The effect of levetiracetam on status epilepticus-induced neuronal death in the rat hippocampus.

Abstract

PURPOSE:

Levetiracetam has been reported to be well tolerated and effective in status epilepticus (SE) refractory to benzodiazepine. Because of little preclinical or clinical data concerning the outcomes of LEV in SE-induced neuronal death and vasogenic edema, we investigated the effect of LEV on SE-induced injury in comparison to diazepam (DZP), and valproate (VPA).

METHODS:

Two hours after pilocarpine-induced SE, rats were given one of the following drugs; (1) DZP, (2) LEV, (3) VPA, (4) DZP+LEV, (5) DZP+VPA, and (6) DZP+oxiracetam. Three-four days after SE, neuronal damage and vasogenic edema were evaluated by Fluoro-Jade B (FJB) staining and serum-protein extravasation, respectively.

RESULTS:

LEV (≥50 mg/kg) was effective to protect neuronal damage from SE in comparison to DZP and VPA. LEV as an add-on drug with DZP could not alleviate neuronal damage as compared to LEV alone. VPA (≥100 mg/kg) was effective to protect neuronal damage from SE, as compared to DZP. VPA as an add-on drug with DZP reduced neuronal damage, as compared to DZP alone.

CONCLUSION:

These findings suggest that LEV may negatively interact with DZP, and be more effective to prevent SE-induced neuronal death as a first line drug than as a second line therapy after BDZ treatment.

• Authors: Duk-Shin Lee, Hea Jin Ryu, Ji-Eun Kim, Hui-Chul Choi, Yeong-In Kim, Hong-Ki Song, Tae-Cheon Kang
• Journal: Seizure (Seizure) Vol. 22 Issue 5 Pg. 368-77 (Jun 2013) ISSN: 1532-2688 [Electronic] England
• PMID: 23490457 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Fluoresceins
• fluoro jade
• Pilocarpine
• Levetiracetam
• Valproic Acid
• Diazepam
• Piracetam

Topics

• Animals
• Behavior, Animal (drug effects)
• Cell Death (drug effects)
• Diazepam (therapeutic use)
• Disease Models, Animal
• Drug Therapy, Combination (methods)
• Fluoresceins (therapeutic use)
• Hippocampus (drug effects)
• Levetiracetam
• Neurons (drug effects)
• Pilocarpine (therapeutic use)
• Piracetam (analogs & derivatives, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Status Epilepticus (chemically induced, drug therapy, pathology)
• Valproic Acid (therapeutic use)