The systemic kainic acid rat model of temporal lobe epilepsy: Long-term EEG monitoring

Animal models reproducing the characteristics of human epilepsy are essential for the elucidation of the pathophysiological mechanisms. In epilepsy research there is ongoing debate on whether the epileptogenic process is a continuous process rather than a step function. The aim of this study was to assess progression of epileptogenesis over the long term and to evaluate possible correlations between SE duration and severity with the disease progression in the kainic acid model. Rats received repeated KA injections (5 mg/kg) until a self-sustained SE was elicited. Continuous depth EEG recording started before KA injection and continued for 30 weeks. Mean seizure rate progression could be expressed as a sigmoid function and increased from 1 +/- 0.2 seizures per day during the second week after SE to 24.4 +/- 6.4 seizures per day during week 30. Seizure rate progressed to a plateau phase 122 +/- 9 days after SE. However, the individual seizure rate during this plateau phase varied between 14.5 seizures and 48.6 seizures per day. A circadian rhythm in seizure occurrence was observed in all rats. Histological characterization of damage to the dentate gyrus in the ICA treated rats confirmed the presence of astrogliosis and aberrant mossy fiber sprouting in the dentate gyrus. This long-term EEG monitoring study confirms that epileptogenesis is a continuous process rather than a step function. (C) 2015 Elsevier B.V. All rights reserved.