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Dissertation
Neuroprotective and neuroregenerative strategies after contusion spinal cord injury
Doctor of Philosophy (Ph.D.), Drexel University
18 Dec 2008
DOI:
https://doi.org/10.17918/00008837
Abstract
Spinal cord injury (SCI) results in a devastating and permanent injury to the central nervous system. Damage to the spinal cord interrupts transmission of ascending and descending information which creates sensory and motor deficits. The degree of impairment is dependent upon the level and severity of the injury. Cervical (C) contusion injuries are most common resulting in a bruising or compression of the cord. Due to the prevalence of this form of SCI the rodent model chosen was a severe unilateral cervical contusion SCI. A mid cervical injury was created with the Infinite Horizon impactor using a force of 200 Kdyne. The first study using a C4 injury investigated function after aspiration of the lesion site and apposition of one end of a pre-degenerated peripheral nerve graft during an acute (7 day) and chronic (28 day) situation. A change in injury level was requires for subsequent studies because of the remarkable spontaneous recovery after the two initial studies with a C4 injury. Results indicated that function atter the C4 injury was not further impaired with removal of the lesion site debris of either time point. Remaining studies used the C5 injury model to investigate the neuroprotective and/or neuroregenerative consequences of acute treatment with a modified anti-inflammatory agent, pegylated interferon-[beta] (PEG IFN-[beta]). This model also was used for development and for further study of a forced exercise rehabilitation strategy. Short term studies evaluated biochemical changes in spinal cord tissue in response to SCI, exercise or PEG IFN-[beta] alone. Exercise resulted in significantly increased levels of brain-derived neurotrophic factor and reduced inflammatory cell infiltration caudal to the injury. PEG IFN-[beta] treatment resulted in a decrease of some pro-inflammatory cytokines and an increased in some anti-inflammatory cytokines. Long term behavioral assessments revealed accelerated early recovery that plateaued by five weeks post SCI and exercise. Each therapeutic approach led to beneficial effects but in combination they did not act synergistically. These results suggest several possible strategies for neuroprotection and partial recovery after SCI though further studies are needed to achieve full recovery.
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Details
- Title
- Neuroprotective and neuroregenerative strategies after contusion spinal cord injury
- Creators
- Harra Rebecca Sandrow-Feinberg
- Contributors
- John D. Houle (Advisor) - Drexel University, Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- 185 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Other Identifier
- 991021889002204721