Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood-brain barrier damage

Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Disruption of the blood-brain barrier occurs after stroke. Protection of the blood-brain barrier has become an important target of stroke interventions in experimental therapeutic. The objective of the present study was to determine whether curcumin prevents cerebral ischemia/reperfusion injury by protecting blood-brain barrier integrity. We report that a single injection of curcumin (1 and 2 mg/kg, i.v.) 30 min after focal cerebral ischemia/reperfusion in rats significantly diminished infarct volume, improved neurological deficit, decreased mortality, reduced the water content of the brain and the extravasation of Evans blue dye in ipsilateral hemisphere in a dose-dependent manner. In cultured astrocytes, curcumin significantly inhibited inducible nitric oxide synthase (iNOS) expression and NOx (Nitrites/nitrates contents) production induced by lipopolysaccharide (LPS)/tumor necrosis factor alpha (TNF alpha). Furthermore, curcumin prevented ONOO- donor SIN-1-induced cerebral capillaries endothelial cells damage. We concluded that curcumin ameliorates cerebral ischemia/reperfusion injury by preventing ONOO- mediated blood-brain barrier damage. (c) 2007 Elsevier B.V. All rights reserved.