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人类神经干细胞移植可预防帕金森病大鼠模型出现有症状的运动行为障碍。

Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson's disease.

作者信息

Wang Fen, Cheng Xiao-Yu, Zhang Yu-Ting, Bai Qing-Ran, Zhang Xiao-Qi, Sun Xi-Cai, Ma Quan-Hong, Zhao Xiong-Fei, Liu Chun-Feng

机构信息

Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

Institute of Neuroscience, Soochow University, Suzhou, 215123, China.

出版信息

Open Life Sci. 2024 Feb 24;19(1):20220834. doi: 10.1515/biol-2022-0834. eCollection 2024.

Abstract

Parkinson's disease (PD) is a ubiquitous brain cell degeneration disease and presents a significant therapeutic challenge. By injecting 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle, rats were made to exhibit PD-like symptoms and treated by intranasal administration of a low-dose (2 × 10) or high-dose (1 × 10) human neural stem cells (hNSCs). Apomorphine-induced rotation test, stepping test, and open field test were implemented to evaluate the motor behavior and high-performance liquid chromatography was carried out to detect dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindole-3-acetic acid in the striatum of rats. Animals injected with 6-OHDA showed significant motor function deficits and damaged dopaminergic system compared to the control group, which can be restored by hNSCs treatment. Treatment with hNSCs significantly increased the tyrosine hydroxylase-immunoreactive cell count in the substantia nigra of PD animals. Moreover, the levels of neurotransmitters exhibited a significant decline in the striatum tissue of animals injected with 6-OHDA when compared to that of the control group. However, transplantation of hNSCs significantly elevated the concentration of DA and DOPAC in the injured side of the striatum. Our study offered experimental evidence to support prospects of hNSCs for clinical application as a cell-based therapy for PD.

摘要

帕金森病(PD)是一种常见的脑细胞退行性疾病,带来了重大的治疗挑战。通过向大鼠左侧内侧前脑束注射6-羟基多巴胺(6-OHDA),使其表现出类似帕金森病的症状,并通过鼻内给予低剂量(2×10)或高剂量(1×10)的人神经干细胞(hNSCs)进行治疗。实施阿扑吗啡诱导的旋转试验、步测试验和旷场试验以评估运动行为,并进行高效液相色谱法检测大鼠纹状体中的多巴胺(DA)、3,4-二羟基苯乙酸(DOPAC)、血清素和5-羟基吲哚-3-乙酸。与对照组相比,注射6-OHDA的动物表现出明显的运动功能缺陷和多巴胺能系统损伤,而hNSCs治疗可使其恢复。hNSCs治疗显著增加了帕金森病动物黑质中酪氨酸羟化酶免疫反应性细胞计数。此外,与对照组相比,注射6-OHDA的动物纹状体组织中神经递质水平显著下降。然而,hNSCs移植显著提高了纹状体损伤侧DA和DOPAC的浓度。我们的研究提供了实验证据,支持hNSCs作为帕金森病基于细胞的治疗方法用于临床应用的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb28/10921471/d6dbfd341274/j_biol-2022-0834-fig001.jpg

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