Recent work suggests that repetitive
transcranial magnetic stimulation (rTMS) may beneficially alter the pathological status of several
neurological disorders, although the mechanism remains unclear. The current study was designed to investigate the effects of rTMS on behavioral deficits and potential underlying mechanisms in a rat photothrombotic (PT)
stroke model. From day 0 (3 h) to day 5 after the establishment of PT
stroke, 5-min daily continuous theta-burst rTMS (3 pulses of 50 Hz repeated every 200 ms, intensity at 200 G) was applied on the
infarct hemisphere. We report that rTMS significantly attenuated behavioral deficits and
infarct volume after PT
stroke. Further investigation demonstrated that rTMS remarkably reduced synaptic loss and neuronal degeneration in the peri-
infarct cortical region. Mechanistic studies displayed that beneficial effects of rTMS were associated with robust suppression of reactive micro/
astrogliosis and the overproduction of pro-inflammatory
cytokines, as well as oxidative stress and oxidative neuronal damage especially at the late stage following PT
stroke. Intriguingly, rTMS could effectively induce a shift in microglial M1/M2 phenotype activation and an A1 to A2 switch in astrocytic phenotypes. In addition, the release of anti-inflammatory
cytokines and mitochondrial MnSOD in peri-
infarct regions were elevated following rTMS treatment. Finally, rTMS treatment efficaciously preserved mitochondrial membrane integrity and suppressed the intrinsic mitochondrial
caspase-9/3 apoptotic pathway within the peri-
infarct cortex. Our novel findings indicate that rTMS treatment exerted robust neuroprotection when applied at least 3 h after
ischemic stroke. The underlying mechanisms are partially associated with improvement of the local neuronal microenvironment by altering inflammatory and oxidative status and preserving mitochondrial integrity in the peri-
infarct zone. These findings provide strong support for the promising
therapeutic effect of rTMS against ischemic neuronal injury and functional deficits following
stroke.