Artikel
Reduction of epileptiform activity through local valproate-implants in a rat neocortical epilepsy model
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Veröffentlicht: | 4. Juni 2012 |
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Gliederung
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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.