Sleep apnea pathophysiology

Abstract

Objective: The purpose of this study is to examine the pathophysiology underlying sleep apnea (SA).

Background: We consider several critical features of SA including the roles played by the ascending reticular activating system (ARAS) that controls vegetative functions and electroencephalographic findings associated with both SA and normal sleep. We evaluate this knowledge together with our current understanding of the anatomy, histology, and physiology of the mesencephalic trigeminal nucleus (MTN) and mechanisms that contribute directly to normal and disordered sleep. MTN neurons express γ-aminobutyric acid (GABA) receptors which activate them (make chlorine come out of the cells) and that can be activated by GABA released from the hypothalamic preoptic area.

Method: We reviewed the published literature focused on sleep apnea (SA) reported in Google Scholar, Scopus, and PubMed databases.

Results: The MTN neurons respond to the hypothalamic GABA release by releasing glutamate that activates neurons in the ARAS. Based on these findings, we conclude that a dysfunctional MTN may be incapable of activating neurons in the ARAS, notably those in the parabrachial nucleus, and that this will ultimately lead to SA. Despite its name, obstructive sleep apnea (OSA) is not caused by an airway obstruction that prevents breathing.

Conclusions: While obstruction may contribute to the overall pathology, the primary factor involved in this scenario is the lack of neurotransmitters.

Keywords: Ascending reticular activating system; Cyclic alternating pattern; Mesencephalic trigeminal nucleus; Parabrachial nucleus; Sleep apnea.

Fig. 1

Neurons in the POA release GABA to inhibit neurons in ARAS nuclei. GABA from POA activates MTN

Fig. 2

Relationship between LC and MTN

Fig.3

Baseline EEG tracing during NREM sleep

Fig. 4

A cyclic alternating pattern (CAP) was observed on EEG during NREM sleep

Fig. 5

Modulation of EEG responses based on respiratory events. Respiratory events are as indicated within the boxes, including (from left to right) hypopnea, apnea, hypopnea, apnea, and hypopnea. The apneic episodes appeared exclusively during the inhibitory B-phase of NREM sleep and concluded at the beginning of the A-phase of the CAP. Resumption of breathing is always signaled by conversion to an A-phase pattern [24, 32, 33]