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BRAIN DAMAGE AND OXIDATIVE STRESS IN THE PERINATAL PERIOD: MELATONIN AS A NEUROPROTECTIVE NEW DRUG

S. Perrone, S. Bertrando, S. Cornacchione, S. Negro, M.L. Tataranno, M. Tei, G. Stazzoni, G. Buonocore
  • S. Perrone
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy
  • S. Bertrando
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy
  • S. Cornacchione
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy
  • S. Negro
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy
  • M.L. Tataranno
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy
  • M. Tei
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy
  • G. Stazzoni
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy
  • G. Buonocore
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy | buonocore@unisi.it

Abstract

Prenatal factors represent the main determinants of hypoxicischemic encephalopathy (HIE) rather than intra- or post-partum conditions in perinatal period. Oxidative stress (OS) plays a key role in perinatal brain damage. The development of therapeutic strategies to improve the outcomes of babies with HIE is still mandatory. Aim: to evaluate the effectiveness of melatonin as a neuroprotective drug. To investigate the influence of Melatonin on the OS biomarkers production in an animal model of cerebral hypoxia-ischemia. Methods: 30 rat pups were subjected to ligation of the right common carotid artery and exposed for 2.5 hours at an hypoxic condition. A group of 15 rats was administered melatonin at a dose of 15 mg/kg 5 minutes after the procedure (Mel GROUP). At the same time 15 rats received placebo (HI GROUP). A group of 5 healthy rats was used as sham operated (S GROUP). Isoprostanes (IsoPs), neuroprostanes (NPs) and neurofurans (NFs), all markers of OS were measured at 1, 24 and 48 h from ischemic injury in homogenized cerebral cortex of the two sides, right (hypoxia and ischemia) and left (hypoxia). Results: In the HI group were observed: a significant increase of IsoPs on the left side of cortex after 1 h from HI injury (p<0.001); a significant increase of NPs on both sides after 24 h (p<0.05) and a significant increase of NFs on the left (p<0.05) after 24 h. After 48 h in the Mel group was observed a significant increase of IsoPs on the left (p<0.05) and of NPs on both sides of cerebral cortex (p<0.05). Conclusions: Melatonin reduces OS biomarkers in cerebral cortex of HI rats after 24 h from its administration. The drug is no longer effective after 48 h. These results lay the groundwork for future clinical studies in infants.

Keywords

oxidative stress, hypoxia-ischemia, animal model, melatonin

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Submitted: 2012-08-20 16:34:01
Published: 2012-08-20 17:21:05
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Copyright (c) 2012 S. Perrone, S. Bertrando, S. Cornacchione, S. Negro, M.L. Tataranno, M. Tei, G. Stazzoni, G. Buonocore

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