PMID- 25427570
OWN - NLM
STAT- MEDLINE
DCOM- 20150923
LR  - 20150224
IS  - 1421-9786 (Electronic)
IS  - 1015-9770 (Linking)
VI  - 38
IP  - 5
DP  - 2014
TI  - Microvascular plasticity after experimental stroke: a molecular and MRI study.
PG  - 344-53
AB  - BACKGROUND: Microvasculature plays a key role in stroke pathophysiology both 
      during initial damage and extended neural repair. Moreover, angiogenesis 
      processes seem to be a promising target for future neurorestorative therapies. 
      However, dynamic changes of microvessels after stroke still remain unclear, and 
      MRI follow-up could be interesting as an in vivo biomarker of these. METHODS: The 
      aim of this study is to characterize the microvascular plasticity 25 days after 
      ischemic stroke using both in vivo microvascular 7T-MRI (vascular permeability, 
      cerebral blood volume (CBV), vessel size index (VSI), vascular density) and 
      quantification of angiogenic factor expressions by RT-qPCR in a transient middle 
      cerebral artery occlusion rat model. CBV and VSI (perfused vessel caliber) 
      imaging was performed using a steady-state approach with a multi gradient-echo 
      spin-echo sequence before and 2 min after intravenous (IV) injection of 
      ultrasmall superparamagnetic iron particles. Vascular density (per mm2) was 
      derived from the ratio [DeltaR(2)/(DeltaR(2)*)(2)/(3)]. Blood brain barrier leakage was assessed 
      using T(1)W images before and after IV injection of Gd-DOTA. Additionally, 
      microvessel immunohistology was done. RESULTS: 3 successive stages were observed: 
      1) 'Acute stage' from day 1 to day 3 post-stroke (D1-D3) characterized by high 
      levels of angiopoietin-2 (Ang2), vascular endothelial growth factor receptor-2 
      (VEGFR-2) and endothelial NO synthase (eNOS) that may be associated with 
      deleterious vascular permeability and vasodilation; 2) 'Transition stage' (D3-D7) 
      that involves transforming the growth factors beta1 (TGFbeta1), Ang1, and tyrosine 
      kinase with immunoglobulin-like and endothelial growth factor-like domains 1 
      (Tie1), stromal-derived factor-1 (SDF-1), chemokine receptor type 4 (CXCR-4); and 
      3) 'Subacute stage' (D7-D25) with high levels of Ang1, Ang2, VEGF, VEGFR-1 and 
      TGFbeta1 leading to favorable stabilization and maturation of microvessels. In vivo 
      MRI appeared in line with the angiogenic factors changes with a delay of at least 
      1 day. All MRI parameters varied over time, revealing the different aspects of 
      the post-stroke microvascular plasticity. At D25, despite a normal CBV, MRI 
      revealed a limited microvessel density, which is insufficient to support a good 
      neural repair. CONCLUSIONS: Microvasculature MRI can provide imaging of different 
      states of functional (perfused) microvessels after stroke. These results 
      highlight that multiparametric MRI is useful to assess post-stroke angiogenesis, 
      and could be used as a biomarker notably for neurorestorative therapy studies. 
      Additionally, we identified that endogenous vessel maturation and stabilization 
      occur during the 'subacute stage'. Thus, pro-angiogenic treatments, such as 
      cell-based therapy, would be relevant during this subacute phase of stroke.
FAU - Moisan, Anaick
AU  - Moisan A
FAU - Favre, Isabelle M
AU  - Favre IM
FAU - Rome, Claire
AU  - Rome C
FAU - Grillon, Emmanuelle
AU  - Grillon E
FAU - Naegele, Bernadette
AU  - Naegele B
FAU - Barbieux, Marianne
AU  - Barbieux M
FAU - De Fraipont, Florence
AU  - De Fraipont F
FAU - Richard, Marie-Jeanne
AU  - Richard MJ
FAU - Barbier, Emmanuel L
AU  - Barbier EL
FAU - Remy, Chantal
AU  - Remy C
FAU - Detante, Olivier
AU  - Detante O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141123
PL  - Switzerland
TA  - Cerebrovasc Dis
JT  - Cerebrovascular diseases (Basel, Switzerland)
JID - 9100851
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/pathology
MH  - Capillary Permeability
MH  - Disease Models, Animal
MH  - Infarction, Middle Cerebral Artery/pathology
MH  - *Magnetic Resonance Imaging/methods
MH  - Male
MH  - Microvessels/*pathology
MH  - Rats, Sprague-Dawley
MH  - Stroke/complications/*pathology
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2014/11/28 06:00
MHDA- 2015/09/24 06:00
CRDT- 2014/11/28 06:00
PHST- 2014/06/16 00:00 [received]
PHST- 2014/09/23 00:00 [accepted]
PHST- 2014/11/28 06:00 [entrez]
PHST- 2014/11/28 06:00 [pubmed]
PHST- 2015/09/24 06:00 [medline]
AID - 000368597 [pii]
AID - 10.1159/000368597 [doi]
PST - ppublish
SO  - Cerebrovasc Dis. 2014;38(5):344-53. doi: 10.1159/000368597. Epub 2014 Nov 23.