Therapeutic effects of maternal melatonin administration on ischemia/reperfusion-induced oxidative cerebral damage in neonatal rats.
BACKGROUND
We have previously demonstrated that prophylactic administration of melatonin to pregnant rats can protect against ischemia/reperfusion (I/R)-induced oxidative cerebral damage in fetal rats. However, the effects of maternal administration of melatonin after an ischemic episode on the brains of neonatal rats exposed to oxidative stress in utero have not been evaluated.


OBJECTIVE
The purpose of the present study was to investigate whether maternal administration of melatonin after an ischemic episode can prevent oxidative cerebral 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. Melatonin solution (10 mg/kg) or vehicle was injected intraperitoneally at 0, 1, 3, 6, and 12 h after reperfusion. After surgery, melatonin solution (20 microg/ml) or vehicle was administered freely via drinking water up to vaginal delivery. Control rats underwent a sham operation. We collected brain tissue from neonatal rats that were delivered naturally and measured the respiratory control index (RCI) as indicators of mitochondrial respiratory activity. Histological evaluation was performed on the cornu ammonis (CA1) and CA3 regions of the hippocampus.


RESULTS
I/R significantly reduced the RCI, but melatonin administration at postreperfusion hour 0 or 1 reversed I/R-induced reductions in the RCI. In contrast, melatonin administration at postreperfusion hours 3-12 had no protective effect. 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 within 3 h protected against degeneration, administration 6 h after reperfusion failed to protect.


CONCLUSIONS
These results suggest that maternal administration of melatonin within 1 h after an ischemic/oxidative episode can prevent I/R-induced oxidative cerebral damage in neonatal rats.
Hamada
Fumiaki
F
Department of Obstetrics and Gynecology, Kochi Medical University School, Kochi, Japan. boku3240 @ yahoo.co.jp
Watanabe
Kazushi
K
Wakatsuki
Akihiko
A
Nagai
Ryuhei
R
Shinohara
Koichi
K
Hayashi
Yoshihiro
Y
Imamura
Rina
R
Fukaya
Takao
T
D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000517:prevention & control*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D005260:Female; D008550:Melatonin / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
D008550:Melatonin