EFFECTS OF LAMOTRIGINE ON STATUS EPILEPTICUS IN IMMATURE RATS
Abstract number :
2.131
Submission category :
Year :
2003
Submission ID :
3642
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Hana Kubova, Olga Retinskaya, Rastislav Druga, Pavel Mares Dept. of Developmental Epileptology, Institute of Physiology, Academy of Sciences, Prague 4, Czech Republic
To study the effects of lamotrigine (LMG) treatment during the acute phase of status epilepticus in immature rats.
Wistar albino rat pups 12 and 25 days old (P12 and P25) were implanted with cortical and hippocampal recording electrodes 20 hours after pretreatment with lithium chloride (3 mEq/kg i.p.). After a 15-min recording of spontaneous EEG status epilepticus (SE) was induced by pilocarpine (40 mg/kg i.p.). All animals in this study exhibited a clear-cut convulsive SE. Lamotrigine (10 or 20 mg/kg i.p) was injected after one hour of continuous convulsions and one hour later paraldehyde was administered (0.3 and 0.6 ml/kg i.p. in 12- and 25-day-old rats, respectively). EEG was recorded for 24 hours (with interruptions) in younger and continuously for 48 hours in older age group. At least 6 rats formed each age and dose group. Animals were then perfused and brain sections were stained with FluoroJade B (FJB) to demonstrate degenerating neurons. Results were compared with data from seized siblings not receiving lamotrigine.
Amplitude of epileptic EEG activity was decreased by both doses of LMG in P25 rats, especially in the cerebral cortex. Subsequent paraldehyde injection augmented this effect. Similar effect was observed in P12 rat pups only the difference between effects on cortical and hippocampal EEG was not marked. Motor seizures were suppressed in all animals in both age groups but suppression of EEG seizures was only transient in both age groups. Distribution of FJB-positive neurons markedly differed from those in control rats. Older animals exhibited substantial decrease of FJB-positive cells in cerebral cortex and thalamic nuclei whereas limbic structures were not protected. Younger age group where number of FJB-positive cells was lower than in P25 rats even under control conditions exhibited very variable results from nearly complete protection to a marked degeneration especially in the amygdalar complex. No obvious differences were found between the effects of the two doses of LMG in neither age group.
Lamotrigine exhibits age-dependent partial protection against seizure-induced neuronal degeneration in immature rats.
[Supported by: A research grant from Glaxo Wellcome]