Therapeutic time window for the application of chondroitinase ABC after spinal cord injury.
Rats with a crush in the dorsal funiculi of the C4 segment of the spinal cord were treated with chondroitinase ABC delivered to the lateral ventricle, receiving 6 intraventricular injections on alternate days. In order to investigate the time window of efficacy of chondroitinase, treatment was begun at the time of injury or after a 2, 4 or 7 days delay. Behavioural testing over 6 weeks showed that acutely treated animals showed improved skilled forelimb reaching compared to penicillinase controls. Forelimb contact placing recovered in treated animals but not controls, and gait analysis showed recovery towards normal forelimb stride length in treated animals but not controls. Chondroitinase-treated animals showed greater axon regeneration than controls. The treatment effect on contact placing, stride length and axon regeneration was not dependent on the timing of the start of treatment, but in skilled paw reaching acutely treated animals recovered better function. The area of chondroitinase ABC digestion visualized by stub antibody staining included widespread digestion around the lateral ventricles and partial digestion of cervical spinal cord white matter, but not grey matter.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001710:Biotin / Q000031:analogs & derivatives; D019765:Chondroitin ABC Lyase / Q000627:therapeutic use*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003911:Dextrans; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005552:Forelimb / Q000503:physiopathology; D005684:Gait / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D011712:Pyramidal Tracts / Q000187:drug effects / Q000473:pathology; D051381:Rats; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D011508:Chondroitin Sulfate Proteoglycans; D003911:Dextrans; D005904:Glial Fibrillary Acidic Protein; C076397:biotinylated dextran amine; D001710:Biotin; C087857:protein kinase C gamma; D011493:Protein Kinase C; D019765:Chondroitin ABC Lyase