The use of melatonin in hypoxic-ischemic brain damage: an experimental study

J Matern Fetal Neonatal Med. 2012 Apr;25 Suppl 1:119-24. doi: 10.3109/14767058.2012.663232. Epub 2012 Mar 5.

Abstract

Objective: Oxidative stress (OS) plays a key role in perinatal brain damage. The aim of this study is to evaluate the effectiveness of melatonin as a neuroprotective drug by investigating the influence of melatonin on OS and inflammation biomarkers in an animal model of cerebral hypoxia-ischemia.

Methods: Five minutes after hypoxic-ischemic (HI) injury melatonin was administered to 28 rats (HI-Mel group). At the same time, 28 hypoxic-ischemic rats were vehicle-treated (V-HI group). Five rats were used as sham operated controls (CTL). OS biomarkers: isoprostanes (IsoPs), neuroprostanes (NPs) and neurofurans (NFs), and microglial activation markers (glial fibrillary acidic protein [GFAP] and monoclonal antirat CD68 [ED1]) were measured in the cerebral cortex of the two lobes.

Results: A significant increase of IsoPs on the left lobe was observed in V-HI after 1 hour (h) from HI injury (p < 0.001); a significant increase of NPs on both side (p < 0.05) and a significant increase of NFs on the left (p < 0.05) were also observed in V-HI after 24 h. A significant increase of IsoPs on the left (p < 0.05) and of NPs on both lobes (p < 0.05) were observed in HI-Mel after 48 h. The ED1 and GFAP expression was lower in the HI-Mel brain tissue.

Conclusions: Melatonin reduces OS and inflammatory cells recruitment and glial cells activation in cerebral cortex after neonatal HI damage. These results lay the groundwork for future clinical studies in infants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Biomarkers / metabolism
  • Drug Evaluation, Preclinical
  • Female
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / metabolism
  • Melatonin / pharmacology
  • Melatonin / therapeutic use*
  • Microglia / drug effects
  • Monocytes / drug effects
  • Oxidative Stress / drug effects*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Antioxidants
  • Biomarkers
  • 3-nitrotyrosine
  • Tyrosine
  • Melatonin