The molecular mechanism involved in the treatment of ischemic stroke with repeated transcranial magnetic stimulation
10.3760/cma.j.issn.0254-1424.2024.07.003
- VernacularTitle:基于微小核糖核酸-信使核糖核酸网络探讨重复经颅磁刺激治疗缺血性脑卒中的分子机制
- Author:
Jianmin CHEN
1
;
Jing LI
;
Huayao HUANG
;
Zhenqiang CHEN
;
Qingfa CHEN
Author Information
1. 福建医科大学附属第一医院康复医学科，福州 350005
- Keywords:
Ischemia;
Stroke;
Bioinformatics;
Transcranial magnetic stimulation;
GEO database;
miRNA-mRNA regulation
- From:
Chinese Journal of Physical Medicine and Rehabilitation
2024;46(7):593-600
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the molecular mechanism through which repetitive transcranial magnetic stimulation (rTMS) promotes nerve regeneration after ischemic stroke.Methods:The miRNA expression profile in rats after rTMS was downloaded from the GEO database. Differentially-expressed miRNAs were identified using R software, and their corresponding mRNAs were predicted using the online database in order to construct miRNA-mRNA regulatory networks and identify the key miRNAs. The protein interaction network encoded by each gene was constructed by functional enrichment analysis, and the core mRNAs in the network were identified. Twenty-four male Sprague-Dawley rats of a specific pathogen-free grade were randomly divided into a sham operation group, a model group and a magnetic stimulation group, each of 8, and a stroke model was induced in the model and magnetic stimulation groups. The magnetic stimulation group then received rTMS for 7 consecutive days, while the other 2 groups did not. Modified neural function scores (mNSSs) were used to quantify neural function deficits before the experiment and 1, 3 and 7 days after the modeling. Eight days after the modeling, brain tissues were sampled for hematoxylin-eosin and Nishin staining to observe tissue loss and neuron morphology. Real-time fluorescence quantitative polymerase chain reactions were employed to verify the differential gene expression in the ischemic cortex.Results:A total of 167 different miRNAs were screened, and 25 mRNAs were predicted. Enrichment analysis showed that those genes are related to the positive regulation of cell migration and the positive regulation of neurotrophic factor receptor signaling pathways, including adenylate-activated protein kinase, the neurotrophic factor pathway, and rat sarcoma signaling pathways. The miRNA-mRNA regulatory network highlighted miR-206-3p, miR-378a-3p, miR-107-3p, miR-92a-3p and miR-29b-3p as key miRNAs. Integrin subunit β1, aquaporin 4, brain-derived nerve growth factor (BDNF), and member 4 of solutes vector family 2 were identified as key mRNAs by the protein interaction network analysis. Seven days after the modeling, the average mNSS score of the magnetic stimulation group was significantly lower than the model group′s average. Compared with the model group, the expression of miR-206-3p in the right cortex of the magnetic stimulation group had decreased significantly, while BDNF expression had increased significantly.Conclusions:miR-206-3p-BDNF pathways play an important role in neural repair promoted by rTMS.
