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Murine model of eosinophilic chronic rhinosinusitis with nasal polyposis inducing neuroinflammation and olfactory dysfunction - 05/08/24

Doi : 10.1016/j.jaci.2024.02.021 
Wei-Hao Huang, MS a, Yu-Wen Hung, PhD b, Wei Hung, MD a, c, Ming-Ying Lan, MD, PhD a, c, Chien-Fu Yeh, MD, PhD a, c,
a Department of Otorhinolaryngology–Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan 
b Department of Nursing, College of Medical Technology and Nursing, Yuanpei University of Medical Technology, Hsinchu, Taiwan 
c Department of Otorhinolaryngology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan 

Corresponding author: Chien-Fu Yeh, MD, PhD, Department of Otorhinolaryngology–Head and Neck Surgery, Taipei Veterans General Hospital, No. 201, Sec 2, Shipai Rd, Beitou District, Taipei City, 11217, Taiwan.Department of Otorhinolaryngology–Head and Neck SurgeryTaipei Veterans General HospitalNo. 201Sec 2Shipai RdBeitou DistrictTaipei City11217Taiwan

Graphical abstract




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Abstract

Background

Chronic rhinosinusitis (CRS) is a common inflammatory condition affecting the nasal and paranasal sinus mucosa, often accompanied by olfactory dysfunction. Eosinophilic CRS with nasal polyps (ECRSwNP) is a subtype of CRS characterized by eosinophilic infiltration. Animal models for ECRSwNP with olfactory dysfunction are necessary for exploring potential therapeutic strategies.

Objective

The aim of this study was to establish a mouse model of ECRSwNP combined with olfactory dysfunction in a shorter time frame using intranasal ovalbumin and Aspergillus protease (AP) administration. The efficacy of the model was validated by evaluating sinonasal inflammation, cytokine levels, olfactory function, and neuroinflammation in the olfactory bulb.

Methods

Male BALB/c mice were intranasally administered ovalbumin and AP for 6 and 12 weeks to induce ECRSwNP. The resultant ECRSwNP mouse model underwent histologic assessment, cytokine analysis of nasal lavage fluid, olfactory behavioral tests, and gene expression profiling to identify neuroinflammatory markers within the olfactory bulb.

Results

The developed mouse model exhibited substantial eosinophil infiltration, increased levels of inflammatory cytokines in nasal lavage fluid, and confirmed olfactory dysfunction through behavioral assays. Furthermore, olfactory bulb inflammation and reduced mature olfactory sensory neurons were observed in the model.

Conclusion

This study successfully established a validated mouse model of ECRSwNP with olfactory dysfunction within a remarkably short span of 6 weeks, providing a valuable tool for investigating the pathogenesis and potential therapies for this condition. The model offers an efficient approach for future research in CRS with nasal polyps and olfactory dysfunction.

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Key words : Eosinophilic chronic rhinosinusitis, nasal polyp, olfactory dysfunction, neuroinflammation, mouse model, olfactory sensory neuron

Abbreviations used : AC3, AP, BMK-13, CRS, CRSwNP, ECRS, ECRSwNP, Iba1, MCP-1, MPO, NP, OMP, OVA, SEB


Mappa


 The first 3 authors contributed equally to this article, and all should be considered first author.


© 2024  American Academy of Allergy, Asthma & Immunology. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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Vol 154 - N° 2

P. 325 - Agosto 2024 Ritorno al numero
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