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journal article·2021-09Open access

Multimodal Imaging with NanoGd Reveals Spatiotemporal Features of Neuroinflammation after Experimental Stroke

Violaine Hubert, Ines Hristovska, Szilvia Karpati, Sarah Benkeder, Arindam Dey, Chloé Dumot, Camille Amaz, Naura Chounlamountri, Chantal Watrin, Jean‐Christophe Comte, Fabien Chauveau, Emmanuel Brun, Patrice Marche, Fréderic Lerouge, Stéphane Parola, Yves Berthezène, Thomas Vorup‐Jensen, Olivier Pascual, Marlène Wiart

Advanced Science· Volume 8· Issue 17
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Source abstract

Abstract

Abstract The purpose of this study is to propose and validate a preclinical in vivo magnetic resonance imaging (MRI) tool to monitor neuroinflammation following ischemic stroke, based on injection of a novel multimodal nanoprobe, NanoGd, specifically designed for internalization by phagocytic cells. First, it is verified that NanoGd is efficiently internalized by microglia in vitro. In vivo MRI coupled with intravenous injection of NanoGd in a permanent middle cerebral artery occlusion mouse model results in hypointense signals in the ischemic lesion. In these mice, longitudinal two‐photon intravital microscopy shows NanoGd internalization by activated CX3CR1‐GFP/+ cells. Ex vivo analysis, including phase contrast imaging with synchrotron X‐ray, histochemistry, and transmission electron microscopy corroborate NanoGd accumulation within the ischemic lesion and uptake by immune phagocytic cells. Taken together, these results confirm the potential of NanoGd‐enhanced MRI as an imaging biomarker of neuroinflammation at the subacute stage of ischemic stroke. As far as it is known, this work is the first to decipher the working mechanism of MR signals induced by a nanoparticle passively targeted at phagocytic cells by performing intravital microscopy back‐to‐back with MRI. Furthermore, using a gadolinium‐based rather than an iron‐based contrast agent raises future perspectives for the development of molecular imaging with emerging computed tomography technologies.
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Research context

Nanomaterials

OpenAlex topics: Neuroinflammation and Neurodegeneration Mechanisms · Barrier Structure and Function Studies · Extracellular vesicles in disease

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Univ‐Lyon IRIS Team CarMeN Laboratory Inserm U1060 INRA U1397 INSA Lyon Université Claude Bernard Lyon 1 Groupement Hospitalier Est 59 bd. Pinel Bron 69500 France

SYNATAC Team Institut NeuroMyoGène Université Claude Bernard Lyon 1 CNRS UMR 5310, INSERM U1217 Faculté de Médecine et de Pharmacie 8 avenue Rockefeller Lyon 69008 France

Université de Lyon École Normale Supérieure de Lyon CNRS UMR 5182 Université Claude Bernard Lyon 1 Laboratoire de Chimie Lyon F69342 France

Institut pour l'Avancée des Biosciences Centre de Recherche UGA / Inserm U 1209 / CNRS UMR 5309 Site Santé ‐ Allée des Alpes La Tronche 38700 France

Clinical Investigation Center Hospices Civils de Lyon Louis Pradel Hospital 28 avenue Doyen Lépine Bron 69500 France

FORGETTING Team Lyon Neuroscience Research Center (CRNL) CNRS UMR5292 INSERM U1028 Université Claude Bernard Lyon 1 Centre Hospitalier Le Vinatier ‐ Bâtiment 462 ‐ Neurocampus Michel Jouvet 95 boulevard Pinel Bron 69675 France

Université de Lyon Lyon Neuroscience Research Center (CRNL) CNRS UMR5292 INSERM U1028 Université Claude Bernard Lyon 1 Groupement Hospitalier Est ‐ CERMEP 59 bd Pinel Bron Cedex 69677 France

Synchrotron Radiation for Biomedical Research (STROBE) UA7 INSERM Université Grenoble Alpes Medical Beamline at the European Synchrotron Radiation Facility 71 Avenue des Martyrs Grenoble Cedex 9 38043 France

Univ‐Lyon Creatis Laboratory CNRS UMR5220 Inserm U1044 INSA Lyon Villeurbanne Cedex 69621 France

Department of Biomedicine Biophysical Immunology Laboratory Aarhus University Aarhus C DK‐8000 Denmark

Funding

European Synchrotron Radiation Facility

References (60)

