In an attempt to clarify the developmental mechanism of cerebral aneurysms, we studied the elastic skeleton of experimentally induced cerebral aneurysms in rats under scanning electron microscopy after hot formic acid extraction followed by freeze-drying. We produced cerebral aneurysms in 19 rats by unilaterally ligating the common carotid artery, inducing renal hypertension, and feeding /3-aminopropionitrile fumarate. The first noted change was the loss of folds protruding from the internal elastic lamina. Morphologic changes of the internal elastic lamina, considered to be primarily responsible for aneurysmal formation, occurred after the loss or disintegration of the elastic skeleton of first the intima, then the media. In large aneurysms with thick domes, we found proliferation of elastic lamellae that may reduce the risk of rupture. It seems probable that the complex elastic skeleton of the arterial wall may account for the mechanical properties of the artery and that growth of an aneurysm occurs due to disintegration of the elastic skeleton and not simply to rupture of the internal elastic lamina. We believe that such changes in the elastic skeleton are a property of the functional state of the cells that produce elastin. {Stroke 1990;21:1722-1726)A lthough the pathogenesis of cerebral aneu-/ \ rysms is still a matter of debate, many inves-. Z \ . tigators have considered degenerative changes of the internal elastic lamina, including the enlargement of fenestrations, to be responsible for the development of aneurysms. 1 - 4 The results of our previous study of normal cerebral arteries under scanning electron microscopy after hot formic acid extraction 5 showed that the internal elastic lamina was not the sole element, but a part of the complicated architecture of the elastic skeleton. Based on these observations, we considered that the process of various vascular pathologies might be re-evaluated by analyzing morphologic changes of the elastic skeleton in cerebral arteries. Our current study was designed to clarify changes of the elastic skeleton at various stages of aneurysmal formation using experimentally induced cerebral aneurysms.
Materials and MethodsTo produce cerebral aneurysms, in 19 male SpragueDawley rats aged 8 weeks and weighing 250-300 g we Received January 29, 1990; accepted August 17, 1990. ligated the left common carotid artery and posterior branches of both renal arteries under anesthesia with 40 mg/kg i.p. sodium pentobarbital. One week after surgery 1% saline was substituted for the drinking water, and 2 weeks after surgery, the rats were fed a diet containing 0.12% j3-aminopropionitrile fumarate (Tokyo Kasei Co., Tokyo, Japan). We used 12 agematched rats as controls. Four to 16 weeks after surgery, the rats were perfused with heparinized 0.1 M phosphate buffer (pH 7.4) from the descending aorta, followed by fixation with 3 % glutaraldehyde in the same buffer. After perfusion and fixation, the major arteries at the base of the brain were carefully freed under a microscope and immers...