Caggiano Anthony O, Zimber Michael P, Ganguly Anindita, Blight Andrew R, Gruskin Elliott A
Acorda Therapeutics, Inc., Hawthorne, New York 10532, USA.
J Neurotrauma. 2005 Feb;22(2):226-39. doi: 10.1089/neu.2005.22.226.
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.
硫酸软骨素蛋白聚糖在脊髓损伤后合成并沉积于脊髓中。这些蛋白聚糖可能会限制再生和可塑性，并导致损伤后恢复有限。软骨素酶是一种催化蛋白聚糖上硫酸软骨素链水解的细菌酶，已被证明可改善脊髓部分横断损伤后的运动和感觉功能。为了评估软骨素酶在临床相关脊髓损伤模型中的作用，128只雌性Long-Evans大鼠在T9/T10椎体水平接受了严重、中度或轻度挫伤，采用镊子模型，并通过放置在损伤附近的鞘内导管，用每剂量0.06单位的软骨素酶ABCI、青霉素酶或载体对照治疗2周。通过开放场运动测试测量运动行为，并通过测量每日残余尿量监测膀胱功能。在严重和中度脊髓损伤后，用软骨素酶治疗的动物在通过Basso、Beattie和Bresnahan评分系统测量的开放场运动活动方面有显著改善（分别为p<0.05和0.01）。在轻度损伤组中未观察到明显的运动差异。在中度损伤组中，软骨素酶治疗使损伤后2周的残余尿量减少（p<0.05），在严重损伤组中，损伤后6周减少（无统计学意义）。这些结果表明，软骨素酶在临床上相关的挫伤性脊髓损伤后促进躯体和自主运动恢复方面是有效的，并且是人类脊髓损伤治疗的候选药物。
