High-frequency repetitive transcranial magnetic stimulation protects against cerebral ischemia/reperfusion injury in rats: Involving the mitigation of ferroptosis and inflammation

Gui-Juan Zhou; Dan-Ni Liu; Xia-Rong Huang; Qi Wu; Wei-Bin Feng; Ya-Hua Zeng; Hong-Ya Liu; Jing Yu; Zi-Jian Xiao; Jun Zhou

doi:10.1002/brb3.2988

High-frequency repetitive transcranial magnetic stimulation protects against cerebral ischemia/reperfusion injury in rats: Involving the mitigation of ferroptosis and inflammation

Brain Behav. 2023 May;13(5):e2988. doi: 10.1002/brb3.2988. Epub 2023 Apr 16.

Authors

Gui-Juan Zhou^{1

2}, Dan-Ni Liu^{1

2}, Xia-Rong Huang^{1

2}, Qi Wu^{1

2}, Wei-Bin Feng^{1

2}, Ya-Hua Zeng^{1

2}, Hong-Ya Liu^{1

2}, Jing Yu^{1

2}, Zi-Jian Xiao³, Jun Zhou^{1

2}

Affiliations

¹ The First Affiliated Hospital, Department of Rehabilitation, Hengyang Medical School, University of South China, Hengyang, Hunan, P. R. China.
² The First Affiliated Hospital, Rehabilitation Laboratory, Hengyang Medical School, University of South China, Hengyang, Hunan, P. R. China.
³ The First Affiliated Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, Hunan, P. R. China.

Abstract

Background and aim: Repetitive transcranial magnetic stimulation (rTMS) has been found to attenuate cerebral ischemia/reperfusion (I/R) injury. However, its effects and mechanism of action have not yet been clarified. It has been reported that cerebral I/R injury is closely associated not only with ferroptosis but also with inflammation. Hence, the current study aimed to investigate whether high-frequency rTMS attenuates middle cerebral artery occlusion (MCAO)-induced cerebral I/R injury and further to elucidate the mediatory role of ferroptosis and inflammation.

Methods: The protective effects of rTMS on experimental cerebral I/R injury were investigated using transient MCAO model rats. Neurological scores and pathological changes of cerebral ischemic cortex were assessed to evaluate the effects of rTMS on cerebral I/R injury. The involvement of ferroptosis and that of inflammation were examined to investigate the mechanism underlying the effects of rTMS.

Results: High-frequency rTMS remarkably rescued the MCAO-induced neurological deficits and morphological damage. rTMS treatment also increased the mRNA and protein expression of glutathione-dependent peroxidase 4, decreased the mRNA and protein levels of acyl-CoA synthetase long-chain family member 4 and transferrin receptor in the cortex. Moreover, rTMS administration reduced the cerebrospinal fluid IL-1β, IL-6, and TNF-α concentrations.

Conclusion: These findings implicated that high-frequency rTMS alleviates MCAO-induced cerebral I/R injury, and the underlying mechanism could involve the inhibition of ferroptosis and inflammation. Our study identifies rTMS as a promising therapeutic agent for the treatment of cerebral I/R injury. Moreover, the mechanistic insights into ferroptosis and inflammation advance our understanding of it as a potential therapeutic target for diseases beyond cerebral ischemia stroke.

Keywords: cerebral ischemia/reperfusion injury; ferroptosis; inflammation; repetitive transcranial magnetic stimulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Ischemia* / therapy
Ferroptosis*
Infarction, Middle Cerebral Artery
Inflammation / therapy
RNA, Messenger
Rats
Reperfusion Injury* / pathology
Reperfusion Injury* / prevention & control
Stroke*
Transcranial Magnetic Stimulation

Substances

RNA, Messenger