Effect of hydrocephalus on rat brain extracellular compartment

We studied neonatal (newborn) onset hydrocephalus for 1 or 3 weeks, juvenile (3 weeks) onset hydrocephalus for 3–4 weeks or 9 months, and young adult (10 weeks) onset hydrocephalus for 2 weeks, after kaolin injection. Freeze substitution electron microscopy was used to measure the size of the extracellular compartment. Western blotting and immunohistochemistry with quantitative image densitometry was used to study the extracellular matrix constituents, phosphacan, neurocan, NG2, decorin, biglycan, and laminin.The extracellular space in cortical layer 1 was reduced significantly from 16.5 to 9.6% in adult rats with 2 weeks duration hydrocephalus. Western blot and immunohistochemistry showed that neurocan increased only in the periventricular white matter following neonatal induction and 3 weeks duration hydrocephalus. The same rats showed mild decorin increases in white matter and around cortical neurons. Juvenile and adult onset hydrocephalus was associated with no significant changes.We conclude that compositional changes in the extracellular compartment are negligible in cerebral cortex of hydrocephalic rats at various ages. Therefore, the functional change related to extracellular fluid flow should be reversible.Hydrocephalus is characterized by enlargement of the cerebrospinal fluid (CSF)-containing ventricles of the brain. Several factors including tissue compression, stretching of axons, ischemia, and calcium-mediated proteolysis simultaneously contribute to axon injury in periventricular white matter [1,2]. We have also postulated that movement and composition of extracellular fluids are altered with potential reversible effects on neuronal function [3] and Hakim suggested that the brain behaves like a compressed sponge with reduction of the extracellular compartment [4]. Although the periventricular white matter extracellular compartment is enlarged in progressive hydrocephalus [3,5], several types of evidence suggest that the more superficial parts of brain