Cell death, axonal damage, and cell birth in the immature rat brain following induction of hydrocephalus

We hypothesized that hydrocephalus can cause death of brain cells and that generation of new brain cells might compensate for the cell loss. Hydroceph alus was induced in 8-week-old rats by injection of kaolin into the cistern a magna. The brains were studied 1 to 4 weeks later by histochemical, immun ochemical, and ultrastructural methods. The ventricles enlarged progressive ly. Some axons in the corpus callosum were injured as early as 1 week, but axonal damage was not prevalent until 4 weeks when ventriculomegaly became severe. Dying cells detected by DNA end labeling and often identified as ol igodendrocytes by electron microscopy were evident in white matter. Late-st age hydrocephalus was associated with a significant increase in the quantit y of dying cells. Hydrocephalus was associated with increased Ki67 labeling and bromodeoxyuridine incorporation in the subependymal zone. Reactive cha nges were identified among astrocytes, oligodendroglia, and microglia. We c onclude that hydrocephalus causes, in addition to axonal injury, gradual ce ll death in the cerebrum, particularly the white matter. The brain response includes production of new glial cells, but whether the new cells play any beneficial role remains unknown. (C) 1998 Academic Press.