gms | German Medical Science

63rd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Japanese Neurosurgical Society (JNS)

German Society of Neurosurgery (DGNC)

13 - 16 June 2012, Leipzig

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

Meeting Abstract

  • T.M. Freiman - Abteilung für Allgemeine Neurochirurgie, Albert-Ludwigs Universität, Freiburg
  • M.P. Rassner - Sektion für klinische Neuropharmakologie, Albert-Ludwigs Universität, Freiburg
  • J.M. Hebel - Sektion für klinische Neuropharmakologie, Albert-Ludwigs Universität, Freiburg
  • D.M. Altenmüller - Sektion für Epileptologie Neurocentrum, Albert-Ludwigs Universität, Freiburg
  • T.J. Feuerstein - Sektion für klinische Neuropharmakologie, Albert-Ludwigs Universität, Freiburg
  • J. Zentner - Abteilung für Allgemeine Neurochirurgie, Albert-Ludwigs Universität, Freiburg

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocFR.14.10

doi: 10.3205/12dgnc298, urn:nbn:de:0183-12dgnc2988

Published: June 4, 2012

© 2012 Freiman et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Objective: Pharmacological treatment of epilepsies is mainly limited due to side effects of systemically applied anticonvulsive agents in high doses. Moreover, some of most efficient substances cannot cross the blood-brain barrier. To overcome these limitations, we tested in an animal experimental animal model. Our results show the reduction of epileptiform activity through local application of valproate polymers for the first time.

Methods: We have developed a novel experimental technique by inducing a neocortical epileptogenic focus in the M1 region of the rat. Tetanus toxin was injected intracortically and cobalt (II) chloride (CoCl2) was applied locally. Intracortical encephalography (ECoG) electrodes were implanted in all rats and long-term video-ECoG recordings were performed. For local antiepileptic therapy, biodegradable valproate-containing polymer matrices were implanted at the surface of the cortex above the focus. Antiepileptic effects were evaluated by the reduction of clear-cut epileptiform potentials (EPs) per hour (h).

Results: Animals with triple 50 ng tetanus toxin injections plus 10 mg CoCl2 application showed continuous spike-wave discharges. Saline-implanted animals showed a mean of 4.5 EPs/h in the first week, the EP frequency increased to 31.1 EPs/h in the second week. The VPA-implant animals showed a reduction in their EP frequency, amounting to 43.6 EPs/h in the first week and to 13.3 EPs/h in the second week. The increase of EPs/h in saline-implant animals (26.4 EPs/h) was significantly (p=0.04) different from the decrease of EPs/h in VPA-implant animals (–40.1 EPs/h).

Conclusions: Therefore local therapy may be become an alternative treatment modality of epilepsies in the near future.