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

Welin, Anna-Karin,1965Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences (author)

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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
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

Svedin, Pernilla,1979Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xarvpe (author)
Lapatto, Risto (author)
Sultan, Bo,1949Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences (author)
Hagberg, Henrik,1955Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences(Swepub:gu)xhaghe (author)
Gressens, Pierre (author)
Kjellmer, Ingemar,1935Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences(Swepub:gu)xkjing (author)
Mallard, Carina,1963Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xmallc (author)
Göteborgs universitetInstitutionen för kliniska vetenskaper (creator_code:org_t)

In:Pediatric research: Springer Science and Business Media LLC61:2, s. 153-80031-39981530-0447

By the author/editor: Welin, Anna-Kari ...; Svedin, Pernilla ...; Lapatto, Risto; Sultan, Bo, 1949; Hagberg, Henrik, ...; Gressens, Pierre; show more...; Kjellmer, Ingema ...; Mallard, Carina, ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

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