Composite nanofibers incorporating alpha lipoic acid and atorvastatin provide neuroprotection after peripheral nerve injury in rats
Composite nanofibers incorporating alpha lipoic acid and atorvastatin provide neuroprotection after peripheral nerve injury in rats
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DOI：
10.1016/j.ejpb.2020.05.032
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发表时间：
2020-08-01
影响因子：
4.9
通讯作者：
Eroglu, Hakan
中科院分区：
文献类型：
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作者：
Haidar, Mohammad Karim;Timur, Selin Seda;Eroglu, Hakan
尽管近30年来出现了新的治疗策略，但周围神经损伤(PNI)仍然是一个世界性的临床问题。PNIS的发病率为每年1000人中有1人。在本研究中，我们设计了一种复合纳米平台，用于周围神经损伤的双重治疗，并观察了其在大鼠坐骨神经挤压伤模型中的体内疗效。将α-硫辛酸(ALA)负载到聚乳酸-乙醇酸(PLGA)电纺纳米纤维中，以更快的方式释放药物，并将阿托伐他汀(ATR)壳聚糖(CH)纳米颗粒嵌入PLGA纳米纤维中，提供缓释作用。Yasargil夹闭器夹闭坐骨神经，夹持力50g/cm(2)。创伤后立即将纳米纤维制剂注射到受伤的神经上。采用坐骨神经功能指数(SFI)、伸肌姿势推力(EPT)、撤退反射潜伏期(WRL)和Basso、Beattie、Bresna han(BBB)测试评价术后1个月不同时间段大鼠后肢功能恢复情况。除了功能恢复评估外，还对再生的神经纤维进行了超微结构和生化分析。采用小鼠成纤维细胞系L-929和神经母细胞瘤细胞系B35，在体内实验前研究纳米纤维的细胞毒性。在局部植入含有ALA和ATR的复合纳米纤维片后，这些新型纳米复合纤维配方的神经保护潜力已被证明，这有助于在大鼠坐骨神经挤压伤模型中恢复运动和感觉功能以及神经再生。
Despite the new treatment strategies within the last 30 years, peripheral nerve injury (PNI) is still a worldwide clinical problem. The incidence rate of PNIs is 1 in 1000 individuals per year. In this study, we designed a composite nanoplatform for dual therapy in peripheral nerve injury and investigated the in-vivo efficacy in rat sciatic nerve crush injury model. Alpha-lipoic acid (ALA) was loaded into poly lactic-co-glycolic acid (PLGA) electrospun nanofibers which would release the drug in a faster manner and atorvastatin (ATR) loaded chitosan (CH) nanoparticles were embedded into PLGA nanofibers to provide sustained release. Sciatic nerve crush was generated via Yasargil aneurism clip with a holding force of 50 g/cm(2). Nanofiber formulations were administered to the injured nerve immediately after trauma. Functional recovery of operated rat hind limb was evaluated using the sciatic functional index (SFI), extensor postural thrust (EPT), withdrawal reflex latency (WRL) and Basso, Beattie, and Bresnahan (BBB) test up to one month in the post-operative period at different time intervals. In addition to functional recovery assessments, ultrastructural and biochemical analyses were carried out on regenerated nerve fibers. L-929 mouse fibroblast cell line and B35 neuroblastoma cell line were used to investigate the cytotoxicity of nanofibers before in-vivo experiments. The neuroprotection potential of these novel nanocomposite fiber formulations has been demonstrated after local implantation of composite nanofiber sheets incorporating ALA and ATR, which contributed to the recovery of the motor and sensory function and nerve regeneration in a rat sciatic nerve crush injury model.