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

Mark McIntosh,'s picture
PubMed URL: 
Comi AM
Author List: 
Markowitz GJ
Kadam SD
Smith DR
Johnston MV
Comi AM
Epilepsy Res
PubMed ID: 
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. 30mg/kg phenobarbital reduced acute seizures and chronic brain injury, and restored normal weight gain and exploratory behavior. By comparison, 60mg/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.
Published Date: 
May, 2011

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