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Sample records for ath5 neurogenic network

  1. Quantifiable diagnosis of muscular dystrophies and neurogenic atrophies through network analysis

    PubMed Central

    2013-01-01

    Background The diagnosis of neuromuscular diseases is strongly based on the histological characterization of muscle biopsies. However, this morphological analysis is mostly a subjective process and difficult to quantify. We have tested if network science can provide a novel framework to extract useful information from muscle biopsies, developing a novel method that analyzes muscle samples in an objective, automated, fast and precise manner. Methods Our database consisted of 102 muscle biopsy images from 70 individuals (including controls, patients with neurogenic atrophies and patients with muscular dystrophies). We used this to develop a new method, Neuromuscular DIseases Computerized Image Analysis (NDICIA), that uses network science analysis to capture the defining signature of muscle biopsy images. NDICIA characterizes muscle tissues by representing each image as a network, with fibers serving as nodes and fiber contacts as links. Results After a ‘training’ phase with control and pathological biopsies, NDICIA was able to quantify the degree of pathology of each sample. We validated our method by comparing NDICIA quantification of the severity of muscular dystrophies with a pathologist’s evaluation of the degree of pathology, resulting in a strong correlation (R = 0.900, P <0.00001). Importantly, our approach can be used to quantify new images without the need for prior ‘training’. Therefore, we show that network science analysis captures the useful information contained in muscle biopsies, helping the diagnosis of muscular dystrophies and neurogenic atrophies. Conclusions Our novel network analysis approach will serve as a valuable tool for assessing the etiology of muscular dystrophies or neurogenic atrophies, and has the potential to quantify treatment outcomes in preclinical and clinical trials. PMID:23514382

  2. Neurogenic Bladder

    PubMed Central

    Dorsher, Peter T.; McIntosh, Peter M.

    2012-01-01

    Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented. PMID:22400020

  3. Neurogenic cough.

    PubMed

    Altman, Kenneth W; Noordzij, J Pieter; Rosen, Clark A; Cohen, Seth; Sulica, Lucian

    2015-07-01

    We review contemporary concepts of the pathophysiology of neurogenic cough, and its evaluation and treatment based on scientific publications addressing neurogenic cough. Neurogenic cough is thought to be the result of sensory neuropathy, most commonly idiopathic. Because it is principally a sensory phenomenon, clinical evaluation is challenging, the diagnosis most often being made by exclusion. Identification of motor paresis, either by laryngoscopy or laryngeal electromyography, may suggest the presence of sensory neuropathy. The utility of amitriptyline and gabapentin has been demonstrated in randomized clinical trials, and retrospective series and case reports have suggested efficacy of pregabalin, baclofen, and botulinum toxin. Sensory neuropathy appears to be an important cause of chronic refractory cough, and appears amenable to treatment with a variety of pharmacologic agents.

  4. The BAF complex interacts with Pax6 in adult neural progenitors to establish a neurogenic cross-regulatory transcriptional network.

    PubMed

    Ninkovic, Jovica; Steiner-Mezzadri, Andrea; Jawerka, Melanie; Akinci, Umut; Masserdotti, Giacomo; Petricca, Stefania; Fischer, Judith; von Holst, Alexander; Beckers, Johanes; Lie, Chichung D; Petrik, David; Miller, Erik; Tang, Jiong; Wu, Jiang; Lefebvre, Veronique; Demmers, Jeroen; Eisch, Amelia; Metzger, Daniel; Crabtree, Gerald; Irmler, Martin; Poot, Raymond; Götz, Magdalena

    2013-10-03

    Numerous transcriptional regulators of neurogenesis have been identified in the developing and adult brain, but how neurogenic fate is programmed at the epigenetic level remains poorly defined. Here, we report that the transcription factor Pax6 directly interacts with the Brg1-containing BAF complex in adult neural progenitors. Deletion of either Brg1 or Pax6 in the subependymal zone (SEZ) causes the progeny of adult neural stem cells to convert to the ependymal lineage within the SEZ while migrating neuroblasts convert to different glial lineages en route to or in the olfactory bulb (OB). Genome-wide analyses reveal that the majority of genes downregulated in the Brg1 null SEZ and OB contain Pax6 binding sites and are also downregulated in Pax6 null SEZ and OB. Downstream of the Pax6-BAF complex, we find that Sox11, Nfib, and Pou3f4 form a transcriptional cross-regulatory network that drives neurogenesis and can convert postnatal glia into neurons. Taken together, elements of our work identify a tripartite effector network activated by Pax6-BAF that programs neuronal fate.

  5. Neuromodulation in neurogenic bladder

    PubMed Central

    Sanford, Melissa T.

    2016-01-01

    While neuromodulation is a well-established treatment option for patients with non-neurogenic overactive bladder and urinary retention, its applicability to the neurogenic bladder population has only recently been examined more in depth. In this article we will discuss the outcomes, contraindications, and special considerations of sacral and percutaneous tibial nerve stimulation (PTNS) in patients with neurogenic lower urinary tract dysfunction. PMID:26904417

  6. Neurogenic muscle cramps.

    PubMed

    Katzberg, Hans D

    2015-08-01

    Muscle cramps are sustained, painful contractions of muscle and are prevalent in patients with and without medical conditions. The objective of this review is to present updates on the mechanism, investigation and treatment of neurogenic muscle cramps. PubMed and Embase databases were queried between January 1980 and July 2014 for English-language human studies. The American Academy of Neurology classification of studies (classes I-IV) was used to assess levels of evidence. Mechanical disruption, ephaptic transmission, disruption of sensory afferents and persistent inward currents have been implicated in the pathogenesis of neurogenic cramps. Investigations are directed toward identifying physiological triggers or medical conditions predisposing to cramps. Although cramps can be self-limiting, disabling or sustained muscle cramps should prompt investigation for underlying medical conditions. Lifestyle modifications, treatment of underlying conditions, stretching, B-complex vitamins, diltiezam, mexiletine, carbamazepine, tetrahydrocannabinoid, leveteracitam and quinine sulfate have shown evidence for treatment.

  7. Primary neurogenic orthostatic hypotension

    PubMed Central

    Hughes, R. C.; Cartlidge, N. E. F.; Millac, P.

    1970-01-01

    Eight further cases of neurogenic orthostatic hypotension are described together with a necropsy study on one case. Three cases showed evidence of autonomic dysfunction in isolation, while in five cases this was accompanied by evidence of more diffuse central nervous system degeneration. (Parkinsonism, cerebellar ataxia, dementia, pyramidal signs, bulbar weakness, and muscular wasting were all seen in varying proportions.) The various clinical presentations, investigations, pathology, treatment, and prognosis are discussed. In the experience of the authors, when assessed, an abnormal Valsalva response is invariable, confirming the breakdown of the circulatory reflex. A normal vasopressor response is likewise invariable, eliminating an abnormality of blood vessels themselves, and confirming the lesion as neurogenic. The demonstration of loss of sweating to indirect body heating, which also is usual suggests that the defect is central or on the efferent side of the reflex and a normal pilo-erector response to acetylcholine confirms this as preganglionic. Emphasis is laid on the non-specificity of many accepted physiological tests in this disorder and on the delay in diagnosis consequent upon the variable presentation. PMID:5431725

  8. Augmentation cystoplasty in neurogenic bladder

    PubMed Central

    Kocjancic, Ervin; Demirdağ, Çetin

    2016-01-01

    The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction. PMID:27617312

  9. Neurogenic bladder in Hunter's syndrome.

    PubMed Central

    Koyama, K; Moda, Y; Sone, A; Tanaka, H; Hino, Y

    1994-01-01

    We encountered a rare patient with Hunter's syndrome who exhibited urinary retention as a result of a neurogenic bladder, uninhibited detrusor contractions, and detrusor-sphincter dyssynergia. Neurological findings were consistent with cervical myelopathy and cervical MR imaging showed very narrow segments at the cord level C2-4. We speculate that this Hunter's syndrome patient has cervical myelopathy and that this neurological dysfunction causes the neurogenic bladder. PMID:8014981

  10. [Neurogenic foot deformities].

    PubMed

    Senst, S

    2010-01-01

    There is a multitude of neurological diseases which may lead to neuro-orthopaedic problems and subsequently to neurogenic foot deformities. For this reason the diagnostician will be consistently surprised that there is a great multitude of different foot abnormalities and that not only the typical spastic talipes equines dominates. Of particular significance here is that these deformities almost always develop progressively, whereas most diseases persist per se, cerebral palsy being a typical case in point. However, in MMC (myelomeningocele) patients, there is also the danger of a worsening of the basic problem in the case of tethered cord syndrome. Unlike congenital talipes equinovarus, neuro-orthopaedic talipes equinovarus often shows over- or undercorrection postoperatively due to a shift in muscle imbalance. It is important, therefore, that the basis of conservative therapy include regular physiotherapy and orthoses during the day and, if necessary, at night. Botulinum toxin has been established as an additional measure for spasticity; however, this cannot always prevent surgical intervention, but is able to delay this to a better point in the development of the child/patient. The present article describes the diversity of neurological deformities and presents conservative as well as surgical therapeutic approaches.

  11. [Neurogenic stunned myocardium].

    PubMed

    Ruiz Bailén, M; Rucabado Aguilar, L; López Martínez, A

    2006-01-01

    The existence of stunned myocardium and reversible myocardial dysfunction is widely described and accepted in patients suffering ischemic heart disease. However, it cannot be exclusive to coronary disease. Classically, the appearance of electrocardiographic changes in the critical neurological disease has been described. However, at present, it seems to be observed that some of these patients with critical neurological disease could have variable grades of myocardial dysfunction, which is generally reversible in the surviving patients. This myocardial dysfunction, which could affect critically ill neurological patients, has traits similar to stunned myocardium generated in coronary patients since: a) it is generally associated to electrocardiographic changes, b) it can be accompanied by segmental contractility disorders and even c) it may be accompanied by a certain increase of cardiac biomarkers. Although its etiopathogeny is unknown, it could be related with the severity of the primary neurological disease. Its prophylaxis and prognosis are also unknown. It could be related with neurogenic edema, with hemodynamic instability, and could also play a very important role in brain death and in organ donation.

  12. Carotid body overactivity induces respiratory neurone channelopathy contributing to neurogenic hypertension.

    PubMed

    Moraes, Davi J A; Machado, Benedito H; Paton, Julian F R

    2015-07-15

    Why sympathetic activity rises in neurogenic hypertension remains unknown. It has been postulated that changes in the electrical excitability of medullary pre-sympathetic neurones are the main causal mechanism for the development of sympathetic overactivity in experimental hypertension. Here we review recent data suggesting that enhanced sympathetic activity in neurogenic hypertension is, at least in part, dependent on alterations in the electrical excitability of medullary respiratory neurones and their central modulation of sympatho-excitatory networks. We also present results showing a critical role for carotid body tonicity in the aetiology of enhanced central respiratory modulation of sympathetic activity in neurogenic hypertension. We propose a novel hypothesis of respiratory neurone channelopathy induced by carotid body overactivity in neurogenic hypertension that may contribute to sympathetic excess. Moreover, our data support the notion of targeting the carotid body as a potential novel therapeutic approach for reducing sympathetic vasomotor tone in neurogenic hypertension.

  13. Understanding migraine: Potential role of neurogenic inflammation

    PubMed Central

    Malhotra, Rakesh

    2016-01-01

    Neurogenic inflammation, a well-defined pathophysiologial process is characterized by the release of potent vasoactive neuropeptides, predominantly calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A from activated peripheral nociceptive sensory nerve terminals (usually C and A delta-fibers). These peptides lead to a cascade of inflammatory tissue responses including arteriolar vasodilation, plasma protein extravasation, and degranulation of mast cells in their peripheral target tissue. Neurogenic inflammatory processes have long been implicated as a possible mechanism involved in the pathophysiology of various human diseases of the nervous system, respiratory system, gastrointestinal tract, urogenital tract, and skin. The recent development of several innovative experimental migraine models has provided evidence suggestive of the involvement of neuropeptides (SP, neurokinin A, and CGRP) in migraine headache. Antidromic stimulation of nociceptive fibers of the trigeminal nerve resulted in a neurogenic inflammatory response with marked increase in plasma protein extravasation from dural blood vessels by the release of various sensory neuropeptides. Several clinically effective abortive antimigraine medications, such as ergots and triptans, have been shown to attenuate the release of neuropeptide and neurogenic plasma protein extravasation. These findings provide support for the validity of using animal models to investigate mechanisms of neurogenic inflammation in migraine. These also further strengthen the notion of migraine being a neuroinflammatory disease. In the clinical context, there is a paucity of knowledge and awareness among physicians regarding the role of neurogenic inflammation in migraine. Improved understanding of the molecular biology, pharmacology, and pathophysiology of neurogenic inflammation may provide the practitioner the context-specific feedback to identify the novel and most effective therapeutic approach to treatment

  14. Droxidopa in neurogenic orthostatic hypotension

    PubMed Central

    Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto

    2015-01-01

    Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure on standing due to reduced norepinephrine release from sympathetic nerve terminals. nOH is a feature of several neurological disorders that affect the autonomic nervous system, most notably Parkinson disease (PD), multiple system atrophy, pure autonomic failure and other autonomic neuropathies. Droxidopa, an orally active synthetic amino acid that is converted to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (dopa-decarboxylase), was recently approved by the FDA for the short-term treatment of nOH. It is presumed to raise blood pressure by acting at the neurovascular junction to increase vascular tone. This review summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials. PMID:26092297

  15. [Disorders of bladder compliance and neurogenic bladder].

    PubMed

    Chartier-Kastler, E; Comperat, E; Ruffion, A

    2007-05-01

    Bladder compliance is defined as the relationship between change in bladder volume and change in detrusor pressure (DV/DP). The pathophysiology of neurogenic disorders of bladder compliance is still poorly understood. Experimental reduction of blood flow in the bladder wall, bilateral hypogastric nerve section in rats, the study of spinalized rat bladders, and reduction of oestrogen impregnation show that these conditions induce loss of the viscoelastic properties of the bladder. With the arrival of new treatments active on afferent and/or efferent pathways or on the central nervous system, it is very important to improve our understanding of the pathophysiology of neurogenic disorders of bladder compliance. The reversibility of these disorders constitutes a major therapeutic challenge and their functional consequences constitute a crucial prognostic element of neurogenic bladder. Disorders of bladder compliance can be assessed clinically from two points of view: 1) The natural history of onset of these disorders in neurogenic bladder. Clinical experience demonstrates certain risk factors for the development of these disorders, such as the voiding mode (intermittent self-catheterization or by a carer versus indwelling catheter), the level of the spinal cord lesion (suprasacral versus sacral, incomplete versus complete, and cauda equina lesions), and the presence of myelomeningocele. 2) Data derived from conservative management of these disorders in patients with neurogenic bladder: urethral dilatation, various types of sphincterotomy, vesical denervation, alpha-blockers, sympatholytics, vanilloids (resiniferatoxin and capsaicin), intra-detrusor botulinum toxin and intrathecal baclofen have been shown to improve disorders of compliance of neurogenic bladder.

  16. Cervicobrachial pain - How Often is it Neurogenic?

    PubMed Central

    Nair, N. Sreekumaran; Bhat, Anil K; Solomon, John M

    2016-01-01

    Introduction Neck pain associated with pain in the arm (cervicobrachial pain) is a common complaint in patients seeking physiotherapy management. The source of symptoms for this complaint is commonly presumed to be neural. However, this pain pattern could also result from various other innervated tissue structures of the upper quarter. Knowledge about frequency of neural structures being a predominant source of symptoms would help in implementing appropriate therapeutic strategies such as neural tissue mobilization along with other complimentary therapies for optimal outcomes. Aim To determine the frequency of cervicobrachial pain being neurogenic. Materials and Methods Participants (n=361) aged between 20-65 years, reporting cervicobrachial pain were screened for neurogenic nature of symptoms. These physical signs included: active and passive movement dysfunction, adverse responses to neural tissue provocation tests, tenderness on palpating nerve trunks and related cutaneous tissues and evidence of a related local area of pathology (Clinical/radiological). The consistency of all these signs was checked to identify a significant neural involvement. Results Descriptive statistics were used to analyse data. Of 361 participants, 206 were males (44.6 ±10.8 years) and 155 were females (41.8 ± 11.2 years). The frequency of neurogenic cervicobrachial pain was determined to be 19.9% (n=72) and the non-neurogenic sources for symptoms were attributed to 80.1% (n=289) of screened participants. Conclusion Lower frequency of cervicobrachial pain being neurogenic indicates thorough screening for appropriate therapeutic interventions to be successful. PMID:27134988

  17. Neurogenic gene regulatory pathways in the sea urchin embryo.

    PubMed

    Wei, Zheng; Angerer, Lynne M; Angerer, Robert C

    2016-01-15

    During embryogenesis the sea urchin early pluteus larva differentiates 40-50 neurons marked by expression of the pan-neural marker synaptotagmin B (SynB) that are distributed along the ciliary band, in the apical plate and pharyngeal endoderm, and 4-6 serotonergic neurons that are confined to the apical plate. Development of all neurons has been shown to depend on the function of Six3. Using a combination of molecular screens and tests of gene function by morpholino-mediated knockdown, we identified SoxC and Brn1/2/4, which function sequentially in the neurogenic regulatory pathway and are also required for the differentiation of all neurons. Misexpression of Brn1/2/4 at low dose caused an increase in the number of serotonin-expressing cells and at higher dose converted most of the embryo to a neurogenic epithelial sphere expressing the Hnf6 ciliary band marker. A third factor, Z167, was shown to work downstream of the Six3 and SoxC core factors and to define a branch specific for the differentiation of serotonergic neurons. These results provide a framework for building a gene regulatory network for neurogenesis in the sea urchin embryo.

  18. Neurogenic gene regulatory pathways in the sea urchin embryo

    PubMed Central

    Wei, Zheng; Angerer, Lynne M.; Angerer, Robert C.

    2016-01-01

    During embryogenesis the sea urchin early pluteus larva differentiates 40-50 neurons marked by expression of the pan-neural marker synaptotagmin B (SynB) that are distributed along the ciliary band, in the apical plate and pharyngeal endoderm, and 4-6 serotonergic neurons that are confined to the apical plate. Development of all neurons has been shown to depend on the function of Six3. Using a combination of molecular screens and tests of gene function by morpholino-mediated knockdown, we identified SoxC and Brn1/2/4, which function sequentially in the neurogenic regulatory pathway and are also required for the differentiation of all neurons. Misexpression of Brn1/2/4 at low dose caused an increase in the number of serotonin-expressing cells and at higher dose converted most of the embryo to a neurogenic epithelial sphere expressing the Hnf6 ciliary band marker. A third factor, Z167, was shown to work downstream of the Six3 and SoxC core factors and to define a branch specific for the differentiation of serotonergic neurons. These results provide a framework for building a gene regulatory network for neurogenesis in the sea urchin embryo. PMID:26657764

  19. Introduction to Neurogenic Communication Disorders. Fifth Edition.

    ERIC Educational Resources Information Center

    Brookshire, Robert H.

    This book provides an overview of the causes and symptoms, and the typical courses, treatments, and outcomes of neurogenic communication disorders. Chapter 1 reviews the human nervous system and neurologic causes of adult communication disorders. Chapter 2 discusses the neurologic assessment and arriving at a diagnosis, including the neurologist's…

  20. A crucial role for the cortico-striato-cortical loop in the pathogenesis of stroke-related neurogenic stuttering.

    PubMed

    Theys, Catherine; De Nil, Luc; Thijs, Vincent; van Wieringen, Astrid; Sunaert, Stefan

    2013-09-01

    Neurogenic stuttering is an acquired speech disorder characterized by the occurrence of stuttering-like dysfluencies following brain damage. Because the onset of stuttering in these patients is associated with brain lesions, this condition provides a unique opportunity to study the neural processes underlying speech dysfluencies. Lesion localizations of 20 stroke subjects with neurogenic stuttering and 17 control subjects were compared using voxel-based lesion symptom mapping. The results showed nine left-hemisphere areas associated with the presence of neurogenic stuttering. These areas were largely overlapping with the cortico-basal ganglia-cortical network comprising the inferior frontal cortex, superior temporal cortex, intraparietal cortex, basal ganglia, and their white matter interconnections through the superior longitudinal fasciculus and internal capsule. These results indicated that stroke-induced neurogenic stuttering is not associated with neural dysfunction in one specific brain area but can occur following one or more lesion throughout the cortico-basal ganglia-cortical network. It is suggested that the onset of neurogenic stuttering in stroke subjects results from a disintegration of neural functions necessary for fluent speech.

  1. Neurogenic stunned myocardium in subarachnoid hemorrhage.

    PubMed

    Kerro, Ali; Woods, Timothy; Chang, Jason J

    2017-04-01

    "Stunned myocardium," characterized by reversible left ventricular dysfunction, was first described via animal models using transient coronary artery occlusion. However, this phenomenon has also been noted with neurologic pathologies and collectively been labeled "neurogenic stunned myocardium" (NSM). Neurogenic stunned myocardium resulting from subarachnoid hemorrhage (SAH) is a challenging pathology due to its diagnostic uncertainty. Traditional diagnostic criteria for NSM after SAH focus on electrocardiographic and echocardiographic abnormalities and troponemia. However, tremendous heterogeneity still exists. Traditional pathophysiological mechanisms for NSM encompassed hypothalamic and myocardial perivascular lesions. More recently, research on pathophysiology has centered on myocardial microvascular dysfunction and genetic polymorphisms. Catecholamine surging as a mechanism has also gained attention with particular focus placed on the role of adrenergic blockade in both the prehospital and acute settings. Management remains largely supportive with case reports acknowledging the utility of inotropes such as dobutamine and milrinone and intra-aortic balloon pump when NSM is accompanied by cardiogenic shock. Neurogenic stunned myocardium that follows SAH can result in many complications such as arrhythmias, pulmonary edema, and prolonged intubation, which can negatively impact long-term recovery from SAH and increase morbidity and mortality. This necessitates the need to accurately diagnose and treat NSM.

  2. Prolonged Cardiac Dysfunction After Intraparenchymal Hemorrhage and Neurogenic Stunned Myocardium

    PubMed Central

    Krishnamoorthy, Vijay; Wilson, Thomas; Sharma, Deepak; Vavilala, Monica S.

    2015-01-01

    Cardiac dysfunction occurring secondary to neurologic disease, termed neurogenic stunned myocardium, is an incompletely understood phenomenon that has been described after several distinct neurologic processes. We present a case of neurogenic stunned myocardium, discovered intraoperatively after anesthetic induction, in a patient who presented to our operating room with a recent intraparenchymal hemorrhage. We discuss the longitudinal cardiac functional course after neurogenic stunned myocardium. Lastly, we discuss the pathophysiology of neurogenic stunned myocardium, as well as its implications for anesthesiologists caring for neurosurgical patients. PMID:26462162

  3. [Neurogenic urinary incontinence. Value of surgical management].

    PubMed

    Kutzenberger, J

    2008-06-01

    Damage to the CNS, the cauda equina, and the pelvic nerval structures causes neurogenic bladder dysfunction with neurogenic urinary incontinence (NUI). The definitive diagnosis of NUI is made with urodynamic examination methods. The most frequent cause of NUI is neurogenic detrusor overactivity (NDO). The treatment concept must take into account the physical and emotional restrictions. The treatment of NUI due to NDO is a domain of conservative therapy, i.e., mostly antimuscarinics and intermittent catheterization (IC). In about 30%, there is a good chance for therapy failures. An advancement in therapy is the injection of BTX-A into the detrusor. The missing drug approval is a disadvantage.Operative treatments are considered if conservative and minimally invasive therapies are unsuccessful. Sacral deafferentation (SDAF) and sacral anterior root stimulator implantation (SARSI) are available as organ-preserving techniques only for paraplegics with NDO and reflex urinary incontinence and neuromodulation for the other forms of NDO provided that a successful percutaneous nerve evaluation (PNE) test has previously taken place. Augmentation cystoplasty is indicated if SDAF and neuromodulation cannot be used and the bladder wall is damaged irreversibly by fibrosis. Kidney function of at least 25% and acceptance of IC are prerequisites. Myectomy (autoaugmentation) has an indication similar to augmentation cystoplasty but there must not be any fibrosis. Bladder neck insufficiency (BNI) caused by paralysis or iatrogenically can be treated by the implantation of an alloplastic sphincter high at the bladder neck. A stable reservoir function is required. If not all methods are possible, the ileum conduit or the suprapubic bladder fistula can be the last resort.

  4. Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology.

    PubMed

    Chiu, Isaac M; von Hehn, Christian A; Woolf, Clifford J

    2012-07-26

    The peripheral nervous and immune systems are traditionally thought of as serving separate functions. The line between them is, however, becoming increasingly blurred by new insights into neurogenic inflammation. Nociceptor neurons possess many of the same molecular recognition pathways for danger as immune cells, and, in response to danger, the peripheral nervous system directly communicates with the immune system, forming an integrated protective mechanism. The dense innervation network of sensory and autonomic fibers in peripheral tissues and high speed of neural transduction allows rapid local and systemic neurogenic modulation of immunity. Peripheral neurons also seem to contribute to immune dysfunction in autoimmune and allergic diseases. Therefore, understanding the coordinated interaction of peripheral neurons with immune cells may advance therapeutic approaches to increase host defense and suppress immunopathology.

  5. A role for the Drosophila neurogenic genes in mesoderm differentiation.

    PubMed

    Corbin, V; Michelson, A M; Abmayr, S M; Neel, V; Alcamo, E; Maniatis, T; Young, M W

    1991-10-18

    The neurogenic genes of Drosophila have long been known to regulate cell fate decisions in the developing ectoderm. In this paper we show that these genes also control mesoderm development. Embryonic cells that express the muscle-specific gene nautilus are overproduced in each of seven neurogenic mutants (Notch, Delta, Enhancer of split, big brain, mastermind, neuralized, and almondex), at the apparent expense of neighboring, nonexpressing mesodermal cells. The mesodermal defect does not appear to be a simple consequence of associated neural hypertrophy, suggesting that the neurogenic genes may function similarly and independently in establishing cell fates in both ectoderm and mesoderm. Altered patterns of beta 3-tubulin and myosin heavy chain gene expression in the mutants indicate a role for the neurogenic genes in development of most visceral and somatic muscles. We propose that the signal produced by the neurogenic genes is a general one, effective in both ectoderm and mesoderm.

  6. Neurogenic bladder in spinal cord injury patients

    PubMed Central

    Taweel, Waleed Al; Seyam, Raouf

    2015-01-01

    Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury. PMID:26090342

  7. A molecular analysis of neurogenic placode and cranial sensory ganglion development in the shark, Scyliorhinus canicula.

    PubMed

    O'Neill, P; McCole, R B; Baker, C V H

    2007-04-01

    In order to gain insight into the evolution of the genetic control of the development of cranial neurogenic placodes and cranial sensory ganglia in vertebrates, we cloned and analysed the spatiotemporal expression pattern of six transcription factor genes in a chondrichthyan, the shark Scyliorhinus canicula (lesser-spotted dogfish/catshark). As in other vertebrates, NeuroD is expressed in all cranial sensory ganglia. We show that Pax3 is expressed in the profundal placode and ganglion, strongly supporting homology between the separate profundal ganglion of elasmobranchs and basal actinopterygians and the ophthalmic trigeminal placode-derived neurons of the fused amniote trigeminal ganglion. We show that Pax2 is a conserved pan-gnathostome marker for epibranchial and otic placodes, and confirm that Phox2b is a conserved pan-gnathostome marker for epibranchial placode-derived neurons. We identify Eya4 as a novel marker for the lateral line system throughout its development, expressed in lateral line placodes, sensory ridges and migrating primordia, neuromasts and electroreceptors. We also identify Tbx3 as a specific marker for lateral line ganglia in shark embryos. We use the spatiotemporal expression pattern of these genes to characterise the development of neurogenic placodes and cranial sensory ganglia in the dogfish, with a focus on the epibranchial and lateral line placodes. Our findings demonstrate the evolutionary conservation across all gnathostomes of at least some of the transcription factor networks underlying neurogenic placode development.

  8. Neurovascular aspects of skin neurogenic inflammation.

    PubMed

    Aubdool, Aisah A; Brain, Susan D

    2011-12-01

    Neurogenic inflammation is involved in skin inflammation. It is hypothesized that it is involved in the pathogenesis of the common chronic cutaneous vascular disorder rosacea, but the exact mechanism of action is currently unknown. Transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) are widely expressed on primary sensory neuron endings and non-neuronal cells such as keratinocytes. Here we describe the potential for TRPV1 and TRPA1 receptors to be involved in the pathophysiology of rosacea due to their polymodal activation, including cold and hot temperature, pungent products from vegetable and spices, reactive oxygen species, and mechanical stimuli. We discuss the role of both receptors and the sensory neuropeptides that they release in inflammation and pain sensation and evidence suggesting that both TRPV1 and TRPA1 receptors may be promising therapeutic targets for the treatment of the inflammatory symptoms of rosacea.

  9. Urinary tract infection in the neurogenic bladder.

    PubMed

    Vigil, Humberto R; Hickling, Duane R

    2016-02-01

    There is a high incidence of urinary tract infection (UTI) in patients with neurogenic lower urinary tract function. This results in significant morbidity and health care utilization. Multiple well-established risk factors unique to a neurogenic bladder (NB) exist while others require ongoing investigation. It is important for care providers to have a good understanding of the different structural, physiological, immunological and catheter-related risk factors so that they may be modified when possible. Diagnosis remains complicated. Appropriate specimen collection is of paramount importance and a UTI cannot be diagnosed based on urinalysis or clinical presentation alone. A culture result with a bacterial concentration of ≥10(3) CFU/mL in combination with symptoms represents an acceptable definition for UTI diagnosis in NB patients. Cystoscopy, ultrasound and urodynamics should be utilized for the evaluation of recurrent infections in NB patients. An acute, symptomatic UTI should be treated with antibiotics for 5-14 days depending on the severity of the presentation. Antibiotic selection should be based on local and patient-based resistance patterns and the spectrum should be as narrow as possible if there are no concerns regarding urosepsis. Asymptomatic bacteriuria (AB) should not be treated because of rising resistance patterns and lack of clinical efficacy. The most important preventative measures include closed catheter drainage in patients with an indwelling catheter and the use of clean intermittent catheterization (CIC) over other methods of bladder management if possible. The use of hydrophilic or impregnated catheters is not recommended. Intravesical Botox, bacterial interference and sacral neuromodulation show significant promise for the prevention of UTIs in higher risk NB patients and future, multi-center, randomized controlled trials are required.

  10. Neurogenic Pulmonary Edema in Aneurysmal Subarachnoid Hemorrhage.

    PubMed

    Saracen, A; Kotwica, Z; Woźniak-Kosek, A; Kasprzak, P

    2016-01-01

    Neurogenic pulmonary edema (NPE) is observed in cerebral injuries and has an impact on treatment results, being a predictor of fatal prognosis. In this study we retrospectively reviewed medical records of 250 consecutive patients with aneurysmal subarachnoid hemorrhage (SAH) for the frequency and treatment results of NPE. The following factors were taken under consideration: clinical status, aneurysm location, presence of NPE, intracranial pressure (ICP), and mortality. All patients had plain- and angio-computer tomography performed. NPE developed most frequently in case of the aneurysm located in the anterior communicating artery. The patients with grades I-III of SAH, according to the World Federation of Neurosurgeons staging, were immediately operated on, while those with poor grades IV and V had only an ICP sensor's implantation procedure performed. A hundred and eighty five patients (74.4 %) were admitted with grades I to III and 32 patients (12.8 %) were with grade IV and V each. NPE was not observed in SAH patients with grade I to III, but it developed in nine patients with grade IV and 11 patients with grade V. Of the 20 patients with NPE, 19 died. Of the 44 poor grade patients (grades IV-V) without NPE, 20 died. All poor grade patients had elevated ICP in a range of 24-56 mmHg. The patients with NPE had a greater ICP than those without NPE. Gender and age had no influence on the occurrence of NPE. We conclude that the development of neurogenic pulmonary edema in SAH patients with poor grades is a fatal prognostic as it about doubles the death rate to almost hundred percent.

  11. Urinary tract infection in the neurogenic bladder

    PubMed Central

    Vigil, Humberto R.

    2016-01-01

    There is a high incidence of urinary tract infection (UTI) in patients with neurogenic lower urinary tract function. This results in significant morbidity and health care utilization. Multiple well-established risk factors unique to a neurogenic bladder (NB) exist while others require ongoing investigation. It is important for care providers to have a good understanding of the different structural, physiological, immunological and catheter-related risk factors so that they may be modified when possible. Diagnosis remains complicated. Appropriate specimen collection is of paramount importance and a UTI cannot be diagnosed based on urinalysis or clinical presentation alone. A culture result with a bacterial concentration of ≥103 CFU/mL in combination with symptoms represents an acceptable definition for UTI diagnosis in NB patients. Cystoscopy, ultrasound and urodynamics should be utilized for the evaluation of recurrent infections in NB patients. An acute, symptomatic UTI should be treated with antibiotics for 5–14 days depending on the severity of the presentation. Antibiotic selection should be based on local and patient-based resistance patterns and the spectrum should be as narrow as possible if there are no concerns regarding urosepsis. Asymptomatic bacteriuria (AB) should not be treated because of rising resistance patterns and lack of clinical efficacy. The most important preventative measures include closed catheter drainage in patients with an indwelling catheter and the use of clean intermittent catheterization (CIC) over other methods of bladder management if possible. The use of hydrophilic or impregnated catheters is not recommended. Intravesical Botox, bacterial interference and sacral neuromodulation show significant promise for the prevention of UTIs in higher risk NB patients and future, multi-center, randomized controlled trials are required. PMID:26904414

  12. [Neurogenic stunned myocardium in Pediatrics. A case report].

    PubMed

    Alados Arboledas, F J; Millán-Miralles, L; Millán-Bueno, M P; Expósito-Montes, J F; Santiago-Gutierrez, C; Martínez Padilla, M C

    2015-10-01

    Neurogenic stunned myocardium is an unusual clinical entity. It mimics an acute coronary syndrome with electrocardiographic abnormalities, cardiac dysfunction and elevated cardiac enzymes with absence of obstructive coronary disease. It may occur after a neurosurgical procedure. A case is presented of neurogenic stunned myocardium occurring in a child after removal of a posterior fossa medulloblastoma. The patient developed nodal tachycardia with hemodynamic impairment. The clinical course was satisfactory due to antiarrhythmic therapy, with biochemical, echocardiographic, and clinical improvement within a week.

  13. [Primary neurogenic and myogenic disorders of posture].

    PubMed

    Schranz, C; Meinck, H-M

    2004-05-01

    Disturbance of posture may occur in a variety of neurological disorders and occasionally is the presenting or even the only sign. In the majority of cases, the head or the trunk or both are bent forward (bent spine syndrome, dropped head syndrome). A feature of these primary neurogenic or myogenic postural disturbances that is in contrast to antalgic contraction or ankylosis is that they are not fixed, but the trunk or head are easily erected by the examiner and show a characteristic sagging. Neuromuscular disorders are a frequent cause. They may be confined to the paraspinal muscles. Axial computed tomography of the spine, electromyography of the involved muscles, and muscle biopsy help to make the diagnosis. However, also central movement disorders may lead to a sagging of the head or trunk or of both due to a lessened tone of the head and trunk extensors. This is frequently seen in the various parkinsonian syndromes which may, however, occur in association with a focal myopathy of the paraspinal muscles. Occasionally, sagging of the trunk is seen as a side effect of neuropharmacologic medication. Sagging of the trunk or head should be differentiated from a pathologically increased innervation of the ventral muscles in dystonic movement disorders such as antecollis or camptocormia. Pathologic reclination of the head or trunk or both is a rare disturbance of posture. It may occur in dystonia (retrocollis) or, occasionally, as a consequence of musculotendinous contractures secondary to certain neuromuscular disorders such as the rigid spine syndrome.

  14. Microglia participate in neurogenic regulation of hypertension.

    PubMed

    Shen, Xiao Z; Li, You; Li, Liang; Shah, Kandarp H; Bernstein, Kenneth E; Lyden, Patrick; Shi, Peng

    2015-08-01

    Hypertension is associated with neuroinflammation and increased sympathetic tone. Interference with neuroinflammation by an anti-inflammatory reagent or overexpression of interleukin-10 in the brain was found to attenuate hypertension. However, the cellular mechanism of neuroinflammation, as well as its impact on neurogenic regulation of blood pressure, is unclear. Here, we found that hypertension, induced by either angiotensin II or l-N(G)-nitro-l-arginine methyl ester, is accompanied by microglial activation as manifested by microgliosis and proinflammatory cytokine upregulation. Targeted depletion of microglia significantly attenuated neuroinflammation, glutamate receptor expression in the paraventricular nucleus, plasma vasopressin level, kidney norepinephrine concentration, and blood pressure. Furthermore, when microglia were preactivated and transferred into the brains of normotensive mice, there was a significantly prolonged pressor response to intracerebroventricular injection of angiotensin II, and inactivation of microglia eliminated these effects. These data demonstrate that microglia, the resident immune cells in the brain, are the major cellular factors in mediating neuroinflammation and modulating neuronal excitation, which contributes to the elevated blood pressure.

  15. AAEM minimonograph #46: neurogenic muscle hypertrophy.

    PubMed

    Gutmann, L

    1996-07-01

    Muscle hypertrophy occurs uncommonly in several neurogenic disorders including neuropathies, radiculopathies, spinal muscular atrophy, and post-polio syndrome. Its pathogenesis varies in different circumstances. In the presence of generalized myokymia and neuromyotonia (Isaacs' syndrome), symmetrical hypertrophy appears to be the result of continuous spontaneous electrical stimulation of myofibers and, in some cases, results in type 1 myofiber preponderance. Focal hypertrophy occurring with radiculopathies and mononeuropathies was associated with complex repetitive discharges (CRDs) in approximately half the cases. CRDs may play a role in the pathogenesis of myofiber hypertrophy by continuous myofiber stimulation, but in some cases, with and without CRDs, myofiber hypertrophy may be related to mechanical events. Muscle enlargement seen in old polio appears to involve a significant degree of pseudohypertrophy, although some myofiber hypertrophy occurs. The symmetrical occurrence of hypertrophy in genetically determined disorders, such as spinal muscular atrophy, and hereditary motor and sensory neuropathy types 1 and 2 may have both a genetic and a mechanical basis in addition to pseudohypertrophy in some cases.

  16. [Neurogenic bladder: pathophysiology of the disorder of compliance].

    PubMed

    Chartier-Kastler, Emmanuel; Ayoub, Nadim; Even-Schneider, Alexia; Richard, François; Soler, Jean-Marc; Denys, Pierre

    2004-09-01

    Bladder compliance is defined by the ratio of the increase of intravesical pressures to the increase of volume (_V/_P). The pathophysiology of disorders of compliance in neurogenic bladder is still poorly elucidated. It can be evaluated in terms of three elements: 1) The natural history of the appearance of these disorders in neurogenic bladders. Clinical experience shows the existence of prognostic factors that determine the development of these disorders, such as the voiding mode adopted (self-catheterization/hetero-catheterization versus indwelling catheter), the level of the spinal cord lesion (suprasacral versus sacral, incomplete versus complete, and cauda equina lesions), and the presence of meningomyelocele. 2). Data derived from conservative management of these disorders in neurogenic bladders: urethral dilatation, various sphincterotomies, bladder disafferentation, alpha-blockers, vanilloids (resiniferatoxin and capsaicin), intra-detrusor botulinum toxin and intrathecal baclofen, have demonstrated a marked improvement of disorders of compliance associated with neurogenic bladder 3). Data derived from experimentations. Morphometric studies on animal or human bladder strips have demonstrated an increased expression of proteolytic enzymes and endogenous tissue inhibitors of metalloproteinases (MMP-1) and type III collagen mRNA in hypocompliant neurogenic bladders. Reduction of bladder wall blood flow, bilateral section of hypogastric nerves in rats, study of the bladders of spinalized rats, and reduction of oestrogenic hormone impregnation, show that these conditions induce loss of the viscoelastic properties of the bladder With the arrival of new treatments, active on afferent and/or efferent pathways or even on the central nervous system, it is very important to further our understanding of the pathophysiology of disorders of compliance in neurogenic bladders. Reversibility of these disorders constitutes a major therapeutic challenge and its functional

  17. Hereditary sensory radicular neuropathy: defective neurogenic inflammation.

    PubMed

    Westerman, R A; Block, A; Nunn, A; Delaney, C A; Hahn, A; Dennett, X; Carr, R W

    1992-01-01

    Hereditary sensory radicular neuropathy exhibits autosomal dominant inheritance with complete penetrance in males and incomplete penetrance in females. Newer tests of small sensory nerve function were used in screening 8 family members aged between 14 and 66 years. All exhibited some frequent features of the disorder with an onset in the 2nd or 3rd decade, foot ulceration, foot callus, loss of pin prick, thermal and light touch sensation, and some reduction in vibration acuity and proprioception in the lower limbs. The hands were involved in 3 of 8, muscle involvement was present in 5 of 8, but deafness was not detected by audiometry. Nerve conduction velocity, sensory action potentials, latency and amplitude, thermal acuity, vibration acuity and axon reflex flares were measured in all patients. One sural nerve biopsy confirmed the presence of peripheral fibre loss in this predominantly sensory neuropathy. Chemically evoked axon reflex tests were used to evaluate the extent of primary sensory nerve fibre involvement. All patients were tested using a Moor MBF 3-D dual channel laser Doppler velocimeter. Acetylcholine or phenylephrine iontophoretically applied as 16 mC doses evoked absent or tiny axon reflexes in areas of impaired pin prick sensation. By contrast, direct microvascular dilator responses to nitroprusside (smooth muscle dependent) and acetylcholine (endothelium-dependent) were present but somewhat reduced in areas with defective neurogenic inflammation. These results differ significantly from the responses obtained in age-matched healthy controls (P < 0.05). Foot pressure analysis was performed for orthoses in 2 affected members with foot ulceration using the Musgrave Footprint system.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. SUSCEPTIBILITY TO POLLUTANT-INDUCED AIRWAY INFLAMMATION IS NEUROGENICALLY MEDIATED.

    EPA Science Inventory

    Neurogenic inflammation in the airways involves the activation of sensory irritant receptors (capsaicin, VR1) by noxious stimuli and the subsequent release of neuropeptides (e.g., SP, CGRP, NKA) from these fibers. Once released, these peptides initiate and sustain symptoms of ...

  19. Neurogenic hypertension related to basilar impression. Case report.

    PubMed

    Dickinson, L D; Papadopoulos, S M; Hoff, J T

    1993-12-01

    The authors report the resolution of essential hypertension following transoral odontoidectomy and medullary decompression in a 39-year-old woman with basilar invagination. Current understanding of central regulation of the cardiovascular system is discussed and the pertinent neuroanatomy illustrated. Experimental and clinical evidence supporting the role of neurogenic mechanisms in the pathogenesis of hypertension is reviewed.

  20. Neurogenic tumors of the duodenum in patients with neurofibromatosis

    SciTech Connect

    Tishler, J.M.; Han, S.Y.; Colcher, H.; Halpern, N.B.

    1983-10-01

    Neurogenic tumors of the duodenum may occur in patients with neurofibromatosis. They may be solitary or multiple and are located distal to the duodenal bulb. The presenting complaints may be hematemesis, vomiting, or jaundice. The lesions are generally benign and have a low potential for malignant degenertion. Four cases are reported.

  1. Not all neurogenic bladders are the same: a proposal for a new neurogenic bladder classification system

    PubMed Central

    2016-01-01

    Neurogenic bladder (NGB) has long been defined as a clinical entity that describes a heterogeneous collection of syndromes. The common theme is a bladder disorder concomitant with a neurologic disorder. This definition does not give the clinician much information about the bladder disorder, nor how to treat it, or even what the natural history of the disorder is likely to be. It may be time for a new classification scheme to better define the bladder defect and prognosis, as well as inform treatment. We propose a classification system based on seven categories, each having a neurologic defect in a distinct anatomic location. This is termed SALE (Stratify by Anatomic Location and Etiology). In addition, the presence or absence of bowel dysfunction and autonomic dysreflexia will be reported. In the future, as more definite prognostic information can be gleaned from biomarkers, we anticipate adding urinary nerve growth factor (NGF) and urinary brain-derived neurotrophic factor (BDNF) levels to the definition. We expect the SALE system to efficiently describe a patient suffering from NGB and simultaneously inform the most appropriate treatment, follow-up regimen, and long-term prognosis. PMID:26904408

  2. The treatment of erectile dysfunction in patients with neurogenic disease

    PubMed Central

    Brant, William O.

