Abstract
In vivo positron emission tomography of neuroinflammation has mainly focused on the evaluation of glial cell activation using radiolabeled ligands. However, the non-invasive imaging of neuroinflammatory cell proliferation has been scarcely evaluated so far. In vivo and ex vivo assessment of gliogenesis after transient middle cerebral artery occlusion (MCAO) in rats was carried out using PET imaging with the marker of cell proliferation 3′-Deoxy-3′-[18F] fluorothymidine ([18F]FLT), magnetic resonance imaging (MRI) and fluorescence immunohistochemistry. MRI-T2W studies showed the presence of the brain infarction at 24 h after MCAO affecting cerebral cortex and striatum. In vivo PET imaging showed a significant increase in [18F]FLT uptake in the ischemic territory at day 7 followed by a progressive decline from day 14 to day 28 after ischemia onset. In addition, immunohistochemistry studies using Ki67, CD11b, and GFAP to evaluate proliferation of microglia and astrocytes confirmed the PET findings showing the increase of glial proliferation at day 7 after ischemia followed by decrease later on. Hence, these results show that [18F]FLT provides accurate quantitative information on the time course of glial proliferation in experimental stroke. Finally, this novel brain imaging method might guide on the imaging evaluation of the role of gliogenesis after stroke.
Highlights
Gliogenesis is the process by which glial progenitor cells differentiate into mature glia during development, and in the adult brain to maintain and regulate brain function (Lee et al, 2000)
We report here for the first time a novel imaging tool to evaluate glial proliferation using positron emission tomography (PET) imaging
We describe a novel imaging tool to evaluate glial proliferation with PET since [18F]FLT is a radiotracer able to detect cellular proliferation in vivo
Summary
Gliogenesis is the process by which glial progenitor cells differentiate into mature glia during development, and in the adult brain to maintain and regulate brain function (Lee et al, 2000). Previous studies from our group and others showed that the lack of toll-like receptor 4 which is mainly expressed in microglia and astrocytes after brain ischemia, was able to increase neurogenesis using [18F]FLT-PET in the subventricular area after focal ischemia in mice (Caso et al, 2007, 2008; Moraga et al, 2016) Despite these findings, the use of [18F]FLT to monitor proliferation of glial cells has not been explored before. We were interested in clarifying the relationship of the [18F]FLT uptake and proliferative microglia/macrophages and astrocytes in a preclinical model of ischemic stroke in rats These results provide valuable information about the use of a novel imaging methodology to follow up proliferation of glial cells in vivo after cerebral ischemia. This research might contribute to a better design of novel diagnostic and therapeutic strategies for neurologic diseases such as stroke
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