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Modeling and treatment of rat cervical spinal cord injury

Gensel, John Carib
http://rave.ohiolink.edu/etdc/view?acc_num=osu1167753874

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Neuroscience.
Spinal cord injury (SCI) is a long lasting, debilitating condition with no cure. Cervical SCI is the most common form of human SCI, often leaving patients paralyzed with a 15-20 year decrease in life expectancy. The majority of animal SCI contusion models are focused on thoracic injury. SCI at this level results in deficits almost entirely due to white matter damage that disconnects the rostral nervous system from the caudal spinal cord. Damage at the cervical level is different; in addition to the disconnection, gray matter damage affects the neurons controlling the upper extremities and diaphragm. To investigate injury at the cervical level, we characterized a unilateral C5 cervical contusion model in rats. By examining six-week behavioral recovery after SCI, we demonstrated that functional deficits are dependent upon the severity of injury. Analysis of the histopathology revealed that behavioral consequences are a result of damage to both the gray and white matter. Unilateral injury provides within-subject controls and preserves bladder and respiratory function. Many treatments for experimental rat SCI improve behavioral and histological outcomes but have yet to be implemented after human SCI. Treatments must be safe and tested in clinically relevant models to move from animals to humans. We examined the effects of three different clinically acceptable drugs. Methlyprednisolone and minocycline have anti-inflammatory effects if given after injury. Topiramate blocks glutamate receptors and hence excitotoxicity, an important component of secondary injury. Minocycline and methylprednisolone treatment yielded no significant behavioral or histological improvements when tested after moderate-severe unilateral cervical contusion injury. Topiramate was first tested in a model of excitotoxicity and then after cervical SCI and was compared to NBQX, a standard AMPA-receptor antagonists used in animal models of disease. Both drugs preserved neurons after excitotoxic injury, but only topiramate was found to protect neurons after SCI. More small and medium sized neurons were spared in the topiramate treated group compared to control 48 hours after SCI. NBQX treatment increased white matter sparing compared to control, but resulted in worse motor function compared to topiramate. Both treatments were only effective when applied after moderate-severe injury and not after mild injury.
Jacqueline Bresnahan (Advisor)
216 p.
Biology, Neuroscience
spinal cord injury; cervical; contusion; model; gray matter; neuroprotective; grooming; topiramate; minocycline; methylprednisolone; unilateral; hemicontusion; neuroprotection; translational research; excitotoxicity; glutamate; AMPA; excitotoxic; rat

Recommended Citations

Citations

  • Gensel, J. C. (2007). Modeling and treatment of rat cervical spinal cord injury [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1167753874

    APA Style (7th edition)

  • Gensel, John. Modeling and treatment of rat cervical spinal cord injury. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1167753874.

    MLA Style (8th edition)

  • Gensel, John. "Modeling and treatment of rat cervical spinal cord injury." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1167753874

    Chicago Manual of Style (17th edition)

osu1167753874
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This open access ETD is published by The Ohio State University and OhioLINK.