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

Olopade Funmilayo, Shokunbi Matthew, Sirén, Sirén Anna-Leena

Description

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.

Sujets

• Hydrocephalus
• Cognition
• Neuropathology
• Programmed cell death
• Inflammation

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 8
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Olopadeet al. Fluids and Barriers of the CNS2012,9:19 http://www.fluidsbarrierscns.com/content/9/1/19

R E S E A R C H

FLUIDS AND BARRIERS OF THE CNS

Open Access

The relationship between ventricular dilatation, neuropathological and neurobehavioural changes in hydrocephalic rats 1 1,2* 3 Funmilayo Eniola Olopade , Matthew Temitayo Shokunbi and AnnaLeena Sirén

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

Background Hydrocephalus is a relatively common neurological condi tion especially in children, occurring in 0.5–1 per 1,000 live births worldwide [1]. It is most usually characterized by an anomaly in the circulation of cerebrospinal fluid leading to its accumulation within the ventricles of the brain. The motor and cognitive deficits which occur in hydrocephalus are thought to be partly due to axonal damage within the periventricular white matter. In addition, myelin disruption

* Correspondence: [e-mail] 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 Full list of author information is available at the end of the article

is prominent in hydrocephalus [2], accounting for many of the neurological deficits in this disorder, thus necessitating an examination of the role of oligodendrocytes, the myelin producing cells in the central nervous system. The study of the full impact of these changes on behavior is necessary as the behavior of an organism represents the full functional integration of the nervous system [3]. It is reasonable to expect that the degree of ventricular dilata tion in hydrocephalus will determine the span and severity of white matter injury and ultimately, functional deficits. However, previous studies of this relationship have revealed conflicting results. Lorber [4] concluded that even extreme ventricular dilation is compatible with normal physical and intellectual development into adult life after he examined a

© 2012 Olopade et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.