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European Journal of Nuclear Medicine and Molecular Imaging

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01.11.2012 | Original Article

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

verfasst von: 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

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 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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Titel: Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model
verfasst von: 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
Publikationsdatum: 01.11.2012
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 11/2012
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-012-2209-6

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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