Study of the Effect of Prenatal Administration of Pregabalin on Cerebellar Cortex of Albino Rat's Offspring and the Possible Protective Role of Folic Acid

Abstract

Background: Anti-epileptic drugs have harmful effects on the nervous system development. Pregabalin was approved in 2004 as new anti-epileptic drugs. Supplementation of folic acid during pregnancy is associated with a lower incidence of developmental problems in the nervous system. Objective (Aim): Assessment the effects of prenatal administration of pregabalin on the cerebellar cortex of albino rat’s offspring, and evaluation of folic acid's protective potential. Material and methods: 24 pregnant albino rats were divided equally into group I, group II and group III. From gestational day one until birth, Pregabalin (80 mg/kg body weight/day) was given to group I, pregabalin (80 mg/kg body weight/day) and folic acid (400 μg/kg body weight/day) were given to Group III and no medications were given to group I. At the age of two and four weeks, 30 offspring born to the experimental groups were sacrificed (5 offspring from each group for each age). Specimens were taken from the cerebellar cortices of rat’s offspring and were prepared for histological, immunohistochemical and histomorphometric studies. Results: The cerebellar cortex of offspring of group II showed disrupted architecture with marked degenerative changes especially in Purkinje cells. Degeneration of the axons with depletion of myelin sheath was detected. The cerebellar cortex of offspring of group III showed restoration of the normal architecture with improvement of the degenerative changes. Conclusions: Administration of Pregabalin during pregnancy has neurotoxic effects on the developing cerebellar cortex of albino rat’s offspring. In addition, the administration of folic acid alongside Pregabalin can reduce these neurotoxic effects.