ABSTRACT
Hypoglossal motor neurons (HMNs) innervate tongue muscles and play key roles in a variety of physiological functions, including swallowing, mastication, suckling, vocalization, and respiration. Dysfunction of HMNs is associated with several diseases, such as obstructive sleep apnea (OSA) and sudden infant death syndrome. OSA is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states. Identifying the neural mechanisms by which the state-dependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA. However, the presynaptic partners governing the activity of HMNs remain to be elucidated. In the present study, we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice. We identified 53 nuclei targeting HMNs from six brain regions: the amygdala, hypothalamus, midbrain, pons, medulla, and cerebellum. We discovered that GABAergic neurons in the central amygdaloid nucleus, as well as calretinin neurons in the parasubthalamic nucleus, sent monosynaptic projections to HMNs. In addition, HMNs received direct inputs from several regions associated with respiration, such as the pre-Botzinger complex, parabrachial nucleus, nucleus of the solitary tract, and hypothalamus. Some regions engaged in sleep-wake regulation (the parafacial zone, parabrachial nucleus, ventral medulla, sublaterodorsal tegmental nucleus, dorsal raphe nucleus, periaqueductal gray, and hypothalamus) also provided primary inputs to HMNs. These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.
ABSTRACT
<p><b>BACKGROUND</b>Noninvasive positive pressure ventilation (NIPPV) has been proposed to shorten the duration of mechanical ventilation in intubated patients, especially those who fail initial weaning from invasive mechanical ventilation (IMV). However, there are also some discrepancies in terms of weaning success or failure, incidence of re-intubation, complications observed during study and patient outcomes. The primary objective of this update was to specifically investigate the role of NIPPV on facilitating weaning and avoiding re-intubation in patients intubated for different etiologies of acute respiratory failure, by comparing with conventional invasive weaning approach.</p><p><b>METHODS</b>We searched randomized controlled trials (RCTs) comparing noninvasive weaning of early extubation and immediate application of NIPPV with invasive weaning in intubated patients from PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Knowledge and Springerlink databases. Records from conference proceedings and reference lists of relevant studies were also identified.</p><p><b>RESULTS</b>A total of 11 RCTs with 623 patients were available for the present analysis. Compared with IMV, NIPPV significantly increased weaning success rates (odds ratio (OR): 2.50, 95% confidence interval (CI): 1.46 - 4.30, P = 0.0009), decreased mortality (OR: 0.39, 95%CI: 0.20 - 0.75, P = 0.005), and reduced the incidence of ventilator associated pneumonia (VAP) (OR: 0.17, 95%CI: 0.08 - 0.37, P < 0.00001) and complications (OR: 0.22, 95%CI: 0.07 - 0.72, P = 0.01). However, effect of NIPPV on re-intubation did not reach statistical difference (OR: 0.61, 95%CI: 0.33 - 1.11, P = 0.11).</p><p><b>CONCLUSIONS</b>Early extubation and immediate application of NIPPV is superior to conventional invasive weaning approach in increasing weaning success rates, decreasing the risk of mortality and reducing the incidence of VAP and complications, in patients who need weaning from IMV. However, it should be applied with caution, as there is insufficient beneficial evidence to definitely recommend it in terms of avoiding re-intubation.</p>