title: Epileptiform activity preferentially arises outside tumor invasion zone in glioma xenotransplants.
abstract: Seizures occur commonly with brain tumors. The underlying mechanisms are not understood. We analyzed network and cellular excitability changes in tumor-invaded and sham neocortical tissue in vitro using a rat glioblastoma model. Rat C6 glioma cells were transplanted into rat neocortex, yielding diffusely invading gliomas resembling human glioblastomas. We hypothesized that network excitability would increase in regions neighboring the tumor, and that initiation of epileptic discharges might be correlated to a higher density of intrinsically bursting neurones. Voltage-sensitive dye imaging revealed epileptic activity to be initiated in paratumoral zones (1-2 mm from main tumor mass), in contrast to control tissue, where epileptic foci appeared randomly throughout the neocortex. Neuronal firing patterns revealed significantly more intrinsically bursting neurones within these initiation zones than in regions directly adjacent to the tumor or in control tissue. We conclude that gliomas are associated with a higher density of intrinsically bursting neurones, and that these may preferentially initiate epileptiform events.
authors.affiliation: Institute of Physiology, University of Münster, Robert-Koch-Str. 27a, 48149 Münster, Germany. ruediger.koehling@uni-rostock.de
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Köhling
authors.forename: Volker
authors.initials: V
authors.lastname: Senner
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Erwin-Josef
authors.initials: EJ
authors.lastname: Speckmann
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D001932:Brain Neoplasms / Q000150:complications / Q000503:physiopathology*; D016380:Brain Tissue Transplantation; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000209:etiology / Q000503:physiopathology*; D005456:Fluorescent Dyes; D005910:Glioma / Q000150:complications / Q000503:physiopathology*; D008297:Male; D019579:Neocortex / Q000473:pathology / Q000503:physiopathology*; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D009415:Nerve Net / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology; D014183:Transplantation, Heterologous / Q000502:physiology
chemical_list: D005456:Fluorescent Dyes