Effect of Valproic Acid on Pre and Postnatal Development of the Cerebellar Cortex of the Albino Rat and the Possible Protective Role of the Folic Acid

Galal, Ahmed Talaat; Sayed, Sayed A.; Mubarak, Wafaa A.; Farag, Walaa G.

doi:10.21608/ejhm.2022.256326

Effect of Valproic Acid on Pre and Postnatal Development of the Cerebellar Cortex of the Albino Rat and the Possible Protective Role of the Folic Acid

Document Type : Original Article

Authors

Human Anatomy and Embryology

10.21608/ejhm.2022.256326

Abstract

Background: Valproic acid (VPA) is one of antiepileptic drugs that causes neurodevelopmental disorders, including the autism spectrum disorder. Folic acid is essential for DNA synthesis and its periconceptional supplementation protects against several birth defects.
Objective: To clarify the folic acid^’s protective potential against the valproic acid induced neurodevelopmental toxicity on rat cerebellar cortex.
Material and Methods: 60 pregnant albino rats were divided into three groups; group I (control, received saline), group II (valproic acid 50 mg/kg once daily) and group III (valproic and folic acid (400 mg/kg) once daily). The offspring rats were sacrificed at day 15 and 17 prenatally, newborn, and at day 15 and 21 postnatally. Samples of cerebellar cortex were prepared for light and electron microscopic examination, immunohistochemical GFAB study as well as for histomorphometric analysis.
Results: In group II, the rat offspring’s cerebellar cortex showed marked degenerative changes, mostly in Purkinje cells. The cells appeared shrunken, irregular with vacuolated cytoplasm contained damaged organelles and nuclei. The external granular layer appeared decreased in thickness and contained less cells with deeply stained nuclei. The cerebellar cortex of the group III showed restoration of the normal architecture. GFAB immunoreaction in group III appeared comparable to control against the strong positive reaction (gliosis) in group II. All studied morphometric parameters in group III were close to the control group and markedly reduced in group II.
Conclusion: Periconceptional folic acid supplementation reduces VPA neurotoxic effects on rat cerebellar cortex development pre and postnatally.

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