11C-PK11195 PET for the in vivo evaluation of neuroinflammation in the rat brain after cortical spreading depression.
Neurogenic inflammation triggered by extravasation of plasma protein has been hypothesized as a key factor in the generation of the pain sensation associated with migraine. The principal immune cell that responds to this inflammation is the parenchymal microglia of the central nervous system.


METHODS
Using a PET technique with (11)C-(R)-[1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinolinecarboxamide] ((11)C-PK11195), a PET ligand for peripheral type-benzodiazepine receptor, we evaluated the microglial activation in the rat brain after generation of unilateral cortical spreading depression, a stimulation used to bring up an experimental animal model of migraine.


RESULTS
We found a significant increase in the brain uptake of (11)C-PK11195, which was completely displaceable by the excess amounts of unlabeled ligands, in the ipsilateral hemisphere of the spreading depression-generated rats. Moreover, the binding potential of (11)C-PK11195 in the spreading depression-generated rats was significantly higher than that in the sham-operated control rats.


CONCLUSIONS
These results suggest that as an inflammatory reaction, microglial cells are activated in response to the nociceptive stimuli induced by cortical spreading depression in the rat brain. Therefore, the (11)C-PK11195 PET technique could have a potential for diagnostic and therapeutic monitoring of neurologic disorders related to neuroinflammation such as migraine.
Cui
Yilong
Y
Cellular Function Imaging Laboratory, RIKEN Center for Molecular Imaging Science, Kobe, Hyogo, Japan. cuiyl@riken.jp
Takashima
Tadayuki
T
Takashima-Hirano
Misato
M
Wada
Yasuhiro
Y
Shukuri
Miho
M
Tamura
Yasuhisa
Y
Doi
Hisashi
H
Onoe
Hirotaka
H
Kataoka
Yosky
Y
Watanabe
Yasuyoshi
Y
D000577:Amides; D000818:Animals; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D013181:Cortical Spreading Depression; D007150:Immunohistochemistry; D007546:Isoquinolines; D008297:Male; D020078:Neurogenic Inflammation / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley
C504060:(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; D000577:Amides; D007546:Isoquinolines