Wang Ping, Li Jinling, Li Shuntang, Liu Yuanyuan, Gong Jiangu, He Shipei, Wu Weifeng, Tan Guohe, Liu Sijia
Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine & Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration &Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning, Guangxi, China.
Guangxi Key Laboratory of Brain Science & Guangxi Colleges and Universities Key Laboratory of Biological Molecular Medicine Research, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.
Mater Today Bio. 2024 Aug 13;28:101184. doi: 10.1016/j.mtbio.2024.101184. eCollection 2024 Oct.
Currently, the construction of novel biomimetic reduced graphene oxide (RGO)-based nanocomposites to induce neurite sprouting and repair the injured neurons represents a promising strategy in promoting neuronal development or treatment of cerebral anoxia or ischemia. Here, we present an effective method for constructing palladium-reduced graphene oxide (Pd-RGO) nanocomposites by covalently bonding Pd onto RGO surfaces to enhance neurite sprouting of cultured neurons. As described, the Pd-RGO nanocomposites exhibit the required physicochemical features for better biocompatibility without impacting cell viability. Primary neurons cultured on Pd-RGO nanocomposites had significantly increased number and length of neuronal processes, including both axons and dendrites, compared with the control. Western blotting showed that Pd-RGO nanocomposites improved the expression levels of growth associate protein-43 (GAP-43), as well as β-III tubulin, Tau-1, microtubule-associated protein-2 (MAP2), four proteins that are involved in regulating neurite sprouting and outgrowth. Importantly, Pd-RGO significantly promoted neurite length and complexity under oxygen-glucose deprivation/re-oxygenation (OGD/R) conditions, an cellular model of ischemic brain damage, that closely relates to neuronal GAP-43 expression. Furthermore, using the middle cerebral artery occlusion (MCAO) model in rats, we found Pd-RGO effectively reduced the infarct area, decreased neuronal apoptosis in the brain, and improved the rats' behavioral outcomes after MCAO. Together, these results indicate the great potential of Pd-RGO nanocomposites as a novel excellent biomimetic material for neural interfacing that shed light on its applications in brain injuries.
目前,构建新型仿生还原氧化石墨烯(RGO)基纳米复合材料以诱导神经突萌发并修复受损神经元,是促进神经元发育或治疗脑缺氧或缺血的一种有前景的策略。在此,我们提出一种通过将钯共价键合到RGO表面来构建钯还原氧化石墨烯(Pd-RGO)纳米复合材料的有效方法,以增强培养神经元的神经突萌发。如所述,Pd-RGO纳米复合材料展现出所需的物理化学特性,具有更好的生物相容性且不影响细胞活力。与对照组相比,在Pd-RGO纳米复合材料上培养的原代神经元的神经突数量和长度显著增加,包括轴突和树突。蛋白质免疫印迹分析表明,Pd-RGO纳米复合材料提高了生长相关蛋白-43(GAP-43)以及β-III微管蛋白、Tau-1、微管相关蛋白-2(MAP2)的表达水平,这四种蛋白质参与调节神经突的萌发和生长。重要的是,在氧糖剥夺/复氧(OGD/R)条件下,即缺血性脑损伤的细胞模型中,Pd-RGO显著促进了神经突长度和复杂性,这与神经元GAP-43表达密切相关。此外,使用大鼠大脑中动脉闭塞(MCAO)模型,我们发现Pd-RGO有效减小了梗死面积,减少了脑中神经元凋亡,并改善了MCAO后大鼠的行为结果。总之,这些结果表明Pd-RGO纳米复合材料作为一种新型的优秀神经接口仿生材料具有巨大潜力,为其在脑损伤中的应用提供了线索。