Aspirin Inhibits Degenerative Changes of Aneurysmal Wall in a Rat Model

Aneurysmal subarachnoid hemorrhage still has a high mortality and morbidity despite notable advances in surgical approaches to cerebral aneurysm (CA). We examined the role of aspirin in vascular inflammation and degeneration. CA was induced in male Sprague-Dawley rats by ligating left common carotid artery and bilateral posterior renal arteries with or without aspirin treatment. The right anterior cerebral artery/olfactory artery (ACA/OA) bifurcations were stripped and assessed morphologically after Verhoeff's Van Gieson staining. Blood sample was obtained to examine circulating CD34(+) CD133(+) endothelial progenitor cells (EPCs), platelet aggregation and platelet counts. Macrophages infiltration in aneurysmal wall was evaluated by immunohistochemistry. Expression of matrix metalloproteinase-2 and 9 (MMP-2 and 9), nuclear factor kappa B (NF-κB), macrophage chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) was examined by RT-PCR. 2 months after CA induction, surgically treated rats manifested aneurysmal degeneration in ACA/OA bifurcations. Aspirin-treated rats exhibited a significant decrease in degradation of internal elastic lamina (IEL), medial layer thinning, CA size and macrophages infiltration with reduced expression of MMP-2 and 9 compared with rats in the CA group. RT-PCR demonstrated that the upregulation of NF-κB, MCP-1 and VCAM-1 after CA induction was reversed by aspirin treatment. Aspirin treatment following CA induction increased circulating EPCs to near control levels and reduced platelet aggregation without changing platelet counts. The evidence suggested that aspirin significantly reduced degeneration of aneurysm walls by inhibiting macrophages-mediated chronic inflammation and mobilizing EPCs.