Effect of Dynamin-2 Gene Modified OECs on Functional and Molecular Neuroprotection After Spinal Cord Injury in Rats

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Zhijie Yin, Zhiyong Zhang, Haiming Li, Xingping Zhang, Baozhe Jin
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Abstract

Spinal cord injury (SCI) imposes a significant economic burden on individuals and society, with limited options for repairing the central nervous system after injury. Cell transplantation therapy, particularly using olfactory ensheathing cells (OECs), has shown promise. However, the neuroprotective mechanisms underlying genetically modified OECs remain unclear. This study aimed to investigate the effects of Dynamin-2 (Dnm2) gene-modified OECs (Dnm2-OECs) on SCI repair in a rat model. OECs were harvested from three-day-old rats. Adult rats were divided into sham, SCI, SCI-OEC, and SCI-Dnm2-OECs groups. Dnm2-OECs were transplanted one day post-SCI model, and recovery was assessed through BBB scores, histological analyses, and molecular markers of inflammation. Results showed that the purity and infection efficiency of OECs were 87.28 ± 7.65% and 89.04 ± 5.56%, respectively. Dnm2-OECs survived for at least 28 days post-transplantation and significantly improved BBB scores by day 21. Additionally, neuronal counts increased, syringomyelia decreased, demyelination lessened, and mitochondrial structure improved. Dnm2 levels rose in spinal tissue, while NF-κB pathway proteins and pro-inflammatory cytokines (TRAF6, IL-17, IL-1β and TNF-α) were reduced. Microglial cells (Iba1) decreased correspondingly. These results indicate that Dnm2-OECs transplantation enhances neurological recovery after by inhibiting the NF-κB signaling pathway, offering a potential therapeutic strategy for SCI repair.

动力蛋白-2基因修饰oec对大鼠脊髓损伤后神经功能和分子保护的影响。
脊髓损伤(SCI)给个人和社会带来了巨大的经济负担,损伤后中枢神经系统的修复选择有限。细胞移植治疗,特别是使用嗅鞘细胞(OECs),已经显示出希望。然而,转基因oec的神经保护机制尚不清楚。本研究旨在探讨动力蛋白-2 (Dnm2)基因修饰的OECs (Dnm2-OECs)对大鼠脊髓损伤修复的影响。oec取自3天大的大鼠。成年大鼠分为假手术组、SCI组、SCI- oec组和SCI- dnm2 - oec组。dnm2 - oec在脊髓损伤后1天移植,通过BBB评分、组织学分析和炎症分子标志物评估恢复情况。结果oec的纯度为87.28±7.65%,感染效率为89.04±5.56%。Dnm2-OECs在移植后存活至少28天,并在第21天显著改善BBB评分。此外,神经元计数增加,脊髓空洞减少,脱髓鞘减少,线粒体结构改善。脊髓组织Dnm2水平升高,NF-κB通路蛋白和促炎因子(TRAF6、IL-17、IL-1β、TNF-α)降低。小胶质细胞(Iba1)相应减少。这些结果表明,Dnm2-OECs移植通过抑制NF-κB信号通路促进脊髓损伤后的神经恢复,为脊髓损伤修复提供了一种潜在的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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