Several animal models of human asthma have been developed in an attempt to induce the pathology and pathophysiology seen in human conditions. Charles River Discovery Research Services (DRS) offers the Brown Norway lung inflammation model, an established allergen-dependent, pharmacokinetic/ pharmacodynamic asthma model that can be used to investigate the basic pathology of asthma disease and assess the in vivo efficacy of antiasthma drugs. This asthma model features many similarities to human allergic asthma, including the presence of eosinophilic lung inflammation, damage to the airway epithelium, thickening of the basement membrane, acute and late-phase airflow obstruction and the presence of airway hyperresponsiveness after the antigen challenge.
In recent studies, Charles River evaluated the time course of inflammation following antigen sensitization and challenge in the Brown Norway rat and evaluated the effect of glucocorticoids in this model. Total and differential cell counts of inflammatory cells in the lung were performed on the bronchoalveolar lavage (BAL) fluid at various time points to observe the time course of inflammation and evaluate the effects of compounds at 24 or 48 hours post-challenge. Ovalbumin sensitization and challenge resulted in an acute pulmonary neutrophilia and later-phase eosinophilia. Pretreatment with betamethasone, at 0.03, 0.3 and 3 mg/kg 2 hours prior to ovalbumin challenge, resulted in a dose-dependent decrease in neutrophils at 24 hours following dosing and attaining >80% inhibition at 3.0 mg/kg, while a single dose of betamethasone at 3 mg/kg resulted in >80% inhibition of eosinophil accumulation at 48 hours post-challenge.
Neutrophil and Eosinophil Inflammation Time
Course
Effects of Bethamethasone on Neutrophil and
Eosinophil Accumulation at 24 Hours Post
Ovalbumin Challenge
Effects of Bethamethasone on Neutrophil and
Eosinophil Accumulation at 48 Hours Post
Ovalbumin Challenge
Additional services that can be combined with this asthma model include cytokine profiling, histopathologic evaluations and assessments of airway hyperresponsiveness (e.g., Penh assessments in conscious animals or anesthetized assessments of resistance and compliance).
For more information about our asthma model, please contact us at 1.877.CRIVER.1 or askcharlesriver@crl.com.