背景:过度的神经炎症,凋亡,胶质疤痕,脊髓损伤(SCI)引发的脱髓鞘是SCI修复的主要障碍。褐藻多糖,天然海洋植物提取物,具有广谱抗炎和免疫调节作用,被认为是治疗各种疾病的潜在药物,包括神经系统疾病.然而,其在SCI中的作用尚未得到调查。
方法:在本研究中,我们在小鼠中建立了SCI模型,并通过每天腹膜内注射不同剂量的岩藻依聚糖(10和20mg/kg)来干预损伤修复。同时,体外处理原代少突胶质前体细胞(OPCs)以验证岩藻依聚糖对OPCs的分化促进作用。Basso鼠标秤(BMS),路易斯维尔游泳量表(LSS),进行了旋转试验以测量功能恢复。免疫荧光染色,和透射电子显微镜(TEM)进行评估神经炎症,凋亡,胶质疤痕,和髓鞘再生。进行Western印迹分析以阐明髓鞘再生的潜在机制。
结果:我们的结果表明,在SCI模型中,岩藻依聚糖表现出显著的抗炎作用,并促进促炎M1型小胶质细胞/巨噬细胞向抗炎M2型的转化。岩藻依聚糖增强损伤区域的神经元和轴突的存活并改善髓鞘再生。此外,岩藻依聚糖通过激活PI3K/AKT/mTOR通路促进OPCs分化为成熟少突胶质细胞。
结论:岩藻依聚糖通过调节微环境和促进髓鞘再生来改善SCI修复。
BACKGROUND: Excessive neuroinflammation, apoptosis, glial scar, and demyelination triggered by spinal cord injury (SCI) are major obstacles to SCI repair. Fucoidan, a natural marine plant extract, possesses broad-spectrum anti-inflammatory and immunomodulatory effects and is regarded as a potential therapeutic for various diseases, including neurological disorders. However, its role in SCI has not been investigated.
METHODS: In this study, we established an SCI model in mice and intervened in injury repair by daily intraperitoneal injections of different doses of fucoidan (10 and 20 mg/kg). Concurrently, primary oligodendrocyte precursor cells (OPCs) were treated in vitro to validate the differentiation-promoting effect of fucoidan on OPCs. Basso Mouse Scale (BMS), Louisville Swim Scale (LSS), and Rotarod test were carried out to measure the functional recovery. Immunofluorescence staining, and transmission electron microscopy (TEM) were performed to assess the neuroinflammation, apoptosis, glial scar, and remyelination. Western blot analysis was conducted to clarify the underlying mechanism of remyelination.
RESULTS: Our results indicate that in the SCI model, fucoidan exhibits significant anti-inflammatory effects and promotes the transformation of pro-inflammatory M1-type microglia/macrophages into anti-inflammatory M2-type ones. Fucoidan enhances the survival of neurons and axons in the injury area and improves remyelination. Additionally, fucoidan promotes OPCs differentiation into mature oligodendrocytes by activating the PI3K/AKT/mTOR pathway.
CONCLUSIONS: Fucoidan improves SCI repair by modulating the microenvironment and promoting remyelination.