Protective effects of quercetin on rat pial microvascular changes during transient bilateral common carotid artery occlusion and reperfusion

Abstract

The aim of this study was to assess the in vivo effects of quercetin on pial microvascular responses during transient bilateral common carotid artery occlusion (BCCAO) and reperfusion. Rat pial microcirculation was visualized by fluorescence microscopy through a closed cranial window. Pial arterioles were classified in five orders of branchings. Capillaries were assigned order 0, the smallest arterioles order 1, and the largest ones order 5. In ischemic rats, 30 min BCCAO and 60 min reperfusion caused arteriolar diameter decrease (by 14.5 ± 3.3% of baseline in order 2), microvascular leakage [0.47 ± 0.04, normalized gray levels (NGL)], leukocyte adhesion in venules (9 ± 2/100 μm venular length, v.l./30 s), and reduction of capillary perfusion (by 40 ± 7% of baseline). Moreover, at the end of BCCAO and reperfusion there was a significant increase in reactive oxygen species (ROS) formation when compared with baseline. Quercetin highest dose determined dilation in all arteriolar orders (by 40 ± 4% of baseline in order 2) and prevented microvascular permeability (0.15 ± 0.02 NGL), leukocyte adhesion (3 ± 1/100 μm v.l./30 s) as well as ROS formation, while capillary perfusion was protected. Inhibition of endothelial nitric oxide synthase (NOS) prior to quercetin reduced arteriolar dilation (order 2 diameter increase by 10.3 ± 2.5% of baseline) and caused permeability increase (0.29 ± 0.03 NGL); inhibition of neuronal NOS or inducible NOS did not affect quercetin-induced effects. Inhibition of guanylyl cyclase prior to quercetin reversed the quercetin’s effects on pial arteriolar diameter and leakage. In conclusion, quercetin was able to protect pial microcirculation from ischemia–reperfusion damage inducing arteriolar dilation likely by nitric oxide release. Moreover, quercetin scavenger activity blunted ROS formation preserving the blood–brain barrier integrity.

Neuroprotective effects of quercetin in a mouse model of brain ischemic/reperfusion injury via anti-apoptotic mechanisms based on the Akt pathway

“…The present study proved that the motor function was impaired after ischemic insults in rats and was significantly ameliorated by treatment with quercetin. These findings are in accordance with earlier studies where motor deficits were attenuated by treatment with anti-oxidants (4,11,23).…”

“…1) (3). It was reported that quercetin was able to maintain blood-brain barrier integrity by scavenging active oxygen (4). It was suggested that oral treatment with quercetin nanocapsules may exert a protective effect against oxidative damage and prevent pyramidal neurons in the hippocampus from ischemia/reperfusion (I//R) (5).…”

Effect of BCCAO Duration and Animal Models Sex on Brain Ischemic Volume After 24 Hours Reperfusion

“…Shorter duration of ischemia followed by longer reperfusion can lead to striatum and cortex damage. This results differ from research by Lapi et al (2012), which shows striatum ischemia after 30 minutes of induction followed by 60 minute reperfusion in Wistar rat.…”

“…This is because TTC staining can detect the presence of lactate dehydrogenase enzyme (LDH) which makes the healthy tissue to appear red. Meanwhile, ischemic tissue will have a reduced amount of LDH enzyme so it will appear white on macroscopic observation 4,6,10,9 . In addition to TTC, ischemic tissue can be observed by Haematoxyline Eosin (HE) and Toulidin Blue (TB) staining 3 .…”

“…Duration of BCCAO techniques varies between 10 to 30 minutes, while the duration of reperfusion period ranging between 45 minutes to 72 hours. Differences in the duration of occlusion, duration of reperfusion BCCAO and the sex of animal model could lead to different responses to ischemia conditions [2][3][4][5][6][7][8][9] . Ischemic brain region can be observed both macroscopically and microscopically.…”