    2016-01-01

    Erectile dysfunction (ED) related to compromise of the nervous system is an increasingly common occurrence. This may be due to the multifactorial nature of ED, the myriad of disorders affecting the neurotransmission of erectogenic signals, and improved awareness and diagnosis of ED. Nevertheless, neurogenic ED remains poorly understood and characterized. Disease related factors such as depression, decreased physical and mental function, the burden of chronic illness, and loss of independence may preclude sexual intimacy and lead to ED as well. The amount of data regarding treatment options in subpopulations of differing neurologic disorders remains scarce except for men with spinal cord injury. The treatment options including phosphodiesterase inhibitors, intracavernosal or intraurethral vasoactive agents, vacuum erection devices (VED) and penile prosthetic implantation remain constant. This review discusses the options in specific neurologic conditions, and briefly provides insight into new and future developments that may reshape the management of neurogenic ED. PMID:26904415

  3. Neurogenic muscle hypertrophy in a 12-year-old girl.

    PubMed

    Zutelija Fattorini, Matija; Gagro, Alenka; Dapic, Tomislav; Krakar, Goran; Marjanovic, Josip

    2017-01-01

    Muscular hypertrophy secondary to denervation is very rare, but well-documented phenomena in adults. This is the first report of a child with neurogenic unilateral hypertrophy due to S1 radiculopathy. A 12-year-old girl presented with left calf hypertrophy and negative history of low back pain or trauma. The serum creatinine kinase level and inflammatory markers were normal. Magnetic resonance imaging showed muscle hypertrophy of the left gastrocnemius and revealed a protruded lumbar disc at the L5-S1 level. The protruded disc abuts the S1 root on the left side. Electromyography showed mild left S1 radiculopathy. Passive stretching and work load might clarify the origin of neurogenic hypertrophy but there is still a need for further evidence. Clinical, laboratory, magnetic resonance imaging and electromyography findings showed that S1 radiculopathy could be a cause of unilateral calf swelling in youth even in the absence of a history of back or leg pain.

  4. Effects of Radiation Therapy on Established Neurogenic Heterotopic Ossification

    PubMed Central

    2016-01-01

    Heterotopic ossification (HO) is frequently seen on rehabilitation units after spinal cord injuries, fractures, brain injuries, and limb amputations. Currently, there is no effective treatment for HO other than prophylaxis with anti-inflammatory medications, irradiation, and bisphosphonate administration. These prophylactic treatments are not effective for managing ectopic bone once it has formed. Here we describe three cases of established neurogenic HO treated with radiation therapy (RT). All patients had decreased serum alkaline phosphatase (ALP) and bone-specific ALP levels with decreased pain but increased range of motion immediately after RT. Post-treatment X-rays revealed no further growth of the HO. All patients maintained clinical and laboratory improvements 4 or 6 months after the RT. Our results suggest that RT is safe and effective in decreasing pain and activity of neurogenic HO. PMID:28119846

  5. Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome.

    PubMed

    Littlejohn, Geoffrey

    2015-11-01

    Although fibromyalgia and complex regional pain syndrome (CRPS) have distinct clinical phenotypes, they do share many other features. Pain, allodynia and dysaesthesia occur in each condition and seem to exist on a similar spectrum. Fibromyalgia and CRPS can both be triggered by specific traumatic events, although fibromyalgia is most commonly associated with psychological trauma and CRPS is most often associated with physical trauma, which is frequently deemed routine or minor by the patient. Fibromyalgia and CRPS also seem to share many pathophysiological mechanisms, among which the most important are those involving central effects. Nonetheless, peripheral effects, such as neurogenic neuroinflammation, are also important contributors to the clinical features of each of these disorders. This Review highlights the differing degrees to which neurogenic neuroinflammation might contribute to the multifactorial pathogenesis of both fibromyalgia and CRPS, and discusses the evidence suggesting that this mechanism is an important link between the two disorders, and could offer novel therapeutic targets.

  6. Pharmacotherapy in Pediatric Neurogenic Bladder Intravesical Botulinum Toxin Type A

    PubMed Central

    Sager, Cristian; Burek, Carol; Durán, Victor; Corbetta, Juan Pablo; Weller, Santiago; Juan, Bortagaray; López, Juan Carlos

    2012-01-01

    When the neurogenic bladder is refractory to anticholinergics, botulinum toxin type A is used as an alternative. The neurotoxin type A reduces bladder pressure and increases its capacity and wall compliance. Additionally, it contributes to improving urinary continence and quality of life. This novel therapy is ambulatory with a low incidence of adverse effects. Due to its transitory effect, it is necessary to repeat the injections in order to sustain its therapeutic effect. In these review article we talk about Mechanism of Action, Indications, effects, administration and presentations of the Botulinum Neurotoxin Type A in pediatric patients. Also, we make references to controversial issues surrounding its use. A bibliographic search was done selecting articles and revisions from Pubmed. The key words used were botulinum toxin A, neurogenic bladder, and children. The search was limited to patients younger than 18 years of age and reports written in English in the past ten years. PMID:22720170

  7. Medical management of neurogenic bladder with oral therapy

    PubMed Central

    2016-01-01

    This is a review of the most current literature on medical management of the neurogenic bladder (NGB) to treat detrusor overactivity (DO), improve bladder compliance and treat urinary incontinence. The use of antimuscarinics, alpha blockers, tricyclic antidepressants, desmopressin and mirabegron will be discussed along with combination therapy to improve efficacy. These medical therapies will be the focus of this review with surgical therapy and botulinum toxin injections being the subject of other articles in this series. PMID:26904412

  8. A dangerous Cushing response in a child: neurogenic heart damage.

    PubMed

    Ruggieri, Francesco; Calvi, Maria Rosa; Beretta, Luigi

    2014-04-01

    Cushing response, which acts to preserve cerebral blood flow by inducing arterial hypertension, could induce neurogenic heart damage through hyperactivation of autonomic nervous system. Most of clinical reports describe neurogenic heart damage as a self-limiting condition clinically characterized by electrocardiographic abnormalities in the setting of an acute neurologic insult. Here we describe a case of life-threatening cardiac dysfunction immediately after a massive intracerebral hemorrhage in a healthy 7-year-old child. The low probability of ischemic heart disease, the poor increase of cardiac necrosis markers, the localization of regional wall motion abnormalities that are not typical for coronary artery disease, and reversibility after brain surgical decompression are consistent all with neurogenic heart damage. Acute decrease of brain oxygen delivery caused by cardiac dysfunction worsens secondary brain injury in the setting of an acute neurologic insult. Thus, Cushing response, which is a physiological mechanism of cerebral protection, could become a double-edged sword when massive sympathetic activation makes the myocardium stunned.

  9. Exosomes as Novel Regulators of Adult Neurogenic Niches

    PubMed Central

    Bátiz, Luis Federico; Castro, Maite A.; Burgos, Patricia V.; Velásquez, Zahady D.; Muñoz, Rosa I.; Lafourcade, Carlos A.; Troncoso-Escudero, Paulina; Wyneken, Ursula

    2016-01-01

    Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the sub-ventricular zone (SVZ) of the lateral ventricles (LV). SGZ newborn neurons are destined to the granular cell layer (GCL) of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb (OB). The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs), which reside in a unique and specialized microenvironment known as “neurogenic niche”. Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid (CSF) or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs). EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs), proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their

  10. Exosomes as Novel Regulators of Adult Neurogenic Niches.

    PubMed

    Bátiz, Luis Federico; Castro, Maite A; Burgos, Patricia V; Velásquez, Zahady D; Muñoz, Rosa I; Lafourcade, Carlos A; Troncoso-Escudero, Paulina; Wyneken, Ursula

    2015-01-01

    Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the sub-ventricular zone (SVZ) of the lateral ventricles (LV). SGZ newborn neurons are destined to the granular cell layer (GCL) of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb (OB). The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs), which reside in a unique and specialized microenvironment known as "neurogenic niche". Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid (CSF) or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs). EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs), proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their roles

  11. Our patients followed up with a diagnosis of neurogenic pulmonary edema

    PubMed Central

    Sarı, Mehmet Yusuf; Yıldızdaş, Rıza Dinçer; Yükselmiş, Ufuk; Horoz, Özden Ögür

    2015-01-01

    Neurogenic pulmonary edema is a clinical situation which developes as a result of central nervous system injury. It is rare in the childhood. Neurogenic pulmonary edema is a clinical diagnosis. Although the pathogenesis is not elucidated well, there is increase in pulmonary interstitial and alveolar fluid. The main principle in treatment of neurogenic pulmonary edema is supportive treatment and decreasing intracranial pressure as in acute respiratory distress syndrome. In this article, clinical properties of our two patients diagnosed with neurogenic pulmonary edema developed as a result of central nervous system injury are presented. PMID:26884694

  12. Renal function in children with congenital neurogenic bladder

    PubMed Central

    Olandoski, Karen Previdi; Koch, Vera; Trigo‐Rocha, Flavio Eduardo

    2011-01-01

    AIMS: Preservation of renal function in children with congenital neurogenic bladder is an important goal of treatment for the disease. This study analyzed the evolution of renal function in patients with congenital neurogenic bladder. METHODS: We reviewed the records of 58 pediatric patients with respect to the following attributes: gender, age, etiology of neurogenic bladder, reason for referral, medical/surgical management, episodes of treated urinary tract infections, urodynamics, DMSA scintigraphy, weight, height, blood pressure, glomerular filtration rate, microalbuminuria and metabolic acidosis. Statistical analysis was performed, adopting the 5% significance level. RESULTS: The mean age at presentation was 4.2 ± 3.5 years. Myelomeningocele was the most frequent etiology (71.4%). Recurrent urinary tract infection was the reason for referral in 82.8% of the patients. Recurrent urinary tract infections were diagnosed in 84.5% of the patients initially; 83.7% of those patients experienced improvement during follow‐up. The initial mean glomerular filtration rate was 146.7 ± 70.1 mL/1.73 m2/min, and the final mean was 193.6 ± 93.6 mL/1.73 m2/min, p  =  0.0004. Microalbuminuria was diagnosed in 54.1% of the patients initially and in 69% in the final evaluation. Metabolic acidosis was present in 19% of the patients initially and in 32.8% in the final assessment. CONCLUSIONS: Patient referral to a pediatric nephrologist was late. A reduction in the number of urinary tract infections was observed with adequate treatment, but microalbuminuria and metabolic acidosis occurred frequently despite adequate management. PMID:21484032

  13. Curative effect assessment of bandage contact lens in neurogenic keratitis

    PubMed Central

    Sun, Yu-Zhao; Guo, Lei; Zhang, Fu-Sheng

    2014-01-01

    AIM To observe the curative effect of bandage contact lens in neurogenic keratitis. METHODS Twenty cases of neurogenic keratitis were studied at the Department of Ophthalmology, the first Affiliated Hospital of China Medical University, between October 2012 and June 2013. These included 13 males and 7 females, aged from 35 to 88y. Patients were voluntarily divided into an experimental group (lens wearing group, n=10) and control group (drug therapy, n=10). In experimental group patients wore silicone hydrogel bandage soft contact lens. Both groups used the following eyedrops: 0.5% levofloxacin TID; 0.5% Sodium carboxymethyl cellulose QID; fibroblast growth factor BID; ganciclovir BID [cases complicated with herpes simplex virus (HSV)]; compound tropicamide BID (cases concurrent hypopyon). The healing time of corneal ulcer and complication rates were observed in the two groups. RESULTS The healing time of corneal ulcer in the experimental group was 10.80±4.44d versus 46.70±13.88d in the control group (P<0.05). No complications occurred in the experimental group, except for the lens falling off twice in one case, the patient recovered eight days after rewearing the lens. While in the control group, all cases vascularized, 2 cases were complicated with descemetocele that recovered with amniotic membrane transplantation and 1 case was complicated with corneal perforation that recovered by autologous conjunctival flap covering. CONCLUSION Bandage contact lens is a safe and effective method of treating neurogenic keratitis and significantly shortened the healing time of corneal ulcer. PMID:25540750

  14. Neurogenic pulmonary edema: successful treatment with IV phentolamine.

    PubMed

    Davison, Danielle L; Chawla, Lakhmir S; Selassie, Leelie; Tevar, Rahul; Junker, Christopher; Seneff, Michael G

    2012-03-01

    Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant CNS insult. The cause is believed to be a surge of catecholamines that results in cardiopulmonary dysfunction. Although there are myriad case reports describing CNS events that are associated with this syndrome, few studies have identified specific treatment modalities. We present a case of NPE caused by an intracranial hemorrhage from a ruptured arteriovenous malformation. We uniquely document a rise and fall of serum catecholamine levels correlating with disease activity and a dramatic clinical response to IV phentolamine.

  15. Urofacial syndrome: a subset of neurogenic bladder dysfunction syndromes?

    PubMed

    Stamatiou, K; Tyritzis, S; Karakos, C; Skolarikos, A

    2011-10-01

    The urofacial syndrome (Ochoa syndrome) is considered to represent a subgroup of the non-neurogenic bladder dysfunction, characterized by non-neuropathic bladder-sphincter dysfunction, along with a characteristic inversion of the facial expression with laughing. Recent research suggests that it is probably a genetic inherited disease transmitted in an autosomal recessive fashion and might represent a distinct entity. We report a case of this syndrome in a 14-year-old boy who presented with left pyelonephritis, hydronephrosis, and bladder dilation.

  16. Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report.

    PubMed

    Scola, R H; Werneck, L C; Iwamoto, F M; Ribas, L C; Raskin, S; Correa Neto, Y

    2001-06-01

    We report the case of a 3-(1/2)-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA). The serum muscle enzymes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous.

  17. [Advance of neurogenic erectile dysfunction therapy by stem cells].

    PubMed

    Shen, Han-Jian; Zhu, Guang-You

    2010-06-01

    Neurogenic erectile dysfunction (NED) commonly results from erectile nerve damage. Recent researches have focused on the preclinical study of stem cell-based therapies targeted at repairing and protecting nervi erigentes. In this paper, researches of NESCs, MDSCs, ASCs and MSCs in NED are reviewed. Early studies have demonstrated that stem cells and gene modified stem cells were effective to the therapy of ED, even likely to cure ED. Stem cells are expected to be applied in the clinical therapy of NED. Stem cells as a new therapy technique will bring up a new challenge in forensic clinical medicine.

  18. A One Year Prospective Study of Neurogenic Stuttering Following Stroke: Incidence and Co-Occurring Disorders

    ERIC Educational Resources Information Center

    Theys, C.; van Wieringen, A.; Sunaert, S.; Thijs, V.; De Nil, L. F.

    2011-01-01

    In this prospective study, data on incidence, stuttering characteristics, co-occurring speech disorders, and recovery of neurogenic stuttering in a large sample of stroke participants were assessed. Following stroke onset, 17 of 319 participants (5.3%; 95% CI, 3.2-8.3) met the criteria for neurogenic stuttering. Stuttering persisted in at least…

  19. The 'ventral organs' of Pycnogonida (Arthropoda) are neurogenic niches of late embryonic and post-embryonic nervous system development.

    PubMed

    Brenneis, Georg; Scholtz, Gerhard

    2014-01-01

    Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i) immunolabeling, (ii) histology and (iii) scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida), the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions - traditionally designated as 'ventral organs' - detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult) replenishment of olfactory neurons - as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two transient posterior

  20. [Neurological Signs and Symptoms of True Neurogenic Thoracic Outlet Syndrome].

    PubMed

    Higashihara, Mana; Konoeda, Fumie; Sonoo, Masahiro

    2016-05-01

    Thoracic outlet syndrome (TOS) is a well-known disorder, but many aspects of its pathology, including its definition, has been disputed. True neurogenic TOS (TN-TOS) is a rare but well-defined clinical condition. TN-TOS results from the compression of the C8/T1 roots (dominant for the T1 root) or the proximal lower trunk of the brachial plexus by a fibrous band. The band extends from the first rib to either the tip of an elongated C7 transverse process or a rudimentary cervical rib. The most common presenting symptoms of TN-TOS are insidious-onset atrophy and weakness of the intrinsic hand muscles, predominantly in the thenar eminence and radial digit flexors. Nerve conduction studies demonstrate pathognomonic findings: severely attenuated compound muscle action potential of the abductor pollicis brevis muscle, and usually, loss of the sensory nerve action potential of the medial antebrachial cutaneous nerve. Numbness and sensory loss are typically observed, mainly in the medial forearm, although they are usually mild, and may be absent in some patients. Severe pain or paresthesia proximal to the elbow is not observed. The classical concept of TOS underlie nonspecific neurogenic TOS. It has been primarily diagnosed using provocative maneuvers. However, there is controversy regarding its pathological conceptualization and existence, as objective evidence of the disease is still lacking.

  1. Epigenetic regulation of stemness maintenance in the neurogenic niches

    PubMed Central

    Montalbán-Loro, Raquel; Domingo-Muelas, Ana; Bizy, Alexandra; Ferrón, Sacri R

    2015-01-01

    In the adult mouse brain, the subventricular zone lining the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus are two zones that contain neural stem cells (NSCs) with the capacity to give rise to neurons and glia during the entire life of the animal. Spatial and temporal regulation of gene expression in the NSCs population is established and maintained by the coordinated interaction between transcription factors and epigenetic regulators which control stem cell fate. Epigenetic mechanisms are heritable alterations in genome function that do not involve changes in DNA sequence itself but that modulate gene expression, acting as mediators between the environment and the genome. At the molecular level, those epigenetic mechanisms comprise chemical modifications of DNA such as methylation, hydroxymethylation and histone modifications needed for the maintenance of NSC identity. Genomic imprinting is another normal epigenetic process leading to parental-specific expression of a gene, known to be implicated in the control of gene dosage in the neurogenic niches. The generation of induced pluripotent stem cells from NSCs by expression of defined transcription factors, provide key insights into fundamental principles of stem cell biology. Epigenetic modifications can also occur during reprogramming of NSCs to pluripotency and a better understanding of this process will help to elucidate the mechanisms required for stem cell maintenance. This review takes advantage of recent studies from the epigenetic field to report knowledge regarding the mechanisms of stemness maintenance of neural stem cells in the neurogenic niches. PMID:26029342

  2. Midline synovial and ganglion cysts causing neurogenic claudication

    PubMed Central

    Pindrik, Jonathan; Macki, Mohamed; Bydon, Mohamad; Maleki, Zahra; Bydon, Ali

    2013-01-01

    Typically situated posterolateral in the spinal canal, intraspinal facet cysts often cause radicular symptoms. Rarely, the midline location of these synovial or ganglion cysts may cause thecal sac compression leading to neurogenic claudication or cauda equina syndrome. This article summarizes the clinical presentation, radiographic appearance, and management of three intraspinal, midline facet cysts. Three patients with symptomatic midline intraspinal facet cysts were retrospectively reviewed. Documented clinical visits, operative notes, histopathology reports, and imaging findings were investigated for each patient. One patient presented with neurogenic claudication while two patients developed partial, subacute cauda equina syndrome. All 3 patients initially responded favorably to lumbar decompression and midline cyst resection; however, one patient required surgical stabilization 8 mo later. Following the three case presentations, we performed a thorough literature search in order to identify articles describing intraspinal cystic lesions in lateral or midline locations. Midline intraspinal facet cysts represent an uncommon cause of lumbar stenosis and thecal sac compression. Such entities should enter the differential diagnosis of midline posterior cystic lesions. Midline cysts causing thecal sac compression respond favorably to lumbar surgical decompression and cyst resection. Though laminectomy is a commonly performed operation, stabilization may be required in cases of spondylolisthesis or instability. PMID:24364023

  3. Analysis of carbonated thin liquids in pediatric neurogenic dysphagia

    PubMed Central

    Lundine, Jennifer P.; Bates, David G.; Yin, Han

    2015-01-01

    Background Aspiration of liquids is a serious complication of neurological impairments such as traumatic brain injury or stroke. Carbonated liquids have been examined as a possible alternative to thickened liquids to help reduce aspiration in cases of dysphagia in adults, but no published literature to the best of our knowledge has evaluated this technique in children. If carbonated liquids result in safer swallowing in children, they could provide a preferred alternative to thickened liquids. Objective This pilot study examined whether carbonated thin liquids (CARB) improved swallowing compared to noncarbonated thin liquids (NOCARB) for children with neurogenic dysphagia. Materials and methods Twenty-four children admitted to a level I trauma center for acute neurological injury/disease were evaluated via videofluoroscopic swallow studies. Four descriptive outcome measures were contrasted. Results CARB significantly decreased pooling (P=0.0006), laryngeal penetration/aspiration (P=0.0044) and Penetration-Aspiration Scale scores (P=0.0127) when compared to NOCARB. On average, CARB improved scores on the Penetration-Aspiration Scale by 3.7 points for participants who aspirated NOCARB. There was no significant difference in pharyngeal residue noted between CARB and NOCARB (P=0.0625). Conclusion These findings support the hypothesis that carbonated thin liquids may provide an alternative to thickened liquids for children with neurogenic dysphagia. Implications for future research and clinical practice are discussed. PMID:25758792

  4. Midline synovial and ganglion cysts causing neurogenic claudication.

    PubMed

    Pindrik, Jonathan; Macki, Mohamed; Bydon, Mohamad; Maleki, Zahra; Bydon, Ali

    2013-12-16

    Typically situated posterolateral in the spinal canal, intraspinal facet cysts often cause radicular symptoms. Rarely, the midline location of these synovial or ganglion cysts may cause thecal sac compression leading to neurogenic claudication or cauda equina syndrome. This article summarizes the clinical presentation, radiographic appearance, and management of three intraspinal, midline facet cysts. Three patients with symptomatic midline intraspinal facet cysts were retrospectively reviewed. Documented clinical visits, operative notes, histopathology reports, and imaging findings were investigated for each patient. One patient presented with neurogenic claudication while two patients developed partial, subacute cauda equina syndrome. All 3 patients initially responded favorably to lumbar decompression and midline cyst resection; however, one patient required surgical stabilization 8 mo later. Following the three case presentations, we performed a thorough literature search in order to identify articles describing intraspinal cystic lesions in lateral or midline locations. Midline intraspinal facet cysts represent an uncommon cause of lumbar stenosis and thecal sac compression. Such entities should enter the differential diagnosis of midline posterior cystic lesions. Midline cysts causing thecal sac compression respond favorably to lumbar surgical decompression and cyst resection. Though laminectomy is a commonly performed operation, stabilization may be required in cases of spondylolisthesis or instability.

  5. Msxb is a core component of the genetic circuitry specifying the dorsal and ventral neurogenic midlines in the ascidian embryo.

    PubMed

    Roure, Agnès; Darras, Sébastien

    2016-01-01

    The tail ascidian larval peripheral nervous system is made up of epidermal sensory neurons distributed more or less regularly in ventral and dorsal midlines. Their formation occurs in two-steps: the ventral and dorsal midlines are induced as neurogenic territories by Fgf9/16/20 and Admp respectively. The Delta2/Notch interaction then controls the number of neurons that form. The genetic machinery acting between the inductive processes taking place before gastrulation and neuron specification at tailbud stages are largely unknown. The analysis of seven transcription factors expressed in the forming midlines revealed an unexpected complexity and dynamic of gene expression. Their systematic overexpression confirmed that these genes do not interact following a linear cascade of activation. However, the integration of our data revealed the distinct key roles of the two upstream factors Msxb and Nkx-C that are the earliest expressed genes and the only ones able to induce neurogenic midline and ESN formation. Our data suggest that Msxb would be the primary midline gene integrating inputs from the ventral and dorsal inducers and launching a pan-midline transcriptional program. Nkx-C would be involved in tail tip specification, in maintenance of the pan-midline network and in a posterior to anterior wave controlling differentiation.

  6. GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease.

    PubMed

    Kamphuis, Willem; Mamber, Carlyn; Moeton, Martina; Kooijman, Lieneke; Sluijs, Jacqueline A; Jansen, Anne H P; Verveer, Monique; de Groot, Lody R; Smith, Vanessa D; Rangarajan, Sindhoo; Rodríguez, José J; Orre, Marie; Hol, Elly M

    2012-01-01

    Glial fibrillary acidic protein (GFAP) is the main astrocytic intermediate filament (IF). GFAP splice isoforms show differential expression patterns in the human brain. GFAPδ is preferentially expressed by neurogenic astrocytes in the subventricular zone (SVZ), whereas GFAP(+1) is found in a subset of astrocytes throughout the brain. In addition, the expression of these isoforms in human brain material of epilepsy, Alzheimer and glioma patients has been reported. Here, for the first time, we present a comprehensive study of GFAP isoform expression in both wild-type and Alzheimer Disease (AD) mouse models. In cortex, cerebellum, and striatum of wild-type mice, transcripts for Gfap-α, Gfap-β, Gfap-γ, Gfap-δ, Gfap-κ, and a newly identified isoform Gfap-ζ, were detected. Their relative expression levels were similar in all regions studied. GFAPα showed a widespread expression whilst GFAPδ distribution was prominent in the SVZ, rostral migratory stream (RMS), neurogenic astrocytes of the subgranular zone (SGZ), and subpial astrocytes. In contrast to the human SVZ, we could not establish an unambiguous GFAPδ localization in proliferating cells of the mouse SVZ. In APPswePS1dE9 and 3xTgAD mice, plaque-associated reactive astrocytes had increased transcript levels of all detectable GFAP isoforms and low levels of a new GFAP isoform, Gfap-ΔEx7. Reactive astrocytes in AD mice showed enhanced GFAPα and GFAPδ immunolabeling, less frequently increased vimentin and nestin, but no GFAPκ or GFAP(+1) staining. In conclusion, GFAPδ protein is present in SVZ, RMS, and neurogenic astrocytes of the SGZ, but also outside neurogenic niches. Furthermore, differential GFAP isoform expression is not linked with aging or reactive gliosis. This evidence points to the conclusion that differential regulation of GFAP isoforms is not involved in the reorganization of the IF network in reactive gliosis or in neurogenesis in the mouse brain.

  7. Urofacial syndrome: A subset of neurogenic bladder dysfunction syndromes?

    PubMed Central

    Stamatiou, K. N.; Karakos, C. D.

    2010-01-01

    The urofacial syndrome is probably a subset of neurogenic bladder dysfunction syndromes characterized by detrusor-sphincter discoordination along with a characteristic inversion of facial expression with laughing. This characteristic facial expression can facilitate early detection of this disorder, which leads to poor bladder emptying with high residual urine, hydro-nephrosis with vesico-ureteral reflux and potentially renal failure if left untreated. The etiology of the urofacial syndrome is unknown. In our case, a 12-year-old boy of Middle-Eastern origin presented to the Outpatient Department of our hospital with left pyelonephritis, hydronephrosis and bladder dilatation. Voiding cystourethrography performed 15 days later revealed left vesicoureteral reflux. Cystoscopy revealed bladder trabeculation however an anatomic urethral obstruction was not noticed. Both, neurological examination and radiography of the lumbosacral spine were normal. Urodynamic evaluation revealed the typical findings of detrusor-sphincter discoordination. PMID:21369396

  8. Urofacial syndrome: A subset of neurogenic bladder dysfunction syndromes?

    PubMed

    Stamatiou, K N; Karakos, C D

    2010-10-01

    The urofacial syndrome is probably a subset of neurogenic bladder dysfunction syndromes characterized by detrusor-sphincter discoordination along with a characteristic inversion of facial expression with laughing. This characteristic facial expression can facilitate early detection of this disorder, which leads to poor bladder emptying with high residual urine, hydro-nephrosis with vesico-ureteral reflux and potentially renal failure if left untreated. The etiology of the urofacial syndrome is unknown. In our case, a 12-year-old boy of Middle-Eastern origin presented to the Outpatient Department of our hospital with left pyelonephritis, hydronephrosis and bladder dilatation. Voiding cystourethrography performed 15 days later revealed left vesicoureteral reflux. Cystoscopy revealed bladder trabeculation however an anatomic urethral obstruction was not noticed. Both, neurological examination and radiography of the lumbosacral spine were normal. Urodynamic evaluation revealed the typical findings of detrusor-sphincter discoordination.

  9. Neurogenic inflammation in the gastrointestinal tract of the rat.

    PubMed

    Sann, H; Dux, M; Schemann, M; Jancsó, G

    1996-11-29

    In contrast to the skin and some visceral organs the capability of capsaicin-sensitive sensory nerves of evoking an inflammatory response in the gastrointestinal tract is equivocal. We have therefore investigated the neurogenic plasma extravasation induced by local application of capsaicin to the stomach, duodenum, jejunum, ileum and colon of the rat. Permeable vessels were visualised histologically with the vascular labelling technique using colloidal silver. In the smooth muscle layer of the small intestine, capsaicin elicited a 3-fold increase in the density of labelled blood vessels (diameter, 7-35 microns). Significant capsaicin-evoked plasma extravasation was also observed in the submucosa of the jejunum and ileum, and in the basal layer of the jejunal mucosa. Capsaicin-induced extravasation was not noted in the stomach and the colon. The data suggest the involvement of capsaicin-sensitive afferents in inflammatory processes in the rat small intestine.

  10. Persistent neurogenic bladder dysfunction due to infantile botulism.

    PubMed

    Breinbjerg, Anders; Rittig, Søren; Kamperis, Konstantinos

    2014-01-13

    We present a child, 5 months of age, diagnosed with infantile botulism, showing the signs of neurogenic bladder dysfunction. The patient presented with progressive muscle weakness, hypotonia, suckling and swallowing problems and absent peripheral reflexes at clinical examination. Botulinum neurotoxin type A was detected in her serum, confirming the diagnosis. Starting at day 6, the girl presented with a urinary retention initially necessitating free bladder drainage and subsequently intermittent catheterisation. After 6 weeks in intensive care, the patient recovered but the bladder underactivity persisted. Four months following recovery, a urodynamic evaluation was performed, showing a near normal detrusor activity and normal bladder emptying, and the catheterisation was ceased. At 6 months, the girl was diagnosed with a urinary tract infection and bladder emptying problems, which persisted, and clean intermittent catheterisation was started. The final urodynamic evaluation, a year and a half after her initial presentation, revealed a normal detrusor activity and an adequate bladder emptying.

  11. Neurogenic cardiomyopathy in rabbits with experimentally induced rabies.

    PubMed

    Kesdangsakonwut, S; Sunden, Y; Yamada, K; Nishizono, A; Sawa, H; Umemura, T

    2015-05-01

    Cardiomyopathies have been rarely described in rabbits. Here we report myocardial necrosis of the ventricular wall in rabbits with experimentally induced rabies. Myocardial lesions were found only in rabbits with brain lesions, and the severity of the cardiac lesions was proportional to that of the brain lesions. Neither the frequency nor the cumulative dose of anesthesia was related to the incidence or the severity of the myocardial lesions. The myocardial lesions were characterized by degeneration and/or necrosis of myocardial cells and were accompanied by contraction band necrosis, interstitial fibrosis, and infiltration of inflammatory cells. The brain lesions due to rabies virus infection were most prominent in the cerebral cortex, thalamus, hypothalamus, brainstem, and medulla. Rabies virus antigen was not found in the hearts of any rabbits. Based on these findings, the myocardial lesions were classified as neurogenic cardiomyopathy.

  12. Unlocking the Neurogenic Potential of Mammalian Müller Glia

    PubMed Central

    Xia, Xiaohuan; Ahmad, Iqbal

    2016-01-01

    Müller glia (MG) are the primary support cells in the vertebrate retina, regulating homeostasis in one of the most metabolically active tissues. In lower vertebrates such as fish, they respond to injury by proliferating and reprogramming to regenerate retinal neurons. In mammals, MG may also react to injury by proliferating, but they fail to initiate regeneration. The barriers to regeneration could be intrinsic to mammalian MG or the function of the niche that cannot support the MG reprogramming required for lineage conversion or both. Understanding these mechanisms in light of those being discovered in fish may lead to the formulation of strategies to unlock the neurogenic potential of MG and restore regeneration in the mammalian retina. PMID:27572710

  13. Medial antebrachial cutaneous sensory studies in the evaluation of neurogenic thoracic outlet syndrome.

    PubMed

    Kothari, M J; Macintosh, K; Heistand, M; Logigian, E L

    1998-05-01

    Over 3 years, we studied 8 patients with neurogenic thoracic outlet syndrome (TOS) and tested the medial antebrachial sensory response (MASR) to determine its diagnostic value. The MASR and ulnar sensory response (USR) were abnormal in all 8 patients. Seven had a low median motor response (MMR) with a low USR. In 1, the MASR and USR were abnormal but the MMR was normal. We conclude that the MASR is of diagnostic value in patients with neurogenic TOS.

  14. Drinking to near death--acute water intoxication leading to neurogenic stunned myocardium.

    PubMed

    Losonczy, Lia I; Lovallo, Emily; Schnorr, C Daniel; Mantuani, Daniel

    2016-01-01

    Neurogenic stunned myocardium is a rare disease entity that has been typically described as a consequence of subarachnoid hemorrhage and, less commonly, seizures. Here we describe a case of a healthy young woman who drank excessive free water causing acute hyponatremia complicated by cerebral edema and seizure, leading to cardiogenic shock from neurogenic stunned myocardium. Two days later, she had complete return of her normal cardiac function.

  15. Molecular analyses of neurogenic defects in a human pluripotent stem cell model of fragile X syndrome.

    PubMed

    Boland, Michael J; Nazor, Kristopher L; Tran, Ha T; Szücs, Attila; Lynch, Candace L; Paredes, Ryder; Tassone, Flora; Sanna, Pietro Paolo; Hagerman, Randi J; Loring, Jeanne F

    2017-03-01

    New research suggests that common pathways are altered in many neurodevelopmental disorders including autism spectrum disorder; however, little is known about early molecular events that contribute to the pathology of these diseases. The study of monogenic, neurodevelopmental disorders with a high incidence of autistic behaviours, such as fragile X syndrome, has the potential to identify genes and pathways that are dysregulated in autism spectrum disorder as well as fragile X syndrome. In vitro generation of human disease-relevant cell types provides the ability to investigate aspects of disease that are impossible to study in patients or animal models. Differentiation of human pluripotent stem cells recapitulates development of the neocortex, an area affected in both fragile X syndrome and autism spectrum disorder. We have generated induced human pluripotent stem cells from several individuals clinically diagnosed with fragile X syndrome and autism spectrum disorder. When differentiated to dorsal forebrain cell fates, our fragile X syndrome human pluripotent stem cell lines exhibited reproducible aberrant neurogenic phenotypes. Using global gene expression and DNA methylation profiling, we have analysed the early stages of neurogenesis in fragile X syndrome human pluripotent stem cells. We discovered aberrant DNA methylation patterns at specific genomic regions in fragile X syndrome cells, and identified dysregulated gene- and network-level correlates of fragile X syndrome that are associated with developmental signalling, cell migration, and neuronal maturation. Integration of our gene expression and epigenetic analysis identified altered epigenetic-mediated transcriptional regulation of a distinct set of genes in fragile X syndrome. These fragile X syndrome-aberrant networks are significantly enriched for genes associated with autism spectrum disorder, giving support to the idea that underlying similarities exist among these neurodevelopmental diseases.

  16. [A case of death due to neurogenic shock].

    PubMed

    Ogata, M; Ago, K; Ago, M; Tsuganezawa, O

    1992-04-01

    An autopsy case of death due probably to neurogenic shock (primary shock) is reported. A 14-year-old boy got into a fight with his elder brother and received blows against the chest and abdomen. The young boy fell down senseless on the floor and had a spasm. An ambulance was called, but he was dead on arrival at a hospital. An autopsy revealed no external injuries on the chest and abdomen. There was no evidence of preexisting disease. On histological examination, there were signs of acute cardiac failure; edema of the lungs, liver and gall bladder, partial myofibrillar degeneration and cytoplasmic vacuoles in the media of a small coronary artery. Thus, the autopsy did not give any explanation of the fatality. It seems probable, however, that the blow(s) against the abdomen (the solar plexus) caused a fatal shock (vagal inhibition). In addition, the adrenal cortices (especially the zona fasciculata) were narrowed and the aorta was slightly narrow in caliber. It is likely that these hypoplasia might affect the fatal shock consequent to very slight injuries.

  17. Stem cells with neurogenic potential and steroid hormones.

    PubMed

    Velasco, Iván

    2011-01-01

    Pluripotent and multipotent stem cells with differentiation potential to neural phenotypes have been described and characterized in the last decades. Embryonic stem cells, as well as neural stem cells from developing and adult nervous system, can differentiate into different types of neurons, astrocytes or oligodendrocytes. Although the initially identified actions of estradiol, progesterone and testosterone are related to sexual reproductive functions, recent evidence shows that these steroid hormones modulate development, physiology and survival of nerve cells. Furthermore, neurosteroids can be synthesized in the developing and adult nervous system. A description of the molecular modulatory actions of sex steroid hormones on the Central Nervous System is presented. The main focus of this review is to summarize the described effects of steroid hormones (progesterone, allopregnanolone, dehydroepiandrosterone, estradiol and androgens) on cell parameters relevant to stem cells, both in vitro and in vivo. The overall conclusion is that steroid hormones influence stem cell behavior by several mechanisms, namely regulation of gene expression by binding to their cognate receptors, activation of intracellular pathways involving kinases or intracellular calcium signaling, and modulation of receptors for neurotransmitters; in some instances, these hormones can substitute or modulate the action of growth factors, and also directly influence self-renewal, proliferation, differentiation or cell death of neurogenic stem cells.

  18. Botulinum toxin injections for treating neurogenic detrusor overactivity

    PubMed Central

    Bayrak, Ömer; Sadioğlu, Erkan; Onur, Rahmi

    2015-01-01

    Neurogenic detrusor overactivity (NDO) is a disorder that can cause high intravesical pressure, decreased capacity, decreased bladder compliance, and upper urinary system damage. The current treatment options for NDO are established on the basis of agents that block parasympathetic innervation of the detrusor and inhibit involuntary bladder contractions. Several side effects, such as dryness of mouth, constipation, dyspepsia, changes in visual accommodation, somnolence, and being unable to obtain consistently favorable results, caused by anticholinergic agents, which are frequently used for this purpose, decrease the patient’s compliance to treatment. Procedures such as neuromodulation, auto-augmentation, and enterocystoplasty are surgical options, and they could be used as the last alternative. Thus, botulinum toxin (BTX) injections to the detrusor have been commonly performed in recent years and lead to satisfactory results. The mechanism of action of BTX in NDO is based on the principal of smooth muscle relaxation in the bladder by the transient inhibition of neuromuscular nerve signals. The aim is to decrease acetylcholine secretion by blocking presynaptic vesicles in the neuromuscular junction. When studies were evaluated, it was observed that BTX injections to the detrusor muscle are a necessary and effective option in patients with incontinence caused by NDO. This treatment option could be indicated in situations where anticholinergic agents are not effective or could not be tolerated, and it could be a valuable alternative to major surgical treatments. In this review, we evaluated the effectiveness and reliability of BTX in patients with NDO. PMID:26623152

  19. Characterization of the spectrum of hemodynamic profiles in trauma patients with acute neurogenic shock☆

    PubMed Central

    Summers, Richard L.; Baker, Stephen D.; Sterling, Sarah A.; Porter, John M; Jones, Alan E.

    2014-01-01

    Objective Neurogenic shock considered a distributive type of shock secondary to loss of sympathetic outflow to the peripheral vasculature. In this study, we examine the hemodynamic profiles of a series of trauma patients with a diagnosis of neurogenic shock. Methods Hemodynamic data were collected on a series of trauma patients determined to have spinal cord injuries with neurogenic shock. A well-established integrated computer model of human physiology was used to analyze and categorize the hemodynamic profiles from a system analysis perspective. A differentiation between these categories was presented as the percent of total patients. Results Of the 9 patients with traumatic neurogenic shock, the etiology of shock was decrease in peripheral vascular resistance (PVR) in 3 (33%; 95% confidence interval, 12%–65%), loss of vascular capacitance in 2 (22%; 6%–55%) and mixed peripheral resistance and capacitance responsible in 3 (33%; 12%–65%), and purely cardiac in 1 (11%; 3%–48%). The markers of sympathetic outflow had no correlation to any of the elements in the patients' hemodynamic profiles. Conclusions Results from this study suggest that hypotension of neurogenic shock can have multiple mechanistic etiologies and represents a spectrum of hemodynamic profiles. This understanding is important for the treatment decisions in managing these patients. PMID:23566731

  20. Neurogenic Fever after Acute Traumatic Spinal Cord Injury: A Qualitative Systematic Review

    PubMed Central

    Savage, Katherine E.; Oleson, Christina V.; Schroeder, Gregory D.; Sidhu, Gursukhman S.; Vaccaro, Alexander R.

    2016-01-01

    Study Design  Systematic review. Objective  To determine the incidence, pathogenesis, and clinical outcomes related to neurogenic fevers following traumatic spinal cord injury (SCI). Methods  A systematic review of the literature was performed on thermodysregulation secondary to acute traumatic SCI in adult patients. A literature search was performed using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus. Using strict inclusion and exclusion criteria, seven relevant articles were obtained. Results  The incidence of fever of all origins (both known and unknown) after SCI ranged from 22.5 to 71.7% with a mean incidence of 50.6% and a median incidence of 50.0%. The incidence of fever of unknown origin (neurogenic fever) ranged from 2.6 to 27.8% with a mean incidence of 8.0% and a median incidence of 4.7%. Cervical and thoracic spinal injuries were more commonly associated with fever than lumbar injuries. In addition, complete injuries had a higher incidence of fever than incomplete injuries. The pathogenesis of neurogenic fever after acute SCI is not thoroughly understood. Conclusion  Neurogenic fevers are relatively common following an acute SCI; however, there is little in the scientific literature to help physicians prevent or treat this condition. The paucity of research underscored by this review demonstrates the need for further studies with larger sample sizes, focusing on incidence rate, clinical outcomes, and pathogenesis of neurogenic fever following acute traumatic SCI. PMID:27556002

  1. Non-neurogenic SVZ-like niche in dolphins, mammals devoid of olfaction.

    PubMed

    Parolisi, Roberta; Cozzi, Bruno; Bonfanti, Luca

    2017-02-25

    Adult neurogenesis has been implicated in brain plasticity and brain repair. In mammals, it is mostly restricted to specific brain regions and specific physiological functions. The function and evolutionary history of mammalian adult neurogenesis has been elusive so far. The largest neurogenic site in mammals (subventricular zone, SVZ) generates neurons destined to populate the olfactory bulb. The SVZ neurogenic activity appears to be related to the dependence of the species on olfaction since it occurs at high rates throughout life in animals strongly dependent on this function for their survival. Indeed, it dramatically decreases in humans, who do not depend so much on it. This study investigates whether the SVZ neurogenic site exists in mammals devoid of olfaction and olfactory brain structures, such as dolphins. Our results demonstate that a small SVZ-like region persists in these aquatic mammals. However, this region seems to have lost its neurogenic capabilities since neonatal stages. In addition, instead of the typical newly generated neuroblasts, some mature neurons were observed in the dolphin SVZ. Since cetaceans evolved from terrestrial ancestors, non-neurogenic SVZ may indicate extinction of adult neurogenesis in the absence of olfactory function, with the retention of an SVZ-like anatomical region either vestigial or of still unknown role.

  2. PET imaging of neurogenic activity in the adult brain: Toward in vivo imaging of human neurogenesis.

    PubMed

    Tamura, Yasuhisa; Kataoka, Yosky

    2017-01-01

    Neural stem cells are present in 2 neurogenic regions, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), and continue to generate new neurons throughout life. Adult hippocampal neurogenesis is linked to a variety of psychiatric disorders such as depression and anxiety, and to the therapeutic effects of antidepressants, as well as learning and memory. In vivo imaging for hippocampal neurogenic activity may be used to diagnose psychiatric disorders and evaluate the therapeutic efficacy of antidepressants. However, these imaging techniques remain to be established until now. Recently, we established a quantitative positron emission tomography (PET) imaging technique for neurogenic activity in the adult brain with 3'-deoxy-3'-[(18)F]fluoro-L-thymidine ([(18)F]FLT) and probenecid, a drug transporter inhibitor in blood-brain barrier. Moreover, we showed that this PET imaging technique can monitor alterations in neurogenic activity in the hippocampus of adult rats with depression and following treatment with an antidepressant. This PET imaging method may assist in diagnosing depression and in monitoring the therapeutic efficacy of antidepressants. In this commentary, we discuss the possibility of in vivo PET imaging for neurogenic activity in adult non-human primates and humans.

