Congenital Infection and Disorders of Brain Development: With Special Reference to Congenital Cytomegalovirus Infection

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  • Congenital infection and disorders of b

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ABSTRACT Intrauterine infections of various microorganisms have the potential to induce brain abnormalities in the fetus and newborn infant. Among the infectious pathogens, cytomegalovirus (CMV) is the most significant infectious cause of brain abnormalities, with variations from fatal cytomegalic inclusion disease to functional brain disorders, such as mental retardation or epilepsy. Here, we present three autopsy cases of congenital CMV infection, and we review the features of the brain abnormalities of congenital CMV infection. A ventriculofugal spread of infection seems to be characteristics of congenital CMV-infected brains and is suggested to be the cause of neuronal migration disorders, resulting in brain malformations, such as microcephaly, lissencephaly and polymicrogyria. We also present an experimental animal model for congenital CMV infection. With the model we showed that murine cytomegalovirus (MCMV) infection in the developing mouse brain caused a disturbance of neuronal migration and neuronal cell loss, detected with morphometric measurements by labeling the neuronal precursor cells with BrdU. As shown by immunohistochemical double staining of BrdU and viral-antigen, infected neuronal cells constituted only a part of the disordered neuronal cells, suggesting that an indirect effect of vital infection on neuronal cells also contributes the migration disorders presumably mediated by cytokines or the induction of apoptosis. Neuronal migration dis- orders caused by MCMV infection are also discussed with reference to those caused by X-irradiation.

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