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Reduced PBR/TSPO Expression After Minocycline Treatment in a Rat Model of Focal Cerebral Ischemia: A PET Study Using [18F]DPA-714

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Abstract

Background

Many new candidate pharmaceuticals designed to improve recovery after stroke have been proposed recently, but there are still too few molecular imaging methods capable to assess their efficacy. A hallmark of the inflammatory reaction that follows focal cerebral ischemia is overexpression of the mitochondrial peripheral benzodiazepine receptor/18 kDa translocator protein (PBR/TSPO) in the monocytic lineage and astrocytes. This overexpression can be imaged with positron emission tomography (PET) using PBR/TSPO-selective radioligands such as [18F]DPA-714.

Purpose

Here, we tested whether PET with [18F]DPA-714 would evidence the effect of minocycline, a broad spectrum antibiotic presently tested as neuroprotective agent after stroke, on the inflammatory reaction induced in an experimental model of stroke.

Procedures

Ten rats were subjected to a 2-h transient middle cerebral artery occlusion with reperfusion. Minocycline or saline was intravenously administrated 1 h after reperfusion and daily during the following 6 days. PET studies were performed using [18F]DPA-714 at 7 days after cerebral ischemia.

Results

In vivo PET imaging showed a significant decrease in [18F]DPA-714 uptake at 7 days after cerebral ischemia in rats treated with minocycline with respect to saline-treated animals. Minocycline treatment had no effect on the size of the infarcted area.

Conclusion

Minocycline administered daily during 7 days after ischemia decreases [18F]DPA-714 binding, suggesting that the drug exerts an anti-inflammatory activity. [18F]DPA-714 PET is a useful biomarker to study novel anti-inflammatory strategies in experimental cerebral ischemia.

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Acknowledgments

We thank A. Blossier for technical assistance in the PET studies. This work was funded in part by the EU-FP6 network EMIL (LSHC-CT-2004-503569) and the EU-FP6 network DiMI (LSHB-CT-2005-512146).

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Authors and Affiliations

  1. CEA, DSV, I²BM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale; INSERM U803, 4, Place Géneral Leclerc, 91406, Orsay Cedex, France

    Abraham Martín, Raphaël Boisgard & Bertrand Tavitian

  2. Department of Medical Radiation Sciences and School of Chemistry, University of Sydney, Sydney, NSW, Australia

    Michael Kassiou

  3. CEA, DSV, I²BM, SHFJ, Orsay, France

    Frédéric Dollé

Authors
  1. Abraham Martín
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  2. Raphaël Boisgard
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  3. Michael Kassiou
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  4. Frédéric Dollé
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  5. Bertrand Tavitian
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Correspondence to Bertrand Tavitian.

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Martín, A., Boisgard, R., Kassiou, M. et al. Reduced PBR/TSPO Expression After Minocycline Treatment in a Rat Model of Focal Cerebral Ischemia: A PET Study Using [18F]DPA-714. Mol Imaging Biol 13, 10–15 (2011). https://doi.org/10.1007/s11307-010-0324-y

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