Nervous Network Research Articles

Neurovascular Proximity in the Diaphragm Muscle of Adult Mice

Regional blood flow to the diaphragm muscle varies with the workload of inspiration. To provide anatomical insight into coupling between muscle fiber recruitment and oxygen supply, we tested whether arterioles are physically associated with motor nerve branches of the diaphragm. Following vascular casting, intact diaphragm muscles of C57BL/6 and CD-1 mice were stained for motor innervation. Arteriolar networks and nerve networks were mapped (~2 μm resolution) to evaluate their physical proximity. Neurovascular proximity was similar between muscle regions and mouse strains. Of total mapped nerve lengths (C57BL/6, 70 ± 15 mm; CD-1, 87 ± 13 mm), 80 ± 14% and 67 ± 10% were ≤250 μm from the nearest arteriole and associated predominantly with arterioles ≤45 μm in diameter. Distances to the nearest arteriole encompassing 50% of total nerve length (D(50)) were consistently within 200 μm. With nerve networks repositioned randomly within muscle borders, D(50) values nearly doubled (p < 0.05). Reference lines within anatomical boundaries reduced proximity to arterioles (p < 0.05) as they deviated from the original location of motor nerves. Across two strains of mice, motor nerves and arterioles of the diaphragm muscle are more closely associated than can be explained by chance. We hypothesize that neurovascular proximity facilitates local perfusion upon muscle fiber recruitment.

Can simple rules control the development of central nervous networks generating behaviour in response to sensory stimulation?

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Late-onset, insidious course and invasive treatment of congenital central hypoventilation syndrome in a case with the Phox2B mutation: case report

Congenital central hypoventilation syndrome (CCHS) is a rare disorder of respiratory control characterized by ventilatory impairment that results in arterial hypoxemia. This condition is worse during sleep and occurs in patients with normal mechanical properties of the lung. It is diagnosed in the absence of primary neuromuscular disease, identifiable brainstem lesions, and other sleep disturbances or substance use [1]. Amiel et al. [2] identified a mutation in the Phox2B gene associated with CCHS, characterized by five to nine alanine expansions within a 20-residue polyalanine region in exon 3 of the Phox2B gene. Several reports confirmed the findings of Amiel et al., supporting the view that this gene is a master switch for the development of the autonomic nervous system network linked to respiratory control [3–6]. Transgenic animals carrying the human Phox2B mutation develop a similar phenotype and lack glutamatergic neurons located in the parafacial region in the brainstem, which are involved in breathing control [7]. Although patients typically present with CCHS as newborns and rarely in later infancy, there have been reports of patients presenting with CCHS in adulthood. In cases of late-onset CCHS, most patients report having had some symptoms since childhood, and they have parents with a history of CCHS. Symptoms of right-sided heart failure are generally observed at the time of diagnosis, and nocturnal noninvasive ventilation is frequently indicated [8–15]. L. R. A. Bittencourt (*) :M. Pedrazzoli : F. Yagihara : G. P. Luz : S. Garbuio :G. A. Moreira : S. Tufik Disciplina de Medicina e Biologia do Sono, Departamento de Psicobiologia, Universidade Federal de Sao Paulo, Rua Napoleao de Barros, 925, 04024-002 Sao Paulo, Sao Paulo, Brazil e-mail: lia@psicobio.epm.br

Physiological basis of food intolerance in VLBW

To provide an overview on the role of gut immunity, nervous system and motility patterns in the development of feeding intolerance in newborns. Maturation of the GI is important not only for digestion and absorption, but for endocrine and exocrine function as well. There is little data available about the development of the motility function and of the mucosal barrier of the human gut, and in particular about the motility patterns and mucosal changes in newborns during early days of life. It is known that functional maturation of the gastrointestinal tract is quite different over time with respect to its anatomical development. Besides, the gastrointestinal tract through innate and specific immunologic factors, acts as a defense against ingested antigens. In addition to the mucous membrane integrity and digestion, numerous specific immunologic cells and mediators orchestrate such defensive mechanisms. In case of food antigens, the outcome is usually in favor of tolerance. Defects in that barrier, however, can lead to the development of aberrant immunologic responses, including hypersensitivity reactions. It is obvious that an appropriate feeding regimen during early infancy is in favor of food tolerance. However, in addition to genetic predisposition, development of tolerance is facilitated by an adequate gut barrier (immune or nonimmune), well-coordinated GI motility and nervous network, and appropriate food regimen.

