Stimulation with a low frequency electromagnetic field (LF-EMF) has proven to represent a powerful method for the suppression of seizures, as demonstrated in select clinical and laboratory studies. However, the mechanism by which LF-EMF suppresses seizures remains unclear. The purpose of the present study was to explore the modulatory effect of LF-EMF on epileptiform discharges (EDs) using rat hippocampal slices and investigate the underlying mechanisms that mediate these effects. EDs in hippocampal slices was induced by magnesium-free (zero-Mg2+) artificial cerebrospinal fluid (ACSF) and recorded using an in vitro micro-electrode array (MEA). A small sub-decimeter coil was designed and incorporated in a flexible magnetic stimulation device that allowed electromagnetic fields with different parameters to be delivered to slices. After a stable ED event was recorded, magnetic fields of 0.5 Hz (30 min) with a magnetic intensity of 0.13 mT (5 Vpp voltage input) and 0.25 mT (20 Vpp voltage input) were applied. The results indicated that a high-amplitude 0.5 Hz magnetic field could lead to persistent suppression of ictal discharges (IDs), while low-amplitude magnetic fields did not influence IDs. The persistent suppression of complex ED was prevented if the magnetic fields were applied in the presence of 10 μmol/L bicuculline (BIC), a γ-aminobutyric acid type A (GABAA) receptor antagonist, while the application of BIC subsequent to a magnetic field application led to the reappearance of ID. The addition of BIC resulted in EDs that had previously been inhibited by magnetic fields, reappearing. Low-frequency magnetic stimulation was able to inhibit the conversion from interictal discharges (IIDs) or preictal discharges (PIDs) to IDs. This suppression was attributed to the modulation of GABAA receptor activity.
Keywords: GABA(A) receptors; epileptiform discharges; hippocampus; low frequency electromagnetic field (LF-EMF); microelectrode array (MEA).
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