Different effects of high- and low-dose phenobarbital on post-stroke seizure suppression and recovery in immature CD1 mice

Geoffrey J. Markowitz, Shilpa D. Kadam, Dani R. Smith, Michael V. Johnston, Anne M. Comi

Research output: Contribution to journalArticle

Abstract

Neonatal stroke presents with seizures that are usually treated with phenobarbital. We hypothesized that anticonvulsants would attenuate ischemic injury, but that the dose-dependent effects of standard anticonvulsants would impact important age-dependent and injury-dependent consequences. In this study, ischemia induced by unilateral carotid ligation in postnatal day 12 (P12) CD1 mice was immediately followed by an i.p. dose of vehicle, low-dose or high-dose phenobarbital. Severity of acute behavioral seizures was scored. 5-Bromo-2′-deoxyuridine (BrdU) was administered from P18 to P20, behavioral testing performed, and mice perfused at P40. Atrophy quantification and counts of BrdU/NeuN-labeled cells in the dentate gyrus were performed. Blood phenobarbital concentrations were measured 30 mg/kg phenobarbital reduced acute seizures and chronic brain injury, and restored normal weight gain and exploratory behavior. By comparison, 60 mg/kg was a less efficacious anticonvulsant, was not neuroprotective, did not restore normal weight gain, and impaired behavioral and cognitive recovery. Hippocampal neurogenesis was not different between treatment groups. These results suggest a protective effect of lower-dose phenobarbital, but a lack of this effect at higher concentrations after stroke in P12 mice.

Original languageEnglish (US)
Pages (from-to)138-148
Number of pages11
JournalEpilepsy Research
Volume94
Issue number3
DOIs
StatePublished - May 1 2011

Keywords

  • Anticonvulsant
  • Behavioral testing
  • Dose-dependence
  • Neurogenesis
  • Neuroprotection
  • Phenobarbital

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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