From positron emission tomography to cell analysis of the 18-kDa Translocator Protein in mild traumatic brain injury

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.

The Mitochondrial 18 kDa Translocator Protein as a Biomarker of Radiation-Induced Neuroinflammatory

“…Несмотря на то, что научная и клиническая значимость исследований нейровоспаления методом ПЭТ с радиолигандами TSPO очевидна, этот метод клинической диагностики имеет довольно низкую специфичность. Так, было показано, что ПЭТ-анализ с использованием [ 18 F]-FEPP не выявлял повышенной экспрессии TSPO у экспериментальных животных через 1 и 3 сут после травмы мозга, в то время как регистрировалась активация микроглии и нейровоспаление, а значимое повышение экспрессии TSPO в головном мозге определялось методом проточной цитометрии [61].…”

Relationship between Uveitis and the Differential Reactivity of Retinal Microglia

“…Those differences lead to the individual expression of microglial genes, which challenges people to propose exclusive biomarkers to differentiate microglia subsets. Nowadays, such a finding has aroused mighty attention that heaps of biomarkers used to be adopted in the past, including F4/80, CD11b (alias OX42), ionized calcium binding adapter molecule-1 (also known as allograft inflammatory factor-1), chemokine (C-X3-C motif) receptor 1, colony-stimulating factor-1 receptor, and translocator protein, which can also be presented on the surface of infiltrating macrophages and other cells [28‒30]. Thus, there are many limitations to continue to take them as indicators of microglia.…”