Caspase activation in fetal rat brain following experimental intrauterine inflammation

Sharangpani, Aditi; Takanohashi, Asako; Bell, Michael J.

doi:10.1016/j.brainres.2008.01.045

Cited by 19 publications

(5 citation statements)

References 52 publications

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“…We recently found that neuronal cell death differs within hours of birth in mice born into a germ-free vs. a conventional environment (43). Similarly, perinatal rats show increased expression of cell death genes in the brain at 2-8 h after exposure to lipopolysaccharide, a component of bacterial cell walls (44,45). Microbial invasion at birth is associated with the release of inflammatory cytokines (17), and vaginally-born and C-section-born subjects have differing blood cytokine levels (46,47).…”

Section: Discussionmentioning

confidence: 99%

Birth delivery mode alters perinatal cell death in the mouse brain

Castillo‐Ruiz

Mosley

Jacobs

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Labor and a vaginal delivery trigger changes in peripheral organs that prepare the mammalian fetus to survive ex utero. Surprisingly little attention has been given to whether birth also influences the brain, and to how alterations in birth mode affect neonatal brain development. These are important questions, given the high rates of cesarean section (C-section) delivery worldwide, many of which are elective. We examined the effect of birth mode on neuronal cell death, a widespread developmental process that occurs primarily during the first postnatal week in mice. Timed-pregnant dams were randomly assigned to C-section deliveries that were yoked to vaginal births to carefully match gestation length and circadian time of parturition. Compared with rates of cell death just before birth, vaginally-born offspring had an abrupt, transient decrease in cell death in many brain regions, suggesting that a vaginal delivery is neuroprotective. In contrast, cell death was either unchanged or increased in C-section–born mice. Effects of delivery mode on cell death were greatest for the paraventricular nucleus of the hypothalamus (PVN), which is central to the stress response and brain–immune interactions. The greater cell death in the PVN of C-section–delivered newborns was associated with a reduction in the number of PVN neurons expressing vasopressin at weaning. C-section–delivered mice also showed altered vocalizations in a maternal separation test and greater body mass at weaning. Our results suggest that vaginal birth acutely impacts brain development, and that alterations in birth mode may have lasting consequences.

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Section: Discussionmentioning

confidence: 99%

Birth delivery mode alters perinatal cell death in the mouse brain

Castillo‐Ruiz

Mosley

Jacobs

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…A strong case can be made for a role of the microbiome. Castillo-Ruiz et al (1) previously reported that altering the microbiomial environment increases cell death in the PVN a few hours after birth [i.e., in germ-free mice (6)], and others have found differences in cell death-related genes in response to altering the bacterial environment of neonates (7,8). Furthermore, the microbiome is associated with the immune system, including cytokines that can cross into the CNS via the blood-brain barrier.…”

Section: Searching For a Mechanismmentioning

confidence: 99%

Consequences of cesarean delivery for neural development

Swift‐Gallant¹,

Jordan²,

Breedlove³

2018

Proc. Natl. Acad. Sci. U.S.A.

