Antiepileptic drugs lamotrigine and valproate differentially affect neuronal maturation in the developing chick embryo, yet with PAX6 as a potential common mediator.

Exposing the immature nervous system to specific antiepileptic drugs (AEDs) during pregnancy is linked to neurodevelopmental disorders such as autism spectrum disorder (ASD). Newer AEDs like lamotrigine (LTG) are hailed as safer, but recent epidemiological data suggest that even LTG carries a risk, although much lower than that associated with valproic acid (VPA), an older AED, which is also known to cause morphological alterations in the developing brain. Increasing evidence highlights cerebellar abnormalities as important in ASD pathophysiology.

Chicken embryo as animal model to study drug distribution to the developing brain.

Introduction: Rodent models are routinely used to assess the safety and developmental toxicity of pharmaceuticals, along with analysis of their distribution. These models require sacrifice of parent females, have challenges in the estimation of the number of embryos and stage of development, and are expensive and time-consuming. In this study, we used fertilized chicken eggs as an alternative model to address drug distribution to the developing brain of two antiepileptic drugs, valproic acid (VPA) and lamotrigine (LTG) at two developmental stages.