Antioxidant Therapies: A Potential Role in Perinatal Medicine

Miller, Stephanie; Wallace, Euan M.; Walker, David

doi:10.1159/000336378

Cited by 77 publications

(72 citation statements)

References 169 publications

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“…Antioxidant therapy may prevent or ameliorate brain tissue damage following hypoxia [19,20,21,22]. In support of this proposal, we have shown that the administration of melatonin prior to an acute hypoxic event in the late gestation sheep fetus abolishes both the primary and secondary increases in brain hydroxyl radical formation and reduces cerebral lipid peroxidation [23].…”

Section: Introductionmentioning

confidence: 87%

Mechanisms of Melatonin-Induced Protection in the Brain of Late Gestation Fetal Sheep in Response to Hypoxia

et al. 2012

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Melatonin has diverse physiological actions in addition to its well-recognized maintenance roles in circadian and seasonal timing. In particular, melatonin may have a direct protective action on the developing fetal brain. We examined the cellular processes by which melatonin provides protection following an acute late gestation hypoxic insult. 15 fetal sheep at 126 days' gestation were instrumented with a brachial artery catheter and a silastic cuff around the umbilical cord. At ∼130 days' gestation, the cuff was inflated for 10 min in 10 fetuses, causing complete umbilical cord occlusion (UCO). 5 UCO fetuses received intravenous melatonin maternally for 2 h, before and after UCO (UCO + melatonin). The remaining 5 fetuses had no UCO performed (sham-operated controls). At 48 h after UCO, the fetal brain was collected from each animal. Compared to controls, UCO caused significant hypoxia, hypercapnia and acidosis in UCO and UCO + melatonin fetuses. In the UCO-alone animals there were significant increases in pyknotic cell death, in the hippocampus (>7-fold) and the cerebellum (3-fold). Maternal melatonin administration ameliorated cellular pyknosis in UCO fetuses. UCO was also associated with astrogliosis, increased albumin uptake, activated microglia and lipid peroxidation. Melatonin prevented these effects. There were no significant differences in the number of brain macrophages or microglia between any of the groups. Following acute severe hypoxia in the late gestation fetus, melatonin reduces neuronal lipid peroxidation and prevents loss of blood-brain barrier integrity and astrogliosis. These are likely key mechanisms underlying the neuroprotective actions of melatonin in the fetal brain.

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Section: Introductionmentioning

confidence: 87%

Mechanisms of Melatonin-Induced Protection in the Brain of Late Gestation Fetal Sheep in Response to Hypoxia

et al. 2012

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“…Much research has been devoted into antenatal therapies to improve placental blood flow, e.g., sildenafil (83), or to reduce oxidative stress by the use of antioxidants, e.g., melatonin (84). These therapies may offer potential new treatment strategies to ameliorate the negative effects of chronic fetal hypoxia on the developing cardiovascular system.…”

Section: Prenatal Interventionmentioning

confidence: 99%

Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy

et al. 2016

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Intrauterine growth restriction (IUGR) refers to the situation where a fetus does not grow according to its genetic growth potential. One of the main causes of IUGR is uteroplacental vascular insufficiency. Under these circumstances of chronic oxygen and nutrient deprivation, the growth-restricted fetus often displays typical circulatory changes, which in part represent adaptations to the suboptimal intrauterine environment. These fetal adaptations aim to preserve oxygen and nutrient supply to vital organs such as the brain, the heart, and the adrenals. These prenatal circulatory adaptations are thought to lead to an altered development of the cardiovascular system and "program" the fetus for life long cardiovascular morbidities. In this review, we discuss the alterations to cardiovascular structure, function, and control that have been observed in growth-restricted fetuses, neonates, and infants following uteroplacental vascular insufficiency. We also discuss the current knowledge on early life surveillance and interventions to prevent progression into chronic disease. Intrauterine growth restriction (IUGR) refers to the situation where a fetus does not grow according to its genetic growth potential. The main cause of IUGR in developed countries is uteroplacental vascular insufficiency (1), which drives the fetus to redistribute its cardiac output to preserve oxygen and nutrient supply to the brain, heart, and adrenals. Although these adaptive circulatory changes are beneficial during intrauterine life, they are thought to cause dysfunctional development of the cardiovascular system and "program" the fetus for life long cardiovascular morbidities (2). This is also known as the Developmental Origins of Health and Disease hypothesis, which postulates that insults during intrauterine and early postnatal development can permanently change the body's structure, function, and metabolism and influence susceptibility to adult noncommunicable diseases (2). Despite their increased risk of cardiovascular disease, infants born growth restricted usually do not receive long-term cardiovascular follow-up. Depending on the definition used, IUGR can occur in up to 10% of pregnancies, and as cardiovascular disease is the number one cause of death worldwide (3), early identification of cardiovascular risk factors and targeted interventions in this high-risk population are of major clinical importance. In this review, we discuss the alterations of cardiovascular structure, function, and control that have been observed in infants born growth restricted and their implications for surveillance and intervention to prevent progression into chronic disease. CHALLENGES IN IDENTIFYING IUGRThe current literature uses many different definitions of IUGR, which may explain some of the contradicting findings discussed in this review. Traditionally, and most commonly, IUGR is defined as a birth weight below the 10th percentile for gestational age on the normative population growth curve (4). This definition, however, merely describes those who ...

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“…This developmental difference could help explain the correlation between greater cerebral immaturity and worse impairment after TBI. [5][6][7][8][9][10][11][12][13][14] Docosahexaenoic acid (DHA) is a candidate neuroprotectant that decreases neuroinflammation in the adult rat. 15 DHA is an essential nutrient for normal brain function and development and is the most abundant omega-3 polyunsaturated fatty acid (22:6n-3) in the mammalian brain.…”

mentioning

confidence: 99%

Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury

Schober

Requena

Abdullah

et al. 2016

Journal of Neurotrauma

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Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the preweanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short-and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI.

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Antioxidant Therapies: A Potential Role in Perinatal Medicine

Cited by 77 publications

References 169 publications

Mechanisms of Melatonin-Induced Protection in the Brain of Late Gestation Fetal Sheep in Response to Hypoxia

Mechanisms of Melatonin-Induced Protection in the Brain of Late Gestation Fetal Sheep in Response to Hypoxia

Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy

Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury

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