Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury

• DOI: 10.1073/pnas.0905437106
• Publication Date: 2009-11-03T03:17:52Z
• Authors: Hyunjung Lee; Robert J. McKeon; Ravi V. Bellamkonda
• Keywords: Glial scar

Chondroitin sulfate proteoglycans (CSPGs) are a major class of axon growth inhibitors that up-regulated after spinal cord injury (SCI) and contribute to regenerative failure. Chondroitinase ABC (chABC) digests glycosaminoglycan chains on CSPGs can thereby overcome CSPG-mediated inhibition. But chABC loses its enzymatic activity rapidly at 37 °C, necessitating the use repeated injections or local infusions for period days weeks. These infusion systems invasive, infection-prone, clinically problematic. To this limitation, we have thermostabilized developed system sustained delivery in vivo, obviating need chronically implanted catheters pumps. Thermostabilized remained active °C vitro up 4 CSPG levels low vivo 6 weeks post-SCI when was delivered by hydrogel-microtube scaffold system. Axonal functional recovery following release versus single treatment unstabilized demonstrated significant differences digestion. Animals treated with combination neurotrophin-3 showed improvement locomotor function enhanced cholera toxin B subunit–positive sensory axons sprouting serotonergic fibers. Therefore, improving thermostability facilitates minimally sustained, is potentially effective overcoming Combination therapy neurotrophic factors enhances axonal regrowth, sprouting, SCI.