Early treatment with atorvastatin exerts parenchymal and vascular protective effects in experimental cerebral ischaemia

Background and Purpose

From the clinical and experimental data available, statins appear to be interesting drug candidates for preventive neuroprotection in ischaemic stroke. However, their acute protective effect is, as yet, unconfirmed.

Experimental Approach

Male C57Bl6/JRj mice were subjected to middle cerebral artery occlusion and treated acutely with atorvastatin (10–20 mg·kg⁻¹ day⁻¹; 24 or 72 h). Functional recovery (neuroscore, forelimb gripping strength and adhesive removal test) was assessed during follow‐up and lesion volume measured at the end. Vasoreactivity of the middle cerebral artery (MCA), type IV collagen and FITC‐dextran distribution were evaluated to assess macrovascular and microvascular protection. Activated microglia, leucocyte adhesion and infiltration were chosen as markers of inflammation.

Key Results

Acute treatment with atorvastatin provided parenchymal and cerebral protection only at the higher dose of 20 mg·kg⁻¹·day⁻¹. In this treatment group, functional recovery was ameliorated, and lesion volumes were reduced as early as 24 h after experimental stroke. This was associated with vascular protection as endothelial function of the MCA and the density and patency of the microvascular network were preserved. Acute atorvastatin administration also induced an anti‐inflammatory effect in association with parenchymal and vascular mechanisms; it reduced microglial activation, and decreased leucocyte adhesion and infiltration.

Conclusions and Implications

Acute atorvastatin provides global cerebral protection, but only at the higher dose of 20 mg·kg⁻¹·day⁻¹; this was associated with a reduction in inflammation in both vascular and parenchymal compartments. Our results suggest that atorvastatin could also be beneficial when administered early after stroke.

Abbreviations

AT

atorvastatin

IR

ischaemia‐reperfusion

MCA

middle cerebral artery

MCAO

middle cerebral artery occlusion

Phe

phenylephrine