Parkinson__s disease is a progressive neurodegenerative disease, which is composed of many components, each caused by interplay of a number of genetic and nongenetic causes. As the blood-brain... Show moreParkinson__s disease is a progressive neurodegenerative disease, which is composed of many components, each caused by interplay of a number of genetic and nongenetic causes. As the blood-brain barrier (BBB) is a key player in the relationship between plasma and brain pharmacokinetics, the influences of disease states on BBB functionality in the various stages of the disease is important in order to judge on drug effects. This warrants a systems pharmacology approach to the development of novel drug treatments of Parkinson__s disease. Animal models of disease are an essential asset in this research. The research described in this thesis shows that the intracerebral rotenone rat model is a chronic and progressive animal model for Parkinson__s disease, displaying alpha-synuclein immunoreactivity and aggregation in several cases. The model has also shown that no changes were found in passive BBB permeability, nor in BBB transport modes of L-DOPA. However, a diseased condition was present as indicated by the clear effect of rotenone on the levels and elimination rates of DOPAC and HVA in brain that provided information on decreased dopamine concentrations at the diseased brain side. Altogether, it can be concluded that the intracerebral rotenone rat model is an animal model which is suitable as a tool in systems pharmacology research on Parkinson__s disease. Show less