Pretreatment with intravenous levetiracetam in the rhesus monkey Coriaria lactone-induced status epilepticus model.

Abstract

PURPOSE:

To investigate the antiepileptic and protective effects of intravenous levetiracetam (iv LEV) in the rhesus monkey model of acute status epilepticus (SE).

METHODS:

Thirty minutes before intraperitoneal induction of SE by Coriaria lactone (CL), rhesus monkeys were treated with LEV (15 or 150 mg/kg) delivered intravenously as a single bolus. CL dose and epileptic behavior were recorded. Electroencephalography (EEG) was performed before and during the experiment. All rhesus monkeys were killed after 1-month video monitoring and processed for pathological investigation of neuronal injury, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, and glial fibrillary acidic protein (GFAP) staining.

RESULTS:

No animal exhibited spontaneous seizures during 1-month video monitoring. Development of acute SE was significantly inhibited in the group given 150 mg/kg LEV, compared with controls and the 15 mg/kg LEV group. Delayed latency, reduction of SE duration, decreased cumulative time of tonic convulsions, slight severity of SE, and a high CL induction dose were observed in the high LEV dose group (p<0.05). The EEG showed less frequent epileptic discharges in the group administered with 150 mg/kg LEV. Hematoxylin and eosin (H&E) staining, ultrastructural examination, TUNEL and GFAP staining revealed serious damage, including neuron loss, swollen mitochondrion, and strong positivity for TUNEL in the hippocampus and thalamus of controls, whereas moderate damage in the group administered with 15 mg/kg LEV, and very mild damage in the 150 mg/kg LEV group. Gliosis was found in the hippocampus of controls, not in the LEV groups and normal rhesus monkey.

CONCLUSION:

The study supports the antiepileptic and protective effect of pretreatment with intravenous LEV in rhesus monkey model with SE.

• Authors: Lan Cheng, Song Lei, Si-Han Chen, Zhen Hong, Tian-Hua Yang, Li Li, Fei Chen, Hong-Xia Li, Dong Zhou, Jin-Mei Li
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 348 Issue 1-2 Pg. 111-20 (Jan 15 2015) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 25579413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Anticonvulsants
• Lactones
• Levetiracetam
• coriaria lactone
• Piracetam

Topics

• Administration, Intravenous
• Animals
• Anticonvulsants (administration & dosage, pharmacology)
• Disease Models, Animal
• Humans
• Lactones (pharmacology)
• Levetiracetam
• Macaca mulatta
• Male
• Neurons (drug effects, pathology)
• Piracetam (administration & dosage, analogs & derivatives, pharmacology)
• Status Epilepticus (chemically induced, prevention & control)