Effect of valproic acid administration during pregnancy on postnatal development of cerebellar cortex of albino rat and the possible protective role of folic acid : Histological, histomorphometric and ultrastructural study / Eid Nassar Ali ; Supervised Saber Ibrahim Shona , Ayman Aboelenein Rizk , Abir Oueida Elsadik

Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Anatomy

Introduction: Valproic acid is one of the most commonly used drugs in treatment of epilepsy. Folic acid supplementation is associated with a reduction in birth defects, as well as positive maternal outcomes during pregnancy. Aim of work: This study was conducted to investigate the effect of prenatal valproic acid exposure on postnatal cerebellar cortex and the protective role of folic acid. Material and methods: 24 pregnant female rats were used, divided into 3 groups: Group I (control), Group II (valproic acid treated pregnant females) and Group III (valproic acid and folic acid treated pregnant females). The Offspring rats of each group (5 rats in each age) were sacrificed by cervical dislocation at 2 weeks, 4 weeks and 12 weeks of age. Samples of cerebellar cortex were taken and prepared for histological examination, immunohistochemical and histo-morphometric analysis. Results: histological examination showed degeneration of purkinje cells which were decreased in number, shrunken, disorganized and surrounded by haloes. The granule cells showed pyknotic nuclei. The thickness of cerebellar cortex layers was decreased. The ultra-structure examination confirmed the results. On the other hand, offspring of group III showed obvious improvement regarding the histological and ultrastructural changes.Conclusion: prenatal valproic acid exposure had a neurtoxic effect on the cerebellar cortex of the off spring and folic acid supplementation could protect against such cerebellar neurotoxicity

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