Functional Coordination of Motor Activity in Colonic Smooth Muscles in Rat Experimental Model

Spontaneous and electrically-elicited motor activity was recorded by triple organ bath in rat segment-model preparation as display of excitation of local nerve networks and ascending or descending reflex pathways underlying contractile potency and functional coordination of colonic longitudinal and circular muscles. Spontaneous high-amplitude contractions, but not relaxations, appeared synchronously in both muscles. Electrical field stimulation applied to proximal or distal part of segments elicited both tetrodotoxin (0.1 microM)-sensitive local motor responses of the stimulated part and ascending or descending motor responses of the contralateral, nonstimulated part of the preparations. Contractions characterized the local response of longitudinal muscle. The circular muscle responded with relaxation followed by contraction. Synchronous ascending contractions and descending contraction of the longitudinal muscle and relaxation followed by contraction of the circular muscle were observed when the middle part of segments was stimulated, thus indicating that locally-induced nerve excitation propagated via intrinsic ascending or descending nerve pathways that could be synchronously coactivated by one and the same stimulus. The ascending motor responses were more pronounced and the motor responses of longitudinal muscle were expressed more than those of circular muscle suggesting an essential role of ascending reflex pathways and longitudinal muscle in the coordinated motor activity of colon.

Somatic vigilance: An unrecognized cause of orthostatic intolerance

Background: Visceral sensations are relayed to the brain through a network of afferent nerves. Awareness of these sensations differs among individuals, likely due to different thresholds and CNS processing characteristics. Differences in the conscious awareness of bodily sensations may explain specific cardiovascular phenotypes. Thus, our goal was to evaluate the role, if any, of conscious awareness of body sensations and their relationship with hemodynamic responses to tilt in patients with orthostatic intolerance.

L’essor des sciences du neurone au xxe siècle

A great revolution in the field of neuroscience started in the 1940s and took place after the Second World War. Before the War, the fundamental questions at stake dealt with the nature of neurotransmission, chemical or electrical. The first turning point occurred in the distinguished field of neurophysiology, where a better understanding of neuronal electrogenesis and fine dissections of nervous networks followed the introduction of the new intracellular recording technique. This technique is associated with biophysics, electron microscopy and ultracentrifugation. Consequently, the chemical theory of neurotransmission is uniformly adopted with the emergence of the quantal theory and the vesicular theory. There is a new opportunity for the discovery of neurotransmitters with the help of biochemical methods. Noradrenergic and aminergic paths are described with novel histological techniques, whereas electrophysiology is used to find their functions. All disciplines work together in the study of the synaptic organisations of nerve centres and local inhibition phenomena. Neuronal sciences adopt neuropharmacology to create a novel neurochemistry. New dissection procedures, morphological network tracing tools and surgical techniques offer novel ways of intervention and manipulation. These innovations of the 1950s and 1960s are central in building a new international community unified by the American neuroscience movement.

Modular and functionally-different descending recto-anal motor pathways in a rat model

Abstract We evaluated the motor responses in recto-anal preparations obtained from rats, in terms of the excitation displayed by modules of nerve networks and descending distally directed pathways, when subjected to the mechanographic on-line technique, a partitioned organ bath, electrical stimulation (EFS, 0.8 ms, 5 Hz) and distension. EFS elicited modular contractions, which increased in amplitude distally, in circular muscle rings isolated from the proximal, middle or distal rectum. The modular responses of the internal anal sphincter or anal canal were relaxation or contraction, respectively. The application of EFS to the distal rectum induced a descending contractile response in the anal canal (5.24±0.34 mN), while distension by balloon evoked a descending response consisting of contraction (1.72±0.20 mN) followed by relaxation (3.42±0.24 mN). The responses were sensitive to tetrodotoxin. Atropine considerably depressed the contractions in all preparations. Whether or not atropine was present, L-NNA increased the excitatory responses, while L-arginine decreased the contractions and extended the relaxation of internal anal sphincter and anal canal. The results suggest that excitatory neurotransmission(s) expressed in the distal rectum dominate modular nerve networks. Functionally-different descending pathways are involved in the motor activity of the anal canal. Stimulatory cholinergic pathways are dependent on the electrically-induced excitation, and inhibitory nitrergic pathways are sensitive to distension of rectal wall.

