Characterization of BBB Permeability in a Preclinical Model of Cryptococcal Meningoencephalitis Using Magnetic Resonance Imaging-Reference-Cited by-同舟云学术

Characterization of BBB Permeability in a Preclinical Model of Cryptococcal Meningoencephalitis Using Magnetic Resonance Imaging

Published:2008-12-10 Issue:3 Volume:29 Page:545-553
ISSN:0271-678X
Container-title:Journal of Cerebral Blood Flow & Metabolism
language:en
Short-container-title:J Cereb Blood Flow Metab

Author:

Pai Manjunath P¹,Sakoglu Unal²,Peterson Steven L¹,Lyons C Richard³,Sood Rohit⁴⁵

Affiliation:

1. College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USA

2. The MIND Institute, University of New Mexico, Albuquerque, New Mexico, USA

3. Department of Hematology and Oncology, University of New Mexico, Albuquerque, New Mexico, USA

4. Department of Neurology, Health Sciences Center, University of New Mexico, Albuquerque, New Mexico, USA

5. The BRaIN Center, University of New Mexico, Albuquerque, New Mexico, USA

Abstract

Cryptococcus neoformans meningoencephalitis (CNME) is a leading fungal cause of death among acquired immunodeficiency syndrome patients. Innovative preclinical systems that permit high throughput in vivo evaluation of novel agents are desperately needed. Magnetic resonance imaging (MRI) was evaluated as a tool to develop a rat model of CNME and to quantify noninvasively blood—brain barrier (BBB) disruption secondary to this disease. The aim of this study was to identify MRI changes compared with histopathology and fungal burden measurements as potential biomarkers. A well-characterized strain of C neoformans (CN) var grubii was used to infect rats using intravenous inoculation. An inoculum-finding study was performed by infecting rats with 103, 105, and 107 colony-forming units (CFUs). Animals underwent dynamic MRI on days 4 and 7 after inoculation. An inoculum-confirming study was performed by infecting rats with 105, 106, and 107 CFU and fungal burden was determined in the brain, lung, and spleen. Animals infected with 107 CFU of CN developed lesions that appeared hyperintense on T2-weighted images on day 4. The histopathology results correlated well with MRI data. Diffusion weighted and permeability estimates were 1.4 and 6.1-fold higher, respectively, in lesions compared with healthy tissue. Magnetic resonance imaging is a promising preclinical tool to evaluate effects of antifungal and adjunctive agents.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Neurology (clinical),Neurology

Link

http://journals.sagepub.com/doi/pdf/10.1038/jcbfm.2008.144

Reference32 articles.

1. Cryptococcus meningoencephalitis in AIDS: parenchymal and meningeal forms

2. Cryptococcal meningitis

3. Baseline Correlation and Comparative Kinetics of Cerebrospinal Fluid Colony‐Forming Unit Counts and Antigen Titers in Cryptococcal Meningitis

4. Capsule Structure Changes Associated with Cryptococcus neoformans Crossing of the Blood-Brain Barrier

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