Reduction of epileptiform activity through local valproate-implants in a rat neocortical epilepsy model

Purpose: 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 50 ng TeT injections plus CoCl2 application (20/10 mg) showed consistent EPs. NaCl-implanted animals (n = 6) showed a mean of 10.5 EPs/h after the first week, the EP frequency increased to 53.5 EPs/h after the second week. VPA-implant animals (n = 5) showed a reduction in EP frequency from 71.6 to 4.8 EPs/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 (+42.9 EPs/h) was different (p = 0.0087) from the mean EPs/h decrease in VPA-implanted rats (-66.8 EPs/h). Conclusion: 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. (C) 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.