Sleep and Inflammation: Psychoneuroimmunology in the Context of Cardiovascular Disease

Poor sleep is prospectively linked to all-cause and cardiovascular mortality. Inflammatory processes may be an important biological mechanism linking poor sleep to cardiovascular disease. Such processes involve active participation of signaling molecules called cytokines in development of atherosclerotic plaques. I review evidence from experimental sleep deprivation and clinical observational studies suggesting a bidirectional relationship between sleep and inflammatory cytokines. Findings from sleep deprivation studies indicate that sleep loss is associated with increases in these cytokines. Similarly, studies in clinical populations with sleep problems, such as primary insomnia patients and those diagnosed with major depression, also show elevations in these same cytokines. Bidirectional communication between the brain and the immune system is carried out through a complex network of autonomic nerves, endocrine hormones, and cytokines. Disturbed sleep appears to perturb the functioning of this network and therefore contribute to elevations in inflammatory mediators linked to cardiovascular disease.

Influence of A.D. Bio-Phyto-Dynamic Modulators to Stress, Panic Attacks and Depression

Psychic Normality is influenced by physical, emotional and mental balance. These matters are conditioned to endogenous and exogenous factors. Resonance principle acts in a way and in the other, positive or negative, they are influenced and triggered by stress factor. Latest research shows that approximately 80% of diseases are caused, exacerbated or generated by stress. The body accepts easily changes when is opened, relaxed and in a community with external factors. When a change is introduced in crystalline or rigid structure, it will tend to break. Similarly, the network of body nerves (information) functions as strings. If they are blocked, obstructed and information energy of stress, information energy flux cannot flow freely and imbalance or disease is developed.

Anatomy of the brachial plexus

The brachial plexus is a complex anatomical network of nerves that mainly supplies the upper limb. A thorough understanding of the anatomy of this region provides the clinician with valuable clinical information that is crucial for evaluating and planning treatment for patients with obstetrical brachial plexus palsy. We will highlight the anatomy of the brachial plexus and relevant clinical correlation between physical findings and the anatomical location of the level of the injury.

Removal of foreskin remnants in circumcised adults for treatment of premature ejaculation

Background and Aim:Premature ejaculation (PE) is the most prevalent sexual dysfunction in every country. There are many types of treatment, but the main limitation of medical treatment for premature ejaculation is recurrence after withdrawal of medicine. The prepuce is a specific erogenous zone that contains a rich and complex network of nerves. Circumcision radically desensitizes the penis, but incomplete circumcision may cause premature ejaculation. We evaluate the effect of removal of foreskin remnants in adults on PE.Materials and Methods:The sensitive area of penile skin and the remaining parts of foreskin in adult men were recognized in 47 selective patients. Under local anesthesia, the remnant parts of foreskin were incised and removed. They were asked to fill the investigating questionnaire about the changes of intravaginal latency ejaculatory time (IVELT), patients and their sexual partners’ satisfaction with sexual life, control over ejaculation, and penile sensitivity, before and after treatment.Results:There were no signs of inflammation and no serious adverse reactions in all cases after operation. IVELT significantly increased from 64.25 before surgery to 731.49 sec after surgery (P<0.001). The percentage of postoperative satisfaction in both the patient and his partner significantly increased (P<0.001). After surgery, 95.7% of men had better control over their ejaculation. This surgery significantly decreased sensitivity of penis (P<0.001), but it did not change glans penis insensitivity.Conclusions:These results indicate that removal of foreskin remnants in adults is an effective modality in selective patients of PE.

Ependymal cells of chordate larvae are stem-like cells that form the adult nervous system

In ascidian tunicates, the metamorphic transition from larva to adult is accompanied by dynamic changes in the body plan. For instance, the central nervous system (CNS) is subjected to extensive rearrangement because its regulating larval organs are lost and new adult organs are created. To understand how the adult CNS is reconstructed, we traced the fate of larval CNS cells during ascidian metamorphosis by using transgenic animals and imaging technologies with photoconvertible fluorescent proteins. Here we show that most parts of the ascidian larval CNS, except for the tail nerve cord, are maintained during metamorphosis and recruited to form the adult CNS. We also show that most of the larval neurons disappear and only a subset of cholinergic motor neurons and glutamatergic neurons are retained. Finally, we demonstrate that ependymal cells of the larval CNS contribute to the construction of the adult CNS and that some differentiate into neurons in the adult CNS. An unexpected role of ependymal cells highlighted by this study is that they serve as neural stem-like cells to reconstruct the adult nervous network during chordate metamorphosis. Consequently, the plasticity of non-neuronal ependymal cells and neuronal cells in chordates should be re-examined by future studies.

