Simvastatin blocks blood-brain barrier disruptions induced by elevated cholesterol both in vivo and in vitro

Area of Science:

• Neuroscience
• Pharmacology
• Cardiovascular Research

Background:

• Hypercholesterolemia and blood brain barrier (BBB) disruptions are linked to Alzheimer's disease (AD) pathogenesis.
• The precise mechanism of simvastatin's potential benefit in AD remains unclear.
• Investigating simvastatin's effect on cholesterol-induced BBB disruption is crucial.

Purpose of the Study:

• To determine if simvastatin can prevent or reverse BBB disruption caused by high cholesterol.
• To evaluate simvastatin's efficacy in both animal models and cell cultures.

Main Methods:

• Rabbits were fed a cholesterol-enriched diet with or without simvastatin; serum and brain cholesterol levels were measured.
• Blood brain barrier integrity was assessed using Evan's blue dye leakage.
• Rat brain microvascular endothelial cells (RBMECs) were treated with cholesterol and simvastatin in vitro to evaluate BBB disruption via TEER and BSA passage.

Main Results:

• Simvastatin administration prevented Evan's blue dye leakage in rabbits on a cholesterol-rich diet.
• While serum cholesterol was affected, brain cholesterol levels remained unchanged by simvastatin.
• In vitro, simvastatin counteracted high-cholesterol-induced decreases in TEER and increased transendothelial albumin passage in RBMECs.

Conclusions:

• This study provides the first evidence that simvastatin improves blood brain barrier function compromised by hypercholesterolemia.
• Simvastatin demonstrates protective effects against BBB disruption in both in vivo and in vitro models.
• These findings suggest simvastatin may be a valuable therapeutic agent for mitigating BBB dysfunction associated with high cholesterol levels.