Effects of melatonin and luzindole during ischemia reperfusion injury in rat pial microcirculation

This study aimed to investigate the role of melatonin [MT] againstbrain ischemia-reperfusion injury after MT receptor inhibition byluzindole [LZ]. The pial microcirculation of male Wistar rats wasobserved by fluorescence microscopy through a cranial window, using fluorescent dextran [70 K] as a tracer. Vessel diameter, permeability increase [PI], leukocytes adhering to venular walls [LA], capillary red blood cell velocity [CVRBC] and perfused capillary length [PCL] were determined by computerized methods. MT [0.5-1-2 mg/Kg body wt.,i.v.] was infused 10 min before ischemia, induced by bilateral occlusion of common carotid arteries for 30 min, and at the beginning of reperfusion lasting 60 min. In the control group, ischemia caused constriction of arterioles, while reperfusion induced constriction, dilation andconstriction within 40 min. At the end of reperfusion vessel permeability and adhering leukocytes increased; CVRBC and PCL were reduced. MT dose-dependently decreased arteriolar constriction during ischemia and reperfusion. At 40 min of reperfusion MT highest dosage caused dilation of all arterioles. PI and LA were reduced, CVRBC and PCL increased compared to control [p<0.01]. LZ [2 mg/Kg body wt.] prior to MT [2mg/Kg body wt.] prevented arteriolar dilation observed at 40 min ofreperfusion, but did not influence the effects of MT against interstitial edema and leukocyte adhesion. CVRBC and PCL did not differ from baseline. In conclusion, MT appears to cause dilatation of pial arterioles through MT1 and MT2 receptors and protection against blood brain barrier disruption likely acting as a free radical scavenger.