Repetitive transcranial magnetic stimulation alleviates radiation-induced brain injury in rats: involving the inhibition of ferroptosis.

Radiation-induced brain injury (RIBI) is a prevalent complication following radiotherapy for head and neck tumors, and its effective therapeutic strategies are lacking. Ferroptosis, an iron-dependent cell death, has recently emerged as an important mechanism of radiation-induced cell death. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuro-interventional technique with antioxidant and neuroprotective properties. The present study aimed to explore whether rTMS attenuates RIBI by inhibiting ferroptosis. We demonstrated that rTMS alleviated neuronal injury and death in the hippocampus of RIBI rats. rTMS also improved the mitochondrial ultrastructure in the hippocampus of RIBI rats. Moreover, rTMS reduces the accumulation of iron, reactive oxygen species (ROS), and lipid peroxidation products in the hippocampus of RIBI rats. In addition, rTMS increased the expression of Glutathione peroxidase 4 (GPX4), Solute carrier family 7 member 11 (SLC7A11), and Ferritin heavy chain 1 (FTH1) and decreased the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4). These findings indicate that rTMS attenuates RIBI and the underlying mechanism involves the inhibition of ferroptosis. Our study highlights rTMS as a potentially effective therapeutic intervention for treating RIBI. The mechanistic insights shed light on the role of ferroptosis and expand our knowledge of its potential as a therapeutic target for diseases beyond RIBI.