66. Evidence for neuroplastic changes in the brainstem following TH2 lung inflammation: A role for the central nervous system in contributing to the symptoms of asthma and investigating a potential target for therapy

Abstract

Inflammatory events in the lung, such as atopic asthma, induce changes in neuronal activity of afferent airway vagal fibres and neurons in the brainstem, as well as changes in cough, anxiety and depression. Here, we investigated the effect of acute and chronic Th2 lung inflammation on behaviour an expression of neuroplasticity and inflammatory genes in the brainstem. Allergic lung inflammation was induced using the well-established Ovalbumin (OVA) model of asthma. Open field activity and the elevated plus maze were used to asses behavioural changes; brainstem tissue including the nucleus of the solitary tract was collected for analysis of gene expression; bronchial lavage fluid (BALF) and serum was collected for cytokine measurement. We found increased levels of serum and BALF IL-5 and IL-4 and increased numbers of eosinophils, confirming robust Th2 mediated inflammation. Despite this, we did not find significant changes in open field or anxiety behaviour nor in central inflammatory gene expression. In contrast, significant increases were found in the expression of c-fos, as well as a subset of glutamate and neurotrophin receptors in the brainstem, changes most pronounced following chronic lung inflammation. Our results show that robust, lung inflammation does not result in behavioural changes, despite evidence of immune-to-brain communication. We are currently investigating if immunomodulation of lung inflammation with TLR agonists induces changes in behaviour and central neuronal and inflammatory gene expression.