Broccoli sprout supplementation during pregnancy prevents brain injury in the newborn rat following placental insufficiency

Black, Amy M.; Armstrong, Edward A.; Scott, Olive; Juurlink, Bernard; Yager, Jerome Y.

doi:10.1016/j.bbr.2015.05.033

Cited by 43 publications

(24 citation statements)

References 30 publications

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“…Another pathway that may affect recovery is free radical production, increases in which are associated with greater neurological injury after HI 53 . Physiological increases in free radicals such as reactive oxygen species (ROS) are also associated with increased mitochondrial function and improved cellular antioxidant status, at least in part through activation of nuclear factor (erythroid-2)-related factor 2 (Nrf2), which has been shown to be involved in the mechanism of multiple neuroprotective strategies 54 55 56 57 . While HT is generally thought to suppress production of ROS, deeper HT may increase ROS production, as well as inhibit ROS clearance due to slower enzyme kinetics 45 54 58 .…”

Section: Discussionmentioning

confidence: 99%

Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia

Wood

Osredkar

Puchades

et al. 2016

Sci Rep

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Therapeutic hypothermia (HT) is standard care for moderate and severe neonatal hypoxic-ischaemic encephalopathy (HIE), the leading cause of permanent brain injury in term newborns. However, the optimal temperature for HT is still unknown, and few preclinical studies have compared multiple HT treatment temperatures. Additionally, HT may not benefit infants with severe encephalopathy. In a neonatal rat model of unilateral hypoxia-ischaemia (HI), the effect of five different HT temperatures was investigated after either moderate or severe injury. At postnatal-day seven, rat pups underwent moderate or severe HI followed by 5 h at normothermia (37 °C), or one of five HT temperatures: 33.5 °C, 32 °C, 30 °C, 26 °C, and 18 °C. One week after treatment, neuropathological analysis of hemispheric and hippocampal area loss, and CA1 hippocampal pyramidal neuron count, was performed. After moderate injury, a significant reduction in hemispheric and hippocampal loss on the injured side, and preservation of CA1 pyramidal neurons, was seen in the 33.5 °C, 32 °C, and 30 °C groups. Cooling below 33.5 °C did not provide additional neuroprotection. Regardless of treatment temperature, HT was not neuroprotective in the severe HI model. Based on these findings, and previous experience translating preclinical studies into clinical application, we propose that milder cooling should be considered for future clinical trials.

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Section: Discussionmentioning

confidence: 99%

Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia

Wood

Osredkar

Puchades

et al. 2016

Sci Rep

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“…evident in animal models of growth restriction with demonstrated neuronal and white matter disruption [21][22][23][24][25][26][27][28][29][30]. Neuronal loss and disruption are observed in IUGR animal models throughout many regions of the brain including the hippocampus [29,31].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Review: Neuroinflammation in intrauterine growth restriction

et al. 2017

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Disruption to the maternal environment during pregnancy from events such as hypoxia, stress, toxins, inflammation, and reduced placental blood flow can affect fetal development. Intrauterine growth restriction (IUGR) is commonly caused by chronic placental insufficiency, interrupting supply of oxygen and nutrients to the fetus resulting in abnormal fetal growth. IUGR is a major cause of perinatal morbidity and mortality, occurring in approximately 5-10% of pregnancies. The fetal brain is particularly vulnerable in IUGR and there is an increased risk of long-term neurological disorders including cerebral palsy, epilepsy, learning difficulties, behavioural difficulties and psychiatric diagnoses. Few studies have focused on how growth restriction interferes with normal brain development in the IUGR neonate but recent studies in growth restricted animal models demonstrate increased neuroinflammation. This review describes the role of neuroinflammation in the progression of brain injury in growth restricted neonates. Identifying the mediators responsible for alterations in brain development in the IUGR infant is key to prevention and treatment of brain injury in these infants.

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“…Here, we used this model to investigate the impact of this fetal stress on body composition and metabolic function in the offspring. We have previously shown that this prenatal intervention causes altered postnatal growth trajectories and a number of neurodevelopmental deficits that persist into adulthood 17 . Here, our results show that the late phase of gestation in the rat is important in dictating body composition in addition to metabolic function 9 , and these effects are influenced by the sex of the offspring.…”

Section: Discussionmentioning

confidence: 99%

Late-pregnancy uterine artery ligation increases susceptibility to postnatal Western diet-induced fat accumulation in adult female offspring

Jahandideh

Bourque

Armstrong

et al. 2020

Sci Rep

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Stressors during the fetal and postnatal period affect the growth and developmental trajectories of offspring, causing lasting effects on physiologic regulatory systems. Here, we tested whether reduced uterine artery blood flow in late pregnancy would alter body composition in the offspring, and whether feeding offspring a western diet (WD) would aggravate these programming effects. Pregnant rats underwent bilateral uterine artery ligation (BUAL) or sham surgery on gestational day (GD)18 (term = GD22). At weaning, offspring from each group received either a normal diet (ND) or a WD. BUAL surgery increased fetal loss and caused offspring growth restriction, albeit body weights were no longer different at weaning, suggesting postnatal catch-up growth. BUAL did not affect body weight gain, fat accumulation, or plasma lipid profile in adult male offspring. In contrast, while ND-fed females from BUAL group were smaller and leaner than their sham-littermates, WD consumption resulted in excess weight gain, fat accumulation, and visceral adiposity. Moreover, WD increased plasma triglycerides and cholesterol in the BUAL-treated female offspring without any effect on sham littermates. These results demonstrate that reduced uterine artery blood flow during late pregnancy in rodents can impact body composition in the offspring in a sex-dependent manner, and these effects may be exacerbated by postnatal chronic WD consumption. The last few decades have seen a global rise in the incidence and prevalence of obesity. The World Health Organization estimates that obesity affects 650 million people worldwide, with an additional 1.9 billion classified as overweight 1. Although this trend is attributed, at least in part, to the consumption of energy-rich diets and increasingly sedentary lifestyles, a newly defined contributor to the obesity epidemic is the programming effects caused by stressors during development. The developmental origins of health and disease (DOHaD) theory posits that stressors during the fetal and immediate postnatal period can alter the growth and developmental trajectories of offspring, causing lasting effects on a number of physiologic regulatory systems. Stressors such as hypoxia, anemia, and nutrient imbalances can confer lasting metabolic dysfunction in the offspring, characterized by a propensity for excess fat accumulation 2 , as well as altered glucose metabolism and dyslipidemia 3. Our group has previously characterized a rat model of bilateral uterine artery ligation (BUAL) to reduce uterine artery blood flow, causing antepartum fetal ischemia, growth restriction, and neurodevelopmental outcomes broadly characteristic of cerebral palsy and developmental disability 4,5. The BUAL surgery is performed at gestational day (GD) 18 (term = GD22), and therefore, constitutes a comparatively narrow exposure period of fetal

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Broccoli sprout supplementation during pregnancy prevents brain injury in the newborn rat following placental insufficiency

Cited by 43 publications

References 30 publications

Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia

Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia

Review: Neuroinflammation in intrauterine growth restriction

Late-pregnancy uterine artery ligation increases susceptibility to postnatal Western diet-induced fat accumulation in adult female offspring

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