Therapeutic effect of Keratanase for chronic spinal cord injury

角蛋白酶治疗慢性脊髓损伤的疗效

• 批准号: 22791370
• 负责人: IMAGAMA Shiro
• 金额: $ 2.58万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791370/
• 关键词: 脊髄損傷; 慢性期; プロテオグリカン; ケラタン硫酸; ケラタナーゼ; 運動機能回復; 齧歯類; 慢性期治療; 酵素持続投与; 電気生理学的検討

Failure of axonal regrowth is a major obstacle to the treatment of injuries of the adult central nervous system, and proteoglycans are strong inhibitory cues. Chondroitin sulfate chains of the proteoglycan moiety have been thought to be principal in this inhibition, as the chondroitin sulfate-degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury. Here we show that the keratan sulfate-degrading enzyme keratanase II promoted the recovery of both motor and sensory function after spinal cord injury in rats. Consistent with this, keratanase II promoted axonal regrowth in vivo and in vitro. Functional recovery after spinal cord injury in rats with administration of Keratanase II in chronic phase was significantly better than those of vehicle control, but slightly more inferior than those in acute phase. This study showed that administration of Keratanase II in chronic phase was one of the therapeutic method for spinal cord injury, but further investigation would be needed, including degradation of glial scar, combination of several drugs, and rehabilitation.

轴突再生失败是成人中枢神经系统损伤治疗的主要障碍，而蛋白多糖是强烈的抑制信号。蛋白多糖部分的硫酸软骨素链被认为是这种抑制的主要原因，因为硫酸软骨素降解酶软骨素酶ABC促进了脊髓损伤后的功能恢复。在这里，我们证明了角蛋白硫酸盐降解酶-角聚糖酶II促进了大鼠脊髓损伤后运动和感觉功能的恢复。与此一致的是，角聚糖酶II促进了体内和体外的轴突再生。慢性期应用角聚糖酶II的大鼠脊髓损伤后功能恢复明显好于赋形剂对照组，但略逊于急性期。本研究表明，慢性期应用角聚糖酶II是治疗脊髓损伤的方法之一，但还需要进一步研究，包括胶质瘢痕的降解，几种药物的联合应用，以及康复。

项目成果

N-Acetylglucosamine 6-O-Sulfotransferase-1-Deficient Mice Show Better Functional Recovery after Spinal Cord Injury

• DOI: 10.1523/jneurosci.2570-09.2010
• 发表时间: 2010-04-28
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Ito, Zenya;Sakamoto, Kazuma;Kadomatsu, Kenji
• 通讯作者: Kadomatsu, Kenji

Keratan Sulfate Restricts Neural Plasticity after Spinal Cord Injury

• DOI: 10.1523/jneurosci.5120-10.2011
• 发表时间: 2011-11-23
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Imagama, Shiro;Sakamoto, Kazuma;Kadomatsu, Kenji
• 通讯作者: Kadomatsu, Kenji