Hydrocephalus is commonly viewed as a disorder of cerebrospinal fluid (CSF) accumulation and ventricular enlargement. However, as the ventricles progressively expand, the surrounding brain is exposed to substantial mechanical deformation. Structures immediately adjacent to the ventricles, including the corpus callosum and overlying cortex, may therefore be particularly vulnerable to injury. Using a rat model of genetic congenital hydrocephalus, we asked a simple but important question:
What happens to neurons in the cortex surrounding the enlarged ventricles?
We found markedly enlarged neurons
When we examined the pericallosal cingulate cortex, one of the most striking observations was the presence of unusually enlarged neuronal cell bodies in hydrocephalic animals. These neurons were located within regions showing substantial cortical disorganization and compression of surrounding white-matter structures.
To confirm the identity of these cells, we used NeuN, a marker of mature neurons, together with CTIP2, a marker associated with deep-layer cortical neurons. CTIP2 and NeuN showed strong overlap across experimental groups, confirming that the pathological analyses were being performed within a consistent deep-layer neuronal population. Importantly, the enlarged neurons observed in the hydrocephalic cortex were also NeuN+/CTIP2+ cells.
Quantitative analysis showed that the average neuronal soma area increased in hydrocephalic animals, more than a two-fold increase in neuronal size. This pronounced neuronal enlargement or hypertrophy suggests that hydrocephalus affects not only the overall architecture of the brain but also the morphology of individual neurons.
Why is this important?
These findings reinforce an important concept: hydrocephalus affects much more than ventricular size. The expanding ventricles are surrounded by living brain tissue containing neurons, glia, white-matter tracts, and vascular structures. Understanding what happens to these cells as hydrocephalus progresses is therefore essential when evaluating potential therapies.
Link to the full article here: https://doi.org/10.1186/s12974-026-04031-7