Effect of gabapentin on fetal rat brain and its amelioration by ginger

Intrauterine exposure to antiepileptic drugs (AEDs) is associated with neurodevelopmental alterations causing postnatal behavioral and cognitive alterations. These disorders are associated with the interference of these AEDs with the developing cerebral cortex and hippocampal neurons. Therefore, it is crucial to identify the drugs that should be avoided during pregnancy in order to prevent AED mediated developmental alterations. The present study was conducted to investigate the effects of prenatal exposure to the antiepileptic drug gabapentin (GBP) on the rat fetal brain during the organogenesis phase and to examine the potential ameliorative effect of ginger (Zingiber officinale). Consequently, the current study addressed the developmental neural changes on the histological, immuno-histochemical and ultrastructural levels. The brain of fetuses from the GBP group showed a highly significant decrease in their weight. Histologically, the cerebral cortex and hippocampus regions of fetuses maternally injected with GBP showed layer disorganization, vacuolated neuropil and massive cell degeneration. The expression of Caspase 3 was significantly increased in the brain of GBP fetuses, unlike the expression of Bcl-2 which was significantly decreased. On the ultrastructure level, the neurons showed pyknotic and chromatolytic nuclei. The cytoplasm was rarefied with swollen organelles. Co-administration of ginger evidently ameliorated most of these effects. In conclusion, GBP administration during pregnancy could possibly affect the developing fetal brain and ginger may have ameliorating effect against the induced GBP neurotoxicity and should be taken in parallel.