10.6084/m9.figshare.4650169.v1
Moisan A.
Moisan
A.
Favre I.M.
Favre
I.M.
Rome C.
Rome
C.
Grillon E.
Grillon
E.
Naegele B.
Naegele
B.
Barbieux M.
Barbieux
M.
De Fraipont F.
De Fraipont F.
Richard M.-J.
Richard
M.-J.
Barbier E.L.
Barbier
E.L.
Rémy C.
Rémy
C.
Detante O.
Detante
O.
Supplementary Material for: Microvascular Plasticity After Experimental Stroke: A Molecular and MRI Study
Karger Publishers
2017
Cerebral ischemia
Angiogenic factors
Angiogenesis
Microvascular MRI
Stroke
Pathophysiology
Microvasculature
Vessel size index
Brain plasticity
2017-02-14 15:21:01
Dataset
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Microvascular_Plasticity_After_Experimental_Stroke_A_Molecular_and_MRI_Study/4650169
<p><b><i>Background:</i></b> 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. <b><i>Methods:</i></b>
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 mm<sup>2</sup>) was derived from the ratio [ΔR<sub>2</sub>/(ΔR<sub>2</sub>*)<sup>2/3</sup>]. Blood brain barrier leakage was assessed using T<sub>1</sub>W images before and after IV injection of Gd-DOTA. Additionally, microvessel immunohistology was done. <b><i>Results:</i></b>
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 β1 (TGFβ1), 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 TGFβ1 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. <b><i>Conclusions:</i></b>
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.</p>