Restorative and neuroprotective treatment strategies for Parkinson’s disease: tudies on fetal dopamine cell transplants and GDNF delivery by intracerebral injections and recombinant AAV vectors.

The intrastriatal 6-hydroxydopamine lesion model in rats is particularly useful in studies testing new therapeutic strategies for Parkinson’s disease. This thesis work (1) describes the characterization of the motor deficits after different types of intrastriatal lesions and identifies the four-site terminal lesion as a model of symptomatic Parkinson’s disease; (2) using the same model, provides evidence that the functional impact of the dopamine cell grafts are dependent on interactions with the host brain; (3) demonstrates that protection or restitution of normal motor function after 6-hydroxydopamine lesions can be achieved if glial cell line-derived neurotrophic factor is administered in the striatum at the time of the terminal fiber degeneration. The findings have implications for the development of effective neuroprotective and restorative therapeutic interventions for Parkinson’s disease.