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Brain stem localization of vagal preganglionic neurons.

The central distribution of vagal preganglionic neurons has been examined using the retrograde transport of horseradish peroxidase (HRP). In 27 adult cats, the entire vagus nerve was exposed to HRP. In 13 other cats we examined the brain stem following microinjections of HRP (10 microliter) into individual visceral organs - lung, heart and stomach. Comparison of individual cases led to the conclusion that different patterns exist for each visceral organ. The preganglionic (parasympathetic) innervation of the entire vagus nerve arises from the dorsal motor nucleus of the vagus (dmnX), nucleus ambiguus (nA), nucleus retroambigualis (nRA), nucleus dorso-medialis (ndm), spinal nucleus of the accessory (nspA) and from the reticular formation between the dmnX and nA. Axons arising from the nA do not traverse the medulla laterally; rather they are initially directed dorso-medially toward the dmnX where they bend at right angles and accompany axons of neurons in the dmnX. The motor nuclei innervating the lungs, heart and stomach are dmnX, the nA and nRA: the dmnX contributes fibers to the heart, lungs and stomach from a region of 10 mm of medulla rostrocaudally; the nA contributes efferents to the 3 viscera studied from the entire 6 mm contributing vagal efferents; the nRA contributes efferents to the stomach in addition to providing innervation to the larynx and trachea (see 19). The area postrema (ap) receives afferent input from the lungs, heart and stomach, as indicated by extraperikaryal grains of HRP reaction product resulting from transganglionically transported HRP (through the ganglion nodosum). Sensory terminal labeling in the various subnuclei of the nucleus of the tractus solitarius (nTS) was also examined and it was found that no specific region of the medulla is devoted to receiving input from any one visceral organ; rather the rostro-caudal extent of vagal afferent terminals in the medulla spans the entire length of the medulla. Differences between the central representation of different viscera seemed to lie within the organization of the nuclear subgroups of the nTS.

Afferent Pathways↗

Trigeminal autonomic cephalgias (TACs).

The concept of a group of headaches whose pathophysiological focus revolves around the trigeminal-autonomic reflex fills a useful gap in characterising a number of primary headache syndromes. Broadly, these syndromes involve activation of trigeminovascular nociceptive pathways with reflex cranial autonomic activation. Clinically, this physiology predicts pain with some combination of lacrimation, conjunctival injection, nasal congestion, or eyelid oedema. Several of the primary neurovascular headaches, notably cluster headache, paroxysmal hemicrania and short-lasting neuralgiform pain with conjunctival injection and tearing (SUNCT), seem to immediately fit this classification. This physiology also explains why some patients with migraine present cranial autonomic features, and the concept is thus broadly useful for clinicians seeking a pathophysiological understanding of the primary neurovascular headaches. Given the known pathophysiology one can place the various treatments aimed at preventing these headaches or indeed treating the acute attacks, into context.

Autonomic Nervous System Diseases↗

Influence of the autonomic nervous system on calcium homeostasis in the rat.

The local surgical manipulation of sympathetic and parasympathetic nerves innervating the thyroid-parathyroid territory was employed to search for the existence of a peripheral neuroendocrine link controlling parathyroid hormone (PTH) and calcitonin (CT) release. From 8 to 24 h after superior cervical ganglionectomy (SCGx), at the time of wallerian degeneration of thyroid-parathyroid sympathetic nerve terminals, an alpha-adrenergic inhibition, together with a minor beta-adrenergic stimulation, of hypercalcemia-induced CT release, and an alpha-adrenoceptor inhibition of hypocalcemia-induced PTH release were found. In chronically SCGx rats PTH response to EDTA was slower, and after CaCl2 injection, serum calcium attained higher levels in face of normal CT levels. SCGx blocked the PTH increase found in sham-operated rats stressed by a subcutaneous injection of turpentine oil, but did not affect the greater response to EDTA. The higher hypocalcemia seen after turpentine oil was no longer observed in SCGx rats. The effects of turpentine oil stress on calcium and CT responses to a bolus injection of CaCl2 persisted in rats subjected to SCGx 14 days earlier. Interruption of thyroid-parathyroid parasympathetic input conveyed by the thyroid nerves (TN) and the inferior laryngeal nerves (ILN) caused a fall in total serum calcium, an increase of PTH levels and a decrease of CT levels, when measured 10 days after surgery. Greater responses of serum CT and PTH were detected in TN-sectioned, and in TN- or ILN-sectioned rats, respectively. Physiological concentrations of CT decreased, and those of PTH increased, in vitro cholinergic activity in rat SCG, measured as specific choline uptake, and acetylcholine synthesis and release. The results indicate that cervical autonomic nerves constitute a pathway through which the brain modulates calcium homeostasis.

