PDF(Pubmed)
Abstract：
Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function.
摘要：
脊髓损伤（SCI）是一种严重的中枢神经系统疾病，导致不可逆转的日常活动和残疾。SCI涉及过度的炎症反应，其特征是存在高水平的促炎M1巨噬细胞，神经元线粒体能量缺乏，加重二次损伤，阻碍轴突再生。本研究深入研究SCI的机制复杂性，从神经免疫调节和线粒体功能的角度提供见解，导致促纤维化巨噬细胞表型和能量供应不足。为了应对这些挑战，我们开发了一种智能支架，将模拟酶的纳米颗粒-氧化铈（COPs）掺入纳米纤维（NS@COP）中，旨在开创一种有针对性的神经免疫修复策略，拯救巨噬细胞上的CGRP受体，同时重塑线粒体功能。我们的发现表明，整合的COP通过上调受体活性修饰蛋白1（RAMP1）恢复促炎巨噬细胞对降钙素基因相关肽（CGRP）信号的反应，CGRP受体的重要组成部分。这促进了巨噬细胞命运对抗炎促分辨率M2表型的承诺，然后减轻胶质瘢痕的形成。此外,NS@COP植入还保护神经元线粒体功能。总的来说，我们的研究结果表明,将纳米酶COP纳米颗粒整合到纳米纤维支架中的策略通过合理调节神经免疫通讯和线粒体功能,为脊髓创伤提供了一个有前景的治疗候选方案.
