Benefit of chondroitinase ABC on sensory axon regeneration in a laceration model of spinal cord injury in the rat.
BACKGROUND
Chondroitin sulfate proteoglycans are up-regulated in the spinal cord after SCI, creating a molecular barrier inhibitory to axon growth. Chondroitinase ABC degrades CSPGs in vitro and in vivo.


METHODS
We studied whether IT ChABC promotes axonal regeneration in a laceration model of SCI. Three groups of Sprague-Dawley rats were used: control and rats treated with low-dose and high-dose IT ChABC. Chondroitin sulfate proteoglycan breakdown products were measured by 2-B-6 expression, and intact CSPGs by CS-56 expression. Sensory axonal regeneration was traced after CTB injection into the median, ulnar, and sciatic nerves.


RESULTS
CS-56 expression was down-regulated and 2-B-6 expression was increased in the groups treated with IT ChABC but not in the control. Laminin and GFAP immunoreactivity was unaltered in the ChABC groups. The number of axons growing into the scar was 3.1 times greater (P < .01) in the high-dose ChABC group and 2.1 times greater (P < .01) in the low-dose group compared with the controls. The length of axonal growth after high- and low-dose ChABC was 9.9 (P < .01) and 8.3 (P < .01) times greater, respectively, than in the control group. Axons extended across the lesion gap and into the distal spinal cord stump in 2 of 8 (low dose) and in 3 of 9 (high dose) rats compared with none in the control group.


CONCLUSIONS
Intrathecal ChABC administration caused a slight decrease in CSPGs in the scar after a laceration SCI with a minimal increase in sensory axonal regeneration into and across the laceration gap.
Shields
Lisa B E
LB
Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Zhang
Yi Ping
YP
Burke
Darlene A
DA
Gray
Rebecca
R
Shields
Christopher B
CB
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002574:Cervical Vertebrae; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage / Q000494:pharmacology*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007278:Injections, Spinal; D022125:Lacerations / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D011508:Chondroitin Sulfate Proteoglycans; D019765:Chondroitin ABC Lyase