Direct current stimulation as a non-invasive therapeutic alternative for treating autonomic or non-autonomic neurological disorders affecting breathing.

Direct current stimulation (DCS) is a non-invasive approach to stimulate the nervous system that is now considered a powerful tool for treating neurological diseases such as those affecting cognitive or locomotor functions. DCS, as applied clinically today, is an approach built on early uses in antiquity and knowledge gained over time. Its current use makes use of specific devices and takes into account knowledge of the mechanisms by which this approach modulates functioning of the nervous system at the cellular level.

Key Brainstem Structures Activated during Hypoxic Exposure in One-day-old Mice Highlight Characteristics for Modeling Breathing Network in Premature Infants.

We mapped and characterized changes in the activity of brainstem cell groups under hypoxia in one-day-old newborn mice, an animal model in which the central nervous system at birth is particularly immature. The classical biphasic respiratory response characterized by transient hyperventilation, followed by severe ventilation decline, was associated with increased c-FOS immunoreactivity in brainstem cell groups: the nucleus of the solitary tract, ventral reticular nucleus of the medulla, retrotrapezoid/parafacial region, parapyramidal group, nucleus, lateral, and medial parabrachial nucleus, and dorsal subcoeruleus nucleus. In contrast, the hypoglossal nucleus displayed decreased c-FOS immunoreactivity.

The c-FOS Protein Immunohistological Detection: A Useful Tool As a Marker of Central Pathways Involved in Specific Physiological Responses In Vivo and Ex Vivo.

Many studies seek to identify and map the brain regions involved in specific physiological regulations. The proto-oncogene c-fos, an immediate early gene, is expressed in neurons in response to various stimuli. The protein product can be readily detected with immunohistochemical techniques leading to the use of c-FOS detection to map groups of neurons that display changes in their activity.

Desogestrel enhances ventilation in ondine patients: Animal data involving serotoninergic systems.

Congenital central hypoventilation syndrome (CCHS) is a neurorespiratory disease characterized by life-threatening sleep-related hypoventilation involving an alteration of CO2/H(+) chemosensitivity. Incidental findings have suggested that desogestrel may allow recovery of the ventilatory response to CO2. The effects of desogestrel on resting ventilation have not been reported.

Apelin counteracts vasopressin-induced water reabsorption via cross talk between apelin and vasopressin receptor signaling pathways in the rat collecting duct.

Apelin receptors (ApelinRs) are expressed along an increasing cortico-medullary gradient in collecting ducts (CDs). We showed here that iv injection of apelin 17 (K17F) in lactating rats characterized by increases in both synthesis and release of arginine vasopressin (AVP) increased diuresis concomitantly with a significant decrease in urine osmolality and no change in Na(+) and K(+) excretion. Under these conditions, we also observed a significant decrease in apical aquaporin-2 immunolabeling in CD, with a cortico-medullary gradient, suggesting that K17F-induced diuresis could be linked to a direct action of apelin on CD.

The kreisler mutation leads to the loss of intrinsically hypoxia-activated spots in the region of the retrotrapezoid nucleus/parafacial respiratory group.

Acute hypoxia elicits a biphasic respiratory response characterized in the newborn by a transient hyperventilation followed by a severe decrease in respiratory drive known as hypoxic respiratory depression. Medullary O(2) chemosensitivity is known to contribute to respiratory depression induced by hypoxia, although precise involvement of cell populations remains to be determined. Having a thorough knowledge of these populations is of relevance because perturbations in the respiratory response to hypoxia may participate in respiratory diseases in newborns.

Data supporting a new physiological role for brain apelin in the regulation of hypothalamic oxytocin neurons in lactating rats.

Apelin is a bioactive peptide identified as the endogenous ligand of the human orphan G protein-coupled receptor APJ in 1998. The present data show that apelin modulates the activity of magnocellular and parvocellular oxytocin (OXY) neurons in the lactating rat. A combination of in situ hybridization and immunohistochemistry demonstrated the presence of apelin receptor mRNA in hypothalamic OXY neurons.

Effect of apelin on glomerular hemodynamic function in the rat kidney.