Cardiovascular autonomic neuropathy in spontaneously diabetic rats with and without application of EGb 761.

Cardiovascular autonomic neuropathy causes abnormalities in the diabetic heart with various clinical sequelae, including exercise intolerance, arrhythmias and painless myocardial infarction. Little is known about (ultra)structural alterations of the myocardial nervous network. On the assumption that this diabetes-specific neuropathy develops due to permanently increased oxidative stress by liberation of oxygen-free radicals, adjuvant application of antioxidative therapeutics appears promising in preventing or delaying long-term diabetic complications. We have investigated the effects of Ginkgo biloba extract (EGb 761), a radical scavenger, against diabetes-induced myocardial nervous damage in spontaneously diabetic BioBreeding/Ottawa Karlsburg (BB/OK) rats. Morphological and morphometric parameters were evaluated by electron microscopy. We used immunohistochemistry to investigate protein expression of protein gene product 9.5, S100 protein, and thyroxin hydroxylase as a neuronal marker. Alterations of cardiac sympathetic activity were measured using the in vivo 123I-metaiodobenzyl-guanidine imaging, and the immunofluorescent labeling of beta1-adrenergic receptors and adenylate cyclase. Our results revealed that A) Diabetes results in slight to moderate ultrastructural alterations (hydrops, disintegration of substructure) of autonomic nerve fibers and related Schwann cells in untreated BB diabetic rats; B) Cardiac sympathetic integrity and activity is impaired due to alterations in the presynaptic nerve terminals and the postsynaptic ß1-AR-AC coupling system; C) Pre-treatment of diabetic myocardium with EGb results in an improvement of most of these parameters compared to unprotected myocardium. In conclusion, EGb may act as a potent therapeutic adjuvant in diabetics with respect to cardiovascular autonomic neuropathy, which may contribute to the prevention of late complications in diabetes.

Brachial Plexus Cords: a Morphological Study

The brachial plexus represents an important network of nerves, commonly approached in nerve blocks prior to surgical procedures. Therefore, the knowledge of its anatomy is indispensable so those procedures can be carried out accordingly. The objective of the present study was to analyze the morphology of brachial plexus cords with special emphasis to its topographic relationships. This study was undertaken by dissecting the cervical, axillary, and brachial regions of a human cadaver fixed in 10% phormol, from the Human Anatomy Laboratory of the Morphology Department of Universidade Federal de Santa Maria. Access to the cords was obtained by pushing back the pectoralis minor and pectoralis major muscles, clavicular section, and extraction of part of the subclavius muscle. Cords originated from the anterior and posterior divisions of the trunks (upper, middle, and lower) of the brachial plexus. The lateral fascicle originated from the anterior divisions of the upper and middle trunks; the posterior, from the posterior divisions of the trunks; and the middle fascicle consisted from the continuation of the anterior division of the lower trunk. The cords showed relationships with the axillary artery, and they were located posteriorly to the pectoralis minor muscle, close to its insertion on the coracoid process. The results were in concordance with the anatomical descriptions of classical authors. This study allowed the analysis of the morphology of the brachial plexus cords, demonstrating its main topographic relationships.

From central pattern generator to sensory template in the evolution of birdsong

Central nervous networks, be they a part of the human brain or a group of neurons in a snail, may be designed to produce distinct patterns of movement. Central pattern generators can account for the development and production of normal vocal signals without auditory feedback in non-songbirds. Songbirds need auditory feedback to develop and maintain the normal song of their species. The prerequisite for the use of auditory feedback for the control of song is a set of acoustic criteria or a template to which voice must match. The template method perhaps evolved to free birds from fixed central pattern generators, resulting in the evolution of diverse and complex songs among oscine songbirds. The evolution of human speech may have followed a similar course.

