Basic fibroblast growth factor may repair experimental cerebral aneurysms in rats.

Abstract

To determine whether basic fibroblast growth factor (FGF) can induce proliferative response of endothelial cells and/or smooth muscle cells in aneurysmal lesions, we investigated the effect of the intravenous administration of basic FGF on experimental cerebral aneurysms. Cerebral aneurysms were induced in rats by ligation of the unilateral common carotid artery, producing hypertension. Three months later, basic FGF was intravenously injected in two groups of randomly divided rats on days 1, 3, and 5 at two different doses (low dose: 2 micrograms/100 g body wt per day; high dose: 5 micrograms/100 g body wt per day). In a control group, normal saline was similarly injected. The junctions of the anterior cerebral artery (ACA) and the olfactory artery (OA) were examined with a light microscope. Aneurysmal changes were defined as the lesions with discontinuity of the internal elastic lamina in more than half of the outward dilated wall. Depending on whether the smooth muscle cell layer was present in the whole wall, the lesions were divided into two stages: early aneurysmal lesion (whole area) and saccular aneurysm (not totally preserved). The control and the low-dose groups presented no obvious intimal thickening in the intact ACA-OA junctions of both nonligated and ligated sides as well as in the aneurysmal changes. In contrast, in the high-dose group, various degrees of intimal thickening in the wall were detected in 7 of 15 early aneurysmal lesions (P = .019, Fisher's exact test). Immunohistochemistry showed the proliferated cells to be smooth muscle cells. These results demonstrate that exogenous basic FGF induces the proliferative response of smooth muscle cells in aneurysmal lesions in rats.