Acute Treatment with Rosuvastatin Protects Insulin Resistant (C57BL/6J ob/ob) Mice against Transient Cerebral Ischemia

Abstract

The purpose of this study was to investigate the short-term effects of rosuvastatin (RSV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on transient, focal cerebral ischemia in C57BL/6J ob/ob mice with insulin resistance (IR). Male ob/ob, lean, or wild-type (WT) mice were treated with RSV (10 mg/kg per day, i.p.) or vehicle for 3 days. Ischemia was induced by 60 mins of middle cerebral artery occlusion (MCAO) and cortical blood flow (CBF) was monitored by laserDoppler flowmetry. Infarct volumes were measured 24 h after reperfusion. IR mice exhibited a higher infarct volume compared with Lean or WT mice, and RSV reduced infarct volume only in obese mice (40%±3% versus 32%±3%, P < 0.05). Blood cholesterol and insulin levels were elevated in ob/ob mice but were unaffected by RSV. The CBF reductions during MCAO were similar in all groups and were not affected by RSV. Although RSV did not increase cortical endothelial NO synthase (eNOS) levels in the ob/ob mice, it attenuated the increased cortical expression of intracellular adhesion molecule-1 (ICAM-1) after MCAO from ob/ob mice. Thus, RSV protects against stroke in IR mice by a mechanism independent of effects on the lipid profile, CBF, or eNOS but dependent on suppression of post-MCAO ICAM-1 expression.

Role of Mitochondria in Cerebral Vascular Function: Energy Production, Cellular Protection, and Regulation of Vascular Tone

“…We and others have characterized many of the general cardiovascular effects of this disease (19,(51)(52)(53)85,87,94,112,119) and have shown that tissue and vascular inflammation and increased basal levels of ROS from both mitochondrial and nonmitochondrial sources are responsible for vascular and cardiac dysfunction (19,119).…”

Modeling Risk Factors and Confounding Effects in Stroke

“…However, our own experience suggests that despite marginally extended surgery times, subcutaneous adiposity does not unduly affect success rates. This is also borne out by the recent studies that have emerged combining experimental obesity and stroke (119)(120)(121)(122). All such studies have found that the severity of brain damage is markedly increased in obese rodents compared to corresponding wild-types (see below).…”

“…It is only in the last 2 years that studies investigating the impact of obesity on experimental stroke in rodents have emerged (119)(120)(121)(122). All studies have found significantly increased ischemic brain damage in the obese group (see Table).…”

The DREAM Protein Negatively Regulates the NMDA Receptor through Interaction with the NR1 Subunit

“…Mice were anesthetized with pentobarbital sodium (0.06 g/kg) by intraperitoneal injection. Focal ischemia was induced with minor modifications of Tamura's middle cerebral artery occlusion (MCAO) model (Mayanagi et al, 2008). Briefly, the left common and external carotid arteries were exposed through a ventral midline neck incision and were ligated, respectively.…”