Research Report Resveratrol ameliorates hypoxia/ischemia-induced behavioral deficits and brain injury in the neonatal rat brain Filippos Karalis a, ⁎ , Vassiliki Soubasi b , Thomas Georgiou a , Christos T. Nakas b , Constantina Simeonidou a , Olympia Guiba-Tziampiri a , Evangelia Spandou a a Department of Physiology and Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki Greece b Department of Neonatology, Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki Greece ARTICLE INFO ABSTRACT Article history: Accepted 22 September 2011 Available online 29 September 2011 Hypoxia–ischemia (HI) induced injury of the neonatal brain accounts for behavioral deficits concerning mainly neurological reflexes, sensorimotor functions and learning/memory disabilities that may evolve throughout development. The positive biological effects of resveratrol, a natural compound with anti-oxidant/anti-inflammatory properties found mainly in red wine have been indicated recently. Aim of this study was to investigate the delayed outcome of early administration of resveratrol in an experimental model of hypox- ic–ischemic encephalopathy, by means of behavioral analysis and late neuropathological examination. Seven-day-old (P7) rats were separated into 3 groups: Group 1 underwent HI and treated with resveratrol. Group 2 (HI-treated) was subjected to HI and received same volume of saline. Group 3 (sham-operated) was the control group. A battery of behavioral tests was performed from days P8–P66, during which early reflexes (righting reflex, gait, geotaxis), sensorimotor (rope suspension, beam walking, rotarod) and learning/memory function (passive avoidance, Morris water-maze) were examined. Significant difference among the groups was observed in righting reflex, rotarod and water maze tests in which the resveratrol group almost reached the performance of the control animals. The other be- havioral tests showed that control and resveratrol groups were better compared to HI, al- though not significant. Neuropathology study revealed a remarkable reduction of the infarct and preservation of myelination after resveratrol treatment, which was in most cases correlated with the better performance of the resveratrol group. These findings indi- cate that long-term neuroprotective effect of resveratrol on neonatal HI-induced gray and white matter damage might be associated with the preservation of behavioral functions. © 2011 Elsevier B.V. All rights reserved. Keywords: Hypoxia–ischemia Neonatal brain Resveratrol Behavior Water maze Corpus callosum 1. Introduction Increasing amount of evidence indicates recently the neuropro- tective properties of resveratrol (RVT) (Huang et al., 2001; Tsai et al., 2007; Wang et al., 2004; West et al., 2007), a natural compound of red wine, grapes, peanuts and other dietary products (Soleas et al., 2001). Enormous scientific interest about this phytoalexin (3,5,4′-trihydroxystilbene) occurred especially due to the “French Paradox” (Sun et al., 2002; Virgili and Contestabile, 2000) and re- search at that time focused on experimental models of heart BRAIN RESEARCH 1425 (2011) 98 – 110 ⁎ Corresponding author. Fax. + 30 2310999079. E-mail address: fkaralis@med.auth.gr (F. Karalis). Available online at www.sciencedirect.com www.elsevier.com/locate/brainres 0006-8993/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2011.09.044