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Multipotent, self-renewing neural stem cells and their progeny [collectively referred to as neural precursor cells (NPCs)] represent a population of cells with great promise for CNS repair. To effectively harness their potential for therapeutic applications, the factors that regulate NPC behavior and/or fate must be well understood. The ability of immunomodulatory molecules to affect NPC behavior is of interest because of recent work elucidating the complex interactions between the immune system and nervous system. Herein, we examined the effects of cyclosporin A, a commonly used immunosuppressive molecule, on NPC proliferation kinetics, survival, and fate using in vitro assays at the population level and at the single-cell level. The use of pure populations of NPCs revealed a direct effect of cyclosporin A on cell survival, resulting in increased numbers and larger colonies, with no effect on proliferation kinetics. Cyclosporin A did not alter the differentiation profile of NPC colonies, indicating that it did not promote selective survival of a particular neural lineage. Additionally, we observed decreased cell-cell adhesions in developing cyclosporin A-treated NPC colonies. Consistent with the in vitro observations, in vivo administration of cyclosporin A to adult animals increased the numbers of NPCs within the neurogenic niche lining the lateral ventricles. Together, our findings establish that cyclosporin A has direct effects on NPCs both in vitro and in vivo, making it a promising candidate molecule for developing clinically relevant strategies to stimulate NPCs for brain repair.

Abstract. In this paper we present a CTL-like logic which i s i n terpreted over the state spaces of Coloured Petri Nets. The logic has been designed to express properties of both state and transition information. This is possible because the state spaces are labelled transition systems. We compare the expressiveness of our logic with CTL's. Then, we present a model checking algorithm which for e ciency reasons utilises strongly connected components and formula reduction rules. We present empirical results for non-trivial examples and compare the performance of our algorithm with that of Clarke, Emerson, and Sistla.

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We study the complexity of several standard problems for 1-safe Petri nets and some of its subclasses. We prove that reachability, liveness, and deadlock are all PSPACE-complete for 1-safe nets. We also prove that deadlock is NP-complete for free-choice nets and for 1-safe free-choice nets. Finally, we prove that for arbitrary Petri nets, deadlock is equivalent to reachability and liveness.