Statins Protect the Blood Brain Barrier Acutely after Experimental Intracerebral Hemorrhage.

Abstract

Objectives: The goal of this study was to measure the impact of simvastatin and atorvastatin treatment on blood brain barrier (BBB) integrity after experimental intracerebral hemorrhage (ICH).

Methods: Primary ICH was induced in 27 male Wistar rats by stereotactic injection of 100 µL of autologous blood into the striatum. Rats were divided into three groups (n= 9/group): 1) oral treatment (2 mg/kg) of atorvastatin, 2) oral treatment (2 mg/kg) simvastatin, or 3) phosphate buffered saline daily starting 24-hours post-ICH and continuing daily for the next 3 days. On the fourth day, the animals underwent magnetic resonance imaging (MRI) for measurements of T_1sat (a marker for BBB integrity), T₂ (edema), and cerebral blood flow (CBF). After MRI, the animals were sacrificed and immunohistology or Western blotting was performed.

Results: MRI data for animals receiving simvastatin treatment showed significantly reduced BBB dysfunction and improved CBF in the ICH rim compared to controls (P<0.05) 4 days after ICH. Simvastatin also significantly reduced edema (T₂) in the rim at 4 days after ICH (P<0.05). Both statin-treated groups demonstrated increased occludin and endothelial barrier antigen levels within the vessel walls, indicating better preservation of BBB function (P<0.05) and increased number of blood vessels (P<0.05).

Conclusions: Simvastatin treatment administered acutely after ICH protects BBB integrity as measured by MRI and correlative immunohistochemistry. There was also evidence of improved CBF and reduced edema by MRI. Conversely, atorvastatin showed a non-significant trend by MRI measurement.