Background: Statins are cholesterol lowering drugs that improve stroke outcome in pre-clinical models. Clinical trials of statin use after stroke have not replicated this effect. We hypothesise that statins enhance collateral vessel blood flow due to the growth of new leptomeningeal collateral vessels (LMC) via angiogenesis (neo-collateral formation, NCF). If NCF, which can take weeks to occur, is a key protective mechanism of statins, this would explain why prescribing statins after stroke has failed to improve outcome.

Aim: Determine whether simvastatin treatment reduces collateral flow resistance and if so, is this because of increased LMC number and/or increased LMC diameters.

Methods: Two mouse strains, one LMC-rich (C57BL/6) and one LMC-poor (BALB/c), were given 10 mg/kg of Simvastatin orally daily for four weeks. Animals were euthanised and a yellow silicone cast (Microfil™) of the cerebral vasculature made. Number, diameter, and length of LMCs were measured and resistance to LMC blood flow was estimated.

Results: Simvastatin treated BALB/c mice had lower estimated resistance to LMC blood flow compared to controls [statin: 0.023±0.017, vehicle: 0.10±0.09; p=0.037] and had higher number of LMC [statin: 4.0±3.16, vehicle: 1.55±1.63; p=0.037]. There was no significant difference in estimated LMC flow resistance between C57BL/6 treatment groups, however there was a region-specific increase in LMC number [statin: 9.45±2.29, vehicle: 7.69±1.84; p=0.0401] and decrease in LMC diameter [statin: 14.0±1.42 µm, vehicle: 16.3±1.75 µm, p= 0.0083].

Conclusion: Simvastatin stimulates NCF in collateral poor and rich mouse strains. In collateral poor mice this results in a decrease in estimated collateral flow resistance.