Fate of cortical motoneurons after spinal cord injury

Since the cells of origin of the corticospinal tract (CST) were first discovered 100 years ago, the question of whether these neurons die following axonal injury has been debated. To date, no study has definitively demonstrated whether retrograde cell death of the CST following spinal cord injury (SCI) is a therapeutic target. The aim of this dissertation is to resolve this controversy definitively; both by targeting retrograde cell death therapeutically, as well to prove whether this is in fact a therapeutic target following SCI.;This question was tested using an axotomizing model of SCI in Sprague Dawley rats. To test whether we could target this therapeutically, electroconvulsive seizures (ECS) were the treatment paradigm used following SCI to upregulate endogenous brain derived neurotrophic factor (BDNF). Forelimb recovery was measured to determine if animals significantly recovered gripping ability and preferential limb use following SCI with the ECS treatment. Results from this study demonstrated that ECS treatment inhibited the ability to recover forelimb function following SCI, leading us to question whether this is a therapeutic target.;Additional experiments using axotomizing and contusive SCI in rats were conducted to assess retrograde degeneration of the CST, both by looking at their cell bodies in the cortex, and their axons in the medullary pyramid. Retrograde tracing and stereology was used to count cells over time, and cell death markers were used to test whether cells displayed any signs of degeneration. Additionally, axons of the CST that pass from the brain to the spinal cord were assessed in the medullary pyramid. If the cell bodies were dying following SCI, we would see evidence of this in the medullary pyramid. Results from these studies demonstrated that the cell bodies did not display any signs of degeneration, and there were no signs of degeneration of the axons in the medullary pyramid as a result of injury. These findings conclude that CST neurons survive SCI, and that retrograde cell death of the CST is not a therapeutic target following SCI.