Administration of diazepam during status epilepticus reduces development and severity of epilepsy in rat

Pitkänen, Asla, Kharatishvili, Irina, Narkilahti, Susanna, Lukasiuk, Katarzyna and Nissinen, Jari (2005) Administration of diazepam during status epilepticus reduces development and severity of epilepsy in rat. Epilepsy Research, 63 1: 27-42. doi:10.1016/j.eplepsyres.2004.10.003

Author Pitkänen, Asla
Kharatishvili, Irina
Narkilahti, Susanna
Lukasiuk, Katarzyna
Nissinen, Jari
Title Administration of diazepam during status epilepticus reduces development and severity of epilepsy in rat
Journal name Epilepsy Research   Check publisher's open access policy
ISSN 0920-1211
Publication date 2005-01
Year available 2004
Sub-type Article (original research)
DOI 10.1016/j.eplepsyres.2004.10.003
Volume 63
Issue 1
Start page 27
End page 42
Total pages 6
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Formatted abstract
Prevention of epileptogenesis after brain insults, such as status epilepticus (SE), head trauma, or stroke, remains a challenge. Even if epilepsy cannot be prevented, it would be beneficial if the pathologic process could be modified to result in a less severe disease. We examined whether early discontinuation of SE reduces the risk of epilepsy or results in milder disease. Epileptogenesis was triggered with SE induced by electrical stimulation of the amygdala. Animals (n = 72) were treated with vehicle or diazepam (DZP, 20 mg/kg) 2 h or 3 h after the beginning of SE. Electrode-implanted non-stimulated rats served as controls for histology. All animals underwent continuous long-term video-electroencephalography monitoring 7-9 weeks and 11-15 weeks later to detect the occurrence and severity of spontaneous seizures. As another outcome measure, the severity of hippocampal damage was assessed in histologic sections. In the vehicle group, 94% of animals developed epilepsy. DZP treatment reduced the percentage of epileptic animals to 42% in the 2-h DZP group and to 71% in the 3-h DZP group (p < 0.001 and p < 0.05 compared to the vehicle group, respectively). If epilepsy developed, the seizures were less frequent in DZP-treated animals compared to the vehicle group (median 16.4 seizures/day), particularly in the 2-h DZP group (median 0.4 seizures/day). Finally, if DZP treatment was started 2 h, but not 3 h after SE, the severity of hippocampal cell loss was milder and the density of mossy-fiber sprouting was lower than in the vehicle group. These data indicate that treatment of SE with DZP within 2 h reduces the risk of epilepsy later in life, and if epilepsy develops, it is milder.
© 2004 Elsevier B.V. All rights reserved.
Keyword Amygdala
Disease modification
Mossy fiber sprouting
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Available online 28 December 2004

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Advanced Imaging Publications
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Created: Wed, 30 Mar 2011, 11:37:30 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging