Transcutaneous Electrical Nerve Stimulation (TENS) Alleviates Brain Ischemic Injury by Regulating Neuronal Oxidative Stress, Pyroptosis, and Mitophagy

Background. As a noninvasive treatment, transcutaneous electrical nerve stimulation (TENS) has been utilized to treat various diseases in clinic. However, whether TENS can be an effective intervention in the acute stage of ischemic stroke still remains unclear. In the present study, we aimed to expl...

Full description

Saved in:
Bibliographic Details
Main Authors: Zixuan Tan, Fang Dong, Linyu Wu, Yashuo Feng, Min Zhang, Feng Zhang
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2023/5677865
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832547888790503424
author Zixuan Tan
Fang Dong
Linyu Wu
Yashuo Feng
Min Zhang
Feng Zhang
author_facet Zixuan Tan
Fang Dong
Linyu Wu
Yashuo Feng
Min Zhang
Feng Zhang
author_sort Zixuan Tan
collection DOAJ
description Background. As a noninvasive treatment, transcutaneous electrical nerve stimulation (TENS) has been utilized to treat various diseases in clinic. However, whether TENS can be an effective intervention in the acute stage of ischemic stroke still remains unclear. In the present study, we aimed to explore whether TENS could alleviate brain infarct volume, reduce oxidative stress and neuronal pyroptosis, and activate mitophagy following ischemic stroke. Methods. TENS was performed at 24 h after middle cerebral artery occlusion/reperfusion (MCAO/R) in rats for 3 consecutive days. Neurological scores, the volume of infarction, and the activity of SOD, MDA, GSH, and GSH-px were measured. Moreover, western blot was performed to detect the related protein expression, including Bcl-2, Bax, TXNIP, GSDMD, caspase-1, NLRP3, BRCC3, HIF-1α, BNIP3, LC3, and P62. Real-time PCR was performed to detect NLRP3 expression. Immunofluorescence was performed to detect the levels of LC3. Results. There was no significant difference of neurological deficit scores between the MCAO group and the TENS group at 2 h after MCAO/R operation (P>0.05), while the neurological deficit scores of TENS group significantly decreased in comparison with MCAO group at 72 h following MACO/R injury (P<0.05). Similarly, TENS treatment significantly reduced the brain infarct volume compared with the MCAO group (P<0.05). Moreover, TENS decreased the expression of Bax, TXNIP, GSDMD, caspase-1, BRCC3, NLRP3, and P62 and the activity of MDA as well as increasing the level of Bcl-2, HIF-1α, BNIP3, and LC3 and the activity of SOD, GSH, and GSH-px (P<0.05). Conclusions. In conclusion, our results indicated that TENS alleviated brain damage following ischemic stroke via inhibiting neuronal oxidative stress and pyroptosis and activating mitophagy, possibly via the regulation of TXNIP, BRCC3/NLRP3, and HIF-1α/BNIP3 pathways.
format Article
id doaj-art-f9034907c5fc411caa882ddf3ae6f7ca
institution Kabale University
issn 1466-1861
language English
publishDate 2023-01-01
publisher Wiley
record_format Article
series Mediators of Inflammation
spelling doaj-art-f9034907c5fc411caa882ddf3ae6f7ca2025-02-03T06:43:02ZengWileyMediators of Inflammation1466-18612023-01-01202310.1155/2023/5677865Transcutaneous Electrical Nerve Stimulation (TENS) Alleviates Brain Ischemic Injury by Regulating Neuronal Oxidative Stress, Pyroptosis, and MitophagyZixuan Tan0Fang Dong1Linyu Wu2Yashuo Feng3Min Zhang4Feng Zhang5Department of Rehabilitation MedicineDepartment of Clinical Laboratory MedicineDepartment of Rehabilitation MedicineDepartment of Rehabilitation MedicineDepartment of PathophysiologyDepartment of Rehabilitation MedicineBackground. As a noninvasive treatment, transcutaneous electrical nerve stimulation (TENS) has been utilized to treat various diseases in clinic. However, whether TENS can be an effective intervention in the acute stage of ischemic stroke