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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2020

01-12-2020 | Research

Lipopolysaccharide-induced changes in the neurovascular unit in the preterm fetal sheep brain

Authors: Clémence Disdier, Fares Awa, Xiaodi Chen, Simerdeep K. Dhillon, Robert Galinsky, Joanne O. Davidson, Christopher A. Lear, Laura Bennet, Alistair J. Gunn, Barbara S. Stonestreet

Published in: Journal of Neuroinflammation | Issue 1/2020

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Abstract

Background

Exposure to inflammation during pregnancy can predispose to brain injury in premature infants. In the present study, we investigated the effects of prolonged exposure to inflammation on the cerebrovasculature of preterm fetal sheep.

Methods

Chronically instrumented fetal sheep at 103–104 days of gestation (full term is ~ 147 days) received continuous low-dose lipopolysaccharide (LPS) infusions (100 ng/kg over 24 h, followed by 250 ng/kg/24 h for 96 h plus boluses of 1 μg LPS at 48, 72, and 96 h) or the same volume of normal saline (0.9%, w/v). Ten days after the start of LPS exposure at 113–114 days of gestation, the sheep were killed, and the fetal brain perfused with formalin in situ. Vessel density, pericyte and astrocyte coverage of the blood vessels, and astrogliosis in the cerebral cortex and white matter were determined using immunohistochemistry.

Results

LPS exposure reduced (P < 0.05) microvascular vessel density and pericyte vascular coverage in the cerebral cortex and white matter of preterm fetal sheep, and increased the activation of perivascular astrocytes, but decreased astrocytic vessel coverage in the white matter.

Conclusions

Prolonged exposure to LPS in preterm fetal sheep resulted in decreased vessel density and neurovascular remodeling, suggesting that chronic inflammation adversely affects the neurovascular unit and, therefore, could contribute to long-term impairment of brain development.
Appendix
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Metadata
Title
Lipopolysaccharide-induced changes in the neurovascular unit in the preterm fetal sheep brain
Authors
Clémence Disdier
Fares Awa
Xiaodi Chen
Simerdeep K. Dhillon
Robert Galinsky
Joanne O. Davidson
Christopher A. Lear
Laura Bennet
Alistair J. Gunn
Barbara S. Stonestreet
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-020-01852-y

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