Chlorogenic acid ameliorates brain damage and edema by inhibiting matrix metalloproteinase-2 and 9 in a rat model of focal cerebral ischemia

Abstract

Chlorogenic acid (CGA) has been reported to have various beneficial effects on the cardiovascular and central nervous systems. The purpose of the current study was to investigate whether CGA has protective effects against cerebral ischemia and whether these effects are due to modification of brain edema-related vascular factors. In a rat model of transient middle cerebral artery occlusion (MCAo, 2h of occlusion followed by 22h of reperfusion), we measured infarct volume and performed behavioral test to evaluate the effects of CGA on brain damage and sensory-motor functional deficits. Brain water content and Evans blue extravasation were measured to evaluate brain edema and blood brain barrier (BBB) damage. Lipid peroxidation (LPO) and the expressions and activities of matrix metalloproteinase (MMP)-2 and MMP-9 were measured to investigate the mechanisms of action. Intraperitoneal injection of CGA (3, 10, and 30mg/kg) at 0h and 2h after MCAo dose-dependently reduced infarct volume and sensory-motor functional deficits. It also reduced brain water content and Evans blue extravasation. Mechanistically, CGA reduced LPO and MMPs expressions and activities. These results suggest that CGA reduces brain damage, BBB damage and brain edema by radical scavenging activity and the inhibitory effects on MMP-2 and MMP-9.