PMID- 27898024
OWN - NLM
STAT- MEDLINE
DCOM- 20170508
LR  - 20181113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 17
IP  - 12
DP  - 2016 Nov 25
TI  - Perinatal Arterial Ischemic Stroke Is Associated to Materno-Fetal Immune 
      Activation and Intracranial Arteritis.
LID - 1980
AB  - The medium-size intra-cranial arteries arising from the carotid bifurcation are 
      prone to perinatal arterial ischemic strokes (PAIS). PAIS' physiopathology needs 
      to be better understood to develop preventive and therapeutic interventions that 
      are currently missing. We hypothesized that materno-fetal inflammation leads to a 
      vasculitis affecting selectively the carotidian tree and promoting a focal 
      thrombosis and subsequent stroke. Dams were injected with saline or 
      lipopolysaccharide (LPS) from Escherichia coli. A prothrombotic stress was 
      applied on LPS-exposed vs. saline (S)-exposed middle cerebral arteries (MCA). 
      Immunolabeling detected the inflammatory markers of interest. In S-exposed 
      newborn pups, a constitutive higher density of macrophages combined to higher 
      expressions of tumor necrosis factor-alpha (TNF-alpha), and interleukin 1beta (IL-1beta) was 
      observed within the wall of intra- vs. extra-cranial cervicocephalic arteries. 
      LPS-induced maternal and placental inflammatory responses mediated by IL-1beta, 
      TNF-alpha and monocyte chemotactic protein 1 (MCP-1) were associated with: (i) 
      increased density of pro-inflammatory macrophages (M1 phenotype); and (ii) 
      pro-inflammatory orientation of the IL-1 system (IL-1beta/IL-1 receptor antagonist 
      (IL-1Ra) ratio) within the wall of LPS-, vs. S-exposed, intra-cranial arteries 
      susceptible to PAIS. LPS plus photothrombosis, but not sole photothrombosis, 
      triggered ischemic strokes and subsequent motor impairments. Based on these 
      preclinical results, the combination of pro-thrombotic stress and selective 
      intra-cranial arteritis arising from end gestational maternal immune activation 
      seem to play a role in the pathophysiology of human PAIS.
FAU - Guiraut, Clemence
AU  - Guiraut C
AD  - Departement de Pediatrie, Universite de Sherbrooke, Sherbrooke, QC J1H 5N4, 
      Canada. clemence.guiraut@usherbrooke.ca.
FAU - Cauchon, Nicole
AU  - Cauchon N
AD  - Departement de Medecine Nucleaire et Radiobiologie, Universite de Sherbrooke, 
      Sherbrooke, QC J1H 5N4, Canada. nicole.cauchon@usherbrooke.ca.
FAU - Lepage, Martin
AU  - Lepage M
AD  - Departement de Medecine Nucleaire et Radiobiologie, Universite de Sherbrooke, 
      Sherbrooke, QC J1H 5N4, Canada. martin.lepage@usherbrooke.ca.
FAU - Sebire, Guillaume
AU  - Sebire G
AD  - Departement de Pediatrie, Universite de Sherbrooke, Sherbrooke, QC J1H 5N4, 
      Canada. guillaume.sebire@mcgill.ca.
AD  - Child Neurology Division, Department of Pediatrics, McGill University, Montreal, 
      QC H4A 3J1, Canada. guillaume.sebire@mcgill.ca.
LA  - eng
PT  - Journal Article
DEP - 20161125
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Arteritis/*etiology/*immunology/metabolism
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Hypoxia-Ischemia, Brain/*complications/*immunology/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Pregnancy
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vasculitis/etiology/immunology/metabolism
PMC - PMC5187780
OTO - NOTNLM
OT  - gestational inflammation
OT  - lipopolysaccharide
OT  - perinatal arterial ischemic stroke
OT  - vasculitis
COIS- The authors declare no conflict of interest. The founding sponsors had no role in 
      the design of the study; in the collection, analyses, or interpretation of data; 
      in the writing of the manuscript, and in the decision to publish the results.
EDAT- 2016/11/30 06:00
MHDA- 2017/05/10 06:00
PMCR- 2016/12/01
CRDT- 2016/11/30 06:00
PHST- 2016/09/07 00:00 [received]
PHST- 2016/11/14 00:00 [revised]
PHST- 2016/11/21 00:00 [accepted]
PHST- 2016/11/30 06:00 [entrez]
PHST- 2016/11/30 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2016/12/01 00:00 [pmc-release]
AID - ijms17121980 [pii]
AID - ijms-17-01980 [pii]
AID - 10.3390/ijms17121980 [doi]
PST - epublish
SO  - Int J Mol Sci. 2016 Nov 25;17(12):1980. doi: 10.3390/ijms17121980.