Induction of congenital hydrocephalus in hamsters with parainfluenza type 2 virus

Abstract

We describe induction of obstructive hydrocephalus by intra-amniotic inoculation of parainfluenza type 2 virus into 10- to 12-day pregnant hamsters. As determined by cytoplasmic inclusions, specific immunofluorescence, cytopathic effects, inflammation, and/or gross and microscopic lesions, 144 of 264 exposed fetuses were infected. Fetuses harvested at term showed initial infection of yolk sac endoderm, transmission to fetuses via oronasal portals, and early spread along respiratory mucosa. Mild meningoencephalitis, principally involving ependyma and usually sparing brain parenchyma, was also observed in 58 animals. While pneumonitis tended to regress without significant sequellae, destruction of ependyma led to gliovascular outgrowth over ventricular walls, adhesions, and aqueductal stenosis. Ultimately, as observed in four animals, obstructive hydrocephalus resulted. The aqueductal lesion, a consequence of repair, resembled a developmental rather than a postinfectious defect. This is the second example of the experimental induction of this entity by an intrauterine systemic viral infection, the other causative agent being mumps. These two sets of studies, which bear close comparison, support the postulate that congenital hydrocephalus in humans may be the result of intrauterine infection by common viruses, which only infrequently invade the developing nervous system and induce mild, self-limited, but strategically localized disease.