Animals↗

Organization of the efferent projections from the pontine parabrachial area to the bed nucleus of the stria terminalis and neighboring regions: a PHA-L study in the rat.

The organization of efferent projections from the pontine parabrachial (pPB) area to the forebrain rostral to the central nucleus of the amygdala (Ce) was studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin (PHA-L), into subregions of the pPB area. The present study is a follow-up of a former study (Bernard et al. [1993] J. Comp. Neurol. 329:201-229) which examines pPB projections onto the Ce. The results demonstrate that: (1) the pPB(m) region (the medial, the ventral lateral subnuclei and the waist area) diffusely projects to the lateral division (BSTL) of the bed nucleus of the stria terminalis (BST), the Ce-BSTL continuum (including, the dorsal portion of substantia innominata, the ventral portion of globus pallidus, the fundus striatum, and the substriatal area) and to a lesser extent the agranular insular cortex; (2) the pPB(1) region [the central lateral (pPBcl) and the outer portion of external lateral subnuclei] densely projects to the dorsal lateral subnucleus of BST (BSTdl); only the pPBcl subnucleus projects to the median, the anteroventral and the periventricular nuclei of the preoptic hypothalamus; and (3) the remaining pPB area (the dorsal lateral, part of the external lateral and the external medial subnuclei) projects to the nucleus of horizontal limb of diagonal band but does not project onto the BST and the preoptic hypothalamus. It is suggested that the pPB(m)-BSTL "diffuse pathway" is mainly implicated in motivational and autonomic aspects of taste. The pPB(1)-BSTdl and hypothalamic "concentrated pathways" could be implicated in autonomic and nociceptive processes.

Amygdala↗

Central control of the cardiovascular and erection systems: possible mechanisms and interactions.

Sexual activity is accompanied by vascular changes mediated by parasympathetic and sympathetic outflow to the peripheral organs. The brain stem and spinal cord contain the neurons that innervate the cardiovascular system and the penis. Heart rate and blood pressure increase, suggesting a decrease of the cranial parasympathetic outflow and an increase of the activity of sympathetic efferent pathways. In contrast, penile erection occurs in response to increased activity of the sacral parasympathetic innervation and a decreased activity of sympathetic pathways. A modulation of the balance between sympathetic and parasympathetic activities may result from an adaptation of an intraspinal network that (1) would be the recipient of peripheral and supraspinal information; and (2) would coordinate the activity of the different efferent pathways. A variety of nuclei in the medulla, pons, and hypothalamus contain premotor neurons that exert an influence on brain stem and spinal autonomic motoneurons. These descending pathways release amines (noradrenaline, adrenaline, serotonin, dopamine) and peptides. A fine tuning of brain stem and spinal activity is made possible by the great variety of receptor subtypes through which these neuromediators act. More recently, the role of nitric oxide, synthesized and released by different cell populations, has been evaluated in the brain and spinal control of the cardiovascular system and penile erection. Depending on its central neural target, nitric oxide may either activate or inhibit the cardiovascular system. In contrast, its role on the central control of penile erection is only excitatory.

Animals↗

Importance of imidazoline receptors in the cardiovascular responses to clonidine and rilmenidine in conscious rabbits.

