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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/14347

Title: Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model
Authors: Vandeputte, Caroline
Casteels, Cindy
Struys, Tom
Koole, Michel
van Veghel, Daisy
Evens, Nele
Gerits, Anneleen
Dresselaers, Tom
Lambrichts, Ivo
Himmelreich, Uwe
Bormans, Guy
Van Laere, Koen
Issue Date: 2012
Publisher: SPRINGER
Abstract: 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. CB1 and CB2 microPET imaging was performed at regular time-points up to 2 weeks after stroke using [F-18]MK-9470 and [C-11]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). [F-18]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. [C-11]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. 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.
Notes: [Van Laere, Koen] UZ Leuven, Div Nucl Med, B-3000 Louvain, Belgium. [Vandeputte, Caroline; Casteels, Cindy; Koole, Michel; Gerits, Anneleen; Van Laere, Koen] Katholieke Univ Leuven, Div Nucl Med, Louvain, Belgium. [Vandeputte, Caroline; Casteels, Cindy; Koole, Michel; van Veghel, Daisy; Evens, Nele; Gerits, Anneleen; Dresselaers, Tom; Himmelreich, Uwe; Bormans, Guy; Van Laere, Koen] Katholieke Univ Leuven, MoSAIC, Mol Small Anim Imaging Ctr, Louvain, Belgium. [Struys, Tom; Lambrichts, Ivo] Hasselt Univ, Biomed Res Inst, Histol Lab, Hasselt, Belgium. [Struys, Tom; Dresselaers, Tom; Himmelreich, Uwe] Katholieke Univ Leuven, Biomed NMR Unit, Louvain, Belgium. [van Veghel, Daisy; Evens, Nele; Bormans, Guy] Katholieke Univ Leuven, Lab Radiopharm, Louvain, Belgium.
URI: http://hdl.handle.net/1942/14347
DOI: 10.1007/s00259-012-2209-6
ISI #: 000309562600016
ISSN: 1619-7070
Category: A1
Type: Journal Contribution
Validation: ecoom, 2013
Appears in Collections: Research publications

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