Inducing Neural Plasticity After Spinal Cord Injury To Recover Impaired Voluntary Movement
Borrell, Jordan Alexander
University of Kansas
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Spinal cord injury (SCI) is often an incapacitating neural injury most commonly caused by a traumatic blow to the spine. A SCI causes damage to the axons that carry sensory and motor signals between the brain and spinal cord, and in turn, the rest of the body. Depending on the severity and location of a SCI, many corticospinal axons and other descending motor pathways can remain intact. Moderate spontaneous functional recovery occurs in patients and animal models following incomplete SCI. This recovery is linked to changes occurring via the remaining pathways and throughout the entire nervous system, which is generally referred to as neuronal plasticity. It has been shown that plasticity can be induced via electrical stimulation of the brain and spinal cord targeting specific descending pathways, which can further improve impaired motor function. Most importantly, it has been shown that activity dependent stimulation (ADS), which is based on mechanisms of spike timing-dependent plasticity, can strengthen remaining pathways and promote functional recovery in various preclinical injury models of the central nervous system. The purpose of this dissertation was to determine if precisely-timed stimulation of the spinal cord triggered by the firing of neurons in the hindlimb motor cortex would result in potentiation of corticospinal connections as well as enhance hindlimb motor recovery after spinal cord contusion. In order to achieve this, we needed to determine the optimal neurophysiological conditions which would allow activity dependent stimulation (ADS) to facilitate enhanced communication between the cerebral cortex and spinal cord motor neurons. Thus, this dissertation project investigated three specific aims. The first study determined the effects of a contusive spinal cord injury on spinal motor neuron activity, corticospinal coupling, and conduction time in rats. It was discovered that spinal cord responses could still be evoked after spinal cord contusion, most likely via the cortico-reticulo-spinal pathway. The second study determined the optimal spike-stimulus delay for increasing synaptic efficacy in descending motor pathways using an ADS paradigm in an acute, anesthetized rat model of SCI. It was discovered that bouts of ADS conditioning can increase synaptic efficacy in intact descending motor pathways, as measured by cortically evoked activity in the spinal cord, after SCI. The third study determined whether spike-triggered intraspinal microstimulation (ISMS), using optimized spike-stimulus delays, results in improved motor performance in an ambulatory rat model of SCI. It was determined that ADS therapy can enhance the behavioral recovery of locomotor function after spinal cord injury. The results from this study indicate that activity-dependent stimulation is an effective treatment for behavioral recovery following a moderate spinal cord contusion in the rodent. The implications of these results have the potential to lead to a novel treatment for a variety of neurological disease and disorders.
- Dissertations 
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