The Protective Mechanism of Continuous Theta Burst Stimulation in the Acute Phase of Stroke Through Modulation of the Calcineurin/AKT/FOXO1 Signaling Pathway.

AIMS: To investigate the neuroprotective effects of continuous theta-burst stimulation (cTBS) during the acute phase of ischemic stroke and its impact on neuronal apoptosis in the peri-infarct region.

METHODS

MCAO was induced in mice using the Longa method. cTBS was administered daily for seven days. Motor function and limb coordination were assessed behaviorally. Transcriptomic and proteomic analyses of the peri-infarct region were performed to explore mechanisms. Immunofluorescence and Western blot analyzed key proteins in the calcineurin/AKT/FOXO1 pathway, while TUNEL staining assessed neuronal apoptosis. AAV-mediated gene knockdown was used to validate the pathway's role in apoptosis.

RESULTS

cTBS improved motor performance, reduced infarct volume, and preserved peri-infarct tissue architecture. It suppressed calcineurin expression, enhanced calcineurin/AKT/FOXO1 pathway activation, and decreased neuronal apoptosis.

CONCLUSION

cTBS exerts neuroprotection by modulating the calcineurin/AKT/FOXO1 pathway, ultimately inhibiting neuronal apoptosis in the peri-infarct region.