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Regenerative Medicine Approaches to Spinal Cord Injury

Mohrman, Ashley E
http://rave.ohiolink.edu/etdc/view?acc_num=akron1491495476427594

Abstract Details

2017, Doctor of Philosophy, University of Akron, Chemical Engineering.
Hundreds of thousands of people suffer from spinal cord injuries in the U.S.A. alone, with very few patients ever experiencing complete recovery. Complexity of the tissue and inflammatory response contribute to this lack of recovery, as the proper function of the central nervous system relies on its highly specific structural and spatial organization. The overall goal of this dissertation project is to study the central nervous system in the healthy and injured state so as to devise appropriate strategies to recover tissue homeostasis, and ultimately function, from an injured state. A specific spinal cord injury model, syringomyelia, was studied; this condition presents as a fluid filled cyst within the spinal cord. Molecular evaluation at three and six weeks post-injury revealed a large inflammatory response including leukocyte invasion, losses in neuronal transmission and signaling, and upregulation in important osmoregulators. These included osmotic stress regulating metabolites betaine and taurine, as well as the betaine/GABA transporter (BGT-1), potassium chlodride transporter (KCC4), and water transporter aquaporin 1 (AQP1). To study cellular behavior in native tissue, adult neural stem cells from the subventricular niche were differentiated in vitro. These cells were tested under various culture conditions for cell phenotype preferences. A mostly pure (>80%) population of neural stem cells could be specified using soft, hydrogel substrates with a laminin coating and interferon-¿ supplementation. To guide and possibly recruit native stem cells, as well as reduce injury in the spinal cord, an injectable delivery iv strategy is necessary. An in situ cross-linking hydrogel could increase latency and localization of treatments. In this project, a chitosan/PEG based hydrogel was tailored for CNS tissues with low swelling post-gelation, a low elastic modulus (0.37 kPa), and very low cytotoxicity. When injected into the spinal cord parenchyma, the hydrogel elicited close to the same response as the saline injected surgical sham group. Overall, these platforms can be used to manufacture future strategies to locally deliver therapeutics that combat spinal cord injury.
Nic Leipzig (Advisor)
George Chase (Committee Member)
Gang Cheng (Committee Member)
Chelsea Monty (Committee Member)
Abraham Joy (Committee Member)
Rebecca Willits (Committee Member)
264 p.
Biomedical Research; Materials Science; Neurobiology
spinal cord injury; neural stem cells; chitosan; central nervous system

Recommended Citations

Citations

  • Mohrman, A. E. (2017). Regenerative Medicine Approaches to Spinal Cord Injury [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1491495476427594

    APA Style (7th edition)

  • Mohrman, Ashley. Regenerative Medicine Approaches to Spinal Cord Injury. 2017. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1491495476427594.

    MLA Style (8th edition)

  • Mohrman, Ashley. "Regenerative Medicine Approaches to Spinal Cord Injury." Doctoral dissertation, University of Akron, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=akron1491495476427594

    Chicago Manual of Style (17th edition)

akron1491495476427594
552
© 2017, all rights reserved.
This open access ETD is published by University of Akron and OhioLINK.