Evaluation of anti-epileptic Lacosamide treatment on neural tube development: Chick embryo experimental model

Abstract

Objective: Even if epileptic women can give birth to healthy babies, the rates of premature birth, low birth weight, fetal and neonatal death risk, congenital malformations and growth retardation in pregnant women who use the antiepileptic drugs (AEDs) are high compared to the population. The present study aimed to examine the effects of AED Lacosamide (LCM) during pregnancy on the fetus in terms of neuronal and embryonic development in 48-hour chick embryo model. Material and Methods: 40SPF fertilized eggs divided into 4 equal numbers. At the 28th hour, LCM was applied in the sub-blastoderm, and the experiment was terminated at the 48th hour. Embryos were evaluated morphologically by neural tube position, somite number, and cranio-caudal length. Histopathologically, hematoxylin-eosin, Caspase-3 immunohistochemistry, and TUNEL staining were performed and and assessed for cell death. Results: LCM adversely affected neural tube position in groups 3 and 4 compared to control. In addition, it regressed embryonic development by decreasing somite number and craniocaudal length in groups 3 and 4. When evaluated in terms of apoptotic cell death, LCM increased caspase-3 immunoreactivity and the number of TUNEL-positive cells in groups 3 and 4, respectively (p=0.002), (p≤0.001). Conclusion: LCM was caused to regression of embryonic development and impaired neural tube position in early chick embryo model, dose-dependent manner. It increased cell death and showed teratogenic effects in the early embryo model. The usage of LCM for pregnant women should be considered carefully. It is obvious that more preclinic studies are needed to demonstrate LCM effects comprehensively.