title: Prophylactic administration of melatonin to the mother throughout pregnancy can protect against oxidative cerebral damage in neonatal rats.
abstract: OBJECTIVE
  The purpose of this study was to investigate whether prophylactic administration of melatonin to the mother throughout pregnancy could protect against ischemia/reperfusion (I/R)-induced oxidative brain damage in neonatal rats.
  
  
  METHODS
  The utero-ovarian arteries were occluded bilaterally for 30 min in female Wistar rats on day 16 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation. A sham operation was performed in control rats. Melatonin solution or vehicle alone was administrated orally throughout pregnancy. We collected brain mitochondria from neonatal rats, evaluated mitochondrial structure by electron microscopy, and measured the respiratory control index (RCI) as an indicator of mitochondrial respiratory activity as well as the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress. Histological analysis was performed at the Cornu Ammonis 1 (CA1) and Cornu Ammonis 3 (CA3) regions of the hippocampus.
  
  
  RESULTS
  I/R significantly reduced the RCI and significantly elevated the concentration of TBARS. Melatonin treatment reversed these effects, resulting in values similar to that in untreated, sham-ischemic animals. Electron microscopic evaluation showed that the number of intact mitochondria decreased in the I/R group, while melatonin treatment preserved them. Histological analysis revealed a decrease in the ratio of normal to whole pyramidal cell number in the CA1 and CA3 regions in the I/R group. While melatonin administration protected against degeneration.
  
  
  CONCLUSIONS
  These results indicate that prophylactic administration of melatonin to the mother throughout pregnancy may prevent I/R-induced oxidative brain damage in neonatal rats.
authors.affiliation: Department of Obstetrics and Gynecology, Aichi Medical University School, Aichi, Japan. kw446433@yahoo.co.jp
authors.forename: Kazushi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Hamada
authors.forename: Akihiko
authors.initials: A
authors.lastname: Wakatsuki
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Nagai
authors.forename: Koichi
authors.initials: K
authors.lastname: Shinohara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Rina
authors.initials: R
authors.lastname: Imamura
authors.forename: Takao
authors.initials: T
authors.lastname: Fukaya
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D054022:Cerebrum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D018890:Chemoprevention / Q000379:methods; D019610:Cytoprotection / Q000187:drug effects*; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005260:Female; D008550:Melatonin / Q000008:administration & dosage* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy / Q000187:drug effects; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D008550:Melatonin