Abstract
BackgroundTranslocator protein (TSPO) imaging can be used to detect neuroinflammation (including microglial activation) after acute cerebral infarction. However, longitudinal changes of TSPO binding after mild ischemia that induces selective neuronal loss (SNL) without acute infarction are not well understood. Here, we performed TSPO imaging with [18F]DPA-714 to determine the time course of neuroinflammation and SNL after mild focal ischemia.ResultsMild focal ischemia was induced by middle cerebral artery occlusion (MCAO) for 20 min. In MCAO rats without acute infarction investigated by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, in vitro ARG revealed a significant increase of [18F]DPA-714 binding in the ipsilateral striatum compared with that in the contralateral side at 1, 2, 3, and 7 days after MCAO. Increased [18F]DPA-714 binding was observed in the cerebral cortex penumbra, reaching maximal values at 7 days after MCAO. Activation of striatal microglia and astrocytes was observed with immunohistochemistry of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) at 2, 3, and 7 days after MCAO. SNL was investigated with Nissl staining and neuronal nuclei (NeuN) immunostaining and observed in the ischemic core region of the striatum on days 3 and 7 after MCAO. We confirmed that total distribution volume of [18F]DPA-714 in the ipsilateral striatum was significantly increased at 2 and 7 days after MCAO using positron emission tomography (PET).Conclusions[18F]DPA-714 binding measured with in vitro ARG was increased before SNL appeared, and this change was detected by in vivo PET. These findings suggest that TSPO PET imaging might be useful for detection of neuroinflammation leading to SNL after focal ischemia.
Highlights
Translocator protein (TSPO) imaging can be used to detect neuroinflammation after acute cerebral infarction
In cases of severe ischemia in which acute infarction is induced, a number of studies have reported that increased TSPO binding after ischemia with infarction can be detected with positron emission tomography (PET) and ARG [2, 3, 27, 28]
In severe focal ischemia models, necrosis response can be induced in the ischemic core, and subsequent increased TSPO binding can be induced
Summary
Translocator protein (TSPO) imaging can be used to detect neuroinflammation (including microglial activation) after acute cerebral infarction. Longitudinal changes of TSPO binding after mild ischemia that induces selective neuronal loss (SNL) without acute infarction are not well understood. We performed TSPO imaging with [18F]DPA-714 to determine the time course of neuroinflammation and SNL after mild focal ischemia. Neuroinflammation is widely accepted as a contributing factor in the pathophysiology of ischemic stroke and neuronal cell death [4]. Microglial activation exerts a cytotoxic effect by releasing inflammatory mediators (including cytokines, chemokines, proteases, and reactive oxygen species) that trigger neuronal damage [7, 8]. Astrocyte activation induces the release of large amounts of tumor necrosis factor-α, resulting in abundant
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