Effects of Chondroitinase and Training in Acute SCI

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) inflicts trauma to the cells and tissues of the central nervous system and typically results in debilitating loss of function below the level of injury, for which no effective treatment exists. Chondroitin Sulfate Proteoglycans (CSPGs) an important component of the glial scar. The majority are potently inhibitory for axonal growth and hence contribute to the failure of these axons to regenerate and form functional synapses following SCI. Chondroitinase, a bacterial enzyme that catalyzes the breakdown of CSPGs, has been shown to improve motor and sensory function and enhance regeneration following SCI in various studies. It also re-establishes a period of plasticity in the ocular dominance columns when injected in the parenchyma of the visual cortex. Physical therapy in the form of various exercise paradigms, such as treadmill training or swimming has shown to improve functional recovery in both clinical and experimental settings. These training paradigms have been accompanied by increases in the levels of expression of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) and neurotrophin 4 (NT-4). There is also evidence in the literature supporting instrumental learning and plasticity in the spinal cord. Based on recent evidence comparing various training paradigms that involve either rhythmicity and/or load on recovery of sensory function, we wanted to examine the effects of acute treatment of Chondroitinase combined with training in the forceps compression model of SCI. Results of these experiments will help us understand the effects of different types of training alone and in combination with Chondroitinase on various functional and histological outcome measures. The ultimate goal is to develop Chondroitinase as a potential therapeutic for the treatment of SCI and examine its potential role in the population of patients undergoing various types of physical therapy on a routine basis.