The pathogenic process leading from the development of cerebrovascular or extracranial atherosclerosis to the occurrence of acute ischemic stroke and consequent cell damage is complex. Much of the intermediary damage is complex and many of the intermediary steps are not completely understood.
Ischemic stroke may arise from the atherosclerotic large cerebral arteries (eg, carotid, middle cerebral, and basilar arteries) or atherosclerotic small cerebral arteries (eg, lenticulostriate, basilar penetrating, and medullary arteries); ischemic stroke may also be cardioembolic in origin. Most investigations of atherogenesis have focused on the coronary arteries, but, with some possible exceptions, similar processes occur in the cerebral circulation. In the brain, the process is better characterized in the larger arteries than in small arteries supplying deep cerebral white matter. Some evidence suggests that the underlying pathogenetic process in small arteries may differ from that described in larger arteries [DeGraba TJ, et al. In: Barnett HJM, et al (eds). Stroke. Pathophysiology, Diagnosis, and Management. New York, Churchill Livingstone, 1992:29].
Atherogenesis is a decades-long process in which the lumen of a blood vessel becomes narrowed by cellular and extracellular substances to the point of obstruction [Breslow JL. Science. 1996;272:685]. An autopsy study of coronary arteries and aortas in 1,160 people who died between full-term birth and age 29 years found that the earliest lesion of atherosclerosis is the fatty streak [Stary HC. Atherosclerosis. 1989;9 (suppl 1): 119]. Approximately 65% of children between ages 12 and 14 years had such lesions. Fatty streaks, which are grossly visible as areas of yellowish discoloration of the surface of the intimal layer of the vessel wall, are widely distributed throughout the coronary arterial vasculature. On microscopy, the lesions primarily consist of lipid-filled macrophages (foam cells).
The autopsy study revealed that an additional 8% of children in late childhood or early adolescence had progressed beyond the fatty-streak stage and had developed more advanced, focal lesions. These lesions, which occur only in areas of eccentric thickening (ie, at branch points of the arterial vessel), are characterized by the addition of massive extra-cellular lipids that displaced normal cells and matrix.
In the third decade of life, some atheromatous lesions evolve into complicated fibrous plaques, consisting of a central acellular area of lipid covered by a cap of smooth muscle cells and collagen. Caps tend to form slowly at first, but with deposition of platelets and fibrin on the surface—which appears to be the result of endothelial injury—the caps thicken quickly, possibly as a result of thrombosis-dependent fibrotic organization.
The progression of early atherosclerotic lesions to clinically relevant advanced atherosclerotic lesions occurs with increased frequency in persons with risk factors for atherosclerotic disease (eg, heypercholesterolemia, hypertension, cigarette smoking) [Ip JH, et al, 1994].
Acute Ischemic Stroke: New Concepts of Care
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