Effect of systemic and intracortical administration of phenytoin in two genetic models of absence epilepsy

1 Spontaneous 7–10 Hz spike‐wave discharges (SWDs) are the electroencephalographic hallmark of absence seizures, as can be observed in WAG/Rij as well as in GAERS, two commonly used well‐validated genetic rat models of absence epilepsy. A local upregulation of sodium channels within the perioral reg...

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Published in:	British journal of pharmacology Vol. 148; no. 8; pp. 1076 - 1082
Main Authors:	Gurbanova, Ayten A, Aker, Rezzan, Berkman, Kemal, Onat, Filiz Yilmaz, Rijn, Clementana M, Luijtelaar, Gilles
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-08-2006 Nature Publishing Nature Publishing Group
Subjects:	absence epilepsy Action Potentials Animals Anticonvulsants - administration & dosage Biological and medical sciences Cortical focus theory Disease Models, Animal Drug Administration Routes Electroencephalography Epilepsy, Absence - genetics Epilepsy, Absence - physiopathology ethosuximide GAERS genetic models Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Male Medical sciences Mice Nervous system (semeiology, syndromes) Neurology Pharmacology. Drug treatments phenytoin Phenytoin - administration & dosage spike‐wave discharges translation research WAG/Rij absence epilepsy Nervous system diseases Ethosuximide Epilepsy spike-wave discharges Petit mal WAG/Rij Anticonvulsant GAERS genetic models Genetic translation Cerebral disorder Central nervous system disease Genetics Models Cortical focus theory translation research Phenytoin
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Summary:	1 Spontaneous 7–10 Hz spike‐wave discharges (SWDs) are the electroencephalographic hallmark of absence seizures, as can be observed in WAG/Rij as well as in GAERS, two commonly used well‐validated genetic rat models of absence epilepsy. A local upregulation of sodium channels within the perioral region of the primary somatosensory cortex indicated an initiation site for SWDs in WAG/Rij rats, in line with a new theory that assumes that SWDs have a cortical focal origin in the perioral region of the somatosensory cortex. We tested whether bilateral microinfusion at this focal site of the sodium channel blocker phenytoin, which is known to aggravate SWDs after systemic administration, reduces SWDs in both models. 2 WAG/Rij rats and GAERS, chronically provided with cortical EEG electrodes and bilateral cortical cannula's, were used. The EEGs were recorded before and after or systemic or bilateral infusion of phenytoin. 3 Microinfusion of phenytoin at the perioral region of the somatosensory cortex produced an immediate cessation of seizure activity in WAG/Rij rats, while systemic injection produced an increase in both genetic models. Microinfusion of the same and higher concentrations of phenytoin in GAERS at the same stereotactic coordinates showed no effect. Phenytoin was effective in GAERS 2 mm more posteriorly. 4 The data suggest that both genetic models have a cortical area at which diametrically opposite effects of phenytoin can be found compared to systemic injections: a decrease after local microinfusion and aggravation after systemic administration, although the exact cortical location may be different. Moreover, a deficit in sodium channels might be an ethiological factor underlying an increased probability for the initiation of SWDs in the somatosensory cortex. British Journal of Pharmacology (2006) 148, 1076–1082. doi:10.1038/sj.bjp.0706791
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0007-1188 1476-5381
DOI:	10.1038/sj.bjp.0706791