Abstracts

RATIONALE: Periodic lateralizing epileptiform discharges (PLEDs) are an electroencephalographic finding occurring in variety of clinical states associated with severe brain dysfunction. The underlying pathophysiology of PLEDs and whether PLEDs represent interictal or seizure activity remains unresolved. The periodic bursting of hippocampal area CA3 produced by elevated extracellular potassium (K+o) is a well-studied model of physiological and pathological network synchronization; we propose to use this as an in-vitro model to study PLEDs. METHODS: Spontaneous bursting of area CA3 in the adult rat hippocampal slice was induced by increasing K+o from 2.5 to 8.5 mM. Periodic CA3 population bursts were characterized by measuring interburst interval (IBI) and burst length (LEN). RESULTS: In 8.5mM K+o, spontaneous bursts of CA3 had an IBI of 3.5 b 0.2 sec and LEN 94 b 11 msec. Decreasing K+o from 10.5mM to 4.5mM caused IBI to increase from 2.8 to 20.7 sec and LEN to increase from 118 to 154 msec (n=5). Addition of pentobarbital (Pb)(100uM) caused the IBI to decrease by 16 b 4% and LEN to decrease by 7 b 2%. Combining Pb with acetazolamide (10uM) caused IBI to decrease by 8 b 7% and LEN to decrease by 10 b 5% (n=10). CONCLUSIONS: PLEDs resemble the CA3 population bursts in morphology, time course, constancy of periodicity over the course of the same tracing, and response to anticonvulsants. The CA3 model, which has been useful for studying interictal spikes as well as the spread of seizure activity, may also be useful to study PLEDs under appropriate experimental conditions such as elevated K+o. Our data suggests that a primary pathophysiological mechanism underlying PLEDs may be compromised ionic homeostasis with consequent pathological depolarization of a population of neurons, a condition that is common to all of the clinical conditions in which PLEDs are observed.