Defense Date

2006

Document Type

Thesis

Degree Name

Master of Science

Department

Anatomy & Neurobiology

First Advisor

Dr. William C. Broaddus

Abstract

Convection-enhanced delivery (CED) is a proven method for targeted drug delivery to the brain that circumvents the blood-brain barrier (BBB). Little study has been conducted in understanding CED in pathological brain states. This is of importance when dealing with chemotherapeutic agent delivery to brain tumors, where vasogenic edema (VE) exists. The current study aims to characterize a model of VE suitable for studying CED.VE was produced in the right hemisphere of the rat brain using multiple infusions of hyperosmotic mannitol (0.25mL/kg/s over 30 seconds) delivered through the right internal carotid artery. Magnetic resonance imaging (MRI) revealed consistent edema formation and high water levels in the ipsilateral gray and white matter within an hour of the first infusion. Evan's Blue (EB) staining verified that VE has formed. However, apparent diffusion coefficient (ADC) and histological examination revealed also that some possible cytotoxic edema formed.This model provides a reproducible technique for generating a large area of edema for CED study. Further studies with lower doses of mannitol, while titrating to changes in ADC and values for fractional water content, may modify this model with a greater component of VE and less cerebral toxicity.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

June 2008

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