The Effect of Irradiation and Cis-diamminedichloroplatinum (II) in the Rat Brain : Analysis of Histopathology at 3 and 6 Months after Treatment

Lee, Kyung Ja; Chang, Seung Hee; Koo, Heasoo

Abstract

PURPOSE: To evalute the late effect (3 and 6 months) of cis-diamminedichloroplatinum (II) (cisplatin) on the radiation brain damage when the cisplatin was intraperitoneally infused immediately after whole brain irradiation in the rats.
MATERIALS AND METHODS
The histolopathological findings of the brain were examined in rat brains at 3 and 6 months after the treatment. The rats were irradiated (20 or 22.5 Gy, RT) or cisplatin was injected intraperitoneally (2, 4, or 8mg/kg, CT) and in combined treatment group, cisplatin (2mg/kg) was injected immediately after irradiation (20 or 22.5 Gy). Histopathological examination was done mostly in irradiation or cisplatin alone groups, because the rats in combined group died during experimental period except 2 rats.
RESULTS
The rats treated with cisplatin showed marked epithelial vacuolation with perivascular edema and vascular dilatation in choroid plexus at 3 months as well as multifocal necrosis involving fimbria and cerebellar hemispheres at 3 and 6 months. The changes were more prominent in rats with 2mg/kg injection compared to rats with 8mg/kg injection.The rats with RT and combined CT and RT showed characteristic delayed irradiation effects such as focal coagulation necrosis and vascular changes, which were more marked than previous reports. Prominent perivascular and leptomeningeal astrocytic proliferation was well documented by anti-GFAP antibody. Cisplatin treatment did not enhance the effect of radiation-induced changes of blood vessels and astrocytic proliferation.
CONCLUSION
The focal necrosis was the most consistently noted finding in this study, it suggested the possibility to use this as an evaluation factor for combined effects of RT and cisplatin.