Effect of quercetin pretreatment on permeability of blood-brain barrier in a rat model of global cerebral ischemia-reperfusion

Abstract

Objective To evaluate the effect of quercetin pretreatment on the permeability of blood-brain barrier in a rat model of global cerebral ischemia-reperfusion (I/R). Methods Sixty-three clean-grade healthy male Sprague-Dawley rats, weighing 300-350 g, aged 4-5 months, were divided into 3 groups (n=21 each) using a random number table method: sham operation group (group S), group I/R and quercetin pretreatment group (group Q). Global cerebral I/R was induced by occlusion of bilateral common carotid arteries combined with hypotension (mean arterial pressure was maintained at 35-45 mmHg) in chloral hydrate-anesthetized rats.Quercetin 25 μmol/kg was injected intraperitoneally twice a day for 3 consecutive days starting from 3 days before establishment of the model in group Q, while the equal volume of normal saline was given instead at the corresponding time points in group S and group I/R, respectively.The animals were sacrificed at 24 h of reperfusion and brains were removed to determine the brain water content, Evans blue (EB) content and expression of occludin protein in cerebral cortex (by Western blot) and to observe the ultrastructure of blood-brain barrier. Results Compared with group S, the brain water content and EB content were significantly increased, the expression of occludin protein was down-regulated (P<0.05), and the injury to ultrastructure of blood-brain barrier was accentuated in I/R and Q groups.Compared with group I/R, the brain water content and EB content were significantly decreased, the expression of occludin protein was up-regulated (P<0.05), and the injury to ultrastructure of blood-brain barrier was significantly attenuated in group Q. Conclusion Quercetin pretreatment can decrease the permeability of blood-brain barrier and attenuate brain edema, and the mechanism may be related to up-regulated expression of occludin protein in a rat model of global cerebral I/R. Key words: Quercetin; Cerebral; Ischemia-reperfusion; Blood-brain barrier