Pathogenesis of lacuna-like cyst formation and diffuse degeneration of the white matter in the brain of stroke-prone spontaneously hypertensive rats.

1. In an attempt to clarify the developmental mechanisms of lacuna and diffuse degeneration of the white matter in the brain in chronic hypertension, we investigated histologically the cerebral changes and histochemically, as well as biochemically, the lysosomal enzymes in the brain of stroke-prone spontaneously hypertensive rats (SHRSP). 2. The most prominent advanced lesions observed in SHRSP were cyst formation in the cortex and subcortical white matter, and diffuse degeneration of the white matter. On the other hand, the early cerebral changes were all related to blood-brain barrier dysfunction. The localization of cystic lesions and degeneration of the white matter corresponded very well with the extent of brain oedema demonstrated by immunostaining for leaked fibrinogen. All lysosomal enzyme activities in the adult SHRSP, both in the cortex and white matter, were higher than those in the controls. Histochemical investigation showed that SHRSP had an increased number of cells, reactive astrocytes and microglial cells, with positive reaction to lysosomal enzymes in the oedematous portion. 3. These findings suggest that chronic oedema due to blood-brain barrier dysfunction causes cystic changes as well as diffuse degeneration of the white matter, and that activated lysosomal enzymes in the reactive astrocytes and microglia play an important role in the development of such hypertensive lesions.