Chondroitinase ABCI Improves Locomotion and Bladder Function following Contusion Injury of the Rat Spinal Cord

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Abstract
Chondroitin sulfate proteoglycans are synthesized and deposited in the spinal cord following injury. These proteoglycans may restrict regeneration and plasticity and contribute to the limited recovery seen after an injury. Chondroitinase, a bacterial enzyme that catalyzes the hydrolysis of the chondroitin chains on proteoglycans, has been shown to improve motor and sensory function following partial transection lesions of the spinal cord. To assess the effects of chondroitinase in a clinically relevant model of spinal cord injury, 128 female Long-Evans rats received either a severe, moderate, or mild contusion injury at the vertebral level T9/T10 with a forceps model and were treated for 2 weeks with chondroitinase ABCI at 0.06 Units per dose, penicillinase, or vehicle control via an intrathecal catheter placed near the injury. Motor behavior was measured by open-field testing of locomotion and bladder function monitored by measuring daily residual urine volumes. Animals treated with chondroitinase showed significant improvements in open-field locomotor activity as measured by the Basso, Beattie and Bresnahan scoring system after both severe and moderate SCI (p<0.05 and 0.01, respectively). No significant locomotor differences were observed in the mild injury group. In the moderate injury group, residual urine volumes were reduced with chondroitinase treatment by 2 weeks after injury (p<0.05) and in the severe injury group, by 6 weeks after injury (NS). These results demonstrate that chondroitinase is effective at promoting both somatic and autonomic motor recovery following a clinically relevant contusion spinal cord injury and is a candidate as a therapeutic for human spinal cord injury.