Direct vagus nerve stimulation: A new tool to control allergic airway inflammation through α7 nicotinic acetylcholine receptor.

Background And Purpose: Asthma is characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. The use of nicotinic agents to mimic the cholinergic anti-inflammatory pathway (CAP) controls experimental asthma. Yet, the effects of vagus nerve stimulation (VNS)-induced CAP on allergic inflammation remain unknown.

Higher baseline heart rate variability in CCHS patients with progestin-associated recovery of hypercapnic ventilatory response.

After a fortuitous observation of two cases of chemosensitivity recovery in women with congenital central hypoventilation syndrome (CCHS) who took desogestrel, we aimed to evaluate the ventilatory response to hypercapnia of five CCHS patients with or without treatment consisting of desogestrel (DESO) or levonorgestrel (LEVO). Only two patients became responsive to hypercapnia under treatment, according to their basal vagal heart rate variability. These results suggest that heart rate variability may be promising tool to discriminate patients susceptible to become responsive to hypercapnia under DESO-LEVO treatment.

Heart rate variability and slow-paced breathing:when coherence meets resonance.

Clinical research on the beneficial effects induced by slow-paced breathing has been increasingly extended in the past twenty years. Improvements in cardiovascular functioning, executive functions, or stress management appear to be among the most prominent observations in these studies. However, the mechanisms underlying these effects are multiple and complex.

Experience from five Asia-Pacific countries during the first wave of the COVID-19 pandemic: Mitigation strategies and epidemiology outcomes.

Background: With no vaccines or specific treatments, non-pharmaceutical interventions are the only tools for controlling the human-to-human transmission of the COVID-19 disease, which appeared in Wuhan, China last December and has spread globally since. Here we describe and compare the first-wave mitigation strategies and epidemiology of five Asia-Pacific countries that responded rapidly to the epidemic.

Methods: From January to April 2020, mitigation measures and epidemiological data for Singapore, South Korea, Japan, Taiwan, Hong Kong were screened from official local government websites and a review of investigational studies was conducted.

Rostral cuneiform nucleus and the defence reaction: Direct and indirect midbrain-medullary 5-HT mechanisms in baroreflex inhibition.

Background And Purpose: Activation of the defence reaction inhibits the baroreflex response via the intermediate rostro-ventromedial medulla (B3 raphé) and nucleus tractus solitarius (NTS). Our aim was to determine whether and how baroreflex inhibition, induced by the disinhibition of the rostral cuneiform nucleus (part of the defence pathway), involves 5-HT neurons in B3 and 5-HT receptors in the NTS.

Experimental Approach: We performed immunohistochemistry and anatomical experiments to determine whether raphé 5-HT cells expressing Fos were directly targeted by the rostral cuneiform nucleus.

Social defeat: Vagal reduction and vulnerability to ventricular arrhythmias.

Previously, a sub-population of defeated anesthetized rats (Dlow) was characterized by persistent low blood levels of brain-derived neurotrophic factor (BDNF) at day 29 and autonomic alteration at day 30 after social challenge, while the other population (Dhigh) was similar to non-defeated (ND) animals. The aims of this study were to determine the time-course of autonomic dysfunction in awake animals, and whether Dhigh and/or Dlow were vulnerable to cardiac events. Defeated animals were exposed to four daily episodes of social defeats from day 1 to day 4.

Combined Treatment with Peptide-Conjugated Phosphorodiamidate Morpholino Oligomer-PPMO and AAV-U7 Rescues the Severe DMD Phenotype in Mice.

Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease caused by an absence of the dystrophin protein, which is essential for muscle fiber integrity. Among the developed therapeutic strategies for DMD, the exon-skipping approach corrects the frameshift and partially restores dystrophin expression. It could be achieved through the use of antisense sequences, such as peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) or the small nuclear RNA-U7 carried by an adeno-associated virus (AAV) vector.

Vulnerability to stress consequences induced by repeated social defeat in rats: Contribution of the angiotensin II type 1 receptor in cardiovascular alterations associated to low brain derived neurotrophic factor.