  3. Urodynamic and physiologic patterns associated with the common causes of neurogenic bladder in adults.

    PubMed

    Allio, Bryce Andrew; Peterson, Andrew Charles

    2016-02-01

    The clinical presentation of the neurogenic bladder can be as vast as the pathologic causes however urodynamics (UDS) can help guide clinical decision-making and help simplify a complex disease state. UDS may be considered as the gold standard in helping to break down complex and multifactorial voiding dysfunction into manageable goals; these include protecting the upper tracts, limiting urinary tract infections (UTI) via avoiding urinary stasis, and maintaining quality of life. Included within are examples of normal to pathologic tracings including normal filling and voiding, detrusor sphincteric coordination, changes in compliance, etc. Additionally we have provided expected UDS findings based on neurogenic disease process, including but not limited to, Parkinson's, dementia, multiple sclerosis (MS) and spinal cord injury based on lesion location. Pattern recognition and understanding of UDS can help lead to quality of life improvements and optimal management for the patient with neurogenic bladder dysfunction.

  4. Urodynamic and physiologic patterns associated with the common causes of neurogenic bladder in adults

    PubMed Central

    Peterson, Andrew Charles

    2016-01-01

    The clinical presentation of the neurogenic bladder can be as vast as the pathologic causes however urodynamics (UDS) can help guide clinical decision-making and help simplify a complex disease state. UDS may be considered as the gold standard in helping to break down complex and multifactorial voiding dysfunction into manageable goals; these include protecting the upper tracts, limiting urinary tract infections (UTI) via avoiding urinary stasis, and maintaining quality of life. Included within are examples of normal to pathologic tracings including normal filling and voiding, detrusor sphincteric coordination, changes in compliance, etc. Additionally we have provided expected UDS findings based on neurogenic disease process, including but not limited to, Parkinson’s, dementia, multiple sclerosis (MS) and spinal cord injury based on lesion location. Pattern recognition and understanding of UDS can help lead to quality of life improvements and optimal management for the patient with neurogenic bladder dysfunction. PMID:26904410

  5. A comparison of hyperalgesia and neurogenic inflammation induced by melittin and capsaicin in humans.

    PubMed

    Sumikura, H; Andersen, O K; Drewes, A M; Arendt-Nielsen, L

    2003-02-13

    Melittin (a main compound of bee venom) and capsaicin were injected intradermally in healthy human volunteers: (1) to study secondary mechanical hyperalgesia (static hyperalgesia and dynamic hyperalgesia) around the injection site; and (2) to correlate the sensory changes to the neurogenic inflammation assessed by laser-doppler blood flowmetry. Melittin 50 microg and capsaicin 10 microg induced comparable spontaneous pain and increased blood flow (neurogenic inflammation). Intradermal injection of melittin induced regions of secondary mechanical hyperalgesia around the injection site, however, they were not as large as the hyperalgesia induced by capsaicin. This is the first report studying mechanical hyperalgesia induced by melittin in humans, and the results were in agreement with the previous observations in rats. Melittin seems to be a valuable model to study a possible contribution of neurogenic inflammation to hyperalgesia in humans.

  6. Characterization of multiciliated ependymal cells that emerge in the neurogenic niche of the aged zebrafish brain.

    PubMed

    Ogino, Takashi; Sawada, Masato; Takase, Hiroshi; Nakai, Chiemi; Herranz-Pérez, Vicente; Cebrián-Silla, Arantxa; Kaneko, Naoko; García-Verdugo, José Manuel; Sawamoto, Kazunobu

    2016-10-15

    In mammals, ventricular walls of the developing brain maintain a neurogenic niche, in which radial glial cells act as neural stem cells (NSCs) and generate new neurons in the embryo. In the adult brain, the neurogenic niche is maintained in the ventricular-subventricular zone (V-SVZ) of the lateral wall of lateral ventricles and the hippocampal dentate gyrus. In the neonatal V-SVZ, radial glial cells transform into astrocytic postnatal NSCs and multiciliated ependymal cells. On the other hand, in zebrafish, radial glial cells continue to cover the surface of the adult telencephalic ventricle and maintain a higher neurogenic potential in the adult brain. However, the cell composition of the neurogenic niche of the aged zebrafish brain has not been investigated. Here we show that multiciliated ependymal cells emerge in the neurogenic niche of the aged zebrafish telencephalon. These multiciliated cells appear predominantly in the dorsal part of the ventral telencephalic ventricular zone, which also contains clusters of migrating new neurons. Scanning electron microscopy and live imaging analyses indicated that these multiple cilia beat coordinately and generate constant fluid flow within the ventral telencephalic ventricle. Analysis of the cell composition by transmission electron microscopy revealed that the neurogenic niche in the aged zebrafish contains different types of cells, with ultrastructures similar to those of ependymal cells, transit-amplifying cells, and migrating new neurons in postnatal mice. These data suggest that the transformation capacity of radial glial cells is conserved but that its timing is different between fish and mice. J. Comp. Neurol. 524:2982-2992, 2016. © 2016 Wiley Periodicals, Inc.

  7. The ‘Ventral Organs’ of Pycnogonida (Arthropoda) Are Neurogenic Niches of Late Embryonic and Post-Embryonic Nervous System Development

    PubMed Central

    Brenneis, Georg; Scholtz, Gerhard

    2014-01-01

    Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i) immunolabeling, (ii) histology and (iii) scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida), the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions – traditionally designated as ‘ventral organs’ – detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult) replenishment of olfactory neurons – as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two transient

  8. Improving Outcomes in Patients With Refractory Idiopathic and Neurogenic Detrusor Overactivity: Management Strategies.

    PubMed

    Ginsberg, David A; Schneider, Lynne Kolton; Watanabe, Thomas K

    2015-09-01

    Neurogenic detrusor overactivity (NDO) is a lower urinary tract dysfunction commonly seen in rehabilitation settings. The emotional, medical, and financial consequences of NDO can be substantial and management typically requires a multidisciplinary team approach. Physiatrists need to be able to identify patients who require referral to specialists for diagnostic testing or higher-tiered treatment and need to engender open lines of communication between their patients and all treating clinicians. This requires an understanding of the evaluation, diagnosis, and treatment of neurogenic lower urinary tract dysfunctions.

  9. Neurogenic Language Disorders in Children. International Association of Logopedics and Phoniatrics

    ERIC Educational Resources Information Center

    Fabbro, Franco, Ed.

    2004-01-01

    Language disorders in children are one of the most frequent causes of difficulties in communication, social interaction, learning and academic achievement. It has been estimated that over 5% of children present with some kind of language disorder. This volume illustrates the state of the art in neurogenic language disorders in children. The most…

  10. Central Neurogenic Hyperventilation Related to Post-Hypoxic Thalamic Lesion in a Child

    PubMed Central

    Gençpinar, Pinar; Karaali, Kamil; Haspolat, Şenay; Dursun, Oğuz

    2016-01-01

    Central neurogenic hyperventilation (CNH) is a rare clinical condition, whose mechanism is still unclear. Here, we report a 3-year-old male patient, who had bilateral thalamic, putaminal and globus pallideal infarction resulted in CNH without brainstem involvement. This case may illustrate a possible role for the thalamus in regulating ventilation. PMID:27127601

  11. Comprehensive Expression Map of Transcription Regulators in the Adult Zebrafish Telencephalon Reveals Distinct Neurogenic Niches

    PubMed Central

    Diotel, Nicolas; Rodriguez Viales, Rebecca; Armant, Olivier; März, Martin; Ferg, Marco; Rastegar, Sepand; Strähle, Uwe

    2015-01-01

    The zebrafish has become a model to study adult vertebrate neurogenesis. In particular, the adult telencephalon has been an intensely studied structure in the zebrafish brain. Differential expression of transcriptional regulators (TRs) is a key feature of development and tissue homeostasis. Here we report an expression map of 1,202 TR genes in the telencephalon of adult zebrafish. Our results are summarized in a database with search and clustering functions to identify genes expressed in particular regions of the telencephalon. We classified 562 genes into 13 distinct patterns, including genes expressed in the proliferative zone. The remaining 640 genes displayed unique and complex patterns of expression and could thus not be grouped into distinct classes. The neurogenic ventricular regions express overlapping but distinct sets of TR genes, suggesting regional differences in the neurogenic niches in the telencephalon. In summary, the small telencephalon of the zebrafish shows a remarkable complexity in TR gene expression. The adult zebrafish telencephalon has become a model to study neurogenesis. We established the expression pattern of more than 1200 transcription regulators (TR) in the adult telencephalon. The neurogenic regions express overlapping but distinct sets of TR genes suggesting regional differences in the neurogenic potential. J. Comp. Neurol. 523:1202–1221, 2015. © 2015 Wiley Periodicals, Inc. PMID:25556858

  12. A Clinician Survey of Speech and Non-Speech Characteristics of Neurogenic Stuttering

    ERIC Educational Resources Information Center

    Theys, Catherine; van Wieringen, Astrid; De Nil, Luc F.

    2008-01-01

    This study presents survey data on 58 Dutch-speaking patients with neurogenic stuttering following various neurological injuries. Stroke was the most prevalent cause of stuttering in our patients, followed by traumatic brain injury, neurodegenerative diseases, and other causes. Speech and non-speech characteristics were analyzed separately for…

  13. Leiomyosarcoma of the Oropharynx and Neurogenic Tumors in a Young Patient With Turner's Syndrome

    PubMed Central

    Apice, Gaetano; Silvestro, Giustino; Losito, Simona; Botti, Gerardo; Ionna, Francesco; De Rosa, Vincenzo; Borghese, Annamaria; Ninfo, Vito

    2001-01-01

    Patient: A case of Turner's syndrome developing a leiomyosarcoma of the oropharynx and metachronous neurogenic tumors (mediastinal ‘ganglioneuroblastoma intermixed’, subcutaneous neurilemoma) is described. Discussion: To our knowledge, this case is the second reported leiomyosarcoma in a patient with Turner's syndrome. Also the site of involvement (palate and oropharynx) is particularly unusual for the already rare leiomyosarcomas in the young age. PMID:18521442

  14. Paroxetine Can Enhance Neurogenesis during Neurogenic Differentiation of Human Adipose-derived Stem Cells

    PubMed Central

    Jahromi, Maliheh; Razavi, Shahnaz; Amirpour, Nushin; Khosravizadeh, Zahra

    2016-01-01

    Background: Some antidepressant drugs can promote neuronal cell proliferation in vitro as well as hippocampal neurogenesis in human and animal models. Furthermore, adipose tissue is an available source of adult stem cells with the ability to differentiate in to multiple lineages. Therefore, human Adipose-Derived Stem Cells (hAD-SCs) may be a suitable source for regenerative medical applications. Since there is no evidence for the effect of Paroxetine as the most commonly prescribed antidepressant drug for neurogenic potential of hADSCs, an attempt was made to determine the effect of Paroxetine on proliferation and neural differentiation of hADSCs. Methods: ADSCs were isolated from human abdominal fat. These cells differentiated to neuron-like cells and were treated with Paroxetine. 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay and immunofluorescence technique were used for assessment of cell proliferation and neurogenic differentiation potential of induced cells, respectively. Results: MTT assay analysis showed that Paroxetine significantly increased the proliferation rate of induced hADSCs (p<0.05), while immunofluorescent staining indicated that Paroxetine treatment during neurogenic differentiation could enhance the mean percentage of Nestin and MAP2 (Microtubule-associated protein-2) positive cells but the mean percentage of GFAP (Glial acidic fibrillary protein) positive cells significantly decreased relative to control group (p<0.05). Conclusion: Our results provide evidence that Paroxetine can promote proliferation and differentiation rate during neurogenic differentiation of hADSCs. Moreover, Paroxetine can reduce gliogenesis of induced hADSCs during neurogenic differentiation. PMID:27920882

  15. Differential expression of neurogenes among breast cancer subtypes identifies high risk patients

    PubMed Central

    Fernández-Nogueira, Patricia; Bragado, Paloma; Almendro, Vanessa; Ametller, Elisabet; Rios, Jose; Choudhury, Sibgat

    2016-01-01

    The nervous system is now recognized to be a relevant component of the tumor microenvironment. Receptors for neuropeptides and neurotransmitters have been identified in breast cancer. However, very little is known about the role of neurogenes in regulating breast cancer progression. Our purpose was to identify neurogenes associated with breast cancer tumorigenesis with a potential to be used as biomarker and/or targets for treatment. We used three databases of human genes: GeneGo, GeneCards and Eugenes to generate a list of 1266 relevant neurogenes. Then we used bioinformatics tools to interrogate two published breast cancer databases SAGE and MicMa (n=96) and generated a list of 7 neurogenes that are differentially express among breast cancer subtypes. The clinical potential was further investigated using the GOBO database (n=1881). We identified 6 neurogenes that are differentially expressed among breast cancer subtypes and whose expression correlates with prognosis. Histamine receptor1 (HRH1), neuropilin2 (NRP2), ephrin-B1 (EFNB1), neural growth factor receptor (NGFR) and amyloid precursor protein (APP) were differentially overexpressed in basal and HER2-enriched tumor samples and syntaxin 1A (STX1A) was overexpressed in HER2-enriched and luminal B tumors. Analysis of HRH1, NRP2, and STX1A expression using the GOBO database showed that their expression significantly correlated with a shorter overall survival (p < 0.0001) and distant metastasis-free survival (p < 0.0001). In contrast, elevated co-expression of NGFR, EFNB1 and APP was associated with longer overall (p < 0.0001) and metastasis-free survival (p < 0.0001). We propose that HRH1, NRP2, and STX1A can be used as prognostic biomarkers and therapeutic targets for basal and HER2-enriched breast cancer subtypes. PMID:26673618

  16. Networks.

    ERIC Educational Resources Information Center

    Maughan, George R.; Petitto, Karen R.; McLaughlin, Don

    2001-01-01

    Describes the connectivity features and options of modern campus communication and information system networks, including signal transmission (wire-based and wireless), signal switching, convergence of networks, and network assessment variables, to enable campus leaders to make sound future-oriented decisions. (EV)

  17. Circadian Kinetics of Cell Cycle Progression in Adult Neurogenic Niches of a Diurnal Vertebrate.

    PubMed

    Akle, Veronica; Stankiewicz, Alexander J; Kharchenko, Vasili; Yu, Lili; Kharchenko, Peter V; Zhdanova, Irina V

    2017-02-15

    The circadian system may regulate adult neurogenesis via intracellular molecular clock mechanisms or by modifying the environment of neurogenic niches, with daily variation in growth factors or nutrients depending on the animal's diurnal or nocturnal lifestyle. In a diurnal vertebrate, zebrafish, we studied circadian distribution of immunohistochemical markers of the cell division cycle (CDC) in 5 of the 16 neurogenic niches of adult brain, the dorsal telencephalon, habenula, preoptic area, hypothalamus, and cerebellum. We find that common to all niches is the morning initiation of G1/S transition and daytime S-phase progression, overnight increase in G2/M, and cycle completion by late night. This is supported by the timing of gene expression for critical cell cycle regulators cyclins D, A2, and B2 and cyclin-dependent kinase inhibitor p20 in brain tissue. The early-night peak in p20, limiting G1/S transition, and its phase angle with the expression of core clock genes, Clock1 and Per1, are preserved in constant darkness, suggesting intrinsic circadian patterns of cell cycle progression. The statistical modeling of CDC kinetics reveals the significant circadian variation in cell proliferation rates across all of the examined niches, but interniche differences in the magnitude of circadian variation in CDC, S-phase length, phase angle of entrainment to light or clock, and its dispersion. We conclude that, in neurogenic niches of an adult diurnal vertebrate, the circadian modulation of cell cycle progression involves both systemic and niche-specific factors.SIGNIFICANCE STATEMENT This study establishes that in neurogenic niches of an adult diurnal vertebrate, the cell cycle progression displays a robust circadian pattern. Common to neurogenic niches located in diverse brain regions is daytime progression of DNA replication and nighttime mitosis, suggesting systemic regulation. Differences between neurogenic niches in the phase and degree of S-phase entrainment to the

  18. Circadian Kinetics of Cell Cycle Progression in Adult Neurogenic Niches of a Diurnal Vertebrate

    PubMed Central

    Stankiewicz, Alexander J.; Kharchenko, Vasili; Yu, Lili; Kharchenko, Peter V.

    2017-01-01

    The circadian system may regulate adult neurogenesis via intracellular molecular clock mechanisms or by modifying the environment of neurogenic niches, with daily variation in growth factors or nutrients depending on the animal's diurnal or nocturnal lifestyle. In a diurnal vertebrate, zebrafish, we studied circadian distribution of immunohistochemical markers of the cell division cycle (CDC) in 5 of the 16 neurogenic niches of adult brain, the dorsal telencephalon, habenula, preoptic area, hypothalamus, and cerebellum. We find that common to all niches is the morning initiation of G1/S transition and daytime S-phase progression, overnight increase in G2/M, and cycle completion by late night. This is supported by the timing of gene expression for critical cell cycle regulators cyclins D, A2, and B2 and cyclin-dependent kinase inhibitor p20 in brain tissue. The early-night peak in p20, limiting G1/S transition, and its phase angle with the expression of core clock genes, Clock1 and Per1, are preserved in constant darkness, suggesting intrinsic circadian patterns of cell cycle progression. The statistical modeling of CDC kinetics reveals the significant circadian variation in cell proliferation rates across all of the examined niches, but interniche differences in the magnitude of circadian variation in CDC, S-phase length, phase angle of entrainment to light or clock, and its dispersion. We conclude that, in neurogenic niches of an adult diurnal vertebrate, the circadian modulation of cell cycle progression involves both systemic and niche-specific factors. SIGNIFICANCE STATEMENT This study establishes that in neurogenic niches of an adult diurnal vertebrate, the cell cycle progression displays a robust circadian pattern. Common to neurogenic niches located in diverse brain regions is daytime progression of DNA replication and nighttime mitosis, suggesting systemic regulation. Differences between neurogenic niches in the phase and degree of S-phase entrainment to

  19. The use of laser acupuncture for the treatment of neurogenic pruritus in a child--a case history.

    PubMed

    Stellon, Anthony

    2005-03-01

    This report describes the successful treatment using laser acupuncture of a six year old girl with neurogenic pruritus of the abdomen. It is the first case report of neurogenic pruritus treated by laser acupuncture. The main advantage of using low energy laser, as opposed to acupuncture needles, to stimulate points, is that low energy laser causes little or no sensation, which is particularly useful when treating children.

  20. Neurogenic pathways in remote ischemic preconditioning induced cardioprotection: Evidences and possible mechanisms

    PubMed Central

    Aulakh, Amritpal Singh; Randhawa, Puneet Kaur; Singh, Nirmal

    2017-01-01

    Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (noncardiac) increases the tolerance of the myocardium to sustained ischemiareperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection. PMID:28280407

  1. Precocious puberty: clinical and endocrine profile and factors indicating neurogenic precocity in Indian children.

    PubMed

    Bajpai, Anurag; Sharma, Jyoti; Kabra, Madhulika; Kumar Gupta, Arun; Menon, P S N

    2002-01-01

    The objective of this study was to evaluate the clinical and endocrine profile of patients with precocious puberty followed up in a tertiary care hospital. Records of 140 patients (114 girls, 26 boys) with precocious puberty were reviewed. Clinical features including age of onset, stage of pubertal development, presenting symptoms, features suggestive of CNS involvement and family history were analyzed. Endocrine investigations included basal and GnRH-stimulated levels of LH and FSH as well as 17OHP, DHEA, hCG and thyroid profile. Abdominal and pelvic ultrasonography and CNS imaging were correlated with clinical features. Girls outnumbered boys in this series (4.4:1). Neurogenic central isosexual precocious puberty (CIPP) was more common in boys (10 out of 18, 55.6%) than girls (16 out of 77, 20.8%). The most common cause of neurogenic CIPP was hypothalamic hamartoma present in five girls and four boys. Other causes of neurogenic CIPP included neurotuberculosis, pituitary adenoma, hydrocephalus, post radiotherapy, CNS tumors and malformations. Peripheral precocious puberty (PPP) was secondary to adrenal causes in boys and ovarian cysts in girls. Benign variants of precocious puberty, such as premature thelarche and premature adrenarche, were present in 23 and six girls, respectively. Hypothyroidism was present in four girls and McCune-Albright syndrome in one girl. Girls with neurogenic CIPP had a lower age of onset as compared to idiopathic CIPP (3.6 +/- 2.7 years vs 5.4 +/- 2.5 years, p = 0.014). The lowest age of onset was seen in girls with hypothalamic hamartoma (1.6 +/- 0.9 years). Forty-seven girls with CIPP (seven neurogenic and 40 idiopathic) presented after the age of 6 years. Features of CNS involvement, in the form of seizures, mental retardation, raised intracranial tension or focal neurological deficits, were present in seven girls (43.8%) and four boys (40%), and gelastic seizures were present in three children. Girls with CIPP had greater bone age

  2. Evaluation and Management of Neurogenic Bladder: What Is New in China?

    PubMed Central

    Liao, Limin

    2015-01-01

    Neurogenic bladder (NB) or neurogenic lower urinary tract dysfunction (NLUTD), a dysfunction of the urinary bladder and urethra due to disease of the central nervous system or peripheral nerves, is a major global medical and social problem. Numerous nervous system abnormalities, such as: stroke, Alzheimer’s and Parkinson’s diseases, traumatic spinal cord injury, spinal cord tumors, congenital spina bifida, and diabetes, can cause NB/NLUTD. There are two major types of bladder control problems associated with NB/NLUTD: the bladder becomes either overactive or underactive depending on the nature, level, and extent of nerve damage. This review specifically focuses on the diagnosis and management of NB/NLUTD in China as well as on recent efforts to treat this disease. PMID:26266405

  3. Emphysematous Pyelonephritis Caused by Citrobacter freundii in a Patient with Type 2 Diabetes and Neurogenic Bladder.

    PubMed

    Kim, Min Jeong; Park, Ji Sang; Lim, Hye Jin; Jung, Jihye; Shin, Dong Geum; Lee, Ki-Deok; Jung, Yoon Young; Min, Kyung Wan; Han, Kyung-Ah

    2013-09-01

    Emphysematous pyelonephritis (EPN) is a rare, life-threatening complication of upper urinary tract infections that is characterized by the presence of gas in the renal parenchyma and perirenal space. It commonly occurs in diabetic patients. Escherichia coli are the most common causative organisms, with few reports implicating Citrobacter freundii as the etiologic agent in EPN. A 57-year-old woman with diabetes and neurogenic bladder visited at our department with confused mentality, myalgia, and general weakness. Further investigation revealed that the patient suffered from unilateral EPN with sepsis caused by C. freundii. The patient's condition was improved considerably with percutaneous drainage and use of intravenous antibiotics for several weeks. However, renal function eventually deteriorated to permanent renal failure, which required hemodialysis. In conclusion, C. freundii may be the causative pathogen of EPN in a patient with type 2 diabetes and neurogenic bladder.

  4. [A case of true neurogenic thoracic outlet syndrome accompanied by an aberrant right subclavian artery].

    PubMed

    Sekiguchi, Kenji; Saito, Takanori; Yokota, Ichiro; Kowa, Hisatomo; Kanda, Fumio; Toda, Tatsushi

    2015-01-01

    A 65-year-old woman experienced progressive intrinsic muscle wasting on the right hand over a period of 7 years. The distribution of muscular atrophy and weakness was consistent with the area innervated by the right C8 and Th1 nerve roots. Neurophysiological examination suggested a right lower trunk lesion. An elongated right transverse process of the C7 vertebra and an aberrant subclavian artery were detected on computed tomography images, and the right lower trunk of the brachial plexus appeared to be lifted upward on magnetic resonance images. The patient was diagnosed with true neurogenic thoracic outlet syndrome. A fibrous band extending from the elongated transverse process was found during surgery, and symptoms did not progress further after resection of the band. True neurogenic thoracic outlet syndrome can cause monomelic amyotrophy, and localized neuroimaging and detailed neurophysiological examination were useful for diagnosis.

  5. A Case of Neuro-Behcet’s Disease Presenting with Central Neurogenic Hyperventilation

    PubMed Central

    Alkhachroum, Ayham M.; Saeed, Saba; Kaur, Jaspreet; Shams, Tanzila; De Georgia, Michael A.

    2016-01-01

    Patient: Female, 46 Final Diagnosis: Central hyperventilation Symptoms: Hyperventilation Medication: — Clinical Procedure: None Specialty: Neurology Objective: Unusual clinical course Background: Behcet’s disease is a chronic inflammatory disorder usually characterized by the triad of oral ulcers, genital ulcers, and uveitis. Central to the pathogenesis of Behcet’s disease is an autoimmune vasculitis. Neurological involvement, so called “Neuro-Behcet’s disease”, occurs in 10–20% of patients, usually from a meningoencephalitis or venous thrombosis. Case Report: We report the case of a 46-year-old patient with Neuro-Behcet’s disease who presented with central neurogenic hyperventilation as a result of brainstem involvement from venulitis. Conclusions: To the best of our knowledge, central neurogenic hyperventilation has not previously been described in a patient with Neuro-Behcet’s disease. PMID:26965646

  6. Spinal TRPA1 ion channels contribute to cutaneous neurogenic inflammation in the rat.

    PubMed

    Wei, Hong; Koivisto, Ari; Pertovaara, Antti

    2010-08-02

    In the spinal dorsal horn, TRPA1 ion channels on central terminals of peptidergic primary afferent nerve fibers regulate transmission to glutamatergic and GABAergic interneurons. Here we determine the cutaneous anti-inflammatory effect of a spinally administered TRPA1 channel antagonist to test the hypothesis that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation induced by sustained noxious stimulation. According to the hypothesis, spinal TRPA1 channels facilitate transmission of injury discharge to GABAergic interneurons that induce a dorsal root reflex, which results in increased release of proinflammatory compounds in the skin. Intraplantar capsaicin, a TRPV1 channel agonist, was used to induce neurogenic inflammation in anesthetized rats that were pretreated intrathecally (i.t.), intraplantarly (i.pl.) or intraperitoneally (i.p.) with vehicle or Chembridge-5861526 (CHEM, a TRPA1 channel antagonist). For assessment of neurogenic inflammation, the capsaicin-induced increase of cutaneous blood flow was determined adjacent to the capsaicin-treated skin site with a laser Doppler flowmeter. Capsaicin-induced a marked increase in cutaneous blood flow. The capsaicin-induced blood flow increase was attenuated in a dose-related fashion by i.t. pretreatment with CHEM (3-10microg). Pretreatment with CHEM at a dose of 3mg/kg i.p. or 20microg i.pl. failed to attenuate the capsaicin-induced increase of blood flow. The results indicate that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation adjacent to the injury site, probably by facilitating a dorsal root reflex in peptidergic primary afferent nerve fibers.

  7. Brain ACE2 shedding contributes to the development of neurogenic hypertension

    PubMed Central

    Chhabra, Kavaljit H.; Lazartigues, Eric

    2015-01-01

    Rationale Over-activity of the brain Renin Angiotensin System (RAS) is a major contributor to neurogenic hypertension. While over-expression of Angiotensin-Converting Enzyme type 2 (ACE2) has been shown to be beneficial in reducing hypertension by transforming Angiotensin (Ang)-II into Ang-(1-7), several groups have reported decreased brain ACE2 expression and activity during the development of hypertension. Objective We hypothesized that ADAM17-mediated ACE2 shedding results in decreased membrane-bound ACE2 in the brain, thus promoting the development of neurogenic hypertension. Methods and Results To test this hypothesis, we used the DOCA-salt model of neurogenic hypertension in non-transgenic (NT) and syn-hACE2 mice over-expressing ACE2 in neurons. DOCA-salt treatment in NT mice led to significant increases in blood pressure, hypothalamic Ang-II levels, inflammation, impaired baroreflex sensitivity, autonomic dysfunction, as well as decreased hypothalamic ACE2 activity and expression, while these changes were blunted or prevented in syn-hACE2 mice. In addition, reduction of ACE2 expression and activity in the brain paralleled a rise in ACE2 activity in the cerebrospinal fluid of NT mice following DOCA-salt treatment and was accompanied by enhanced ADAM17 expression and activity in the hypothalamus. Chronic knockdown of ADAM17 in the brain blunted the development of hypertension and restored ACE2 activity and baroreflex function. Conclusions Our data provide the first evidence that ADAM17-mediated shedding impairs brain ACE2 compensatory activity, thus contributing to the development of neurogenic hypertension. PMID:24014829

  8. Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries.

    PubMed

    Chen, Mei-Fang; Lai, Su-Yu; Kung, Po-Cheng; Lin, Yo-Cheng; Yang, Hui-I; Chen, Po-Yi; Liu, Ingrid Y; Lua, Ahai Chang; Lee, Tony Jer-Fu

    2016-08-15

    The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine>methamphetamine>hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation

  9. Droxidopa and Reduced Falls in a Trial of Parkinson Disease Patients With Neurogenic Orthostatic Hypotension

    PubMed Central

    Hauser, Robert A.; Heritier, Stephane; Rowse, Gerald J.; Hewitt, L. Arthur; Isaacson, Stuart H.

    2016-01-01

    Objectives Droxidopa is a prodrug of norepinephrine indicated for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure including Parkinson disease (PD). The objective of this study was to compare fall rates in PD patients with symptomatic neurogenic orthostatic hypotension randomized to droxidopa or placebo. Methods Study NOH306 was a 10-week, phase 3, randomized, placebo-controlled, double-blind trial of droxidopa in PD patients with symptomatic neurogenic orthostatic hypotension that included assessments of falls as a key secondary end point. In this report, the principal analysis consisted of a comparison of the rate of patient-reported falls from randomization to end of study in droxidopa versus placebo groups. Results A total of 225 patients were randomized; 222 patients were included in the safety analyses, and 197 patients provided efficacy data and were included in the falls analyses. The 92 droxidopa patients reported 308 falls, and the 105 placebo patients reported 908 falls. In the droxidopa group, the fall rate was 0.4 falls per patient-week; in the placebo group, the rate was 1.05 falls per patient-week (prespecified Wilcoxon rank sum P = 0.704; post hoc Poisson-inverse Gaussian test P = 0.014), yielding a relative risk reduction of 77% using the Poisson-inverse Gaussian model. Fall-related injuries occurred in 16.7% of droxidopa-treated patients and 26.9% of placebo-treated patients. Conclusions Treatment with droxidopa appears to reduce falls in PD patients with symptomatic neurogenic orthostatic hypotension, but this finding must be confirmed. PMID:27332626

  10. GABAergic signalling in a neurogenic niche of the turtle spinal cord

    PubMed Central

    Reali, Cecilia; Fernández, Anabel; Radmilovich, Milka; Trujillo-Cenóz, Omar; Russo, Raúl E

    2011-01-01

    Abstract The region that surrounds the central canal (CC) in the turtle spinal cord is a neurogenic niche immersed within already functional circuits, where radial glia expressing brain lipid binding protein (BLBP) behave as progenitors. The behaviour of both progenitors and neuroblasts within adult neurogenic niches must be regulated to maintain the functional stability of the host circuit. In the brain, GABA plays a major role in this kind of regulation but little is known about GABAergic signalling in neurogenic niches of the postnatal spinal cord. Here we explored the action of GABA around the CC of the turtle spinal cord by combining patch-clamp recordings of CC-contacting cells, immunohistochemistry for key components of GABAergic signalling and Ca2+ imaging. Two potential sources of GABA appeared around the CC: GABAergic terminals and CC-contacting neurones. GABA depolarized BLBP+ progenitors via GABA transporter-3 (GAT3) and/or GABAA receptors. In CC-contacting neurones, GABAA receptor activation generated responses ranging from excitation to inhibition. This functional heterogeneity appeared to originate from different ratios of activity of the Na+–K+–2Cl− co-transporter (NKCC1) and the K+–Cl− co-transporter (KCC2). In both progenitors and immature neurones, GABA induced an increase in intracellular Ca2+ that required extracellular Ca2+ and was blocked by the selective GABAA receptor antagonist gabazine. Our study shows that GABAergic signalling around the CC shares fundamental properties with those in the embryo and adult neurogenic niches, suggesting that GABA may be part of the mechanisms regulating the production and integration of neurones within operational spinal circuits in the turtle. PMID:21911613

  11. Neurogenic period of ascending tract neurons in the upper lumbar spinal cord of the rat

    SciTech Connect

    Nandi, K.N.; Beal, J.A.; Knight, D.S. )

    1990-02-01

    Although the neurogenic period for neurons in the lumbar spinal cord has been clearly established (Days 12 through 16 of gestation), it is not known when the neurogenesis of ascending tract neurons is completed within this period. The purpose of the present study was to determine the duration of the neurogenic period for projection neurons of the ascending tracts. To label neurons undergoing mitosis during this period, tritiated thymidine was administered to fetal rats on Embryonic (E) Days E13 through E16 of gestation. Ascending tract neurons of the lumbar cord were later (Postnatal Days 40-50) labeled in each animal with a retrograde tracer, Fluoro-Gold, applied at the site of a hemisection at spinal cord segment C3. Ascending tract neurons which were undergoing mitosis in the upper lumbar cord were double labeled, i.e., labeled with both tritiated thymidine and Fluoro-Gold. On Day E13, 89-92% of the ascending tract neurons were double labeled; on Day E14, 35-37%; and on Day E15, 1-4%. Results showed, then, that some ascending tract neurons were double labeled through Day E15 and were, therefore, proliferating in the final one-third of the neurogenic period. Ascending tract neurons proliferating on Day E15 were confined to laminae III, IV, V, and X and the nucleus dorsalis. Long tract neurons in the superficial dorsal horn (laminae I and II), on the other hand, were found to have completed neurogenesis on Day E14 of gestation. Results of the present study show that spinal neurogenesis of ascending projection neurons continues throughout most of the neurogenic period and does not completely follow the well-established ventral to dorsal gradient.

  12. Botulinum toxin type A reduces capsaicin-evoked pain and neurogenic vasodilatation in human skin.

    PubMed

    Tugnoli, Valeria; Capone, Jay Guido; Eleopra, Roberto; Quatrale, Rocco; Sensi, Mariachiara; Gastaldo, Ernesto; Tola, Maria Rosaria; Geppetti, Pierangelo

    2007-07-01

    The effect of Botulinum Toxin type A (BoNT/A) on pain and neurogenic vasodilatation induced by application to the human skin of thermal stimuli and capsaicin was evaluated in a double blind study. A capsaicin cream (0.5 ml of a 0.075%) was applied to the skin of both forearms of eighteen subjects randomly pretreated with either BoNT/A (Botox) or 0.9% saline (NS). Capsaicin was applied to a skin area either inside (protocol A) or adjacent to the BoNT/A treated area (protocol B). Pre-treatment with BoNT/A did not affect thermal-specific and thermal-pain thresholds (by quantitative sensory testing). However, capsaicin-induced pain sensation (by a visual analogue scale), flare area (by acetate sheet) and changes in cutaneous blood flow (CBF, by laser Doppler flowmetry) were reduced when capsaicin was administered inside (protocol A) the BoNT/A treated area. In Protocol B, capsaicin-induced pain was unchanged, and capsaicin-induced flare/increase in CBF were reduced only in the area treated with BoNT/A, but not in the BoNT/A untreated area. Results indicate that (i) BoNT/A reduces capsaicin-induced pain and neurogenic vasodilatation without affecting the transmission of thermal and thermal-pain modalities; (ii) reduction in capsaicin-induced pain occurs only if capsaicin is administered into the BoNT/A pretreated area; (iii) reduction in neurogenic vasodilatation by BoNT/A does not contribute to its analgesic action. BoNT/A could be tested for the treatment of conditions characterised by neurogenic inflammation and inflammatory pain.

  13. Effect of sertraline on proliferation and neurogenic differentiation of human adipose-derived stem cells

    PubMed Central

    Razavi, Shahnaz; Jahromi, Maliheh; Amirpour, Nushin; Khosravizadeh, Zahra

    2014-01-01

    Background: Antidepressant drugs are commonly employed for anxiety and mood disorders. Sertraline is extensively used as antidepressant in clinic. In addition, adipose tissue represents an abundant and accessible source of adult stem cells with the ability to differentiate in to multiple lineages. Therefore, human adipose-derived stem cells (hADSCs) may be useful for autologous transplantation. Materials and Methods: In the present study, we assessed the effect of antidepressant drug Sertraline on the proliferation and neurogenic differentiation of hADSCs using MTT assay and immunofluorescence technique respectively. Results: MTT assay analysis showed that 0.5 μM Sertraline significantly increased the proliferation rate of hADSCs induced cells (P < 0.05), while immunofluorescent staining indicated that Sertraline treatment during neurogenic differentiation could be decreased the percentage of glial fibrillary acidic protein and Nestin-positive cells, but did not significantly effect on the percentage of MAP2 positive cells. Conclusion: Overall, our data show that Sertraline can be promoting proliferation rate during neurogenic differentiation of hADSCs after 6 days post-induction, while Sertraline inhibits gliogenesis of induced hADSCs. PMID:24800186

  14. Changes of neural markers expression during late neurogenic differentiation of human adipose-derived stem cells

    PubMed Central

    Razavi, Shahnaz; Khosravizadeh, Zahra; Bahramian, Hamid; Kazemi, Mohammad

    2015-01-01

    Background: Different studies have been done to obtain sufficient number of neural cells for treatment of neurodegenerative diseases, spinal cord, and traumatic brain injury because neural stem cells are limited in central nerves system. Recently, several studies have shown that adipose-derived stem cells (ADSCs) are the appropriate source of multipotent stem cells. Furthermore, these cells are found in large quantities. The aim of this study was an assessment of proliferation and potential of neurogenic differentiation of ADSCs with passing time. Materials and Methods: Neurosphere formation was used for neural induction in isolated human ADSCs (hADSCs). The rate of proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and potential of neural differentiation of induced hADSCs was evaluated by immunocytochemical and real-time reverse transcription polymerase chain reaction analysis after 10 and 14 days post-induction. Results: The rate of proliferation of induced hADSCs increased after 14 days while the expression of nestin, glial fibrillary acidic protein, and microtubule-associated protein 2 was decreased with passing time during neurogenic differentiation. Conclusion: These findings showed that the proliferation of induced cells increased with passing time, but in early neurogenic differentiation of hADSCs, neural expression was higher than late of differentiation. Thus, using of induced cells in early differentiation may be suggested for in vivo application. PMID:26605238

  15. Development of mechanisms associated with neurogenic-mediated skin inflammation during the growth of rats.

    PubMed

    Ohshima, Mihoko; Miyake, Mio; Takeda, Masanori; Muto, Taichiro; Ueda, Norishi; Ito, Komei; Sakamoto, Tatsuo

    2010-04-01

    Neurogenic-mediated inflammation may be associated with several inflammatory skin diseases including atopic dermatitis. However, age-dependent differences in neurogenic-mediated skin responses are not fully understood. We compared skin plasma leakage in rats aged 2 and 8 wk, which was induced by topical capsaicin, topical formalin, and intracutaneous substance P, whose effects are mediated via tachykinin NK1 receptors. Evans blue dye extravasation served as an index of the increase in skin vascular permeability. Capsaicin, formalin, and substance P caused a skin response in a dose-dependent manner in both age groups. However, the skin response was much greater in adults than in pups. In addition, the localization of sensory C-fibers and tachykinin NK1 receptors in the skin was investigated by immunofluorescent staining with antisubstance P and antitachykinin NK1 receptor antibodies, respectively. Substance P-immunoreactive nerves were detected throughout the dermis and tachykinin NK1 receptors were mainly detected in blood vessel walls in the dermis in both age groups. However, they were more sparsely distributed in pups. In conclusion, the weak neurogenic-mediated skin inflammation in pups is probably because of immature neural mechanisms associated with skin inflammation such as reduced innervation of sensory C-fibers and low expression of tachykinin NK1 receptors.

  16. Neurogenic and myogenic motor patterns of rabbit proximal, mid, and distal colon.

    PubMed

    Dinning, P G; Costa, M; Brookes, S J; Spencer, N J

    2012-07-01

    The rabbit colon consists of four distinct regions. The motility of each region is controlled by myogenic and neurogenic mechanisms. Associating these mechanisms with specific motor patterns throughout all regions of the colon has not previously been achieved. Three sections of the colon (the proximal, mid, and distal colon) were removed from euthanized rabbits. The proximal colon consists of a triply teniated region and a single tenia region. Spatio-temporal maps were constructed from video recordings of colonic wall diameter, with associated intraluminal pressure recorded from the aboral end. Hexamethonium (100 μM) and tetrodotoxin (TTX; 0.6 μM) were used to inhibit neural activity. Four distinct patterns of motility were detected: 1 myogenic and 3 neurogenic. The myogenic activity consisted of circular muscle (CM) contractions (ripples) that occurred throughout the colon and propagated in both antegrade (anal) and retrograde (oral) directions. The neural activity of the proximal colon consisted of slowly (0.1 mm/s) propagating colonic migrating motor complexes, which were abolished by hexamethonium. These complexes were observed in the region of the proximal colon with a single band of tenia. In the distal colon, tetrodotoxin-sensitive, thus neurally mediated, but hexamethonium-resistant, peristaltic (anal) and antiperistaltic (oral) contractions were identified. The distinct patterns of neurogenic and myogenic motor activity recorded from isolated rabbit colon are specific to each anatomically distinct region. The regional specificity motor pattern is likely to facilitate orderly transit of colonic content from semi-liquid to solid composition of feces.

  17. Neurogenic pruritus: an unrecognised problem? A retrospective case series of treatment by acupuncture.

    PubMed

    Stellon, Anthony

    2002-12-01

    Intractable localised segmental pruritus without a rash has been reported over the years under various titles depending on the area of the body affected. Notalgia paresthetica and brachioradial pruritus are the two terms used for what is believed to be a form of neuropathy. The clinical observations reported here suggest that other localised cases of pruritus exist that share common clinical features, and the term neurogenic pruritus is suggested to encompass these under one clinical condition. Acupuncture has been used to treat skin conditions, of which pruritus is one symptom. This retrospective study looked at the symptomatic relief of neurogenic pruritus in 16 patients using acupuncture. In 12 cases the affected dermatomes of the body were innervated by cervical spinal nerves, seven innervated by dorsal spinal nerves and four innervated by the lumbar spinal nerves. Seven patients had areas affected by two different regions of the spine. Restricted neck or back movements were noted in patients as were areas of paravertebral spasm or tenderness of the muscles. Total resolution of symptoms as judged by VAS occurred in 75% of patients. Relapse occurred in 37% of patients within 1-12 months following treatment. Acupuncture appeared to be effective in alleviating the distressing symptom of itching in patients presenting with neurogenic pruritus.

  18. Networking.

    ERIC Educational Resources Information Center

    Duvall, Betty

    Networking is an information giving and receiving system, a support system, and a means whereby women can get ahead in careers--either in new jobs or in current positions. Networking information can create many opportunities: women can talk about how other women handle situations and tasks, and previously established contacts can be used in…

  19. Adaptive Control of Visually Guided Grasping in Neural Networks

    DTIC Science & Technology

    1990-03-12

    U01ITU S.WM NONnumsen Adaptive Control of Visually Guided Grasping in Neural Networks AFOSR-89-&CO030 88-NL-209 L AUTHOrSF 2313/A8 00 61102F (V) Dr...FINAL REPORT ADAPTIVE CONTROL OF VISUALLY GUIDED GRASPING IN NEURAL NETWORKS Neurogen Laboratories Inc. Project Summary Research performed for AFOSR...arm’s length in position and 6 degrees in orientation. Keywords: Neural Networks , Adaptive Motor Control, Sensory-Motor sensation Introduction The human

  20. Organization and cellular arrangement of two neurogenic regions in the adult ferret (Mustela putorius furo) brain.

    PubMed

    Takamori, Yasuharu; Wakabayashi, Taketoshi; Mori, Tetsuji; Kosaka, Jun; Yamada, Hisao

    2014-06-01

    In the adult mammalian brain, two neurogenic regions have been characterized, the subventricular zone (SVZ) of the lateral ventricle (LV) and the subgranular zone (SGZ) of the dentate gyrus (DG). Despite remarkable knowledge of rodents, the detailed arrangement of neurogenic regions in most mammals is poorly understood. In this study, we used immunohistochemistry and cell type-specific antibodies to investigate the organization of two germinal regions in the adult ferret, which belongs to the order Carnivora and is widely used as a model animal with a gyrencephalic brain. From the SVZ to the olfactory bulb, doublecortin-positive cells tended to organize in chain-like clusters, which are surrounded by a meshwork of astrocytes. This structure is homologous to the rostral migratory stream (RMS) described in other species. Different from rodents, the horizontal limb of the RMS emerges directly from the LV, and the anterior region of the LV extends rostrally and reached the olfactory bulb. In the DG, glial fibrillary acidic protein-positive cells with long radial processes as well as doublecortin-positive cells are oriented in the SGZ. In both regions, doublecortin-positive cells showed characteristic morphology and were positive for polysialylated-neural cell adhesion molecule, beta-III tubulin, and lamin B1 (intense staining). Proliferating cells were detected in both regions using antibodies against proliferating cell nuclear antigen and phospho-histone H3. These observations demonstrate that the two neurogenic regions in ferrets have a similar cellular composition as those of other mammalian species despite anatomical differences in the brain.

