Abstract
High dose (700 or 500mg/kg/day) of 2, 5-hexanedione was orally administered to female Sprague-Dawley rats for 2 to 6 weeks. and the cerebellar and vestibular nuclei were examined ultrastructurally. Abnormal gait was observed at the 2nd week (700mg/kg) or the 3rd week (500mg/kg) of treatment, and one of six animals dosed 700mg/kg died at the 4th week of experiment. In the histopathological examination of the dead rat, edema and petechial hemorrhage were noted in the thalamus and vacuolation was observed in the cerebellar nuclei. Ultrastructural examination of the cerebellar and vestibular nuclei of the rats, which were dosed 700mg/kg for 2 weeks and fixed with an isotonic neutral fixative by gentle perfusion method, revealed dilatation of the periaxonal space, axonal degeneration, and extracellular edema. Nerve endings in these nuclei were occasionally detached from the nerve cells, and some of the endings were degenerated or destroyed. In the animals which survived and administered for a longer period, however, there were accumulation of neurofilaments and swelling of the nerve endings.