Abstract
To investigate thiophene-induced vascular damage in the rat cerebellum, we employed aged spontaneously hypertensive rats (SHR), which have vascular vulnerability. The animals were given a daily subcutaneous injection of 0.15ml of thiophene for 3 to 6 days. The cerebellum was then studied by light and electron microscopy, horseradish peroxidase (HRP) methods, and the quantitative determination of thiophene at sequential stages after administration. Well-demarcated regions of degeneration appeared, and these spread extensively in the cerebellar rostral folia and/or focally in the caudal folia. In these lesions, tangled villi or oil droplets with an osmiophilic homogeneous substance were found both within and/or outside the lumina of blood vessels, especially capillaries and venules. They were membrane-trophic and located in the degenerated endothelial cells and then disappeared from the lumina at a late stage. Platelet thrombi occupied the lumina of blood vessels in the pia mater and parenchyma from the early to late stage. A lack of reaction product and its extravascular leakage were clearly revealed using HRP. Thiophene and/or its metabolites were detected quantitatively at an early stage in the damaged cerebellum. These lesions were replaced by gliosis and/or cysts in surviving animals. It is concluded that thiophene or its metabolites cause vascular damage and granule cell degeneration, producing circulatory disturbance in aged SHR.
