Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice: Electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy

Human mesial temporal lobe epilepsy is characterized by hippocampal seizure s associated with pyramidal cell loss in the hippocampus and dispersion of dentate gyrus granule cells. A similar histological pattern was recently de scribed in a model of extensive neuroplasticity in adult mice after injecti on of kainate into the dorsal hippocampus [Suzuki et al. (1995) Neuroscienc e 64, 665-674]. The aim of the present study was to determine whether (i) r ecurrent seizures develop in mice after intrahippocampal injection of kaina te, and (ii) the electroencephalographic, histopathological and behavioural changes in such mice are similar to those in human mesial temporal lobe ep ilepsy. Adult mice receiving a unilateral injection of kainate (0.2 mu g; 5 0 nl) or saline into the dorsal hippocampus displayed recurrent paroxysmal discharges on the electroencephalographic recordings associated with immobi lity, staring and, occasionally, clonic components. These seizures started immediately after kainate injection and recurred for up to eight months. Ep ileptiform activities occurred most often during sleep but occasionally whi le awake. The pattern of seizures did not change over time nor did they sec ondarily generalize. Glucose metabolic changes assessed by [C-14]2-deoxyglu cose autoradiography were restricted to the ipsilateral hippocampus for 30 days, but had spread to the thalamus by 120 days after kainate. Ipsilateral cell loss was prominent in hippocampal pyramidal cells and hilar neurons. An unusual pattern of progressive enlargement of the dentate gyrus was obse rved with a marked radial dispersion of the granule cells associated with r eactive astrocytes. Mossy fibre sprouting occurred both in the supragranula r molecular layer and infrapyramidal stratum oriens layer of CA3. The expre ssion of the embryonic form of the neural cell adhesion molecule coincided over time with granule cell dispersion. Our data describe the first histological, electrophysiological and behaviou ral evidence suggesting that discrete excitotoxic lesions of the hippocampu s in mice can be used as an isomorphic model of mesial temporal lobe epilep sy. (C) 1999 IBRO. Published by Elsevier Science Ltd.