  1. A mathematical model of salt-sensitive hypertension: the neurogenic hypothesis.

    PubMed

    Averina, Viktoria A; Othmer, Hans G; Fink, Gregory D; Osborn, John W

    2015-07-15

    Salt sensitivity of arterial pressure (salt-sensitive hypertension) is a serious global health issue. The causes of salt-sensitive hypertension are extremely complex and mathematical models can elucidate potential mechanisms that are experimentally inaccessible. Until recently, the only mathematical model for long-term control of arterial pressure was the model of Guyton and Coleman; referred to as the G-C model. The core of this model is the assumption that sodium excretion is driven by renal perfusion pressure, the so-called 'renal function curve'. Thus, the G-C model dictates that all forms of hypertension are due to a primary shift of the renal function curve to a higher operating pressure. However, several recent experimental studies in a model of hypertension produced by the combination of a high salt intake and administration of angiotensin II, the AngII-salt model, are inconsistent with the G-C model. We developed a new mathematical model that does not limit the cause of salt-sensitive hypertension solely to primary renal dysfunction. The model is the first known mathematical counterexample to the assumption that all salt-sensitive forms of hypertension require a primary shift of renal function: we show that in at least one salt-sensitive form of hypertension the requirement is not necessary. We will refer to this computational model as the 'neurogenic model'. In this Symposium Review we discuss how, despite fundamental differences between the G-C model and the neurogenic model regarding mechanisms regulating sodium excretion and vascular resistance, they generate similar haemodynamic profiles of AngII-salt hypertension. In addition, the steady-state relationships between arterial pressure and sodium excretion, a correlation that is often erroneously presented as the 'renal function curve', are also similar in both models. Our findings suggest that salt-sensitive hypertension is not due solely to renal dysfunction, as predicted by the G-C model, but may

  2. Neurogenic bowel management after spinal cord injury: A systematic review of the evidence

    PubMed Central

    Krassioukov, Andrei; Eng, Janice J.; Claxton, Geri; Sakakibara, Brodie M.; Shum, Serena

    2011-01-01

    OBJECTIVE To systematically review evidence for the management of neurogenic bowel in individuals with spinal cord injuries (SCI). DATA SOURCES Literature searches were conducted for relevant articles, as well as practice guidelines, using numerous electronic databases. Manual searches of retrieved articles from 1950 to July 2009 were also conducted to identify literature. STUDY SELECTION Randomized controlled trials, prospective cohort, case-control, and pre-post studies, and case reports that assessed pharmacological and non-pharmacological intervention for the management of the neurogenic bowel in SCI were included. DATA EXTRACTION Two independent reviewers evaluated each study’s quality, using the PEDro scale for RCTs and the Downs & Black scale for all other studies. Results were tabulated and levels of evidence assigned. DATA SYNTHESIS 2956 studies were found as a result of the literature search. Upon review of the titles and abstracts, 52 studies met the inclusion criteria. Multi-faceted programs are the first approach to neurogenic bowel and are supported by lower levels of evidence. Of the non-pharmacological (conservative and non-surgical) interventions, transanal irrigation is a promising treatment to reduce constipation and fecal incontinence. When conservative management is not effective, pharmacological interventions (e.g., prokinetic agents) are supported by strong evidence for the treatment of chronic constipation. When conservative and pharmacological treatments are not effective, surgical interventions may be considered and are supported by lower levels of evidence in reducing complications. CONCLUSIONS Often, more than one procedure is necessary to develop an effective bowel routine. Evidence is low for non-pharmacological approaches and high for pharmacological interventions. PMID:20212501

  3. Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches

    PubMed Central

    Pérez-Martín, Margarita; Rivera, Patricia; Blanco, Eduardo; Lorefice, Clara; Decara, Juan; Pavón, Francisco J.; Serrano, Antonia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2016-01-01

    Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα−/− mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2′-deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα−/− mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα−/−-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα−/− mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments. PMID:27013951

  4. Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches.

    PubMed

    Pérez-Martín, Margarita; Rivera, Patricia; Blanco, Eduardo; Lorefice, Clara; Decara, Juan; Pavón, Francisco J; Serrano, Antonia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2016-01-01

    Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα(-/-) mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα(-/-) mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα(-/-)-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα(-/-) mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments.

  5. Brain-targeted ACE2 overexpression attenuates neurogenic hypertension by inhibiting COX mediated inflammation

    PubMed Central

    Sriramula, Srinivas; Xia, Huijing; Xu, Ping; Lazartigues, Eric

    2014-01-01

    Overactivity of the renin angiotensin system (RAS), oxidative stress, and cyclooxygenases (COX) in the brain are implicated in the pathogenesis of hypertension. We previously reported that Angiotensin-Converting Enzyme 2 (ACE2) overexpression in the brain attenuates the development of DOCA-salt hypertension, a neurogenic hypertension model with enhanced brain RAS and sympathetic activity. To elucidate the mechanisms involved, we investigated whether oxidative stress, mitogen activated protein kinase signaling and cyclooxygenase (COX) activation in the brain are modulated by ACE2 in neurogenic hypertension. DOCA-salt hypertension significantly increased expression of Nox-2 (+61 ±5 %), Nox-4 (+50 ±13 %) and nitrotyrosine (+89 ±32 %) and reduced activity of the antioxidant enzymes, catalase (−29 ±4 %) and SOD (−31 ±7 %), indicating increased oxidative stress in the brain of non-transgenic mice. This increased oxidative stress was attenuated in transgenic mice overexpressing ACE2 in the brain. DOCA-salt-induced reduction of nNOS expression (−26 ±7 %) and phosphorylated eNOS/total eNOS (−30 ±3 %), and enhanced phosphorylation of Akt and ERK1/2 in the paraventricular nucleus (PVN), were reversed by ACE2 overexpression. In addition, ACE2 overexpression blunted the hypertension-mediated increase in gene and protein expression of COX-1 and COX-2 in the PVN. Furthermore, gene silencing of either COX-1 or COX-2 in the brain, reduced microglial activation and accompanied neuro-inflammation, ultimately attenuating DOCA-salt hypertension. Together, these data provide evidence that brain ACE2 overexpression reduces oxidative stress and COX-mediated neuro-inflammation, improves anti-oxidant and nitric oxide signaling, and thereby attenuates the development of neurogenic hypertension. PMID:25489058

  6. Neurogenic claudication and root claudication treated with calcitonin. A double-blind trial.

    PubMed

    Porter, R W; Miller, C G

    1988-09-01

    Forty-two patients with either neurogenic claudication or unilateral root claudication were analyzed in a double-blind comparison of salmon calcitonin (SCT) and placebo, receiving either 100 IU SCT or 1 ml saline four times a week for 8 weeks. Five of 20 SCT and one of 22 placebo patients were classified as responders. There was no statistically significant difference between the treatment groups in the proportion of responders. Seven of eighteen of the placebo group who later received salmon calcitonin improved their walking distance. The authors have not established that this is an organic response.

  7. Transient Receptor Potential Ankyrin 1 (TRPA1) Channel and Neurogenic Inflammation in Pathogenesis of Asthma

    PubMed Central

    Yang, Hang; Li, ShuZhuang

    2016-01-01

    Asthma is characterized by airway inflammation, airway obstruction, and airway hyperresponsiveness (AHR), and it affects 300 million people worldwide. However, our current understanding of the molecular mechanisms that underlie asthma remains limited. Recent studies have suggested that transient receptor potential ankyrin 1 (TRPA1), one of the transient receptor potential cation channels, may be involved in airway inflammation in asthma. The present review discusses the relationship between TRPA1 and neurogenic inflammation in asthma, hoping to enhance our understanding of the mechanisms of airway inflammation in asthma. PMID:27539812

  8. How botulinum toxin in neurogenic detrusor overactivity can reduce upper urinary tract damage?

    PubMed Central

    Baron, Maximilien; Grise, Philippe; Cornu, Jean-Nicolas

    2016-01-01

    Intradetrusor injections of botulinum toxin are the cornerstone of medical treatment of neurogenic detrusor overactivity. The primary aim of this treatment is to ensure a low pressure regimen in the urinary bladder, but the mechanisms leading to long-term protection of the urinary tract remain poorly understood. In this paper, we highlight the potential benefits of intradetrusor injections of botulinum toxin regarding local effects on the bladder structures, urinary tract infections, stone disease, vesico ureteral reflux, hydronephrosis, renal function based on a comprehensive literature review. PMID:26981445

  9. Back Pain, Neurogenic Symptoms, and Physical Function in Relation to Spondylolisthesis among Elderly Men

    PubMed Central

    Denard, Patrick J.; Holton, Kathleen F.; Miller, Jessica; Fink, Howard A.; Kado, Deborah M.; Marshall, Lynn M.; Yoo, Jung U.

    2010-01-01

    Background Context Degenerative spondylolisthesis is a presumed cause of back pain. Previous studies of spondylolisthesis and back pain included only women or combined results for men and women. Comparisons of the frequency of back pain, neurogenic symptoms, and functional limitations specifically among elderly men with and without spondylolisthesis are needed. Purpose To determine associations of prevalent spondylolisthesis with back pain symptoms, neurogenic symptoms, and functional limitations among elderly men. Study Design/ Setting: Cross-sectional epidemiologic study conducted within the Osteoporotic Fractures in Men (MrOS) cohort. The MrOS cohort is comprised of 5,995 community dwelling men ages ≥65 years who were recruited at 6 US academic medical centers. Extensive self-reported data and lumbar spine radiographs were obtained for all MrOS participants at baseline. Patient Sample For this study, 300 men were selected at random specifically for the evaluation of spondylolisthesis on the baseline spine radiographs. Outcome Measures Standardized questionnaires were used to assess self-reported back pain, leg pain (radiculopathy), lower extremity numbness (paresthesias) and lower extremity weakness occurring in the past 12 months, and to ascertain current difficulty with activities of daily living. Methods In the present study, radiographic spondylolisthesis was classified as forward slip of ≥5%. Prevalence of back pain, neurogenic symptoms and difficulty with activities of daily living were compared between men with and without spondylolisthesis using chisquare or Fisher’s exact tests. Results Spondylolisthesis was present among 92 (31%) men. Among men with and without spondylolisthesis, back pain (63% vs. 67%, p=0.46) and moderate/severe back pain (41% vs. 38%, p=0.76) were reported with similar frequency. Men with spondylolisthesis more often reported radiculopathy (33% vs. 22%, p=0.06), paresthesias (18% vs. 11%, p= 0.10) and weakness (18% vs. 9%, p=0

  10. H3 receptor-mediated inhibition of the neurogenic vasopressor response in pithed rats.

    PubMed

    Malinowska, B; Schlicker, E

    1991-12-03

    In pithed rats, the H3 agonist R-(-)-alpha-methylhistamine (R alpha MeHA) inhibited the electrically induced increase in blood pressure without affecting the vasopressor response to exogenous noradrenaline. The effect of R alpha MeHA was not affected by the H1 and H2 antagonists dimetindene and ranitidine, but attenuated by the H3 antagonist thioperamide. At higher doses, R alpha MeHA itself increased basal blood pressure; this effect was not affected by the H1, H2 and H3 antagonists. In conclusion, the neurogenic vasopressor response can be modulated via H3 receptors, probably located presynaptically on postganglionic sympathetic nerve fibres.

  11. [Neurogenic oropharyngeal dysphagia is a frequent condition in patients admitted to the ICU].

    PubMed

    Pedersen, Anette Barbre; Kjærsgaard, Annette; Larsen, Jens Kjærgaard Rolighed; Nielsen, Lars Hedemann

    2015-03-02

    Neurogenic oropharyngeal dysphagia (NOD) is a frequent condition in neurological patients admitted to the ICU, particularly in patients with brainstem lesions. The CNS damage itself can predispose to dysphagia, but also the treatment and preventive measures may predispose to and exacerbate the condition. Frequent pneumonia in a neurological patient is a warning signal that should cause screening for dysphagia. Complications are serious and can be fatal. Neurological patients should be examined for NOD before decannulation. Treatment is difficult, so prevention and multidisciplinary neurological rehabilitation is important.

  12. Congenital causes of neurogenic bladder and the transition to adult care

    PubMed Central

    Loftus, Christopher J.

    2016-01-01

    The population of patients with congenital genitourinary disorders has unique healthcare demands that require an additional interpersonal and medical skillset. Adults with congenital neurogenic bladder may have complex urinary anatomy, abnormal bladder function and atypical voiding mechanisms. While initial surgery and care of these patients is typically managed by a pediatric urologist, growth and development into adulthood necessitates transition of care to an adult care team. Failure of transition to adult care has been demonstrated to result in lower quality healthcare and increased risk of developing preventable complications. PMID:26904411

  13. From network structure to network reorganization: implications for adult neurogenesis

    NASA Astrophysics Data System (ADS)

    Schneider-Mizell, Casey M.; Parent, Jack M.; Ben-Jacob, Eshel; Zochowski, Michal R.; Sander, Leonard M.

    2010-12-01

    Networks can be dynamical systems that undergo functional and structural reorganization. One example of such a process is adult hippocampal neurogenesis, in which new cells are continuously born and incorporate into the existing network of the dentate gyrus region of the hippocampus. Many of these introduced cells mature and become indistinguishable from established neurons, joining the existing network. Activity in the network environment is known to promote birth, survival and incorporation of new cells. However, after epileptogenic injury, changes to the connectivity structure around the neurogenic niche are known to correlate with aberrant neurogenesis. The possible role of network-level changes in the development of epilepsy is not well understood. In this paper, we use a computational model to investigate how the structural and functional outcomes of network reorganization, driven by addition of new cells during neurogenesis, depend on the original network structure. We find that there is a stable network topology that allows the network to incorporate new neurons in a manner that enhances activity of the persistently active region, but maintains global network properties. In networks having other connectivity structures, new cells can greatly alter the distribution of firing activity and destroy the initial activity patterns. We thus find that new cells are able to provide focused enhancement of network only for small-world networks with sufficient inhibition. Network-level deviations from this topology, such as those caused by epileptogenic injury, can set the network down a path that develops toward pathological dynamics and aberrant structural integration of new cells.

  14. The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

    PubMed Central

    Guan, Yong; Wendong, Sun; Zhao, Shengtian; Liu, Tongyan; Liu, Yuqiang; Zhang, Xiulin; Yuan, Mingzhen

    2015-01-01

    ABSTRACT Erectile dysfunction (ED) is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5) questionnaire. Nocturnal penile tumescence (NPT) testing confirmed the occurrence of ED in 96 (80%) patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30%) were demonstrated only with vascular abnormality, 41 (42.7%) were detected only with neural abnormality, 26 (27.1%) revealed mixed abnormalities. Of the 55 patients (29+26) with vascular problems, 7 patients (12.7%) with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine), 31 (56.4%) with corporal veno-occlusive dysfunction and 17 (30.9%) had both problems. Of the 67 (41+26) patients with abnormal neurophysiological outcomes, 51 (76.1%) with abnormal bulbocavernosus reflex (BCR), 20 (29.9%) with pathological pudendal nerve evoked potentials (PDEPs) and 25 (37.3%) with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs). Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED. PMID:26689522

  15. Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging

    PubMed Central

    Zanni, Giulia; Michno, Wojciech; Di Martino, Elena; Tjärnlund-Wolf, Anna; Pettersson, Jean; Mason, Charlotte Elizabeth; Hellspong, Gustaf; Blomgren, Klas; Hanrieder, Jörg

    2017-01-01

    Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain. PMID:28098178

  16. Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging.

    PubMed

    Zanni, Giulia; Michno, Wojciech; Di Martino, Elena; Tjärnlund-Wolf, Anna; Pettersson, Jean; Mason, Charlotte Elizabeth; Hellspong, Gustaf; Blomgren, Klas; Hanrieder, Jörg

    2017-01-18

    Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain.

  17. Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases.

    PubMed

    Herrera-Arozamena, Clara; Martí-Marí, Olaia; Estrada, Martín; de la Fuente Revenga, Mario; Rodríguez-Franco, María Isabel

    2016-09-01

    The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer's disease (AD) and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT) and nuclear erythroid 2-related factor (Nrf2).

  18. ASCL1 reprograms mouse Müller glia into neurogenic retinal progenitors

    PubMed Central

    Pollak, Julia; Wilken, Matthew S.; Ueki, Yumi; Cox, Kristen E.; Sullivan, Jane M.; Taylor, Russell J.; Levine, Edward M.; Reh, Thomas A.

    2013-01-01

    Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia (MG) that activate the gene encoding the proneural factor Achaete-scute homolog 1 (Ascl1; also known as Mash1 in mammals) and de-differentiate into progenitor cells. By contrast, mammalian MG have a limited regenerative response and fail to upregulate Ascl1 after injury. To test whether ASCL1 could restore neurogenic potential to mammalian MG, we overexpressed ASCL1 in dissociated mouse MG cultures and intact retinal explants. ASCL1-infected MG upregulated retinal progenitor-specific genes and downregulated glial genes. Furthermore, ASCL1 remodeled the chromatin at its targets from a repressive to an active configuration. MG-derived progenitors differentiated into cells that exhibited neuronal morphologies, expressed retinal subtype-specific neuronal markers and displayed neuron-like physiological responses. These results indicate that a single transcription factor, ASCL1, can induce a neurogenic state in mature MG. PMID:23637330

  19. A case of small round cell tumor of the thoracopulmonary region with myogenic and neurogenic elements.

    PubMed

    Goji, J; Sano, K; Murakami, R; Nakamura, H; Ninomiya, M; Ito, H

    1992-02-01

    We here report a unique case of a young boy with an intrathoracic tumor which consisted of neurogenic and myogenic elements. The initial pathological diagnosis was alveolar rhabdomyosarcoma. The tumor tissue from surgical resection was composed of three parts, each showing a different histological appearance, i.e. a monotonous small cell area, an alveolar area, and an area consisting of pleomorphic rhabdomyoblasts. The small round cells in the monotonous area were immunoreactive with the antibodies for Leu7, neuron-specific enolase (NSE), neurofilament proteins (NFP), and beta 2 microglobulin, but not with the antibody for desmin. These cells also had dense core granules. The tumor cells in the alveolar area were immunoreactive with the antibodies for Leu7 and desmin, but not with the antibody for NFP. Pleomorphic rhabdomyoblasts were immunoreactive with the antibody for desmin, but not with the antibodies for Leu7 and NFP. These findings imply that this tumor consisted of neurogenic and myogenic elements and is considered to be a special type of rhabdomyosarcoma.

  20. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    PubMed Central

    Coste, Cécile; Neirinckx, Virginie; Gothot, André; Wislet, Sabine; Rogister, Bernard

    2015-01-01

    Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC) function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL) 12-abundant reticular (CAR) cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs), which have been recently identified as neural crest-derived cells (NCSCs). Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system. PMID:26136659

  1. The current state of the neurogenic theory of depression and anxiety.

    PubMed

    Miller, Bradley R; Hen, René

    2015-02-01

    Newborn neurons are continuously added to the adult hippocampus. Early studies found that adult neurogenesis is impaired in models of depression and anxiety and accelerated by antidepressant treatment. This led to the theory that depression results from impaired adult neurogenesis and restoration of adult neurogenesis leads to recovery. Follow up studies yielded a complex body of often inconsistent results, and the veracity of this theory is uncertain. We propose five criteria for acceptance of this theory, we review the recent evidence for each criterion, and we draw the following conclusions: Diverse animal models of depression and anxiety have impaired neurogenesis. Neurogenesis is consistently boosted by antidepressants in animal models only when animals are stressed. Ablation of neurogenesis in animal models impairs cognitive functions relevant to depression, but only a minority of studies find that ablation causes depression or anxiety. Recent human neuroimaging and postmortem studies are consistent with the neurogenic theory, but they are indirect. Finally, a novel drug developed based on the neurogenic theory is promising in animal models.

  2. Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation.

    PubMed

    Pereira, Ulysse; Garcia-Le Gal, Caridad; Le Gal, Grégoire; Boulais, Nicholas; Lebonvallet, Nicolas; Dorange, Germaine; Lefeuvre, Luc; Gougerot, Agnés; Misery, Laurent

    2010-09-01

    Sangre de drago (SD) is a viscous bright red resin collected from Croton lechleri trees that grow in the South American jungle. This sap is used extensively in the native pharmacopoeia to treat skin disorders. Its effectiveness as an inhibitor of neurogenic inflammation has been recently demonstrated. To understand the underlying mechanisms of these effects, we examined the ability of SD to reduce substance P (SP) release in an in vitro model of cutaneous neurogenic inflammation (CNI). This model is based on an enzyme immunoassay of SP (an inducer of CNI) in a porcine co-culture of dorsal root ganglion neurons and keratinocytes. After incubation with different concentrations of SD, we noted an immediate and significant dose-dependent decrease in basal SP release, with average values of 32% at 1% SD (v/v) and 26% at 0.1% (v/v). On the other hand, pretreatment (72 or 1 h) of the co-culture with 1% SD (v/v) was sufficient to induce a 111% (72 h) or 65% (1 h) inhibition of capsaicin-induced SP release, while 0.1% SD (v/v) triggered a 109% (72 h) or 30% (1 h) inhibition. We conclude that sangre de drago is a potent inhibitor of CNI through direct inhibition of neuropeptide release by sensory afferent nerves.

  3. SVCT2 vitamin C transporter expression in progenitor cells of the postnatal neurogenic niche

    PubMed Central

    Pastor, Patricia; Cisternas, Pedro; Salazar, Katterine; Silva-Alvarez, Carmen; Oyarce, Karina; Jara, Nery; Espinoza, Francisca; Martínez, Agustín D.; Nualart, Francisco

    2013-01-01

    Known as a critical antioxidant, recent studies suggest that vitamin C plays an important role in stem cell generation, proliferation and differentiation. Vitamin C also enhances neural differentiation during cerebral development, a function that has not been studied in brain precursor cells. We observed that the rat neurogenic niche is structurally organized at day 15 of postnatal development, and proliferation and neural differentiation increase at day 21. In the human brain, a similar subventricular niche was observed at 1-month of postnatal development. Using immunohistochemistry, sodium-vitamin C cotransporter 2 (SVCT2) expression was detected in the subventricular zone (SVZ) and rostral migratory stream (RMS). Low co-distribution of SVCT2 and βIII-tubulin in neuroblasts or type-A cells was detected, and minimal co-localization of SVCT2 and GFAP in type-B or precursor cells was observed. Similar results were obtained in the human neurogenic niche. However, BrdU-positive cells also expressed SVCT2, suggesting a role of vitamin C in neural progenitor proliferation. Primary neurospheres prepared from rat brain and the P19 teratocarcinoma cell line, which forms neurospheres in vitro, were used to analyze the effect of vitamin C in neural stem cells. Both cell types expressed functional SVCT2 in vitro, and ascorbic acid (AA) induced their neural differentiation, increased βIII-tubulin and SVCT2 expression, and amplified vitamin C uptake. PMID:23964197

  4. Microneedle Electrode Array for Electrical Impedance Myography to Characterize Neurogenic Myopathy.

    PubMed

    Li, Zhao; Li, Yi; Liu, Mingsheng; Cui, Liying; Yu, Yude

    2016-05-01

    Electrical impedance myography (EIM) is a noninvasive technique for neuromuscular assessment, wherein a low-intensity alternating current is applied to a muscle, and the consequent surface voltage patterns are evaluated. Commercial wet electrodes are most commonly used for EIM. However, these electrodes are not suitable for use on small muscles, as they do not effectively solve the problem of high electrode-skin contact impedance (ESCI) that negatively influences the quality of recorded biopotentials. To address this problem, we fabricated a novel microneedle electrode array (MEA) that consists of 124-µm-long microneedles. Compared to wet electrodes, the MEA could pierce through the outer skin surface in a painless and micro-invasive manner, and could thus effectively reduce ESCI. The MEA has excellent test-retest reproducibility, with intraclass correlation coefficients exceeding 0.920. When used in combination with EIM, the MEA differentiated the affected muscles from the unaffected muscles in patients with neurogenic myopathy, by using EIM parameters of reactance and phase (p = 0.023 and 0.008, respectively). Thus, the novel MEA is a practical and reusable device for EIM assessment in cases of neurogenic myopathy. However, further refinement of the electrode is needed to enhance the clinical application of the system.

  5. p73 is required for ependymal cell maturation and neurogenic SVZ cytoarchitecture.

    PubMed

    Gonzalez-Cano, L; Fuertes-Alvarez, S; Robledinos-Anton, N; Bizy, A; Villena-Cortes, A; Fariñas, I; Marques, M M; Marin, Maria C

    2016-07-01

    The adult subventricular zone (SVZ) is a highly organized microenvironment established during the first postnatal days when radial glia cells begin to transform into type B-cells and ependymal cells, all of which will form regenerative units, pinwheels, along the lateral wall of the lateral ventricle. Here, we identify p73, a p53 homologue, as a critical factor controlling both cell-type specification and structural organization of the developing mouse SVZ. We describe that p73 deficiency halts the transition of the radial glia into ependymal cells, leading to the emergence of immature cells with abnormal identities in the ventricle and resulting in loss of the ventricular integrity. p73-deficient ependymal cells have noticeably impaired ciliogenesis and they fail to organize into pinwheels, disrupting SVZ niche structure and function. Therefore, p73 is essential for appropriate ependymal cell maturation and the establishment of the neurogenic niche architecture. Accordingly, lack of p73 results in impaired neurogenesis. Moreover, p73 is required for translational planar cell polarity establishment, since p73 deficiency results in profound defects in cilia organization in individual cells and in intercellular patch orientation. Thus, our data reveal a completely new function of p73, independent of p53, in the neurogenic architecture of the SVZ of rodent brain and in the establishment of ependymal planar cell polarity with important implications in neurogenesis. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 730-747, 2016.

  6. Effects of electroacupuncture combined with bladder training on the bladder function of patients with neurogenic bladder after spinal cord injury

    PubMed Central

    Xia, Li-Ping; Fan, Fan; Tang, Ai-Ling; Ye, Wen-Qin

    2014-01-01

    Neurogenic bladder is a common complication of spinal cord injury and results in urinary bladder dysfunction through lost control of micturition, or urination. Although several treatment options exist, the efficacies of many of these treatments are unknown. In particular, electroacupuncture and bladder training have had some success as individual treatments. The aim of this study was to explore effects of electroacupuncture combined with bladder training on bladder function of patients with neurogenic bladder after spinal cord injury (SCI) above the sacral segment. Forty-two patients with neurogenic bladder after SCI were evenly divided into two groups (n=21) and given only bladder function training (control group) or electroacupuncture combined with bladder function training (treatment group). Urodynamic changes, IPSS score, and therapeutic efficacy were compared between groups pre- and post-treatment. After either treatment, patients had higher bladder volume and bladder compliance, but lower residual urine volume, bladder pressure, rectal pressure, and detrusor pressure, compared to pre-treatment (P<0.05). Compared to controls, treatment group patients had significantly increased bladder volume and bladder compliance, but significantly decreased residual urine volume, bladder pressure, rectal pressure, and detrusor pressure (P<0.05). Treatment group patients had lower IPSS scores post-treatment (P<0.05) and better therapeutic efficacy (P<0.05) than control group patients. Altogether, our results suggest that electroacupuncture combined with bladder function training can clinically improve bladder function of patients with neurogenic bladder after SCI above the sacral segment. PMID:24995093

  7. Inhibitory effect of botulinum toxin type A on the NANC system in rat respiratory models of neurogenic inflammation.

    PubMed

    Chien, Chiang-Ting; Lee, Hsin-Min; Wu, Chia-Ching Josh; Li, Ping-Chia

    2012-08-15

    This study investigated whether botulinum toxin type A (BTX-A) inhibits respiratory neurogenic inflammation in the non-adrenergic, non-cholinergic (NANC) transmitter system in rats. Neurogenic inflammation models were induced in Sprague Dawley (SD) rats through bilateral cerebral artery occlusion (BCAO) for different times (0, 30 and 60 min) or by stimulation with capsaicin at different doses (5 or 15 g/kg). Pre-Bötzinger Complex-Spikes and the expression of substance P, synaptosomal-associated protein-25 (SNAP-25), and reactive oxygen species (ROS) were detected with or without pretreatment of rats with BTX-A (15 or 30 U/kg). BCAO reduced pre-Bot C spike activity (spike/s) and increased the breath rate (breaths/s) in an unstable pattern in comparison to controls, while pretreatment with BTX-A slightly reduced this phenomenon. Pretreatment with BTX-A inhibited BCAO- or capsaicin-induced increases in expression of SNAP-25, substance P, and ROS in a dose-dependent manner in brainstem and lung tissue. BTX-A exerts a suppressive effect on neurogenic inflammation via non-adrenergic, non-cholinergic transmitters. These results add to the body of evidence elucidating the non-cholinergic effects of BTX-A in the context of neurogenic inflammation.

  8. Neurogenic bladder

    MedlinePlus

    ... cause skin to break down and lead to pressure sores Kidney damage if the bladder becomes too full, ... More Tumor Patient Instructions Multiple sclerosis - discharge Preventing pressure ulcers Review Date 5/30/2016 Updated by: Amit ...

  9. Neurogenic Stuttering

    MedlinePlus

    ... even depression about the difficulty they encounter in speaking. This may be accompanied by other behaviors, which ... speech production; movements of head or limbs while speaking; reduced eye contact; Postponement or delay in attempting ...

  10. The selective PAC1 receptor agonist maxadilan inhibits neurogenic vasodilation and edema formation in the mouse skin.

    PubMed

    Banki, E; Hajna, Zs; Kemeny, A; Botz, B; Nagy, P; Bolcskei, K; Toth, G; Reglodi, D; Helyes, Zs

    2014-10-01

    We have earlier shown that PACAP-38 decreases neurogenic inflammation. However, there were no data on its receptorial mechanism and the involvement of its PAC1 and VPAC1/2 receptors (PAC1R, VPAC1/2R) in this inhibitory effect. Neurogenic inflammation in the mouse ear was induced by topical application of the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor activator mustard oil (MO). Consequent neurogenic edema, vasodilation and plasma leakage were assessed by measuring ear thickness with engineer's micrometer, detecting tissue perfusion by laser Doppler scanning and Evans blue or indocyanine green extravasation by intravital videomicroscopy or fluorescence imaging, respectively. Myeloperoxidase activity, an indicator of neutrophil infiltration, was measured from the ear homogenates with spectrophotometry. The selective PAC1R agonist maxadilan, the VPAC1/2R agonist vasoactive intestinal polypeptide (VIP) or the vehicle were administered i.p. 15 min before MO. Substance P (SP) concentration of the ear was assessed by radioimmunoassay. Maxadilan significantly diminished MO-induced neurogenic edema, increase of vascular permeability and vasodilation. These inhibitory effects of maxadilan may be partially due to the decreased substance P (SP) levels. In contrast, inhibitory effect of VIP on ear swelling was moderate, without any effect on MO-induced plasma leakage or SP release, however, activation of VPAC1/2R inhibited the increased microcirculation caused by the early arteriolar vasodilation. Neither the PAC1R, nor the VPAC1/2R agonist influenced the MO-evoked increase in tissue myeloperoxidase activity. These results clearly show that PAC1R activation inhibits acute neurogenic arterial vasodilation and plasma protein leakage from the venules, while VPAC1/2R stimulation is only involved in the attenuation of vasodilation.

  11. Neurogenic pulmonary edema combined with febrile seizures in early childhood-A report of two cases.

    PubMed

    Tasaka, Keiji; Matsubara, Kousaku; Hori, Masayuki; Nigami, Hiroyuki; Iwata, Aya; Isome, Kenichi; Kawasaki, Yu; Nagai, Sadayuki

    2016-01-01

    Neurogenic pulmonary edema (NPE) is a clinical entity that can occur following central nervous system disorders. However, NPE occurs quite rarely in early childhood, and there has only been one report about pediatric NPE associated with febrile seizures. Two cases are reported here. One case involved a 2-year-old girl who presented with febrile seizures, which rapidly progressed to severe NPE. Since the NPE occurred in the emergency department room, the patient was able to be resuscitated via immediate endotracheal intubation. The other case involved an 11-month-old boy who developed respiratory distress following a 50-min episode of febrile status epilepticus. Both patients required respiratory management in the intensive care unit. However their conditions were dramatically improved within several days and fully recovered without any sequelae.

  12. TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins.

    PubMed

    Meseguer, Victor; Alpizar, Yeranddy A; Luis, Enoch; Tajada, Sendoa; Denlinger, Bristol; Fajardo, Otto; Manenschijn, Jan-Albert; Fernández-Peña, Carlos; Talavera, Arturo; Kichko, Tatiana; Navia, Belén; Sánchez, Alicia; Señarís, Rosa; Reeh, Peter; Pérez-García, María Teresa; López-López, José Ramón; Voets, Thomas; Belmonte, Carlos; Talavera, Karel; Viana, Félix

    2014-01-01

    Gram-negative bacterial infections are accompanied by inflammation and somatic or visceral pain. These symptoms are generally attributed to sensitization of nociceptors by inflammatory mediators released by immune cells. Nociceptor sensitization during inflammation occurs through activation of the Toll-like receptor 4 (TLR4) signalling pathway by lipopolysaccharide (LPS), a toxic by-product of bacterial lysis. Here we show that LPS exerts fast, membrane delimited, excitatory actions via TRPA1, a transient receptor potential cation channel that is critical for transducing environmental irritant stimuli into nociceptor activity. Moreover, we find that pain and acute vascular reactions, including neurogenic inflammation (CGRP release) caused by LPS are primarily dependent on TRPA1 channel activation in nociceptive sensory neurons, and develop independently of TLR4 activation. The identification of TRPA1 as a molecular determinant of direct LPS effects on nociceptors offers new insights into the pathogenesis of pain and neurovascular responses during bacterial infections and opens novel avenues for their treatment.

  13. Vertebrate neurogenic placode development: historical highlights that have shaped our current understanding.

    PubMed

    Stark, Michael R

    2014-10-01

    With the flood of published research encountered today, it is important to occasionally reflect upon how we arrived at our current understanding in a particular scientific discipline, thereby positioning new discoveries into proper context with long-established models. This historical review highlights some of the important scientific contributions in the field of neurogenic placode development. By viewing cumulatively the rich historical data, we can more fully appreciate and apply what has been accomplished. Early descriptive work in fish and experimental approaches in amphibians and chick yielded important conceptual models of placode induction and cellular differentiation. Current efforts to discover genes and their molecular functions continue to expand our understanding of the placodes. Carefully considering the body of work may improve current models and help focus modern experimental design.

  14. TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins

    NASA Astrophysics Data System (ADS)

    Meseguer, Victor; Alpizar, Yeranddy A.; Luis, Enoch; Tajada, Sendoa; Denlinger, Bristol; Fajardo, Otto; Manenschijn, Jan-Albert; Fernández-Peña, Carlos; Talavera, Arturo; Kichko, Tatiana; Navia, Belén; Sánchez, Alicia; Señarís, Rosa; Reeh, Peter; Pérez-García, María Teresa; López-López, José Ramón; Voets, Thomas; Belmonte, Carlos; Talavera, Karel; Viana, Félix

    2014-01-01

    Gram-negative bacterial infections are accompanied by inflammation and somatic or visceral pain. These symptoms are generally attributed to sensitization of nociceptors by inflammatory mediators released by immune cells. Nociceptor sensitization during inflammation occurs through activation of the Toll-like receptor 4 (TLR4) signalling pathway by lipopolysaccharide (LPS), a toxic by-product of bacterial lysis. Here we show that LPS exerts fast, membrane delimited, excitatory actions via TRPA1, a transient receptor potential cation channel that is critical for transducing environmental irritant stimuli into nociceptor activity. Moreover, we find that pain and acute vascular reactions, including neurogenic inflammation (CGRP release) caused by LPS are primarily dependent on TRPA1 channel activation in nociceptive sensory neurons, and develop independently of TLR4 activation. The identification of TRPA1 as a molecular determinant of direct LPS effects on nociceptors offers new insights into the pathogenesis of pain and neurovascular responses during bacterial infections and opens novel avenues for their treatment.

  15. Brain Ischemia Suppresses Immunity in the Periphery and Brain via Different Neurogenic Innervations.

    PubMed

    Liu, Qiang; Jin, Wei-Na; Liu, Yaou; Shi, Kaibin; Sun, Haoran; Zhang, Fang; Zhang, Chao; Gonzales, Rayna J; Sheth, Kevin N; La Cava, Antonio; Shi, Fu-Dong

    2017-03-21

    Brain ischemia inhibits immune function systemically, with resulting infectious complications. Whether in stroke different immune alterations occur in brain and periphery and whether analogous mechanisms operate in these compartments remains unclear. Here we show that in patients with ischemic stroke and in mice subjected to middle cerebral artery occlusion, natural killer (NK) cells display remarkably distinct temporal and transcriptome profiles in the brain as compared to the periphery. The activation of catecholaminergic and hypothalamic-pituitary-adrenal axis leads to splenic atrophy and contraction of NK cell numbers in the periphery through a modulated expression of SOCS3, whereas cholinergic innervation-mediated suppression of NK cell responses in the brain involves RUNX3. Importantly, pharmacological or genetic ablation of innervation preserved NK cell function and restrained post-stroke infection. Thus, brain ischemia compromises NK cell-mediated immune defenses through mechanisms that differ in the brain versus the periphery, and targeted inhibition of neurogenic innervation limits post-stroke infection.

  16. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

    PubMed

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

    2016-02-29

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

  17. Self-maintenance of neurogenic inflammation contributes to a vicious cycle in skin.

    PubMed

    Gouin, Olivier; Lebonvallet, Nicolas; L'Herondelle, Killian; Le Gall-Ianotto, Christelle; Buhé, Virginie; Plée-Gautier, Emmanuelle; Carré, Jean-Luc; Lefeuvre, Luc; Misery, Laurent

    2015-10-01

    Cutaneous neurogenic inflammation (CNI) is frequently associated with skin disorders. CNI is not limited to the retrograde signalling of nociceptive sensory nerve endings but can instead be regarded as a multicellular phenomenon. Thus, soluble mediators participating in communication among sensory nerves, skin and immune cells are key components of CNI. These interactions induce the self-maintenance of CNI, promoting a vicious cycle. Certain G protein-coupled receptors (GPCRs) play a prominent role in these cell interactions and contribute to self-maintenance. Protease-activated receptors 2 and 4 (PAR-2 and PAR-4, respectively) and Mas-related G protein-coupled receptors (Mrgprs) are implicated in the synthesis and release of neuropeptides, proteases and soluble mediators from most cutaneous cells. Regulation of the expression and release of these mediators contributes to the vicious cycle of CNI. The authors propose certain hypothetical therapeutic options to interrupt this cycle, which might reduce skin symptoms and improve patient quality of life.

  18. Endocannabinoids via CB1 receptors act as neurogenic niche cues during cortical development

    PubMed Central

    Díaz-Alonso, Javier; Guzmán, Manuel; Galve-Roperh, Ismael

    2012-01-01

    During brain development, neurogenesis is precisely regulated by the concerted action of intrinsic factors and extracellular signalling systems that provide the necessary niche information to proliferating and differentiating cells. A number of recent studies have revealed a previously unknown role for the endocannabinoid (ECB) system in the control of embryonic neuronal development and maturation. Thus, the CB1 cannabinoid receptor in concert with locally produced ECBs regulates neural progenitor (NP) proliferation, pyramidal specification and axonal navigation. In addition, subcellularly restricted ECB production acts as an axonal growth cone signal to regulate interneuron morphogenesis. These findings provide the rationale for understanding better the consequences of prenatal cannabinoid exposure, and emphasize a novel role of ECBs as neurogenic instructive cues involved in cortical development. In this review the implications of altered CB1-receptor-mediated signalling in developmental disorders and particularly in epileptogenesis are briefly discussed. PMID:23108542

  19. Neurogenic thoracic outlet syndrome: current diagnostic criteria and advances in MRI diagnostics.

    PubMed

    Magill, Stephen T; Brus-Ramer, Marcel; Weinstein, Philip R; Chin, Cynthia T; Jacques, Line

    2015-09-01

    Neurogenic thoracic outlet syndrome (nTOS) is caused by compression of the brachial plexus as it traverses from the thoracic outlet to the axilla. Diagnosing nTOS can be difficult because of overlap with other complex pain and entrapment syndromes. An nTOS diagnosis is made based on patient history, physical exam, electrodiagnostic studies, and, more recently, interpretation of MR neurograms with tractography. Advances in high-resolution MRI and tractography can confirm an nTOS diagnosis and identify the location of nerve compression, allowing tailored surgical decompression. In this report, the authors review the current diagnostic criteria, present an update on advances in MRI, and provide case examples demonstrating how MR neurography (MRN) can aid in diagnosing nTOS. The authors conclude that improved high-resolution MRN and tractography are valuable tools for identifying the source of nerve compression in patients with nTOS and can augment current diagnostic modalities for this syndrome.

  20. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche

    PubMed Central

    Chang, Eun Hyuk; Adorjan, Istvan; Mundim, Mayara V.; Sun, Bin; Dizon, Maria L. V.; Szele, Francis G.

    2016-01-01

    Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI. PMID:27531972

  1. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

    PubMed Central

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

    2016-01-01

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

  2. Long-term outcomes of urinary tract reconstruction in patients with neurogenic urinary tract dysfunction.

    PubMed

    Johnson, E U; Singh, Gurpreet

    2013-10-01

    The advent of specialized spinal units and better understanding of the pathophysiology of neurogenic urinary tract dysfunction has made long-term survival of these patients a reality. This has, in turn, led to an increase in quality and choice of management modalities offered to these patients including complex anatomic urinary tract reconstructive procedures tailored to the unique needs of each individual with variable outcomes. We performed a literature review evaluating the long-term outcomes of these reconstructive procedures. To achieve this, we conducted a world-wide electronic literature search of long-term outcomes published in English. As the premise of this review is long-term outcomes, we have focused on pathologies where evidence of long-term outcome is available such as patients with spinal injuries and spina bifida. Therapeutic success following urinary tract reconstruction is usually measured by preservation of renal function, improvement in quality-of-life, the satisfactory achievement of agreed outcomes and the prevention of serious complications. Prognostic factors include neuropathic detrusor overactivity; sphincter dyssynergia; bladder over distension; high pressure storage and high leak point pressures; vesicoureteric reflex, stone formation and urinary tract infections. Although, the past decade has witnessed a reduction in the total number of bladder reconstructive surgeries in the UK, these procedures are essentially safe and effective; but require long-term clinical and functional follow-up/monitoring. Until tissue engineering and gene therapy becomes more mainstream, we feel there is still a place for urinary tract reconstruction in patients with neurogenic lower urinary tract dysfunction.

  3. Long-term outcomes of urinary tract reconstruction in patients with neurogenic urinary tract dysfunction

    PubMed Central

    Johnson, E. U.; Singh, Gurpreet

    2013-01-01

    The advent of specialized spinal units and better understanding of the pathophysiology of neurogenic urinary tract dysfunction has made long-term survival of these patients a reality. This has, in turn, led to an increase in quality and choice of management modalities offered to these patients including complex anatomic urinary tract reconstructive procedures tailored to the unique needs of each individual with variable outcomes. We performed a literature review evaluating the long-term outcomes of these reconstructive procedures. To achieve this, we conducted a world-wide electronic literature search of long-term outcomes published in English. As the premise of this review is long-term outcomes, we have focused on pathologies where evidence of long-term outcome is available such as patients with spinal injuries and spina bifida. Therapeutic success following urinary tract reconstruction is usually measured by preservation of renal function, improvement in quality-of-life, the satisfactory achievement of agreed outcomes and the prevention of serious complications. Prognostic factors include neuropathic detrusor overactivity; sphincter dyssynergia; bladder over distension; high pressure storage and high leak point pressures; vesicoureteric reflex, stone formation and urinary tract infections. Although, the past decade has witnessed a reduction in the total number of bladder reconstructive surgeries in the UK, these procedures are essentially safe and effective; but require long-term clinical and functional follow-up/monitoring. Until tissue engineering and gene therapy becomes more mainstream, we feel there is still a place for urinary tract reconstruction in patients with neurogenic lower urinary tract dysfunction. PMID:24235796

  4. Hippocampal transcriptional and neurogenic changes evoked by combination yohimbine and imipramine treatment.

    PubMed

    Husain, Basma Fatima Anwar; Nanavaty, Ishira N; Marathe, Swananda V; Rajendran, Rajeev; Vaidya, Vidita A

    2015-08-03

    Adjunct α2-adrenoceptor antagonism is a potential strategy to accelerate the behavioral effects of antidepressants. Co-administration of the α2-adrenoceptor antagonist yohimbine hastens the behavioral and neurogenic effects of the antidepressant imipramine. We examined the transcriptional targets of short duration (7days), combination treatment of yohimbine and imipramine (Y+I) within the adult rat hippocampus. Using microarray and qPCR analysis we observed functional enrichment of genes involved in intracellular signaling cascades, plasma membrane, cellular metal ion homeostasis, multicellular stress responses and neuropeptide signaling pathways in the Y+I transcriptome. We noted reduced expression of the α2A-adrenoceptor (Adra2a), serotonin 5HT2C receptor (Htr2c) and the somatostatin receptor 1 (Sstr1), which modulate antidepressant action. Further, we noted a regulation of signaling pathway genes like inositol monophosphatase 2 (Impa2), iodothyronine deiodinase 3 (Dio3), regulator of G-protein signaling 4 (Rgs4), alkaline ceramidase 2 (Acer2), doublecortin-like kinase 2 (Dclk2), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (Nfkbia) and serum/glucocorticoid-regulated kinase 1 (Sgk1), several of which are implicated in the pathophysiology of mood disorders. Comparative analysis revealed an overlap in the hippocampal regulation of Acer2, Nfkbia, Sgk1 and Impa2 between Y+I treatment, the fast-acting electroconvulsive seizure (ECS) paradigm, and the slow-onset chronic (21days) imipramine treatment. Further, Y+I treatment enhanced the quiescent neural progenitor pool in the hippocampal neurogenic niche similar to ECS, and distinct from chronic imipramine treatment. Taken together, our results provide insight into the molecular and cellular targets of short duration Y+I treatment, and identify potential leads for the development of rapid-action antidepressants.

