Abstracts

Rationale: Adenosine is a naturally occurring antiepileptic neurotransmitter. In acute animal models of epilepsy, adenosine administration aborts ongoing seizures. Further, microdialysis within the seizure focus demonstrates a post-ictal increase of adenosine 6 to 31 fold in human temporal lobe epilepsy. Adenosine s neurochemical dynamics, however, are not well understood peri-ictally due to the poor temporal resolution of microdialysis. Fast scan cyclic voltammetry (FSCV) is an electrochemical technique capable of measuring adenosine concentration changes on sub-second timescales. Here we use FSCV to investigate the peri-ictal temporal dynamics of adenosine in an acute model of seizures. We hypothesized that adenosine concentration increases during neocortical epileptiform activity in response to an acute chemoconvulsant. Methods: White farm swine were used in an acute cortical model of epilepsy induced by penicillin injection (5500 Units). Electrophysiology was recorded from microelectrode arrays (Neuralynx Inc., bandwidth DC - 9 kHz, sampling at 32 kHz). Acute seizures were defined as synchronized continuous runs of epileptiform activity over 3.5 Hz. Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) based FSCV was recorded using a triangular waveform from -0.4 to 1.5 Volts sampling at 10 times per second. Results: Relative adenosine increase, as identified by unique FSCV oxidation peaks at approximately 1.5V and 1.0V (representing the first and second oxidation peaks of adenosine), occurs during and shortly after seizures. Average seizure duration was 26 6 seconds. Time locked EEG and electrochemistry demonstrates an initial adenosine rise at 20 9 seconds after electrographic seizure onset and peak adenosine level at 21 10 seconds after seizure termination. The delay from the initial adenosine rise to seizure termination was -6 9 seconds. Of these, the lowest variance was observed for the latency between seizure offset and adenosine rise, suggesting the adenosine rise may be associated with the termination of the seizure. The duration of seizure activity had a positive Pearson s correlation with adenosine rise duration (0.62). Conclusions: WINCS based FSCV recording is capable of detecting extracellular adenosine concentration changes peri-ictally in this acute pig model of epileptiform activity. Simultaneous electrochemistry and electrophysiology show the least variance between initial adenosine increases and seizure termination, suggesting that adenosine rises at the termination of seizures.