Chondroitinase ABC improves basic and skilled locomotion in spinal cord injured cats

• Published in: Experimental neurology Vol. 209; no. 2; pp. 483 - 496
• Main Authors: Tester, Nicole J., Howland, Dena R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2008
• Subjects: Animals; Behavior, Animal; Behavioral recovery; Cats; Chondroitin ABC Lyase - therapeutic use; Chondroitin sulfate glycosaminoglycans; Chondroitin sulfate proteoglycans; Disease Models, Animal; Exercise Test; Gene Expression Regulation - drug effects; Hemisection; Hindlimb - physiopathology; Locomotion - drug effects; Motor Skills - drug effects; Myelin Proteins - metabolism; Plasticity; Receptors, Cell Surface - metabolism; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - physiopathology; Time Factors; Behavioral recovery; Chondroitin sulfate glycosaminoglycans; Hemisection; Plasticity; Chondroitin sulfate proteoglycans
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2007.07.019

Chondroitin sulfate proteoglycans (CSPGs) are upregulated in the central nervous system following injury. Chondroitin sulfate glycosaminoglycan (CS GAG) side chains substituted on this family of molecules contribute to the limited functional recovery following injury by restricting axonal growth and synaptic plasticity. In the current study, the effects of degrading CS GAGs with Chondroitinase ABC (Ch'ase ABC) in the injured spinal cords of adult cats were assessed. Three groups were evaluated for 5 months following T10 hemisections: lesion-only, lesion + control, and lesion + Ch'ase ABC. Intraspinal control and Ch'ase ABC treatments to the lesion site began immediately after injury and continued every other day, for a total of 15 treatments, using an injectable port system. Delivery and in vivo cleavage were verified anatomically in a subset of cats across the treatment period. Recovery of skilled locomotion (ladder, peg, and beam) was significantly accelerated, on average, by > 3 weeks in Ch'ase ABC-treated cats compared to controls. Ch'ase ABC-treated cats also showed greater recovery of specific skilled locomotor features including intralimb movement patterns and significantly greater paw placement onto pegs. Although recovery of basic locomotion (bipedal treadmill and overground) was not accelerated, intralimb movement patterns were more normal in the Ch'ase ABC-treated cats. Qualitative assessment of serotonergic immunoreactivity also suggested that Ch'ase ABC treatment enhanced plasticity. Finally, analyses using fluorophore-assisted carbohydrate electrophoresis (FACE) indicate CS GAG content is similar in cat and human. These findings show, for the first time, that intraspinal cleavage of CS GAGs can enhance recovery of function following spinal cord injury in large animals with sophisticated motor behaviors and axonal growth requirements similar to those encountered in humans.