title: Antiepileptic effects of levetiracetam in a rodent neonatal seizure model.
abstract: BACKGROUND
  Neonatal seizures can result in chronic epilepsy and long-term behavioral and cognitive deficits. Levetiracetam (LEV), an antiepileptic drug that binds to the synaptic vesicle protein 2A (SV2A), has been increasingly used off-label for the therapy of neonatal seizures. Preclinical data regarding the acute or long-term efficacy of LEV are lacking.
  
  
  METHODS
  We tested the anticonvulsant efficacy of LEV in a rat model of hypoxia-induced neonatal seizures. In addition, we evaluated the protective effects of postnatal day (P)10 LEV treatment on later-life kainic acid (KA)-induced seizure susceptibility and seizure-induced neuronal injury. Western blot and immunohistochemistry were used to assess the developmental regulation of SV2A in the rat and human brain.
  
  
  RESULTS
  LEV pretreatment at P10 significantly decreased the cumulative duration of behavioral and electrographic seizures at both 25 and 50 mg/kg. At P40, KA-induced seizures and neuronal loss were significantly diminished in rats previously treated with LEV. LEV target SV2A is present in both neonatal rat and human brain and increases steadily to adulthood.
  
  
  CONCLUSIONS
  LEV suppressed acute seizures induced by perinatal hypoxia and diminished later-life seizure susceptibility and seizure-induced neuronal injury, providing evidence for disease modification. These results support consideration of a clinical trial of LEV in neonatal seizures.
authors.affiliation: Department of Neurology, Children's Hospital Boston, Boston, MA, USA.
authors.forename: Delia M
authors.initials: DM
authors.lastname: Talos
authors.forename: Meayoung
authors.initials: M
authors.lastname: Chang
authors.forename: Bela
authors.initials: B
authors.lastname: Kosaras
authors.forename: Erin
authors.initials: E
authors.lastname: Fitzgerald
authors.forename: Andrew
authors.initials: A
authors.lastname: Murphy
authors.forename: Rebecca Dunn
authors.initials: RD
authors.lastname: Folkerth
authors.forename: Frances E
authors.initials: FE
authors.lastname: Jensen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity; D000077287:Levetiracetam; D008562:Membrane Glycoproteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010889:Piracetam / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*
chemical_list: D000927:Anticonvulsants; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C076414:SV2A protein, human; D000077287:Levetiracetam; D007608:Kainic Acid; D010889:Piracetam