  5. Stroke Increases Neural Stem Cells and Angiogenesis in the Neurogenic Niche of the Adult Mouse

    PubMed Central

    Zhang, Rui Lan; Chopp, Michael; Roberts, Cynthia; Liu, Xianshuang; Wei, Min; Nejad-Davarani, Siamak P.; Wang, Xinli; Zhang, Zheng Gang

    2014-01-01

    The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP) positive neural stem cells that are in contact with the cerebrospinal fluid (CSF) via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction. PMID:25437857

  6. Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall

    PubMed Central

    2012-01-01

    Background The cancer stem cell (CSC) hypothesis posits that deregulated neural stem cells (NSCs) form the basis of brain tumors such as glioblastoma multiforme (GBM). GBM, however, usually forms in the cerebral white matter while normal NSCs reside in subventricular and hippocampal regions. We attempted to characterize CSCs from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall. Methods We described isolating CSCs from a GBM involving the lateral ventricles and characterized these cells with in vitro molecular biomarker profiling, cellular behavior, ex vivo and in vivo techniques. Results The patient’s MRI revealed a heterogeneous mass with associated edema, involving the left subventricular zone. Histological examination of the tumor established it as being a high-grade glial neoplasm, characterized by polygonal and fusiform cells with marked nuclear atypia, amphophilic cytoplasm, prominent nucleoli, frequent mitotic figures, irregular zones of necrosis and vascular hyperplasia. Recurrence of the tumor occurred shortly after the surgical resection. CD133-positive cells, isolated from the tumor, expressed stem cell markers including nestin, CD133, Ki67, Sox2, EFNB1, EFNB2, EFNB3, Cav-1, Musashi, Nucleostemin, Notch 2, Notch 4, and Pax6. Biomarkers expressed in differentiated cells included Cathepsin L, Cathepsin B, Mucin18, Mucin24, c-Myc, NSE, and TIMP1. Expression of unique cancer-related transcripts in these CD133-positive cells, such as caveolin-1 and −2, do not appear to have been previously reported in the literature. Ex vivo organotypic brain slice co-culture showed that the CD133+ cells behaved like tumor cells. The CD133-positive cells also induced tumor formation when they were stereotactically transplanted into the brains of the immune-deficient NOD/SCID mice. Conclusions This brain tumor involving the neurogenic lateral ventricular wall was comprised of tumor-forming, CD133-positive cancer stem cells, which are likely

  7. Diabetic Neuropathy and Axon Reflex-Mediated Neurogenic Vasodilatation in Type 1 Diabetes

    PubMed Central

    Bril, Vera; Orszag, Andrej; Ng, Eduardo; Nwe, Patti; Perkins, Bruce A.

    2012-01-01

    Objective Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating may reflect early, pre-clinical small fibre dysfunction. We aimed to evaluate the distribution of the vascular flare area measured by laser doppler imaging (“LDIFLARE area”) in type 1 diabetes and in healthy volunteers. Research and Methods Concurrent with clinical and electrophysiological examination to classify diabetic sensorimotor polyneuropathy (DSP), LDIFLARE area (cm2) was determined in 89 type 1 diabetes subjects matched to 64 healthy volunteers. We examined the association and diagnostic performance of LDI with clinical and subclinical measures of DSP and its severity. Results Compared to the 64 healthy volunteers, the 56 diabetes controls without DSP had significantly lower LDIFLARE area (p = 0.006). The 33 diabetes cases with DSP had substantially lower LDIFLARE area as compared to controls without DSP (p = 0.002). There was considerable overlap in LDIFLARE area between all groups such that the ROC curve had an AUC of 0.72 and optimal sensitivity of 70% for the detection of clinical DSP. Use of a subclinical definition for DSP, according to subclinical sural nerve impairment, was associated with improved AUC of 0.75 and sensitivity of 79%. In multivariate analysis higher HbA1c and body mass index had independent associations with smaller LDIFLARE area. Conclusions Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating is a biomarker of early nerve dysfunction in DSP. Its independent association with glycemic exposure in diabetes subjects and both glycemic exposure and BMI in healthy volunteers highlights the existence of small-fibre dysfunction in the natural history of DSP. PMID:22529938

  8. Reconstitution of experimental neurogenic bladder dysfunction using skeletal muscle-derived multipotent stem cells.

    PubMed

    Nitta, Masahiro; Tamaki, Tetsuro; Tono, Kayoko; Okada, Yoshinori; Masuda, Maki; Akatsuka, Akira; Hoshi, Akio; Usui, Yukio; Terachi, Toshiro

    2010-05-15

    BACKGROUND.: Postoperative neurogenic bladder dysfunction is a major complication of radical hysterectomy for cervical cancer and is mainly caused by unavoidable damage to the bladder branch of the pelvic plexus (BBPP) associated with colateral blood vessels. Thus, we attempted to reconstitute disrupted BBPP and blood vessels using skeletal muscle-derived multipotent stem cells that show synchronized reconstitution capacity of vascular, muscular, and peripheral nervous systems. METHODS.: Under pentobarbital anesthesia, intravesical pressure by electrical stimulation of BBPP was measured as bladder function. The distal portion of BBPP with blood vessels was then cut unilaterally (experimental neurogenic bladder model). Measurements were performed before, immediately after, and at 4 weeks after transplantation as functional recovery. Stem cells were obtained from the right soleus and gastrocnemius muscles after enzymatic digestion and cell sorting as CD34/45 (Sk-34) and CD34/45 (Sk-DN). Suspended cells were autografted around the damaged region, whereas medium alone and CD45 cells were transplanted as control groups. To determine the morphological contribution of the transplanted cells, stem cells obtained from green fluorescent protein transgenic mouse muscles were transplanted into a nude rat model and were examined by immunohistochemistry and immunoelectron microscopy. RESULTS.: At 4 weeks after surgery, the transplantation group showed significantly higher functional recovery ( approximately 80%) than the two controls ( approximately 28% and 24%). The transplanted cells showed an incorporation into the damaged peripheral nerves and blood vessels after differentiation into Schwann cells, perineurial cells, vascular smooth muscle cells, pericytes, and fibroblasts around the bladder. CONCLUSION.: Transplantation of multipotent Sk-34 and Sk-DN cells is potentially useful for the reconstitution of damaged BBPP.

  9. Evaluation of educational content of YouTube videos relating to neurogenic bladder and intermittent catheterization

    PubMed Central

    Ho, Matthew; Stothers, Lynn; Lazare, Darren; Tsang, Brian; Macnab, Andrew

    2015-01-01

    Introduction: Many patients conduct internet searches to manage their own health problems, to decide if they need professional help, and to corroborate information given in a clinical encounter. Good information can improve patients’ understanding of their condition and their self-efficacy. Patients with spinal cord injury (SCI) featuring neurogenic bladder (NB) require knowledge and skills related to their condition and need for intermittent catheterization (IC). Methods: Information quality was evaluated in videos accessed via YouTube relating to NB and IC using search terms “neurogenic bladder intermittent catheter” and “spinal cord injury intermittent catheter.” Video content was independently rated by 3 investigators using criteria based on European Urological Association (EAU) guidelines and established clinical practice. Results: In total, 71 videos met the inclusion criteria. Of these, 12 (17%) addressed IC and 50 (70%) contained information on NB. The remaining videos met inclusion criteria, but did not contain information relevant to either IC or NB. Analysis indicated poor overall quality of information, with some videos with information contradictory to EAU guidelines for IC. High-quality videos were randomly distributed by YouTube. IC videos featuring a healthcare narrator scored significantly higher than patient-narrated videos, but not higher than videos with a merchant narrator. About half of the videos contained commercial content. Conclusions: Some good-quality educational videos about NB and IC are available on YouTube, but most are poor. The videos deemed good quality were not prominently ranked by the YouTube search algorithm, consequently user access is less likely. Study limitations include the limit of 50 videos per category and the use of a de novo rating tool. Information quality in videos with healthcare narrators was not higher than in those featuring merchant narrators. Better material is required to improve patients

  10. Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities

    PubMed Central

    Salgado, Antonio J.; Sousa, Joao C.; Costa, Bruno M.; Pires, Ana O.; Mateus-Pinheiro, António; Teixeira, F. G.; Pinto, Luisa; Sousa, Nuno

    2015-01-01

    Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) share few characteristics apart from self-renewal and multipotency. In fact, the neurogenic and osteogenic stem cell niches derive from two distinct embryonary structures; while the later originates from the mesoderm, as all the connective tissues do, the first derives from the ectoderm. Therefore, it is highly unlikely that stem cells isolated from one niche could form terminally differentiated cells from the other. Additionally, these two niches are associated to tissues/systems (e.g., bone and central nervous system) that have markedly different needs and display diverse functions within the human body. Nevertheless they do share common features. For instance, the differentiation of both NSCs and MSCs is intimately associated with the bone morphogenetic protein family. Moreover, both NSCs and MSCs secrete a panel of common growth factors, such as nerve growth factor (NGF), glial derived neurotrophic factor (GDNF), and brain derived neurotrophic factor (BDNF), among others. But it is not the features they share but the interaction between them that seem most important, and worth exploring; namely, it has already been shown that there are mutually beneficially effects when these cell types are co-cultured in vitro. In fact the use of MSCs, and their secretome, become a strong candidate to be used as a therapeutic tool for CNS applications, namely by triggering the endogenous proliferation and differentiation of neural progenitors, among other mechanisms. Quite interestingly it was recently revealed that MSCs could be found in the human brain, in the vicinity of capillaries. In the present review we highlight how MSCs and NSCs in the neurogenic niches interact. Furthermore, we propose directions on this field and explore the future therapeutic possibilities that may arise from the combination/interaction of MSCs and NSCs. PMID:26217178

  11. NSI-189, a Small Molecule with Neurogenic Properties, Exerts Behavioral and Neurostructural Benefits in Stroke Rats.

    PubMed

    Tajiri, Naoki; Quach, David M; Kaneko, Yuji; Wu, Stephanie; Lee, David; Lam, Tina; Hayama, Ken L; Hazel, Thomas G; Johe, Karl; Wu, Michael C; Borlongan, Cesar V

    2017-02-09

    Enhancing neurogenesis may be a powerful stroke therapy. Here, we tested in a rat model of ischemic stroke the beneficial effects of NSI-189, an orally active, new molecular entity (mol. wt. 366) with enhanced neurogenic activity, and indicated as an anti-depressant drug in a clinical trial (Fava et al., 2015) and being tested in a Phase 2 efficacy trial (ClinicalTrials.gov, 2016) for treatment of major depression. Oral administration of NSI-189 in adult Sprague-Dawley rats starting at 6 hours after middle cerebral artery occlusion, and daily thereafter over the next 12 weeks resulted in significant amelioration of stroke-induced motor and neurological deficits, which was maintained up to 24 weeks post-stroke. Histopathological assessment of stroke brains from NSI-189-treated animals revealed significant increments in neurite outgrowth as evidenced by MAP2 immunoreactivity that was prominently detected in the hippocampus and partially in the cortex. These results suggest NSI-189 actively stimulated remodeling of the stroke brain. Parallel in vitro studies further probed this remodeling process and demonstrated that oxygen glucose deprivation and reperfusion (OGD/R) initiated typical cell death processes, which were reversed by NSI-189 treatment characterized by significant attenuation of OGD/R-mediated hippocampal cell death and increased Ki67 and MAP2 expression, coupled with upregulation of neurogenic factors such as BDNF and SCF. These findings support the use of oral NSI-189 as a therapeutic agent well beyond the initial 6-hour time window to accelerate and enhance the overall functional improvement in the initial 6 months post stroke. This article is protected by copyright. All rights reserved.

  12. Central neurogenic diabetes insipidus, syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome in traumatic brain injury.

    PubMed

    John, Cynthia A; Day, Michael W

    2012-04-01

    Central neurogenic diabetes insipidus, syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome are secondary events that affect patients with traumatic brain injury. All 3 syndromes affect both sodium and water balance; however, they have differences in pathophysiology, diagnosis, and treatment. Differentiating between hypernatremia (central neurogenic diabetes insipidus) and the 2 hyponatremia syndromes (syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome) is critical for preventing worsening neurological outcomes in patients with head injuries.

  13. An Investigation into the Nature of Non-Voiding Contractions Resulting from Detrusor Hyperreflexia in Neurogenic Bladders Following Spinal Cord Injury

    DTIC Science & Technology

    2015-06-01

    Neurogenic Bladders Following Spinal Cord Injury PRINCIPAL INVESTIGATOR: Matthew O. Fraser, Ph.D. CONTRACTING ORGANIZATION: Institute for Medical...Contractions Resulting from Detrusor Hyperreflexia in Neurogenic Bladders Following Spinal Cord Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0445...behind non-voiding contractions (NVC) of the bladder seen with filling following suprasacral spinal cord injury (SCI). The most significant findings

  14. Cerebral cortical neurons with activity linked to central neurogenic spontaneous and evoked elevations in cerebral blood flow

    NASA Technical Reports Server (NTRS)

    Golanov, E. V.; Reis, D. J.

    1996-01-01

    We recorded neurons in rat cerebral cortex with activity relating to the neurogenic elevations in regional cerebral blood flow (rCBF) coupled to stereotyped bursts of EEG activity, burst-cerebrovascular wave complexes, appearing spontaneously or evoked by electrical stimulation of rostral ventrolateral medulla (RVL) or fastigial nucleus (FN). Of 333 spontaneously active neurons only 15 (5%), in layers 5-6, consistently (P < 0.05, chi-square) increased their activity during the earliest potential of the complex, approximately 1.3 s before the rise of rCBF, and during the minutes-long elevation of rCBF elicited by 10 s of stimulation of RVL or FN. The results indicate the presence of a small population of neurons in deep cortical laminae whose activity correlates with neurogenic elevations of rCBF. These neurons may function to transduce afferent neuronal signals into vasodilation.

  15. Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.

    PubMed

    Bifari, Francesco; Decimo, Ilaria; Pino, Annachiara; Llorens-Bobadilla, Enric; Zhao, Sheng; Lange, Christian; Panuccio, Gabriella; Boeckx, Bram; Thienpont, Bernard; Vinckier, Stefan; Wyns, Sabine; Bouché, Ann; Lambrechts, Diether; Giugliano, Michele; Dewerchin, Mieke; Martin-Villalba, Ana; Carmeliet, Peter

    2016-11-17

    Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2(+) neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex.

  16. Primary Sacral Hydatid Cyst Mimicking a Neurogenic Tumor in Chronic Low Back Pain: Case Report and Review of the Literature

    PubMed Central

    Segura-Trepichio, Manuel; Montoza-Nuñez, Jose Manuel; Candela-Zaplana, David; Herrero-Santacruz, Josefa; Pla-Mingorance, Fernando

    2016-01-01

    Hydatid disease is caused by infection of Echinococcus granulosus. Bone hydatid cyst presentation without hepatic affectation is infrequent and occurs in 0,5-2% of cases. This rare condition makes clinicians not always aware of the disease, and as a result, misdiagnosis of spinal echinococcosis is common. We present a case of a 48-year-old female patient with primary sacral hydatidosis. Chronic low back pain radiating to the left buttock was the only symptom. The magnetic resonance imaging (MRI) suggested a neurogenic tumor versus giant cell tumor. Biopsy and pathological study revealed a hydatid cyst. Anthelmintic and surgical treatment was performed. At 12 months after surgery, the patient is free of recurrence. In patients with chronic low back pain and a MR suggestive of neurogenic tumor, spinal hydatid cyst should be considered in the differential diagnosis. It is recommended the assistance of an anesthesiologist during biopsy to avoid an anaphylactic shock. PMID:28163523

  17. An integrative review of standardized clinical evaluation tool utilization in anticholinergic drug trials for neurogenic lower urinary tract dysfunction

    PubMed Central

    Stothers, L; Tsang, B; Nigro, M; Lazare, D; Macnab, A

    2016-01-01

    Study design: To review prospective and randomized trials studying anticholinergic therapy for neurogenic bladder in SCI to identify whether trials included standardized clinical evaluation tools and reporting measures now recognized to enhance clinical trial data. Methods: A systematic search via EMBASE, MEDLINE, CENTRAL, CINAHL (Cumulative Index to Nursing and Allied Health Literature), HTA (Health Technology Assessment), CMR (Comprehensive Microbial Resource), HAPI (Health and Psychosocial Instruments) and PsycINFO using the key term spinal cord injury crossed with oxybutynin, tolterodine, darifenacin, solifenacin, fesoterodine, trospium chloride, propiverine, propantheline and anticholinergic(s) for 1946–2015 inclusive. We then collated whether standardized clinical tools, measures and descriptors were used within each study identified: American Spine Injury Association (ASIA) impairment scale; symptom scores validated in SCI; technical methodology for urodynamics/video urodynamics; urinary diaries; and standardized urologic terminology. Results: A total of 1225 entries with 610 unique articles were identified, 14 randomized and 16 prospective studies. In 6/30 the population comprised SCI patients with neurogenic bladder alone; the remainder included mixed neurogenic etiologies. Classification using the ASIA impairment scale was used in <10% of studies; none used symptom scores validated in SCI; <50% reported urodynamic test methodology fully, incorporated urinary diaries or used International Continence Society Standardization Subcommittee urinary tract terminology. Conclusion: Integrative review of trials from 1946 to 2015 identified infrequent use of standardized clinical evaluation tools and reporting measures. Data from future trials evaluating therapies for neurogenic bladder would likely be more applicable to specific SCI patients if current standardized classification and descriptors now available were used consistently: for example, the ASIA scale

  18. Regional comparison of the neurogenic effects of CNTF-derived peptides and cerebrolysin in AβPP transgenic mice.

    PubMed

    Rockenstein, Edward; Ubhi, Kiren; Doppler, Edith; Novak, Philipp; Moessler, Herbert; Li, Bin; Blanchard, Julie; Grundke-Iqbal, Inge; Iqbal, Khalid; Mante, Michael; Adame, Anthony; Crews, Leslie; Masliah, Eliezer

    2011-01-01

    Adult neurogenesis, the production of new neurons in certain brain regions, is known to decrease with age and the loss of neurogenic potential has been implicated in Alzheimer's disease (AD), a leading cause of dementia in the elderly. Cerebrolysin (CBL) has been shown to increase neurogenesis in models of stroke and AD. CBL is composed of small peptides with activity similar to neurotrophic factors including ciliary neurotrophic factor (CNTF), which may mediate its neurogenic effects. This study compares the effects of CBL and two peptides with corresponding to an active region of CNTF (Peptide 6 and 6A) across neurogenic brain regions in amyloid-β protein precursor (AβPP) transgenic (tg) mice. Both CBL and Peptides 6 and 6A were able to increase the numbers of neuroblasts (DCX+ cells) and BrdU+ cells in a regionally specific manner across the subventricular zone, olfactory bulb, and hippocampus. The increased generation of new cells and cell survival in animals treated with Peptides 6 and 6A was accompanied by an increase in PCNA+ cells. In contrast, AβPP tg mice treated with CBL displayed reduced levels of TUNEL staining, while levels of PCNA were unaltered. Collectively these results demonstrate that while CBL and Peptides 6 and 6A all potentiate neurogenesis in the AβPP tg mice, their relative modes of action may differ with CBL associated with reduced apoptosis and Peptides 6 and 6A working by augmenting cell proliferation. These results are consistent with a potential therapeutic relevance for Peptides 6 and 6A in AD and other disorders characterized by neurogenic deficits.

  19. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.

    PubMed

    Trevisani, Marcello; Siemens, Jan; Materazzi, Serena; Bautista, Diana M; Nassini, Romina; Campi, Barbara; Imamachi, Noritaka; Andrè, Eunice; Patacchini, Riccardo; Cottrell, Graeme S; Gatti, Raffaele; Basbaum, Allan I; Bunnett, Nigel W; Julius, David; Geppetti, Pierangelo

    2007-08-14

    TRPA1 is an excitatory ion channel expressed by a subpopulation of primary afferent somatosensory neurons that contain substance P and calcitonin gene-related peptide. Environmental irritants such as mustard oil, allicin, and acrolein activate TRPA1, causing acute pain, neuropeptide release, and neurogenic inflammation. Genetic studies indicate that TRPA1 is also activated downstream of one or more proalgesic agents that stimulate phospholipase C signaling pathways, thereby implicating this channel in peripheral mechanisms controlling pain hypersensitivity. However, it is not known whether tissue injury also produces endogenous proalgesic factors that activate TRPA1 directly to augment inflammatory pain. Here, we report that recombinant or native TRPA1 channels are activated by 4-hydroxy-2-nonenal (HNE), an endogenous alpha,beta-unsaturated aldehyde that is produced when reactive oxygen species peroxidate membrane phospholipids in response to tissue injury, inflammation, and oxidative stress. HNE provokes release of substance P and calcitonin gene-related peptide from central (spinal cord) and peripheral (esophagus) nerve endings, resulting in neurogenic plasma protein extravasation in peripheral tissues. Moreover, injection of HNE into the rodent hind paw elicits pain-related behaviors that are inhibited by TRPA1 antagonists and absent in animals lacking functional TRPA1 channels. These findings demonstrate that HNE activates TRPA1 on nociceptive neurons to promote acute pain, neuropeptide release, and neurogenic inflammation. Our results also provide a mechanism-based rationale for developing novel analgesic or anti-inflammatory agents that target HNE production or TRPA1 activation.

  20. Health promotion in motion: improving quality of life for persons with neurogenic bladder and bowel using assistive technology.

    PubMed

    Kachourbos, M J; Creasey, G H

    2000-01-01

    The neurogenic bladder and bowel lead to many complications in individuals with spinal cord injury (SCI). Management of these neurological complications is a multidimensional challenge for persons with SCI and their caregivers, and can affect the person medically, economically, socially, and personally. This may result in social isolation, poor self-image, and overall decreased quality of life (QOL). When facing this challenge, nurses working with persons with SCI must expand their practice to include more than traditional preventive care. A newly available technique for promoting health with a neurogenic bladder and bowel is the VOCARE Bladder and Bowel Control System. Sixteen persons with SCI who received this system were interviewed by telephone and asked for their recollections of health and QOL pre-operatively in relation to bladder and bowel care and to rate changes in their QOL post-implant. Post-operatively, the recipients reported improved health, a decrease in costs of management of their neurogenic bladder and bowel, increased independence leading to less social isolation, increased sense of control, increased feelings of self-worth, and overall improvement in QOL. These outcomes illustrate the global impact that can be made on the lives of persons with SCI by health services that go beyond prevention of complications and into the realm of health promotion.

  1. bicaudal-C is required for the formation of anterior neurogenic ectoderm in the sea urchin embryo.

    PubMed

    Yaguchi, Shunsuke; Yaguchi, Junko; Inaba, Kazuo

    2014-10-31

    bicaudal-C (bicC) mRNA encodes a protein containing RNA-binding domains that is reported to be maternally present with deflection in the oocytes/eggs of some species. The translated protein plays a critical role in the regulation of cell fate specification along the body axis during early embryogenesis in flies and frogs. However, it is unclear how it functions in eggs in which bicC mRNA is uniformly distributed, for instance, sea urchin eggs. Here, we show the function of BicC in the formation of neurogenic ectoderm of the sea urchin embryo. Loss-of-function experiments reveal that BicC is required for serotonergic neurogenesis and for expression of ankAT-1 gene, which is essential for the formation of apical tuft cilia in the neurogenic ectoderm of the sea urchin embryo. In contrast, the expression of FoxQ2, the neurogenic ectoderm specification transcription factor, is invariant in BicC morphants. Because FoxQ2 is an upstream factor of serotonergic neurogenesis and ankAT-1 expression, these data indicate that BicC functions in regulating the events that are coordinated by FoxQ2 during sea urchin embryogenesis.

  2. Memantine inhibits α3β2-nAChRs-mediated nitrergic neurogenic vasodilation in porcine basilar arteries.

    PubMed

    Lee, Reggie Hui-Chao; Tseng, Ting-Yi; Wu, Celeste Yin-Chieh; Chen, Po-Yi; Chen, Mei-Fang; Kuo, Jon-Son; Lee, Tony Jer-Fu

    2012-01-01

    Memantine, an NMDA receptor antagonist used for treatment of Alzheimer's disease (AD), is known to block the nicotinic acetylcholine receptors (nAChRs) in the central nervous system (CNS). In the present study, we examined by wire myography if memantine inhibited α3β2-nAChRs located on cerebral perivascular sympathetic nerve terminals originating in the superior cervical ganglion (SCG), thus, leading to inhibition of nicotine-induced nitrergic neurogenic dilation of isolated porcine basilar arteries. Memantine concentration-dependently blocked nicotine-induced neurogenic dilation of endothelium-denuded basilar arteries without affecting that induced by transmural nerve stimulation, sodium nitroprusside, or isoproterenol. Furthermore, memantine significantly inhibited nicotine-elicited inward currents in Xenopous oocytes expressing α3β2-, α7- or α4β2-nAChR, and nicotine-induced calcium influx in cultured rat SCG neurons. These results suggest that memantine is a non-specific antagonist for nAChR. By directly inhibiting α3β2-nAChRs located on the sympathetic nerve terminals, memantine blocks nicotine-induced neurogenic vasodilation of the porcine basilar arteries. This effect of memantine is expected to reduce the blood supply to the brain stem and possibly other brain regions, thus, decreasing its clinical efficacy in the treatment of Alzheimer's disease.

  3. Limb girdle muscular dystrophy type 2G with myopathic-neurogenic motor unit potentials and a novel muscle image pattern

    PubMed Central

    2014-01-01

    Background Limb girdle muscular dystrophy type 2G (LGMD2G) is a subtype of autosomal recessive muscular dystrophy caused by mutations in the telethonin gene. There are few LGMD2G patients worldwide reported, and this is the first description associated with early tibialis anterior sparing on muscle image and myopathic-neurogenic motor unit potentials. Case presentation Here we report a 31 years old caucasian male patient with progressive gait disturbance, and severe lower limb proximal weakness since the age of 20 years, associated with subtle facial muscle weakness. Computed tomography demonstrated soleus, medial gastrocnemius, and diffuse thigh muscles involvement with tibialis anterior sparing. Electromyography disclosed both neurogenic and myopathic motor unit potentials. Muscle biopsy demonstrated large groups of atrophic and hypertrophic fibers, frequent fibers with intracytoplasmic rimmed vacuoles full of autophagic membrane and sarcoplasmic debris, and a total deficiency of telethonin. Molecular investigation identified the common homozygous c.157C > T in the TCAP gene. Conclusion This report expands the phenotypic variability of telethoninopathy/ LGMD2G, including: 1) mixed neurogenic and myopathic motor unit potentials, 2) facial weakness, and 3) tibialis anterior sparing. Appropriate diagnosis in these cases is important for genetic counseling and prognosis. PMID:25298746

  4. GABAergic responses of mammalian ependymal cells in the central canal neurogenic niche of the postnatal spinal cord.

    PubMed

    Corns, Laura F; Deuchars, Jim; Deuchars, Susan A

    2013-10-11

    The area surrounding the central canal of the postnatal mammalian spinal cord is a highly plastic region that exhibits many similarities to other postnatal neurogenic niches, such as the subventricular zone. Within this region, ependymal cells have been identified as neural stem cells however very little is known about their properties and how the local environment, including neurotransmitters, is capable of affecting them. The neurotransmitter GABA is present around the central canal and is known to affect cells within other postnatal neurogenic niches. This study used whole cell patch clamp electrophysiology and intracellular dye-loading in in vitro Wistar rat spinal cord slices to characterise ependymal cells and their ability to respond to GABA. Ependymal cells were defined by their passive response properties and low input resistances. Extensive dye-coupling was observed between ependymal cells; this was confirmed as gap junction coupling using the gap junction blocker, 18β-glycyrrhetinic acid, which significantly increased the input resistance of ependymal cells. GABA depolarised all ependymal cells tested; the partial antagonism of this response by bicuculline and gabazine indicates that GABA(A) receptors contribute to this response. A lack of effect by baclofen suggests that GABA(B) receptors do not contribute to the GABAergic response. The ability of ependymal cells to respond to GABA suggests that GABA could be capable of influencing the proliferation and differentiation of cells within the neurogenic niche of the postnatal spinal cord.

  5. Neurogenic thoracic outlet syndrome: A case report and review of the literature

    PubMed Central

    Boezaart, André P; Haller, Allison; Laduzenski, Sarah; Koyyalamudi, Veerandra B.; Ihnatsenka, Barys; Wright, Thomas

    2010-01-01

    Neurogenic thoracic outlet syndrome (NTOS) is an oft-overlooked and obscure cause of shoulder pain, which regularly presents to the office of shoulder surgeons and pain specialist. With this paper we present an otherwise healthy young female patient with typical NTOS. She first received repeated conservative treatments with 60 units of botulinium toxin injected into the anterior scalene muscle at three-month intervals, which providing excellent results of symptom-free periods. Later a trans-axillary first rib resection provided semi-permanent relief. The patient was followed for 10 years after which time the symptoms reappeared. We review the literature and elaborate on the anatomy, sonoanatomy, etiology and characteristics, symptoms, diagnostic criteria and treatment modalities of NTOS. Patients with NTOS often get operated upon – even if just a diagnostic arthroscopy, and an interscalene or other brachial plexus block may be performed. This might put the patient in jeopardy of permanent nerve injury, and the purpose of this review is to minimize or prevent this. PMID:21072145

  6. Nociception, neurogenic inflammation and thermoregulation in TRPV1 knockdown transgenic mice.

    PubMed

    Tóth, Dániel Márton; Szoke, Eva; Bölcskei, Kata; Kvell, Krisztián; Bender, Balázs; Bosze, Zsuzsanna; Szolcsányi, János; Sándor, Zoltán

    2011-08-01

    Transgenic mice with a small hairpin RNA construct interfering with the expression of transient receptor potential vanilloid 1 (TRPV1) were created by lentiviral transgenesis. TRPV1 expression level in transgenic mice was reduced to 8% while the expression of ankyrin repeat domain 1 (TRPA1) was unchanged. Ear oedema induced by topical application of TRPV1 agonist capsaicin was completely absent in TRPV1 knockdown mice. Thermoregulatory behaviour in relation to environmental thermopreference (30 vs. 35°C) was slightly impaired in male knockdown mice, but the reduction of TRPV1 function was not associated with enhanced hyperthermia. TRPV1 agonist resiniferatoxin induced hypothermia and tail vasodilatation was markedly inhibited in knockdown mice. In conclusion, shRNA-mediated knock down of the TRPV1 receptor in mice induced robust inhibition of the responses to TRPV1 agonists without altering the expression, gating function or neurogenic oedema provoked by TRPA1 activation. Thermoregulatory behaviour in response to heat was inhibited, but enhanced hyperthermia was not observed.

  7. A clinically authentic mouse model of enterovirus 71 (EV-A71)-induced neurogenic pulmonary oedema

    PubMed Central

    Victorio, Carla Bianca Luena; Xu, Yishi; Ng, Qimei; Chua, Beng Hooi; Alonso, Sylvie; Chow, Vincent T. K.; Chua, Kaw Bing

    2016-01-01

    Enterovirus 71 (EV-A71) is a neurotropic virus that sporadically causes fatal neurologic illness among infected children. Animal models of EV-A71 infection exist, but they do not recapitulate in animals the spectrum of disease and pathology observed in fatal human cases. Specifically, neurogenic pulmonary oedema (NPE)—the main cause of EV-A71 infection-related mortality—is not observed in any of these models. This limits their utility in understanding viral pathogenesis of neurologic infections. We report the development of a mouse model of EV-A71 infection displaying NPE in severely affected animals. We inoculated one-week-old BALB/c mice with an adapted EV-A71 strain and identified clinical signs consistent with observations in human cases and other animal models. We also observed respiratory distress in some mice. At necropsy, we found their lungs to be heavier and incompletely collapsed compared to other mice. Serum levels of catecholamines and histopathology of lung and brain tissues of these mice strongly indicated onset of NPE. The localization of virally-induced brain lesions also suggested a potential pathogenic mechanism for EV-A71-induced NPE. This novel mouse model of virally-induced NPE represents a valuable resource for studying viral mechanisms of neuro-pathogenesis and pre-clinical testing of potential therapeutics and prophylactics against EV-A71-related neurologic complications. PMID:27357918

  8. Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche

    PubMed Central

    Luarte, Alejandro; Bátiz, Luis Federico; Wyneken, Ursula; Lafourcade, Carlos

    2016-01-01

    Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer's Disease, Parkinson's Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been tested in vivo and in vitro as therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future. PMID:27195011

  9. Premature aging of the hippocampal neurogenic niche in adult Bmal1‐ deficient mice

    PubMed Central

    Ali, Amira A. H.; Schwarz‐Herzke, Beryl; Stahr, Anna; Prozorovski, Timour; Aktas, Orhan; von Gall, Charlotte

    2015-01-01

    Hippocampal neurogenesis undergoes dramatic age‐related changes. Mice with targeted deletion of the clock gene Bmal1 (Bmal1‐/‐) show disrupted regulation of reactive oxygen species homeostasis, accelerated aging, neurodegeneration and cognitive deficits. As proliferation of neuronal progenitor/precursor cells (NPCs) is enhanced in young Bmal1‐/‐ mice, we tested the hypothesis that this results in premature aging of hippocampal neurogenic niche in adult Bmal1‐/‐ mice as compared to wildtype littermates. We found significantly reduced pool of hippocampal NPCs, scattered distribution, enhanced survival of NPCs and an increased differentiation of NPCs into the astroglial lineage at the expense of the neuronal lineage. Immunoreaction of the redox sensitive histone deacetylase Sirtuine 1, peroxisomal membrane protein at 70kDa and expression of the cell cycle inhibitor p21 Waf1/CIP1 were increased in adult Bmal1‐/‐ mice. In conclusion, genetic disruption of the molecular clockwork leads to accelerated age‐dependent decline in adult neurogenesis presumably as a consequence of oxidative stress. PMID:26142744

  10. The enigma of neurogenic thoracic outlet syndrome following motor vehicle collisions

    PubMed Central

    Munro, A. Ian; McPherson, G. Duncan

    2016-01-01

    Background The concept of neurogenic thoracic outlet syndrome (N-TOS) including upper and lower plexus syndromes secondary to soft tissue neck injury after motor vehicle collisions (MVCs) has been contentious. We considered that analysis of objective data from this group of patients could provide insight into this controversial type of N-TOS. Methods During the 10-year period January 2001 through December 2010 we examined patients who had received a diagnosis of N-TOS following an MVC. We graded the principal diagnosis based on the objective data from our physical examination. Results In total 263 patients received a diagnosis of N-TOS during the study period. At the highest accuracy level of diagnosis there were 56 patients with ulnar entrapment syndrome (UES), 40 with carpal tunnel syndrome (CTS) and 55 with nonorganic disease (NOD), for a total of 151 (57.4%) cases in which the diagnosis of N-TOS was brought into question. The elevated arm stress test (EAST) reproduced the symptoms of UES in 33 of the 56 patients of UES (58.9%) and reproduced the symptoms of CTS in 18 of the 40 patients with CTS (45.0%). Conclusion There appears to be a high incidence of misdiagnosis of N-TOS following MVCs. The EAST is not a prime test for N-TOS. PMID:27454840

  11. Comparison of neurogenic effects of fluoxetine, duloxetine and running in mice

    PubMed Central

    Marlatt, Michael W.; Lucassen, Paul J.; van Praag, Henriette

    2010-01-01

    Hippocampal neurogenesis can be regulated by extrinsic factors, such as exercise and antidepressants. While there is evidence that the serotonin re-uptake inhibitor (SSRI) fluoxetine (Prozac) enhances neurogenesis, the new dual serotonin/noradrenaline reuptake inhibitor (SNRI) duloxetine has not been evaluated in this context. In addition, it is unclear whether effects of antidepressants and running on cell genesis and behavior are of similar magnitude in mice. Here,we assessed neurogenesis and open field behavior in 2 month old female C57Bl/6 mice after 28 days of treatment with either fluoxetine (18 mg/kg), duloxetine (2, 6 or 18 mg/kg) or exercise. New cell survival, as measured by 5-bromo-2´-deoxyuridine (BrdU) labeled cells, was enhanced by 200% in the running group only. Both running and fluoxetine, but not duloxetine, increased the percentage of new cells that became neurons. In the open field test, animals treated with either drug spent less time in the center than controls and runners. In addition, fluoxetine treatment resulted in reduced locomotor activity. Together, these data not only show that the neurogenic response to exercise is much stronger than to antidepressants, but also imply a low likelihood that reported effects of these two drugs on anxiety are mediated by adult neurogenesis in C57Bl/6 mice. PMID:20381469

  12. Premature aging of the hippocampal neurogenic niche in adult Bmal1-deficient mice.

    PubMed

    Ali, Amira A H; Schwarz-Herzke, Beryl; Stahr, Anna; Prozorovski, Timour; Aktas, Orhan; von Gall, Charlotte

    2015-06-01

    Hippocampal neurogenesis undergoes dramatic age-related changes. Mice with targeted deletion of the clock geneBmal1 (Bmal1(-/-)) show disrupted regulation of reactive oxygen species homeostasis, accelerated aging, neurodegeneration and cognitive deficits. As proliferation of neuronal progenitor/precursor cells (NPCs) is enhanced in young Bmal1(-/-) mice, we tested the hypothesis that this results in premature aging of hippocampal neurogenic niche in adult Bmal1(-/-) mice as compared to wildtype littermates. We found significantly reduced pool of hippocampal NPCs, scattered distribution, enhanced survival of NPCs and an increased differentiation of NPCs into the astroglial lineage at the expense of the neuronal lineage. Immunoreaction of the redox sensitive histone deacetylase Sirtuine 1, peroxisomal membrane protein at 70 kDa and expression of the cell cycle inhibitor p21(Waf1/CIP1) were increased in adult Bmal1(-/-) mice. In conclusion, genetic disruption of the molecular clockwork leads to accelerated age-dependent decline in adult neurogenesis presumably as a consequence of oxidative stress.

  13. Neurogenic orthostatic hypotension in Parkinson’s disease: evaluation, management, and emerging role of droxidopa

    PubMed Central

    Isaacson, Stuart H; Skettini, Julia

    2014-01-01

    Neurogenic orthostatic hypotension (nOH) is due to failure of the autonomic nervous system to regulate blood pressure in response to postural changes due to an inadequate release of norepinephrine, leading to orthostatic hypotension and supine hypertension. nOH is common in Parkinson’s disease (PD). Prevalence varies throughout the course of PD, ranging from 40% to 60%, and resulting in symptomatic nOH in approximately half. Symptomatic nOH, including lightheadedness, can limit daily activities and lead to falls. Symptomatic nOH can also limit therapeutic options for treating PD motor symptoms. Clinical evaluation should routinely include symptom assessment and blood pressure measurement of supine, sitting, and 3-minute standing; 24-hour ambulatory blood pressure monitoring can also be helpful. Non-pharmacological management of symptomatic nOH involves education, physical maneuvers, and adequate hydration. Current pharmacological treatment of symptomatic nOH includes salt supplement, fludrocortisone, midodrine, pyridostigmine, and other empiric medications. Despite these options, treatment of symptomatic nOH remains suboptimal, often limited by severe increases in supine blood pressure. Droxidopa, an oral prodrug converted by decarboxylation to norepinephrine, is a promising therapeutic option for symptomatic nOH in PD, improving symptoms of nOH, daily activities, falls, and standing systolic blood pressure in several recent trials. These trials demonstrated short-term efficacy and tolerability, with comparable increases in standing and supine blood pressures. Longer-term studies are ongoing to confirm durability of treatment effect. PMID:24729712

  14. Heated indoor swimming pools, infants, and the pathogenesis of adolescent idiopathic scoliosis: a neurogenic hypothesis

    PubMed Central

    2011-01-01

    Background In a case-control study a statistically significant association was recorded between the introduction of infants to heated indoor swimming pools and the development of adolescent idiopathic scoliosis (AIS). In this paper, a neurogenic hypothesis is formulated to explain how toxins produced by chlorine in such pools may act deleteriously on the infant's immature central nervous system, comprising brain and spinal cord, to produce the deformity of AIS. Presentation of the hypothesis Through vulnerability of the developing central nervous system to circulating toxins, and because of delayed epigenetic effects, the trunk deformity of AIS does not become evident until adolescence. In mature healthy swimmers using such pools, the circulating neurotoxins detected are chloroform, bromodichloromethane, dibromochloromethane, and bromoform. Cyanogen chloride and dichloroacetonitrile have also been detected. Testing the hypothesis In infants, the putative portals of entry to the blood could be dermal, oral, or respiratory; and entry of such circulating small molecules to the brain are via the blood-brain barrier, blood-cerebrospinal fluid barrier, and circumventricular organs. Barrier mechanisms of the developing brain differ from those of adult brain and have been linked to brain development. During the first 6 months of life cerebrospinal fluid contains higher concentrations of specific proteins relative to plasma, attributed to mechanisms continued from fetal brain development rather than immaturity. Implications of the hypothesis The hypothesis can be tested. If confirmed, there is potential to prevent some children from developing AIS. PMID:21975145

  15. Genetic Evaluation of E. coli Strains Isolated from Asymptomatic Children with Neurogenic Bladders

    PubMed Central

    Kryger, John; Burleigh, Alexandra; Christensen, Melissa; Hopkins, Walter

    2015-01-01

    This study was conducted to describe the genetic profiles of E. coli that colonize asymptomatic pediatric neurogenic bladders. E. coli was isolated from 25 of 80 urine samples. Patients were excluded if they presented with symptomatic urinary tract infection or received treatment with antibiotics in the preceding three months. Multiplex PCR was performed to determine E. coli phylotype (A, B1, B2, and D) and the presence of seven pathogenicity islands (PAIs) and 10 virulence factors (VFs). E. coli strains were predominantly of the B1 and B2 phylotype, with few strains in the A or D phylotype. The PAIs IV536, ICFT073, and IICFT073 had the highest prevalence: 76%, 64%, and 48%, respectively. The PAIs II536, IJ96, and IIJ96 were less prevalent: 28%, 20%, and 24%, respectively. The most prevalent VF was vat (40%), while the least prevalent VFs were sfa (8%) and iha (12%). None of the strains carried the VF fyuA, which is very common in uropathogenic E. coli (UPEC). The genetic profiles of E. coli in this cohort seem to be more similar to UPEC than to commensal E. coli. However, they appear to have reduced virulence potential that allows them to colonize asymptomatically. PMID:26609542

  16. Videothoracoscopy in the treatment of benign neurogenic tumours of the posterior mediastinum

    PubMed Central

    Brzeziński, Daniel; Kozak, Józef

    2014-01-01

    Introduction The indications for videothoracoscopy are very broad and include the treatment of mediastinal tumours. Aim To present our experience of using the minimally invasive technique in treating benign neurogenic tumours. Material and methods Twenty-two patients were treated due to tumours of the posterior mediastinum from 2003 to 2012. The size of the tumours ranged from 2 cm to 25 cm. Tumours up to the size of 6 cm were treated using videothoracoscopy (VT), bigger ones through thoracotomy. Results The videothoracoscopy technique was used in 17 patients, thoracotomy in 5. In 2 cases conversion was required due to adhesions in the pleural cavity preventing VT treatment. Complications related to the procedure were not observed. The average time of hospital stay after VT treatment was 4 days, while after thoracotomy it was 6 days. Histologically, tumours of benign nature were found in all cases. Schwannoma was diagnosed in 15 patients, ganglioneuroma in 3 patients, neurofibroma in 3 patients, and chemodectoma in 1 patient. None of the 3 cases of neurofibroma was associated with Recklinghausen's disease. At a mean follow-up of 60 months no recurrence of the tumour was found. Conclusions In the case of tumours up to 6 cm the best surgical technique is videothoracoscopy. In the case of large tumours the best access is the open technique. The minimally invasive technique allows one to shorten the patient's treatment time, reduce postoperative pain and obtain a good cosmetic effect of the treatment. PMID:25337152

  17. High-dose insulin therapy for neurogenic-stunned myocardium after stroke

    PubMed Central

    Devos, Justine; Peeters, André; Wittebole, Xavier; Hantson, Philippe

    2012-01-01

    A 44-year-old woman with a history of complicated type 2 diabetes mellitus presented with a diagnosis of right-hemispheric ischaemic stroke. She developed acute respiratory distress with radiological evidence of pulmonary oedema. The ECG showed poorly significant ST-segment changes, with a minimal increase of cardiac biomarkers. Echocardiography showed a severely depressed left ventricular function, with also low values of cardiac output at invasive monitoring. The possibility of neurogenic-stunned myocardium was discussed and a metabolic resuscitation with high-dose insulin was proposed. An intravenous bolus of 80 units of insulin (0.72 IU/kg) was followed by a continuous infusion at the rate of 160 IU/h (1.45 IU/kg/h). The treatment led to a rapid and sustained improvement of the haemodynamic condition and was well tolerated. In comparison with dobutamine, insulin had significant inotropic effects without tachycardia. The patient unfortunately died on day 35, from respiratory complications after poor neurological recovery. PMID:23175002

  18. Neurogenic differentiation factor NeuroD confers protection against radiation-induced intestinal injury in mice

    PubMed Central

    Li, Ming; Du, Aonan; Xu, Jing; Ma, Yanchao; Cao, Han; Yang, Chao; Yang, Xiao-Dong; Xing, Chun-Gen; Chen, Ming; Zhu, Wei; Zhang, Shuyu; Cao, Jianping

    2016-01-01

    The gastrointestinal tract, especially the small intestine, is particularly sensitive to radiation, and is prone to radiation-induced injury as a result. Neurogenic differentiation factor (NeuroD) is an evolutionarily-conserved basic helix-loop-helix (bHLH) transcription factor. NeuroD contains a protein transduction domain (PTD), which allows it to be exogenously delivered across the membrane of mammalian cells, whereupon its transcription activity can be unleashed. Whether NeuroD has therapeutic effects for radiation-induced injury remains unclear. In the present study, we prepared a NeuroD-EGFP recombinant protein, and explored its protective effects on the survival and intestinal damage induced by ionizing radiation. Our results showed that NeuroD-EGFP could be transduced into small intestine epithelial cells and tissues. NeuroD-EGFP administration significantly increased overall survival of mice exposed to lethal total body irradiation (TBI). This recombinant NeuroD also reduced radiation-induced intestinal mucosal injury and apoptosis, and improved crypt survival. Expression profiling of NeuroD-EGFP-treated mice revealed upregulation of tissue inhibitor of metalloproteinase 1 (TIMP-1), a known inhibitor of apoptosis in mammalian cells. In conclusion, NeuroD confers protection against radiation-induced intestinal injury, and provides a novel therapeutic clinical option for the prevention of intestinal side effects of radiotherapy and the treatment of victims of incidental exposure. PMID:27436572

  19. Midbrain dopamine neurons associated with reward processing innervate the neurogenic subventricular zone.

    PubMed

    Lennington, Jessica B; Pope, Sara; Goodheart, Anna E; Drozdowicz, Linda; Daniels, Stephen B; Salamone, John D; Conover, Joanne C

    2011-09-14

    Coordinated regulation of the adult neurogenic subventricular zone (SVZ) is accomplished by a myriad of intrinsic and extrinsic factors. The neurotransmitter dopamine is one regulatory molecule implicated in SVZ function. Nigrostriatal and ventral tegmental area (VTA) midbrain dopamine neurons innervate regions adjacent to the SVZ, and dopamine synapses are found on SVZ cells. Cell division within the SVZ is decreased in humans with Parkinson's disease and in animal models of Parkinson's disease following exposure to toxins that selectively remove nigrostriatal neurons, suggesting that dopamine is critical for SVZ function and nigrostriatal neurons are the main suppliers of SVZ dopamine. However, when we examined the aphakia mouse, which is deficient in nigrostriatal neurons, we found no detrimental effect to SVZ proliferation or organization. Instead, dopamine innervation of the SVZ tracked to neurons at the ventrolateral boundary of the VTA. This same dopaminergic neuron population also innervated the SVZ of control mice. Characterization of these neurons revealed expression of proteins indicative of VTA neurons. Furthermore, exposure to the neurotoxin MPTP depleted neurons in the ventrolateral VTA and resulted in decreased SVZ proliferation. Together, these results reveal that dopamine signaling in the SVZ originates from a population of midbrain neurons more typically associated with motivational and reward processing.

