School of Medicine, Zhejiang University, Hangzhou, China.
College of Basic Medical Sciences, Second Military Medical University, Shanghai, China.
Neurotox Res. 2021 Apr;39(2):456-466. doi: 10.1007/s12640-020-00304-y. Epub 2020 Nov 28.
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.
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。
