8 | Perivascular macrophages and endothelial cell interactions during stroke

Endothelial activation is a hallmark of brain inflammation, acting either as a cause or a consequence of the diseases. To date, we lack suitable methods to measure endothelial activation in vivo. In our group, we have developed a magnetic resonance imaging (MRI) method allowing non-invasive endothelial activation mapping, targeting adhesion molecules such as VCAM-1 and P-selectin. In clinically relevant contexts in mice (including stroke and multiple sclerosis), we provided evidence that this method allows detecting endothelial activation before any clinical manifestation (Gauberti et al., Theranostics, 2018 for review). Using such MRI method, we will study the link between perivascular macrophages and endothelium during the inflammatory response in mouse models of brain diseases, especially ischaemic stroke.

Publications

Martinez de Lizarrondo S, Gakuba C, Herbig BA, Repessé Y, Ali C, Denis CV, Lenting P, Touzé E, Diamond SL, Vivien D, Gauberti M. Potent Thrombolytic Effect of N-Acetylcysteine on Arterial Thrombi. Circulation 2017;136:646-660.

Fournier AP, Quenault A, Martinez de Lizarrondo S, Gauberti M, Defer G, Vivien D, Docagne F, Macrez R. Prediction of disease activity in models of multiple sclerosis by molecular magnetic resonance imaging of P-selectin. Proc Natl Acad Sci U S A 2017;114:6116-6121.

Marcos-Contreras OA, Martinez de Lizarrondo S, Bardou I, Orset C, Pruvost M, Anfray A, Frigout Y, Hommet Y, Lebouvier L, Montaner J, Vivien D*, Gauberti M*. Hyperfibrinolysis increases blood brain barrier permeability by a plasmin and bradykinin-dependent mechanism. Blood 2016;128:2423-2434 (* equal contribution).

Macrez R, Ortega MC, Bardou I, Mehra A, Fournier A, Van der Pol SMA, Haelewyn B, Maubert E, Lesept F, Chevilley A, de Castro F, De Vries HE, Vivien D, Clemente D, Docagne F. Neuroendothelial NMDA receptors as therapeutic targets in experimental autoimmune encephalomyelitis. Brain 2016;139:2409-2416.

Le Behot A, Gauberti M, Martinez De Lizarrondo S, Montagne A, Lemarchand E, Repesse Y, Guillou S, Denis CV, Maubert E, Orset C, Vivien D. GpIbα-VWF blockade restores vessel patency by dissolving platelet aggregates formed under very high shear rate in mice. Blood. 2014;123:3354-63.

Potential secondments

EMHAS (Ádám Dénes), month 9-11; BOEHRINGER (Sebastian Kreuz), month 20-23; CSIC (Anna Planas), month 28.