Abstracts

This study was part of our ongoing effort to identify an ideal drug combination for seizure-controlling subdural Hybrid Neuroprostheses. We have recently shown that in freely moving rats, epidurally delivered pentobarbital can prevent and terminate neocortical seizures induced by localized acetylcholine (Ach) application (Ludvig et al., Epilepsia, 2006; in press). The present experiments were designed to obtain information on whether epidurally applied neurotransmitters, specifically GABA and adenosine, can also exert similar effects in rats., Each rat was implanted with an epidural cup placed above the right parietal cortex. Epidural EEG electrodes were positioned adjacent to the posterior edge of the cup. After a 6-7-day recovery period, bipolar EEG recordings were conducted in a Faraday cage, using a cable with built-in operational amplifiers to eliminate movement artifacts. For focal seizure induction, 274 mM Ach was delivered into the epidural cup. After a 15-min exposure to Ach, a combination of 250 mM GABA and 5 mM adenosine was delivered into the cup and kept there for a 10-min period. Fast Fourier Transform (FFT) was used to determine the maximum and average power ([micro]V²) of the low-beta (13-20 Hz) frequency band before drug deliveries, during Ach exposure and after the delivery of the GABA/adenosine combination., Ach induced EEG seizures within 390 [plusmn] 30 (mean [plusmn] S.E.M.) sec, which were accompanied by clonic convulsions. During EEG seizures, there was an increase in maximum power from 13.8 [plusmn] 10.3 to 36.2 [plusmn] 22 along with an increase in average power from 4.7 [plusmn] 2.8 to 8.9 [plusmn] 4.9. Delivery of the GABA/adenosine combination fully terminated the ongoing Ach-induced EEG seizures and convulsions within 33.5 [plusmn] 21.5 sec. This GABA/adenosine effect was reflected in the reduction of the maximum power from 36.2 [plusmn] 22 to 17.2 [plusmn] 9.2 and that of the average power from 8.9 [plusmn] 4.9 to 3.9 [plusmn] 2.3. The EEG power values after GABA/adenosine delivery were comparable to those obtained in the normal, pre-seizure state. Abnormal electrographic signs following epidural exposure to this drug combination were not observed., The combination of GABA and adenosine, delivered onto the surface of dura mater, can fully terminate Ach-induced neocortical EEG seizures and their behavioral manifestations. This suggests that: (1) at least a portion of the GABA and/or adenosine molecules can diffuse through the meninges into the underlying neocortical tissue, and (2) this treatment can terminate locally induced neocortical seizures. Further studies are required to thoroughly determine the efficacy of GABA and adenosine in terminating, and perhaps preventing, focal neocortical seizures upon epidural/subdural deliveries., (Supported by NYU/FACES.)