title: Reduction of epileptiform activity through local valproate-implants in a rat neocortical epilepsy model.
abstract: OBJECTIVE
  Pharmacotherapy of epilepsies is limited due to low concentrations at epileptogenic foci, side effects of high systemic doses and that some potentially efficient substances do not pass the blood-brain barrier. To overcome these limitations, we tested the efficacy of local valproate (VPA)-containing polymer implants in a model of necocortical injected tetanus toxin (TeT) in the rat.
  
  
  METHODS
  Tetanus toxin was injected intracortically and cobalt (II) chloride (CoCl2) was applied on the cortical surface. Video-electrocorticography recordings with intracortical electrodes were performed. VPA-containing polymers were implanted above the cortical focus. Antiepileptic effects were evaluated as reductions of epileptiform potentials (EPs) per hour in comparison to saline (NaCl)-containing polymer implants.
  
  
  RESULTS
  Triple 50ng TeT injections plus CoCl2 application (20/10mg) showed consistent EPs. NaCl-implanted animals (n=6) showed a mean of 10.5EPs/h after the first week, the EP frequency increased to 53.5EPs/h after the second week. VPA-implant animals (n=5) showed a reduction in EP frequency from 71.6 to 4.8EPs/h after the second week. The EP frequency after the second week was higher in the NaCl-implanted animals than in the VPA-implanted (p=0.0303). The mean EPs/h increase in NaCl-implanted rats (+42.9EPs/h) was different (p=0.0087) from the mean EPs/h decrease in VPA-implanted rats (-66.8EPs/h).
  
  
  CONCLUSIONS
  Despite former publications no clear seizures could be reproduced but it was possible to establish focal EPs, which proved to be a reliable marker for epileptic activity. Local antiepileptic therapy with VPA has shown efficacy in decreasing EP frequency.
authors.affiliation: Section of Clinical Neuropharmacology, Department of Neurosurgery, Neurocenter, University Medical Center, Albert-Ludwigs-University, Breisacher Straße 64, 79106 Freiburg im Breisgau, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Rassner
authors.affiliation: Section of Clinical Neuropharmacology, Department of Neurosurgery, Neurocenter, University Medical Center, Albert-Ludwigs-University, Breisacher Straße 64, 79106 Freiburg im Breisgau, Germany; Epilepsy Center Hamburg, Protestant Hospital Alsterdorf, Bodelschwinghstr. 24, 22337 Hamburg, Germany.
authors.forename: Jonas M
authors.initials: JM
authors.lastname: Hebel
authors.affiliation: Epilepsy Center, Department of Neurosurgery, Neurocenter, University Medical Center, Albert-Ludwigs-University, Breisacher Straße 64, 79106 Freiburg im Breisgau, Germany.
authors.forename: Dirk-Matthias
authors.initials: DM
authors.lastname: Altenmüller
authors.affiliation: Section of Clinical Neuropharmacology, Department of Neurosurgery, Neurocenter, University Medical Center, Albert-Ludwigs-University, Breisacher Straße 64, 79106 Freiburg im Breisgau, Germany.
authors.forename: Silvanie
authors.initials: S
authors.lastname: Volz
authors.affiliation: Section of Clinical Neuropharmacology, Department of Neurosurgery, Neurocenter, University Medical Center, Albert-Ludwigs-University, Breisacher Straße 64, 79106 Freiburg im Breisgau, Germany.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Herrmann
authors.affiliation: Section of Clinical Neuropharmacology, Department of Neurosurgery, Neurocenter, University Medical Center, Albert-Ludwigs-University, Breisacher Straße 64, 79106 Freiburg im Breisgau, Germany; Freiburg Institute for Advanced Studies (FRIAS), Albert-Ludwigs-University, Albertstraße 19, 79104 Freiburg im Breisgau, Germany.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Feuerstein
authors.affiliation: Department of Neurosurgery, Center of Neurology and Neurosurgery, University Hospital, Goethe-University, Schleusenweg 2-16, 60528 Frankfurt am Main, Germany. Electronic address: freiman@med.uni-frankfurt.de.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Freiman
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D003035:Cobalt; D004195:Disease Models, Animal; D004343:Drug Implants; D000069280:Electrocorticography / Q000379:methods; D004576:Electromyography; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology; D011108:Polymers; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology; D013703:Temporal Muscle / Q000503:physiopathology; D013744:Tetanus Toxin; D014635:Valproic Acid / Q000008:administration & dosage*; D014741:Video Recording / Q000379:methods
chemical_list: D000927:Anticonvulsants; D004343:Drug Implants; D011108:Polymers; D013744:Tetanus Toxin; D003035:Cobalt; D014635:Valproic Acid; C018021:cobaltous chloride
keywords: Animal model; Cobalt; Epilepsy; Tetanus toxin; Valproate