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[电针联合康复训练通过促进星形胶质细胞转分化改善脑缺血小鼠的神经功能]

[Electroacupuncture combined with rehabilitation training improves neurological function of mice with cerebral ischemia by promoting astrocyte transdifferentiation].

作者信息

Tang Dongning, Kang Yunyun, He Wenjie, Xia Qing

机构信息

Research Center of Experimental Acupuncture, Dongguan 523000, China.

Dongguan Rehabilitation Experimental School, Dongguan 523000, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2025 Jul 20;45(7):1434-1441. doi: 10.12122/j.issn.1673-4254.2025.07.09.

DOI:10.12122/j.issn.1673-4254.2025.07.09
PMID:40673305
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12268914/
Abstract

OBJECTIVES

To explore the effects of acupuncture combined with rehabilitation training for promoting transdifferentiation of astrocytes into neurons in mice after cerebral ischemia.

METHODS

Male C57/BL6J mice were subjected to intracerebral microinjection of an adeno-associated virus carrying the GFAP promoter for NeuroD1 and Ngn2 overexpression in the astrocytes, followed 3 or 12 days later by electrocoagulation of the distal middle cerebral artery. After modeling, the mice were randomly divided into model group without interventions and intervention group treated with electroacupuncture at the acupoints Baihui (GV20), left Hegu (LI4), Neiguan (PC6), Zusanli (ST36), and Yanglingquan (GB34) 24 h after surgery. The mice in the intervention group were housed individually in cages with running wheels, and their activity was recorded every 24 h. Neurological function scores of the mice were assessed on the 1st, 14th, and 21st days after modeling. Transdifferentiation of astrocytes in the target brain regions was observed using double immunofluorescence staining.

RESULTS

Compared with those in the model group, the mice receiving eletroacupuncture and rehabilitation training showed significant improvement of neurological deficits at 14 and 21 days after modeling. The GFAP promoter of the AAV2/5 vector specifically labeled the local astrocytes, and compared with that that in the model group, the number of AAV-positive cells colabeled with the neuronal marker DCX significantly increased after 14 days of electroacupuncture and rehabilitation intervention, and the number of AAV-positive cells colabeled with the neuronal marker NeuN significantly increased after 21 days of intervention.

CONCLUSIONS

In mice with cerebral ischemia, electroacupuncture and rehabilitation training can promote transdifferentiation of astrocytes into neurons in the ischemic brain region, and the efficiency of transdifferentiation is positively correlated with the improvement of motor function.

摘要

目的

探讨针刺联合康复训练对脑缺血小鼠星形胶质细胞向神经元转分化的影响。

方法

雄性C57/BL6J小鼠经脑内微量注射携带GFAP启动子的腺相关病毒,使星形胶质细胞中NeuroD1和Ngn2过表达,3天或12天后行大脑中动脉远端电凝术。造模后,将小鼠随机分为不干预的模型组和术后24小时接受百会(GV20)、左侧合谷(LI4)、内关(PC6)、足三里(ST36)和阳陵泉(GB34)穴位电针治疗的干预组。干预组小鼠单独饲养在带跑轮的笼子里,每24小时记录其活动情况。在造模后第1、14和21天评估小鼠的神经功能评分。采用双重免疫荧光染色观察目标脑区星形胶质细胞的转分化情况。

结果

与模型组相比,接受电针和康复训练的小鼠在造模后14天和21天神经功能缺损有显著改善。AAV2/5载体的GFAP启动子特异性标记局部星形胶质细胞,与模型组相比,电针和康复干预14天后,与神经元标记物DCX共标记的AAV阳性细胞数量显著增加,干预21天后,与神经元标记物NeuN共标记的AAV阳性细胞数量显著增加。

结论

在脑缺血小鼠中,电针和康复训练可促进缺血脑区星形胶质细胞向神经元转分化,且转分化效率与运动功能改善呈正相关。

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本文引用的文献

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Neuronal repair after spinal cord injury by in vivo astrocyte reprogramming mediated by the overexpression of NeuroD1 and Neurogenin-2.通过过表达 NeuroD1 和 Neurogenin-2 介导的体内星形胶质细胞重编程实现脊髓损伤后的神经元修复。
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Ectopic Expression of Neurod1 Is Sufficient for Functional Recovery following a Sensory-Motor Cortical Stroke.神经分化因子1(Neurod1)的异位表达足以促进感觉运动皮层卒中后的功能恢复。
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