A strain-cue hypothesis for biological network formation

The direction of migration of a cell invading a host population is assumed to be controlled by the magnitude of the strains in the host medium (cells plus extracellular matrix) that arise as the host medium deforms to accommodate the invader. The single assumption that invaders are cued by strains external to themselves is sufficient to generate network structures. The strain induced by a line of invaders is greatest at the extremity of the line and thus the strain field breaks symmetry, stabilizing branch formation. The strain cue also triggers sprouting from existing branches, with no further model assumption. Network characteristics depend primarily on the ratio of the rate of advance of the invaders to the rate of relaxation of the host cells after their initial deformation. Intra-cell mechanisms that govern these two rates control network morphology. The strain field that cues an individual invader is a collective response of the combined cell populations, involving the nearest 100 cells, to order of magnitude, to any invader. The mechanism does not rely on the pre-existence of the entire host medium prior to invasion; the host cells need only maintain a layer several cells thick around each invader. Consistent with recent experiments, networks result only from a strain cue that is based on strain magnitudes. Spatial strain gradients do not break symmetry and therefore cannot stabilize branch formation. The theory recreates most of the geometrical features of the nervous network in the mouse gut when the most influential adjustable parameter takes a value consistent with one inferred from human and mouse amelogenesis. Because of similarity in the guiding local strain fields, strain cues could also be a participating factor in the formation of vascular networks.

Nitroxidergic innervation of human cerebral arteries

A dense network of nerves containing neuronal nitric oxide synthase is present in cerebral vessels from experimental animals. The nerves may regulate cerebrovascular tone, protect the brain from stroke, and contribute to cluster headaches in humans; but studies in humans have shown only modest nitroxidergic innervation of cerebral vessels. We tested the hypothesis that nerve fibers containing neuronal nitric oxide synthase richly innervate human cerebral arteries. We used immunohistochemical techniques at post mortem and found dense neuronal nitric oxide synthase nerve staining in human cerebral vessel walls consistent with participation of nitroxidergic fibers in human physiological and pathophysiological processes.

Neuroanatomy of the brachial plexus: normal and variant anatomy of its formation

The brachial plexus is the complex network of nerves, extending from the neck to the axilla, which supplies motor, sensory, and sympathetic fibers to the upper extremity. Typically, it is formed by the union of the ventral primary rami of the spinal nerves, C5-C8 & T1, the so-called "roots" of the brachial plexus. By examining the neural architecture of the brachial plexus, the most constant arrangement of nerve fibers can be delineated, and the most predominate variations in the neural architecture defined. A thorough understanding of the neuroanatomy of the brachial plexus, with an appreciation of the possible anatomic variations that may occur is necessary for effective clinical practice.

Euglycemic Infusion of Insulin Detemir Compared With Human Insulin Appears to Increase Direct Current Brain Potential Response and Reduces Food Intake While Inducing Similar Systemic Effects

OBJECTIVEIn the treatment of diabetic patients, the long-acting insulin analog insulin detemir is less prone to induce weight gain than other insulin formulations. Assuming that because of its pharmacologic properties, detemir displays stronger central nervous anorexigenic efficacy than human insulin, we compared acute effects of human insulin and detemir on electroencephalography (EEG) measures and food intake.RESEARCH DESIGN AND METHODSFrontocortical EEG direct current (DC) potentials were recorded in 15 healthy men during two hyperinsulinemic-euglycemic clamps that included an insulin bolus injection (human insulin, 17.75 mU/kg body wt; detemir, 90 mU/kg body wt) followed by a steady 90-min infusion (1.0 vs. 2.0 mU · kg−1 · min−1). A higher dosage was chosen for detemir to compensate for its delay in impact relative to human insulin and to elicit similar systemic effects. At 20 min after infusion, subjects were allowed to eat ad libitum from a test buffet.RESULTSMean glucose infusions to maintain euglycemia (P > 0.93) and blood glucose concentrations (P > 0.34) did not differ between conditions. Detemir infusion induced a negative DC-potential shift, averaging −372.2 μV from 21 to 90 min that was not observed during human insulin infusion (146.5 μV, P = 0.02). Detemir, in comparison with human insulin, reduced subsequent food intake by 303 kcal (1,257 vs. 1,560, P < 0.04).CONCLUSIONSWhile inducing comparable peripheral effects, detemir exerts stronger acute effects on brain functions than human insulin and triggers a relative decrease in food consumption, suggesting an enhanced anorexigenic impact of detemir compared with human insulin on central nervous networks that control nutrient uptake.