Gabapentin neuroprotection and seizure suppression in immature mouse brain ischemia.
Stroke is a major cause of neurologic morbidity in neonates and children. Because neonatal and pediatric stroke frequently present with seizures, the question of which anticonvulsant best blocks acute ischemic seizures and reduces injury is clinically relevant. The purpose of this study was to determine the extent to which gabapentin is neuroprotective and suppresses acute seizures in this model of ischemic injury in the immature brain. Postnatal day 12 CD1 mice underwent right common carotid artery ligation and immediately after ligation received a 0, 50, 100, 150, or 200 mg/kg dose of gabapentin intraperitoneally. Acute seizure activity was behaviorally scored and hemispheric brain atrophy measured. In vehicle-treated mice, severity of acute seizures correlated with hemispheric brain atrophy 4 wks later. Gabapentin significantly decreased acute seizures at 200 mg/kg and reduced brain atrophy at doses of 150 and 200 mg/kg but not at lower doses. These results suggest that gabapentin effectively reduces acute seizures and injury after ischemia in the immature brain. When analyzed by animal sex, the data suggest that gabapentin may more effectively reduce acute seizures and injury in male pups vs. female pups.
Traa
Beatrix S
BS
Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland 21205, USA.
Mulholland
Justin D
JD
Kadam
Shilpa D
SD
Johnston
Michael V
MV
Comi
Anne M
AM
D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001284:Atrophy; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D000077206:Gabapentin; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D012640:Seizures / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012737:Sex Factors; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D018696:Neuroprotective Agents; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin