Neuroprotective and regenerative effects of melatonin on hypoxic-ischemic brain injury in neonatal rats

To investigate the neuroprotective effect of melatonin against hypoxic-ischemic brain injury in neonatal rats and the mechanisms involved. Neonatal rats with hypoxic-ischemic brain injury were treated with melatonin at 0.01 mg per gram body weight for 7 days. The damaged area and volume of the rat brains were quantified by threedimensional (3D) reconstructive technology. Apoptosis, regeneration, and repair of neurons in the rat brain were evaluated using terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), 5-bromo-2’-deoxyuridine (BrdU), double cortin (DCX), and hexaribonucleotide-binding protein-3 (NeuN) assays. Seven days after hypoxicischemic brain injury, the damaged area and volume of the injury (16.24 ± 0.33 mm2 and 47.8 ± 0.30 mm3, respectively) were significantly greater than those in melatonin-treated rats (9.38 ± 0.23 mm2 and 26.3 ± 0.28 mm3, respectively). The TUNEL assay showed that the proportion of apoptotic neurons in the hypoxia-ischemia rats (12.2%) was significantly greater than that in melatonin-treated rats (4.3%). The percentages of DCX+/BrdU+ and NeuN+/ BrdU+ neurons in melatonin-treated rats (15.3% and 11.2%, respectively) were significantly higher than those in untreated rats (5.2% and 0.2%). In conclusion, melatonin may not only reduce hypoxia-ischemia-induced brain injury but also promote nerve regeneration in neonatal rats.