Seizures in the intrahippocampal kainic acid epilepsy model: characterization using long-term video-EEG monitoring in the rat Introduction Medial temporal lobe epilepsy (TLE) is the most common type of symptomatic epilepsy and is characterized by complex partial seizures with or without secondary generalization originating from the temporal lobe regions (1). TLE development covers three phases: (i) an initial precipitating insult of the brain such as febrile seizures, head trauma, status epilepticus (SE) or stroke initiating a cascade of events; (ii) a period of epileptogenesis during which molecular and ⁄ or structural changes occur; (iii) chronic epilepsy characterized by the occurrence of spontaneous seizures. The most common histopathological finding in TLE is atrophy of the hippocampus associated with neuronal loss in all hippocampal areas (2, 3). The combination of neuronal loss and gliosis is termed hippocampal sclerosis. Another characteristic phenomenon in TLE is sprouting of the axons of granule cells or mossy fibres. This mossy fibre sprouting is believed to enhance excitability (4–7). Animal models for chronic TLE need to resemble the epileptic state in which spontaneous and recurrent seizures occur (8, 9). In rodents, spontaneous seizures are provoked by brain infarction (10, 11), traumatic brain damage (12), febrile seizures (13), kindling (14) and SE. The SE model of chronic TLE has been extensively studied (9, 15–37). SE is the precipitating insult that initiates histopathological changes in temporal lobe regions and epileptogenesis resulting in the occurrence of spontaneous seizures (38–42). SE can be induced either by electrical or chemical stimulation [kainic acid (KA), pilocarpine] of the various brain regions. Electrical stimulation is administrated in the perforant path (25, 32), ventral hippocampus (17, 31) or the amygdala Acta Neurol Scand 2009: 119: 293–303 DOI: 10.1111/j.1600-0404.2008.01108.x Copyright Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard ACTA NEUROLOGICA SCANDINAVICA Raedt R, Van Dycke A, Van Melkebeke D, De Smedt T, Claeys P, Wyckhuys T, Vonck K, Wadman W, Boon P. Seizures in the intrahippocampal kainic acid epilepsy model: characterization using long- term video-EEG monitoring in the rat. Acta Neurol Scand 2009: 119: 293–303. Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard. Objective – Intrahippocampal injection of kainic acid (KA) in rats evokes a status epilepticus (SE) and leads to spontaneous seizures. However to date, precise electroencephalographic (EEG) and clinical characterization of spontaneous seizures in this epilepsy model using long-term video-EEG monitoring has not been performed. Materials and Methods – Rats were implanted with bipolar hippocampal depth electrodes and a cannula for the injection of KA (0.4 lg ⁄ 0.2 ll) in the right hippocampus. Video-EEG monitoring was used to determine habitual parameters of spontaneous seizures such as seizure frequency, severity, progression and day–night rhythms. Results – Spontaneous seizures were detected in all rats with 13 out of 15 animals displaying seizures during the first eight weeks after SE. A considerable fraction (35%) of the spontaneous seizures did not generalize secondarily. Seizure frequency was quite variable and the majority of the KA- treated animals had less than one seizure per day. A circadian rhythm was observed in all rats that showed sufficient seizures per day. Conclusions – This study shows that the characteristics of spontaneous seizures in the intrahippocampal KA model display many similarities to other SE models and human temporal lobe epilepsy. R. Raedt 1 , A. Van Dycke 1 , D. Van Melkebeke 1 , T. De Smedt 1 , P. Claeys 1 , T. Wyckhuys 1 , K. Vonck 1 , W. Wadman 2 , P. Boon 1 1 Laboratory for Clinical and Experimental Neurophysiology, Department of Neurology, Ghent University Hospital, Belgium; 2 Centre for Neuroscience, Swammerdam Institute of Life Sciences, University of Amsterdam, The Netherlands Key words: kainic acid; video-EEG monitoring; seizures; temporal lobe epilepsy; intrahippocampal; status epilepticus; characterization Raedt Robrecht, University Hospital Ghent, De Pintelaan 185, 9000 Ghent, Belgium. Tel.: 0032 9 240 33 55 Fax: 0032 9 240 33 60 e-mail: Robrecht.Raedt@UGent.be Accepted for publication August 12, 2008 293