Abstracts

Rationale: Temporal lobe epilepsy (TLE) is the most common form of refractory epilepsy syndrome. Mechanism implicated in TLE ictogenesis and epileptogenesis are not clear yet. We recently demonstrated in an acute model of limbic seizures in-vitro guinea pig brain preparation that early onset phase of seizures is characterized by interneuron activation, suggesting that the GABAergic networks are directly implicated in seizure initiation. To better clarify this hypothesis in a chronic model we developed and here characterize the guinea pig model of TLE induced by intrahippocampal administration of kainic acid (KA: 1?g/1?l).Methods: We followed animals from the acute to chronic phase by daily video EEG monitoring carried out acutely after KA injection and at alternate weeks for the following 2 months. Histological analysis were conducted after 2 months to identify tissue changes and network rearrangements.Results: Direct injection of KA in CA1 induced EEG and behavior seizures lasting several hours with subsequent spontaneously relief. In the acute phase behavior associated with seizure did not follow a linear severity scale as suggested by Racine (Racine 1972) and often similar EEG patterns were associated to different behavior evidence. In the chronic phase at least 50% of animal develop clear EEG and behavioral seizures with a very low rate of recurrence. Generalized tonic-clinic seizures were rarely observed. All animals showed marked interictal epileptiform activities. Unilateral hippocampal alterations similar to classical features associated with TLE (CA1 cellular depauperation, gliosis and zinc-enriched band in the dentate gyrus external molecular layer) were observed in all animals. Conclusions: Video-EEG recording and histological analysis, suggest that intrahippocampal injection of KA in guinea pig induce a model of TLE that ricapitulates the main features of human TLE. The study was supported by a grant of the Ministero della Sanital of the Italian Government (N. RF2007).