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Open Access 01-12-2018 | Original research

Detection of neuroinflammation before selective neuronal loss appearance after mild focal ischemia using [¹⁸F]DPA-714 imaging

Authors: Natsumi Miyajima, Miwa Ito, Takemi Rokugawa, Hitoshi Iimori, Sotaro Momosaki, Shigeki Omachi, Eku Shimosegawa, Jun Hatazawa, Kohji Abe

Published in: EJNMMI Research | Issue 1/2018

Abstract

Background

Translocator 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.

Results

Mild 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.

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Title: Detection of neuroinflammation before selective neuronal loss appearance after mild focal ischemia using [18F]DPA-714 imaging
Authors: Natsumi Miyajima
Miwa Ito
Takemi Rokugawa
Hitoshi Iimori
Sotaro Momosaki
Shigeki Omachi
Eku Shimosegawa
Jun Hatazawa
Kohji Abe
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2018
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-018-0400-x

At a glance: The STEP trials

Springer Medicine

Detection of neuroinflammation before selective neuronal loss appearance after mild focal ischemia using [¹⁸F]DPA-714 imaging

Abstract

Background

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusions

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