The possible neuroprotective role of grape seed extract on the histopathological changes of the cerebellar cortex of rats prenatally exposed to Valproic Acid: animal model of autism

Abstract

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disease characterized by defect in verbal and nonverbal communications. As, the cerebellum has the greatest number of neurons and synapses in the central nervous system so, the cerebellum has emerged as one of the target brain areas affected in autism. The aim of this work was to study the biochemical, immunohistochemical and ultrastructural characteristics of autism and the possible neuroprotective role of grape seed extract. In this study 28 male pups were divided into Control groups; Group I (saline), Group II (GSE 400 mg/kg), Group III (VPA 500 mg/kg) and Group IV (VPA and GSE). Cerebellar hemispheres were dissected out and prepared to determine the oxidative stress markers, histological, immunohistochemical and morphometric study were done. A significant elevation in oxidative stress markers in off spring of VPA treated rats in comparison to control group was detected. A significant decrease in the Purkinje cell count and nuclear size were observed. Numerous shrunken cells with hyperchromatic nuclei and ultrastructural degeneration of cytoplasmic organelles were detected. A significant rise in the area percentage of GFAP-positive immune stained cells in comparison to that of the control groups was seen. Strikingly, GSE revealed significant improvement in the oxidative stress markers and then the histological and morphometric picture of the cerebellum. GSE has neuroprotective effect on the cerebellum of VPA treated rats through its potent antioxidant effect.

Keywords: Autism; Cerebellar cortex; Grape seed; Valproic Acid.