Abstract
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Objectives 18F-DPA714 is a new generation PET tracer for translocator protein (TSPO) which has high specific binding affinity. The purpose of this study was to evaluate the longitudinal change of glial activation after traumatic brain injury (TBI) in mice using 18F-DPA714 PET.
Methods TBI was induced over the left sensorimotor cortex in C57BL/6J male mice (n=28, 8-9 weeks old) using a stereotaxic frame and pneumatic impact device under anesthesia. Evaluation periods were 1, 4, 7, 14, 21, 42, 63, and 98 days after the induction of TBI. Static PET scans (10 min duration) were performed 20 min after the administration of 18F-DPA714. Maximum uptakes in the brain lesion were compared between TBI and sham groups. Immunohistochemical stainings were performed after the PET study using CD11b, glial fibrillary acidic protein (GFAP), and TSPO antibody.
Results SUVmax of the TBI group was significantly higher than that of the sham group at day 4, 7, 14, 21, 63, and 98 (p≦0.05 by Mann-Whitney test, all). There were two peaks in TBI group at day 7 and 21 (SUVmax = 0.81 ± 0.14 at day 1, 1.22 ± 0.15 at day 4, 1.38 ± 0.11 at day 7, 1.12 ± 0.12 at day 14, 1.33 ± 0.11 at day 21, 1.30 ± 0.27 at day 42, 1.26 ± 0.14 at day 63, and 1.21 ± 0.05 at day 98, respectively). It was suggested that glial activation occurred in two stages. Immunohistochemical analysis revealed numerous co-stained cells of CD11b and TSPO in the high uptake area of TSPO PET, indicating high expression of TSPO was observed in the activated microglia.
Conclusions 18F-DPA714 PET revealed bimodal increase of TSPO uptake both in the acute phase and the sub-acute to chronic phase, suggesting the involvement of bipolar microglial activation in the time course of TBI.