CONTINUED PRESENCE OF INTRASTRIATAL BUT NOT INTRAVENTRICULAR POLYMER-ENCAPSULATED PC12 CELLS IS REQUIRED FOR ALLEVIATION OF BEHAVIORAL DEFICITS IN PARKINSONIAN RODENTS

To date, few studies have systematically evaluated the most appropriat e location for grafting catecholaminergic cells as a potential treatme nt for Parkinson's disease (PD). The following study was conducted to determine 1) if placement of catecholamine-secreting encapsulated PC12 cells into the lateral ventricle of 6-OHDA-treated rats is as effecti ve as intrastriatal implants on reducing apomorphine-induced rotationa l behavior, and 2) to determine if the survival of encapsulated PC12 c ells is differentially affected by the implant site. Polymer-encapsula ted PC12 cells were implanted into either the striatum or lateral vent ricle of unilateral 6-OHDA-lesioned rats. Animals were tested for apom orphine-induced rotations over a 6-wk period. Only those animals that received intrastriatal implants of encapsulated PC12 cells showed a re duction in rotation behavior. Moreover, removal of the devices from th e striatum resulted in a return to preimplant rotation levels. Postexp lant neurochemical analyses demonstrated that the potassium-evoked L-d opa device output increased in vivo while the potassium-evoked dopamin e output from the devices decreased over time in vivo. The location of the implant significantly affected catecholamine output from the PC12 cell-loaded devices. The increase in potassium-evoked L-dopa output w as greatest, as was the decrease in potassium-evoked dopamine output, from those devices implanted in the striatum. Basal output of dopamine and DOPAC was also significantly higher from devices explanted from t he lateral ventricle. These results demonstrate that the continued pre sence of intrastriatal implants of encapsulated PC12 cells is required to maintain the behavioral effects in 6-OHDA-lesioned rats. In additi on, the site of implantation appears to affect device output. These re sults provide additional support for intraparenchymal delivery of L-do pa and dopamine via polymer encapsulation as a possible treatment for PD.