Neurodegenerative diseases, such as multiple sclerosis (MS), are adversely affected by both stress and inflammation. Theiler's murine encephalomyelitis virus infection is an excellent animal model of MS, allowing examination of central nervous system inflammation during the acute phase of infection. Social disruption stress exacerbates acute Theiler's virus infection. Both social disruption stress and Theiler's virus infection elevate the proinflammatory cytokine, Interleukin-6 (IL-6). The current study examined the necessity and sufficiency of IL-6 in mediating the negative effects of social disruption stress in acute Theiler's virus infection. Experiment 1 blocked IL-6 function with a neutralizing antibody administered simultaneously with social disruption stress. All mice were then infected, and measures of illness, motor impairment and physiological signs of disease were collected up to 21 d postinfection. Experiment 2 administered exogenous IL-6 for one week (replacing social disruption with the cytokine treatment), followed by infection. Measures identical to those collected in Experiment 1 were collected for up to 21 d postinfection. Results indicate that IL-6 is necessary for the development of the sickness, motor impairment, and immunological effects of social stress in acute Theiler's virus infection. In contrast, IL-6 alone can induce some, but not all, of the sickness behavior exacerbations, and was not sufficient for the development of either motor impairment or immunological effects previously associated with social disruption stress. These results have many important implications for further research in the effects of social stress on Theiler's virus infection, as well as clinical implications for both MS and other inflammatory mediated diseases, such as Alzheimer's disease and Parkinson's disease.

Thèse de doctorat : Biologie Cellulaire et Nutrition : Nancy 1 : 2008. / Titre provenant de l'écran-titre.

Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 96-112). Also available in print.

Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: stem cells, cytokines. Includes bibliographical references (p. 79-83).

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 181-207). Also available in print.

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

published_or_final_version / Medicine / Master / Master of Research in Medicine

published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy

published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy

Two experiments were designed to study endometritis in postpartum dairy cows. In the first experiment, 30 cows 28 to 41 days in milk (DIM) and without evidence of clinical endometritis were sampled using cytobrush cytology. Cytobrush sampling provided sufficient endometrial material to prepare cytologic specimens and to extract endometrial mRNA. Pro-inflammatory cytokines were analyzed in harvested endometrial tissue taken from cows with and without endometritis. Cytokine expression varied between experimental groups with 30-fold higher IL-6 expression levels (P=0.01), greater than 50-fold higher IL-8 expression levels (P=0.0001), and 20-fold higher TNF-&#945; expression levels (P=0.001) in endometritis-positive versus negative cows. Regression analysis of cytokine expression levels (Ct) and the percentage of PMNs in subclinical endometritis-positive cows showed that for each additional threshold cycle required for IL-8 detection, which corresponded to two-fold less mRNA, the percentage of PMN decreased by 3.3% (P=0.00001). Similarly, for each additional threshold cycle required to detect IL-6 and TNF-&#945;, the percentage of PMNs in endometritis-positive cows decreased by 2.3% (P=0.015) and 2.4% (P=0.054), respectively. Cows with > 18% PMNs required significantly fewer amplification cycles to detect IL-6 (P = 0.01), IL-8 (P =0.0001) and TNF-&#945; (P=0.053) mRNA than cows with 15%) cows in this study were defined as those with the lowest percentage of PMNs that was associated with a significant positive treatment effect. Treated cows with >15% PMNs required 31 fewer days (P=0.041) to become pregnant and had 2.5 times fewer services per conception (P=0.0001) than untreated cows with >15% PMNs. The likelihood of there being CLs at the time of examination in cows with >15% PMNs in endometrial cytobrush cytology was 2.3 times significantly higher (P=0.04). The treatment of cows with ultrasonographically detectable fluid in the uterine lumen with benzathine cephapirin had no effect on days open compared to treatment of cows without fluid in the uterus (P=0.39). Cervical diameter and endometrial thicknesses did not differ between groups of cows with >, < 15%PMNs (P=0.46, P=0.36, respectively). In summary, based on the response to a single treatment with benzathine cephapirin, and the analysis of pro-inflammatory cytokine gene expression, we recommend that a threshold of >18% PMNs be used to define endometritis-positive disease status in cows 28 to 41 DIM. Cervical diameter, ultrasonographic evidence of uterine fluid and ultrasonographic measurement of endometrial thickness were not useful for diagnosing benzathine cephapirin responsive endometritis.