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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 11/2012

01-11-2012 | Original Article

Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model

Authors: Caroline Vandeputte, Cindy Casteels, Tom Struys, Michel Koole, Daisy van Veghel, Nele Evens, Anneleen Gerits, Tom Dresselaers, Ivo Lambrichts, Uwe Himmelreich, Guy Bormans, Koen Van Laere

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2012

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Abstract

Purpose

Recent ex vivo and pharmacological evidence suggests involvement of the endocannabinoid system in the pathophysiology of stroke, but conflicting roles for type 1 and 2 cannabinoid receptors (CB1 and CB2) have been suggested. The purpose of this study was to evaluate CB1 and CB2 receptor binding over time in vivo in a rat photothrombotic stroke model using PET.

Methods

CB1 and CB2 microPET imaging was performed at regular time-points up to 2 weeks after stroke using [18F]MK-9470 and [11C]NE40. Stroke size was measured using MRI at 9.4 T. Ex vivo validation was performed via immunostaining for CB1 and CB2. Immunofluorescent double stainings were also performed with markers for astrocytes (GFAP) and macrophages/microglia (CD68).

Results

[18F]MK-9470 PET showed a strong increase in CB1 binding 24 h and 72 h after stroke in the cortex surrounding the lesion, extending to the insular cortex 24 h after surgery. These alterations were consistently confirmed by CB1 immunohistochemical staining. [11C]NE40 did not show any significant differences between stroke and sham-operated animals, although staining for CB2 revealed minor immunoreactivity at 1 and 2 weeks after stroke in this model. Both CB 1 + and CB 2 + cells showed minor immunoreactivity for CD68.

Conclusion

Time-dependent and regionally strongly increased CB1, but not CB2, binding are early consequences of photothrombotic stroke. Pharmacological interventions should primarily aim at CB1 signalling as the role of CB2 seems minor in the acute and subacute phases of stroke.
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Metadata
Title
Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model
Authors
Caroline Vandeputte
Cindy Casteels
Tom Struys
Michel Koole
Daisy van Veghel
Nele Evens
Anneleen Gerits
Tom Dresselaers
Ivo Lambrichts
Uwe Himmelreich
Guy Bormans
Koen Van Laere
Publication date
01-11-2012
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2012
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-012-2209-6

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