Related Experiment Videos
Development of a murine model of cerebral aspergillosis
Tom M Chiller1, Javier Capilla Luque, Raymond A Sobel
1Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, California, USA.
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.
Insights
Researchers developed a new mouse model for studying invasive fungal infections of the central nervous system (CNS). This model uses immunosuppressed mice and shows consistent mortality, enabling further research into CNS aspergillosis treatments.
Area of Science:
- Mycology
- Infectious Diseases
- Neuroscience
Background:
- Central nervous system (CNS) Aspergillus infection is nearly fatal in humans.
- A lack of suitable animal models hinders research into CNS aspergillosis.
- Existing studies in non-immunosuppressed mice yielded inconsistent results.
Purpose of the Study:
- To develop a reliable murine model for studying CNS aspergillosis.
- To establish a platform for investigating immune responses and therapeutic strategies.
Main Methods:
- Intracranial injection of Aspergillus fumigatus conidia into mice.
- Use of cyclophosphamide to induce immunosuppression in CD-1 mice.
- Dose-finding studies to determine lethal fungal load (5 x 10^6 conidia/mouse).
- Histological examination of brain tissue and assessment of fungal dissemination.
Main Results:
- Immunosuppressed CD-1 mice infected with A. fumigatus showed 100% mortality between days 5-8.
- Histology revealed focal abscesses with Aspergillus hyphae in the brain.
- Higher fungal burden was observed in the brain compared to other organs, with dissemination to kidneys and spleen.
Conclusions:
- A reproducible murine model for CNS aspergillosis has been established.
- This model allows for the study of immune responses in an immunologically defined and genetically manipulable host.
- The model is suitable for evaluating potential therapeutic interventions for CNS fungal infections.