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

B Van Nieuwenhuyse; R Raedt; M Sprengers; I Dauwe; S Gadeyne; E Carrette; J Delbeke; W J Wadman; P Boon; K Vonck

doi:10.1016/j.brainres.2015.08.016

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

Brain Res. 2015 Nov 19:1627:1-11. doi: 10.1016/j.brainres.2015.08.016. Epub 2015 Sep 14.

Authors

B Van Nieuwenhuyse¹, R Raedt², M Sprengers³, I Dauwe⁴, S Gadeyne⁵, E Carrette⁶, J Delbeke⁷, W J Wadman⁸, P Boon⁹, K Vonck¹⁰

Affiliations

¹ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology, and Neuropsychology, Department of Neurology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: Bregt.vannieuwenhuyse@ugent.be.
² Laboratory for Clinical and Experimental Neurophysiology, Neurobiology, and Neuropsychology, Department of Neurology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: Robrecht.Raedt@ugent.be.
³ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology, and Neuropsychology, Department of Neurology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: mathieu.sprengers@ugent.be.
⁴ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology, and Neuropsychology, Department of Neurology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: ine.dauwe@uzgent.be.
⁵ Swammerdam Institute of Life Sciences, University of Amsterdam, Sciencepark 904, 1098 XH Amsterdam, The Netherlands. Electronic address: stefanie.gadeyne@uzgent.be.
⁶ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology, and Neuropsychology, Department of Neurology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium.
⁷ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology, and Neuropsychology, Department of Neurology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: Jdelbeke@gmail.com.
⁸ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology, and Neuropsychology, Department of Neurology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium; Swammerdam Institute of Life Sciences, University of Amsterdam, Sciencepark 904, 1098 XH Amsterdam, The Netherlands. Electronic address: wjwadman@gmail.com.
⁹ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology, and Neuropsychology, Department of Neurology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: paul.boon@ugent.be.
¹⁰ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology, and Neuropsychology, Department of Neurology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: kristl.vonck@ugent.be.

PMID: 26381287
DOI: 10.1016/j.brainres.2015.08.016

Abstract

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 (5mg/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 KA 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.

Keywords: animal model; kainic acid; long-term EEG monitoring; seizures; temporal lobe epilepsy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
Brain / drug effects
Brain / physiopathology
Brain Waves / drug effects*
Circadian Rhythm / drug effects
Disease Models, Animal
Electroencephalography*
Epilepsy, Temporal Lobe / chemically induced*
Excitatory Amino Acid Agonists / toxicity*
Kainic Acid / toxicity*
Male
Monitoring, Physiologic
Rats
Rats, Sprague-Dawley

Substances

Excitatory Amino Acid Agonists
Kainic Acid