Single, high-dose intraspinal injection of chondroitinase reduces glycosaminoglycans in injured spinal cord and promotes corticospinal axonal regrowth after hemisection but not contusion
Single, high-dose intraspinal injection of chondroitinase reduces glycosaminoglycans in injured spinal cord and promotes corticospinal axonal regrowth after hemisection but not contusion
复制标题
DOI：
10.1089/neu.2007.0289
复制
发表时间：
2008-04-01
影响因子：
4.2
通讯作者：
Grumet, Martin
中科院分区：
文献类型：
--
作者：
Iseda, Tsutomu;Okuda, Tetsuhito;Grumet, Martin
硫酸软骨素蛋白聚糖 (CSPG) 抑制轴突生长，软骨素酶 ABC 治疗可促进某些中枢神经系统 (CNS) 损伤模型中的轴突再生。本研究的目的是（1）比较脊髓挫伤和半切模型之间 CSPG 表达的时空表现，以及（2）评估软骨素酶治疗对两种损伤模型中轴突再生的效果。半切后，损伤部位的 CSPG 免疫反应性 (IR) 在 18 天时达到峰值，但随后在 49 天时急剧下降；相比之下，CSPG-IR 在挫伤后至少 49 天仍保持较高水平。半切后，许多顺行标记的皮质脊髓束 (CST) 轴突仍靠近富含 CSPG 的病变部位，但挫伤后，大多数 CST 轴突从最富含 CSPG 的囊肿的喙部回缩约 1 毫米。损伤后 0、1、2 和 4 周椎管内注射软骨素酶可在 4 天内显着降低两种损伤模型中的 CSPG-IR，并且 CSPG-IR 在至少 3 周内保持较低水平。软骨素酶治疗后，在半切的脊髓中，许多轴突在病变部位周围生长，但在挫伤的脊髓中则没有。我们认为，半切脊髓中轴突生长的改善是由于位于切断的 CST 轴突附近的 CSPG 降解导致的抑制减少所致。然而，在脊髓挫伤中，尽管软骨素酶能有效降解，但回缩的 CST 轴突无法生长穿过富含 CSPG 的损伤部位周围的神经胶质细胞区域，这表明轴突生长的其他抑制剂持续存在于神经胶质细胞区域。
Chondroitin sulfate proteoglycans (CSPGs) inhibit axonal growth, and treatment with chondroitinase ABC promotes axonal regeneration in some models of central nervous system (CNS) injury. The aims of this study were (1) to compare the spatiotemporal appearance of CSPG expression between spinal cord contusion and hemisection models, and (2) to evaluate chondroitinase treatment effects on axonal regrowth in the two injury models. After hemisection, CSPG-immunoreactivity (IR) in the injury site rose to peak levels at 18 days but then decreased dramatically by 49 days; in contrast, CSPG-IR remained high for at least 49 days after contusion. After hemisection, many anterogradely labeled corticospinal tract (CST) axons remained close to CSPG- rich lesion sites, but after contusion, most CST axons retracted by similar to 1 mm rostral from the rostral-most CSPG- rich cyst. Intraspinal injection of chondroitinase at 0, 1, 2, and 4 weeks following injury dramatically reduced CSPG- IR in both injury models within 4 days, and CSPG- IR remained low for at least 3 weeks. After the chondroitinase treatment, many axons grew around the lesion site in hemisected spinal cords but not in contused spinal cords. We propose that improved axonal growth in hemisected spinal cords is due to decreased inhibition resulting from degradation of CSPGs located adjacent to severed CST axons. However, in spinal cord contusions, retracted CST axons fail to grow across gliotic regions that surround CSPG- rich injury sites despite efficient degradation with chondroitinase, suggesting that other inhibitors of axonal growth persist in the gliotic regions.