Chondroitin sulfate proteoglycans in spinal cord contusion injury and the effects of chondroitinase treatment.
Chondroitinase treatment of experimental spinal cord injury improves recovery of sensory, motor, and autonomic functions. Chondroitinase catalyzes the cleavage of glycosaminoglycans (GAGs) from the core proteins of chondroitin sulfate proteoglycans (CSPGs). Little is known about changes in production of these proteoglycans in the clinically relevant contusion model of spinal cord injury or if CSPG content is altered by chondroitinase treatment. Female Long-Evans rats were injured with a forceps contusion injury and treated on alternate days with chondroitinase ABCI or control enzyme via an intrathecal catheter. Spinal cords were analyzed at specific times after injury. The cord was divided in 4 mm long segments, one containing the lesion, two rostral and two caudal to the lesion. These segments were assessed for CSPG protein and message content (NG2, neurocan and phosphacan) by Western blotting and real-time PCR. CSPG protein content was increased by one day post injury for all CSPGs investigated, and was increased in all segments examined rostral and caudal to the lesion site. Significant increases in CSPG were observed with peak content detected at 7, 7 and 14 days post injury for NG2, neurocan and phosphacan, respectively. Chondroitinase treatment had little impact upon the CPSG protein content. Changes in message levels of these CSPGs are also reported. This demonstrates that expression patterns of CSPGs in contusion injury are similar to those surrounding surgical hemisection lesions and demonstrates that the sensory and motor function enhancing effects of chondroitinase are likely due to removal of GAG chains rather than reduction in CSPG content.
Iaci
Jennifer F
JF
Acorda Therapeutics, Inc., Hawthorne, New York 10532, USA.
Vecchione
Andrea M
AM
Zimber
Michael P
MP
Caggiano
Anthony O
AO
D000818:Animals; D019765:Chondroitin ABC Lyase / Q000627:therapeutic use*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D003288:Contusions / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism*; D013904:Thoracic Vertebrae; D013997:Time Factors
D011508:Chondroitin Sulfate Proteoglycans; D012333:RNA, Messenger; D019765:Chondroitin ABC Lyase