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紫杉醇改性胶原支架植入促进犬长距离脊髓完全横断后的功能恢复。

Taxol-modified collagen scaffold implantation promotes functional recovery after long-distance spinal cord complete transection in canines.

机构信息

Department of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha, Hunan 410008, China.

出版信息

Biomater Sci. 2018 May 1;6(5):1099-1108. doi: 10.1039/c8bm00125a.

DOI:10.1039/c8bm00125a
PMID:29528079
Abstract

Treatment of spinal cord injury (SCI) remains a clinical challenge worldwide because of the complicated inhibitory microenvironment formed post-injury, reduced axonal regenerative ability of spinal cord neurons, and scarcity of endogenous neurogenesis within the lesion center. Taxol, in addition to stabilizing microtubules, has shown potential for decreasing axonal degeneration and reducing scar formation after SCI in rodents. In this study, we further verified the therapeutic effects and clinical potential of Taxol on restriction of scar formation and promotion of neuronal regeneration and functional recovery after severe spinal cord transection in a large animal (canine) model. A linear-ordered collagen scaffold (LOCS) combined with Taxol was implanted into the injury site after the complete removal of 1 cm of spinal tissue. Afterwards, diligent nursing and multi-system rehabilitation were carried out during a half-year period of observation. The results showed that LOCS + Taxol implantation markedly promoted motor-evoked potentials and locomotion recovery. Moreover, histological analysis demonstrated that LOCS + Taxol implantation significantly increased neurogenesis and axon regeneration to reconnect the spinal cord stumps. Additionally, reduced glial scar formation was observed within the lesion site. Thus, LOCS + Taxol implantation treatment is a promising combinatorial therapy for the treatment of acute long-distance spinal cord defects.

摘要

治疗脊髓损伤 (SCI) 仍然是全球范围内的临床挑战,因为损伤后形成的复杂抑制性微环境、脊髓神经元的轴突再生能力降低以及损伤中心内内源性神经发生的缺乏。紫杉醇除了稳定微管外,还显示出减少 SCI 后轴突变性和减少疤痕形成的潜力。在这项研究中,我们在大型动物(犬)模型中进一步验证了紫杉醇在限制疤痕形成以及促进严重脊髓横断后神经元再生和功能恢复方面的治疗效果和临床潜力。在完全切除 1 厘米脊髓组织后,将线性有序胶原支架 (LOCS) 与紫杉醇联合植入损伤部位。之后,在半年的观察期间进行精心护理和多系统康复。结果表明,LOCS + Taxol 植入显著促进了运动诱发电位和运动功能的恢复。此外,组织学分析表明,LOCS + Taxol 植入显著增加了神经发生和轴突再生,以重新连接脊髓断端。此外,在损伤部位观察到少突胶质细胞疤痕形成减少。因此,LOCS + Taxol 植入治疗是治疗急性长距离脊髓缺损的一种有前途的联合治疗方法。

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