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Open Access Highly Accessed Research

The relationship between ventricular dilatation, neuropathological and neurobehavioural changes in hydrocephalic rats

Funmilayo Eniola Olopade1, Matthew Temitayo Shokunbi12* and Anna-Leena Sirén3

Author Affiliations

1 Department of Anatomy, College of Medicine, University of Ibadan, Ibadan, Nigeria

2 Department of Neurological Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria

3 Department of Neurosurgery, University of Wuerzburg, 97080, Wuerzburg, Germany

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Fluids and Barriers of the CNS 2012, 9:19  doi:10.1186/2045-8118-9-19

Published: 1 September 2012

Abstract

Background

The motor and cognitive deficits observed in hydrocephalus are thought to be due to axonal damage within the periventricular white matter. This study was carried out to investigate the relationship between ventricular size, cellular changes in brain, and neurobehavioural deficits in rats with experimental hydrocephalus.

Methods

Hydrocephalus was induced in three-week old rats by intracisternal injection of kaolin. Behavioural and motor function were tested four weeks after hydrocephalus induction and correlated to ventricular enlargement which was classified into mild, moderate or severe. Gross brain morphology, routine histology and immunohistochemistry for oligodendrocytes (CNPase), microglia (Iba-1) and astrocytes (GFAP) were performed to assess the cellular changes.

Results

Decreases in open field activity and forelimb grip strength in hydrocephalus correlated with the degree of ventriculomegaly. Learning in Morris water maze was significantly impaired in hydrocephalic rats. Gradual stretching of the ependymal layer, thinning of the corpus callosum, extracellular oedema and reduced cortical thickness were observed as the degree of ventriculomegaly increased. A gradual loss of oligodendrocytes in the corpus callosum and cerebral cortex was most marked in the severely-hydrocephalic brains, whereas the widespread astrogliosis especially in the subependymal layer was most marked in the brains with mild hydrocephalus. Retraction of microglial processes and increase in Iba-1 immunoreactivity in the white matter was associated ventriculomegaly.

Conclusions

In hydrocephalic rats, oligodendrocyte loss, microglia activation, astrogliosis in cortical areas and thinning of the corpus callosum were associated with ventriculomegaly. The degree of ventriculomegaly correlated with motor and cognitive deficits.

Keywords:
Hydrocephalus; Cognition; Neurobehavioural tests; Neuropathology; Cell death; Inflammation