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

• Published in: Journal of the neurological sciences Vol. 348; no. 1; pp. 111 - 120
• Main Authors: Cheng, Lan, Lei, Song, Chen, Si-Han, Hong, Zhen, Yang, Tian-Hua, Li, Li, Chen, Fei, Li, Hong-Xia, Zhou, Dong, Li, Jin-Mei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.01.2015
• Subjects: Administration, Intravenous; Animals; Anticonvulsants - administration & dosage; Anticonvulsants - pharmacology; Coriaria lactone; Disease Models, Animal; Humans; Intravenous levetiracetam; Lactones - pharmacology; Macaca mulatta; Male; Neurology; Neuronal injury; Neurons - drug effects; Neurons - pathology; Piracetam - administration & dosage; Piracetam - analogs & derivatives; Piracetam - pharmacology; Pretreatment; Rhesus monkey; Status epilepticus; Status Epilepticus - chemically induced; Status Epilepticus - prevention & control; antiepileptic drugs; electroencephalography; EEG; terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining; Neuronal injury; CL; AEDs; GFAP; Coriaria lactone; status epilepticus; iv LEV; Rhesus monkey; SE; TUNEL; SSSE; Pretreatment; LEV; self-sustaining status epilepticus; glial fibrillary acidic protein; intravenous levetiracetam; levetiracetam; Intravenous levetiracetam; Status epilepticus
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2014.11.017

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.