Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model.
OBJECTIVE
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 (CB(1) and CB(2)) have been suggested. The purpose of this study was to evaluate CB(1) and CB(2) receptor binding over time in vivo in a rat photothrombotic stroke model using PET.


METHODS
CB(1) and CB(2) microPET imaging was performed at regular time-points up to 2 weeks after stroke using [(18)F]MK-9470 and [(11)C]NE40. Stroke size was measured using MRI at 9.4 T. Ex vivo validation was performed via immunostaining for CB(1) and CB(2). Immunofluorescent double stainings were also performed with markers for astrocytes (GFAP) and macrophages/microglia (CD68).


RESULTS
[(18)F]MK-9470 PET showed a strong increase in CB(1) 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 CB(1) immunohistochemical staining. [(11)C]NE40 did not show any significant differences between stroke and sham-operated animals, although staining for CB(2) 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.


CONCLUSIONS
Time-dependent and regionally strongly increased CB(1), but not CB(2), binding are early consequences of photothrombotic stroke. Pharmacological interventions should primarily aim at CB(1) signalling as the role of CB(2) seems minor in the acute and subacute phases of stroke.
Division of Nuclear Medicine, KU Leuven, Leuven, Belgium.
Caroline
C
Vandeputte
Cindy
C
Casteels
Tom
T
Struys
Michel
M
Koole
Daisy
D
van Veghel
Nele
N
Evens
Anneleen
A
Gerits
Tom
T
Dresselaers
Ivo
I
Lambrichts
Uwe
U
Himmelreich
Guy
G
Bormans
Koen
K
Van Laere
D000818:Animals; D004195:Disease Models, Animal; D049268:Positron-Emission Tomography; D011725:Pyridines; D011804:Quinolines; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D020521:Stroke / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism; D013927:Thrombosis / Q000150:complications
C576981:2-oxo-7-methoxy-8-butyloxy-1,2-dihydroquinoline-3-carboxylic acid cyclohexylamide; C528731:MK-9470; D011725:Pyridines; D011804:Quinolines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2