Real-Time Evaluation of Magnetoelectric Nanoparticle-Induced Neurostimulation in Ex Vivo Human Brain

OBJECTIVES: Magnetoelectric nanoparticles (MENPs) represent a wireless neuromodulation strategy capable of converting externally applied magnetic fields into localized electric stimulation. Although MENPs have shown neurostimulatory effects in cellular and rodent models, their ability to activate viable adult human brain tissue remains insufficiently explored. This study evaluated whether MENPs can induce neuronal activation in ex vivo adult human cortical brain slices.

MATERIALS AND METHODS: Organotypic human brain slice cultures were prepared from resected temporal lobe tissue obtained during epilepsy surgery. Slices were transduced with a neuron specific GCaMP7 calcium indicator and microinjected with CoFe2O4-BaTiO3 MENPs. Magnetic stimulation was delivered using a 6 mT, 140 Hz alternating magnetic field superimposed on a 220 mT direct-current bias. Calcium imaging was performed before, during, and after stimulation. Control conditions included sham stimulation, reversed coil stimulation, field only and MENPs only conditions, and calcium-channel blockade with CdCl2 or NNC 55-0396.

RESULTS: MENPs implanted slices exposed to the magnetic field showed increased neuronal calcium activity, reflected by a higher percentage of significantly responsive regions of interest during and/or after stimulation. Comparable activation was not observed in MENPs-only (sham controls) or field-only controls. Reversed coil stimulation reduced the response. Calcium-channel blockade attenuated stimulation-associated activity, supporting involvement of voltage-gated calcium dependent mechanisms.

CONCLUSIONS: MENPs can evoke neuronal activity in viable adult human cortical tissue ex vivo. These findings provide translational evidence supporting MENPs as a potential wireless neuromodulation platform and establish human brain slice cultures as a relevant model for preclinical evaluation of nanoparticle mediated neurostimulation.