Abstracts

Treiman et al. ([italic]Epilepsy Res[/italic] 5:49-60, 1990) described five stages of progressive electroencephalographic (EEG) changes during clinical and experimental status epilepticus (SE), which reflect the underlying severity of the episode of SE. Longer duration of SE and later EEG stages translate to increased problematic cessation of seizures, perhaps due to progressive attenuation of GABA-mediated inhibition. We hypothesized that marked electrophysiologic changes in GABA[sub]A[/sub] receptor function correlate with a specific EEG stage during experimental SE in rats., Ten-week-old Sprague-Dawley rats were injected (i.p.) with 3 mM LiCl followed by 30 mg/kg pilocarpine 24 h later to induce SE. Animals were sacrificed before initiation of SE (control), or during EEG Stages I, III, or V, and brains were rapidly removed, placed in cold (4[deg]C) artificial cerebrospinal fluid (ACSF) for 1 min, sliced using a vibratome, and then oxygenated for 1 h in ACSF at room temperature. Paired-pulse responses with interpulse intervals (IPI) of 30, 50, 100 and 150 msec were induced by stimulation of Schaffer collaterals and recorded from the cell-body layer of the CA1 region of the hippocampus. [gamma] oscillations (30-80 Hz) were then elicited by tetanic stimulation at a voltage twice that of threshold and were also recorded from CA1. Some Stage V hippocampal slices were perfused with 100 [mu]M GABA or 1 [mu]M diazepam following initial electrophysiological recordings., Paired-pulse stimulation resulted in increased inhibition in Stage I hippocampal slices compared to control slices (p [lt] 0.05, IPI = 50 msec) but decreased inhibition in Stage V slices compared to Stage I slices (p [lt] 0.05, IPI = 50 msec). [gamma] oscillations were progressively attenuated in slices from later EEG stages. Amplitude (p [lt] 0.01), duration (p [lt] 0.05) and spike count (p [lt] 0.05) were all reduced in Stage V slices compared to control slices. Perfusion with GABA, and to a lesser extent with diazepam, resulted in recovery of [gamma] oscillations in Stage V slices., These results are consistent with other reports of attenuation of GABA-mediated inhibition during prolonged SE, which may explain the increased refractoriness of later stages of SE to treatment. In addition, our results indicate a possible impairment of presynaptic release of GABA occurred in this model. This observation suggests GABA reuptake inhibitors could be useful for the treatment of refractory status epilepticus. We also report the new finding that paired-pulse inhibition is greater during Stage I compared to control slices and speculate that this may represent an initial compensatory response to excessive excitation before GABA-mediated inhibition begins to deteriorate as SE progresses., (Supported by Barrow Neurological Foundation.)