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

Bradley L. Schlaggar, M.D., Ph.D., Named President and CEO of Kennedy Krieger Institute

We’re thrilled to welcome Bradley L. Schlaggar, M.D., Ph.D., to the Kennedy Krieger family as our next President and CEO.

Learn more.

Appointments & Referrals



Read inspiring stories, news and updates about the Institute's patient care, research, special education, professional training, and community programs.


Resource Finder


A free resource that provides access to information and support for individuals and families living with developmental disabilities.