  20. Inosine attenuates spontaneous activity in the rat neurogenic bladder through an A2B pathway

    PubMed Central

    Doyle, Claire; Cristofaro, Vivian; Sack, Bryan S.; Lukianov, Stefan N.; Schäfer, Mattias; Chung, Yeun Goo; Sullivan, Maryrose P.; Adam, Rosalyn M.

    2017-01-01

    Neurogenic detrusor overactivity (NDO) is among the most challenging complications of spinal cord injury (SCI). A recent report by us demonstrated an improvement in NDO in SCI rats following chronic systemic treatment with the purine nucleoside inosine. The objective of this study was to investigate the mechanism of action of inosine underlying improvement of NDO. Male Sprague-Dawley rats underwent complete spinal cord transection at T8. Inosine (1 mM) delivered intravesically to SCI rats during conscious cystometry significantly decreased the frequency of spontaneous non-voiding contractions. In isolated tissue assays, inosine (1 mM) significantly decreased the amplitude of spontaneous activity (SA) in SCI bladder muscle strips. This effect was prevented by a pan-adenosine receptor antagonist CGS15943, but not by A1 or A3 receptor antagonists. The A2A antagonist ZM241385 and A2B antagonist PSB603 prevented the effect of inosine. The effect of inosine was mimicked by the adenosine receptor agonist NECA and the A2B receptor agonist BAY60-6583. The inhibition of SA by inosine was not observed in the presence of the BK antagonist, iberiotoxin, but persisted in the presence of KATP and SK antagonists. These findings demonstrate that inosine acts via an A2B receptor-mediated pathway that impinges on specific potassium channel effectors. PMID:28294142

  1. Botulinum toxin in spinal cord injury patients with neurogenic detrusor overactivity

    PubMed Central

    Cho, Young Sam; Kim, Khae Hawn

    2016-01-01

    Evidence for the efficacy and safety of intravesical onabotulinum toxin A (onabotA) injections has led to them being licensed in many countries, including Korea, for the treatment of patients with urinary incontinence due to neurogenic detrusor overactivity (NDO) resulting from spinal cord injury or multiple sclerosis who are refractory or intolerant to anticholinergic medications. OnabotA injections have an inhibitory effect on acetylcholine release for up to 10 months, with a recommended dose of 200 U. OnabotA treatment has a beneficial effect not only on urinary symptoms, but also on quality of life. Several clinical studies have shown onabotA to have better effects than placebo in achieving continence, reducing incontinence episodes, improving urodynamic parameters, and improving health-related quality of life. Urinary tract infections and postvoid residual volume are the most prevalent side effects. In patients with residual volume, clean intermittent catheterization may be necessary. In patients with spinal cord injury or multiple sclerosis, it is recommended to evaluate physical and cognitive function before intravesical onabotA injection to ensure that the patient and caregiver are able to perform catheterization if necessary. Further controlled trials should assess the optimal dose, injection technique, long-term safety of repeated injections, and optimal timing of onabotA treatment in the treatment of NDO. PMID:28119887

  2. Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism.

    PubMed

    Tyler, Christina R; Solomon, Benjamin R; Ulibarri, Adam L; Allan, Andrea M

    2014-09-01

    Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism.

  3. Serial specification of diverse neuroblast identities from a neurogenic placode by Notch and Egfr signaling

    PubMed Central

    Hwang, Helen J.; Rulifson, Eric

    2011-01-01

    We used the brain insulin-producing cell (IPC) lineage and its identified neuroblast (IPC NB) as a model to understand a novel example of serial specification of NB identities in the Drosophila dorsomedial protocerebral neuroectoderm. The IPC NB was specified from a small, molecularly identified group of cells comprising an invaginated epithelial placode. By progressive delamination of cells, the placode generated a series of NB identities, including the single IPC NB, a number of other canonical Type I NBs, and a single Type II NB that generates large lineages by transient amplification of neural progenitor cells. Loss of Notch function caused all cells of the placode to form as supernumerary IPC NBs, indicating that the placode is initially a fate equivalence group for the IPC NB fate. Loss of Egfr function caused all placodal cells to apoptose, except for the IPC NB, indicating a requirement of Egfr signaling for specification of alternative NB identities. Indeed, both derepressed Egfr activity in yan mutants and ectopic EGF activity produced supernumerary Type II NBs from the placode. Loss of both Notch and Egfr function caused all placode cells to become IPC NBs and survive, indicating that commitment to NB fate nullified the requirement of Egfr activity for placode cell survival. We discuss the surprising parallels between the serial specification of neural fates from this neurogenic placode and the fly retina. PMID:21653613

  4. MDM2 Inhibition rescues neurogenic and cognitive deficits in fragile X mice

    PubMed Central

    Li, Yue; Stockton, Michael E.; Bhuiyan, Ismat; Eisinger, Brian E.; Gao, Yu; Miller, Jessica L.; Bhattacharyya, Anita; Zhao, Xinyu

    2016-01-01

    Fragile X syndrome, the most common form of inherited intellectual disability, is caused most often by a lack of fragile X mental retardation protein (FMRP). However, the mechanism remains unclear and effective treatment is lacking. Here we show that a loss of FMRP leads to activation of adult neural stem cells (NSCs) and a subsequent reduction in neuronal production. We identified ubiquitin ligase MDM2 as a target of FMRP. FMRP regulates Mdm2 mRNA stability, and loss of FMRP results in elevated mRNA and MDM2 protein levels. We further found that increased MDM2 levels lead to reduced P53 in NSCs, which alters NSC proliferation and differentiation. Treatment with Nutlin-3, a small molecule undergoing clinical trials for cancer, specifically inhibits MDM2 and P53 interaction, and rescues the neurogenic and cognitive deficits in FMRP-deficient mice. Our data unveil a regulatory role for FMRP and a potential new treatment for fragile X syndrome. PMID:27122614

  5. Pathological mechanism of lumbar disc herniation resulting in neurogenic muscle hypertrophy.

    PubMed

    Walcott, Brian P; Nahed, Brian V; Redjal, Navid; Stein, Thor D; Kahle, Kristopher T; Coumans, Jean-Valery

    2011-12-01

    We present a 33-year-old man with 5-year history of low back pain who presented with an enlarging right calf. The patient underwent an extensive workup including biopsy without diagnosis. The patient's examination was significant for diminished pinprick sensation in the right L5/S1 dermatome. Reflexes were absent in the right ankle. The circumference of the right calf (58 cm) was twice that of the left. MRI revealed a herniated lumbar disc at the L5/S1 level. He then underwent a L5/S1 microdiscectomy. Following this surgery, the patient noted complete resolution of all sensory deficits in his lower extremity. His calf circumference had decreased by 5 cm at 4 months and by a total of 8 cm at his 2-year post-operative visit. Histological examination of the affected muscle demonstrated severe grouped atrophy of both type I and type II fibers. There was also evidence of compensatory fiber hypertrophy as well as fiber splitting. We concluded that the patient suffered from a herniated lumbar disc causing radiculopathy with calf hypertrophy (neurogenic hypertrophy). To our knowledge this is the first report of both grouped atrophy and compensatory hypertrophy of both muscle fiber types seen in this phenomenon.

  6. Bulbocavernosus Reflex Test for Diagnosis of Pudendal Nerve Injury in Female Patients with Diabetic Neurogenic Bladder

    PubMed Central

    Niu, Xiaoting; Wang, Xun; Huang, Huanjie; Ni, Peiqi; Lin, Yuanshao; Shao, Bei

    2016-01-01

    The study was designed to investigate the clinical application and significance of the bulbocavernosus reflex (BCR) test for diagnosing diabetic neurogenic bladder (DNB) in female subjects. In this study, 68 female patients with DNB and 40 female normal controls were subjected to a nerve conduction study (NCS) of all four limbs and the BCR test. The data were analyzed and compared, and the corresponding diagnostic sensitivities were discussed. Mean BCR latency for female DNB patients was significantly prolonged, compared to that of the control group, suggesting pudendal nerve injuries in female DNB patients. Moreover, DNB patients were categorized according to the diabetes course. Compared to that of Group A (diabetes course < 5 y), the mean BCR latency was significantly prolonged in Group B (diabetes course between 5 and 10 y) and then further prolonged in Group C (diabetes course > 10 y), which were all longer than the control group. Furthermore, compared with that of the controls, the mean BCR latency was prolonged in DNB patients with or without NCS abnormalities in limbs. Nevertheless, no significant difference was observed in BCR latency between DNB patients with and without NCS abnormalities. Significantly increasing trends were also observed in the NCS and BCR abnormality rates along with increased diabetes course. Most importantly, compared with the NCS of limbs, the BCR test was more sensitive in diagnosing DNB in the female subjects. Overall, our findings suggest that the BCR test would help to assess the pudendal nerve injury in female DNB patients, which might be a potential diagnostic tool in the clinic. PMID:28053822

  7. Sensory and other neurogenic effects of exposures to airborne office dust

    NASA Astrophysics Data System (ADS)

    Mølhave, L.; Kjærgaard, S. K.; Attermann, J.

    This Danish Office Dust Experiment investigated the response of 24 healthy non-sensitive adult subjects to exposure to normal office dust in the air (7 μg m -3 clean air, 136 and 390 μg m -3 TSP). The dust had no major identifiable specific reactive components. The exposure duration was 5 1/4 h and was arranged in a climate chamber in controlled atmospheric conditions. Measurements were made acutely at exposure onset, subacutely at exposure end and next day (late). As secondary aims the time course and threshold of any observed effect of the exposures, and the characteristics of any hyperresponding subgroup were investigated. In a questionnaire with 36 questions the dust exposures caused increased acute, subacute and late perceptions of reduced air quality, acute and subacute increased odor intensity, acute eye irritation, acute and late heavy head, subacute feeling of perspiration, and subacute general irritation. Cough increased subacutely during exposures. In addition, a performance test showed effects of dust exposures which also affected "Mood Scale" ratings. No effect was seen on an addition test for distraction, and objective measurements of skin humidity. The overall conclusion of the study is that healthy subjects without hypersensitivity reactions seem to respond to airborne house dust. The responses are both subjective sensory reactions and other neurogenic effects even at exposure levels within the range found in normal buildings. Some of the effects appeared acutely and decreased through adaptation while others increased during prolonged exposure and remained for more than 17 h after the exposure ended. The findings may indicate for this type of dust a threshold level for the dose-response relationships below 140 μg m -3.

  8. Staphylococcus saprophyticus native valve endocarditis in a diabetic patient with neurogenic bladder: A case report.

    PubMed

    Magarifuchi, Hiroki; Kusaba, Koji; Yamakuchi, Hiroki; Hamada, Yohei; Urakami, Toshiharu; Aoki, Yosuke

    2015-09-01

    A 61-year-old man was admitted to our hospital with 2-day history of malaise and dyspnea. He had mitral prolapse and type II diabetes mellitus with neurogenic bladder, which was cared for by catheterization on his own. On arrival the patient was in septic condition with hypoxemia, and physical examination revealed systolic murmur at the apex. Transthoracic echocardiography revealed vegetation of the mitral and the aortic valve. The presence of continuous bacteremia was confirmed by multiple sets of blood culture, whereby gram-positive cocci was retrieved and identified as Staphylococcus saprophyticus (S. saprophyticus) both phenotypically and genetically. Because two major criteria of the Modified Duke Criteria were met, the patient was diagnosed with native valve endocarditis due to S. saprophyticus. The urine culture was also positive for gram-positive cocci, phenotypically identified as Staphylococcus warneri, which was subsequently identified as S. saprophyticus with the use of 16S rRNA gene sequence analysis and MALDI-TOF MS (matrix-assisted laser desorption ionization time of flight mass spectrometry), indicating strongly that the intermittent catheterization-associated urinary tract infection resulted in bacteremia that eventually lead to infective endocarditis. This patient was treated with vancomycin and clindamycin. Because of multiple cerebral infarctions, the patient underwent mitral and aortic valve replacement on hospital day 5. Blood culture turned negative at 6th hospital day. Antibiotic therapy was continued for six weeks after surgery. The patient's clinical course was uneventful thereafter, and was discharged home. This is the first case report of native valve endocarditis caused by S. saprophyticus of confirmed urinary origin.

  9. Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency.

    PubMed

    Tailor, Jignesh; Kittappa, Raja; Leto, Ketty; Gates, Monte; Borel, Melodie; Paulsen, Ole; Spitzer, Sonia; Karadottir, Ragnhildur Thora; Rossi, Ferdinando; Falk, Anna; Smith, Austin

    2013-07-24

    Stem cell lines that faithfully maintain the regional identity and developmental potency of progenitors in the human brain would create new opportunities in developmental neurobiology and provide a resource for generating specialized human neurons. However, to date, neural progenitor cultures derived from the human brain have either been short-lived or exhibit restricted, predominantly glial, differentiation capacity. Pluripotent stem cells are an alternative source, but to ascertain definitively the identity and fidelity of cell types generated solely in vitro is problematic. Here, we show that hindbrain neuroepithelial stem (hbNES) cells can be derived and massively expanded from early human embryos (week 5-7, Carnegie stage 15-17). These cell lines are propagated in adherent culture in the presence of EGF and FGF2 and retain progenitor characteristics, including SOX1 expression, formation of rosette-like structures, and high neurogenic capacity. They generate GABAergic, glutamatergic and, at lower frequency, serotonergic neurons. Importantly, hbNES cells stably maintain hindbrain specification and generate upper rhombic lip derivatives on exposure to bone morphogenetic protein (BMP). When grafted into neonatal rat brain, they show potential for integration into cerebellar development and produce cerebellar granule-like cells, albeit at low frequency. hbNES cells offer a new system to study human cerebellar specification and development and to model diseases of the hindbrain. They also provide a benchmark for the production of similar long-term neuroepithelial-like stem cells (lt-NES) from pluripotent cell lines. To our knowledge, hbNES cells are the first demonstration of highly expandable neuroepithelial stem cells derived from the human embryo without genetic immortalization.

  10. Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth

    NASA Astrophysics Data System (ADS)

    Yao, Shenglian; Liu, Xi; Yu, Shukui; Wang, Xiumei; Zhang, Shuming; Wu, Qiong; Sun, Xiaodan; Mao, Haiquan

    2016-05-01

    The development of novel biomaterials that deliver precise regulatory signals to direct stem cell fate for nerve regeneration is the focus of current intensive research efforts. In this study, a hierarchically aligned fibrillar fibrin hydrogel (AFG) that was fabricated through electrospinning and the concurrent molecular self-assembly process mimics both the soft and oriented features of nerve tissue, thus providing hybrid biophysical cues to instruct cell behavior in vitro and in vivo. The electrospun hydrogels were examined by scanning electron microscopy (SEM), polarized light microscopy, small angle X-ray scattering assay and atomic force microscopy (AFM), showing a hierarchically linear-ordered structure from the nanoscale to the macroscale with a soft elastic character (elasticity ~1 kPa). We found that this low elasticity and aligned topography of AFG exhibit co-effects on promoting the neurogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) in comparison to random fibrin hydrogel (RFG) and tissue culture plate (TCP) control after two week cell culture in growth medium lacking supplementation with soluble neurogenic induction factors. In addition, AFG also induces dorsal root ganglion (DRG) neurons to rapidly project numerous long neurite outgrowths longitudinally along the AFG fibers for a total neurite extension distance of 1.96 mm in three days in the absence of neurotrophic factor supplementation. Moreover, the AFG implanted in a rat T9 dorsal hemisection spinal cord injury model was found to promote endogenous neural cell fast migration and axonal invasion along AFG fibers, resulting in aligned tissue cables in vivo. Our results suggest that matrix stiffness and aligned topography may instruct stem cell neurogenic differentiation and rapid neurite outgrowth, providing great promise for biomaterial design for applications in nerve regeneration.The development of novel biomaterials that deliver precise regulatory signals to

  11. Programmed hyperphagia in offspring of obese dams: Altered expression of hypothalamic nutrient sensors, neurogenic factors and epigenetic modulators.

    PubMed

    Desai, Mina; Han, Guang; Ross, Michael G

    2016-04-01

    Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation. HF offspring were exposed to maternal overnutrition (high fat diet; HF) during pregnancy and lactation. We determined the protein expression of energy sensors (mTOR, pAMPK), epigenetic factors (DNA methylase, DNMT1; histone deacetylase, SIRT1/HDAC1), neurogenic factors (Hes1, Mash1, Ngn3) and appetite/satiety neuropeptides (AgRP/POMC) in newborn hypothalamus and adult arcuate nucleus (ARC). Despite maternal obesity, male offspring born to obese dams had similar body weight at birth as Controls. However, when nursed by the same dams, male offspring of obese dams exhibited marked adiposity. At 1 day of age, HF newborn males had significantly decreased energy sensors, DNMT1 including Hes1 and Mash1, which may impact neuroprogenitor cell proliferation and differentiation. This is consistent with increased AgRP in HF newborns. At 6 months of age, HF adult males had significantly increased energy sensors and decreased histone deactylases. In addition, the persistent decreased Hes1, Mash1 as well as Ngn3 are consistent with increased AgRP and decreased POMC. Thus, altered energy sensors and epigenetic responses which modulate gene expression and adult neuronal differentiation may contribute to hyperphagia and obesity in HF male offspring.

  12. Brain-targeted angiotensin-converting enzyme 2 overexpression attenuates neurogenic hypertension by inhibiting cyclooxygenase-mediated inflammation.

    PubMed

    Sriramula, Srinivas; Xia, Huijing; Xu, Ping; Lazartigues, Eric

    2015-03-01

    Overactivity of the renin-angiotensin system, oxidative stress, and cyclooxygenases (COX) in the brain are implicated in the pathogenesis of hypertension. We previously reported that angiotensin-converting enzyme 2 (ACE2) overexpression in the brain attenuates the development of deoxycorticosterone acetate-salt hypertension, a neurogenic hypertension model with enhanced brain renin-angiotensin system and sympathetic activity. To elucidate the mechanisms involved, we investigated whether oxidative stress, mitogen-activated protein kinase signaling and cyclooxygenase (COX) activation in the brain are modulated by ACE2 in neurogenic hypertension. Deoxycorticosterone acetate-salt hypertension significantly increased expression of Nox-2 (+61±5%), Nox-4 (+50±13%), and nitrotyrosine (+89±32%) and reduced activity of the antioxidant enzymes, catalase (-29±4%) and superoxide dismutase (-31±7%), indicating increased oxidative stress in the brain of nontransgenic mice. This increased oxidative stress was attenuated in transgenic mice overexpressing ACE2 in the brain. Deoxycorticosterone acetate-salt-induced reduction of neuronal nitric oxide synthase expression (-26±7%) and phosphorylated endothelial nitric oxide synthase/total endothelial nitric oxide synthase (-30±3%), and enhanced phosphorylation of protein kinase B and extracellular signal-regulated kinase 1/2 in the paraventricular nucleus, were reversed by ACE2 overexpression. In addition, ACE2 overexpression blunted the hypertension-mediated increase in gene and protein expression of COX-1 and COX-2 in the paraventricular nucleus. Furthermore, gene silencing of either COX-1 or COX-2 in the brain, reduced microglial activation and accompanied neuroinflammation, ultimately attenuating Deoxycorticosterone acetate-salt hypertension. Together, these data provide evidence that brain ACE2 overexpression reduces oxidative stress and COX-mediated neuroinflammation, improves antioxidant and nitric oxide signaling, and

  13. The potential of dental stem cells differentiating into neurogenic cell lineage after cultivation in different modes in vitro.

    PubMed

    Yang, Chao; Sun, Liang; Li, Xinghan; Xie, Li; Yu, Mei; Feng, Lian; Jiang, Zongting; Guo, Weihua; Tian, Weidong

    2014-10-01

    Trauma or degenerative diseases of the central nervous system (CNS) cause the loss of neurons or glial cells. Stem cell transplantation has become a vital strategy for CNS regeneration. It is necessary to effectively induce nonneurogenic stem cells to differentiate into neurogenic cell lineages because of the limited source of neurogenic stem cells, relatively difficult cultivation, and ethical issues. Previous studies have found that dental stem cells can be used for transplantation therapy. The aim of this study was to explore a better inductive mode and time point for dental stem cells to differentiate into neural-like cells and evaluate a better candidate cell. In this study, dental follicle stem cells (DFSCs), dental papilla stem cells (DPSCs), and stem cells from apical papilla (SCAPs) were cultivated in five different modes. The proliferation ability, morphology, and expression of neural marker genes were analyzed. Results showed that DFSCs showed a higher proliferation potential. The proliferation was decreased after cultivation in chemical inductive medium as cultivation modes 3 and 5. The cells could present neural-like cell morphology after cultivation with human epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF) as cultivation modes 4 and 5. The vast majority of DFSCs gene expression levels in mode 4 on the third day was upregulated significantly. In conclusion, our data suggested that different dental stem cells exhibited different neural differentiation potentials. DFSCs might be the better candidate cell type. Furthermore, cultivation mode 4 and timing of the third day may promote differentiation into neurogenic cell lineages more effectively before transplantation to treat neurological diseases.

  14. Recombinant human TAT-OP1 to enhance NGF neurogenic potential: preliminary studies on PC12 cells.

    PubMed

    Di Liddo, R; Grandi, C; Venturini, M; Dalzoppo, D; Negro, A; Conconi, M T; Parnigotto, P P

    2010-11-01

    Osteogenic protein 1 (OP1), also known as bone morphogenic protein-7 (BMP7), is a multifunctional cytokine with demonstrated neurogenic potential. As the recombinant OP1 (rhOP1) was shown to provide axonal guidance cues and to prevent the reduction of dendritic growth in the injury-induced cortical cultures, it was suggested that an in vivo efficient rhOP1 delivery could enhance neurite growth and functional reconnectivity in the damaged brain. In the present work, we engineered a chimeric molecule in which rhBMP7 was fused to a protein transduction domain derived from HIV-1 TAT protein to deliver the denatured recombinant BMP7 into cells and obtain its chaperone-mediated folding, circumventing the expensive and not much efficient in vitro refolding procedures. When tested on rat PC12 cells, a widely used in vitro neurogenic differentiation model, the resulting fusion protein (rhTAT-OP1) demonstrated to enter fastly into the cells, lose HIV-TAT sequence and interact with membrane receptors activating BMP pathway by SMAD 1/5/8 phosphorylation. In comparison with nerve growth factor (NGF) and BMP7, it proved itself effective to induce the formation of more organized H and M neurofilaments. Moreover, if used in combination with NGF, it stimulated a significant (P < 0.05) and more precocious dendritic outgrowth with respect to NGF alone. These results indicate that rhTAT-OP1 fused with TAT transduction domain shows neurogenic activity and may be a promising enhancer factor in NGF-based therapies.

  15. Exposure to N-Ethyl-N-Nitrosourea in Adult Mice Alters Structural and Functional Integrity of Neurogenic Sites

    PubMed Central

    Capilla-Gonzalez, Vivian; Gil-Perotin, Sara; Ferragud, Antonio; Bonet-Ponce, Luis; Canales, Juan Jose; Garcia-Verdugo, Jose Manuel

    2012-01-01

    Background Previous studies have shown that prenatal exposure to the mutagen N-ethyl-N-nitrosourea (ENU), a N-nitroso compound (NOC) found in the environment, disrupts developmental neurogenesis and alters memory formation. Previously, we showed that postnatal ENU treatment induced lasting deficits in proliferation of neural progenitors in the subventricular zone (SVZ), the main neurogenic region in the adult mouse brain. The present study is aimed to examine, in mice exposed to ENU, both the structural features of adult neurogenic sites, incorporating the dentate gyrus (DG), and the behavioral performance in tasks sensitive to manipulations of adult neurogenesis. Methodology/Principal Findings 2-month old mice received 5 doses of ENU and were sacrificed 45 days after treatment. Then, an ultrastructural analysis of the SVZ and DG was performed to determine cellular composition in these regions, confirming a significant alteration. After bromodeoxyuridine injections, an S-phase exogenous marker, the immunohistochemical analysis revealed a deficit in proliferation and a decreased recruitment of newly generated cells in neurogenic areas of ENU-treated animals. Behavioral effects were also detected after ENU-exposure, observing impairment in odor discrimination task (habituation-dishabituation test) and a deficit in spatial memory (Barnes maze performance), two functions primarily related to the SVZ and the DG regions, respectively. Conclusions/Significance The results demonstrate that postnatal exposure to ENU produces severe disruption of adult neurogenesis in the SVZ and DG, as well as strong behavioral impairments. These findings highlight the potential risk of environmental NOC-exposure for the development of neural and behavioral deficits. PMID:22238669

  16. Hydrogen sulfide and neurogenic inflammation in polymicrobial sepsis: involvement of substance P and ERK-NF-κB signaling.

    PubMed

    Ang, Seah-Fang; Moochhala, Shabbir M; MacAry, Paul A; Bhatia, Madhav

    2011-01-01

    Hydrogen sulfide (H(2)S) has been shown to induce transient receptor potential vanilloid 1 (TRPV1)-mediated neurogenic inflammation in polymicrobial sepsis. However, endogenous neural factors that modulate this event and the molecular mechanism by which this occurs remain unclear. Therefore, this study tested the hypothesis that whether substance P (SP) is one important neural element that implicates in H(2)S-induced neurogenic inflammation in sepsis in a TRPV1-dependent manner, and if so, whether H(2)S regulates this response through activation of the extracellular signal-regulated kinase-nuclear factor-κB (ERK-NF-κB) pathway. Male Swiss mice were subjected to cecal ligation and puncture (CLP)-induced sepsis and treated with TRPV1 antagonist capsazepine 30 minutes before CLP. DL-propargylglycine (PAG), an inhibitor of H(2)S formation, was administrated 1 hour before or 1 hour after sepsis, whereas sodium hydrosulfide (NaHS), an H(2)S donor, was given at the same time as CLP. Capsazepine significantly attenuated H(2)S-induced SP production, inflammatory cytokines, chemokines, and adhesion molecules levels, and protected against lung and liver dysfunction in sepsis. In the absence of H(2)S, capsazepine caused no significant changes to the PAG-mediated attenuation of lung and plasma SP levels, sepsis-associated systemic inflammatory response and multiple organ dysfunction. In addition, capsazepine greatly inhibited phosphorylation of ERK(1/2) and inhibitory κBα, concurrent with suppression of NF-κB activation even in the presence of NaHS. Furthermore, capsazepine had no effect on PAG-mediated abrogation of these levels in sepsis. Taken together, the present findings show that H(2)S regulates TRPV1-mediated neurogenic inflammation in polymicrobial sepsis through enhancement of SP production and activation of the ERK-NF-κB pathway.

  17. Reversible T-wave inversions and neurogenic myocardial stunning in a patient with recurrent stress-induced cardiomyopathy.

    PubMed

    Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Suyama, Jumpei; Toshida, Tsutomu; Kayano, Hiroyuki; Shinozuka, Akira; Gokan, Takehiko; Kobayashi, Youichi

    2014-05-01

    A 72-year-old female was diagnosed as a stress-induced cardiomyopathy from apical ballooning pattern of left ventricular dysfunction without coronary artery stenosis after the mental stress. ECG showed the transient T-wave inversions after the ST-segment elevations. By the mental stress after 1 year, she showed a transient dysfunction with similar ECG changes again. T-wave inversions recovered earlier, and cardiac sympathetic dysfunction showed a lighter response corresponding to the less severe dysfunction than those after the first onset. Wellens' ECG pattern was associated with the degree of neurogenic myocardial stunning with sympathetic hyperinnervation caused by mental stress.

  18. Neurogenic Hyperadrenergic Orthostatic Hypotension – A Newly-recognized Variant of Orthostatic Hypotension in Older Adults with Elevated Norepinephrine

    PubMed Central

    Mar, Philip L; Shibao, Cyndya A.; Garland, Emily M; Black, Bonnie K; Biaggioni, Italo; Diedrich, André; Paranjape, Sachin Y; Robertson, David; Raj, Satish R

    2015-01-01

    Patients with neurogenic orthostatic hypotension (OH) typically have impaired sympathetic nervous system tone and therefore low levels of upright plasma norepinephrine. We report a subset of patients who clinically have typical neurogenic OH but who paradoxically have elevated upright levels of plasma norepinephrine. We retrospectively studied 83 OH patients evaluated at the Vanderbilt Autonomic Dysfunction Center between August 2007 and May 2013. Based upon standing norepinephrine, patients were dichotomized into a hyperadrenergic orthostatic hypotension group (hyperOH: upright NE ≥3.55 nmol/L [600 pg/mL], n=19) or a non-hyperadrenergic orthostatic hypotension group (nOH: upright NE < 3.55 nmol/L [600 pg/mL], n=64). Medical history and data from autonomic testing, including the Valsalva maneuver (VM), were analyzed. HyperOH patients had profound orthostatic falls in blood pressure, but less severe than in nOH (change in SBP: −53±31 mmHg vs. −68±33 mmHg, P=0.050; change in DBP: −18±23 mmHg vs. −30±17 mmHg, P=0.01). The expected compensatory increase in standing heart rate was similarly blunted in both hyperOH and nOH groups (84±15 bpm vs. 82±14 bpm; P=0.6). HyperOH patients had less severe sympathetic failure as evidenced by smaller falls in DBP during phase 2 of VM, and a shorter VM phase 4 blood pressure recovery time (16.5±8.9 sec vs. 31.6±16.6 sec; P<0.001) than nOH patients. Neurogenic hyperOH patients have severe neurogenic orthostatic hypotension, but have less severe adrenergic dysfunction than nOH patients. Further work is required to understand if hyperOH patients will progress to nOH or if this represents a different disorder. PMID:25706983

  19. MiR-124 Promote Neurogenic Transdifferentiation of Adipose Derived Mesenchymal Stromal Cells Partly through RhoA/ROCK1, but Not ROCK2 Signaling Pathway

    PubMed Central

    Wang, Ye; Wang, Desheng; Guo, Dawen

    2016-01-01

    Objective Some recent studies suggest that multiple miRNAs might regulate neurogenic transdifferentiation of mesenchymal stromal cells (MSCs). In the present study, we hypothesized that the miR-124 can repress the expression of RhoA upon the neurogenesis of adipose derived MSCs (ADMSCs). Methods MiRNA expression dynamics during neurogenic transdifferentiation of ADMSCs were measured. The expression of neuron-specific enolase (NSE), Tuj-1 (Neuron-specific class III beta-tubulin) and glial fibrillary acidic protein (GFAP), as well as electrophysiological properties, were detected after neurogenic transdifferentiation. The targeting of miR-124 over RhoA was verified by dual luciferase assay, qRT-PCR and western blot. The functions of miR-124 and the RhoA/ROCK signaling pathway were studied using gain and loss of function experiments in vitro. Results MiR-124 is significantly upregulated during neurogenic transdifferentiation of ADMSCs. Knockdown of endogenous miR-124 hampered neurogenic transdifferentiation and the acquired electrophysiological properties. MiR-124 could directly target RHOA mRNA and repress its expression, through which it increased the proportion of transdifferentiated (transdiff.) cells with positive NSE, Tuj-1 and GFAP. RhoA/ROCK1, but not ROCK2 is a downstream signaling pathway of miR-124 in the process of transdifferentiation. Conclusion MiR-124 is an important miRNA modulating neurogenic transdifferentiation of ADMSCs at least partly via the miR-124/RhoA/ROCK1 signaling pathway. These findings provided some fundamental information for future use of ADMSCs as an agent for regenerative medicine and cell therapy for neurological diseases. PMID:26745800

  20. Histamine H3 receptor activation inhibits neurogenic sympathetic vasoconstriction in porcine nasal mucosa.

    PubMed

    Varty, LoriAnn M; Hey, John A

    2002-10-11

    Histamine release from mast cells is a primary mediator of rhinorrhea, nasal mucosal swelling, increased secretion, sneezing, pruritus and congestion that occur in allergic rhinitis. It is well known that histamine H(1) receptor antagonists inhibit the itch and rhinorhea, but do not block the allergic nasal congestion. A growing body of evidence shows that in addition to histamine H(1) receptors, activation of H(3) receptors may contribute to the procongestant nasal actions of histamine. Activation of the prejunctional histamine H(3) receptor modulates sympathetic control of nasal vascular tone and resistance. The present study was conducted to further characterize the role of histamine H(3) receptors on neurogenic sympathetic vascular contractile responses in isolated porcine nasal turbinate mucosa. We presently found that the histamine H(3) receptor agonist, (R)-alpha-methylhistamine (10-1000 nM), inhibited electrical field stimulation-induced sympathetic vasomotor contractions in a concentration-dependent fashion. Pretreatment with either of the selective histamine H(3) receptor antagonists, thioperamide and clobenpropit, blocked the sympathoinhibitory effect of (R)-alpha-methylhistamine in porcine turbinate mucosa. The effect of compound 48/80, an agent that elicits the release of endogenous histamine from mast cells on nasal sympathetic contractile responses, was also tested. The action of compound 48/80 to release mast cell-derived histamine in the nose mimics many of the nasal responses associated with allergic rhinitis, extravascular leakage and decreased nasal patency. We presently found that compound 48/80 also inhibited the electrical field stimulation-induced sympathetic response. Pretreatment with the H(3) receptor antagonist clobenpropit blocked the sympathoinhibitory action of compound 48/80 on sympathetic contractile responses in nasal mucosa. Taken together, these studies indicate that histamine H(3) receptors modulate vascular contractile

  1. Neuroinflammation and oxidative stress in rostral ventrolateral medulla contribute to neurogenic hypertension induced by systemic inflammation

    PubMed Central

    2012-01-01

    intercellular adhesion molecule-1. Finally, the LPS-promoted long-term pressor response and the reduction in expression of voltage-gated potassium channel, Kv4.3 in RVLM were antagonized by minocycline, NS398, pentoxifylline, or a superoxide dismutase mimetic, tempol, either infused into cisterna magna or microinjected bilaterally into RVLM. The same treatments, on the other hand, were ineffective against LPS-induced systemic inflammation. Conclusion These results suggest that systemic inflammation activates microglia in RVLM to induce COX-2-dependent neuroinflammation that leads to an increase in O2·- production. The resultant oxidative stress in RVLM in turn mediates neurogenic hypertension. PMID:22958438

  2. Properties of doublecortin-(DCX)-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice.

    PubMed

    Klempin, Friederike; Kronenberg, Golo; Cheung, Giselle; Kettenmann, Helmut; Kempermann, Gerd

    2011-01-01

    The piriform cortex receives input from the olfactory bulb and (via the entorhinal cortex) sends efferents to the hippocampus, thereby connecting the two canonical neurogenic regions of the adult rodent brain. Doublecortin (DCX) is a cytoskeleton-associated protein that is expressed transiently in the course of adult neurogenesis. Interestingly, the adult piriform cortex, which is usually considered non-neurogenic (even though some reports exist that state otherwise), also contains an abundant population of DCX-positive cells. We asked how similar these cells would be to DCX-positive cells in the course of adult hippocampal neurogenesis. Using BAC-generated transgenic mice that express GFP under the DCX promoter, we studied DCX-expression and electrophysiological properties of DCX-positive cells in the mouse piriform cortex in comparison with the dentate gyrus. While one class of cells in the piriform cortex indeed showed features similar to newly generated immature granule neurons, the majority of DCX cells in the piriform cortex was mature and revealed large Na+ currents and multiple action potentials. Furthermore, when proliferative activity was assessed, we found that all DCX-expressing cells in the piriform cortex were strictly postmitotic, suggesting that no DCX-positive "neuroblasts" exist here as they do in the dentate gyrus. We conclude that DCX in the piriform cortex marks a unique population of postmitotic neurons with a subpopulation that retains immature characteristics associated with synaptic plasticity. DCX is thus, per se, no marker of neurogenesis but might be associated more broadly with plasticity.

  3. PET-Scan Shows Peripherally Increased Neurokinin 1 Receptor Availability in Chronic Tennis Elbow: Visualizing Neurogenic Inflammation?

