Acute neurovascular unit protection by simvastatin in transient cerebral ischemia

Acute vascular-and neuroprotective effects of simvastatin were evaluated in a rat model of transient, focal cerebral ischemia. Male, Wistar rats (n = 12) underwent transient middle cerebral artery (MCA) occlusion for 3 hours followed by 3 hours of reperfusion. After 30 minutes of MCA occlusion, four rats each were subcutaneously injected with either 20 or 40 mg/kg of simvastatin. At the end of 3 hours of reperfusion, tissue injury and blood-brain barrier (BBB) opening were quantified by histology and [C-14]-alpha-aminoisobutyric acid (AIB)-based quantitative autoradiography (QAR), respectively. Compared with untreated rats, those treated with simvastatin (20 mg/kg) had reduced volumes of AIB leakage, tissue pallor and distribution space for AIB (p < 0.05). No additional effects were seen with the higher drug dose (40 mg/kg). These data suggest that the acute neuroprotective effects of statins are in part owing to attenuation of stroke-induced changes in BBB permeability.