Single injection of a novel nerve growth factor coacervate improves structural and functional regeneration after sciatic nerve injury in adult rats
Single injection of a novel nerve growth factor coacervate improves structural and functional regeneration after sciatic nerve injury in adult rats
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单次注射新型神经生长因子凝聚层可改善成年大鼠坐骨神经损伤后的结构和功能再生
DOI：
10.1016/j.expneurol.2016.10.015
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发表时间：
2017-02-01
影响因子：
5.3
通讯作者：
Xiao, Jian
中科院分区：
文献类型：
--
作者：
Li, Rui;Wu, Jiang;Xiao, Jian
神经生长因子（nerve growth factor，NGF）是一种典型的神经营养因子，在中枢和周围神经系统的许多神经元的发育和维持中起着重要作用，并能促进成年期周围神经损伤后的功能恢复。然而，周围神经缺损的修复受到NGF在体内的短半衰期的阻碍，并且单独使用NGF或合成神经导管中含有的NGF的治疗劣于使用神经自体移植物（当前的金标准）。我们使用分子、组织学和行为学方法，在坐骨神经挤压损伤后的成年大鼠中测试了含有聚阳离子-聚（乙烯天冬氨酸二甘油酯; PEAD）、肝素和NGF的多价凝聚物的单次局部注射的修复能力。体外实验表明，NGF以接近100%的效率被加载到凝聚层中，并且被保护免于蛋白水解降解。在体内，凝聚体增强了NGF的生物利用度，导致30天后运动功能的显著改善（步行分析）。神经生长因子凝聚处理也与更好的体重增加和腓肠肌萎缩的减少有关。此外，光学和电子显微镜显示，有髓轴突的数量和轴突纤维比（G比）显着高于NGF凝聚处理组大鼠与对照组相比。神经组织再生标志物（MAP-2、S-100 β、MBP和GAP-43）的表达以及增殖的雪旺细胞和髓鞘-轴突关系（GFAP和NF 200）的表达也增加。这些观察结果表明，即使单次施用NGF凝聚物也可以对周围神经再生和功能恢复具有治疗价值。(C)2016 Elsevier Inc. All rights reserved.
The prototypical neurotrophin, nerve growth factor (NGF), plays an important role in the development and maintenance of many neurons in both the central and peripheral nervous systems, and can promote functional recovery after peripheral nerve injury in adulthood. However, repair of peripheral nerve defects is hampered by the short half-life of NGF in vivo, and treatment with either NGF alone or NGF contained in synthetic nerve conduits is inferior to the use of nerve autografts, the current gold standard. We tested the reparative ability of a single local injection of a polyvalent coacervate containing polycation-poly(ethylene argininylaspartate diglyceride; PEAD), heparin, and NGF, in adult rats following sciatic nerve crush injury, using molecular, histological and behavioral approaches. In vitro assays demonstrated that NGF was loaded into the coacervate at nearly 100% efficiency, and was protected from proteolytic degradation. In vivo, the coacervate enhanced NGF bioavailability, leading to a notable improvement in motor function (track walking analysis) after 30 days. The NGF coacervate treatment was also associated with better weight gain and reduction in atrophy of the gastrocnemius muscle. Furthermore, light and electron microscopy showed that the number of myelinated axons and axon to -fiber ratio (G-ratio) were significantly higher in NGF coacervate-treated rats compared with control groups. Expression of markers of neural tissue regeneration (MAP-2, S-100 beta, MBP and GAP-43), as well as proliferating Schwann cells and myelin-axon relationships (GFAP and NF200), were also increased. These observations suggest that even a single administration of NGF coacervate could have therapeutic value for peripheral nerve regeneration and functional recovery. (C) 2016 Elsevier Inc. All rights reserved.