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The effects of T-lymphocytes on secondary neurodegeneration and recovery of function after experimental spinal contusion injury

Jones, T. Bucky
http://rave.ohiolink.edu/etdc/view?acc_num=osu1090010517

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Neuroscience.
Spinal cord injury (SCI) disrupts nerve fibers carrying information between the brain and the body. The initial trauma activates secondary degenerative processes that continue for days to weeks, causing further loss of neurons and glia and expanding the region of tissue damage. The protracted nature of secondary injury provides an opportunity to intervene and rescue cells that may otherwise undergo secondary cell death. Cells of the peripheral immune system, including T-lymphocytes reactive with myelin proteins, infiltrate the injured spinal cord and contribute to post-injury sequelae. These cells can cause demyelination and axonal transection in the CNS yet also produce neurotrophic factors that may promote neuronal survival after injury. To clarify the role of myelin-reactive T-cells in SCI, transgenic (Tg) mice with a T-cell repertoire biased toward recognition of myelin proteins, were evaluated for their ability to recover from spinal contusion injury. Recovery of overground locomotor ability and reflex function were significantly impaired in Tg mice compared with non-Tg littermates. Motor deficits were associated with reduced myelin sparing at the impact site and exacerbation of neuropathology over the rostro-caudal spinal cord. Because the kinetics and magnitude of the T-cell response to SCI differ between mice and rats, the myelin-reactive T-cell response to SCI in Lewis rats was boosted by immunization with myelin basic protein (MBP). Similar to Tg mice, immunized rats demonstrated enhanced functional deficits and exacerbated neuropathology. Interestingly, rats that were immunized with adjuvants in the absence of myelin antigen demonstrated enhanced recovery of hind limb function compared with PBS-treated controls. These results raise the possibility that other T-cells, responsive to an undefined constituent of the adjuvant confer benefit to the injured spinal cord. In conclusion, the data suggest that myelin-reactive T-cells that infiltrate the injured spinal cord contribute to secondary neurodegeneration and loss of function. However, T-cells of other antigen specificities, as yet undefined, could confer benefit in the injured spinal cord. Thus, effective neuroprotection may be achieved by limiting deleterious T-cell functions, for example by inhibiting the autoimmune response to SCI, while promoting reparative functions of T-cells in the environment of the injured spinal cord.
Phillip Popovich (Advisor)
161 p.
spinal cord injury; T-lymphocytes; neuroinflammation; secondary injury

Recommended Citations

Citations

  • Jones, T. B. (2004). The effects of T-lymphocytes on secondary neurodegeneration and recovery of function after experimental spinal contusion injury [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1090010517

    APA Style (7th edition)

  • Jones, T.. The effects of T-lymphocytes on secondary neurodegeneration and recovery of function after experimental spinal contusion injury. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1090010517.

    MLA Style (8th edition)

  • Jones, T.. "The effects of T-lymphocytes on secondary neurodegeneration and recovery of function after experimental spinal contusion injury." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1090010517

    Chicago Manual of Style (17th edition)

osu1090010517
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© 2004, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.