HMG-CoA reductase inhibition causes increased necrosis and apoptosis in an in vivo mouse glioblastoma multiforme model.

BACKGROUND: Statins are thought to have tumorolytic properties, reducing angiogenesis by inhibiting pro-angiogenic factors and inducing apoptosis of mural pericytes within the tumor vascular tree. MATERIALS AND METHODS: An orthotopic mouse glioblastoma (GL-26) model was used to investigate the effect of simvastatin on glioblastoma vasculature in vivo. GL-26 cells were implanted into the striatum of C5LKa mice treated with either control, low- or high-dose simvastatin. Brains were analyzed for necrotic volume, apoptosis, morphology and pericytic cells within the vascular tree. RESULTS: Low-dose simvastatin increased necrosis and apoptosis compared to both control and high-dose simvastatin groups. High-dose simvastatin increased vessel caliber by reducing pericytic cells along the tumor vessel wall compared to both control and low-dose simvastatin groups. CONCLUSION: Simvastatin has a dual effect on tumorigenesis. At high doses, it may worsen instead of 'normalizing' tumor angio-architecture, albeit low doses affect tumor cell survival by promoting necrosis and apoptosis.

The transition from hunterian ligation to intracranial aneurysm clips: a historical perspective.

The description of cerebral aneurysms dates back to antiquity. Little was known, however, about the pathological mechanisms of aneurysm formation and treatment options for this disease until 200 years ago. The modern era of aneurysm treatment began with the hunterian ligation of the proximal artery, followed by clip and coil occlusion. In this article, the authors describe the transition from conservative therapy to internal carotid artery (ICA) ligation and gradual occlusion of the ICA to the direct placement of clips on aneurysms. The driving forces and rationale behind each major advancement are summarized, and the authors attempt to predict what these innovations mean for the future of intracranial aneurysm management.