dc.contributor.author |
Kelly, Sharmony B |
|
dc.contributor.author |
Stojanovska, Vanesa |
|
dc.contributor.author |
Zahra, Valerie A |
|
dc.contributor.author |
Moxham, Alison |
|
dc.contributor.author |
Miller, Suzanne L |
|
dc.contributor.author |
Moss, Timothy JM |
|
dc.contributor.author |
Hooper, Stuart B |
|
dc.contributor.author |
Nold, Marcel F |
|
dc.contributor.author |
Nold-Petry, Claudia A |
|
dc.contributor.author |
Dean, Justin M |
|
dc.contributor.author |
Bennet, Laura |
|
dc.contributor.author |
Polglase, Graeme R |
|
dc.contributor.author |
Gunn, Alistair J |
|
dc.contributor.author |
Galinsky, Robert |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2021-10-15T00:56:09Z |
|
dc.date.available |
2021-10-15T00:56:09Z |
|
dc.date.issued |
2021-8-31 |
|
dc.identifier.citation |
Journal of neuroinflammation 18(1):189 31 Aug 2021 |
|
dc.identifier.issn |
1742-2094 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/56989 |
|
dc.description.abstract |
<h4>Background</h4>Increased systemic and tissue levels of interleukin (IL)-1β are associated with greater risk of impaired neurodevelopment after birth. In this study, we tested the hypothesis that systemic IL-1 receptor antagonist (Ra) administration would attenuate brain inflammation and injury in near-term fetal sheep exposed to lipopolysaccharide (LPS).<h4>Methods</h4>Chronically instrumented near-term fetal sheep at 0.85 of gestation were randomly assigned to saline infusion (control, n = 9), repeated LPS infusions (0 h = 300 ng, 24 h = 600 ng, 48 h = 1200 ng, n = 8) or repeated LPS plus IL-1Ra infusions (13 mg/kg infused over 4 h) started 1 h after each LPS infusion (n = 9). Sheep were euthanized 4 days after starting infusions for histology.<h4>Results</h4>LPS infusions increased circulating cytokines and were associated with electroencephalogram (EEG) suppression with transiently reduced mean arterial blood pressure, and increased carotid artery perfusion and fetal heart rate (P < 0.05 vs. control for all). In the periventricular and intragyral white matter, LPS-exposure increased IL-1β immunoreactivity, numbers of caspase 3+ cells and microglia, reduced astrocyte and olig-2+ oligodendrocyte survival but did not change numbers of mature CC1+ oligodendrocytes, myelin expression or numbers of neurons in the cortex and subcortical regions. IL-1Ra infusions reduced circulating cytokines and improved recovery of EEG activity and carotid artery perfusion. Histologically, IL-1Ra reduced microgliosis, IL-1β expression and caspase-3+ cells, and improved olig-2+ oligodendrocyte survival.<h4>Conclusion</h4>IL-1Ra improved EEG activity and markedly attenuated systemic inflammation, microgliosis and oligodendrocyte loss following LPS exposure in near-term fetal sheep. Further studies examining the long-term effects on brain maturation are now needed. |
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dc.format.medium |
Electronic |
|
dc.language |
eng |
|
dc.publisher |
Springer Science and Business Media LLC |
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dc.relation.ispartofseries |
Journal of neuroinflammation |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Brain |
|
dc.subject |
Inflammation |
|
dc.subject |
Interleukin-1 |
|
dc.subject |
1103 Clinical Sciences |
|
dc.subject |
1107 Immunology |
|
dc.subject |
1109 Neurosciences |
|
dc.title |
Interleukin-1 blockade attenuates white matter inflammation and oligodendrocyte loss after progressive systemic lipopolysaccharide exposure in near-term fetal sheep. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1186/s12974-021-02238-4 |
|
pubs.issue |
1 |
|
pubs.begin-page |
189 |
|
pubs.volume |
18 |
|
dc.date.updated |
2021-09-04T00:26:23Z |
|
dc.rights.holder |
Copyright: The author |
en |
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/34465372 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Journal Article |
|
pubs.elements-id |
865275 |
|
dc.identifier.eissn |
1742-2094 |
|
dc.identifier.pii |
10.1186/s12974-021-02238-4 |
|
pubs.number |
189 |
|
pubs.online-publication-date |
2021-8-31 |
|