Difference in vulnerability of cerebral arterial bifurcation and straight portion for development of endothelial damage

Abstract

Cerebral atherosclerotic changes develop most commonly on the lateral side of the bifurcation, one of the sites where the wall shear stress is lowest in the cerebral arteries. Endothelial cells exposed to the lower shear stress appear to be more vulnerable to stimuli such as free radicals. We hypothesized that the difference in endothelial vulnerability on cerebral arteries may be involved in the local preference of atherogenesis. To clarify this hypothesis, the present study was carried out by using a laser-dye technique that causes cell damage by heat and free radicals. A helium-neon laser in the presence of circulating Evans blue was used to illuminate three sites of the rat middle cerebral artery; the straight portion, the apex of the bifurcation, and the lateral side of the bifurcation. The magnitude of endothelial damage was morphologically estimated with the electron microscope. After the laser irradiation, the straight portion and the lateral side of the bifurcation developed severe endothelial damage. However, the apex of the bifurcation developed no appreciable damage, showing significantly milder changes compared with other sites. The results suggest that endothelial cells are more vulnerable to stimuli by free radicals at the straight portion and the lateral side of the bifurcation than at the apex. We conclude that the imbalance between the strength of stress stimuli, such as free radicals, and the vulnerability of endothelium is likely to be one of the key requirements for the development of cerebral atherosclerotic changes.