After social stress, rats become vulnerable to depression, and this state is characterized by persistent low blood levels of brain-derived neurotrophic factor (BDNF). The aim of this study was to determine whether low BDNF levels are associated with long term autonomic changes. Defeated animals were subjected to four daily episodes of social defeats.

A hypothalamo-midbrain-medullary pathway involved in the inhibition of the respiratory chemoreflex response induced by potassium cyanide in rodents.

Recent studies have demonstrated that a mild stimulation of the dorsomedian nucleus of the hypothalamus (DMH), a defense area, induces the inhibition of the carotid chemoreflex tachypnea. DMH activation reduces the cardiac chemoreflex response via the dorsolateral part of the periaqueductal grey matter (dlPAG) and serotonin receptors (5-HT subtype) in the nucleus tractus solitarius (NTS). The objectives of this study were to assess whether dlPAG and subsequent NTS 5-HT receptors are involved in chemoreflex tachypnea inhibition during mild activation of the DMH.

Experimental dyspnea as a stressor: differential cardiovegetative responses to inspiratory threshold loading in healthy men and women.

Dyspnea is associated with an emotional reaction that involves limbic activation. The inspiratory threshold load (ITL) is known to elicit a dyspneic response in healthy subjects. Laboratory-induced stress conditions have been shown to elicit sex-related differences in cardiovascular responses.

Long-lasting bradypnea induced by repeated social defeat.

Repeated social defeat in the rat induces long-lasting cardiovascular changes associated with anxiety. In this study, we investigated the effects of repeated social defeat on breathing. Respiratory rate was extracted from the respiratory sinus arrhythmia (RSA) peak frequency of the ECG in rats subjected to social defeat for 4 consecutive days.

Key role of 5-HT receptors in the nucleus tractus solitarii in cardiovagal stress reactivity.

Serotonin plays a modulatory role in central control of the autonomic nervous system (ANS). The nucleus tractus solitarii (NTS) in the medulla is an area of viscerosomatic integration innervated by both central and peripheral serotonergic fibers. Influences from different origins therefore trigger the release of serotonin into the NTS and exert multiple influences on the ANS.

Respiratory chemoreflex response inhibition by dorsomedian hypothalamic nucleus activation in rats.

Recent observations from our group seem to indicate that repeated stress-evoked dorsomedian hypothalamic nucleus (DMH) activation in rats can lead to persistent bradypnea. One possibility was that respiratory responses to peripheral chemoreceptor activation were reduced by DMH stimulation. In the present study, we therefore investigated the effect of minimal supra-threshold DMH stimulation on respiratory carotid chemoreflex responses.

Respiratory sinus arrhythmia as a surrogate measure of respiratory frequency: validity and robustness to activity in rats.

Recording of breathing frequency is a basic requirement for respiratory physiology. Usual techniques are invasive and constraining. Respiratory sinus arrhythmia (RSA) has recently been demonstrated to be a simple way to obtain respiration frequency at rest.

Involvement of the dorsomedial hypothalamus and the nucleus tractus solitarii in chronic cardiovascular changes associated with anxiety in rats.

Anxiety disorders in humans reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). Both may contribute to sudden death. To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions on four consecutive days.

Noxious stimulation excites serotonergic neurons: a comparison between the lateral paragigantocellular reticular and the raphe magnus nuclei.

The present study was designed to record electrophysiological responses to graded noxious thermal stimuli of serotonergic and nonserotonergic neurons in the lateral paragigantocellular reticular (LPGi) and the raphe magnus (RMg) nuclei in rats. All of the neurons recorded were juxtacellularly filled with neurobiotin and identified with double immunofluorescent labeling for both neurobiotin and serotonin. Under halothane anesthesia (0.

Brain circuits mediating baroreflex bradycardia inhibition in rats: an anatomical and functional link between the cuneiform nucleus and the periaqueductal grey.

Defence responses triggered experimentally in rats by stimulation of the dorsomedial nucleus of the hypothalamus (DMH) and the dorsolateral periaqueductal grey matter (PAG) inhibit the cardiac baroreflex response (i.e. bradycardia).

Inhibition of cardiac baroreflex by noxious thermal stimuli: a key role for lateral paragigantocellular serotonergic cells.

