The Effect of Hyperoxia on Reactive Oxygen Species (ROS) in Petrosal and Nodose Ganglion Neurons during Development (Using Organotypic Slices)

Abstract

Peripheral arterial chemoreceptors, within the carotid body (CB), are critical in maintaining respiratory and cardiac hemostasis by uniquely sensing changes in O2 tension. The components of the peripheral arterial chemoreceptors are found within the CB, but the physiologic effects of activation of these located in the bifurcation of the carotid artery and consists of three major neuronal components that include: 1) type I chemosensory cells, also known as glomus cells, which contain neurotransmitters and autoreceptors; 2) type II cells, which are similar to supportive glial cells; and 3) chemoafferent nerve fibers from the carotid sinus nerve, a branch of the IX cranial nerve, with cell bodies in the petrosal ganglion (PG) (Verna 1997). Numerous studies, in several mammalian models, support a role for peripheral arterial chemoreceptors in contributing to stable ventilation at a critical period of development during early postnatal life, which establishes rhythmogenesis that is sustained throughout life (for review, Gauda et al. 2004; Carroll 2003). Chronic hyperoxia, during early postnatal development (PND), depresses ventilatory responses to subsequent acute hypoxia in newborn animals and in premature infants (Ling et al., 1997; Ling et al., 1997). Furthermore, histological evidence suggests that hyperoxia is cytotoxic to the CB and its associated chemoafferent neurons (Erickson et al. 1998). In other model systems, hyperoxia is associated with increased production of reactive oxygen species (ROS), including superoxide (O2-), hydroxyl radical (OHx), and 22 between intracellular oxidants and antioxidants is disturbed, ROS contribute to cellular damage via lipid peroxidation, enzyme inactivation, and protein and nucleic acid oxidation, resulting in apoptosis or necrosis. We hypothesize that hyperoxia leads to an increased production of ROS and subsequent cytotoxic response in PG neurons.