DOI: 10.1186/s13550-018-0400-xPages: 1-12

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

1. Shionogi & Co., Ltd., Translational Research Unit, Biomarker R&D Department

2. Shionogi & Co., Ltd., Department of Applied Chemistry and Analysis, Research Laboratory for Development

3. Shionogi & Co., Ltd., Department of medical affairs

4. Osaka University Graduate School of Medicine, Department of Molecular Imaging in Medicine

5. Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics

6. Osaka University Graduate School of Medicine, PET Molecular Imaging Center

Correspondence to:
Natsumi Miyajima
Tel: +81-6-6331-7413
Email: natsumi.imamoto@shionogi.co.jp

Close

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.

This article is freely available, click here to access the full text/PDF

  • Accepted: May 23, 2018
  • Online: Jun 8, 2018

Article Tools

eanm
EJNMMI Ad