still remains unclear. In the present study, we aimed to explore whether TENS could alleviate brain infarct volume, reduce oxidative stress and neuronal pyroptosis, and activate mitophagy following ischemic stroke. Methods. TENS was performed at 24 h after middle cerebral artery occlusion/reperfusion (MCAO/R) in rats for 3 consecutive days. Neurological scores, the volume of infarction, and the activity of SOD, MDA, GSH, and GSH-px were measured. Moreover, western blot was performed to detect the related protein expression, including Bcl-2, Bax, TXNIP, GSDMD, caspase-1, NLRP3, BRCC3, HIF-1α, BNIP3, LC3, and P62. Real-time PCR was performed to detect NLRP3 expression. Immunofluorescence was performed to detect the levels of LC3. Results. There was no significant difference of neurological deficit scores between the MCAO group and the TENS group at 2 h after MCAO/R operation (P>0.05), while the neurological deficit scores of TENS group significantly decreased in comparison with MCAO group at 72 h following MACO/R injury (P<0.05). Similarly, TENS treatment significantly reduced the brain infarct volume compared with the MCAO group (P<0.05). Moreover, TENS decreased the expression of Bax, TXNIP, GSDMD, caspase-1, BRCC3, NLRP3, and P62 and the activity of MDA as well as increasing the level of Bcl-2, HIF-1α, BNIP3, and LC3 and the activity of SOD, GSH, and GSH-px (P<0.05). Conclusions. In conclusion, our results indicated that TENS alleviated brain damage following ischemic stroke via inhibiting neuronal oxidative stress and pyroptosis and activating mitophagy, possibly via the regulation of TXNIP, BRCC3/NLRP3, and HIF-1α/BNIP3 pathways.http://dx.doi.org/10.1155/2023/5677865
spellingShingle Zixuan Tan
Fang Dong
Linyu Wu
Yashuo Feng
Min Zhang
Feng Zhang
Transcutaneous Electrical Nerve Stimulation (TENS) Alleviates Brain Ischemic Injury by Regulating Neuronal Oxidative Stress, Pyroptosis, and Mitophagy
Mediators of Inflammation
title Transcutaneous Electrical Nerve Stimulation (TENS) Alleviates Brain Ischemic Injury by Regulating Neuronal Oxidative Stress, Pyroptosis, and Mitophagy
title_full Transcutaneous Electrical Nerve Stimulation (TENS) Alleviates Brain Ischemic Injury by Regulating Neuronal Oxidative Stress, Pyroptosis, and Mitophagy
title_fullStr Transcutaneous Electrical Nerve Stimulation (TENS) Alleviates Brain Ischemic Injury by Regulating Neuronal Oxidative Stress, Pyroptosis, and Mitophagy
title_full_unstemmed Transcutaneous Electrical Nerve Stimulation (TENS) Alleviates Brain Ischemic Injury by Regulating Neuronal Oxidative Stress, Pyroptosis, and Mitophagy
title_short Transcutaneous Electrical Nerve Stimulation (TENS) Alleviates Brain Ischemic Injury by Regulating Neuronal Oxidative Stress, Pyroptosis, and Mitophagy
title_sort transcutaneous electrical nerve stimulation tens alleviates brain ischemic injury by regulating neuronal oxidative stress pyroptosis and mitophagy
url http://dx.doi.org/10.1155/2023/5677865
work_keys_str_mv AT zixuantan transcutaneouselectricalnervestimulationtensalleviatesbrainischemicinjurybyregulatingneuronaloxidativestresspyroptosisandmitophagy
AT fangdong transcutaneouselectricalnervestimulationtensalleviatesbrainischemicinjurybyregulatingneuronaloxidativestresspyroptosisandmitophagy
AT linyuwu transcutaneouselectricalnervestimulationtensalleviatesbrainischemicinjurybyregulatingneuronaloxidativestresspyroptosisandmitophagy
AT yashuofeng transcutaneouselectricalnervestimulationtensalleviatesbrainischemicinjurybyregulatingneuronaloxidativestresspyroptosisandmitophagy
AT minzhang transcutaneouselectricalnervestimulationtensalleviatesbrainischemicinjurybyregulatingneuronaloxidativestresspyroptosisandmitophagy
AT fengzhang transcutaneouselectricalnervestimulationtensalleviatesbrainischemicinjurybyregulatingneuronaloxidativestresspyroptosisandmitophagy