A New Rat Model of Seizures Suitable for Screening Antiepileptic Electrical Stimulation Therapies.

The antiepileptic effects of the electrical stimulation therapies developed for patients with intractable epilepsies depend critically on the stimulation parameters, including the pulse duration, current, and frequency. Consequently, optimization of such therapies requires many animals for testing each of the stimulation parameters alone or in combination, which is costly and time consuming. This drawback could be reduced by testing several stimulation paradigms in each animal, but this requires an animal model of long-lasting seizures allowing such repetitive tests. This study was performed to validate such a model of long-lasting seizures. The present analysis was performed on electrocorticogram and intracortical signals collected from the somatosensory cortex of 11 Sprague Dawley rats. A protocol of controlled intravenous infusion of pentylenetetrazol (PTZ) was developed to induce spike-and-wave (SW) seizures and maintain stable those seizures for the whole experimental time. SW discharges were induced and maintained stable for 2 h in all rats through a two-stage infusion of PTZ. During the first stage, the SW discharges were induced by 2.5 min infusion of 10 mg/kg/min PTZ. During the second stage, the SW discharges were maintained at a stable level of frequency and power for 2 h via a 0.21 mg/kg/min PTZ infusion rate. The proposed animal model of seizures is characterized by SW discharges which remain stable for 2 h. This 2-h long time interval allows repetitive tests with different stimulation parameters in each animal, which may lead to a significant reduction of the number of animals necessary for optimizing electrical stimulation therapies developed to inhibit seizures.

Stimulation selectivity of the "thin-film longitudinal intrafascicular electrode" (tfLIFE) and the "transverse intrafascicular multi-channel electrode" (TIME) in the large nerve animal model.

Neural prostheses are limited by the availability of peripheral neural electrodes to record the user's intention or provide sensory feedback through functional electrical stimulation. Our objective was to compare the ability of the novel "transverse intrafascicular multi-channel electrode" (TIME) and an earlier generation "thin-film longitudinal intrafascicular electrode" (tfLIFE) to selectively stimulate nerve fascicles and activate forelimb muscles in pigs. TIME was designed to access a larger subpopulation of fascicles than tfLIFE and should therefore be able to selectively activate a larger number of muscles. Electrodes were implanted in the median nerve, and sequential electric stimulation was applied to individual contacts. The compound muscle action potentials of seven muscles were recorded to quantify muscle recruitment. As expected, TIME was able to recruit more muscles with higher selectivity than tfLIFE (significant difference when comparing the performance of an entire electrode); a similar activation current was used (no significant difference). Histological analysis revealed that electrodes were located between fascicles, which influenced the selectivity and activation current level. In conclusion, TIME is a viable neural interface for selective activation of multiple fascicles in human-sized nerves that may assist to pave the way for future neuroprosthesis applications.