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A novel model of invasive fungal rhinosinusitis in rats
Fang Zhang1, Yunfang An, Zeqing Li
1Department of Otorhinolaryngology-Head and Neck Surgery, Second Hospital of Shanxi Medical University, Taiyuan, China.
Background:
Invasive fungal rhinosinusitis (IFRS) is a life-threatening inflammatory disease that affects immunocompromised patients, but animal models of the disease are scarce. This study aimed to develop an IFRS model in neutropenic rats.
Methods:
The model was established in three consecutive steps: unilateral nasal obstruction with Merocel sponges, followed by administration of cyclophosphamide (CPA), and, finally, nasal inoculation with Aspergillus fumigatus. Fifty healthy Wistar rats were randomly divided into five groups, with group I as the controls, group II undergoing unilateral nasal obstruction alone, group III undergoing nasal obstruction with fungal inoculation, group IV undergoing nasal obstruction with administration of CPA, and group V undergoing nasal obstruction with administration of CPA and fungal inoculation. Hematology, histology, and mycology investigations were performed.
Results:
The changes in the rat absolute neutrophil counts (ANCs) were statistically different across the groups. The administration of CPA decreased the ANCs, whereas nasal obstruction with fungal inoculation increased the ANCs, and nasal obstruction did not change them. Histological examination of the rats in group V revealed the hyphal invasion of sinus mucosa and bone, thrombosis, and tissue infarction. No pathology indicative of IFRS was observed in the remaining groups. Positive rates of fungal culture in tissue homogenates from the maxillary sinus (62.5%) and lung (25%) were found in group V, whereas groups I, II, III, and IV showed no fungal culture in the homogenates.
Conclusion:
A rat IFRS model was successfully developed through nasal obstruction, CPA-induced neutropenia, and fungal inoculation. The disease model closely mimics the pathophysiology of anthropic IFRS.
Insights
Researchers developed a new animal model for invasive fungal rhinosinusitis (IFRS) in neutropenic rats. This model, using nasal obstruction, cyclophosphamide, and Aspergillus fumigatus, accurately replicates human IFRS.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Animal Models
Background:
- Invasive fungal rhinosinusitis (IFRS) is a severe condition primarily affecting immunocompromised individuals.
- A scarcity of reliable animal models hinders research into IFRS pathogenesis and treatment.
- This study addresses the need for a robust preclinical model of IFRS.
Purpose of the Study:
- To establish a novel animal model for invasive fungal rhinosinusitis (IFRS) in neutropenic rats.
- To mimic the key pathological features of human IFRS in a preclinical setting.
Main Methods:
- A three-step protocol involving unilateral nasal obstruction, cyclophosphamide (CPA)-induced neutropenia, and Aspergillus fumigatus inoculation was employed.
- Wistar rats were divided into five groups, including controls and groups with varying combinations of obstruction, CPA, and fungal inoculation.
- Hematological, histological, and mycological analyses were conducted to assess disease development.
Main Results:
- Cyclophosphamide significantly reduced absolute neutrophil counts (ANCs), confirming neutropenia.
- Group V rats (obstruction, CPA, and fungal inoculation) exhibited hyphal invasion, thrombosis, and tissue infarction, characteristic of IFRS.
- Histopathology and positive fungal cultures (62.5% in maxillary sinus, 25% in lung) were exclusively observed in Group V, validating the model.
Conclusions:
- A reproducible rat model for invasive fungal rhinosinusitis was successfully developed.
- The model effectively recapitulates the pathophysiology of human IFRS, offering a valuable tool for future research.