    PubMed Central

    Peterson, Magnus; Svärdsudd, Kurt; Appel, Lieuwe; Engler, Henry; Aarnio, Mikko; Gordh, Torsten; Långström, Bengt; Sörensen, Jens

    2013-01-01

    In response to pain, neurokinin 1 (NK1) receptor availability is altered in the central nervous system. The NK1 receptor and its primary agonist, substance P, also play a crucial role in peripheral tissue in response to pain, as part of neurogenic inflammation. However, little is known about alterations in NK1 receptor availability in peripheral tissue in chronic pain conditions and very few studies have been performed on human beings. Ten subjects with chronic tennis elbow were therefore examined by positron emission tomography (PET) with the NK1 specific radioligand [11C]GR205171 before and after treatment with graded exercise. The radioligand signal intensity was higher in the affected arm as compared with the unaffected arm, measured as differences between the arms in volume of voxels and signal intensity of this volume above a reference threshold set as 2.5 SD above mean signal intensity of the unaffected arm before treatment. In the eight subjects examined after treatment, pain ratings decreased in all subjects but signal intensity decreased in five and increased in three. In conclusion, NK1 receptors may be activated, or up-regulated in the peripheral, painful tissue of a chronic pain condition. This up-regulation does, however, have moderate correlation to pain ratings. The increased NK1 receptor availability is interpreted as part of ongoing neurogenic inflammation and may have correlation to the pathogenesis of chronic tennis elbow. Trial Registration ClinicalTrials.gov NCT00888225 http://clinicaltrials.gov/ PMID:24155873

  4. Efficacy and Adverse Events Associated With Use of OnabotulinumtoxinA for Treatment of Neurogenic Detrusor Overactivity: A Meta-Analysis

    PubMed Central

    2017-01-01

    Purpose OnabotulinumtoxinA is used widely for the treatment of neurogenic detrusor overactivity. We conducted a systematic review and meta-analysis to assess its efficacy and safety for neurogenic detrusor overactivity treatment. Methods A systematic literature review was performed to identify all published randomized double-blind, placebo-controlled trials of onabotulinumtoxinA for neurogenic detrusor overactivity treatment. MEDLINE, Embase, and the CENTRAL were employed. Reference lists of retrieved studies were reviewed carefully. Results Six publications involving 871 patients, which compared onabotulinumtoxinA with a placebo were analyzed. Efficacy of onabotulinumtoxinA treatment was shown as a reduction of the mean number of urinary incontinence episodes per day (mean difference, -1.41; 95% confidence interval [CI], -1.70 to -1.12; P<0.00001), maximum cystometric capacity (135.48; 95% CI, 118.22–152.75; P<0.00001), and maximum detrusor pressure (-32.98; 95% CI, -37.33 to -28.62; P<0.00001). Assessment of adverse events revealed that complications due to onabotulinumtoxinA injection were localized primarily to the urinary tract. Conclusions This meta-analysis suggests that onabotulinumtoxinA is an effective treatment for neurogenic detrusor overactivity with localized advent events. PMID:28361515

  5. The effect of spinal cord-injury level on the outcome of neurogenic bladder treatment using OnabotulinumtoxinA

    PubMed Central

    Al Taweel, Waleed; Alzyoud, Khalil Mohammed

    2015-01-01

    Aim: The aim was to report the effectiveness and safety OnabotulinumtoxinA (Botox, Allergan, Inc., Irvine, CA, USA) intradetrusor injections in spinal cord-injured (SCI) patients with refractory neurogenic detrusor overactivity. And to assess the result based on SCI level. Materials and Methods: We reviewed the chart of 103 patients with neurogenic bladder secondary to SCI at the rehab center who received OnabotulinumtoxinA in our Neurourology Department for treatment of lower urinary tract symptoms between January 2007 and December 2013. All patients had a clinical examination, urinalysis, and an urodynamic study at baseline and 3 months after treatment as well as a visual analogue scale (VAS; range scale: 0–10) and a bladder diary checked for 3 days. 300 IU of OnabotulinumtoxinA, detrusor muscle injections were performed in 30 sites under cystoscopic guidance. Outcome measures included frequency of urge urinary incontinence collected by bladder diaries; changes in urodynamic parameters such as maximum cystometric bladder capacity, reflex volume, maximum detrusor pressure; side-effects; antimuscarinic drug consumption and quality of life (QOL) measured with VAS. Results: The study includes 32 female and 71 male with a mean patient age of 29 years (range: 18–56 year). The effect of Botox injection on bladder function was observed within 1–2 week after treatment. The urodynamic parameters were improved significantly after treatment compared with baseline values. There were significant reductions in the frequencies of incontinence episodes after treatment as seen in the voiding diary. A significant improvement in patient satisfaction was found after treatment which was expressed on the VAS assessment, with an improvement of the mean of 3 points. Patients with thoracic and lumbar injury have better result compare to cervical injury patients. The earliest recurrence of clinical symptoms was at 10 weeks. Overall, the mean duration of symptomatic improvement was 8

  6. Inhaled nitric oxide for the brain dead donor with neurogenic pulmonary edema during anesthesia for organ donation: a case report

    PubMed Central

    Park, Eun Sun; Lee, A-Ran; Lee, Sang Hyun; Kim, An Suk; Park, Soon Eun; Cho, Young Woo

    2014-01-01

    Neurogenic pulmonary edema (NPE) in brain dead organ donors occurring after an acute central nervous system insult threatens organ preservation of potential organ donors and the outcome of organ donation. Hence the active and immediate management of NPE is critical. In this case, a 50-year-old male was admitted to the intensive care unit (ICU) for organ donation. He was hypoxic due to NPE induced by spontaneous intracerebral hemorrhage and intraventricular hemorrhage. Protective ventilatory management, intermittent recruitment maneuvers, and supportive treatment were maintained in the ICU and the operating room (OR). Despite this management, the hypoxemia worsened after the OR admission. So inhaled nitric oxide (NO) therapy was performed during the operation, and the hypoxic phenomena showed remarkable improvement. The organ retrieval was successfully completed. Therefore, NO inhalation can be helpful in the improvement of hypoxemia caused by NPE in brain dead organ donors during anesthesia for the organ donation. PMID:25237451

  7. Extracorporeal Shock Wave Therapy for Painful Chronic Neurogenic Heterotopic Ossification After Traumatic Brain Injury: A Case Report

    PubMed Central

    Choi, Yong Min; Hong, Seok Hyun; Lee, Chang Hyun; Kang, Jin Ho

    2015-01-01

    Neurogenic heterotopic ossification (NHO) is a process of benign bone formation and growth in soft tissues surrounding major synovial joints and is associated with central nervous system (CNS) injuries. It is a common complication in major CNS injuries, such as traumatic brain injury, spinal cord injury, and stroke. Here, we report the case of a 72-year-old male, who experienced a traumatic brain injury and painful chronic NHO around the left hip joint. Three applications of extracorporeal shock wave therapy (ESWT) were administered to the area of NHO, which resulted in pain relief and an improvement in the loss of motion in the left hip joint. Improvements were also noted in walking performance and activities of daily living, although the size of NHO remained unchanged. Therapeutic effects of ESWT lasted for 12 weeks. PMID:25932431

  8. Childhood Neurogenic Stuttering Due to Bilateral Congenital Abnormality in Globus Pallidus: A Case Report and Review of the Literature

    PubMed Central

    SAEEDI, Mohammad Javad; ESFANDIARY, Ebrahim; ALMASI DOOGHAEE, Mostafa

    2016-01-01

    Objective The basal ganglia are a group of structures that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex and thalamus. Some speech disorders such as stuttering can resulted from disturbances in the circuits between the basal ganglia and the language motor area of the cerebral cortex. Stuttering consists of blocks, repetitive, prolongation or cessation of speech. We present a 7.5 -year-old male child with bilateral basal ganglia lesion in globus pallidus with unclear reason. The most obvious speech disorders in patient was stuttering, but also problems in swallowing, monotone voice, vocal tremor, hypersensitivity of gag reflex and laryngeal dystonia were seen. He has failed to respond to drug treatment, so he went on rehabilitation therapy when his problem progressed. In this survey, we investigate the possible causes of this type of childhood neurogenic stuttering. PMID:27843470

  9. Voltage-gated K+ channels sensitive to stromatoxin-1 regulate myogenic and neurogenic contractions of rat urinary bladder smooth muscle

    PubMed Central

    Chen, Muyan; Kellett, Whitney F.

    2010-01-01

    Members of the voltage-gated K+ (KV) channel family are suggested to control the resting membrane potential and the repolarization phase of the action potential in urinary bladder smooth muscle (UBSM). Recent studies report that stromatoxin-1, a peptide isolated from tarantulas, selectively inhibits KV2.1, KV2.2, KV4.2, and KV2.1/9.3 channels. The objective of this study was to investigate whether KV channels sensitive to stromatoxin-1 participate in the regulation of rat UBSM contractility and to identify their molecular fingerprints. Stromatoxin-1 (100 nM) increased the spontaneous phasic contraction amplitude, muscle force, and tone in isolated UBSM strips. However, stromatoxin-1 (100 nM) had no effect on the UBSM contractions induced by depolarizing agents such as KCl (20 mM) or carbachol (1 μM). This indicates that, under conditions of sustained membrane depolarization, the KV channels sensitive to stromatoxin-1 have no further contribution to the membrane excitability and contractility. Stromatoxin-1 (100 nM) increased the amplitude of the electrical field stimulation-induced contractions, suggesting also a role for these channels in neurogenic contractions. RT-PCR experiments on freshly isolated UBSM cells showed mRNA expression of KV2.1, KV2.2, and KV9.3, but not KV4.2 channel subunits. Protein expression of KV2.1 and KV2.2 channels was detected using Western blot and was further confirmed by immunocytochemical detection in freshly isolated UBSM cells. These novel findings indicate that KV2.1 and KV2.2, but not KV4.2, channel subunits are expressed in rat UBSM and play a key role in opposing both myogenic and neurogenic UBSM contractions. PMID:20393158

  10. Traumatic brain injury and recovery mechanisms: peptide modulation of periventricular neurogenic regions by the choroid plexus–CSF nexus

    PubMed Central

    Stopa, Edward; Baird, Andrew; Sharma, Hari

    2010-01-01

    In traumatic brain injury (TBI), severe disruptions occur in the choroid plexus (CP)–cerebrospinal fluid (CSF) nexus that destabilize the nearby hippocampal and subventricular neurogenic regions. Following invasive and non-invasive injuries to cortex, several adverse sequelae harm the brain interior: (i) structural damage to CP epithelium that opens the blood–CSF barrier (BCSFB) to protein, (ii) altered CSF dynamics and intracranial pressure (ICP), (iii) augmentation of leukocyte traffic across CP into the CSF–brain, (iv) reduction in CSF sink action and clearance of debris from ventricles, and (v) less efficient provision of micronutritional and hormonal support for the CNS. However, gradual post-TBI restitution of the injured CP epithelium and ependyma, and CSF homeostatic mechanisms, help to restore subventricular/subgranular neurogenesis and the cognitive abilities diminished by CNS damage. Recovery from TBI is faciltated by upregulated choroidal/ependymal growth factors and neurotrophins, and their secretion into ventricular CSF. There, by an endocrine-like mechanism, CSF bulk flow convects the neuropeptides to target cells in injured cortex for aiding repair processes; and to neurogenic niches for enhancing conversion of stem cells to new neurons. In the recovery from TBI and associated ischemia, the modulating neuropeptides include FGF2, EGF, VEGF, NGF, IGF, GDNF, BDNF, and PACAP. Homeostatic correction of TBI-induced neuropathology can be accelerated or amplified by exogenously boosting the CSF concentration of these growth factors and neurotrophins. Such intraventricular supplementation via the CSF route promotes neural restoration through enhanced neurogenesis, angiogenesis, and neuroprotective effects. CSF translational research presents opportunities that involve CP and ependymal manipulations to expedite recovery from TBI. PMID:20936524

  11. Histamine H3 Receptor Integrates Peripheral Inflammatory Signals in the Neurogenic Control of Immune Responses and Autoimmune Disease Susceptibility

    PubMed Central

    Martin, Rebecca A.; Subramanian, Meenakumari; Noubade, Rajkumar; Rio, Roxana Del; Mawe, Gary M.; Bond, Jeffrey P.; Poynter, Matthew E.; Blankenhorn, Elizabeth P.; Teuscher, Cory

    2013-01-01

    Histamine H3 receptor (Hrh3/H3R) is primarily expressed by neurons in the central nervous system (CNS) where it functions as a presynaptic inhibitory autoreceptor and heteroreceptor. Previously, we identified an H3R-mediated central component in susceptibility to experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis (MS), related to neurogenic control of blood brain barrier permeability and peripheral T cell effector responses. Furthermore, we identified Hrh3 as a positional candidate for the EAE susceptibility locus Eae8. Here, we characterize Hrh3 polymorphisms between EAE-susceptible and resistant SJL and B10.S mice, respectively, and show that Hrh3 isoform expression in the CNS is differentially regulated by acute peripheral inflammatory stimuli in an allele-specific fashion. Next, we show that Hrh3 is not expressed in any subpopulations of the immune compartment, and that secondary lymphoid tissue is anatomically poised to be regulated by central H3R signaling. Accordingly, using transcriptome analysis, we show that, inflammatory stimuli elicit unique transcriptional profiles in the lymph nodes of H3RKO mice compared to WT mice, which is indicative of negative regulation of peripheral immune responses by central H3R signaling. These results further support a functional link between the neurogenic control of T cell responses and susceptibility to CNS autoimmune disease coincident with acute and/or chronic peripheral inflammation. Pharmacological targeting of H3R may therefore be useful in preventing the development and formation of new lesions in MS, thereby limiting disease progression. PMID:23894272

  12. Differential neurogenic effects of casein-derived opioid peptides on neuronal stem cells: implications for redox-based epigenetic changes.

    PubMed

    Trivedi, Malav; Zhang, Yiting; Lopez-Toledano, Miguel; Clarke, Andrew; Deth, Richard

    2016-11-01

    Food-derived peptides, such as β-casomorphin BCM7, have potential to cross the gastrointestinal tract and blood-brain barrier and are associated with neurological disorders and neurodevelopmental disorders. We previously established a novel mechanism through which BCM7 affects the antioxidant levels in neuronal cells leading to inflammatory consequences. In the current study, we elucidated the effects of casein-derived peptides on neuronal development by using the neurogenesis of neural stem cells (NSCs) as an experimental model. First, the transient changes in intracellular thiol metabolites during NSC differentiation (neurogenesis) were investigated. Next, the neurogenic effects of food-derived opioid peptides were measured, along with changes in intracellular thiol metabolites, redox status and global DNA methylation levels. We observed that the neurogenesis of NSCs was promoted by human BCM7 to a greater extent, followed by A2-derived BCM9 in contrast to bovine BCM7, which induced increased astrocyte formation. The effect was most apparent when human BCM7 was administered for 1day starting on 3days postplating, consistent with immunocytochemistry. Furthermore, neurogenic changes regulated by bovine BCM7 and morphine were associated with an increase in the glutathione/glutathione disulfide ratio and a decrease in the S-adenosylmethionine/S-adenosylhomocysteine ratio, indicative of changes in the redox and the methylation states. Finally, bovine BCM7 and morphine decreased DNA methylation in differentiating NSCs. In conclusion, these results suggest that food-derived opioid peptides and morphine regulated neurogenesis and differentiation of NSCs through changes in the redox state and epigenetic regulation.

  13. Success of sildenafil treatment in neurogenic female sexual dysfunction caused by L5-S1 intervertebral disk rupture: a case report.

    PubMed

    Ferrara, Dean; Zaslau, Stanley

    2007-06-01

    Female sexual dysfunction can be founded by disorders of sexual desire, arousal, orgasm, and sexual pain. Physiologic sexual dysfunction can, in many cases, be the result of impaired neurovascular tone to the clitoris and vagina. The vagina and clitoris both contain erectile tissue and phosphodiesterase type 5 (PDE5). Accordingly, the use of sildenafil, a PDE5 inhibitor, has been studied in relation to neurogenic female sexual dysfunction. The present case report addresses neurogenic female sexual dysfunction from the result of a ruptured L5-S1 intervertebral disk. The patient was treated with sildenafil, and her symptoms were recorded using a Female Sexual Function Index score. Discussion of the use of sildenafil in women, with an emphasis on female neurovascular sexual physiology and function, is reviewed.

  14. Increases in transient receptor potential vanilloid-1 mRNA and protein in primary afferent neurons stimulated by protein kinase C and their possible role in neurogenic inflammation

    PubMed Central

    Xu, Xijin; Wang, Peng; Zou, Xiaoju; Li, Dingge; Fang, Li; Lin, Qing

    2008-01-01

    A recent study by our group demonstrates pharmacologically that the transient receptor potential vanilloid-1 (TRPV1) is activated by intradermal injection of capsaicin to initiate neurogenic inflammation by the release of neuropeptides in the periphery. In this study, expression of TRPV1, phosphorylated protein kinase C (p-PKC) and calcitonin gene-related peptide (CGRP) in dorsal root ganglion (DRG) neurons were visualized using immunofluorescence, real-time PCR and Western blots to examine whether increases in TRPV1 mRNA and protein levels evoked by capsaicin injection are subject to modulation by the activation of PKC and to analyze the role of this process in the pathogenesis of neurogenic inflammation. Capsaicin injection into the hindpaw skin of anesthetized rats evoked increases in the expression of TRPV1, CGRP and p-PKC in mRNA and/or protein levels and in the number of single labeled TRPV1, p-PKC and CGRP neurons in ipsilateral L4–5 DRGs. Co-expressions of TRPV1 with p-PKC and/or CGRP in DRG neurons were also significantly increased after CAP injection. These evoked expressions both at molecular and cellular levels were significantly inhibited after TRPV1 receptors were blocked by 5′-iodoresiniferatoxin (5 μg) or PKC was inhibited by chelerythrine chloride (5 μg). Taken together, these results provide evidence that up-regulation of TRPV1 mRNA and protein levels under inflammatory conditions evoked by capsaicin injection is subject to modulation by the PKC cascade in which increased CGRP level in DRG neurons may be related to the initiation of neurogenic inflammation. Thus, up-regulation of TRPV1 receptors in DRG neurons seems critical for initiating acute neurogenic inflammation. PMID:18752301

  15. Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation

    PubMed Central

    Vincent, Lucile; Vang, Derek; Nguyen, Julia; Benson, Barbara; Lei, Jianxun; Gupta, Kalpna

    2016-01-01

    Sickle cell anemia is a manifestation of a single point mutation in hemoglobin, but inflammation and pain are the insignia of this disease which can start in infancy and continue throughout life. Earlier studies showed that mast cell activation contributes to neurogenic inflammation and pain in sickle mice. Morphine is the common analgesic treatment but also remains a major challenge due to its side effects and ability to activate mast cells. We, therefore, examined cannabinoid receptor-specific mechanisms to mitigate mast cell activation, neurogenic inflammation and hyperalgesia, using HbSS-BERK sickle and cannabinoid receptor-2-deleted sickle mice. We show that cannabinoids mitigate mast cell activation, inflammation and neurogenic inflammation in sickle mice via both cannabinoid receptors 1 and 2. Thus, cannabinoids influence systemic and neural mechanisms, ameliorating the disease pathobiology and hyperalgesia in sickle mice. This study provides ‘proof of principle’ for the potential of cannabinoid/cannabinoid receptor-based therapeutics to treat several manifestations of sickle cell anemia. PMID:26703965

  16. Effects of some natural carotenoids on TRPA1- and TRPV1-induced neurogenic inflammatory processes in vivo in the mouse skin.

    PubMed

    Horváth, Györgyi; Kemény, Ágnes; Barthó, Loránd; Molnár, Péter; Deli, József; Szente, Lajos; Bozó, Tamás; Pál, Szilárd; Sándor, Katalin; Szőke, Éva; Szolcsányi, János; Helyes, Zsuzsanna

    2015-05-01

    Mechanisms of the potent anti-inflammatory actions of carotenoids are unknown. Since carotenoids are incorporated into membranes, they might modulate transient receptor potential ankyrin 1 and vanilloid 1 (TRPA1 and TRPV1) activation predominantly on peptidergic sensory nerves. We therefore investigated the effects of three carotenoids (β-carotene, lutein and lycopene) on cutaneous neurogenic inflammation. Acute neurogenic edema and inflammatory cell recruitment were induced by smearing the TRPA1 agonist mustard oil (5%) or the TRPV1 activator capsaicin (2.5%) on the mouse ear. Ear thickness was then determined by micrometry, microcirculation by laser Doppler imaging and neutrophil accumulation by histopathology and spectrophotometric determination of myeloperoxidase activity. The effects of lutein on the stimulatory action of the TRPA1 agonist mustard oil were also tested on the guinea-pig small intestine, in isolated organ experiments. Mustard oil evoked 50-55% ear edema and granulocyte influx, as shown by histology and myeloperoxidase activity. Swelling was significantly reduced between 2 and 4 h after administration of lutein or β-carotene (100 mg/kg subcutane three times during 24 h). Lutein also decreased neutrophil accumulation induced by TRPA1 activation, but did not affect mustard oil-evoked intestinal contraction. Lycopene had no effect on any of these parameters. None of the three carotenoids altered capsaicin-evoked inflammation. It is proposed that the dihydroxycarotenoid lutein selectively inhibits TRPA1 activation and consequent neurogenic inflammation, possibly by modulating lipid rafts.

  17. Gelatin Directly Enhances Neurogenic Differentiation Potential in Bone Marrow-Derived Mesenchymal Stem Cells Without Stimulation of Neural Progenitor Cell Proliferation.

    PubMed

    Lee, Hyun; Han, Na Rae; Hwang, Jae Yeon; Yun, Jung Im; Kim, Choonghyo; Park, Kyu Hyun; Lee, Seung Tae

    2016-09-01

    Gelatin has been reported to induce generation of mesenchymal stem cells (MSCs) with enhanced potential of differentiation into neuronal lineage cells. However, the presence of various cell types besides MSCs in bone marrow has raised doubts about the effects of gelatin. In the following report, we determined whether gelatin can directly enhance neurogenic differentiation potential in MSCs without proliferation of neural progenitor cells (NPCs). MSCs comprised a high proportion of bone marrow-derived primary cells (BMPCs) and gelatin induced significant increases in MSC proliferation during primary culture, and the proportion of MSCs was maintained at more than 99% throughout the subculture. However, NPCs comprised a low percentage of BMPCs and a decrease in proliferation was detected despite gelatin treatment during the primary culture, and the proportion of subcultured NPCs gradually decreased. In a similar manner, MSCs exposed to gelatin during primary culture showed more enhanced neurogenic differentiation ability than those not exposed to gelatin. Together, these results demonstrate that gelatin directly enhances neurogenic differentiation in bone marrow-derived MSCs without stimulating NPC proliferation.

  18. CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells.

    PubMed

    Pfenninger, Cosima V; Roschupkina, Teona; Hertwig, Falk; Kottwitz, Denise; Englund, Elisabet; Bengzon, Johan; Jacobsen, Sten Eirik; Nuber, Ulrike A

    2007-06-15

    Human brain tumor stem cells have been enriched using antibodies against the surface protein CD133. An antibody recognizing CD133 also served to isolate normal neural stem cells from fetal human brain, suggesting a possible lineage relationship between normal neural and brain tumor stem cells. Whether CD133-positive brain tumor stem cells can be derived from CD133-positive neural stem or progenitor cells still requires direct experimental evidence, and an important step toward such investigations is the identification and characterization of normal CD133-presenting cells in neurogenic regions of the embryonic and adult brain. Here, we present evidence that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in the adult subventricular zone. Our findings suggest two principal possibilities for the origin of brain tumor stem cells: a derivation from CD133-expressing cells, which are normally not present in the adult brain (embryonic neural stem cells and an early postnatal intermediate radial glial/ependymal cell type), or from CD133-positive ependymal cells in the adult brain, which are, however, generally regarded as postmitotic. Alternatively, brain tumor stem cells could be derived from proliferative but CD133-negative neurogenic astrocytes in the adult brain. In the latter case, brain tumor development would involve the production of CD133.

  19. Neurogenic abnormalities in Alzheimer's disease differ between stages of neurogenesis and are partly related to cholinergic pathology.

    PubMed

    Perry, Elaine K; Johnson, Mary; Ekonomou, Antigoni; Perry, Robert H; Ballard, Clive; Attems, Johannes

    2012-08-01

    Neurogenesis occurs in the subventricular zone and the sub-granular layer of the hippocampus and is thought to take place in 5 stages, including proliferation, differentiation, migration, targeting, and integration phases, respectively. In Alzheimer's disease (AD) both increased and decreased neurogenesis has been reported and cholinergic activity is assumed to be involved in neurogenesis. The aim of this study was to systematically assess different phases of neurogenesis and their relation to AD and cholinergic pathology. We investigated post-mortem brain tissue from 20 AD patients and 21 non-demented controls that was neuropathologically characterized according to standardized criteria. Hippocampal sections were stained with antibodies against neurogenic markers Musashi-1, nestin, PSA-NCAM, doublecortin, and β-III-tubulin as well as ChAT (choline-acetyltransferase). Using image analysis immunoreactivity was assessed in the subventricular zone, the sub-granular layer, and the granule cell layer by determining the integrated optical density. In the sub-granular layer and the granule cell layer Musashi-1 and ChAT immunoreactivities were significantly lower in AD and decreased with increasing Braak stages. Conversely, immunorreactivities of both nestin and PSA-NCAM were significantly higher in AD and increased with increasing Braak stages while no changes were seen for doublecortin and β-III-tubulin, except for significantly higher doublecortin levels in the granule cell layer of AD cases. Of note, Musashi-1 immunoreactivity significantly correlated with ChAT immuonoreactivity across different Braak stages. In the subventricular zone only nestin immunoreactivity was significantly higher in AD and significantly increased with increasing Braak stages, while no significant differences were seen for all other markers. Our finding of a reduction of ChAT and Musashi-1 levels in AD is compatible with the assumption that cholinergic pathology per se has a detrimental

  20. Sympathetic α₃β₂-nAChRs mediate cerebral neurogenic nitrergic vasodilation in the swine.

    PubMed

    Lee, Reggie Hui-Chao; Liu, Yi-Qing; Chen, Po-Yi; Liu, Chin-Hung; Chen, Mei-Fang; Lin, Hung-Wen; Kuo, Jon-Son; Premkumar, Louis S; Lee, Tony Jer-Fu

    2011-08-01

    The α(7)-nicotinic ACh receptor (α(7)-nAChR) on sympathetic neurons innervating basilar arteries of pigs crossed bred between Landrace and Yorkshire (LY) is known to mediate nicotine-induced, β-amyloid (Aβ)-sensitive nitrergic neurogenic vasodilation. Preliminary studies, however, demonstrated that nicotine-induced cerebral vasodilation in pigs crossbred among Landrace, Yorkshire, and Duroc (LYD) was insensitive to Aβ and α-bungarotoxin (α-BGTX). We investigated nAChR subtype on sympathetic neurons innervating LYD basilar arteries. Nicotine-induced relaxation of porcine isolated basilar arteries was examined by tissue bath myography, inward currents on nAChR-expressing oocytes by two-electrode voltage recording, and mRNA and protein expression in the superior cervical ganglion (SCG) and middle cervical ganglion (MCG) by reverse transcription PCR and Western blotting. Nicotine-induced basilar arterial relaxation was not affected by Aβ, α-BGTX, and α-conotoxin IMI (α(7)-nAChR antagonists), or α-conotoxin AuIB (α(3)β(4)-nAChR antagonist) but was inhibited by tropinone and tropane (α(3)-containing nAChR antagonists) and α-conotoxin MII (selective α(3)β(2)-nAChR antagonist). Nicotine-induced inward currents in α(3)β(2)-nAChR-expressing oocytes were inhibited by α-conotoxin MII but not by α-BGTX, Aβ, or α-conotoxin AuIB. mRNAs of α(3)-, α(7)-, β(2)-, and β(4)-subunits were expressed in both SCGs and MCGs with significantly higher mRNAs of α(3)-, β(2)-, and β(4)-subunits than that of α(7)-subunit. The Aβ-insensitive sympathetic α(3)β(2)-nAChR mediates nicotine-induced cerebral nitrergic neurogenic vasodilation in LYD pigs. The different finding from Aβ-sensitive α(7)-nAChR in basilar arteries of LY pigs may offer a partial explanation for different sensitivities of individuals to Aβ in causing diminished cerebral nitrergic vasodilation in diseases involving Aβ.

  1. α-Lipoic acid reduces neurogenic hypertension by blunting oxidative stress-mediated increase in ADAM17

    PubMed Central

    de Queiroz, Thyago M.; Xia, Huijing; Filipeanu, Catalin M.; Braga, Valdir A.

    2015-01-01

    We previously reported that type 2 angiotensin-converting enzyme (ACE2) compensatory activity is impaired by the disintegrin and metalloprotease 17 (ADAM17), and lack of ACE2 is associated with oxidative stress in neurogenic hypertension. To investigate the relationship between ADAM17 and oxidative stress, Neuro2A cells were treated with ANG II (100 nM) 24 h after vehicle or α-lipoic acid (LA, 500 μM). ADAM17 expression was increased by ANG II (120.5 ± 9.1 vs. 100.2 ± 0.8%, P < 0.05) and decreased after LA (69.0 ± 0.3 vs. 120.5 ± 9.1%, P < 0.05). In another set of experiments, LA reduced ADAM17 (92.9 ± 5.3 vs. 100.0 ± 11.2%, P < 0.05) following its overexpression. Moreover, ADAM17 activity was reduced by LA in ADAM17-overexpressing cells [109.5 ± 19.8 vs. 158.0 ± 20.0 fluorescence units (FU)·min−1·μg protein−1, P < 0.05], in which ADAM17 overexpression increased oxidative stress (114.1 ± 2.5 vs. 101.0 ± 1.0%, P < 0.05). Conversely, LA-treated cells attenuated ADAM17 overexpression-induced oxidative stress (76.0 ± 9.1 vs. 114.1 ± 2.5%, P < 0.05). In deoxycorticosterone acetate (DOCA)-salt hypertensive mice, a model in which ADAM17 expression and activity are increased, hypertension was blunted by pretreatment with LA (119.0 ± 2.4 vs. 131.4 ± 2.2 mmHg, P < 0.05). In addition, LA improved dysautonomia and baroreflex sensitivity. Furthermore, LA blunted the increase in NADPH oxidase subunit expression, as well as the increase in ADAM17 and decrease in ACE2 activity in the hypothalamus of DOCA-salt hypertensive mice. Taken together, these data suggest that LA might preserve ACE2 compensatory activity by breaking the feedforward cycle between ADAM17 and oxidative stress, resulting in a reduction of neurogenic hypertension. PMID:26254330

  2. SOX9 is an astrocyte-specific nuclear marker in the adult brain outside the neurogenic regions.

    PubMed

    Sun, Wei; Cornwell, Adam; Li, Jiashu; Peng, Sisi; Osorio, M Joana; Su Wanga, Nadia Aalling; Benraiss, Abdellatif; Lou, Nanhong; Goldman, Steven A; Nedergaard, Maiken

    2017-03-23

    Astrocytes have in recent years become the focus of intense experimental interest, yet markers for their definitive identification remain both scarce and imperfect. Astrocytes may be recognized as such by their expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), glutamate transporter 1 (GLT1)quaporin-4 (AQP4)ldehyde dehydrogenase 1 family member L1 (ALDH1L1)nd other proteins. Yet these proteins may all be regulated both developmentally and functionally, restricting their utility. To identify a nuclear marker pathognomonic of astrocytic phenotype, we assessed differential RNA expression by FACS-purified adult astrocytesnd on that basis evaluated the expression of the transcription factor SOX9 in both mouse and human brain. We found that SOX9 is almost selectively expressed by astrocytes in the adult brain except for ependymal cells and in the neurogenic regions, where SOX9 is also expressed by neural progenitor cells. Transcriptome comparisons of SOX9+ cells with GLT1+ cells showed that the two populations of cells exhibit largely overlapping gene expression. Expression of SOX9 did not decrease during agingnd was instead upregulated by reactive astrocytes in a number of settings, including a murine model of amyotrophic lateral sclerosis (SOD1G93A), middle cerebral artery occlusion (MCAO)nd multiple mini-strokes. We quantified the relative number of astrocytes using the isotropic fractionator technique in combination with SOX9 immunolabeling. The analysis showed that SOX9+ astrocytes constitute 10%∼20% of the total cell number in most CNS regions smaller fraction of total cell number than previously estimated in the normal adult brain.Significance Statement Astrocytes are traditionally identified immuno-histochemically by antibodies that target cell-specific antigens in the cytosol or plasma membrane. We show here that SOX9 is an astrocyte-specific nuclear marker in all major areas of the central nervous system outside of the neurogenic

  3. Serum atrial natriuretic peptide (ANP) as an objective indicator for the diagnosis of neurogenic shock: animal experiment and human case report.

    PubMed

    Zhao, Min-Zhu; Li, Yong-Guo; Zhang, Peng; Xiong, Jin-Cheng; Zhu, Shi-Sheng; Xiao, Xuan; Li, Jian-Bo

    2017-03-01

    In forensic medicine, the diagnosis of death due to neurogenic shock is considered to be an aporia, as lacking objective indicators and presenting atypical symptoms in autopsy. Medico-legal disputes and complaints occasionally result from this ambiguity. To explore potential objective indicators of neurogenic shock, we set up a model of neurogenic shock by applying an external mechanical force on the carotid sinus baroreceptor in rabbits. The serum atrial natriuretic peptide (ANP) level was measured by radioimmunoassay in the control group (n = 8), survival group (n = 15) and death group (n = 5) both before and after the insult. The serum ANP level showed a significant increase after the insult in the death group compared with the serum obtained before the insult (P = 0.006), while the serum ANP level after the insult in the survival group and control group was not statistically significant compared with the serum obtained before the insult (P = 0.332 and P = 0.492, respectively). To verify the repeatability of the model and the postmortem behavior of serum ANP, five healthy adult rabbits underwent the same procedure as the experimental group. The mortality rate was consistent with the former experiment (20 %). There were no significant changes in serum ANP level in vitro and in vivo (within 48 and 24 h, respectively). But there was a significant decrease in serum ANP level at 48 h postmortem in vivo (P = 0.001). A female patient who expired due to neurogenic shock during a hysteroscopy was reported. Neither fatal primary disease nor evidence for mechanical injuries or intoxication was found according to the autopsy. The serum ANP level was assayed as a supplementary indicator and was found to be three-fold higher than the normal maximum limit. Combined with the animal experiment, this case highlights that serum ANP has the potential to be an objective indicator for the diagnosis of death due to neurogenic shock.

  4. Protocol for a randomized, placebo-controlled, double-blind clinical trial investigating sacral neuromodulation for neurogenic lower urinary tract dysfunction

    PubMed Central

    2014-01-01

    Background Sacral neuromodulation has become a well-established and widely accepted treatment for refractory non-neurogenic lower urinary tract dysfunction, but its value in patients with a neurological cause is unclear. Although there is evidence indicating that sacral neuromodulation may be effective and safe for treating neurogenic lower urinary tract dysfunction, the number of investigated patients is low and there is a lack of randomized controlled trials. Methods and design This study is a prospective, randomized, placebo-controlled, double-blind multicenter trial including 4 sacral neuromodulation referral centers in Switzerland. Patients with refractory neurogenic lower urinary tract dysfunction are enrolled. After minimally invasive bilateral tined lead placement into the sacral foramina S3 and/or S4, patients undergo prolonged sacral neuromodulation testing for 3–6 weeks. In case of successful (defined as improvement of at least 50% in key bladder diary variables (i.e. number of voids and/or number of leakages, post void residual) compared to baseline values) prolonged sacral neuromodulation testing, the neuromodulator is implanted in the upper buttock. After a 2 months post-implantation phase when the neuromodulator is turned ON to optimize the effectiveness of neuromodulation using sub-sensory threshold stimulation, the patients are randomized in a 1:1 allocation in sacral neuromodulation ON or OFF. At the end of the 2 months double-blind sacral neuromodulation phase, the patients have a neuro-urological re-evaluation, unblinding takes place, and the neuromodulator is turned ON in all patients. The primary outcome measure is success of sacral neuromodulation, secondary outcome measures are adverse events, urodynamic parameters, questionnaires, and costs of sacral neuromodulation. Discussion It is of utmost importance to know whether the minimally invasive and completely reversible sacral neuromodulation would be a valuable treatment option for

  5. Nicotine-induced neurogenic relaxation in the mouse colon: changes with dextran sodium sulfate-induced colitis.

    PubMed

    Murakami, Ikuo; Hamada, Yuri; Yamane, Satoshi; Fujino, Hiromichi; Horie, Shunji; Murayama, Toshihiko

    2009-01-01

    Nicotine has been shown to reduce both tone and muscular activity in the human colon by releasing nitric oxide (NO) from nerves. To our knowledge, however, the effect of nicotine on mouse colon has not been elucidated, and the response in tissue from ulcerative colitis (UC) has not been investigated. We examined nicotine-induced responses in colon from control mice and mice with dextran sodium sulfate (DSS)-induced UC. In controls, bath application of nicotine caused a transient relaxation in longitudinal preparations from the transverse and distal colons but not from the rectum. The response was observed in the presence of bethanechol, abolished by treatment with tetrodotoxin and hexamethonium, and mediated partially (>50%) by the NO pathway. In longitudinal preparations of the distal colon from DSS-treated mice, spontaneous contractions decreased markedly, and nicotine caused contraction without relaxation in half of the preparations tested. Nicotine-induced relaxation in the presence of bethanechol was significantly decreased in the DSS-treated distal colon without changing bethanechol-induced contractions. These data suggest that 1) responses to nicotine differ dependent on colon regions, 2) DSS treatment predominantly caused nicotine-sensitive neurogenic changes in distal colon, and 3) DSS treatment may reverse the direction of nicotine-evoked responses in the colon, in mice.

  6. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension.

    PubMed

    Gibbons, Christopher H; Schmidt, Peter; Biaggioni, Italo; Frazier-Mills, Camille; Freeman, Roy; Isaacson, Stuart; Karabin, Beverly; Kuritzky, Louis; Lew, Mark; Low, Phillip; Mehdirad, Ali; Raj, Satish R; Vernino, Steven; Kaufmann, Horacio

    2017-01-03

    Neurogenic orthostatic hypotension (nOH) is common in patients with neurodegenerative disorders such as Parkinson's disease, multiple system atrophy, pure autonomic failure, dementia with Lewy bodies, and peripheral neuropathies including amyloid or diabetic neuropathy. Due to the frequency of nOH in the aging population, clinicians need to be well informed about its diagnosis and management. To date, studies of nOH have used different outcome measures and various methods of diagnosis, thereby preventing the generation of evidence-based guidelines to direct clinicians towards 'best practices' when treating patients with nOH and associated supine hypertension. To address these issues, the American Autonomic Society and the National Parkinson Foundation initiated a project to develop a statement of recommendations beginning with a consensus panel meeting in Boston on November 7, 2015, with continued communications and contributions to the recommendations through October of 2016. This paper summarizes the panel members' discussions held during the initial meeting along with continued deliberations among the panel members and provides essential recommendations based upon best available evidence as well as expert opinion for the (1) screening, (2) diagnosis, (3) treatment of nOH, and (4) diagnosis and treatment of associated supine hypertension.

  7. Rocking bed and prolonged independence from nocturnal non-invasive ventilation in neurogenic respiratory failure associated with limb weakness

    PubMed Central

    Cormican, L; Higgins, S; Davidson, A; Howard, R; Williams, A

    2004-01-01

    A 40 year old mother of three with autosomal dominant scapuloperoneal muscular dystrophy presented with severe neurogenic respiratory failure requiring nocturnal non-invasive ventilation (NIV). Because of the development of profound proximal muscular weakness as a consequence of the progressive nature of her neurological disease, she eventually was unable to apply and remove the facial interface to set up her NIV circuit. She therefore became dependent on her children and carers to start and stop NIV during the night. A rocking bed was successfully employed as an alternative to nocturnal NIV. Ventilation was facilitated by the passive movement of the diaphragm as a consequence of the movement of the abdominal contents under the effect of gravity. Benefit was demonstrated objectively by pulse oximetry and subjectively by the improvement in the patient's symptomatology and continued independence at night. The ease of use of a rocking bed should be borne in mind when the necessity for nocturnal ventilatory support in neuromuscular disease results in the potential loss of independence for a patient. PMID:15192173

  8. Potential Role of JAK-STAT Signaling Pathway in the Neurogenic-to-Gliogenic Shift in Down Syndrome Brain.

    PubMed

    Lee, Han-Chung; Tan, Kai-Leng; Cheah, Pike-See; Ling, King-Hwa

    2016-01-01

    Trisomy of human chromosome 21 in Down syndrome (DS) leads to several phenotypes, such as mild-to-severe intellectual disability, hypotonia, and craniofacial dysmorphisms. These are fundamental hallmarks of the disorder that affect the quality of life of most individuals with DS. Proper brain development involves meticulous regulation of various signaling pathways, and dysregulation may result in abnormal neurodevelopment. DS brain is characterized by an increased number of astrocytes with reduced number of neurons. In mouse models for DS, the pool of neural progenitor cells commits to glia rather than neuronal cell fate in the DS brain. However, the mechanism(s) and consequences of this slight neurogenic-to-gliogenic shift in DS brain are still poorly understood. To date, Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling has been proposed to be crucial in various developmental pathways, especially in promoting astrogliogenesis. Since both human and mouse models of DS brain exhibit less neurons and a higher percentage of cells with astrocytic phenotypes, understanding the role of JAK-STAT signaling in DS brain development will provide novel insight into its role in the pathogenesis of DS brain and may serve as a potential target for the development of effective therapy to improve DS cognition.

  9. Neurogenic differentiation of human umbilical cord mesenchymal stem cells on aligned electrospun polypyrrole/polylactide composite nanofibers with electrical stimulation

    NASA Astrophysics Data System (ADS)

    Zhou, Junfeng; Cheng, Liang; Sun, Xiaodan; Wang, Xiumei; Jin, Shouhong; Li, Junxiang; Wu, Qiong

    2016-09-01

    Adult central nervous system (CNS) tissue has a limited capacity to recover after trauma or disease. Recent medical cell therapy using polymeric biomaterialloaded stem cells with the capability of differentiation to specific neural population has directed focuses toward the recovery of CNS. Fibers that can provide topographical, biochemical and electrical cues would be attractive for directing the differentiation of stem cells into electro-responsive cells such as neuronal cells. Here we report on the fabrication of an electrospun polypyrrole/polylactide composite nanofiber film that direct or determine the fate of mesenchymal stem cells (MSCs), via combination of aligned surface topography, and electrical stimulation (ES). The surface morphology, mechanical properties and electric properties of the film were characterized. Comparing with that on random surface film, expression of neurofilament-lowest and nestin of human umbilical cord mesenchymal stemcells (huMSCs) cultured on film with aligned surface topography and ES were obviously enhanced. These results suggest that aligned topography combining with ES facilitates the neurogenic differentiation of huMSCs and the aligned conductive film can act as a potential nerve scaffold.

  10. Potential Role of JAK-STAT Signaling Pathway in the Neurogenic-to-Gliogenic Shift in Down Syndrome Brain

    PubMed Central

    Lee, Han-Chung; Tan, Kai-Leng; Cheah, Pike-See; Ling, King-Hwa

    2016-01-01

    Trisomy of human chromosome 21 in Down syndrome (DS) leads to several phenotypes, such as mild-to-severe intellectual disability, hypotonia, and craniofacial dysmorphisms. These are fundamental hallmarks of the disorder that affect the quality of life of most individuals with DS. Proper brain development involves meticulous regulation of various signaling pathways, and dysregulation may result in abnormal neurodevelopment. DS brain is characterized by an increased number of astrocytes with reduced number of neurons. In mouse models for DS, the pool of neural progenitor cells commits to glia rather than neuronal cell fate in the DS brain. However, the mechanism(s) and consequences of this slight neurogenic-to-gliogenic shift in DS brain are still poorly understood. To date, Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling has been proposed to be crucial in various developmental pathways, especially in promoting astrogliogenesis. Since both human and mouse models of DS brain exhibit less neurons and a higher percentage of cells with astrocytic phenotypes, understanding the role of JAK-STAT signaling in DS brain development will provide novel insight into its role in the pathogenesis of DS brain and may serve as a potential target for the development of effective therapy to improve DS cognition. PMID:26881131

  11. Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells

    PubMed Central

    2016-01-01

    Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory–motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra, we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors (Dlx, Dlx1, DMBX1/Manacle, Ets1, Gli3, KLF11, LMX1A, ZNF436, Shox1), epitheliopeptides (Arminins, PW peptide), neurosignalling components (CAMK1D, DDCl2, Inx1), ligand-ion channel receptors (CHRNA1, NaC7), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution. PMID:26598723

  12. Antiangiogenic and Neurogenic Activities of Sleeping Beauty-Mediated PEDF-Transfected RPE Cells In Vitro and In Vivo.

    PubMed

    Johnen, Sandra; Djalali-Talab, Yassin; Kazanskaya, Olga; Möller, Theresa; Harmening, Nina; Kropp, Martina; Izsvák, Zsuzsanna; Walter, Peter; Thumann, Gabriele

    2015-01-01

    Pigment epithelium-derived factor (PEDF) is a potent multifunctional protein that inhibits angiogenesis and has neurogenic and neuroprotective properties. Since the wet form of age-related macular degeneration is characterized by choroidal neovascularization (CNV), PEDF would be an ideal candidate to inhibit CNV and support retinal pigment epithelial (RPE) cells. However, its short half-life has precluded its clinical use. To deliver PEDF to the subretinal space, we transfected RPE cells with the PEDF gene using the Sleeping Beauty transposon system. Transfected cells expressed and secreted biologically active recombinant PEDF (rPEDF). In cultures of human umbilical vein endothelial cells, rPEDF reduced VEGF-induced cumulative sprouting by ≥47%, decreased migration by 77%, and increased rate of apoptosis at least 3.4 times. rPEDF induced neurite outgrowth in neuroblastoma cells and protected ganglion and photoreceptor cells in organotypic retinal cultures. In a rat model of CNV, subretinal transplantation of PEDF-transfected cells led to a reduction of the CNV area by 48% 14 days after transplantation and decreased clinical significant lesions by 55% and 40% after 7 and 14 days, respectively. We showed that transplantation of pigment epithelial cells overexpressing PEDF can restore a permissive subretinal environment for RPE and photoreceptor maintenance, while inhibiting choroidal blood vessel growth.

  13. Melatonin-receptor-1-deficiency affects neurogenic differentiation factor immunoreaction in pancreatic islets and enteroendocrine cells of mice.

    PubMed

    Shalabi, Andree; Fischer, Claudia; Korf, Horst-Werner; von Gall, Charlotte

    2013-09-01

    Neurogenic differentiation factor (NeuroD) is a transcription factor involved in the differentiation of neurons and in the control of energy balance and metabolism. It plays a key role in type 1 and type 2 diabetes. Melatonin is an important rhythmic endocrine signal within the circadian system of mammals and modulates insulin secretion and glucose metabolism. In the mouse pars tuberalis, NeuroD mRNA levels show day/night variation, which is independent of the molecular clock gene mPER1 but depends on the functional melatonin receptor 1 (MT1). So far, little is known about the effect of melatonin on NeuroD synthesis in the gastrointestinal tract. Thus, NeuroD protein levels and cellular localization were analyzed by immunohistochemistry in pancreatic islets and duodenal enteroendocrine cells of MT1- and mPER1-deficienct mice. In addition, the localization of NeuroD-positive cells was analyzed by double-immunofluorescence and confocal laser microscopy. In duodenal enteroendocrine cells and pancreatic islets of WT and PER1-deficient mice, NeuroD immunoreaction showed a peak during the early subjective night. In contrast, this peak was absent in MT1-deficent mice. These data suggest that melatonin, by acting on MT1 receptors, affects NeuroD expression in the gastrointestinal tract and thus might contribute to circadian regulation in metabolic functions.

