About this Research Topic
Respiratory control entails coordinated activities of chemoreceptors (peripheral and/or central) and central respiratory network within the brain stem. Peripheral chemoreceptors (mainly c-fiber terminals and carotid bodies), through afferent nerve as well as nodose/jugular ganglia neurons, connect with the central respiratory nuclei, forming the reflex activities, such as cough, tachypnea, bradypnea, or apnea, et al. An important function of these activities, which react to chemical stimulants or the level of arterial pCO2 and/or pO2, is to protect respiratory system and further to maintain normal breathing. However, the chemoreflex could be remolded in many infected diseases or non-infected respiratory challenges. One of the most common remodeling is hypersensitivity, which may occur in any part/s of chemoreflex pathway according to different stimulus (acute or chronic) and/or stimulants (chemical or pathogen). The changes occurred in the hypersensitivity process are considered including protein and gene expression reregulating, neuropeptide synthesis altering, and the function of specific chemical receptors varying, et al. However, it is not clear the details of these changes, such as the changes in subtype of receptors, the interaction between neuropeptide and chemical receptors, as well as the specific gene related with this, et al. Thus, it is necessary to elucidate some important questions in chemoreflex research as following:
1. It is important to clarify fully the chemoreflex pathway. Even it has known that most second order neurons located in nucleus tractus solitaries (NTS), and pre-Bötzinger complex (PBC) or retrotrapezoid nucleus (RTN) should be as a central respiratory center, more details are still needed on the chemoreflex pathway. It is necessary to know where the accurate locations of second, third or more order neurons are, what subtype of chemical receptors are involved in a specific pathway, and how they cooperated as a network to emit a reflex activity.
2. The location of central chemoreceptors is another interesting issue. Peripheral chemoreceptors are not only one to react to the stimulus, and the central chemoreceptors are also play an important role in the chemoreflex. For example, it is known that carotid body is a sensor for hypoxia reflex, but after carotid body denervation, the hypoxia reflexes still exist after short time surgery recovery. Some candidates for central chemoreceptors, such as Phox2b-containing neurons of RTN, serotonergic neurons of the medullary raphé, has classified, but they are not all and chemoreceptor neurons existed in multiple sites within the brain stem are unknown.
3. Chemoreflex hypersensitivity is one of important plasticity in respiratory nerve system, which usually happened in chronic respiratory challenges or diseases. In these situations, repeated peripheral chemoreceptor input mediated by the nucleus of the solitary tract induces plastic changes in respiratory circuits that alter respiratory reaction and sympathetic motor outputs, resulting in chemoreflex sensitization. But how it has happened and what changes involved in are needed to be clarified.
The elucidations of these issues not only are important for respiratory research but also benefit to the therapy and prognosis of respiratory diseases.
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