The present paper summarizes our studies concerning the involvement of imidazoline and alpha 2-adrenoceptors in the cardiovascular actions of centrally acting drugs rilmenidine, clonidine and methyldopa. We have found that they produce very similar cardiovascular autonomic effects which relate directly to the function of central monoamine neurotransmitters. They mimic certain elements of the noradrenergic neuron system in the central nervous system, in particular the brainstem actions which involve hypotension, bradycardia and resetting of the baroreceptor heart rate reflex. By contrast they turn off serotonergic pathways that are pressor, produce tachycardia and inhibit the baroreceptor heart rate reflex. Recent studies using specific receptors antagonist drugs idazoxan and 2-methoxy-idazoxan indicate that in conscious rabbits the imidazoline receptor actions of rilmenidine is of primary importance at doses which would be considered clinically relevant. We further conclude that the alpha 2-adrenoceptors and the imidazoline receptors are likely to be located in series i.e. along the same cardiovascular autonomic pathways in the brainstem but presumably at different sites.

Adrenergic alpha-Agonists↗

Glutamatergic neural transmission in the nucleus tractus solitarius: N-methyl-D-aspartate receptors.

1. The nucleus tractus solitarius (NTS) is the first central site where the reflex control of autonomic, including baroreceptor, reflex function is coordinated. Autonomic signals are transmitted from the first-order visceral afferent fibres to second-order NTS neurons by L-glutamate. It is well established that activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptors, which mediate the fast component of L-glutamate signalling, is required for generating changes in membrane potentials of the second-order NTS neurons. The contribution of the slower-developing, longer-lasting N-methyl-D-aspartate (NMDA) receptor-mediated component of glutamate signalling to synaptic transmission at these synapses is less well understood. 2. The aim of this work is to highlight evidence that functional NMDA receptors exist on second-order NTS neurons in autonomic, including baroreceptor, afferent pathways by determining whether NMDA receptors can be activated by: (i) exogenous application of NMDA; and (ii) endogenous release of L-glutamate from autonomic afferent fibres. Studies were performed on second-order neurons in transverse and horizontal brainstem slices containing the intermediate NTS and the tractus solitarius. Second-order NTS neurons were identified by electrophysiological criteria or by attached fluorescent-labelled aortic depressor nerve (ADN) boutons. 3. N-Methyl-D-aspartate (50 nmol(-2) micromol) dose-dependently evoked excitatory post-synaptic currents in second-order NTS neurons (P = 0.004; n = 4). The NMDA receptor-mediated currents were also synaptically evoked by low-frequency stimulation of the autonomic afferent fibres in the tractus solitarius. The NMDA receptor-mediated currents were blocked by the NMDA receptor antagonist AP5 (n = 7; P = 0.027). 4. The findings suggest that functional NMDA receptors exist on second-order NTS neurons. While the NMDA receptor- mediated currents may not be required for signal transmission when the second-order neurons are at resting membrane potential, their activation may help to modulate autonomic signal transmission in the NTS under conditions in which the membrane is depolarized by high frequency or convergent inputs.

Animals↗

Autonomic afferents at T1 in elicitation of volume-induced tachycardia in the dog.

Intravenous infusion of blood elicited tachycardia in anesthetized dogs with beta-receptor blockade (dogs with vagal efferents intact but cardiac sympathetic efferents blocked) and bradycardia in dogs with combined beta-receptor blockade and rhizotomy at T1 (dogs with vagal efferents intact but cardiac sympathetic efferents plus autonomic afferents at T1 blocked). This suggests that tachycardia elicited by volume in infusion may be partly due to a reflex with its afferent pathway at the T1 segment of the spinal cord and its efferent pathway in the vagi. Moreover, infusion evoked bradycardia in dogs with right-sided rhizotomy at T1, which was not significantly different from the response elicited in dogs with bilateral rhizotomy at T1. Additionally, the tachycardia response induced in dogs with ventral or dorsal rhizotomy at T1 was significantly different from the bradycardia response elicited in dogs with both dorsal and ventral rhizotomy at T1. These results suggest that the afferent pathway predominates on the right side, and its entry at T1 may be via both dorsal and ventral roots.