Show source-provided references
1. Iadecola C. · Nat. Med. · 2011 · 17 · 1078
2. 10.1016/j.pneurobio.2016.05.00110.1016/j.pneurobio.2016.05.001 ↗
3. 10.3390/ijms1810213510.3390/ijms18102135 ↗
4. 10.1038/icb.2017.2510.1038/icb.2017.25 ↗
5. Nayak D. · IntraVital · 2012 · 100 · 15378276
6. 10.1126/science.111064710.1126/science.1110647 ↗
7. 10.1038/nature1280810.1038/nature12808 ↗
8. 10.1038/s41598-019-48538-x10.1038/s41598-019-48538-x ↗
9. 10.1016/j.pneurobio.2014.06.00510.1016/j.pneurobio.2014.06.005 ↗
10. Neumann J. · PLoS One · 2018 · 13 · 19326203
11. 10.1161/01.STR.0000226980.95389.0b10.1161/01.STR.0000226980.95389.0b ↗
12. 10.1002/ana.2179610.1002/ana.21796 ↗
13. 10.1016/j.neuroimage.2004.09.03410.1016/j.neuroimage.2004.09.034 ↗
14. 10.7150/thno.2412810.7150/thno.24128 ↗
15. 10.1016/j.addr.2006.09.01310.1016/j.addr.2006.09.013 ↗
16. 10.1111/jon.1231810.1111/jon.12318 ↗
17. 10.5414/CPP4871810.5414/CPP48718 ↗
18. 10.1002/mrm.129010.1002/mrm.1290 ↗
19. Wiart M. · Stroke · 2007 · 38 · 00392499
20. 10.1002/nbm.88110.1002/nbm.881 ↗
21. 10.1097/01.WCB.0000090505.76664.DB10.1097/01.WCB.0000090505.76664.DB ↗
22. 10.1039/D0NR07026B10.1039/D0NR07026B ↗
23. 10.1021/la105070p10.1021/la105070p ↗
24. 10.1007/s00330-012-2567-210.1007/s00330-012-2567-2 ↗
25. 10.1161/STROKEAHA.108.53126910.1161/STROKEAHA.108.531269 ↗
26. 10.1161/01.STR.0000254548.30258.f210.1161/01.STR.0000254548.30258.f2 ↗
27. 10.1159/00011122210.1159/000111222 ↗
28. 10.1016/j.jcmg.2020.12.02210.1016/j.jcmg.2020.12.022 ↗
29. 10.1007/s00401-014-1355-210.1007/s00401-014-1355-2 ↗
30. 10.1007/s00401-018-1954-410.1007/s00401-018-1954-4 ↗
31. 10.1161/STROKEAHA.110.60370410.1161/STROKEAHA.110.603704 ↗
32. 10.1016/j.jneuroim.2010.05.01510.1016/j.jneuroim.2010.05.015 ↗
33. 10.1002/glia.2247410.1002/glia.22474 ↗
34. Chen H. R. · Sci. Adv. · 2020 · 6 · 23752548
35. 10.1093/brain/awq13510.1093/brain/awq135 ↗
36. 10.1016/j.immuni.2013.02.01210.1016/j.immuni.2013.02.012 ↗
37. 10.1093/brain/awt28710.1093/brain/awt287 ↗
38. 10.1111/j.1750-3639.2012.00614.x10.1111/j.1750-3639.2012.00614.x ↗
39. 10.1016/j.expneurol.2017.08.01110.1016/j.expneurol.2017.08.011 ↗
40. 10.1002/ana.2566510.1002/ana.25665 ↗
41. 10.1016/j.bbi.2015.08.01010.1016/j.bbi.2015.08.010 ↗
42. 10.1186/1742-2094-8-17410.1186/1742-2094-8-174 ↗
43. 10.1016/j.irbm.2018.02.00210.1016/j.irbm.2018.02.002 ↗
44. 10.1007/s11307-010-0402-110.1007/s11307-010-0402-1 ↗
45. 10.1073/pnas.160939711310.1073/pnas.1609397113 ↗
46. Lee M. · Immune Network · 2018 · 18 · 1598
47. 10.1016/j.pneurobio.2017.10.00110.1016/j.pneurobio.2017.10.001 ↗
48. 10.1016/j.addr.2011.10.00710.1016/j.addr.2011.10.007 ↗
49. 10.1038/s41563-019-0566-210.1038/s41563-019-0566-2 ↗
50. 10.1016/j.neuron.2014.03.00310.1016/j.neuron.2014.03.003 ↗
51. Daldrup‐Link H. E. · Radiology · 2017 · 284 · 0033
52. Di Marco M. · Int. J. Pharm. · 2007 · 331 · 03785173
53. 10.2147/IJN.S3611110.2147/IJN.S36111 ↗
54. 10.1021/acsabm.8b0019110.1021/acsabm.8b00191 ↗
55. 10.1038/s41598-019-48641-z10.1038/s41598-019-48641-z ↗
56. 10.7150/ntno.4535410.7150/ntno.45354 ↗
57. 10.1007/s11307-013-0639-610.1007/s11307-013-0639-6 ↗
58. 10.1038/jcbfm.2011.810.1038/jcbfm.2011.8 ↗
59. 10.1016/j.neuron.2017.12.00210.1016/j.neuron.2017.12.002 ↗
60. H.Rositi V.Hubert L.Weber E.Ong L.‐P.Berner C.Frindel D.Rousseau C.Olivier M.Langer T.‐H.Cho N.Nighoghossian Y.Berthezene F.Peyrin F.Chauveau M.Wiart presented at12th Annual Meeting of the European Society of Molecular Imaging ‐ European Molecular Imaging Meeting (EMIM 2017) Cologne Germany April2017.