Rat pial microvascular responses to melatonin during bilateral common carotid artery occlusion and reperfusion

Abstract

The present study assessed the in vivo rat pial microvascular responses induced by melatonin during brain hypoperfusion and reperfusion (RE) injury. Pial microcirculation of male Wistar rats was visualized by fluorescence microscopy through a closed cranial window. Hypoperfusion was induced by bilateral common carotid artery occlusion (BCCAO, 30 min); thereafter, pial microcirculation was observed for 60 min. Arteriolar diameter, permeability increase, leukocyte adhesion to venular walls, perfused capillary length (PCL), and capillary red blood cell velocity (V(RBC) ) were investigated by computerized methods. Melatonin (0.5, 1, 2 mg/kg b.w.) was intravenously administered 10 min before BCCAO and at the beginning of RE. Pial arterioles were classified in five orders according to diameter, length, and branchings. In control group, BCCAO caused decrease in order 2 arteriole diameter (by 17.5 ± 3.0% of baseline) that was reduced by 11.8 ± 1.2% of baseline at the end of RE, accompanied by marked leakage and leukocyte adhesion. PCL and capillary V(RBC) decreased. At the end of BCCAO, melatonin highest dosage caused order 2 arteriole diameter reduction by 4.6 ± 2.0% of baseline. At RE, melatonin at the lower dosages caused different arteriolar responses. The highest dosage caused dilation in order 2 arteriole by 8.0 ± 1.5% of baseline, preventing leakage and leukocyte adhesion, while PCL and V(RBC) increased. Luzindole (4 mg/kg b.w.) prior to melatonin caused order 2 arteriole constriction by 12.0 ± 1.5% of baseline at RE, while leakage, leukocyte adhesion, PCL and V(RBC) were not affected. Prazosin (1 mg/kg b.w.) prior to melatonin did not significantly change melatonin's effects. In conclusion, melatonin caused different responses during hypoperfusion and RE, modulating pial arteriolar tone likely by MT1 and MT2 melatonin receptors while preventing blood-brain barrier changes through its free radical scavenging action.

Cortical Venous Filling on Dynamic Computed Tomographic Angiography

“…Moreover, the differences in internal carotid artery filling times were small and had little influence on the interhemispheric difference in optimal CVF times. In experimental studies, additional mechanisms of narrowing of the venous lumen are active vein constriction, 18 obstruction by leukocyte-platelet aggregates 19,20 and compression of thin-walled venules by edema. 16,17,21 Poor venous outflow from the affected hemisphere is associated with poor arterial collateral flow in animal studies.…”

Venous system in acute brain injury: Mechanisms of pathophysiological change and function

“…Leukocyte adhesion to venular walls was observed in the rat model of bilateral common carotid artery occlusion (Lapi et al, 2011). In controlled cortical impact (6 m/sec, 0.5 mm), intermittent rolling of leukocytes on endothelium was found both in arterioles and venules, while leukocyte-platelet aggregates were only observed in post-capillary venules (Schwarzmaier et al, 2010).…”

Remodeling of Cerebral Microcirculation after Ischemia-Reperfusion

“…Moreover, two-vessel occlusion is widely for in vivo assessment of microvascular changes during ischemia and reperfusion, because this method involves the pial microvasculature, causing arteriolar diameter changes, an increase in microvascular permeability and in the number of adherent leukocytes to the venular walls as well as a reduction in capillary perfusion and red blood cell velocity [26,27,28,29,30,31,32,33,34,35,36,37,38]. In the four-vessel occlusion method, the physiological events due to reperfusion cannot be studied because the vertebral artery occlusion is induced by electrocauterization [24].…”