Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts

As part of the DaNeX Study, the uptake and binding of several positron emit ting tracers was recorded in brain of healthy Gottingen minipigs, in minipi gs with a syndrome of parkinsonism due to MPTP intoxication, and in parkins onian minipigs which had received intrastriatal grafts of mesencephalic neu rons from fetal pigs. The specific binding of [C-11]NS 2214 to catecholamin e uptake sites was reduced by two thirds in striatum of the intoxicated ani mals, while the rate constant for the decarboxylation of [F-18]fluorodopa w as reduced by 50% in the intoxicated animals. Several months after grafting , both pre-synaptic markers of dopamine fibres were normal in striatum. Dop amine depletion or grafting were without effect on the cerebral perfusion r ate, measured with [O-15]-water, did not alter the rate of oxygen metabolis m (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 asso ciated with a local increase in the binding of [C-11]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. Howe ver, this apparent immunological response did not preclude the reestablishm ent establishment of normal [F-18]fluorodopa and [C-11]MS 2214 uptake in th e allografted striatum. allografted striatum.