TSPO PET Detects Acute Neuroinflammation but not Diffuse Chronically Activated MHCII Microglia in the Rat
Abstract
Abstract
Background
Accurate and sensitive imaging biomarkers are required to study the progression of white matter (WM) microglial activation in neurological diseases in vivo. The translocator protein (TSPO) is considered a sensitive target for imaging microglial activation with positron emission tomography (PET). This study aimed to test the ability of TSPO to detect WM microglial activation marked by major histocompatibility complex class II (MHCII) molecules in rat models of prodromal Alzheimer’s disease and acute subcortical stroke.
Methods
Fischer 344 wild-type (n = 12) and TgAPP21 (n = 11) rats were imaged with [18F]FEPPA PET and MRI to investigate TSPO tracer uptake in the corpus callosum. Wild-type rats subsequently received an endothelin-1 (ET1)-induced subcortical stroke and were imaged at days 7 and 28 post-stroke before immunohistochemistry of TSPO, GFAP for astrocytes, iNOS for microglia releasing toxic nitrous oxide, and the MHCII rat antigen, OX6.
Results
[18F]FEPPA-PET findings that TSPO expression was not increased in WM of TgAPP21 rats and was only increased in the infarct and proximal WM were confirmed by immunohistochemistry (infarct TSPO cells/mm2: day 7 = 555 ± 181; day 28 = 307 ± 153; proximal WMTSPO cells/mm2: day 7 = 113 ± 93; day 28 = 5 ± 7). TSPO and iNOS were not able to detect the chronic WM microglial activation that was detected with MHCII in the contralateral corpus callosum (day 28 OX6 % area: saline = 0.62 ± 0.38; stroke = 4.30 ± 2.83; P = .029).
Conclusion
Within the regions and groups investigated, TSPO was only expressed in the stroke-induced insult and proximal tissue, and therefore was unable to detect remote and non-insult-related chronically activated microglia overexpressing MHCII in WM.