Ultrastructure of Purkinje cell perikarya and their dendritic processes in the rat cerebellar cortex in experimental encephalopathy induced by chronic application of valproate

摘要: Long-term intragastric administration of the antiepileptic drug sodium valproate (Vuprol Polfa) to rats for 1, 3, 6, 9 and 12 months, once daily at effective dose 200 mg/kg body weight showed morphological evidence encephalopathy, manifested by numerous nonspecific changes within Purkinje cell perikarya their dendritic processes. The first ultrastructural abnormalities appeared after 3 months. They became more severe in animals with longer survival were most pronounced maintained both 1 months withdrawal. Mitochondria severely affected. Damage mitochondria was accompanied disintegration fragmentation granular endoplasmic reticulum, dilation channels cisterns Golgi apparatus, enlargement smooth reticulum elements including submembranous cisterns, accumulation profuse lipofuscin deposits. Frequently, cells as dark ischemic neurones, focally damaged cellular membrane features disintegration. Swollen Bergmann's astrocytes seen among or site loss. general pattern submicroscopic alterations suggested disorders several intercellular biochemical extents, inhibition oxidative phosphorylation abnormal protein synthesis, which could lead lethal damage. Ultrastructural dendrites characterized damage considerably enlarged, formation large vacuolar structures situated deep dendroplasm. Mitochondrial lesions cytoskeletal elements--disintegration microtubules even complete loss--were also observed. organelles processes VPA chronic experimental model imply that there are disturbances detoxication Furthermore these irreversible, they