ISP treatment enhances GAG-CSPG degradation by neurons. A, Systemic ISP enhances GAG-CSPG amelioration following spinal cord injury. Rats received 250k dyne thoracic level 8 contusion and treated for 7 weeks with subcutaneous injections of DMSO vehicle or 22 μg/ml ISP beginning 1 d after injury. Tissue was collected 7 weeks after last ISP treatment and stained to visualize serotonergic (5-HT) axons and GAG-CSPGs (WFA). Noninjured spinal cord of an adult rat was immunostained with WFA to visualize normal GAG-CSPG pattern. Scale bar, 500 μm. B, Quantification of 5-HT (n = 25 sections; t = 3.320, df = 64, p = 0.0015, unpaired t test) and WFA (n = 39 sections; t = 4.657, df = 84, p = 0.0001, unpaired t test) immunoreactivity in sections caudal to the injury site. C, DRG axons (Tuj1) leave digested shadows as they cross the high CSPG gradient (CS-56) in our aggrecan spot assays when treated with low concentrations of ISP (1.25 μm). Scale bar, 50 μm. Red arrows indicate regions of absent GAG-CSPGs colocalized with neuronal expression. Lines indicate median. Boxes represent quartiles. Whiskers indicate range. **p < 0.01, ***p < 0.001.