Effect of chronic administration of sodium valproate on the morphology of the rat brain hemispheres

Effective doses of sodium valproate (200 mg/kg) applied in rats chronically (1, 3, 6, 9 and 12 months) evoked the first morphological changes in the brain hemispheres after 9 months of drug administration. Structural abnormalities of the brain tissue consisted in disseminated nonspecific neuronal lesions and patchy nerve cell loss, more pronounced in the final phase of the experiment. The neuronal lesions were localized predominantly in the 3rd and 5th layers of the neocortex and in the pyramidal cell layer of the hippocampus. They were accompanied by vascular wall alterations, perivascular tissue damage, as well as by microvacuolar changes and spongy degeneration of the subpial and periventricular regions. Vasogenic character of parenchymal changes is stressed by the authors. The possible influence of liver damage on the development of brain pathology is discussed.