Fetal Growth Restriction Alters Cerebellar Development in Fetal and Neonatal Sheep

Yawno, Tamara; Sutherland, Amy E.; Pham, Yen; Castillo‐Melendez, Margie; Jenkin, Graham; Miller, Stephanie

doi:10.3389/fphys.2019.00560

Cited by 21 publications

(18 citation statements)

References 46 publications

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“…We also found increased expression of the astrocyte marker GFAP in VSG pup hypothalami. An early developmental elevation in IBA1 and GFAP has been reported in various intrauterine growth restricted/SGA models in pigs (77), sheep (3,80), and rats (72) in whole brain homogenates (72) and regions, such as the cortex (3,77), cerebellum (80), and hippocampus (25). Many of these early life differences are not present at PND60, indicating an ability to adapt after the pups are no longer nursing.…”

Section: Discussionmentioning

confidence: 92%

Altered immune system in offspring of rat maternal vertical sleeve gastrectomy

Spann

Taylor

Welch

et al. 2019

American Journal of Physiology-Regulatory, Integrative and Comp

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Women undergoing metabolic surgery for weight loss see many improvements in health, including reduced adiposity and treatment of type 2 diabetes. Fertility is also improved by bariatric surgery and the number of large for gestational day births are reduced. Unfortunately, fetal demise and low birth weights are more prevalent following bariatric surgery, and children born small for gestational age are at an increased risk of obesity as adults. We have replicated these findings in a rat model of vertical sleeve gastrectomy (VSG), however, the origin of these poor outcomes in offspring remains unknown. We have previously reported a reduction in plasma T lymphocytes in pregnant female VSG rats compared to pregnant Sham surgery rats, and increased circulating Immunoglobulin G (IgG) protein. We also reported in the placenta increased mRNA levels of interleukin 1 β (IL1B), interleukin 1 receptor antagonist, and matrix metalloproteinase 9 in VSG animals compared to Shams as well as increased TUNEL positive cells indicating apoptosis. We have currently expanded our work in the placenta, finding that mRNA for B cell marker, PTPRC, and cytotoxic T cell marker, CD8A, is elevated in VSG dams. In postnatal day 21 (PND21) pups, we measure lower circulating B lymphocytes in both males and females born to VSG dams compared to pups born to Sham dams, as well as elevated total IgG, while T cells and monocytes were not altered. In the pup hypothalamus at PND21, IL1B mRNA is elevated and this persists until PND120 in males fed chow diet. Transcription of other pro‐inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, is not altered in the hypothalamus. These data suggest that VSG surgery alters the immune system in utero and these changes may affect immune health postnatally. Future work will determine what signalling pathways transduce this immune response and if they contribute to low birth weight and metabolic syndrome in offspring. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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Section: Discussionmentioning

confidence: 92%

Altered immune system in offspring of rat maternal vertical sleeve gastrectomy

Spann

Taylor

Welch

et al. 2019

American Journal of Physiology-Regulatory, Integrative and Comp

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“…For immunofluorescence staining, free float slices were blocked in PBS with 5% donkey serum (#017-000-121, Jackson ImmunoResearch) and 0.3% Triton X-100 for 1 h, then incubated with Primary antibody NeuN (1:500, #ab177487, Abcam) in PBS with 1% donkey serum and 0.3% Triton X-100 overnight at 4 • C. After washing 3 times with PBS, slices were incubated with fluorescencelabeled secondary antibodies (1:500, #A31570, Invitrogen) for 1 h at room temperature, then mounted on glass slides, cover-slipped with mounting medium (#S36939, Life technology), and imaged on a Zeiss LSM 710 NLO confocal microscope (Zeiss, Oberkochen, Germany). The Neural density in the peri-infarct region of each mouse was assessed as previously described [63,64]. Briefly, the coronal sections from bregma 1-3 mm were used.…”

Section: Lectin Infusion and Immunofluorescence Stainingmentioning

confidence: 99%

C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice

Shen

Zhao

et al. 2021

IJMS

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C-type natriuretic peptide (CNP) is an important vascular regulator that is present in the brain. Our previous study demonstrated the innate neuroprotectant role of CNP in the neonatal brain after hypoxic-ischemic (HI) insults. In this study, we further explored the role of CNP in cerebrovascular pathology using both in vivo and in vitro models. In a neonatal mouse HI brain injury model, we found that intracerebroventricular administration of recombinant CNP dose-dependently reduces brain infarct size. CNP significantly decreases brain edema and immunoglobulin G (IgG) extravasation into the brain tissue, suggesting a vasculoprotective effect of CNP. Moreover, in primary brain microvascular endothelial cells (BMECs), CNP dose-dependently protects BMEC survival and monolayer integrity against oxygen-glucose deprivation (OGD). The vasculoprotective effect of CNP is mediated by its innate receptors NPR2 and NPR3, in that inhibition of either NPR2 or NPR3 counteracts the protective effect of CNP on IgG leakage after HI insult and BMEC survival under OGD. Of importance, CNP significantly ameliorates brain atrophy and improves neurological deficits after HI insults. Altogether, the present study indicates that recombinant CNP exerts vascular protection in neonatal HI brain injury via its innate receptors, suggesting a potential therapeutic target for the treatment of neonatal HI brain injury.

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“…In vivo testing is always the key, but given the multitude of cell and developmentally regulated effects of MK, it seems to have even greater importance to prove the validity of MK as a potential therapeutic. It will also be important to understand the roles of MK in animal models of development and injury, which incorporate the maternal-placental-fetal unit, such as the precocial spiny mouse (236,237), or fetal and newborn sheep (165,238). Current data predominantly comes from altricial species but given the high levels of MK in the amniotic fluid, there is the possibility that preterm birth causes an MK deficiency, and the effect of prematurity and brain injury in these infants warrants attention.…”

Section: Resultsmentioning

confidence: 99%

Midkine: The Who, What, Where, and When of a Promising Neurotrophic Therapy for Perinatal Brain Injury

Ross-Munro¹,

Kwa

Kreiner³

et al. 2020

Front. Neurol.

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Midkine (MK) is a small secreted heparin-binding protein highly expressed during embryonic/fetal development which, through interactions with multiple cell surface receptors promotes growth through effects on cell proliferation, migration, and differentiation. MK is upregulated in the adult central nervous system (CNS) after multiple types of experimental injury and has neuroprotective and neuroregenerative properties. The potential for MK as a therapy for developmental brain injury is largely unknown. This review discusses what is known of MK's expression and actions in the developing brain, areas for future research, and the potential for using MK as a therapeutic agent to ameliorate the effects of brain damage caused by insults such as birth-related hypoxia and inflammation.

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Fetal Growth Restriction Alters Cerebellar Development in Fetal and Neonatal Sheep

Cited by 21 publications

References 46 publications

Altered immune system in offspring of rat maternal vertical sleeve gastrectomy

Altered immune system in offspring of rat maternal vertical sleeve gastrectomy

C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice

Midkine: The Who, What, Where, and When of a Promising Neurotrophic Therapy for Perinatal Brain Injury

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