Effect of Baicalin on Matrix Metalloproteinase-9 Expression and Blood–Brain Barrier Permeability Following Focal Cerebral Ischemia in Rats

Abstract

Focal cerebral ischemia results in an increased expression of matrix metalloproteinase-9 (MMP-9), which induces vasogenic brain edema via disrupting the blood-brain barrier (BBB) integrity. Recent studies from our laboratory showed that baicalin reduces ischemic brain damage by inhibiting inflammatory reaction and neuronal apoptosis in a rat model of focal cerebral ischemia. In the present study, we first explored the effect of baicalin on the neuronal damage, brain edema and BBB permeability, then further investigated its potential mechanisms. Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO). Baicalin was administrated by intraperitoneally injected twice at 2 and 12 h after the onset of MCAO. Neuronal damage, brain edema and BBB permeability were measured 24 h following MCAO. Expression of MMP-9 protein and mRNA were determined by western blot and RT-PCR, respectively. Expression of tight junction protein (TJP) occludin was detected by western blot. Neuronal damage, brain edema and BBB permeability were significantly reduced by baicalin administration following focal cerebral ischemia. Elevated expression of MMP-9 protein and mRNA were significantly down-regulated by baicalin administration. In addition, MCAO caused the decreased expression of occludin, which was significantly up-regulated by baicalin administration. Our study suggested that baicalin reduces MCAO-induced neuronal damage, brain edema and BBB permeability, which might be associated with the inhibition of MMP-9 expression and MMP-9-mediated occludin degradation.

Protective effects of baicalin on LPS-induced injury in intestinal epithelial cells and intercellular tight junctions

“…We also found that baicalin up-regulates the expression of ZO-1 protein and keeps it intact in IEC-6 cells injured with LPS. Tu et al reported that baicalin upregulates the expression of occludin in ischemic stroke (Tu et al 2011), but we did not observe obvious improvement in the expression of occludin in IEC-6 cells injured with LPS. These findings imply that baicalin selectively promotes the recovery of LPSdamaged TJs, especially ZO-1.…”

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

“…Occludin, the main component of astrocytes tight junctions, is targeted by the pathogenic activity of MMP-9 and this event usually ends up in alterations of BBB microvascular permeability . Interestingly, in a mouse experimental model, the gene therapy to inhibit MMP-9 improves the outcome when administered after acute events (Hu et al, 2010;Tu et al, 2011).…”

Study of dexamethasone, baicalin and octreotide on brain injury of rats with severe acute pancreatitis

“…Zhu et al [12] propose that baicalin is capable of restoring the barrier function of BBB under ischemic conditions and this beneficial effect may be linked to the decreased expression of tight junctions (TJ) proteins. The study of Tu et al [46] suggested that baicalin can reduce neuronal damage, brain edema and BBB permeability, which might be associated with the inhibition of matrix metalloproteinase-9 (MMP-9) expression and MMP-9-mediated occludin degradation.…”