Apelin is a vasoactive peptide identified as the endogenous ligand of an orphan G protein-coupled receptor called APJ. Apelin and its receptor have been found in the brain and the cardiovascular system. Here we show that the apelin receptor mRNA is highly expressed in the glomeruli while its level of expression is lower in all nephron segments including collecting ducts that express vasopressin V2 receptors.

Orally active aminopeptidase A inhibitors reduce blood pressure: a new strategy for treating hypertension.

Overactivity of the brain renin-angiotensin system has been implicated in the development and maintenance of hypertension. We reported previously that angiotensin II is converted to angiotensin III by aminopeptidase A in the mouse brain. We then used specific and selective aminopeptidase A inhibitors to show that angiotensin III is one of the main effector peptides of the brain renin-angiotensin system, exerting tonic stimulatory control over blood pressure in hypertensive rats.

Aminopeptidase A inhibitors as centrally acting antihypertensive agents.

Among the main bioactive peptides of the brain renin-angiotensin system, angiotensin (Ang) II and AngIII exhibit the same affinity for the type 1 and type 2 Ang receptors. Both peptides, injected intracerebroventricularly, cause similar increase in blood pressure (BP). Because AngII is converted in vivo to AngIII, the identity of the true effector is unknown.

Hypoxia-sensing properties of the newborn rat ventral medullary surface in vitro.

The ventral medullary surface (VMS) is a region known to exert a respiratory stimulant effect during hypercapnia. Several studies have suggested its involvement in the central inhibition of respiratory rhythm caused by hypoxia. We studied brainstem-spinal cord preparations isolated from newborn rats transiently superfused with a very low O(2) medium, causing reversible respiratory depression, to characterize the participation of the VMS in hypoxic respiratory adaptation.

Effect of postnatal exposure to caffeine on the pattern of adenosine A1 receptor distribution in respiration-related nuclei of the rat brainstem.

Caffeine, which belongs to the methylxantine family of compounds, is commonly ingested in a range of beverages such as coffee, tea, and cola drinks. It is also used therapeutically and is frequently employed in the treatment of respiratory disturbances in human neonates. The aim of the present work has been to examine the ontogeny of the adenosine A1 receptor system in the brainstem of the newborn rat following postnatal treatment with caffeine to mimic the therapeutic administration of caffeine to premature human infants.

Caffeine in the milk prevents respiratory disorders caused by in utero caffeine exposure in rats.

Consequences of postnatal caffeine exposure by the milk on ponto-medullary respiratory disturbances observed following an in utero caffeine exposure were analysed. Ponto-medullary-spinal cord preparations from newborn rats exposed to caffeine during gestation but not after the birth display an increase in respiratory frequency and an exaggeration of the hypoxic respiratory depression compared to not treated preparations. These data suggest that tachypneic and apneic episodes encountered in human newborns whose mother consumed caffeine during pregnancy are due in large part to central effect of caffeine at the ponto-medullary level.

Diencephalic and mesencephalic influences on ponto-medullary respiratory control in normoxic and hypoxic conditions: an in vitro study on central nervous system preparations from newborn rat.

We investigated the effects of the diencephalon and mesencephalon on the central respiratory drive originating from ponto-medullary regions in normoxic and hypoxic conditions, using central nervous system preparations from newborn rats. We used two approaches: 1) electrophysiological analysis of respiratory frequency and the amplitude of inspiratory C4 activity and 2) immunohistochemical detection of Fos protein, an activity-dependent neuronal marker. We found that, in normoxic conditions, the mesencephalon moderated respiratory frequency, probably by means of an inhibitory effect on ventral medullary respiratory neurons.

Involvement of adenosinergic A1 systems in the occurrence of respiratory perturbations encountered in newborns following an in utero caffeine exposure. a study on brainstem-spinal cord preparations isolated from newborn rats.

Involvement of adenosinergic A1 systems in the occurrence of respiratory perturbations encountered in newborns following an in utero caffeine exposure has been investigated on pontomedullary-spinal cord, caudal pons-medullary-spinal cord and medullary-spinal cord preparations isolated from newborn rats. According to the drinking fluid of dams (tap water or 0.02% caffeine), two groups of preparations were distinguished, no-caffeine and caffeine.

Endogenous 5-HT(1/2) systems and the newborn rat respiratory control. A comparative in vivo and in vitro study.

