Date of Completion

6-26-2013

Embargo Period

6-26-2013

Advisors

Akiko Nishiyama, Joseph LoTurco

Field of Study

Physiology and Neurobiology

Degree

Master of Science

Open Access

Open Access

Abstract

The ventricles of the brain are lined by a monolayer of ciliated ependymal cells that act as an interface between the circulating cerebrospinal fluid and the underlying tissue. Along the lateral walls of the lateral ventricles, the ependymal cells have additional significance as they are considered one of the cell types that comprise the subventricular zone (SVZ) neurogenic niche. Since lateral ventricle expansion is a well documented occurrence in not only a variety of neurological disorders but also with normal aging, it is important to consider the effect of this expansion on the ependyma. By combining MRI-based 3-D reconstructions of the lateral ventricles with thorough immunohistochemical evaluation of the lateral walls of aged human brains, we confirmed that ventriculomegaly is associated with a severely compromised ependyma and gliosis at the ventricle surface. To determine whether any directionality exists between gliosis and ventricle enlargement, we induced ependymal gliosis in mice, who do not display either gliosis or ventricular expansion with age under normal circumstances. We found that not only are the resulting scars phenotypically similar to those observed in humans, but that the lateral ventricles of mice with widespread scarring caused by neuraminidase have increased volume compared to saline-injected controls. This work establishes a link between periventricular gliosis and enlarged ventricle volumes and supports the hypothesis that damage to the ependyma and the resulting scarring can affect ventricle volume.

Major Advisor

Joanne Conover

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