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For over 50 million years, every single mammal on Earth had to enter the world through a harrowing passage: the birth canal. The hazards of this journey, short in distance but potentially prolonged in duration, may have peaked in our own species, where the evolution of larger and larger brains at birth seems to have been limited by increasing risks to the survival of mother and child. With the development of animal husbandry and the near-mythic arrival of Gaius Julius Caesar, a few individuals began entering via another route, avoiding the "big squeeze" to spring forth fully formed from their mothers' incisions. Today, several factors, including efforts to limit the liability for medical malpractice, have resulted in ever more babies bypassing vaginal delivery in favor of cesarean delivery, accounting for 30% of American births. Because the survival rate after cesarean section (C-section) is excellent for both mother and offspring, the procedure has been largely regarded as benign.Now comes a report in PNAS from Castillo-Ruiz et al.(1) that, in mice, cesarean delivery has a rather unexpected effect on brain development that is both profound and widespread. Using caspase-3 production to identify cells about to "give up the ghost", they surveyed naturally occurring cell death (apoptosis) in 13 different brain regions and carefully controlled for a variety of factors to compare development in cesarean-delivered versus vaginally delivered newborns. The brains of mice delivered the oldfashioned way, through vaginal delivery, exhibited an abrupt and widespread pause in the normal process of cell death in almost every brain region examined, increasing the number of surviving cells. In cesarean-delivered pups, in contrast, the rates of cell death in the brain either continued unabated or even increased at delivery, resulting in a greater loss of cells than was seen in vaginally delivered mice. Mouse pups also differed in their vocalization after maternal separation, depending on whether they had undergone vaginal or cesarean delivery. These results raise a host of questions about whether cesarean delivery has a similar effect in humans, subjecting newborns to a greater loss of brain cells and potential alterations in neonatal behavior that could have lifelong consequences. Castillo-Ruiz et al. (1) cite several studies indicating an increased risk for autism and attention deficit hyperactivity disorder in cesarean-delivered babies, but point out that the studies are controversial, in large part, because of the difficulty in adequately controlling for all of the confounding factors that distinguish women who delivery vaginally versus by C-section. Hence, they examined the question in mice so that they could control for other factors to show unequivocally that the mode of delivery affects brain development.Considering the circumstances around vaginal versus cesarean delivery, it may seem counterintuitive that vaginal delivery would host more benefits than cesarean delivery, because cesarean delivery is generally considered ...

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“…When it comes to bacterial infection, LPS exposure was reported to induce microglia to increase the secretion of TNF- α that increased neuron apoptosis via the caspase-3 pathway in the developing cerebral cortex [ 12 ]. In addition to increased apoptosis, LPS exposure was found to lead to decreased neurogenesis in the brain after [ 13 , 14 ]. Therefore, bacterial meningitis may cause apoptosis of a neuron cell and decease neurogenesis though the NF- κ B and TNF- α pathways.…”

Section: Introductionmentioning

confidence: 99%

Granulocyte Colony‐Stimulating Factor Alleviates Bacterial‐Induced Neuronal Apoptotic Damage in the Neonatal Rat Brain through Epigenetic Histone Modification

Yang

et al. 2018

Oxidative Medicine and Cellular Longevity

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Bacterial meningitis during the perinatal period may cause long-term neurological deficits. The study investigated whether bacterial lipopolysaccharide (LPS) derived from E. coli. led to neuronal apoptosis with an impaired performance of long-term cognitive function involving the activation of histone modification in the TNF-α gene promoter. Further, we looked into the therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) in a neonatal brain suffering from perinatal bacterial meningitis. We applied the following research techniques: neurobehavioral tasks, confocal laser microscopy, chromatin immunoprecipitation, and Western blotting. At postnatal day 10, the animals were subjected to LPS and/or G-CSF. The target brain tissues were then collected at P17. Some animals (P45) were studied using neurobehavioral tasks. The LPS-injected group revealed significantly increased expression of NF-κB phosphorylation and trimethylated H3K4 in the TNFA gene promoter locus. Furthermore, the caspase-3, neuronal apoptosis expression, and an impaired performance in cognitive functions were also found in our study. Such deleterious outcomes described above were markedly alleviated by G-CSF therapy. This study suggests that selective therapeutic action sites of G-CSF through epigenetic regulation in the TNFA gene promoter locus may exert a potentially beneficial role for the neonatal brain suffering from perinatal bacterial-induced meningitis.

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Caspase activation in fetal rat brain following experimental intrauterine inflammation

Cited by 19 publications

References 52 publications

Birth delivery mode alters perinatal cell death in the mouse brain

Birth delivery mode alters perinatal cell death in the mouse brain

Consequences of cesarean delivery for neural development

Granulocyte Colony‐Stimulating Factor Alleviates Bacterial‐Induced Neuronal Apoptotic Damage in the Neonatal Rat Brain through Epigenetic Histone Modification

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