Polysialic-Acid-Based Micelles Promote Neural Regeneration in Spinal Cord Injury Therapy,Nano Letters

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Polysialic-Acid-Based Micelles Promote Neural Regeneration in Spinal Cord Injury Therapy
Nano Letters ( IF 9.6 ) Pub Date : 2019-01-03 00:00:00 , DOI: 10.1021/acs.nanolett.8b04020
Xiao-Juan Wang ₁ , Chen-Han Peng ₁ , Shuo Zhang ₁ , Xiao-Ling Xu ₁ , Gao-Feng Shu _{1,

2} , Jing Qi ₁ , Ya-Fang Zhu ₁ , De-Min Xu ₃ , Xu-Qi Kang ₁ , Kong-Jun Lu ₁ , Fei-Yang Jin ₁ , Ri-Sheng Yu ₃ , Xiao-Ying Ying ₁ , Jian You ₁ , Yong-Zhong Du ₁ , Jian-Song Ji ₂

Affiliation

Spinal cord injury (SCI) routinely causes the immediate loss and disruption of neurons followed by complicated secondary injuries, including inflammation, oxidative stress, and dense glial scar formation. Inhibitory factors in the lesion scar and poor intrinsic neural regeneration capacity restrict functional recovery after injury. Minocycline, which has neuroprotective activity, can alleviate secondary injury, but the long-term administration of this drug may cause toxicity. Polysialic acid (PSA) is a large cell-surface carbohydrate that is critical for central nervous system development and is capable of promoting precursor cell migration, axon path finding, and synaptic remodeling; thus, PSA plays a vital role in tissue repair and regeneration. Here, we developed a PSA-based minocycline-loaded nanodrug delivery system (PSM) for the synergistic therapy of spinal cord injury. The prepared PSM exerted marked anti-inflammatory and neuroprotective activities both in vitro and in vivo. The administration of PSM could significantly protect neurons and myelin sheaths from damage, reduce the formation of glial scar, recruit endogenous neural stem cells to the lesion site, and promote the regeneration of neurons and the extension of long axons throughout the glial scar, thereby largely improving the locomotor function of SCI rats and exerting a superior therapeutic effect. The findings might provide a novel strategy for SCI synergistic therapy and the utilization of PSA in other central nervous system diseases.

中文翻译：

基于聚唾液酸的胶束促进脊髓损伤治疗中的神经再生

脊髓损伤 (SCI) 通常会导致神经元的立即丢失和破坏，然后是复杂的继发性损伤，包括炎症、氧化应激和致密胶质瘢痕形成。损伤疤痕中的抑制因素和内在神经再生能力差，限制了损伤后的功能恢复。米诺环素具有神经保护作用，可减轻继发性损伤，但长期服用该药可能引起毒性反应。聚唾液酸 (PSA) 是一种大型细胞表面碳水化合物，对中枢神经系统发育至关重要，能够促进前体细胞迁移、轴突寻路和突触重塑；因此，PSA在组织修复和再生中起着至关重要的作用。这里，我们开发了一种基于 PSA 的米诺环素负载纳米药物递送系统 (PSM)，用于脊髓损伤的协同治疗。制备的 PSM 在体外和体内均具有显着的抗炎和神经保护活性。PSM的给药可以显着保护神经元和髓鞘免受损伤，减少胶质瘢痕的形成，将内源性神经干细胞募集到病变部位，促进神经元再生和长轴突在整个胶质瘢痕处的延伸，从而在很大程度上改善SCI大鼠的运动功能并发挥优越的治疗效果。这些发现可能为 SCI 协同治疗和 PSA 在其他中枢神经系统疾病中的应用提供一种新策略。制备的 PSM 在体外和体内均具有显着的抗炎和神经保护活性。PSM的给药可以显着保护神经元和髓鞘免受损伤，减少胶质瘢痕的形成，将内源性神经干细胞募集到病变部位，促进神经元再生和长轴突在整个胶质瘢痕处的延伸，从而在很大程度上改善SCI大鼠的运动功能并发挥优越的治疗效果。这些发现可能为 SCI 协同治疗和 PSA 在其他中枢神经系统疾病中的应用提供一种新策略。制备的 PSM 在体外和体内均具有显着的抗炎和神经保护活性。PSM的给药可以显着保护神经元和髓鞘免受损伤，减少胶质瘢痕的形成，将内源性神经干细胞募集到病变部位，促进神经元再生和长轴突在整个胶质瘢痕处的延伸，从而在很大程度上改善SCI大鼠的运动功能并发挥优越的治疗效果。这些发现可能为 SCI 协同治疗和 PSA 在其他中枢神经系统疾病中的应用提供一种新策略。将内源性神经干细胞募集到病变部位，促进神经元再生和长轴突在整个胶质瘢痕处的延伸，从而大大改善SCI大鼠的运动功能，发挥优越的治疗效果。这些发现可能为 SCI 协同治疗和 PSA 在其他中枢神经系统疾病中的应用提供一种新策略。将内源性神经干细胞募集到病变部位，促进神经元再生和长轴突在整个胶质瘢痕处的延伸，从而大大改善SCI大鼠的运动功能，发挥优越的治疗效果。这些发现可能为 SCI 协同治疗和 PSA 在其他中枢神经系统疾病中的应用提供一种新策略。

更新日期：2019-01-03

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