Cerebral changes in chronic hypertension: combined permeability and immunohistochemical studies

Focal areas of recent and old necrosis are a consistent finding in brain in chronic hypertension. The possibility that areas represent foci of increased vascular permeability leading to chronic edema and tissue breakdown was investigated in the present study. Rats with chronic renal hypertension demonstrated increased cerebrovascular permeability in focal cortical areas throughout the 7-week period of study. Combined use of tracers and immunohistochemistry demonstrated that these areas of increased permeability with protein extravasation were of different ages. Stage I lesions showed protein in and around arteriolar walls with no cellular reaction indicating that these were very early lesions and corresponded to the findings using HRP as a tracer. Necrosis of the neuropil and an astrocytic and microglial response associated with diffuse collections of protein in the neuropil characterized stage II lesions. Stage III lesions consisted of glial scars or cystic spaces lined by astroglia and associated with absent or sparse protein deposits. Animals that died or were sick prior to killing and had diffuse cerebral edema showed large stage II cortical lesions associated with widespread serum protein extravasation into the white matter of both hemispheres. The principal mechanism resulting in the permeability alterations was enhanced pinocytotic transport of tracer across the endothelium of penetrating cortical arterioles. Vascular occlusion by thrombi was not observed in pial or intracerebral vessels. Our findings are consistent with the hypothesis that increased vascular permeability leads to chronic edema and tissue necrosis in chronic hypertension.