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 bloodbrain 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 bloodbrain 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.

In an attempt to clarify the role of lysosomal enzymes in the developmental mechanisms of cerebral lesions under chronic hypertensive conditions, we biochemically investigated the activities of acid phosphatase (AcPase), N-acetyl beta-glucosaminidase (NAGase) and cathepsin B (CathB) in the cerebral cortex and subcortical white matter in stroke-prone spontaneously hypertensive rats (SHRSPs). We also investigated enzyme-histochemically the activities of AcPase and NAGase, and immunohistochemically the distribution of CathB. The activities of all enzymes tended to increase with advancing age. The enzyme activities in the aged SHRSPs were in general higher than those in normotensive rats, the differences being significant at 24 weeks of age. Histochemical investigation showed that SHRSPs had an increased number of cells with positive reaction to these enzymes in the edematous cortex with and without vascular changes, and degenerated subcortical white matter. These cells with positive reaction were made up of reactively increased astrocytes and microglia. Neurons in the edematous area also showed slightly intensified enzyme activities. The present studies suggest that chronic hypertension or chronic edema due to hypertension causes increased activities of lysosomal enzymes in the cerebral cortex and subcortical white matter and, thus, that activated lysosomal enzymes may take part in the developmental mechanisms of cystic formation as well as the diffuse degeneration of the white matter.

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