PMID- 34862457
OWN - NLM
STAT- MEDLINE
DCOM- 20220121
LR  - 20220121
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Dec 3
TI  - Prenatal administration of IL-1Ra attenuate the neurodevelopmental impacts 
      following non-pathogenic inflammation during pregnancy.
PG  - 23404
LID - 10.1038/s41598-021-02927-3 [doi]
LID - 23404
AB  - Prenatal inflammation negatively affects placental function, subsequently 
      altering fetal development. Pathogen-associated molecular patterns (PAMPs) are 
      used to mimics infections in preclinical models but rarely detected during 
      pregnancy. Our group previously developed an animal model of prenatal exposure to 
      uric acid (endogenous mediator), leading to growth restriction alongside 
      IL-1-driven placental inflammation (Brien et al. in J Immunol 198(1):443-451, 
      2017). Unlike PAMPs, the postnatal impact of prenatal non-pathogenic inflammation 
      is still poorly understood. Therefore, we investigated the effects of prenatal 
      uric acid exposure on postnatal neurodevelopment and the therapeutic potential of 
      the IL-1 receptor antagonist; IL-1Ra. Uric acid induced growth restriction and 
      placental inflammation, which IL-1Ra protected against. Postnatal evaluation of 
      both structural and functional aspects of the brain revealed developmental 
      changes. Both astrogliosis and microgliosis were observed in the hippocampus and 
      white matter at postnatal day (PND)7 with IL-1Ra being protective. Decreased 
      myelin density was observed at PND21, and reduced amount of neuronal precursor 
      cells was observed in the Dentate Gyrus at PND35. Functionally, motor impairments 
      were observed as evaluated with the increased time to fully turn upward (180 
      degrees) on the inclined plane and the pups were weaker on the grip strength 
      test. Prenatal exposure to sterile inflammation, mimicking most clinical 
      situation, induced growth restriction with negative impact on neurodevelopment. 
      Targeted anti-inflammatory intervention prenatally could offer a strategy to 
      protect brain development during pregnancy.
CI  - (c) 2021. The Author(s).
FAU - Brien, Marie-Eve
AU  - Brien ME
AD  - Ste-Justine Hospital Research Center, Montreal, QC, Canada.
AD  - Department of Microbiology, Infectiology and Immunology, Universite de Montreal, 
      Montreal, QC, Canada.
FAU - Hughes, Katia
AU  - Hughes K
AD  - Ste-Justine Hospital Research Center, Montreal, QC, Canada.
FAU - Girard, Sylvie
AU  - Girard S
AD  - Department of Obstetrics and Gynecology, Universite de Montreal, Montreal, QC, 
      Canada. girard.sylvie@mayo.edu.
AD  - Department of Obstetrics and Gynecology, Department of Immunology, Mayo Clinic, 
      222, 3rd Ave SW, Rochester, MN, 55905, USA. girard.sylvie@mayo.edu.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211203
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 268B43MJ25 (Uric Acid)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain/drug effects/embryology
MH  - Disease Models, Animal
MH  - Female
MH  - Fetal Development/drug effects
MH  - Fetal Growth Retardation/chemically induced/*drug therapy/immunology
MH  - Gliosis/chemically induced/*drug therapy/immunology
MH  - Inflammation/chemically induced/*drug therapy
MH  - Interleukin 1 Receptor Antagonist Protein/*administration & dosage/pharmacology
MH  - Placenta/*drug effects/immunology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Uric Acid/*adverse effects
PMC - PMC8642433
COIS- The authors declare no competing interests.
EDAT- 2021/12/05 06:00
MHDA- 2022/01/22 06:00
PMCR- 2021/12/03
CRDT- 2021/12/04 06:04
PHST- 2021/09/15 00:00 [received]
PHST- 2021/11/24 00:00 [accepted]
PHST- 2021/12/04 06:04 [entrez]
PHST- 2021/12/05 06:00 [pubmed]
PHST- 2022/01/22 06:00 [medline]
PHST- 2021/12/03 00:00 [pmc-release]
AID - 10.1038/s41598-021-02927-3 [pii]
AID - 2927 [pii]
AID - 10.1038/s41598-021-02927-3 [doi]
PST - epublish
SO  - Sci Rep. 2021 Dec 3;11(1):23404. doi: 10.1038/s41598-021-02927-3.