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. CONCLUSION: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.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Talos DM,Chang M,Kosaras B,Fitzgerald E,Murphy A,Folkerth RD,Jensen FE

doi

10.1038/pr.2012.151

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

24-30

issue

1

eissn

0031-3998

issn

1530-0447

pii

pr2012151

journal_volume

73

pub_type

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