Neurovascular Unit Alterations in the Growth-Restricted Newborn Are Improved Following Ibuprofen Treatment.
Astrocytes
Blood-brain barrier
Foetal growth retardation
Immune cells
Microglia
Neonatal brain injury
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
received:
27
04
2021
accepted:
17
11
2021
pubmed:
27
11
2021
medline:
8
4
2022
entrez:
26
11
2021
Statut:
ppublish
Résumé
The developing brain is particularly vulnerable to foetal growth restriction (FGR) and abnormal neurodevelopment is common in the FGR infant ranging from behavioural and learning disorders to cerebral palsy. No treatment exists to protect the FGR newborn brain. Recent evidence suggests inflammation may play a key role in the mechanism responsible for the progression of brain impairment in the FGR newborn, including disruption to the neurovascular unit (NVU). We explored whether ibuprofen, an anti-inflammatory drug, could reduce NVU disruption and brain impairment in the FGR newborn. Using a preclinical FGR piglet model, ibuprofen was orally administered for 3 days from birth. FGR brains demonstrated a proinflammatory state, with changes to glial morphology (astrocytes and microglia), and blood-brain barrier disruption, assessed by IgG and albumin leakage into the brain parenchyma and a decrease in blood vessel density. Loss of interaction between astrocytic end-feet and blood vessels was evident where plasma protein leakage was present, suggestive of structural deficits to the NVU. T-cell infiltration was also evident in the parenchyma of FGR piglet brains. Ibuprofen treatment reduced the pro-inflammatory response in FGR piglets, reducing the number of activated microglia and enhancing astrocyte interaction with blood vessels. Ibuprofen also attenuated plasma protein leakage, regained astrocytic end-feet interaction around vessels, and decreased T-cell infiltration into the FGR brain. These findings suggest postnatal administration of ibuprofen modulates the inflammatory state, allowing for stronger interaction between vasculature and astrocytic end-feet to restore NVU integrity. Modulation of the NVU improves the FGR brain microenvironment and may be key to neuroprotection.
Identifiants
pubmed: 34825315
doi: 10.1007/s12035-021-02654-w
pii: 10.1007/s12035-021-02654-w
doi:
Substances chimiques
Ibuprofen
WK2XYI10QM
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1018-1040Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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