Ultrastructural characteristics of occluded perforating arteries in stroke-prone spontaneously hypertensive rats.

Abstract

We studied ultrastructurally cerebral perforating arteries in 60 stroke-prone spontaneously hypertensive rats (SHRSP), which were sequentially killed at 4-52 weeks of age before showing symptoms of stroke. Another 24 SHRSP were killed soon after they showed symptoms of cerebral infarction. The initial vascular lesions observed in the asymptomatic group included focal cytoplasmic necrosis in the outer layers of the media. This change progressed to widespread medial necrosis with time. In the infarction group, numerous monocytes were seen adhering to the endothelium of the arteries having advanced medial damage. Following the adherence of monocytes to the endothelium, large amounts of plasma components were visible in the arterial wall. The accumulation of the plasma components (especially fibrin) thickened the wall, narrowed the lumen, and resulted in occlusion. These results suggest that monocytes may affect the endothelium, perhaps disturbing the so- T here are many studies on hypertensive vascular lesions in humans and experimental animals.'" 7 Only a few investigators, however, have focused on the long-term effects of hypertension on the perforating arteries in the brain.8 " 12 In the present study we sequentially analyzed the ultrastructure of the perforating arteries in stroke-prone spontaneously hypertensive rats (SHRSP) as developed by Okamoto et al in 1974. 13 We discovered numerous monocytes that adhered to the endothelium. We have therefore tried to clarify the characteristic changes that develop into occlusions and have attempted to explain the role of monocytes in arterial lesions, especially those resulting in occlusion. Materials and MethodsOkamoto et al 13 and Yamori et al 14 developed SHRSP in which stroke (cerebral hemorrhage and/or infarction) develops spontaneously in > 8 0 % of the rats. The cerebral lesions resemble those found in humans. Since the development of this rat strain, we have continued to inbreed them selectively. At present we have > 1,500 SHRSP in our laboratory. A group of 24 SHRSP 28-50 weeks of age with symptoms of stroke composed a cerebral infarction group, and 60 asymptomatic SHRSP 4-52 weeks of age served as controls. Almost half the rats in the infarction group were in an Received October 29, 1986; accepted March 24, 1987. irritable state denoted as "Stage 2," while the other half were lethargic, labelled "Stage 3." 15 Rats in the infarction group were anesthetized with pentobarbital, and the cerebral arteries were perfused with a 1 % formaldehyde-1 .25% glutaraldehyde fixative in 0.1 M cacodylate buffer at pH 7.6 at room temperature 16 via the descending aorta at 180 mm Hg pressure for 4-5 minutes. After perfusion, the brains were carefully removed and fixed with a 2% formaldehyde-2.5% glutaraldehyde mixture in 0.1 M cacodylate buffer for 1 hour at 4° C. The infarcted cortices were then taken out and placed in the same fixative for 3 hours at 4° C and then washed overnight at 4° C in 0.1 M cacodylate buffer. Afterwards, the infarcted cortices were sectioned into sma...

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