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Cyclosporine A (CsA) immunosuppressive treatment has become an adjunctive therapy in neural transplanta tion of dopamine-secreting cells for treatment of Parkinson's disease (PD). Recently, CsA and its analogues have been shown to promote trophic effects against neurodegenerative disorders, and therefore CsA may have direct beneficial effects on dopaminergic neurons and dopamine-mediated behaviors. The present study examined the interaction between the reported CsA-induced hyperactivity and the possible alterations in nigral tyrosine hydroxylase (TH)-immunoreactive neurons in rats with damaged blood-brain barrier. CsA was administered at a therapeutic dose (10 mg/kg/day, IP, for 9 days) used in neural transplantation protocol for PD animal models. CsA-treated animals displayed significantly higher general spontaneous locomotor activity than control animals at drug injection days 7 and 9. Histological assays at day 9 revealed that there was a significant increase in TH-immunoreactive neurons in the nigra of CsA-treated rats compared to that of the vehicle-treated rats. The nigral TH elevation was accompanied by suppressed calcium-phosphotase calcineurin activity, indicating an inhibition of host immune response. This is the first report of CsA exerting simultaneous immunosuppressive and neurotrophic effects, as well as increasing general spontaneous loco motor behavior. These results support the utility of CsA as a therapeutic agent for PD and other movement disorders.

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We investigate the compositions of vesicle formulation by assembling phase diagrams of the ternary components of lauroyl‐glutamyl‐lysil‐lauroyl‐glutamate (C12‐GLG‐C12) peptide‐based gemini‐type amphiphile/citric acid/water using visual and microscopic observations. To clarify interactions between C12‐GLG‐C12 and citric acid, turbidity and zeta potential of the mixtures were investigated. To improve the stability of metastable vesicles, appropriate additives were examined by measuring particle size and zeta potential, visual observation and transmission electron microscopy. The turbidity increased and the absolute value of zeta potential decreased with increasing citric acid concentration in C12‐GLG‐C12/citric acid solutions. Then, a metastable γ region having vesicles was formed. The stability of vesicles increased with increasing cholesterol concentrations. This result suggests that a coacervation has occurred due to the effective cross‐sectional area decreasing with increasing C12‐GLG‐C12 hydrophobicity, which was derived from inhibition of the carboxyl group dissociation. Furthermore, we hypothesized that the orientation of cholesterol between vesicle membranes is a contributing factor to improve the vesicle stability. From transmission electron microscopic observations, it was made clear that the vesicles consisting of cholesterol and C12‐GLG‐C12 at a molar ratio of 2:1 showed multilayered structures. The vesicles consisting of C12‐GLG‐C12, cholesterol and citric acid are expected to be used as transdermal drug delivery system carriers, as they can be easily prepared using biocompatible compounds without the use of organic solvents such as chloroform.