engleski

Immunomodulation influences the course of postnatal brain development in MCMV infected newborn mice

Human cytomegalovirus is a leading viral pathogen of congenital infection of the central nervous system resulting in long term neurological impairment. In our model of murine cytomegalovirus (MCMV) infection in newborn mice we have shown that MCMV impairs postnatal development of the cerebellum (Koontz et al., JEM 2008). Productive infection is successfully controlled by components of both innate and adaptive immune response in which CD8+ T cells play a predominant role (Bantug et al., J. Immunol. 2008). Dexamehtasone, as a known immunomodulator, is widely used in the treatment of functional impairment of premature infants. However, the effect of dexamethasone treatment onto early neurodevelopment is still insufficiently elucidated. The aim of this study was to analyze the effect of dexamethasone treatment onto course of MCMV infection in newborn brain and consequent cerebellar maldevelopment. Newborn mice, infected intraperitoneally at day 0 with wild type MCMV, received deyamethasone on 4, 5 and 6 dpi. Mice were sacrificed at various dpi and their brains were processed for further analysis. Our results show that dexamethasone treatment influenced the viral titers in the brain depending on the time post infection. Virus titer in the brain of infected, dexamethasone treated mice was higher as compared to infected untreated mice, but surprisingly on later time point virus titer dramatically decreased, indicating that dexamethasone modulates immune response during early period of infection. Cerebella of infected, dexamethasone treated mice were smaller, but with thinner ELG layer, and lesions in comparison with infected, untreated ones, suggesting that dexamethasone, at least partially, underpins the effects of MCMV infection and replication in developing brain.

MCMV; brain development

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