A self-assembling peptide reduces glial scarring, attenuates post-traumatic inflammation and promotes neurological recovery following spinal cord injury

被引:86
作者
Liu, Yang [1 ,2 ]
Ye, Hui [1 ,2 ]
Satkunendrarajah, Kajana [1 ,2 ]
Yao, Gordon S. [1 ,2 ]
Bayon, Yves [3 ]
Fehlings, Michael G. [1 ,2 ,4 ,5 ]
机构
[1] Univ Hlth Network, Toronto Western Res Inst, Dept Genet & Dev, Toronto, ON, Canada
[2] Univ Hlth Network, Krembil Neurosci Ctr, Spinal Program, Toronto, ON, Canada
[3] Covidien Sofradim Prod, Trevoux, France
[4] Univ Toronto, Dept Surg, Toronto, ON M5T 2S8, Canada
[5] Univ Toronto, Inst Med Sci, Toronto, ON M5T 2S8, Canada
基金
加拿大健康研究院;
关键词
Spinal cord injury; Self-assembling peptide; Nanofiber; Neurological recovery; NEURAL STEM-CELLS; NANOFIBERS; AXONS; REGENERATION; CNS; DIFFERENTIATION; SCAFFOLDS; APOPTOSIS; SEVERITY;
D O I
10.1016/j.actbio.2013.06.001
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The pathophysiology of spinal cord injury (SCI) involves post-traumatic inflammation and glial scarring which interfere with repair and recovery. Self-assembling peptides (SAPs) are molecules designed for tissue engineering. Here, we tested the performance of K-2(QL)(6)K-2 (QL6), a SAP that attenuates inflammation and glial scarring, and facilitates functional recovery. We injected QL6 into the spinal cord tissue of rats 24 h after clip compression SCI. QL6 led to a significant reduction in post-traumatic apoptosis, inflammation and astrogliosis. It also resulted in significant tissue preservation as determined by quantitative histomorphometry. Furthermore, QL6 promoted axonal preservation/regeneration, demonstrated by BDA anterograde and Fluorogold retrograde tracing. In vitro experiments found that a QL6 scaffold enhanced neuronal differentiation and suppressed astrocytic development. The electrophysiology confirmed that QL6 led to significant functional improvement of axons, including increased conduction velocity, reduced refractoriness and enhanced high-frequency conduction. These neuroanatomical and electrophysiological improvements were associated with significant neurobehavioral recovery as assessed by the Basso-Beattie-Bresnahan technique. As the first detailed examination of the pathophysiological properties of QL6 in SCI, this work reveals the therapeutic potential of SAPs, and may suggest an approach for the reconstruction of the injured spinal cord. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:8075 / 8088
页数:14
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