Melatonin Decreases Circulating Levels of Galectin-3 and Cytokines, Motor Activity, and Anxiety Following Acute Global Cerebral Ischemia in Male Rats

Background. Global cerebral ischemia (GCI) elicits damages to cerebral structures, learning dysfunction, memory impairments, hyperactivity, and anxiety. Circulating levels of galectin-3 (Gal-3) are associated with patient severity and outcome. Aim. To report circulating levels of Gal-3, and cytokines (TNF-alpha, IL-6, IL-10) in the initial hours (acute) following GCI in a four-vessel occlusion (4-VO) rat model and the effect of melatonin treatment. Methods. 4-VO model was used to produce GCI using male Sprague-Dawley rats. Groups were: Sham-Veh, Sham-Mel, Isch-Veh and Isch-Mel. Melatonin was administered 30 min after carotid clamp removal. Gal-3 and cytokines levels were measured at 0, 30 min, 6 h and 24 h after the end of cerebral flow interruption using ELISA kits. Motor activity and anxiety were measured using open-field test. Results. Acute GCI (AGCI) followed by reperfusion decreased serum concentrations of TNF-alpha and increased IL-6 levels 24 h after ischemia, whereas melatonin reduced significantly the concentrations of these cytokines. In all groups IL-10 was higher 30 min and negligible at other times. Circulating levels of Gal-3 were reduced 30 min after ischemia/reperfusion. In the Isch-Mel group the neuroprotective effect generated a reduction in circulating Gal-3 at 6 and 24 h after AGCI, compared with all the groups. Motor activity was increased due to ischemic reperfusion, but acute melatonin treatment reduced locomotion, similar to the control group. Anxiety was reduced in the melatonin group. Conclusions. Melatonin treatment following AGCI reduces pro-inflammatory factors, Gal-3, motility, and anxiety, therefore it should be considered as supplementary treatment following ischemic stroke. (C) 2021 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.