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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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.
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.
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.
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.
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.
Key wordsMinocycline PET Neuroinflammation PBR TSPO DPA-714 Cerebral ischemia
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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