الفهرس 
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Abstract
This study aimed to investigate the effect of exposure to valproic acid during pregnancy on the development of cerebellar cortex in albino rat’s offsprings and to evaluate the possible protective role of L-carnitine.
This study was carried out on thirty-six pregnant albino rats divided into four groups (nine rats each). group A (control group); pregnant rats received distilled water orally daily via gastric tube from the first day of pregnancy until day 14 after delivery. group (B); Pregnant rats received VPA at a dose of 50 mg/kg body weight orally daily via gastric tube from the first day of pregnancy until day 14 after delivery. group (C); received VPA at a dose of 50 mg/kg body weight concomitant with L-canitine at a dose of 500 mg /kg body weight orally daily via gastric tube from the first day of pregnancy until day 14 after delivery. group (D); received L-canitine at a dose of 500 mg/kg body weight orally daily via gastric tube from the first day of pregnancy until day 14 after delivery. At the end of experiment, ten pups from each group were sacrificed on the postnatal day 14. The cerebella were extracted and processed for light microscopic examination using H&E stain and toluidine. Also, immuno-histochemical technique for glial fibrillar acidic protein (GFAP) was applied to demonstrate astrocytes. Morphometric study was conducted to measure the thickness of external granular layer of the cerebellar cortex, count the number of apparently normal Purkinje cells, number of Bergmann glial cells and calculate GFAP percentage area.
The study revealed that the cerebellar cortex of the control group (A) consisted of four layers; the external granular layer, the molecular layer, the Purkinje cell layer and the internal granular layer. The molecular layer appeared pale with few stellate cells and basket cells. The Purkinje cell layer consisted of Purkinje cells arranged in single row with their oval or flask shaped cell bodies, pale central nuclei and apical cytoplasmic cones. The granular layer consisted of deeply stained rounded small granule cells. This general architecture of the cerebellar cortex was greatly affected in group B (valproic acid group) and there was increase in the thickness of the external granular layer which was statistically significant when compared to the control group. The Purkinje cells appeared degenerated with pyknotic nuclei and the number of apparently normal cells was statistically decreased compared to control. The number of Bergmann cells was statistically significantly increased. Also, astrocytes showed a strong positive reaction to GFAP with statistically significant high percentage area compared to the control group. Examination of group C (valopric acid and L-carnitine group) showed apparently normal arrangement of layers, Purkinje cells restored their normal flask shaped appearance and arranged in single row with Bergmann glial cells inbetween. Also, astrocytes gave a mild positive reaction to GFAP similar to control group. Examination of group D (L-carnitine group) showed the same picture of the cotrol group as the cerebellar cortex consisted of four layers; the external granular layer, the molecular layer, the Purkinje cell layer and the internal granular layer. The Purkinje cell layer consisted of one row of oval Purkinje cells with vesicular nuclei. The granular layer consisted of deeply stained rounded small granule cells.
The ultrastructural examination of the control group showed normal Purkinje cell nuclei with regular intact nuclear envelope. The cytoplasm showed large num¬ber of mitochondria and intact rough endoplasmic reticulum. Granule cells appeared with normal hyperchromatic rounded nuclei. In group B (valproic acid group), the nuclei of purkinje cells appeared shrunken with irregular nuclear envelope. The cytoplasm contained many vacuolations. Normal Purkinje cell nuclei ap¬peared in the rats of group C (VPA and L-carnitine group), their nuclei appeared with regular nuclear envelope and prominent nucleoli. The cytoplasm was found nearly normal containing many mitochondria and rough endoplasmic reticula however, some mitochondria appeared degenerated. There were many granu¬lar cells with apparently intact cytoplasmic organells and nuclei. group D (L- carnitine group) showed purkinje cells with large oval euchromatic nuclei. The cytoplasm showed large num¬ber of intact mitochondria and rough endoplasmic reticulum. Granule cells appeared with normal hyperchromatic rounded nuclei with intact nuclear envelop.