Effects of chronic treatment with levetiracetam on hippocampal field responses after pilocarpine-induced status epilepticus in rats

Brain Research Bulletin
Doru-Georg MargineanuHenrik Klitgaard

Abstract

Levetiracetam (Keppra) is a new generation antiepileptic drug characterized by a unique profile of activity in experimental models of epilepsy. It also has a distinct binding site in the brain, i.e. the synaptic vesicle protein type 2 (SV2A). Levetiracetam has been reported to have antiepileptogenic and disease-modifying properties. In the present study the effects of chronic treatment with levetiracetam were assessed in rats that sustained pilocarpine-induced status epilepticus (SE). Hippocampal field potentials were recorded in vivo in anesthetized animals after 3-day washout period that followed 21-day treatment with different doses of levetiracetam (50, 150 or 300 mg/kg/day) administered via ALZET osmotic mini-pumps. Vehicle treated rats together with naive animals (not subjected to SE) were used as control groups. Chronic treatment with levetiracetam yielded clinically relevant plasma concentrations throughout the experiment with complete washout of the drug 3 days after treatment cessation. At this point in time post-SE rats chronically treated with vehicle developed clear signs of hippocampal hyperexcitability, i.e. increased amplitude of population spike (PS) recorded in the dentate gyrus and reduced paired-pulse inhibi...Continue Reading

References

Aug 2, 2002·Epilepsy Research·J P LeiteE A Cavalheiro
Feb 5, 2003·Seizure : the Journal of the British Epilepsy Association·Henrik KlitgaardDoru-Georg Margineanu
Jun 23, 2004·Nature Reviews. Neuroscience·Michael A Rogawski, Wolfgang Löscher
Jun 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Berkley A LynchBruno Fuks
Apr 15, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Krista L Moulder, Steven Mennerick
Apr 11, 2006·Molecular Neurobiology·Krista L MoulderSteven Mennerick
Sep 15, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Krista L MoulderSteven Mennerick

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Citations

May 19, 2010·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Kathryn A Giblin, Hal Blumenfeld
Mar 29, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Rafal M KaminskiHenrik Klitgaard
Sep 30, 2015·Expert Review of Neurotherapeutics·Fangshuo ZhengXuefeng Wang
Jul 1, 2009·Expert Review of Clinical Pharmacology·Armel StockisChristian Otoul
Jul 14, 2010·Epilepsy Research·S H TonekaboniM Ghofrani
Oct 26, 2016·CNS Drugs·Wolfgang LöscherHenrik Klitgaard
Jan 18, 2018·Glycobiology·Bruce Caterson, James Melrose
Feb 27, 2018·Pharmacological Reports : PR·José Luis Cortes-AltamiranoAlfonso Alfaro-Rodriguez

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