ltal. J. Neurol. Sci. 16:39-44, 1995 Kainic acid induced hippocampal seizures in rats: comparisons of acute and chronic seizures using intrahippocampal versus systemic injections Babb T.L. */**, Pereira-Leite J.**, Mathern G.W.***, Pretorius J.K.** * Department of Neurology, ** Brain Research Institute, and *** Division of Neurological Surgery Reed Neurological Research Center, UCLASchool of Medicine, Universityof California, Los Angeles Hyppocampal epilepsy is a recently defined syndrome occurring in 65% of all temporal lobe epilepsies as defined by: 1) electrographic (EEG) onset in the hippocampus (HC) prior to EEG seizures elsewhere, 2) post-resection hippo- campal sclerosis and mossy fiber synaptic reorganizations and 3) relief of typical complex partial se&ures after surgical resection of the hyppocampus. We used intrahippocampal kainic acid injections V2 in rats at different deve- lopmental ages (postnatal 7 through adult) to develop long term spontaneous HC EEG spikes, EEG seizures, and behavioral seizures. Split-screen video/ EEG monitoring demonstrated that this intrahippocampal kainic acid model produced progressive development of" 1) ipsilateral interictal spikes, 2) later polyspike complexes, 3) bilaterally-asynchronous EEG spiking, 4) unilateral HC EEG seizure onsets with occasional secondarily generalized spread to ap- posite HC and motor cortex to elicit complex partial seizures, and 5) in all seizing rats there was mossy fiber synaptic reorganization, even when injected at age 7 days. These results indicate that the intrahippocampal kainic acid injection model is similar to human hippocampal epilepsy. Key Words: temporal lobe epilepsy -- partial seizures -- synaptic reorganization -- developing sei- zures -- EEG/video. In order to develop a rat model of human tem- poral lobe epilepsy, kainic acid (KA) was used to produce hippocampal cell loss and mossy fiber excitatory synaptic reorganizations [18]. These pathologic findings are constant findings in surg- ically-treated human hippocampal epilepsy [2, 4]. Supported by NIH Grants NS 02808, NS 31655 (T.L.B.); K08 NS 1603 (G.W.M.); and Fogarty Fel- lowship TWO 4959 (J.P.L.). Previous rat studies given intraperitoneal KA showed that after several weeks there was an as- sociation between fascia dentata mossy fiber sprouting and "hyperexcitability", as demonstrat- ed by multiple spikes in granule cells in vitro [22] or by observed behavioral seizures [7]. Cavalhei- ro et al. [6] found spontaneous seizures 15 days after intrahippocampal KA, but recordings of EEG and behavior were discontinued after 50 days. Rats given intrahippocampal kainate have also shown sparing of fascia dentata GABAergic neurons and 39