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v CHAPTER 1 GENERAL INTRODUCTION  1 Pathophysiology of spinal cord injury  1 Central nervous system plasticity  11 Clinical translation of chondroitinase ABC  17 Conclusion  24 CHAPTER 2 CLINICAL TRIAL DESIGN  25 Pre-study planning  25 Patient selection and management  28 Patient randomization  33 Chondroitinase ABC preparation and delivery  34 Summary statistics  37 CHAPTER 3 GAIT EVALUATION  40 Introduction  40 Materials and methods  46 Results  50 Discussion  52 CHAPTER 4 ELECTROPHYSIOLOGIC EVALUATION  54 Introduction  54 Materials and methods  57 Results  60 Discussion  63

Phase II Double-blinded Randomized Controlled Clinical Trial of Chondroitinase ABC by Intraspinal Injection for Treatment of Severe Chronic Spinal Cord Injury in 60 Pet Dogs