  14. Antiangiogenic and Neurogenic Activities of Sleeping Beauty-Mediated PEDF-Transfected RPE Cells In Vitro and In Vivo

    PubMed Central

    Johnen, Sandra; Djalali-Talab, Yassin; Kazanskaya, Olga; Möller, Theresa; Harmening, Nina; Kropp, Martina; Izsvák, Zsuzsanna; Walter, Peter; Thumann, Gabriele

    2015-01-01

    Pigment epithelium-derived factor (PEDF) is a potent multifunctional protein that inhibits angiogenesis and has neurogenic and neuroprotective properties. Since the wet form of age-related macular degeneration is characterized by choroidal neovascularization (CNV), PEDF would be an ideal candidate to inhibit CNV and support retinal pigment epithelial (RPE) cells. However, its short half-life has precluded its clinical use. To deliver PEDF to the subretinal space, we transfected RPE cells with the PEDF gene using the Sleeping Beauty transposon system. Transfected cells expressed and secreted biologically active recombinant PEDF (rPEDF). In cultures of human umbilical vein endothelial cells, rPEDF reduced VEGF-induced cumulative sprouting by ≥47%, decreased migration by 77%, and increased rate of apoptosis at least 3.4 times. rPEDF induced neurite outgrowth in neuroblastoma cells and protected ganglion and photoreceptor cells in organotypic retinal cultures. In a rat model of CNV, subretinal transplantation of PEDF-transfected cells led to a reduction of the CNV area by 48% 14 days after transplantation and decreased clinical significant lesions by 55% and 40% after 7 and 14 days, respectively. We showed that transplantation of pigment epithelial cells overexpressing PEDF can restore a permissive subretinal environment for RPE and photoreceptor maintenance, while inhibiting choroidal blood vessel growth. PMID:26697494

  15. Acute abdomen caused by bladder rupture attributable to neurogenic bladder dysfunction following a stroke: a case report

    PubMed Central

    2011-01-01

    Introduction Spontaneous bladder rupture is a rare and serious event with high mortality. It is not often considered in the patient presenting with peritonitis. This often leads to delays in diagnosis. There are very few case reports of true spontaneous rupture in the literature. This is the first such reported case in which bladder rupture was attributable to neurogenic bladder dysfunction following a stroke. Case presentation We report the case of a 67-year-old Caucasian man who presented with lower abdominal pain and a peritonitic abdomen. He had a long-term urethral catheter because of urinary retention following a previous stroke. He was treated conservatively with antibiotics before a surgical opinion was sought. Exploratory laparotomy confirmed the diagnosis of spontaneous bladder rupture. After repair of the defect, he eventually made a full recovery. Conclusion In this unusual case report, we describe an example of a serious event in which delays in diagnosis may lead to increased morbidity and mortality. To date, no unifying theory explaining why rupture occurs has been postulated. We conducted a thorough literature search to examine the etiological factors in other published cases. These etiological factors either increase intra-vesical pressure or decrease the strength of the bladder wall. We hope that by increasing awareness of these etiological factors, spontaneous bladder rupture may be diagnosed earlier and appropriate therapy started. PMID:21714888

  16. An interneuron progenitor maintains neurogenic potential in vivo and differentiates into GABAergic interneurons after transplantation in the postnatal rat brain.

    PubMed

    Wang, Qi; Hong, Peiwei; Gao, Hui; Chen, Yuntian; Yang, Qi; Jiang, Mei; Li, Hedong

    2016-01-11

    Dysfunction of cortical GABAergic interneurons are involved in numerous neurological disorders including epilepsy, schizophrenia and autism; and replenishment of these cells by transplantation strategy has proven to be a feasible and effective method to help revert the symptoms in several animal models. To develop methodology of generating transplantable GABAergic interneurons for therapy, we previously reported the isolation of a v-myc-induced GABAergic interneuron progenitor clone GE6 from embryonic ganglionic eminence (GE). These cells can proliferate and form functional inhibitory synapses in culture. Here, we tested their differentiation behavior in vivo by transplanting them into the postnatal rat forebrain. We found that GE6 cells migrate extensively in the neonatal forebrain and differentiate into both neurons and glia, but preferentially into neurons when compared with a sister progenitor clone CTX8. The neurogenic potential of GE6 cells is also maintained after transplantation into a non-permissive environment such as adult cortex or when treated with inflammatory cytokine in culture. The GE6-derived neurons were able to mature in vivo as GABAergic interneurons expressing GABAergic, not glutamatergic, presynaptic puncta. Finally, we propose that v-myc-induced human interneuron progenitor clones could be an alternative cell source of transplantable GABAergic interneurons for treating related neurological diseases in future clinic.

  17. Differential regulation of cell proliferation in neurogenic zones in mice lacking cystine transport by xCT

    SciTech Connect

    Liu, Richard R.; Brown, Craig E.; Murphy, Timothy H.

    2007-12-21

    The cystine/glutamate exchanger (xCT) supplies intracellular cyst(e)ine for the production of glutathione, a major cellular anti-oxidant. xCT is enriched in brain regions associated with neurogenesis. Previous studies have shown that the malfunction of this protein greatly attenuates cell proliferation in vitro and is associated with brain atrophy in vivo. Using mice that are homozygous for a function-blocking deletion in xCT (Sut mice), we examined in vivo the role of xCT in cell proliferation in neurogenic regions of the subventricular zone (SVZ) and denate gyrus (DG) in the adult brain. Our results indicate that a high level of cellular proliferation in the adult brain persists even in the absence of functional xCT. Furthermore, in both young adult and middle-aged mice (3 and 11 months old), rates of SVZ cell proliferation were comparable between Sut and wild-type controls, although there was trend towards reduced proliferation in Sut mice (12% and 9% reduction, respectively). To our surprise, rates of cell proliferation in the DG were elevated in both 3- and 11-month-old Sut mice relative to controls (22% and 28% increase, respectively). These results demonstrate that xCT expression plays a role in regulating cellular proliferation in the DG, but not the SVZ of adult mice. Furthermore, unlike previous in vitro studies, our in vivo observations clearly indicate that xCT is not essential for ongoing cellular proliferation.

  18. Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells.

    PubMed

    Wenger, Y; Buzgariu, W; Galliot, B

    2016-01-05

    Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory-motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra, we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors (Dlx, Dlx1, DMBX1/Manacle, Ets1, Gli3, KLF11, LMX1A, ZNF436, Shox1), epitheliopeptides (Arminins, PW peptide), neurosignalling components (CAMK1D, DDCl2, Inx1), ligand-ion channel receptors (CHRNA1, NaC7), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution.

  19. The role of brain-derived neurotrophic factor (BDNF) in the development of neurogenic detrusor overactivity (NDO).

    PubMed

    Frias, Bárbara; Santos, João; Morgado, Marlene; Sousa, Mónica Mendes; Gray, Susannah M Y; McCloskey, Karen D; Allen, Shelley; Cruz, Francisco; Cruz, Célia Duarte

    2015-02-04

    Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients.

  20. Neurogenic and non-neurogenic bladder dysfunction.

    PubMed

    Nijman, R J

    2001-11-01

    Children with a neurological defect have a clear cause for their bladder dysfunction; however, in neurologically normal children the cause of their incontinence is usually unclear. When no anatomical abnormalities seem to be present a functional problem is generally the cause. This type of incontinence is referred to as 'functional incontinence'. The different forms of bladder and sphincter dysfunction will be discussed and treatment modalities described. As the treatment modalities in children with neuropathic bladders focus on medical and especially surgical options, special attention is paid to new developments in surgical treatment. For those with functional incontinence treatment options are more variable and the new developments are described.

  1. Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus

    PubMed Central

    Hattiangady, Bharathi

    2016-01-01

    As clinical application of neural stem cell (NSC) grafting into the brain would also encompass aged people, critical evaluation of engraftment of NSC graft-derived cells in the aged hippocampus has significance. We examined the engraftment and differentiation of alkaline phosphatase-positive NSCs expanded from the postnatal subventricular zone (SVZ), 3 months after grafting into the intact young or aged rat hippocampus. Graft-derived cells engrafted robustly into both young and aged hippocampi. Although most graft-derived cells pervasively migrated into different hippocampal layers, the graft cores endured and contained graft-derived neurons expressing neuron-specific nuclear antigen (NeuN) and γ-amino butyric acid in both groups. A fraction of migrated graft-derived cells in the neurogenic subgranular zone-granule cell layer also expressed NeuN. Neuronal differentiation was, however, occasionally seen amid graft-derived cells that had migrated into non-neurogenic regions, where substantial fractions differentiated into S-100β+ astrocytes, NG2+ oligodendrocyte progenitors, or Olig2+ putative oligodendrocytes. In both age groups, graft cores located in non-neurogenic regions displayed many doublecortin-positive (DCX+) immature neurons at 3 months after grafting. Analyses of cells within graft cores using birth dating and putative NSC markers revealed that DCX+ neurons were newly born neurons derived from engrafted cells and that putative NSCs persisted within the graft cores. Thus, both young and aged hippocampi support robust engraftment and similar differentiation of SVZ-NSC graft-derived cells. Furthermore, some grafted NSCs retain the “stemness” feature and produce new neurons even at 3 months after grafting, implying that grafting of SVZ-NSCs into the young or aged hippocampus leads to establishment of new neurogenic niches in non-neurogenic regions. Significance The results demonstrate that advanced age of the host at the time of grafting has no major

  2. A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA.

    PubMed

    Hwang, Do Won; Son, Sejin; Jang, Jaeho; Youn, Hyewon; Lee, Song; Lee, Duhwan; Lee, Yun-Sang; Jeong, Jae Min; Kim, Won Jong; Lee, Dong Soo

    2011-07-01

    Recent advances in efficient microRNA (miRNA) delivery techniques using brain-targeted nanoparticles offer critical information for understanding the functional role of miRNAs in vivo, and for supporting targeted gene therapy in terms of treating miRNA-associated neurological diseases. Here, we report the rabies virus glycoprotein (RVG)-labeled non-toxic SSPEI nanomaterials capable of neuron-specific miR-124a delivery to neuron in vivo. The RVG-labeled BPEI-SS (RVG-SSPEI) nanocarrier showed less toxicity in acetylcholine receptor-positive Neuro2a cells, and electrostatic interaction of RVG-SSPEI with miR-124a exhibited optimal transfection efficacy. The RVG-SSPEI polymer specifically targeted Neuro2a using cy5.5-miR-124a mixed with RVG-SSPEI. The functional action of miR-124a oligomers released from polyplexes in the cytoplasmic region was evaluated by a reporter vector containing a miR-124a -binding sequence, and showed a significantly reduced reporter signal in a dose-dependent manner. Cy5.5-miR-124a/RVG-SSPEI- injected into mice via tail veins displayed the enhanced accumulation of miR-124a in the isolated brain. Hindrance of the efficient penetration of neuronal cells by size limitation of the miR-124a/RVG-SSPEI improved with the help of mannitol through blood-brain barrier disruption. These findings indicated that the RVG peptide combined with mannitol infusion using SSPEI polymer for neuron-specific targeting in vivo is sufficient to deliver neurogenic microRNA into the brain.

  3. NTPDase2 and purinergic signaling control progenitor cell proliferation in neurogenic niches of the adult mouse brain.

    PubMed

    Gampe, Kristine; Stefani, Jennifer; Hammer, Klaus; Brendel, Peter; Pötzsch, Alexandra; Enikolopov, Grigori; Enjyoji, Keiichi; Acker-Palmer, Amparo; Robson, Simon C; Zimmermann, Herbert

    2015-01-01

    Nerve cells are continuously generated from stem cells in the adult mammalian subventricular zone (SVZ) and hippocampal dentate gyrus. We have previously noted that stem/progenitor cells in the SVZ and the subgranular layer (SGL) of the dentate gyrus express high levels of plasma membrane-bound nucleoside triphosphate diphosphohydrolase 2 (NTPDase2), an ectoenzyme that hydrolyzes extracellular nucleoside diphosphates and triphosphates. We inferred that deletion of NTPDase2 would increase local extracellular nucleoside triphosphate concentrations perturbing purinergic signaling and boosting progenitor cell proliferation and neurogenesis. Using newly generated mice globally null for Entpd2, we demonstrate that NTPDase2 is the major ectonucleotidase in these progenitor cell-rich areas. Using BrdU-labeling protocols, we have measured stem cell proliferation and determined long-term survival of cell progeny under basal conditions. Brains of Entpd2 null mice revealed increased progenitor cell proliferation in both the SVZ and the SGL. However, this occurred without noteworthy alterations in long-term progeny survival. The hippocampal stem cell pool and the pool of the intermediate progenitor type-2 cells clearly expanded. However, substantive proportions of these proliferating cells were lost during expansion at around type-3 stage. Cell loss was paralleled by decreases in cAMP response element-binding protein phosphorylation in the doublecortin-positive progenitor cell population and by an increase in labeling for activated caspase-3 levels. We propose that NTPDase2 has functionality in scavenging mitogenic extracellular nucleoside triphosphates in neurogenic niches of the adult brain, thereby acting as a homeostatic regulator of nucleotide-mediated neural progenitor cell proliferation and expansion.

  4. TRPA1 activation leads to neurogenic vasodilatation: involvement of reactive oxygen nitrogen species in addition to CGRP and NO

    PubMed Central

    Aubdool, Aisah A; Kodji, Xenia; Abdul‐Kader, Nayaab; Heads, Richard; Fernandes, Elizabeth S; Bevan, Stuart

    2016-01-01

    Abstract Background and Purpose Transient receptor potential ankyrin‐1 (TRPA1) activation is known to mediate neurogenic vasodilatation. We investigated the mechanisms involved in TRPA1‐mediated peripheral vasodilatation in vivo using the TRPA1 agonist cinnamaldehyde. Experimental Approach Changes in vascular ear blood flow were measured in anaesthetized mice using laser Doppler flowmetry. Key Results Topical application of cinnamaldehyde to the mouse ear caused a significant increase in blood flow in the skin of anaesthetized wild‐type (WT) mice but not in TRPA1 knockout (KO) mice. Cinnamaldehyde‐induced vasodilatation was inhibited by the pharmacological blockade of the potent microvascular vasodilator neuropeptide CGRP and neuronal NOS‐derived NO pathways. Cinnamaldehyde‐mediated vasodilatation was significantly reduced by treatment with reactive oxygen nitrogen species (RONS) scavenger such as catalase and the SOD mimetic TEMPOL, supporting a role of RONS in the downstream vasodilator TRPA1‐mediated response. Co‐treatment with a non‐selective NOS inhibitor L‐NAME and antioxidant apocynin further inhibited the TRPA1‐mediated vasodilatation. Cinnamaldehyde treatment induced the generation of peroxynitrite that was blocked by the peroxynitrite scavenger FeTPPS and shown to be dependent on TRPA1, as reflected by an increase in protein tyrosine nitration in the skin of WT, but not in TRPA1 KO mice. Conclusion and Implications This study provides in vivo evidence that TRPA1‐induced vasodilatation mediated by cinnamaldehyde requires neuronal NOS‐derived NO, in addition to the traditional neuropeptide component. A novel role of peroxynitrite is revealed, which is generated downstream of TRPA1 activation by cinnamaldehyde. This mechanistic pathway underlying TRPA1‐mediated vasodilatation may be important in understanding the role of TRPA1 in pathophysiological situations. PMID:27189253

  5. The role of FDG PET/CT in evaluation of mediastinal masses and neurogenic tumors of chest wall

    PubMed Central

    Tatci, Ebru; Ozmen, Ozlem; Dadali, Yeliz; Biner, Inci Uslu; Gokcek, Atila; Demirag, Funda; Incekara, Funda; Arslan, Nuri

    2015-01-01

    We evaluated the efficiency of FDG PET/CT for the differentiation of malignant from benign mediastinal masses and neurogenic tumors of chest-wall. Methods: The 88 patients with chest wall-mediastinal masses who underwent examination before operation were retrospectively reviewed. Size, CT density (HU mean) and SUVmax of mediastinal and chest wall lesions were determined. Statistical differences of these parameters were compared between groups by Mann-Whitney U test. Receiver-operating characteristic curve (ROC) analysis with respect to SUVmax was performed to determine the best cutoff value for differentiating benign from malignant masses. Results: The overall sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of PET/CT in detection of malignancy were 90%, 55.17%, 67%, 50.94% and 91.43%, respectively. The SUVmax, HU mean and size were higher in malignant cases (P < 0.05). To distinguish benign and malignant lesions, the cut off value of SUVmax was 4.67. The lesion SUVmax was significantly associated with the lesion size and lesion HU mean values (P < 0.05). The value of SUVmax and HU mean were higher in solid benign lesions than those of cystic benign lesions (P < 0.05). The lesion size was higher in cystic lesions (P = 0.000). The mean SUVmax was significantly higher in invasive thymomas than those of non-invasive forms (P = 0.029). Conclusion: FDG PET/CT may be complementary to conventional imaging methods for the evaluation of mediastinal and chest wall masses. PET/CT may reduce unnecessary invasive investigations for diagnosis in patients with nonavid or low avid FDG lesions. However confirmatory tissue sampling is required to confirm PET positive findings for the definite diagnosis. PMID:26379916

  6. Salvinorin A inhibits colonic transit and neurogenic ion transport in mice by activating kappa-opioid and cannabinoid receptors.

    PubMed

    Fichna, J; Schicho, R; Andrews, C N; Bashashati, M; Klompus, M; McKay, D M; Sharkey, K A; Zjawiony, J K; Janecka, A; Storr, M A

    2009-12-01

    The major active ingredient of the plant Salvia divinorum, salvinorin A (SA) has been used to treat gastrointestinal (GI) symptoms. As the action of SA on the regulation of colonic function is unknown, our aim was to examine the effects of SA on mouse colonic motility and secretion in vitro and in vivo. The effects of SA on GI motility were studied using isolated preparations of colon, which were compared with preparations from stomach and ileum. Colonic epithelial ion transport was evaluated using Ussing chambers. Additionally, we studied GI motility in vivo by measuring colonic propulsion, gastric emptying, and upper GI transit. Salvinorin A inhibited contractions of the mouse colon, stomach, and ileum in vitro, prolonged colonic propulsion and slowed upper GI transit in vivo. Salvinorin A had no effect on gastric emptying in vivo. Salvinorin A reduced veratridine-, but not forskolin-induced epithelial ion transport. The effects of SA on colonic motility in vitro were mediated by kappa-opioid receptors (KORs) and cannabinoid (CB) receptors, as they were inhibited by the antagonists nor-binaltorphimine (KOR), AM 251 (CB(1) receptor) and AM 630 (CB(2) receptor). However, in the colon in vivo, the effects were largely mediated by KORs. The effects of SA on veratridine-mediated epithelial ion transport were inhibited by nor-binaltorphimine and AM 630. Salvinorin A slows colonic motility in vitro and in vivo and influences neurogenic ion transport. Due to its specific regional action, SA or its derivatives may be useful drugs in the treatment of lower GI disorders associated with increased GI transit and diarrhoea.

  7. Diminished Neurogenic Femoral Artery Vasoconstrictor Response in a Zucker Obese Rat Model: Differential Regulation of NOS and COX Derivatives

    PubMed Central

    Martínez, Ana Cristina; Hernández, Medardo; Novella, Susana; Martínez, María Pilar; Pagán, Rosa María; Hermenegildo, Carlos; García-Sacristán, Albino; Prieto, Dolores; Benedito, Sara

    2014-01-01

    Objective Peripheral arterial disease is one of the macrovascular complications of type 2 diabetes mellitus. This study addresses femoral artery regulation in a prediabetic model of obese Zucker rats (OZR) by examining cross-talk between endothelial and neural factors. Methods and Results Arterial preparations from lean (LZR) and OZR were subjected to electrical field stimulation (EFS) on basal tone. Nitric oxide synthase (NOS) and cyclooxygenase (COX) isoform expression patterns were determined by immunohistochemical labelling and Western blotting. Results indicate significantly reduced noradrenergic contractions in preparations from OZR compared with those of LZR. Functional inhibition of endothelial NOS (eNOS) indicated a predominant role of this isoform in LZR and its modified activity in OZR. Neural (nNOS) and inducible NOS (iNOS) were activated and their expression was higher in femoral arteries from OZR. Neurotransmission modulated by large-conductance Ca2+-activated (BKCa) or voltage-dependent (KV) K+ channels did not seem compromised in the obese animals. Endothelial COX-1 and COX-2 were expressed in LZR and an additional adventitial location of COX-2 was also observed in OZR, explaining the higher COX-2 protein levels detected in this group. Prostanoids derived from both isoforms helped maintain vasoconstriction in LZR while in OZR only COX-2 was active. Superoxide anion inhibition reduced contractions in endothelium-intact arteries from OZR. Conclusions Endothelial dysfunction led to reduced neurogenic vasoconstriction in femoral arteries from OZR. In a setting of obesity, NO-dependent nNOS and iNOS dilation activity could be an alternative mechanism to offset COX-2- and reactive oxygen species-mediated vasoconstriction, along with impaired endothelial NO relaxation. PMID:25216050

  8. Observations on the Use of Seprafilm® on the Brachial Plexus in 249 Operations for Neurogenic Thoracic Outlet Syndrome

    PubMed Central

    Hammond, Sharon L.; Rao, Neal M.

    2007-01-01

    Purpose Seprafilm® was initially used successfully as a membrane to reduce abdominal adhesions. Subsequently it was tried in a number of other areas to reduce postoperative scarring. Seprafilm® was employed in this study to see if it would reduce postoperative scarring after supraclavicular thoracic outlet decompression for neurogenic thoracic outlet syndrome (NTOS). Material and methods There were 249 operations for primary NTOS (185) and recurrent NTOS (64). Seprafilm® was applied to the nerve roots at the end of each procedure. Diagnosis was established by careful history and extensive physical exam consisting of several provocative maneuvers. Scalene muscle block confirmed the diagnosis. Results Success rates for primary operations, 1–2 years postoperation were 74% for scalenectomy without first rib resection and 70% for scalenectomy with first rib resection. For reoperations, success rate for scalenectomy and neurolysis after transaxillary rib resection was 78% whereas success rate for neurolysis after supraclavicular scalenectomy was 68%. Seprafilm® did not significantly improve overall results compared to our results 15 years ago, although in reoperations there was a trend toward improvement with Seprafilm®. Observations in 10 reoperations after use of Seprafilm® revealed that there were fewer adhesions between fat pad and nerve roots, making it much easier to find the nerve roots. Recurrence was because of scar formation around individual nerve roots. Conclusion Seprafilm® made reoperations easier by reducing scarring between scalene fat pad and brachial plexus. However, it did not prevent scar tissue forming around the individual nerve roots nor did it significantly lower the failure rate for primary operations. The trend supported the use of Seprafilm® in reoperations. PMID:18780049

  9. Influence of enrichment on behavioral and neurogenic effects of antidepressants in Wistar rats submitted to repeated forced swim test.

    PubMed

    Possamai, Fernanda; dos Santos, Juliano; Walber, Thais; Marcon, Juliana C; dos Santos, Tiago Souza; Lino de Oliveira, Cilene

    2015-04-03

    Repeated forced swimming test (rFST) may detect gradual effects of antidepressants in adult rats. Antidepressants, as enrichment, affected behavior and neurogenesis in rats. However, the influence of enrichment on behavioral and neurogenic effects of antidepressants is unknown. Here, effects of antidepressants on rFST and hippocampal neurogenesis were investigated in rats under enriched conditions. Behaviors of male Wistar rats, housed from weaning in standard (SE) or enriched environment (EE), were registered during rFST. The rFST consisted of 15min of swimming (pretest) followed by 5min of swimming in the first (test), seventh (retest 1) and fourteenth (retest 2) days after pretest. One hour before the test, rats received an intraperitoneal injection of saline (1ml/kg), fluoxetine (2.5mg/kg) or imipramine (2.5 or 5mg/kg). These treatments were performed daily until the day of the retest 2. After retest 2, rats were euthanized for the identification of markers for neurogenesis in the hippocampus. Fluoxetine or imipramine decreased immobility in retests 1 and 2, as compared to saline. EE abolished these differences. In EE, fluoxetine or imipramine (5mg/kg) reduced immobility time in retest 2, as compared to the test. Independent of the housing conditions, fluoxetine and imipramine (5mg/kg) increased the ratio of immature neurons per progenitor cell in the hippocampus. In summary, antidepressants or enrichment counteracted the high immobility in rFST. Enrichment changed the effects of antidepressants in rFST depending on the type, and the dose of a substance but failed to change neurogenesis in control or antidepressant treated-rats. Effects of antidepressants and enrichment on rFST seemed neurogenesis-independent.

  10. Neurogenic Maturation of Human Dental Pulp Stem Cells Following Neurosphere Generation Induces Morphological and Electrophysiological Characteristics of Functional Neurons

    PubMed Central

    Struys, Tom; Hilkens, Petra; Bronckaers, Annelies; Ratajczak, Jessica; Politis, Constantinus; Brône, Bert; Lambrichts, Ivo; Martens, Wendy

    2015-01-01

    Cell-based therapies are emerging as an alternative treatment option to promote functional recovery in patients suffering from neurological disorders, which are the major cause of death and permanent disability. The present study aimed to differentiate human dental pulp stem cells (hDPSCs) toward functionally active neuronal cells in vitro. hDPSCs were subjected to a two-step protocol. First, neuronal induction was acquired through the formation of neurospheres, followed by neuronal maturation, based on cAMP and neurotrophin-3 (NT-3) signaling. At the ultrastructural level, it was shown that the intra-spheral microenvironment promoted intercellular communication. hDPSCs grew out of the neurospheres in vitro and established a neurogenic differentiated hDPSC culture (d-hDPSCs) upon cAMP and NT-3 signaling. d-hDPSCs were characterized by the increased expression of neuronal markers such as neuronal nuclei, microtubule-associated protein 2, neural cell adhesion molecule, growth-associated protein 43, synapsin I, and synaptophysin compared with nondifferentiated hDPSCs. Enzyme-linked immunosorbent assay demonstrated that the secretion of brain-derived neurotrophic factor, vascular endothelial growth factor, and nerve growth factor differed between d-hDPSCs and hDPSCs. d-hDPSCs acquired neuronal features, including multiple intercommunicating cytoplasmic extensions and increased vesicular transport, as shown by the electron microscopic observation. Patch clamp analysis demonstrated the functional activity of d-hDPSCs by the presence of tetrodotoxin- and tetraethyl ammonium-sensitive voltage-gated sodium and potassium channels, respectively. A subset of d-hDPSCs was able to fire a single action potential. The results reported in this study demonstrate that hDPSCs are capable of neuronal commitment following neurosphere formation, characterized by distinct morphological and electrophysiological properties of functional neuronal cells. PMID:25203005

  11. The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondrial stressor rotenone

    SciTech Connect

    Baxter, Kristin Kathleen; Uittenbogaard, Martine; Chiaramello, Anne

    2012-10-15

    The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial biogenesis and bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. -- Highlights: Black-Right-Pointing-Pointer NeuroD6 induces mitochondrial biogenesis in neuroprogenitor-like cells. Black-Right-Pointing-Pointer NeuroD6 augments the bioenergetic reserve of the neuronal PC12-NeuroD6 cells. Black-Right-Pointing-Pointer NeuroD6 increases the mitochondrial membrane potential and ATP levels. Black-Right-Pointing-Pointer NeuroD6 confers tolerance to rotenone via an adaptive

  12. Botulinum neurotoxin type A (BoNTA) decreases the mechanical sensitivity of nociceptors and inhibits neurogenic vasodilation in a craniofacial muscle targeted for migraine prophylaxis.

    PubMed

    Gazerani, Parisa; Au, Sammy; Dong, Xudong; Kumar, Ujendra; Arendt-Nielsen, Lars; Cairns, Brian E

    2010-12-01

    The mechanism by which intramuscular injection of BoNTA into the craniofacial muscles decreases migraine headaches is not known. In a blinded study, the effect of BoNTA on the mechanical and chemical responsiveness of individual temporalis muscle nociceptors and muscle neurogenic vasodilation was investigated in female rats. Mechanical threshold was measured for 3h following intramuscular injection of BoNTA or vehicle, and for 10 min after a subsequent injection of the algogen glutamate. Injection of BoNTA significantly increased the mechanical threshold of muscle nociceptors without altering the muscle surface temperature and blocked glutamate-induced mechanical sensitization and neurogenic vasodilation. None of these effects were reproduced by pancuronium-induced muscle paralysis. Western blot analysis of temporalis muscles indicated that BoNTA significantly decreased SNAP-25. Measurement of interstitial glutamate concentration with a glutamate biosensor indicated that BoNTA significantly reduced glutamate concentrations. The mechanical sensitivity of muscle nociceptors is modulated by glutamate concentration through activation of peripheral NMDA receptors. Immunohistochemical experiments were conducted and they indicated that half of the NMDA-expressing temporalis nerve fibers co-expressed substance P or CGRP. Additional electrophysiology experiments examined the effect of antagonists for NMDA, CGRP and NK1 receptors on glutamate-induced effects. Glutamate-induced mechanical sensitization was only blocked by the NMDA receptor antagonist, but muscle neurogenic vasodilation was attenuated by NMDA or CGRP receptor antagonists. These data suggest that injection of BoNTA into craniofacial muscles acts to decrease migraine headaches by rapidly decreasing the mechanical sensitivity of temporalis muscle nociceptors through inhibition of glutamate release and by attenuating the provoked release of CGRP from muscle nociceptors.

  13. Neurogenic Potential of the Vestibular Nuclei and Behavioural Recovery Time Course in the Adult Cat Are Governed by the Nature of the Vestibular Damage

    PubMed Central

    Dutheil, Sophie; Lacour, Michel; Tighilet, Brahim

    2011-01-01

    Functional and reactive neurogenesis and astrogenesis are observed in deafferented vestibular nuclei after unilateral vestibular nerve section in adult cats. The newborn cells survive up to one month and contribute actively to the successful recovery of posturo-locomotor functions. This study investigates whether the nature of vestibular deafferentation has an incidence on the neurogenic potential of the vestibular nuclei, and on the time course of behavioural recovery. Three animal models that mimic different vestibular pathologies were used: unilateral and permanent suppression of vestibular input by unilateral vestibular neurectomy (UVN), or by unilateral labyrinthectomy (UL, the mechanical destruction of peripheral vestibular receptors), or unilateral and reversible blockade of vestibular nerve input using tetrodotoxin (TTX). Neurogenesis and astrogenesis were revealed in the vestibular nuclei using bromodeoxyuridine (BrdU) as a newborn cell marker, while glial fibrillary acidic protein (GFAP) and glutamate decarboxylase 67 (GAD67) were used to identify astrocytes and GABAergic neurons, respectively. Spontaneous nystagmus and posturo-locomotor tests (static and dynamic balance performance) were carried out to quantify the behavioural recovery process. Results showed that the nature of vestibular loss determined the cellular plastic events occurring in the vestibular nuclei and affected the time course of behavioural recovery. Interestingly, the deafferented vestibular nuclei express neurogenic potential after acute and total vestibular loss only (UVN), while non-structural plastic processes are involved when the vestibular deafferentation is less drastic (UL, TTX). This is the first experimental evidence that the vestibular complex in the brainstem can become neurogenic under specific injury. These new data are of interest for understanding the factors favouring the expression of functional neurogenesis in adult mammals in a brain repair perspective, and are of

  14. RF-EMF exposure at 1800 MHz did not elicit DNA damage or abnormal cellular behaviors in different neurogenic cells.

    PubMed

    Su, Liling; Wei, Xiaoxia; Xu, Zhengping; Chen, Guangdi

    2017-04-01

    Despite many years of studies, the debate on genotoxic effects of radiofrequency electromagnetic fields (RF-EMF) continues. To systematically evaluate genotoxicity of RF-EMF, this study examined effects of RF-EMF on DNA damage and cellular behavior in different neurogenic cells. Neurogenic A172, U251, and SH-SY5Y cells were intermittently (5 min on/10 min off) exposed to 1800 MHz RF-EMF at an average specific absorption rate (SAR) of 4.0 W/kg for 1, 6, or 24 h. DNA damage was evaluated by quantification of γH2AX foci, an early marker of DNA double-strand breaks. Cell cycle progression, cell proliferation, and cell viability were examined by flow cytometry, hemocytometer, and cell counting kit-8 assay, respectively. Results showed that exposure to RF-EMF at an SAR of 4.0 W/kg neither significantly induced γH2AX foci formation in A172, U251, or SH-SY5Y cells, nor resulted in abnormal cell cycle progression, cell proliferation, or cell viability. Furthermore, prolonged incubation of these cells for up to 48 h after exposure did not significantly affect cellular behavior. Our data suggest that 1800 MHz RF-EMF exposure at 4.0 W/kg is unlikely to elicit DNA damage or abnormal cellular behaviors in neurogenic cells. Bioelectromagnetics. 38:175-185, 2017. © 2016 Wiley Periodicals, Inc.

  15. Roles of TRPV1 and neuropeptidergic receptors in dorsal root reflex-mediated neurogenic inflammation induced by intradermal injection of capsaicin

    PubMed Central

    Lin, Qing; Li, Dingge; Xu, Xijin; Zou, Xiaoju; Fang, Li

    2007-01-01

    Background Acute cutaneous neurogenic inflammation initiated by activation of transient receptor potential vanilloid-1 (TRPV1) receptors following intradermal injection of capsaicin is mediated mainly by dorsal root reflexes (DRRs). Inflammatory neuropeptides are suggested to be released from primary afferent nociceptors participating in inflammation. However, no direct evidence demonstrates that the release of inflammatory substances is due to the triggering of DRRs and how activation of TRPV1 receptors initiates neurogenic inflammation via triggering DRRs. Results Here we used pharmacological manipulations to analyze the roles of TRPV1 and neuropeptidergic receptors in the DRR-mediated neurogenic inflammation induced by intradermal injection of capsaicin. The degree of cutaneous inflammation in the hindpaw that followed capsaicin injection was assessed by measurements of local blood flow (vasodilation) and paw-thickness (edema) of the foot skin in anesthetized rats. Local injection of capsaicin, calcitonin gene-related peptide (CGRP) or substance P (SP) resulted in cutaneous vasodilation and edema. Removal of DRRs by either spinal dorsal rhizotomy or intrathecal administration of the GABAA receptor antagonist, bicuculline, reduced dramatically the capsaicin-induced vasodilation and edema. In contrast, CGRP- or SP-induced inflammation was not significantly affected after DRR removal. Dose-response analysis of the antagonistic effect of the TRPV1 receptor antagonist, capsazepine administered peripherally, shows that the capsaicin-evoked inflammation was inhibited in a dose-dependent manner, and nearly completely abolished by capsazepine at doses between 30–150 μg. In contrast, pretreatment of the periphery with different doses of CGRP8–37 (a CGRP receptor antagonist) or spantide I (a neurokinin 1 receptor antagonist) only reduced the inflammation. If both CGRP and NK1 receptors were blocked by co-administration of CGRP8–37 and spantide I, a stronger

  16. Hemorrhagic onset of hemangioblastoma located in the dorsal medulla oblongata presenting with tako-tsubo cardiomyopathy and neurogenic pulmonary edema: a case report.

    PubMed

    Gekka, Masayuki; Yamaguchi, Shigeru; Kazumata, Ken; Kobayashi, Hiroyuki; Motegi, Hiroaki; Terasaka, Shunsuke; Houkin, Kiyohiro

    2014-01-01

    Here, we present a case of dorsal medulla oblongata hemangioblastoma with fourth ventricular hemorrhage. A 23-year-old female developed sudden consciousness disturbance, and CT revealed hemorrhage in all cerebral ventricles and a hyperdense mass in the cisterna magna. Although the reddish tumor located in the dorsal medulla oblongata was successfully removed, she suffered from severe tako-tsubo cardiomyopathy (TTC) and neurogenic pulmonary edema (NPE) because of baroreflex failure and damage to the solitary tract nuclei. After intensive care for 12 weeks following surgery, she was discharged without any neurological or radiological deficits. Pathogenesis of TTC/NPE is discussed in this paper.

  17. TRPA1 ion channel in the spinal dorsal horn as a therapeutic target in central pain hypersensitivity and cutaneous neurogenic inflammation.

    PubMed

    Pertovaara, Antti; Koivisto, Ari

    2011-09-01

    Transient receptor potential ankyrin 1 (TRPA1) is a non-selective, calcium permeable cation channel expressed by a subpopulation of primary afferent nociceptive nerve fibers. On peripheral nerve endings, TRPA1 channel contributes to transduction of chemical and physical stimuli, whereas on the central endings in the spinal dorsal horn, which is the topic of this brief review, it regulates glutamatergic transmission. Blockade of the spinal TRPA1 channel has attenuated mechanical pain hypersensitivity particularly to low-intensity stimulation in various pathophysiological conditions, whereas blockade of the TRPA1 channel-mediated regulation of transmission failed to influence baseline pain behavior in healthy control animals. Additionally, blockade of the spinal TRPA1 channel reduced cutaneous neurogenic inflammation, presumably by decreasing drive of spinal interneurons that induce a proinflammatory dorsal root reflex. The spinal TRPA1 channel provides a promising target for development of a selective disease-modifying therapy for central pain hypersensitivity. Blockade of the spinal TRPA1 channel-mediated regulation of transmission may also attenuate cutaneous neurogenic inflammation.

  18. Identification of a sustained neurogenic zone at the dorsal surface of the adult mouse hippocampus and its regulation by the chemokine SDF-1.

    PubMed

    Belmadani, Abdelhak; Ren, Dongjun; Bhattacharyya, Bula J; Rothwangl, Katharina B; Hope, Thomas J; Perlman, Harris; Miller, Richard J

    2015-11-01

    We identified a previously unknown neurogenic region at the dorsal surface of the hippocampus; (the "subhippocampal zone," SHZ) in the adult brain. Using a reporter mouse in which SHZ cells and their progeny could be traced through the expression of EGFP under the control of the CXCR4 chemokine receptor promoter we observed the presence of a pool of EGFP expressing cells migrating in direction of the dentate gyrus (DG), which is maintained throughout adulthood. This population appeared to originate from the SHZ where cells entered a caudal migratory stream (aCMS) that included the fimbria, the meninges and the DG. Deletion of CXCR4 from neural stem cells (NSCs) or neuroinflammation resulted in the appearance of neurons in the DG, which were the result of migration of NSCs from the SHZ. Some of these neurons were ectopically placed. Our observations indicate that the SHZ is a neurogenic zone in the adult brain through migration of NSCs in the aCMS. Regulation of CXCR4 signaling in these cells may be involved in repair of the DG and may also give rise to ectopic granule cells in the DG in the context of neuropathology.

  19. Quick note on tissue engineering-based surgical measures to treat patients with neurogenic bladder-due detrusor/sphincter dyssynergia.

    PubMed

    Alberti, Contardo

    2015-01-01

    To treat the neurogenic bladder-due detrusor/urethral rhabdosphincter dyssynergia, early combined clean intermittent catheterization/ pharmacotherapy (anticholinergic-, β3-adrenoceptor agonist drugs) management may be at times crowned with success of preserving an adequate bladder compliance and renal safe conditions.The persistence, instead, of elevated bladder filling pressure levels with high voiding pressure/uroflow values, together with aberrant urethral rhabdosphincter electromyographic findings, make necessary the resort to surgery strategies, among which - a part from rhabdosphincterotomy or alternatively intrasphincteric botulinum A toxin injection or urethral stent insertion - the bladder augmentation cystoplasty, with either reconfigurated bowel- or gastric segment, is today the most efficacious surgical measure to increase the bladder urinary storage meanwhile lowering bladder filling pressure. Given the enterocistoplasty-dependent both potential systemic metabolic imbalances - such as hyperchloremic acidosis/hypokaliemia, hyperoxaluria, bone demineralization, chologenic diarrhoea/steatorrhoea, vit B12 deficiency - together with bowel prosthetic mucus overproduction-due recurrent stone formation, and, sometimes, malignant complications particularly at the intestinal-urinary tract suture line, tissue engineering techniques have been taken into consideration, more than twenty years ago, as alternative measure for bladder augmentation cystoplasty, until to reach successful clinical validation just in patients suffering from either congenital dysraphism- or acquired spinal cord injury-dependent neurogenic bladder. Nevertheless, also the tissue engineering-made augmentation cistoplasty, as well as that bowel-based one, unfortunately remains influenced by spinal cord neuropathydue dysfunctional effects, hence the tissue engineering research could be today directed to suitably overcome such disadvantageous conditions.

  20. Changes in the social environment induce neurogenic plasticity predominantly in niches residing in sensory structures of the zebrafish brain independently of cortisol levels.

    PubMed

    Lindsey, Benjamin W; Tropepe, Vincent

    2014-11-01

    The social environment is known to modulate adult neurogenesis. Studies in mammals and birds have shown a strong correlation between social isolation and decreases in neurogenesis, whereas time spent in an enriched environment has been shown to restore these deficits and enhance neurogenesis. These data suggest that there exists a common adaptive response among neurogenic niches to each extreme of the social environment. We sought to further test this hypothesis in zebrafish, a social species with distinct neurogenic niches within primary sensory structures and telencephalic nuclei of the brain. By examining stages of adult neurogenesis, including the proliferating stem/progenitor population, their surviving cohort, and the resulting newly differentiated neuronal population, we show that niches residing in sensory structures are most sensitive to changes in the social context, and that social isolation or novelty are both capable of decreasing the number of proliferating cells while increasing the number of newborn neurons within a single niche. Contrary to observations in rodents, we demonstrate that social novelty, a form of enrichment, does not consistently rescue deficits in cell proliferation following social isolation, and that cortisol levels do not negatively regulate changes in adult neurogenesis, but are correlated with the social context. We propose that enhancement or suppression of adult neurogenesis in the zebrafish brain under different social contexts depends largely on the type of niche (sensory or telencephalic), experience from the preceding social environment, and occurs independently of changes in cortisol levels.

  1. OnabotulinumtoxinA Urethral Sphincter Injection as Treatment for Non-neurogenic Voiding Dysfunction – A Randomized, Double-Blind, Placebo-Controlled Study

    PubMed Central

    Jiang, Yuan-Hong; Wang, Chung-Cheng; Kuo, Hann-Chorng

    2016-01-01

    Non-neurogenic voiding dysfunction including dysfunctional voiding and detrusor underactivity caused by a spastic or non-relaxing external urethral sphincter can theoretically be treated by injections of botulinum A toxin into the external urethral sphincter. This randomized, double-blind, placebo-controlled trial was designed to determine the clinical efficacy of onabotulinumtoxinA urethral sphincter injections in patients with dysfunctional voiding or detrusor underactivity. Patients with medically refractory dysfunctional voiding (n = 31) or detrusor underactivity (n = 31) were randomly allocated in a 2:1 ratio to receive either onabotulinumtoxinA (100 U) (n = 38) or placebo (normal saline) (n = 24). There were no significant differences in subjective or objective parameters between patients who received onabotulinumtoxinA and those who received saline injection therapy, and the overall success rate was 43.5% (reduction in Patient perception of Bladder Condition by ≥2: onabotulinumtoxinA 36.8% vs placebo 54.2%, p = 0.114). The results were similar between the dysfunctional voiding and detrusor underactivity subgroups; however, a significant reduction in detrusor voiding pressure was only observed in dysfunctional voiding patients who received onabotulinumtoxinA. Repeat urethral sphincter onabotulinumtoxinA injections offered greater therapeutic effects in both dysfunctional voiding and detrusor underactivity patients. For patients with non-neurogenic voiding dysfunction, the success rate of onabotulinumtoxinA urethral sphincter injection was not superior to placebo. PMID:27958325

  2. Identification of a Sustained Neurogenic Zone at the Dorsal Surface of the Adult Mouse Hippocampus and Its Regulation by the Chemokine SDF-1

    PubMed Central

    Belmadani, Abdelhak; Ren, Dongjun; Bhattacharyya, Bula J.; Rothwangl, Katharina B.; Hope, Thomas J.; Perlman, Harris; Miller, Richard J.

    2015-01-01

    We identified a previously unknown neurogenic region at the dorsal surface of the hippocampus; (the “subhippocampal zone,” SHZ) in the adult brain. Using a reporter mouse in which SHZ cells and their progeny could be traced through the expression of EGFP under the control of the CXCR4 chemokine receptor promoter we observed the presence of a pool of EGFP expressing cells migrating in direction of the dentate gyrus (DG), which is maintained throughout adulthood. This population appeared to originate from the SHZ where cells entered a caudal migratory stream (aCMS) that included the fimbria, the meninges and the DG. Deletion of CXCR4 from neural stem cells (NSCs) or neuroinflammation resulted in the appearance of neurons in the DG, which were the result of migration of NSCs from the SHZ. Some of these neurons were ectopically placed. Our observations indicate that the SHZ is a neurogenic zone in the adult brain through migration of NSCs in the aCMS. Regulation of CXCR4 signaling in these cells may be involved in repair of the DG and may also give rise to ectopic granule cells in the DG in the context of neuropathology. PMID:25656357

  3. Differences between the neurogenic and proliferative abilities of Müller glia with stem cell characteristics and the ciliary epithelium from the adult human eye.

    PubMed

    Bhatia, Bhairavi; Jayaram, Hari; Singhal, Shweta; Jones, Megan F; Limb, G Astrid

    2011-12-01

    Much controversy has arisen on the nature and sources of stem cells in the adult human retina. