Abstract:
:Fetal intrauterine growth restriction (IUGR) is a serious pregnancy complication associated with increased rates of perinatal morbidity and mortality, and ultimately with long-term neurodevelopmental impairments. No intervention currently exists that can improve the structure and function of the IUGR brain before birth. Here, we investigated whether maternal antenatal melatonin administration reduced brain injury in ovine IUGR. IUGR was induced in pregnant sheep at 0.7 gestation and a subset of ewes received melatonin via intravenous infusion until term. IUGR, IUGR + melatonin (IUGR + MLT) and control lambs were born naturally, neonatal behavioral assessment was used to examine neurological function and at 24 hr after birth the brain was collected for the examination of neuropathology. Compared to control lambs, IUGR lambs took significantly longer to achieve normal neonatal lamb behaviors, such as standing and suckling. IUGR brains showed widespread cellular and axonal lipid peroxidation, and white matter hypomyelination and axonal damage. Maternal melatonin administration ameliorated oxidative stress, normalized myelination and rescued axonopathy within IUGR lamb brains, and IUGR + MLT lambs demonstrated significant functional improvements including a reduced time taken to attach to and suckle at the udder after birth. Based on these observations, we began a pilot clinical trial of oral melatonin administration to women with an IUGR fetus. Maternal melatonin was not associated with adverse maternal or fetal effects and it significantly reduced oxidative stress, as evidenced by reduced malondialdehyde levels, in the IUGR + MLT placenta compared to IUGR alone. Melatonin should be considered for antenatal neuroprotective therapy in human IUGR.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
Miller SL,Yawno T,Alers NO,Castillo-Melendez M,Supramaniam VG,VanZyl N,Sabaretnam T,Loose JM,Drummond GR,Walker DW,Jenkin G,Wallace EMdoi
10.1111/jpi.12121subject
Has Abstractpub_date
2014-04-01 00:00:00pages
283-94issue
3eissn
0742-3098issn
1600-079Xjournal_volume
56pub_type
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journal_title:Journal of pineal research
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abstract::Five adult pasture-bred Prim Holstein cows were used to document the time invariance of melatonin disposition in the cow. Melatonin was administered by an intravenous route as a bolus (5 micrograms/kg of body weight) at either 1430 or 2230. Data were analysed according to a three-compartment open model with melatonin ...
journal_title:Journal of pineal research
pub_type: 杂志文章
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journal_title:Journal of pineal research
pub_type: 杂志文章
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journal_title:Journal of pineal research
pub_type: 杂志文章
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abstract::We examined the effects of a single 2.5-mg dose of melatonin on the thermoregulatory and circulatory responses to intermittent exercise at a room temperature of 27.2+/-0.4 degrees C (mean+/-S.D.), a relative humidity of 55+/-3% (mean+/-S.D.), and a light intensity of 200-300 lux. In a double-blind cross-over study, si...
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journal_title:Journal of pineal research
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journal_title:Journal of pineal research
pub_type: 杂志文章
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journal_title:Journal of pineal research
pub_type: 临床试验,杂志文章
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journal_title:Journal of pineal research
pub_type: 杂志文章,评审
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journal_title:Journal of pineal research
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journal_title:Journal of pineal research
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abstract::The known neuroprotective actions of melatonin could be due to its antioxidant or radical scavenging activity, or they could be due to specific interactions of the indole with its receptors. A study of structure-activity relationships may provide useful information when a validated macromolecular target has not been (...
journal_title:Journal of pineal research
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journal_title:Journal of pineal research
pub_type: 杂志文章
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journal_title:Journal of pineal research
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