Effects of inflammation on the developing respiratory system: Focus on hypoglossal (XII) neuron morphology, brainstem neurochemistry, and control of breathing

Breathing is fundamental to life and any adverse change in respiratory function can endanger the health of an organism or even be fatal. Perinatal inflammation is known to adversely affect breathing in preterm babies, but lung infection/inflammation impacts all stages of life from birth to death. Little is known about the role of inflammation in respiratory control, neuronal morphology, or neural function during development. Animal models of inflammation can provide understanding and insight into respiratory development and how inflammatory processes alter developmental phenotype in addition to providing insight into new treatment modalities. In this review, we focus on recent work concerning the development of neurons, models of perinatal inflammation with an emphasis on two common LPS-based models, inflammation and its impact on development, and current and potential treatments for inflammation within the respiratory control circuitry of the mammalian brainstem. We have also discussed models of inflammation in adults and have specifically focused on hypoglossal motoneurons (XII) and neurons of the nucleus tractus solitarii (nTS) as these nuclei have been studied more extensively than other brainstem nuclei participating in breathing and airway control. Understanding the impact of inflammation on the developmental aspects of respiratory control and breathing pattern is critical to addressing problems of cardiorespiratory dysregulation in disease and this overview points out many gaps in our current knowledge.