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

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.