Analysis of age-dependant alteration in the brain gene expression profile following induction of hydrocephalus in rats.

Hydrocephalus is associated with gradual progressive impairment and destruction of cerebral axons and neurons. To provide a comprehensive analysis of gene expression changes in brain due to experimental hydrocephalus we used a DNA microarray screening technique. Hydrocephalus was induced in 3-week-old and 8- to 10-week-old rats by injection of kaolin into cisterna magna. Following induction of hydrocephalus, samples of frontoparietal cerebrum were studied 3 and 36 weeks later in young rats and 1.5 weeks later in adult rats. At the transcriptional level, young rats with subacute hydrocephalus showed overexpression of genes involved in synaptic transmission in parallel to genes associated with protective and compensatory mechanisms. Those with chronic hydrocephalus exhibited some similar changes among synapse-related genes but suppression of other neuronal genes. Expression of myelin-related genes was increased in both groups of rats with early onset hydrocephalus but suppressed in adult rats with acute hydrocephalus. Changes in genes related to extracellular matrix molecules suggest that there might be remodeling in this compartment. Adult rats showed elevated expression of inflammatory genes, likely related to kaolin-induced inflammation, but they failed to show changes in genes involved in compensatory or protective mechanisms. These results indicate that there is an age- and duration-dependent difference in the gene expression profiles of kaolin-induced hydrocephalus and they present avenues for future research.