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载丙戊酸壳聚糖纳米粒促进脊髓损伤后神经干细胞的增殖与分化。

Valproic Acid Labeled Chitosan Nanoparticles Promote the Proliferation and Differentiation of Neural Stem Cells After Spinal Cord Injury.

机构信息

School of Medicine, Zhejiang University, Hangzhou, China.

College of Basic Medical Sciences, Second Military Medical University, Shanghai, China.

出版信息

Neurotox Res. 2021 Apr;39(2):456-466. doi: 10.1007/s12640-020-00304-y. Epub 2020 Nov 28.

Abstract

Chitosan nanoparticles and valproic acid are demonstrated as the protective agents in the treatment of spinal cord injury (SCI). However, the effects of valproic acid-labeled chitosan nanoparticles (VA-CN) on endogenous spinal cord neural stem cells (NSCs) following SCI and the underlying mechanisms involved remain to be elucidated. In this study, the VA-CN was constructed and the effects of VA-CN on NSCs were assessed in a rat model of SCI. We found VA-CN treatment promoted recovery of the tissue and locomotive function following SCI. Moreover, administration of VA-CN significantly enhanced neural stem cell proliferation and the expression levels of neurotrophic factors following SCI. Furthermore, administration of VA-CN led to a decrease in the number of microglia following SCI. In addition, VA-CN treatment significantly increased the Tuj 1- positive cells in the spinal cord of the SCI rats, suggesting that VA-CN could enhance the differentiation of NSCs following SCI. In conclusion, these results demonstrated that VA-CN could improve the functional and histological recovery through promoting the proliferation and differentiation of NSCs following SCI, which would provide a newly potential therapeutic manner for the treatment of SCI.

摘要

壳聚糖纳米粒子和丙戊酸已被证明是治疗脊髓损伤 (SCI) 的保护剂。然而,丙戊酸标记的壳聚糖纳米粒子(VA-CN)对 SCI 后内源性脊髓神经干细胞(NSC)的影响及其潜在机制仍有待阐明。在本研究中,构建了 VA-CN,并在 SCI 大鼠模型中评估了 VA-CN 对 NSCs 的影响。我们发现 VA-CN 治疗可促进 SCI 后组织和运动功能的恢复。此外,VA-CN 的给药可显著增强 SCI 后神经干细胞的增殖和神经营养因子的表达水平。此外,VA-CN 的给药可导致 SCI 后小胶质细胞数量减少。此外,VA-CN 治疗可显著增加 SCI 大鼠脊髓中 Tuj1 阳性细胞的数量,表明 VA-CN 可促进 SCI 后 NSCs 的分化。总之,这些结果表明,VA-CN 可通过促进 SCI 后 NSCs 的增殖和分化来改善功能和组织学恢复,为 SCI 的治疗提供了一种新的潜在治疗方法。

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