Quercetin enhances survival and axonal regeneration of motoneurons after spinal root avulsion and reimplantation: experiments in a rat model of brachial plexus avulsion.

IF 5 3区 医学 Q2 IMMUNOLOGY Inflammation and Regeneration Pub Date : 2022-12-01 DOI:10.1186/s41232-022-00245-3
Yanfeng Huang, Xie Zhang, Qionghui Huang, Yaoxing Dou, Chang Qu, Qingqing Xu, Qiuju Yuan, Yan-Fang Xian, Zhi-Xiu Lin
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引用次数: 1

Abstract

Background: Brachial plexus avulsion (BPA) physically involves the detachment of spinal nerve roots themselves and the associated spinal cord segment, leading to permanent paralysis of motor function of the upper limb. Root avulsion induces severe pathological changes, including inflammatory reaction, oxidative damage, and finally massive motoneuron apoptosis. Quercetin (QCN), a polyphenolic flavonoid found in abundance in fruit and vegetables, has been reported to possess anti-oxidative, anti-inflammatory, and neuroprotective effects in many experimental models of both central nervous system (CNS) and peripheral nervous system (PNS) disorders. The purpose of this study was to investigate whether QCN could improve motor function recovery after C5-7 ventral root avulsion and C6 reimplantation in a rat model of BPA.

Methods: The right fifth cervical (C5) to C7 ventral roots were avulsed followed by re-implantation of only C6 to establish the spinal root avulsion plus re-implantation model in rats. After surgery, rats were treated with QCN (25, 50, and 100 mg/kg) by gavage for 2 or 8 consecutive weeks. The effects of QCN were assessed using behavior test (Terzis grooming test, TGT) and histological evaluation. The molecular mechanisms were determined by immunohistochemistry analysis and western blotting.

Results: Our results demonstrated that QCN significantly expedited motor function recovery in the forelimb as shown by the increased Terzis grooming test score, and accelerated motor axon regeneration as evidenced by the ascending number of Fluoro-Ruby-labeled and P75-positive regenerative motoneurons. The raised ChAT-immunopositive and cresyl violet-stained neurons indicated the enhanced survival of motoneurons by QCN administration. Furthermore, QCN treatment markedly alleviated muscle atrophy, restored functional motor endplates in biceps and inhibited the microglial and astroglia activation via modulating Nrf2/HO-1 and neurotrophin/Akt/MAPK signaling pathway.

Conclusions: Taken together, these findings have for the first time unequivocally indicated that QCN has promising potential for further development into a novel therapeutic in conjunction with reimplantation surgery for the treatment of BPA. .

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槲皮素促进脊髓根撕脱和再植后运动神经元的存活和轴突再生:臂丛撕脱大鼠模型的实验。
背景:臂丛撕脱症(Brachial plexus avulsion, BPA)在物理上涉及脊神经根本身和相关脊髓段的脱离,导致上肢运动功能的永久性瘫痪。根撕脱引起严重的病理改变,包括炎症反应、氧化损伤,最终导致大量运动神经元凋亡。槲皮素(QCN)是一种在水果和蔬菜中大量发现的多酚类黄酮,据报道,槲皮素在中枢神经系统(CNS)和周围神经系统(PNS)疾病的许多实验模型中具有抗氧化、抗炎和神经保护作用。本研究的目的是探讨QCN是否能改善大鼠双酚a模型C5-7腹根撕脱和C6再植后的运动功能恢复。方法:取大鼠右侧第五颈椎(C5) ~ C7椎弓根撕脱后仅C6椎弓根再植入术,建立脊髓根撕脱+再植入术模型。术后大鼠分别给予QCN(25、50、100 mg/kg)灌胃,连续2、8周。采用行为学测试(Terzis grooming test, TGT)和组织学评估QCN的效果。通过免疫组织化学和免疫印迹分析确定其分子机制。结果:我们的研究结果表明,QCN显著加速了前肢运动功能的恢复,这可以从Terzis修饰测试分数的增加中看出;QCN显著加速了前肢运动轴突的再生,这可以从氟红宝石标记和p75阳性再生运动神经元的数量增加中看出。chat免疫阳性和甲酚紫染色神经元升高,表明给药后运动神经元存活增强。此外,QCN通过调节Nrf2/HO-1和神经营养因子/Akt/MAPK信号通路,显著缓解肌肉萎缩,恢复二头肌功能运动终板,抑制小胶质细胞和星形胶质细胞的激活。结论:综上所述,这些发现首次明确表明,QCN有希望进一步发展成为一种新的治疗方法,与再植手术一起治疗BPA。
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来源期刊
CiteScore
11.10
自引率
1.20%
发文量
45
审稿时长
11 weeks
期刊介绍: Inflammation and Regeneration is the official journal of the Japanese Society of Inflammation and Regeneration (JSIR). This journal provides an open access forum which covers a wide range of scientific topics in the basic and clinical researches on inflammation and regenerative medicine. It also covers investigations of infectious diseases, including COVID-19 and other emerging infectious diseases, which involve the inflammatory responses. Inflammation and Regeneration publishes papers in the following categories: research article, note, rapid communication, case report, review and clinical drug evaluation.
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