A model of cerebral aspergillosis in non-immunosuppressed nursing rats

Central nervous system aspergillosis is an often fatal complication of invasive Aspergillus infection. Relevant disease models are needed to study the pathophysiology of cerebral aspergillosis and to develop novel therapeutic approaches. This study presents a model of central nervous system aspergil...

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Bibliographic Details
Published in:Acta neuropathologica 2007-10, Vol.114 (4), p.411-418
Main Authors: Zimmerli, Stefan, Knecht, Urspeter, Leib, Stephen L
Format: Article
Language:English
Subjects:
Abscesses
Animals
Animals, Suckling
Aspergillus fumigatus
Brain Diseases - microbiology
Brain Diseases - pathology
Disease
Disease Models, Animal
Drug dosages
Infections
Male
Mortality
Nervous system
Neuroaspergillosis - microbiology
Neuroaspergillosis - pathology
Nursing
Pathophysiology
Rats
Rats, Wistar
Steroids
Transplants & implants
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Summary:Central nervous system aspergillosis is an often fatal complication of invasive Aspergillus infection. Relevant disease models are needed to study the pathophysiology of cerebral aspergillosis and to develop novel therapeutic approaches. This study presents a model of central nervous system aspergillosis that mimics important aspects of human disease. Eleven-day-old non-immunosuppressed male Wistar rats were infected by an intracisternal injection of 10 mul of a conidial suspension of Aspergillus fumigatus. An inoculum of 7.18 log(10) colony-forming units (CFU) consistently produced cerebral infection and resulted in death of all animals (n = 25) within 3-10 days. Median survival time was 3 days. Histomorphologically, all animals developed intracerebral abscesses (2-26 per brain) containing abundant fungal hyphae and neutrophils. Fungal culture of cortical homogenates yielded maximal growth on day 3 after infection (5.4 log(10) CFU/g, n = 15) that declined over time. Galactomannan concentrations in cortical homogenates, assessed as an index for hyphal burden, peaked on days 3-5. Fungal infection spread to peripheral organs in 83% of animals. Fungal burden in lung, liver, spleen and kidney was two orders of magnitude lower than in the brain. The successful establishment of a model of cerebral aspergillosis in a non-immunosuppressed host provides the opportunity to investigate mechanisms of disease and to develop novel treatment regimens for this commonly fatal infection.
ISSN:0001-6322
1432-0533
DOI:10.1007/s00401-007-0255-0