Consequences of 5-HT(1/2) systems blockade by methysergide on newborn rats respiratory drive were evaluated in vivo with unrestrained animals and in vitro using brainstem-spinal cord preparations. A decrease in respiratory frequency until a plateau level was observed under both in vivo (82.8 +/- 0.

Consequences of in utero caffeine exposure on respiratory output in normoxic and hypoxic conditions and related changes of Fos expression: a study on brainstem-spinal cord preparations isolated from newborn rats.

Several aspects of the central regulation of respiratory control have been investigated on brainstem-spinal cord preparations isolated from newborn rats whose dam was given 0.02% caffeine in water as drinking fluid during the whole period of pregnancy. Analysis of the central respiratory drive estimated by the recording of C4 ventral root activity was correlated to Fos ponto-medullary expression.

Fos study of ponto-medullary areas involved in the in vitro hypoxic respiratory depression.

In this study, the brainstem-spinal cord preparation isolated from newborn rats, an established model for the study of the hypoxic respiratory depression (HRD), has been used. The comparison of Fos expression in ponto-medullary areas in these preparations placed either in normoxic or hypoxic conditions suggests that only the retrotrapezoid nucleus (RTN) and the ventrolateral medulla (VLM) are involved in the in vitro HRD. Hypoxic preparations exhibit a Fos expression enhanced in the RTN, suggesting that the RTN might play a crucial role in the HRD.

5-HT acting on 5-HT(1/2) receptors does not participate in the in vitro hypoxic respiratory depression.

The involvement of serotoninergic mechanisms in the central respiratory depression produced by hypoxia was studied in the newborn rat brainstem-spinal cord preparation. The respiratory frequency measured by the C4 ventral root activity was recorded. 5-HT (30 microM) superfusion elicited a rapid increase in respiratory frequency, prevented by a treatment with methysergide (a 5-HT(1/2) receptor antagonist) (40 microM).

Effect of hypoxia on the activity of respiratory and non-respiratory modulated retrotrapezoid neurons of the cat.

The retrotrapezoid nucleus (RTN), a part of the rostral ventrolateral medulla, is involved in the control of breathing. A recent immunohistological study suggested a possible involvement of the RTN in hypoxic chemoreflex loop. The present electrophysiological study performed in the cat demonstrates that 23 out of 24 RTN neurons were stimulated during the biphasic respiratory response to hypoxia, which consists of a reinforcement followed by a depression of respiratory activity.

Possible role of retrotrapezoid nucleus and parapyramidal area in the respiratory response to anoxia: an in vitro study in neonatal rat.

The brainstem-spinal cord preparation from neonatal rat has been used in several reports to evaluate the central effect of low oxygen level on the respiratory network. We demonstrate that bilateral lesion of retrotrapezoid nucleus and parapyramidal area unmasks an early reinforcement of the respiratory output in response to anoxia. This suggests that neurons in both areas might trigger or relay a central depressive influence of hypoxia on the respiratory network.

Connections between retrotrapezoid nucleus and nucleus tractus solitarii in cat.

The retrotrapezoid nucleus (RTN), a part of the rostral ventrolateral medulla, is involved in the control of breathing. The mechanisms by which the RTN modulate the activity of respiratory neurons during chemoreceptor stimulation are not fully understood. This electrophysiological study performed in the cat demonstrates that 18 out of 22 RTN neurons receive inputs from the commissural subnucleus of the solitary tract (cNTS), the peripheral chemoreceptor afferents projection site.

Efferent projection from the rostral ventrolateral medulla to the area postrema in rats.

The rostral ventrolateral medulla (RVLM) is a region of the brain primarily involved in cardiovascular control. It receives information from several areas of the brainstem, among which the area postrema (AP) and the nucleus of the solitary tract (NTS). The medial subnuclei of the solitary tract (TS) project towards the RVLM, providing cardiopulmonary information, and the AP serves information about circulatory hormones.

Potent inhibition of both the acute and delayed emetic responses to cisplatin in piglets treated with GR205171, a novel highly selective tachykinin NK1 receptor antagonist.

The effects of GR205171, a selective tachykinin NK1 receptor antagonist, were investigated on both the acute and delayed phases of cisplatin-induced nausea-like behaviour and vomiting in the conscious piglet. Animals receiving cisplatin (5.5 mg kg(-1), i.