Date of Award

2014

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Cell Biology, Neurobiology and Anatomy

Abstract

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality globally and often results in long term disability. Unfortunately, the success of rehabilitation techniques as therapy for TBI is limited, which may be due to the growth restrictive environment of the adult central nervous system (CNS). This environment is thought to result from glial scars, lack of neurotrophic factors, and the presence of an array of growth-inhibitory molecules. One such growth-inhibitory molecule is the protein Nogo-A. Our laboratory has shown that neutralization of Nogo-A with anti-Nogo-A immunotherapy after ischemic stroke results in improvement in functional recovery in the skilled forelimb reaching task and is correlated with an increase in axonal plasticity. In the present study, we sought to determine whether anti-Nogo-A immunotherapy following TBI produces similar recovery as with ischemic stroke. Therefore, we hypothesized that anti-Nogo-A immunotherapy following TBI in the adult rat will result in enhanced axonal plasticity and improved recovery of motor function. Accordingly, adult rats were trained in the skilled forelimb reaching task and received either a TBI via controlled cortical impact (CCI) or no TBI. One week later, rats that received a TBI were administered anti-Nogo-A antibody (11C7), control antibody, or no treatment and tested for seven more weeks on the skilled forelimb reaching task to assess functional recovery. Once behavioral testing was completed, an anterograde neuroanatomical tracer was injected into the sensorimotor cortex contralateral to the TBI lesion to assess axonal plasticity. Behavioral analysis did not demonstrate whether or not there was recovery of skilled forelimb function since control animals significantly recovered by week two and almost fully by the end of the study. Subsequent neuroanatomical analysis revealed no increased neuroplasticity at the level of the red nucleus in animals treated with mAB 11C7 at week eight post-TBI. To determine if anti-Nogo-A antibodies increase functional recovery and axonal plasticity following TBI, future studies should aim to produce TBI lesions that induce lasting deficits.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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