A Critical Role for Proinflammatory Behavior of Smooth Muscle Cells in Hemodynamic Initiation of Intracranial Aneurysm
Figure 4
Effects of clodronate (monocyte depletion) on IA formation.
(A) Clodronate liposomes reduced the number of circulating monocytes from 260±110 cells/µl to 70±40 cells/µl at the time of surgery, and the reduction was maintained through the experiment (90±40 cells/µl at sacrifice) (n = 7; * indicates p<0.05). (B) Clodronate liposomes also significantly lowered the number of adventitial macrophages detected by immunostaining of the basilar artery and bifurcation in ligated animals from 0.80±1.0 per mm of vessel (n = 8) to 0.15±0.15 (n = 5, * indicates p<0.05). (C) Immunohistochemistry with RAM-11 antibody shows the distribution of macrophages (brown color, arrows) at the BT in ligated animals (left) and their absence in ligated animals treated with clodronate liposomes (right). (D) Macrophage depletion by clodronate did not affect MMP levels in the media of the BT measured by immunostaining at 5 days. (E) Van Geison staining shows media thinning, bulge formation, and prominent IEL loss at the BT (between arrows) in a clodronate-treated rabbit 5 days after ligation. Bar = 100 (F) The length of vessel exhibiting IEL loss, media thinning, or bulge formation was not significantly different between ligated animals with and without clodronate, nor was the ADS significantly diminished by macrophage depletion (p≤0.05).