The present study was designed to identify the neuronal mechanisms causing cardiac baroreflex inhibition associated with thermal nociception in rats. Under urethane-anesthesia, noxious thermal stimuli > or = 48 degrees C were found to inhibit the cardiac baroreflex, whereas noxious stimuli < or = 46 degrees C had no effect. Using double immunohistochemical labeling, noxious stimuli > or = 48 degrees C were found to evoke primarily a strong expression of Fos protein (Fos) encoded by c-fos gene in serotonergic neurons of lateral paragigantocellular reticular nucleus (LPGi).

Inhibition of the bradycardic component of the von Bezold-Jarisch reflex and carotid chemoreceptor reflex by periaqueductal gray stimulation: involvement of medullary receptors.

Stimulation of the dorsolateral periaqueductal gray matter (dlPAG) and the B3 cell group inhibits the cardiovagal component of the baroreflex in rats. Our aim was to determine whether the defence reaction induces similar modulatory effects on the cardiac response of the von Bezold-Jarisch reflex and the carotid chemoreceptor reflex. We examined the effects of dlPAG stimulation on the reflex bradycardia triggered by systemic administration of phenylbiguanide or potassium cyanide.

Critical role of B3 serotonergic cells in baroreflex inhibition during the defense reaction triggered by dorsal periaqueductal gray stimulation.

The present study was designed to identify the serotonergic pathway causing baroreflex inhibition associated with the defense reaction in rats. Under conditions that produce physiological responses typical of the defense reaction, electrical stimulation of the dorsal periaqueductal gray (dPAG) was found to double c-Fos immunoreactive serotonergic neurons within the mid-rostrocaudal extent of the B3 group (which comprises the raphe magnus and the lateral paragigantocellular reticular nuclei) in anesthetized rats. Local blockade of neuronal activity by microinjection of muscimol (a GABA(A) receptor agonist) directly into the B3 region prevented the inhibitory effect of dPAG activation on the cardiac baroreflex.

5-HT-mediated inhibition of cardiovagal baroreceptor reflex response during defense reaction in the rat.

Previous studies showed that the cardiac response of the baroreceptor reflex (bradycardia) is inhibited during the defense reaction evoked by direct electrical or chemical stimulation of the periaqueductal gray (dPAG) in the rat. Whether central serotonin and nucleus tractus solitarius (NTS) serotonin(3) (5-HT(3)) receptors might participate in this inhibition was investigated in urethane-anesthetized and atenolol-pretreated rats. Our results showed that both electrical and chemical stimulation of the dPAG produced a drastic reduction of the cardiovagal component of the baroreceptor reflex triggered by either intravenous administration of phenylephrine or aortic nerve stimulation.

Antinociceptive effect of cardiopulmonary chemoreceptor and baroreceptor reflex activation in the rat.

The effect on the nociceptive tail-flick (TF) reflex of cardiopulmonary chemoreceptor and arterial baroreceptor activation, producing Bezold-Jarisch like- and baro-reflex responses, respectively, was analysed in lightly halothane-anaesthetized rats. Intra-cardiac administration of phenylbiguanide (5-100 microg/kg, into the right atrium) or veratrine (30-150 microg/kg, into the left ventricle), which both elicited the characteristic Bezold-Jarisch-like cardiovascular reflex responses (hypotension and bradycardia), produced a dose-dependent increase in TF latency. A similar inhibitory influence on the TF reflex was noted upon baroreflex activation by acute administration of phenylephrine (15-50 microg/kg i.

Glutamate and NO mediation of the pressor response to 5-HT3 receptor stimulation in the nucleus tractus solitarii.

The possible participation of glutamate and NO/cGMP in the pressor response to 5-HT3 receptor activation in the nucleus tractus solitarii (NTS) was investigated using selective antagonists in urethane-anaesthetized rats. Intra-NTS administration of NMDA and non-NMDA receptor antagonists, but not metabotropic glutamate receptor antagonists, markedly reduced (70%) the increase in blood pressure caused by local application of the potent 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide. The 5-HT3 receptor-mediated pressor response was also significantly attenuated by the local blockade of nitric oxide synthase and soluble guanylyl cyclase.