Neuroinflammatory Response in Chronic Hydrocephalus in Juvenile Rats

Hydrocephalus is especially prevalent in countries with limited resources, where its treatment is still a challenge. However, long-term neuropathological changes in untreated hydrocephalus remain largely unexplored. The present study looks at cortical parenchyma and neuroinflammation in acquired, chronic hydrocephalus. Intracisternal kaolin injections were performed in 3-week-old rats, followed by -1, 4- and 8-week survival; matched control rats received saline injections. Ventriculomegaly has been previously reported to stabilize by the third week in this model. Single and triple immunocytochemical approaches were used to highlight neurones, astrocytes, microglia, and the pro-inflammatory cytokine interleukin (IL)-1β in the parietal cortex, utilizing cell counts and densitometry. Microglial protein ionized calcium binding adaptor molecule 1 (Iba1) and IL-1β expressions were monitored with Western blotting in the parietal cortex and hippocampus. In the parietal cortex, which showed progressive disruption of cytoarchitecture, neuronal density was significantly increased at 8weeks post-induction but not at earlier time points, indicating on-going cortical damage in chronic hydrocephalus. Astrocyte and microglia hypertrophy, and Iba1 expression indicated glial cell activation which peaked at 4weeks. IL-1β expression also peaked at 4weeks and was then down-regulated. Overall the findings indicate that neuroinflammatory features build up in the first month after hydrocephalus induction implicating marked IL-1β upregulation. The data also show that astrocytes are the main source of IL-1β in this disorder.