Antenatal antioxidant treatment with melatonin to decrease newborn neurodevelopmental deficits and brain injury...

Area of Science:

• Neuroscience
• Obstetrics
• Perinatology

Background:

• Fetal intrauterine growth restriction (IUGR) leads to severe neurodevelopmental impairments.
• Current interventions cannot improve the IUGR brain structure or function in utero.

Purpose of the Study:

• To investigate if maternal antenatal melatonin administration can reduce brain injury in ovine IUGR.
• To assess the neuroprotective effects of melatonin on IUGR lamb brains and behavior.

Main Methods:

• Intrauterine growth restriction (IUGR) was induced in pregnant sheep.
• Melatonin was administered intravenously to a subset of ewes.
• Neonatal behavior and brain neuropathology were assessed in control, IUGR, and IUGR + melatonin lambs.

Main Results:

• IUGR lambs exhibited delayed motor and feeding behaviors and showed significant brain damage, including lipid peroxidation and white matter abnormalities.
• Maternal melatonin treatment ameliorated oxidative stress, normalized myelination, and rescued axonopathy in IUGR lamb brains.
• IUGR + melatonin lambs displayed improved functional outcomes, with reduced time to stand and suckle.

Conclusions:

• Maternal antenatal melatonin administration demonstrates neuroprotective effects in IUGR.
• A pilot clinical trial in humans showed melatonin was safe and reduced oxidative stress in IUGR placentas.
• Melatonin warrants consideration as an antenatal neuroprotective therapy for human IUGR.