Sialidase, chondroitinase ABC, and combination therapy after spinal cord contusion injury.
Sialidase, chondroitinase ABC, and combination therapy after spinal cord contusion injury.
复制标题
DOI：
10.1089/neu.2012.2353
复制
发表时间：
2013-02
影响因子：
4.2
通讯作者：
A. Mountney;M. Zahner;Elizabeth R. Sturgill;Christopher J Riley;J. W. Aston;M. Oudega;L. Schramm;Andrés Hurtado;R. Schnaar
中科院分区：
文献类型：
--
作者：
A. Mountney;M. Zahner;Elizabeth R. Sturgill;Christopher J Riley;J. W. Aston;M. Oudega;L. Schramm;Andrés Hurtado;R. Schnaar
中枢神经系统轴突再生严重受阻，限制了功能恢复。部分原因是内源性轴突再生抑制剂在损伤部位积聚。这些抑制剂及其受体的靶向治疗可能促进轴突生长并增强恢复。采用脊髓挫伤大鼠模型，研究了两种细菌酶疗法对独立轴突再生抑制剂唾液酸酯酶（霍乱弧菌）和软骨素酶ABC（普通变形杆菌）的影响。通过植入渗透泵将这两种酶单独或联合输注到中度胸段脊髓挫伤部位2周。唾液酸苷酶是完全稳定的，而ChABC在2周的输注期间保持了大约30%的活性。免疫组织化学显示，注入唾液酸酶在整个脊髓灰质和白质中都有强大的作用，而ChABC的活性在表面上更强烈。唾液酸酯酶单独治疗可改善行为和解剖结果。仅用唾液酸酯酶处理的大鼠后肢运动功能显著增强，表现为较高的Basso Beattie and Bresnahan （BBB）和BBB评分，以及在水平梯子上行走错误减少。唾液酸酯酶处理的大鼠在损伤尾部也有血清素能轴突的增加。相比而言，ChABC治疗并没有增强中度脊髓挫伤后的功能恢复，也没有改变轴突数量，而双酶治疗组唾液酸酶的反应则受到抑制。我们得出结论，唾液酸酯酶输注增强脊髓挫伤的恢复，而唾液酸酯酶联合ChABC未能改善预后。
Axon regeneration in the central nervous system is severely hampered, limiting functional recovery. This is in part because of endogenous axon regeneration inhibitors that accumulate at the injury site. Therapeutic targeting of these inhibitors and their receptors may facilitate axon outgrowth and enhance recovery. A rat model of spinal cord contusion injury was used to test the effects of two bacterial enzyme therapies that target independent axon regeneration inhibitors, sialidase (Vibrio cholerae) and chondroitinase ABC (ChABC, Proteus vulgaris). The two enzymes, individually and in combination, were infused for 2 weeks via implanted osmotic pumps to the site of a moderate thoracic spinal cord contusion injury. Sialidase was completely stable, whereas ChABC retained>30% of its activity in vivo over the 2 week infusion period. Immunohistochemistry revealed that infused sialidase acted robustly throughout the spinal cord gray and white matter, whereas ChABC activity was more intense superficially. Sialidase treatment alone resulted in improved behavioral and anatomical outcomes. Rats treated exclusively with sialidase showed significantly increased hindlimb motor function, evidenced by higher Basso Beattie and Bresnahan (BBB) and BBB subscores, and fewer stepping errors on a horizontal ladder. Sialidase-treated rats also had increased serotonergic axons caudal to the injury. ChABC treatment, in contrast, did not enhance functional recovery or alter axon numbers after moderate spinal cord contusion injury, and dampened the response of sialidase in the dual enzyme treatment group. We conclude that sialidase infusion enhanced recovery from spinal cord contusion injury, and that combining sialidase with ChABC failed to improve outcomes.