PMID- 34825315
OWN - NLM
STAT- MEDLINE
DCOM- 20220407
LR  - 20220407
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 59
IP  - 2
DP  - 2022 Feb
TI  - Neurovascular Unit Alterations in the Growth-Restricted Newborn Are Improved 
      Following Ibuprofen Treatment.
PG  - 1018-1040
LID - 10.1007/s12035-021-02654-w [doi]
AB  - 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.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Chand, Kirat K
AU  - Chand KK
AD  - UQ Centre for Clinical Research, Faculty of Medicine, The University of 
      Queensland, Brisbane, QLD, Australia.
FAU - Miller, Stephanie M
AU  - Miller SM
AD  - UQ Centre for Clinical Research, Faculty of Medicine, The University of 
      Queensland, Brisbane, QLD, Australia.
FAU - Cowin, Gary J
AU  - Cowin GJ
AD  - National Imaging Facility, Centre for Advanced Imaging, The University of 
      Queensland, Brisbane, QLD, Australia.
FAU - Mohanty, Lipsa
AU  - Mohanty L
AD  - UQ Centre for Clinical Research, Faculty of Medicine, The University of 
      Queensland, Brisbane, QLD, Australia.
FAU - Pienaar, Jany
AU  - Pienaar J
AD  - Perinatal Research Centre, Royal Brisbane and Women's Hospital, Herston, 
      Brisbane, QLD, 4029, Australia.
FAU - Colditz, Paul B
AU  - Colditz PB
AD  - UQ Centre for Clinical Research, Faculty of Medicine, The University of 
      Queensland, Brisbane, QLD, Australia.
AD  - Perinatal Research Centre, Royal Brisbane and Women's Hospital, Herston, 
      Brisbane, QLD, 4029, Australia.
FAU - Bjorkman, Stella Tracey
AU  - Bjorkman ST
AD  - UQ Centre for Clinical Research, Faculty of Medicine, The University of 
      Queensland, Brisbane, QLD, Australia.
FAU - Wixey, Julie A
AU  - Wixey JA
AUID- ORCID: 0000-0002-9716-8170
AD  - UQ Centre for Clinical Research, Faculty of Medicine, The University of 
      Queensland, Brisbane, QLD, Australia. j.wixey@uq.edu.au.
AD  - Perinatal Research Centre, Royal Brisbane and Women's Hospital, Herston, 
      Brisbane, QLD, 4029, Australia. j.wixey@uq.edu.au.
LA  - eng
PT  - Journal Article
DEP - 20211126
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - WK2XYI10QM (Ibuprofen)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism
MH  - *Brain/metabolism
MH  - Humans
MH  - *Ibuprofen/pharmacology/therapeutic use
MH  - Microglia
MH  - Neuroglia
MH  - Swine
OTO - NOTNLM
OT  - Astrocytes
OT  - Blood-brain barrier
OT  - Foetal growth retardation
OT  - Immune cells
OT  - Microglia
OT  - Neonatal brain injury
EDAT- 2021/11/27 06:00
MHDA- 2022/04/08 06:00
CRDT- 2021/11/26 07:05
PHST- 2021/04/27 00:00 [received]
PHST- 2021/11/17 00:00 [accepted]
PHST- 2021/11/27 06:00 [pubmed]
PHST- 2022/04/08 06:00 [medline]
PHST- 2021/11/26 07:05 [entrez]
AID - 10.1007/s12035-021-02654-w [pii]
AID - 10.1007/s12035-021-02654-w [doi]
PST - ppublish
SO  - Mol Neurobiol. 2022 Feb;59(2):1018-1040. doi: 10.1007/s12035-021-02654-w. Epub 
      2021 Nov 26.