Neural stem cell (NSC) transplantation induces recovery in animal models of central nervous system (CNS) diseases, in part by modulating adaptive and innate immune responses. Since metabolism governs the phenotype and function of immune cells, the aim of this thesis was to investigate whether NSCs have the ability to regulate the immunometabolic components underpinning neuroinflammation. Herein I have identified a new mechanism by which transplanted somatic and directly-induced NSCs counteract CNS-compartmentalised chronic inflammation in mice. NSC transplantation reduces the immunometabolite succinate in the cerebrospinal fluid, while decreasing the burden of mononuclear phagocyte (MP) infiltration and secondary CNS damage. Mechanistically, the anti-inflammatory activity of NSCs arises in response to succinate released by inflammatory MPs, which activates succinate receptor 1 (SUCNR1)/GPR91 on NSCs, thus initiating prostaglandin E2 secretion and extracellular succinate scavenging. This work uncovers a succinate-SUCNR1 axis in NSCs that clarifies how stem cells respond to inflammatory metabolic signals to inhibit the activation of pro-inflammatory MPs in the chronically inflamed brain.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009.

This qualitative study explored the psychosocial experiences of children and adolescents with early-onset multiple sclerosis. In particular, an emphasis was placed on examing peer relationships and social behaviours in relation to these experiences. MS is a chronic neurological disease primarily affecting young adults. However, a proportion of MS patients have onset during childhood and adolescence. Very little is know about the psychosocial impact of MS on these children and adolescents. In particular, youth with MS may be at risk for negative peer experiences due to their chronic illness. Previous research suggested that negative peer experiences increase the risk of poor psychosocial development. In addition, research suggested that the social behaviours of these youth also impact the nature of their experiences with peers. Ultimately, this research aimed to provide insight into the psychoscial experiences of youth with MS and the role of their peer relationships. Six linked parent-youth pairs, from the MS Clinic in Calgary, AB, participated in semi-structured interviews to identify the issues that are pertinent to the participants' own experiences. Constant comparison analysis was then used to summarize the rante of psychosocial experiences in the adolescent participants. Data analysis was derived from grounded theory, which provided a framework for examining and categorizing interview data into themes. The categories were then constructed logically and systematically into a theoretical model which represented the data. Through this innovative grounded theory, a theoretical paradigm for understanding the psychosocial experiences of adolescents with MS was developed. The theory was comprised of two core categories: "the grief experience" and "dynamic relationships', each with several sub-categories. There were two primary conclusions drawn from the theory. The first reflected the significance of grief in understanding psychosocial experiences in adolescents with MS. The second identified that peer relationships play a variety of roles in this grief process. The second identified that peer relationships play a variety of roles in this grief process. The results of this study have many implications for the role of counsellors in the treatments of adolescents with MS. This model can act as a foundation for guiding therapeutic treatment of adolescents with MS. This model can act as a foundation for guiding therapeutic treatment and promoting future research in the area of psychosocial development in children and adolescents with early-onset MS. / xiv, 181 leaves ; 28 cm.

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