The present study aims to elucidate the mechanisms underlying locomotor recovery following spinal cord injury (SCI) through the investigation of Brain-Derived Neurotrophic Factor (BDNF) delivery, and inflammatory responses associated with different spinal transection methods.Chapter 2 focuses on characterizing lumbar interneurons' activity during air- stepping following chronic intrathecal BDNF delivery to the lumbar spinal cord. BDNF has demonstrated the potential to elicit full locomotor recovery in untrained spinal animals, suggesting therapeutic benefits for SCI patients. However, the effects of BDNF on large populations of neurons responsible for this recovery are not well understood. The hypothesis is that intrathecal BDNF delivery will result in significantly increased neuronal activity in the L3-L4 segments during air-stepping. A programmable, implantable mini- pump was used to deliver BDNF at 50 ng/day for 35 days post-transection. Kinematic data was collected before and after BDNF delivery, and multiunit extracellular recordings were be obtained using 64-channel microelectrode arrays. Results from analysis suggest that while BDNF evidently increases neuronal excitability in treated cats, development of locomotor recovery seems to be achieved through subtle changes in neuronal activity. Chapter 3 investigates the mechanisms behind instances of spontaneous locomotor recovery observed in the literature, which could involve endogenous BDNF or other beneficial mechanisms. It compares locomotor recovery between open-dura and closed- dura spinal transection methods in cats. Previous studies have reported inconsistent outcomes regarding spontaneous recovery and the need for treadmill training. The ii hypothesis is that an open-dura transection will lead to better recovery during treadmill locomotion in untrained spinal cats. Kinematic data and ground reaction forces were measured to assess locomotor parameters and weight-bearing abilities, providing a quantitative analysis of recovery. The results show that an open-dura transection is associated with the development of spontaneous locomotor recovery in untrained spinal cats. Chapter 3 also examines differences in the inflammatory response at the lower thoracic cord between the two spinal transection methods, given the significant role of inflammation in CNS repair and recovery. The hypothesis is that the open-dura method will result in a higher inflammatory response, characterized by increased macrophages, microglia, and BDNF levels caudal to the transection site. Immunohistochemistry (IHC) and RNA in-situ hybridization assays were used to analyze the cellular and molecular environment near the injury site. Open dura animals show a decrease inflammatory response to injury and show no evidence of endogenous BDNF caudal to the injury. These results suggest the development of spontaneous locomotor recovery associated with a transected dura can be elicited through inflammatory mechanisms alone without the need for neurotrophic intervention. / Bioengineering