Melatonin reduces inflammation and cell death in white matter in the mid-gestation fetal sheep following umbilical cord occlusion.

• The premature infant is at increased risk of cerebral white matter injury. Melatonin is neuroprotective in adult models of focal cerebral ischemia and attenuates ibotenate-induced white matter cysts in neonatal mice. Clinically, melatonin has been used to treat sleep disorders in children without major side effects. The aim of this study was to investigate the protective and anti-inflammatory effects of melatonin in the immature brain following intrauterine asphyxia. Fetal sheep at 90 d of gestation were subjected to umbilical cord occlusion. Melatonin (20 mg/kg, n = 9) or vehicle (n = 10) was administered IV to the fetus, starting 10 min after the start of reperfusion and continued for 6 h. Melatonin treatment resulted in a slower recovery of fetal blood pressure following umbilical cord occlusion, but without changes in fetal heart rate, acid base status or mortality. The production of 8-isoprostanes following umbilical cord occlusion was attenuated and there was a reduction in the number of activated microglia cells and TUNEL-positive cells in melatonin treated fetuses, suggesting a protective effect of melatonin. In conclusion, this study shows that melatonin attenuates cell death in the fetal brain in association with a reduced inflammatory response in the blood and the brain following intrauterine asphyxia in mid-gestation fetal sheep.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Keyword

Animals

Anti-Inflammatory Agents

administration & dosage

pharmacology

therapeutic use

Asphyxia

complications

metabolism

Blood Gas Analysis

Blood Pressure

drug effects

Brain

drug effects

metabolism

Cell Death

Dinoprost

analogs & derivatives

blood

Female

Fetal Diseases

etiology

pathology

prevention & control

Gestational Age

Heart Rate

Fetal

drug effects

Humans

Infant

Newborn

Leukomalacia

Periventricular

etiology

pathology

prevention & control

Melatonin

administration & dosage

pharmacology

therapeutic use

Neuroprotective Agents

administration & dosage

pharmacology

therapeutic use

Pregnancy

Sheep

embryology

Sulfhydryl Compounds

blood

Time Factors

Umbilical Cord

surgery

Publication and Content Type

ref (subject category)

art (subject category)