Diazepam Treatment Has a Disease Modifying Effect on the Developing Epilepsy after Status Epilepticus in Rat.
Abstract number :
2.087
Submission category :
Year :
2001
Submission ID :
2801
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
J.P.T. Nissinen, M.Sc., A.I.Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland; S. Narkilahti, M.Sc., A.I.Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland; K. Lukasiuk, PhD., A.I.Virtanen Insti
RATIONALE: Status epilepticus (SE) is associated with an elevated risk of epilepsy and cognitive decline later in life. A question is: does the treatment of status epilepticus have any antiepileptogenic effects or (b) if the epilepsy develops, is the disease as severe as without treatment. Here, these questions were addresssed in the amygdala stimulation model of epilepsy in rats.
METHODS: Self-sustained status epilepticus (SSSE) was induced by stimulating the lateral nucleus of amygdala of adult Spraque-Dawley rats (n=73) electrically for 20-30 min (100 ms train of 1-ms, 60 Hz bipolar pulses, 400 [mu]A, every 0.5 sec). Thirty-seven of the animals ([dsquote]untreated[dsquote]) were allowed to recover from SSSE spontaneously. In another group of rats (n=36), SSSE was stopped with diazepam (DZP, 20 mg/kg , i.p.) 2.3-3 hours after the induction of SE (an additional dose 5-10 mg/kg was given 6-8 hours later. SSSE and the development of spontaneous seizures were monitored with video-EEG monitoring. The occurrence of epilepsy and seizure frequency were assessed 7-9 weeks after SSSE with a continuous video-EEG monitoring (24 h/day, at least for 7 days).
RESULTS: In the DZP group, the number of animals that developed epilepsy was lower than in the untreated group (51% (19/37) vs. 83% (30/36), p=0.006, Pearson chi-square test). The percentage of epileptic animals with mild epilepsy (seizure frequence [lt]1/day) was 53% (10/19) in the DZP group and 37% (11/30) in the untreated group (no difference). Percentage of animals with no epilepsy or mild epilepsy was 76% (28/37) in the DZP group and 47% (17/36) in the untreated group (p=0.017, Pearson chi-square test). The duration of spontaneous seizures did not differ between the DZP and untreated groups (p[gt]0.05, Mann-Whitney U-test).
CONCLUSIONS: Administration of DZP at about 3 h after the beginning of SE disrupts epileptogenesis in a subgroup of animals. Further, a significantly lower proportion of DZP treated animals develop severe epilepsy ([gt]1 seizures/day). Taken together, our data suggest that discontinuation of SE with DZP has a disease modifying effect on the developing epilepsy.
Support: The Vaajasalo Foundation, The Sigrid Juselius Foundation and The Academy of Finland.