Controlled release of chondroitinase ABC from fibrin gel reduces the level of inhibitory glycosaminoglycan chains in lesioned spinal cord
Controlled release of chondroitinase ABC from fibrin gel reduces the level of inhibitory glycosaminoglycan chains in lesioned spinal cord
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DOI：
10.1016/j.jconrel.2010.06.026
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发表时间：
2010-10-01
影响因子：
10.8
通讯作者：
Martin, Keith R.
中科院分区：
文献类型：
--
作者：
Hyatt, Alex J. T.;Wang, Difei;Martin, Keith R.
软骨素酶ABC（ChABC）是一种细菌酶，可通过降解蛋白聚糖的糖胺聚糖（GAG）侧链来增强中枢神经系统（CNS）损伤后的可塑性。用ChABC治疗的CNS病变通常显示出增强的轴突发芽和改善的功能恢复，因此对ChABC作为人类临床治疗的潜在用途有很大兴趣。当将含有ChABC的高浓度纤维蛋白凝胶植入脊髓病变附近时，在脊髓中可检测到生物活性ChABC至少三周。损伤后3周，当使用纤维蛋白递送系统时，在脊髓中检测到比脊髓内注射ChABC高近6倍的生物活性ChABC（61 +/-30 mU vs. 11 +/-4 mU）。此外，损伤后3周，在用递送系统治疗的损伤脊髓中发现的抑制性GAG水平比用ChABC注射治疗的脊髓中的GAG水平低37%。当使用输送系统时，3周后仍可以在病变中检测到初始ChABC剂量的24.4%，而使用脊柱内注射ChABC时仅为4.4%。(C)2010年爱思唯尔。All rights reserved.
Chondroitinase ABC (ChABC) is a bacterial enzyme that can enhance plasticity following injury to the central nervous system (CNS) by degrading the glycosaminoglycan (GAG) side chains of proteoglycans. CNS lesions treated with ChABC often show enhanced axonal sprouting and improved functional recovery and there is therefore much interest in the potential use of ChABC as a clinical treatment in humans. When highly concentrated fibrin gel containing ChABC was implanted adjacent to a spinal cord lesion, bioactive ChABC was detectable in the spinal cord for at least three weeks. Nearly six times more bioactive ChABC was detected in the spinal cord 3 weeks after injury when the fibrin delivery system was used vs. an intraspinal injection of ChABC (61 +/-30 mU vs. 11 +/-4 mU). Furthermore, 3 weeks after injury the level of inhibitory GAG found in injured spinal cord treated with the delivery system was 37% lower than the level of GAG in spinal cord treated with an injection of ChABC. When using the delivery system, 24.4% of the initial ChABC dose could still be detected in the lesion after 3 weeks, compared to just 4.4% when using an intraspinal injection of ChABC. (C) 2010 Elsevier By. All rights reserved.