Effects of the use of lamotrigine and topiramate during pregnancy on the development of fetal brain, and cognitive functions in rats

2. ABSTRACTEFFECTS OF THE USE OF LAMOTRIGINE AND TOPIRAMATEDURING PREGNANCY ON THE DEVELOPMENT OF FETAL BRAIN, ANDCOGNITIVE FUNCTIONS IN RATSAIM: In this study, it was aimed to investigate the effects of the new generationantiepileptic drugs, lamotrigine and topiramate, on the fetal brain development,cognitive functions, and the expression of S100B, NCAM and GFAP, duringpregnancy.MATERIAL AND METHOD: A total 28 adult Albino-Wistar female rats weredivided to seven groups each including four rats. All rats developed pregnancy and fedwith normal rat foods. The rats in the control group did not receive any medication.Three groups of the rats in the study group were given 25 mg/day topiramate,respectively first, second and third trimesters of the pregnancy. The other three groupsof the study group were given 25 mg/day lamotrigine respectively first, second andthird trimesters of the pregnancy. After the birth, brain tissues of the half of the animalswere decapitated and their brains were removed and stored and -700C until analys glial(GFAP, S100B) and neuronal markers (NCAM). The glial and neuronal markers wereanalyzed by Western Blot. After the breast feeding for 21 days, the second half of theyoung animals were separated according to their sexuality and were put into thedifferent cages. Morris Water Maze Test were performed in the 75 days old offspring.After the learning test is completed, these young animals were also decapitated. Theirbrain tissues were removed and stored at -70 0C. The glial and neuronal markers wereanalyzed by Western Blot .RESULTS: When the cognitive performance of the rats were compared, thetopiramate I and topiramate III groups were retarded regerding to control group (p<0,05and p<0,001, orderly) and topiramate II group was not significant regerding to controlgroup. There was a non-statistically weakness about the cognitive performancesbetween the control group and lamotrigine I group and also there was not anysignificance about the cognitive performance between control group and lamotrigine IIand III groups. Such markers GFAP, NCAM and S100B in the brain tissue, weredecreased particularly in the newborn topiramate I receiving group, and in adult rats, nodifference was observed regarding to the control group.CONCLUSION: According to the obtained results, it was concluded that use oftopiramate during the 1st and 3rd trimesters of pregnancy may cause retardation on thebrain development and cognitive functions, whereas, lamotrigine way be safer forobstetric utilization. Fetal effects should be considered before an antiepileptic ismanaged for any pregnant patient.KEY-WORDS: Lamotrigine, topiramate, pregnancy, fetal brain development,cognitive function, S100B, NCAM, GFAP.