Afferent Pathways↗

Alternating sequence of retrograde atrial activation in patients with dual AV nodal physiology.

Patients with dual AV nodal physiology have been demonstrated to have earliest retrograde activation sequence of the fast pathway in the lower septal right atrium and slow pathway in the proximal coronary sinus, and the posterior atrial septum. This case report describes a patient with dual AV nodal physiology demonstrating a dual sequence of retrograde activation with 2:1 block occurring in the fast pathway causing the conduction to proceed alternately via fast then slow pathway. This sequence was abolished by atropine allowing conduction to proceed via fast pathway. Surgical cure of patients with reentrant AV nodal tachycardia suggests the presence of two anatomically distinct AV nodal-like pathways. This case report confirms this observation and further suggests preferential autonomic modulation of the fast pathway.

Adult↗

The autonomic nervous system is not a purely efferent system.

The concept of the autonomic nervous system as purely efferent does not seem to describe satisfactorily the patterns of its actions and mobilizing mechanisms. It is herein suggested that the autonomic nervous system should be rather considered as composed of functional modules comprising the visceral afferents, the integrating centers and the visceral efferents (sympathetic and parasympathetic).

Afferent Pathways↗

Atrioventricular node properties in patients with accessory pathways.

A study during the era of surgical ablation suggested that atrioventricular (AV) nodal conduction is faster in patients with accessory pathways than in controls. In the present study, AV nodal characteristics were studied in 30 patients who underwent radiofrequency ablation of an accessory pathway and compared to 23 control patients. Sinus cycle length, AH and HV intervals, AV block cycle length, ventriculoatrial (VA) block cycle length, AV nodal effective refractory period, and VA effective refractory periods were measured in control and postablation accessory pathway patients before and after autonomic blockade with 0.04 mg/kg of atropine and 0.2 mg/kg of propranolol. The mean sinus cycle length in the control and accessory pathway groups did not differ significantly at baseline (798 +/- 211 and 766 +/- 156 msec, respectively) or after autonomic blockade (654 +/- 98 and 649 +/- 108 msec, respectively). The mean AH interval in the accessory pathway group (77 +/- 15 msec) was significantly shorter than in the control group (91 +/- 22 msec; p < 0.05) at baseline; however, there was no difference after autonomic blockade. No other significant differences were observed between the accessory pathway and control groups. These results demonstrate that AV nodal properties of patients with accessory pathways are not significantly different from controls and suggest that previously reported differences may have been due to selection bias.

Adult↗

[Treatment and prophylaxis for cluster headaches and other trigeminal autonomic headaches. Revised recommendations of the German Migraine and Headache Society].

Following the new IHS classification, cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT syndrome) are included in the classification as trigeminal autonomic cephalgias (TAC). The similarities of these syndromes suggest a considerable shared pathophysiology. These syndromes have in common that they involve activation of trigeminovascular nociceptive pathways with reflex cranial autonomic activation. Clinically, this physiology predicts pain with some combination of lacrimation, conjunctival injection, nasal congestion, or eyelid edema. Broadly the management of TAC comprises acute and prophylactic treatment. Some types of trigeminal autonomic headaches such as paroxysmal hemicrania and hemicrania continua have, unlike cluster headaches, a very robust response to indomethacin, leading to a consideration of indomethacin-sensitive headaches. This review covers the clinical picture and therapeutic options. Although studies following the criteria of evidence-based medicine (EBM) are rare, most patients can be treated sufficiently.

Analgesics↗

Effects of dopaminergic antagonist and agonist on thermoregulation in rabbits.

