrated to not only treat but prevent the lamellar damage documented to occur in sepsis related laminitis. Therefore, the aims of the first two investigations outlined in this thesis were to characterize the effect of digital hypothermia instituted after the onset of lameness on gene expression of inflammatory mediators in the oligofructose model of sepsis related laminitis. Interestingly, both experiments 1 and 2 demonstrated that, although the histopathology scores demonstrated profound cryoprotection of the lamellar tissue treated with digital hypothermia, this protection did not correlate with a decrease in lamellar inflammatory signaling. These data indicated that the increase in lamellar inflammation long noted to be present in acute sepsis related laminitis may not be the causative event leading to structural failure of the digital lamellae. Since inflammatory signaling was determined unlikely to be the source of the cryoprotective effects of digital hypothermia, growth factor signaling pathways recently investigated in the euglycemic-hyperinsulinemic clamp model of EMSAL were investigated in the oligofructose model of sepsis-related laminitis. Notably, not only were there increases in phosphorylation (indicating activation) of the same downstream effectors of growth factor signaling pathways phosphorylated in sepsis related laminitis as in EMSAL, treatment with digital hypothermia inhibited phosphorylation of these same downstream effector proteins. Thus, experiment 3 serves not only to implicate growth factor signaling pathways in the pathogenesis of sepsis related laminitis (thus establishing a pathophysiological connection between SRL and EMSAL), but also reveals a correlation between a decrease in the activation of growth factor signaling pathways and the cryoprotection conferred by therapeutic digital hypothermia.
James Belknap (Advisor)
102 p.
Veterinary Services
sepsis related laminitis; inflammation; hypothermia; cryotherapy; RPS6; growth factor signaling

Recommended Citations

Citations

  • Dern, K. V. (2017). Evaluation of the Effects of Therapeutic Digital Hypothermia on Lamellar Signaling in Sepsis Related Laminitis [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492639420006617

    APA Style (7th edition)

  • Dern, Kathryn. Evaluation of the Effects of Therapeutic Digital Hypothermia on Lamellar Signaling in Sepsis Related Laminitis. 2017. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1492639420006617.

    MLA Style (8th edition)

  • Dern, Kathryn. "Evaluation of the Effects of Therapeutic Digital Hypothermia on Lamellar Signaling in Sepsis Related Laminitis." Master's thesis, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492639420006617

    Chicago Manual of Style (17th edition)

osu1492639420006617
560
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This open access ETD is published by The Ohio State University and OhioLINK.