title: An in vitro seizure model from human hippocampal slices using multi-electrode arrays.
abstract: Temporal lobe epilepsy is a neurological condition marked by seizures, typically accompanied by large amplitude synchronous electrophysiological discharges, affecting a variety of mental and physical functions. The neurobiological mechanisms responsible for the onset and termination of seizures are still unclear. While pharmacological therapies can suppress the symptoms of seizures, typically 30% of patients do not respond well to drug control. Unilateral temporal lobectomy, a procedure in which a substantial part of the hippocampal formation and surrounding tissue is removed, is a common surgical treatment for medically refractory epilepsy. In this study, we have developed an in vitro model of epilepsy using human hippocampal slices resected from patients suffering from intractable mesial temporal lobe epilepsy. We show that using a planar multi-electrode array system, spatio-temporal inter-ictal like activity can be consistently recorded in high-potassium (8 mM), low-magnesium (0.25 mM) artificial cerebral spinal fluid with 4-aminopyridine (100 μM) added. The induced epileptiform discharges can be recorded in different subregions of the hippocampus, including dentate, CA1 and subiculum. This new paradigm will allow the study of seizure generation in different subregions of hippocampus simultaneously, as well as propagation of seizure activity throughout the intrinsic circuitry of hippocampus. This experimental model also should provide insights into seizure control and prevention, while providing a platform to develop novel, anti-seizure therapeutics.
authors.affiliation: Department of Biomedical Engineering, Center for Neural Engineering, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: mhsiao@usc.edu.
authors.forename: Min-Chi
authors.initials: MC
authors.lastname: Hsiao
authors.affiliation: Department of Biomedical Engineering, Center for Neural Engineering, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: penning@usc.edu.
authors.forename: Pen-Ning
authors.initials: PN
authors.lastname: Yu
authors.affiliation: Department of Biomedical Engineering, Center for Neural Engineering, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: dsong@usc.edu.
authors.forename: Dong
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Neurological Surgery and Neurology, USC Keck School of Medicine, USC Center for Neurorestoration, Department of Biomedical Engineering, and Rancho Los Amigos National Rehabilitation Center, USA. Electronic address: cliu@med.usc.edu.
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Department of Neurology, USC Keck School of Medicine, USC Center for Neurorestoration, Los Angeles, CA 90033, USA. Electronic address: check@med.usc.edu.
authors.forename: Christianne N
authors.initials: CN
authors.lastname: Heck
authors.affiliation: Department of Neurology, USC Keck School of Medicine, USC Center for Neurorestoration, Los Angeles, CA 90033, USA; Rancho Los Amigos National Rehabilitation Center, Downey, CA 90242, USA. Electronic address: millett@med.usc.edu.
authors.forename: David
authors.initials: D
authors.lastname: Millett
authors.affiliation: Department of Biomedical Engineering, Center for Neural Engineering, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: berger@usc.edu.
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Berger
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004566:Electrodes; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques / Q000295:instrumentation / Q000379:methods; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012640:Seizures / Q000473:pathology*
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine; D011188:Potassium
keywords: Human hippocampal slices; In vitro seizure model; Mesial temporal lobe epilepsy; Multi-electrode arrays