Chemoafferent degeneration and carotid body hypoplasia following chronic hyperoxia in newborn rats

Abstract

To define the role of environmental oxygen in regulating postnatal maturation of the carotid body afferent pathway, light and electron microscopic methods were used to compare chemoafferent neurone survival and carotid body development in newborn rats reared from birth in normoxia (21 % O2) or chronic hyperoxia (60 % O2). Four weeks of chronic hyperoxia resulted in a significant 41 % decrease in the number of unmyelinated axons in the carotid sinus nerve, compared with age‐matched normoxic controls. In contrast, the number of myelinated axons was unaffected by hyperoxic exposure. Chemoafferent neurones, located in the glossopharyngeal petrosal ganglion, already exhibited degenerative changes following 1 week of hyperoxia from birth, indicating that even a relatively short hyperoxic exposure was sufficient to derange normal chemoafferent development. In contrast, no such changes were observed in the vagal nodose ganglion, demonstrating that the effect of high oxygen levels was specific to sensory neurones in the carotid body afferent pathway. Moreover, petrosal ganglion neurones were sensitive to hyperoxic exposure only during the early postnatal period. Chemoafferent degeneration in chronically hyperoxic animals was accompanied by marked hypoplasia of the carotid body. In view of previous findings from our laboratory that chemoafferent neurones require trophic support from the carotid body for survival after birth, we propose that chemoafferent degeneration following chronic hyperoxia is due specifically to the loss of target tissue in the carotid body.

Invited Review: Neuroplasticity in respiratory motor control

“…The functional impairment is not due to alterations in pulmonary mechanics or gas exchange (135) or changes in the central integration of carotid chemoafferent inputs (62,134). Rather, carotid chemoreceptor development is impaired because the carotid bodies are hypoplastic (47,66), the number of chemoafferent neurons in the carotid sinus nerve is reduced (47), and carotid sinus nerve afferent responses to cyanide, asphyxia, and hypoxia are reduced (20,62,133). The sensitive developmental period for these changes is within the first 2 postnatal wk (15).…”

The Effect of Hyperoxia on Reactive Oxygen Species (ROS) in Rat Petrosal Ganglion Neurons During Development Using Organotypic Slices

“…Hyperoxic exposure in newborn rat pups is cytotoxic to peripheral arterial chemoreceptors as evidenced by hypoplasia of the carotid body and a 41% reduction in the number of chemoafferent neurons (8). The mechanisms leading to cytotoxic changes in the carotid body and the reduction in chemoreflexes after hyperoxicexposure during early postnatal development are unknown.…”

Long-term effects of the perinatal environment on respiratory control

“…Phrenic nerve responses to electrical stimulation of the carotid sinus nerve are virtually identical between hyperoxia-treated and control rats (33,57), suggesting that central integration of chemoafferent inputs is not impaired. On the other hand, normal phrenic responses to carotid sinus nerve stimulation are somewhat surprising because the number of chemoafferent neurons stimulated is reduced in hyperoxia-treated rats (29). Although this finding could reflect technical limitations of the approach, it may indicate that central neural integration of carotid chemoafferent activity is actually enhanced in adult rats raised in hyperoxia.…”

“…Given the enduring nature of developmental plasticity, structural changes are likely to be involved in many cases. For example, as described above, perinatal hyperoxia (29,109) and neonatal CIH (86) are associated with hypoplasia in the peripheral nervous system and CNS, respectively. The perinatal period is characterized by high rates of synaptogenesis, cellular proliferation, and apoptosis in structures associated with respiratory control (e.g., 104,109,115); these processes generally occur during narrow developmental windows, thereby defining potential critical periods for plasticity.…”

“…Hyperoxia-treated rats develop smaller carotid bodies with fewer O 2 -sensitive (type I) cells and fewer neurons in the carotid sinus nerve (CSN) to carry afferent information to the brain stem (14,29,81). Carotid body hypoplasia appears to result from a failure of the carotid body to grow during the hyperoxic exposure rather than death of existing cells (109, S. E. Piro, E. K. Dmitrieff, and R. W. Bavis, unpublished observations); chemoafferent neuron degeneration may be secondary to the carotid body hypoplasia (29,47). Fewer type I cells and primary afferent neurons likely explain much of the reduction in HVR, but hyperoxia may also impair the O 2 sensitivity of the surviving cells.…”