Prophylactic treatment with levetiracetam after status epilepticus: lack of effect on epileptogenesis, neuronal damage, and behavioral alterations in rats.
Levetiracetam (LEV) is a structurally novel antiepileptic drug (AED) which has demonstrated a broad spectrum of anticonvulsant activities both in experimental and clinical studies. Previous experiments in the kindling model suggested that LEV, in addition to its seizure-suppressing activity, may possess antiepileptogenic or disease-modifying activity. In the present study, we evaluated this possibility by using a rat model in which epilepsy with spontaneous recurrent seizures (SRS), behavioral alterations, and hippocampal damages develop after a status epilepticus (SE) induced by sustained electrical stimulation of the basal amygdala. Two experimental protocols were used. In the first protocol, LEV treatment was started 24h after onset of electrical amygdala stimulation without prior termination of the SE. In the second protocol, the SE was interrupted after 4h by diazepam, immediately followed by onset of treatment with LEV. Treatment with LEV was continued for 8 weeks (experiment #1) or 5 weeks (experiment #2) after SE, using continuous drug administration via osmotic minipumps. The occurrence of SRS was recorded during and after treatment. In addition, the rats were tested in a battery of behavioral tests, including the elevated-plus maze and the Morris water maze. Finally, the brains of the animals were analyzed for histological lesions in the hippocampal formation. With the experimental protocols chosen for these experiments, LEV did not exert antiepileptogenic or neuroprotective activity. Furthermore, the behavioral alterations, e.g., behavioral hyperexcitability and learning deficits, in epileptic rats were not affected by treatment with LEV after SE. These data do not support the idea that administration of LEV after SE prevents or reduces the long-term alterations developing after such brain insult in rats.
Brandt
Claudia
C
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bünteweg 17, D-30559 Hannover, Germany.
Glien
Maike
M
Gastens
Alexandra M
AM
Fedrowitz
Maren
M
Bethmann
Kerstin
K
Volk
Holger A
HA
Potschka
Heidrun
H
Löscher
Wolfgang
W
D000679:Amygdala / Q000502:physiology / Q000528:radiation effects; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects*; D001925:Brain Damage, Chronic / Q000473:pathology / Q000517:prevention & control*; D003975:Diazepam / Q000008:administration & dosage; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004558:Electric Stimulation / Q000009:adverse effects; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006948:Hyperkinesis / Q000188:drug therapy / Q000209:etiology; D000077287:Levetiracetam; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013550:Swimming / Q000523:psychology; D013997:Time Factors
D000927:Anticonvulsants; D000077287:Levetiracetam; D003975:Diazepam; D010889:Piracetam