Target delivery of brain-derived neurotrophic factor using magnetic stimulation in subacute stroke

Brain-derived neurotrophic factor (BDNF) is a macromolecular neurotrophin with potent neurorestorative effects after stroke, but its clinical translation has been hindered by inefficient transport across the blood-brain barrier (BBB). We investigated whether focused magnetic stimulation (MagStim) could serve as a non-invasive platform to enhance BDNF delivery and therapeutic efficacy in stroke. Rats underwent transient middle cerebral artery occlusion, and treatment was initiated 14 days after stroke onset. Animals were assigned to Sham, MCAO Control, BDNF alone, or MagStim combined with BDNF groups. Infarct volume was quantified by TTC staining and magnetic resonance imaging, and functional recovery was assessed. BBB permeability and BDNF brain penetration were evaluated by IVIS imaging, and molecular and cellular responses were characterized by Western blotting, qRT-PCR, ELISA, and immunofluorescence. MagStim combined with BDNF significantly increased BDNF accumulation in the ipsilesional brain compared with BDNF alone (ELISA p = 0.011) and was the only treatment that produced a robust reduction in infarct volume (MRI p = 0.043). Furthermore, while both treatments improved neurological deficit scores, only the MagStim+BDNF combination drove significant motor recovery (p < 0.001), successfully avoiding sustained BBB disruption. At the molecular level, MagStim plus BDNF significantly preserved tight junction proteins, attenuated inflammatory cytokine expression and apoptosis, and upregulated markers of neurogenesis in peri-infarct regions. These findings demonstrate that magnetically controlled, transient BBB modulation can overcome barriers to macromolecular delivery and enhance the therapeutic efficacy of BDNF. This approach provides a translational platform for delivering neurotrophic factor-based therapies aimed at promoting stroke recovery.