Abstract 2817: Simvastatin Reduced The Rupture Of Intracranial Aneurysms In Mice

Abstract

Background and Purpose Subarachnoid hemorrhage resulting from the rupture of intracranial aneurysms causes severe morbidity and high mortality. Statins exert anti-inflammatory and anti-oxidative effects on the vasculature independent of their cholesterol-lowering properties. The protective effects of simvastatin, a common lipophilic statin, have been examined in various diseases. However, the role of statins on the rupture of intracranial aneurysms is still controversial. We hypothesized that simvastatin can prevent intracranial aneurysmal rupture. Methods Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and deoxycorticosterone acetate salt hypertension. Six days after aneurysm induction, daily treatments of vehicle control (n=32), and simvastatin (30mg/kg/day; n=32) were started. Mice were sacrificed when they developed neurological symptoms, or 21 days after aneurysm induction if mice did not have symptoms. In situ zymography and dihydroethidium staining were performed to detect gelatinase activity by matrix metalloproteinases (MMPs) and superoxide production, respectively. Results Simvastatin decreased the incidence of ruptured aneurysms ( Figure ) compared to vehicle control mice (28% vs. 63%, P<0.05). Simvastatin also improved the survival of mice with aneurysms. Simvastatin reduced superoxide production and gelatinase activity in aneurysmal walls, indicating that simvastatin treatment was effective. Conclusion Simvastatin reduced the incidence of intracranial aneurysmal rupture in mice. Furthermore, simvastatin reduced superoxide production and MMP-related gelatinase activity in aneurysmal walls. Simvastatin may have potentially protective effects against intracranial aneurysmal rupture via its anti-inflammatory and anti-oxidative properties..