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Development of a murine model of cerebral aspergillosis.

Abstract
Central nervous system (CNS) Aspergillus infection has a mortality rate in humans that approaches 95%. Because no animal models are available for studying this infection, we sought to develop a murine model of CNS aspergillosis. Inconsistent data were obtained for nonimmunosuppressed CD-1, C57BL/6, and DBA/2N mice after infection by midline intracranial injection of Aspergillus fumigatus. CD-1 mice given cyclophosphamide to produce immunosuppression had continuous pancytopenia. Dose-finding studies in CD-1 mice showed that infection with 5 x 106 conidia/mouse consistently caused 100% mortality by day 5-8; no mice died before day 3. Histologic examination of samples of brain tissue showed focal abscesses containing Aspergillus hyphae. Fungus burdens in brain were higher than those in other organs, although Aspergillus disseminated to the kidneys and the spleen. The model we established provides an opportunity to study immune responses to and therapeutic options for CNS disease in an immunologically defined, genetically manipulable, and inexpensive species.
AuthorsTom M Chiller, Javier Capilla Luque, Raymond A Sobel, Kouros Farrokhshad, Karl V Clemons, David A Stevens
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 186 Issue 4 Pg. 574-7 (Aug 15 2002) ISSN: 0022-1899 [Print] United States
PMID12195389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Immunosuppressive Agents
  • Cyclophosphamide
Topics
  • Animals
  • Aspergillus fumigatus (pathogenicity)
  • Brain (microbiology, pathology)
  • Brain Abscess
  • Brain Diseases (microbiology, pathology)
  • Cyclophosphamide (administration & dosage)
  • Disease Models, Animal
  • Humans
  • Immunosuppression Therapy
  • Immunosuppressive Agents (administration & dosage)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Neuroaspergillosis (microbiology, pathology)

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