Epilepsy is a medical syndrome that produces seizures affecting a variety of mental and physical functions. The actual mechanisms of the onset and termination of the seizure are still unclear. While medical therapies can suppress the symptoms of seizures, 30% of patients do not respond well. New interventions using neuromodulatory devices such as vagus nerve stimulation, deep brain stimulation and responsive neurostimulation are available or under study for the treatment of refractory epilepsy. With an aim of stopping seizure for medically resistant epilepsy patients using electronic device, we developed a seizure model using human brain slices in our previous study. The hippocampal tissue is obtained from patients suffering from intractable mesial temporal lobe epilepsy (MTLE) during curative epilepsy surgery. The surgeries were performed in the standard fashion with no alterations in technique to accommodate the study. The neurosurgeon removes about 1.5 cm of the hippocampal head and body en bloc, and immediately placing it into a petri dish filled with 4 degree C sucrose. The tissue was then quickly sliced to 500 micrometer-thick slices with the vibratome. We applied a planar multi-electrode array (MEA) system, in which the spatio-temporal inter-ictal activity from human hippocampal slices can be consistently recorded in high-potassium (8 mM), low-magnesium (0.25 mM) aCSF with additional 100 μM 4-aminopyridine (4AP). Using this in vitro seizure model, we found that seizures can be suppressed by electrical stimulation.
A photo of a human hippocampal slice submerged in the MEA recording chamber
We are in the progress of evaluating the suppression effect, different features (including mean spike rate, amplitude, interval, and power) of the pre- and post-stimulation data will be analyzed and compared. This lays a foundation for future studies on finding the optimal electrical stimulation parameter for seizure prevention, and will ultimately be used to guide programming of the new stimulating paradigm for electronic device for epilepsy patients.
HiK+-LoMg2+-4AP aCSF induced inter-ictal like activity recorded in SUB, CA1 and DG from human hippocampal slices.