1. The effects of dopaminergic antagonist haloperidol and agonist apomorphine on the thermoregulatory responses of unanaesthetized rabbits to different ambient temperatures (Ta) of 2, 22 and 32 degrees C were assessed. 2. I.V. administration of haloperidol produced dose-dependent hypothermia at 2 and 22 degrees C Ta. At 2 degrees C Ta the hypothermia was due to a decrease in metabolic heat production. At 22 degrees C Ta the hypothermia was brought about by a decrease in metabolism and an increase in ear blood flow. However at 32 degrees C Ta, there was an increase in rectal temperature in response to haloperidol application; this hyperthermia was due to a decrease in both the ear blood flow and respiratory evaporative heat loss (Eres). 3. I.V. administration of apomorphine produced dose-dependent hyperthermia at all the ambient temperatures studied. At 2 degrees C Ta the hyperthermia was due to an increase in metabolism. At both 22 and 32 degrees C, the hyperthermia was brought about by an increase in metabolic heat production and a decrease in ear blood flow. Also, there was an increase in Eres in response to apomorphine at 22 degrees C Ta. 4. The data, in general, indicate that dopamine agonist activates all effector pathways which modulate the autonomic processes of thermoregulation (i.e. respiratory heat loss, peripheral vasomotor tone and metabolism), and that the dopamine antagonist inhibits the activity in all three effector pathways. Such a clear pattern of results is readily expressible in terms of the 'Bligh' model dealing with the aminergic mechanisms of temperature regulation.

Animals↗

The anatomy of the visceral and autonomic nervous systems.

The visceral nervous system has several levels of anatomical organization. Individual viscera, including the heart and the intestines, have neural tissue embedded in their walls that is capable, under some circumstances, of a truly autonomic self-regulation of that organ's activity. This self-regulation will not respond to all the varying needs of the organ control, particularly when external or internal changes affect the whole animal. The parasympathetic, sympathetic, and visceral afferent systems and their CNS connections are the next level of reflex neural organization. A greater degree of central regulation is managed at this level. The third level of visceral control is located in the brainstem and includes the hypothalamus, parts of the reticular formation, and cardiorespiratory centers in the medulla. These visceral upper neuron centers exert a high degree of control over the parasympathetic and sympathetic LMN centers of the brainstem and spinal cord. The reticulobulbar and reticulospinal pathways are the means by which the visceral upper motor neurons communicate with the LMN systems. The hypothalamus-hypophyseal system exerts control by releasing hormones to act on distant target organs. The highest level of organization of visceral function takes place in the limbic system. The limbic system is in a position to integrate sensory information originating from both within (interoceptive) and outside (exteroceptive) the animal. Associations are made at this level and with the help of cortical association areas, memory is integrated with these sensations. The limbic system is then able to influence the hypothalamic and medullary centers as well as the somatic motor centers to develop the appropriate responses for the preservation of the animal.

Afferent Pathways↗

Studies of electrical activity of the peripheral components of the autonomic nervous system in chronic experiments.

The review presented here deals chiefly with the construction of 'contact' and 'penetrating' electrodes used for implantation and recording from nerves of the autonomic nervous system. The major concern was the design of the capsules in which the electrodes were mounted and the nerve was placed. The details of how afferent and efferent discharges were separated from the total impulse flow are presented. Towards this end the technique of local reversible cooling of the nerve trunk was applied. Consideration was given to the problem of exteriorizing electrode leads and cooling device tubes and fixing them on the animal's body surface. Mention is made of the possible uses of these devices for recording visceral reactions.

Afferent Pathways↗

Cancer, a disease of defective glucose metabolism.

The cancer cell appears to contain two non phosphorylating glycolytic pathways in addition to phosphorylating glycolysis and the aerobic citric acid and phosphogluconate cycles. It is hypothesised that these pathways are all interconnected and in the static adult cell non phosphorylating glycolysis is in a state of controlled inactivity. Cancer occurs when one or both non phosphorylating glycolytic pathways escape from control thereby producing an autonomous flow of energy and mitosis. Both pathways appear dependent upon glutathione to convert glucose to lactic acid. The pathways can be differentiated by their responses to ionising and 434MHz non ionising radiation, hyperthermia and biochemical environmental changes in vivo.

Cell Transformation, Neoplastic↗