Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts |
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Authors: | Cumming P Danielsen E H Vafaee M Falborg L Steffensen E Sørensen J C Gillings N Bender D Marthi K Andersen F Munk O Smith D Møller A Gjedde A |
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Institution: | PET Center, Arhus General Hospital, Norrebrogade 44, Arhus, Denmark. paul@pet.auh.dk |
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Abstract: | As part of the DaNeX study, the uptake and binding of several positron emitting tracers was recorded in brain of healthy Göttingen minipigs, in minipigs with a syndrome of parkinsonism due to MPTP intoxication, and in parkinsonian minipigs which had received intrastriatal grafts of mesencephalic neurons from fetal pigs. The specific binding of 11C]NS 2214 to catecholamine uptake sites was reduced by two thirds in striatum of the intoxicated animals, while the rate constant for the decarboxylation of 18F]fluorodopa was reduced by 50% in the intoxicated animals. Several months after grafting, both pre‐synaptic markers of dopamine fibres were normal in striatum. Dopamine depletion or grafting were without effect on the cerebral perfusion rate, measured with 15O]‐water, did not alter the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding potential of tracers for dopamine D1 or D2 receptors in pig striatum. However, the grafting was associated with a local increase in the binding of 11C]PK 11195, a tracer for reactive gliosis, suggesting that an immunological reaction occurs at the site of graft, which might potentially have reduced the graft patency. However, this apparent immunological response did not preclude the re‐establishment of normal 18F]fluorodopa and 11C]NS 2214 uptake in the allografted striatum. |
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Keywords: | blood flow oxygen CMRO2 [11C]NS 2214 [11C]raclopride [11C]NNC 112 [11C]PK 11195 [18F]fluorodopa pig brain MPTP Parkinson's disease dopamine uptake sites dopamine receptors grafting |
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