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反义波形蛋白cDNA联合软骨素酶ABC可促进大鼠脊髓损伤后轴突再生和功能恢复。

Antisense vimentin cDNA combined with chondroitinase ABC promotes axon regeneration and functional recovery following spinal cord injury in rats.

作者信息

Xia Yongzhi, Yan Yi, Xia Haijian, Zhao Tianzhi, Chu Weihua, Hu Shengli, Feng Hua, Lin Jiangkai

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Department of Neurosurgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.

出版信息

Neurosci Lett. 2015 Mar 17;590:74-9. doi: 10.1016/j.neulet.2015.01.073. Epub 2015 Jan 29.

Abstract

The formation of glial scar restricts axon regeneration after spinal cord injury (SCI) in adult mammalian. Chondroitin sulfate proteoglycans (CSPGs) are mostly secreted by reactive astrocytes, which form dense scar tissues after SCI. Chondroitinase ABC (ChABC), which can digest CSPGs, is a promising therapeutic strategy for SCI. However, to date ChABC has exhibited only limited success in the treatment of chronic SCI. The intermediate filament protein vimentin underpins the cytoskeleton of reactive astrocytes. We targeted glial scar in injured spinal cord by sustained infusion of ChABC and antisense vimentin cDNA. Using anterograde tracing, BBB scoring and hind limb placing response, we found that this combined treatment promoted axon regeneration and functional recovery after SCI in rats. Our results indicate that axon regeneration may be promoted by modified physical and biochemical characteristics of intra- and extracellular architecture in glial scar tissues. Theses findings could potentially help us to understand better the composition of glial scar in central nervous system injury.

摘要

在成年哺乳动物中,胶质瘢痕的形成会限制脊髓损伤(SCI)后的轴突再生。硫酸软骨素蛋白聚糖(CSPGs)主要由反应性星形胶质细胞分泌,这些细胞在脊髓损伤后形成致密的瘢痕组织。能够消化CSPGs的软骨素酶ABC(ChABC)是一种很有前景的脊髓损伤治疗策略。然而,迄今为止,ChABC在慢性脊髓损伤治疗中仅取得了有限的成功。中间丝蛋白波形蛋白支撑着反应性星形胶质细胞的细胞骨架。我们通过持续输注ChABC和反义波形蛋白cDNA来靶向损伤脊髓中的胶质瘢痕。通过顺行示踪、BBB评分和后肢放置反应,我们发现这种联合治疗促进了大鼠脊髓损伤后的轴突再生和功能恢复。我们的结果表明,轴突再生可能通过胶质瘢痕组织中细胞内和细胞外结构的物理和生化特性改变而得到促进。这些发现可能有助于我们更好地理解中枢神经系统损伤中胶质瘢痕的组成。

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