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Abstract
Traumatic brain injury (TBI) leads to a deleterious neuroinflammation, originating from microglial activation. Monitoring microglial activation is an indispensable step to develop therapeutic strategies for TBI. In this study, we evaluated the use of the 18-kDa translocator protein (TSPO) in positron emission tomography (PET) and cellular analysis to monitor microglial activation in a mild TBI mouse model. TBI was induced on male Swiss mice. PET imaging analysis with [18F]FEPPA, a TSPO radiotracer, was performed at 1, 3 and 7 days post-TBI and flow cytometry analysis on brain at 1 and 3 days post-TBI. PET analysis showed no difference in TSPO expression between non-operated, sham-operated and TBI mice. Flow cytometry analysis demonstrated an increase in TSPO expression in ipsilateral brain 3 days post-TBI, especially in microglia, macrophages, lymphocytes and neutrophils. Moreover, microglia represent only 58.3% of TSPO+ cells in the brain. Our results raise the question of the use of TSPO radiotracer to monitor microglial activation after TBI. More broadly, flow cytometry results point the lack of specificity of TSPO for microglia and imply that microglia contribute to the overall increase in TSPO in the brain after TBI, but is not its only contributor.
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1 Université Paris Descartes, EA4475 - Pharmacologie de la circulation cérébrale, Faculté de Pharmacie de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Université de Paris, Inserm UMR-S 1144 – Optimisation Thérapeutique en Neuropsychopharmacologie, Faculté de Pharmacie de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602)
2 Université de Paris, Inserm UMR-S 1144 – Optimisation Thérapeutique en Neuropsychopharmacologie, Faculté de Pharmacie de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Hôpital Lariboisière, Assistance Publique – Hôpitaux de Paris (AP-HP), Service de Médecine Nucléaire, Paris, France (GRID:grid.411296.9) (ISNI:0000 0000 9725 279X); Université de Paris, Institut de Recherche Saint-Louis, Unité Claude Kellershohn, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602)
3 Université de Paris, Innovative Therapies in Haemostasis, Inserm, Paris, France (GRID:grid.508487.6); Institut Curie, Cytometry Core, Paris, France (GRID:grid.418596.7) (ISNI:0000 0004 0639 6384); Université de Paris, Inserm UMS 3612 CNRS – US25 Inserm –Faculté de Pharmacie de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602)
4 Université Paris Descartes, EA4475 - Pharmacologie de la circulation cérébrale, Faculté de Pharmacie de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602)
5 Université de Paris, Inserm UMR-S 1144 – Optimisation Thérapeutique en Neuropsychopharmacologie, Faculté de Pharmacie de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602)
6 Université Paris Descartes, EA4475 - Pharmacologie de la circulation cérébrale, Faculté de Pharmacie de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Université de Paris, Inserm UMR-S 1140, Faculté de Pharmacie de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602)
7 Hôpital Lariboisière, Assistance Publique – Hôpitaux de Paris (AP-HP), Service de Médecine Nucléaire, Paris, France (GRID:grid.411296.9) (ISNI:0000 0000 9725 279X); Université de Paris, Institut de Recherche Saint-Louis, Unité Claude Kellershohn, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602)
8 Université de Paris, Institut de Recherche Saint-Louis, Unité Claude Kellershohn, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); CHU de Martinique, Service Pharmacie, Hôpital Pierre Zobda-Quitman, Fort-de-France, France (GRID:grid.412874.c)
9 Université de Paris, Institut de Recherche Saint-Louis, Unité Claude Kellershohn, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Université de Paris, Inserm UMR-S 942, Hôpital Lariboisière, Paris, France (GRID:grid.508487.6)
10 Université de Paris, Inserm UMR-S 1144 – Optimisation Thérapeutique en Neuropsychopharmacologie, Faculté de Pharmacie de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Université de Paris, Institut de Recherche Saint-Louis, Unité Claude Kellershohn, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Assistance Publique – Hôpitaux de Paris (AP-HP), Service Pharmacie, Hôpital Saint-Louis, Paris, France (GRID:grid.413328.f) (ISNI:0000 0001 2300 6614)