Apoptosis of Medial Smooth Muscle Cells in the Development of Saccular Cerebral Aneurysms in Rats

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Abstract
Background and Purpose —Using an animal model, we examined the role of apoptosis in the disappearance of medial smooth muscle cells (SMCs) during the development and growth of cerebral aneurysms. Methods —Various degrees of cerebral aneurysms were induced in the right anterior cerebral artery–olfactory artery bifurcations in 65 Sprague-Dawley rats with ligation of the left common carotid artery and renal hypertension. We performed in situ end labeling of fragmented DNA with the lesions in 45 rats and electron microscopic study in the other 20 rats. Results —With in situ end labeling of fragmented DNA, 4±3 apoptotic medial SMCs were detected in 35 of the 45 bifurcations. Apoptotic SMCs appeared in the medial layer in the “preaneurysm” group, the site speculated to show an aneurysmal change in the near future (6±3), and in the media in the “early aneurysm” group, which showed characteristics such as a small depression (5±3). In the “progressive aneurysm” group, they appeared more frequently at the aneurysmal neck (3±2) than the dome (1±1). By electron microscopic study, shrunken medial SMCs exhibiting morphological apoptotic changes such as chromatin condensation and fragmentation of the cytoplasm and nucleus were observed in the preaneurysm and early aneurysm groups and at the neck portion in the progressive aneurysm group. In the aneurysmal dome, SMCs showed late characteristics of apoptosis such as more advanced nuclear and cytoplasmic condensation and formation of apoptotic bodies. Conclusions —The present findings indicate that there is an association between apoptosis of medial SMCs and the formation of saccular cerebral aneurysms.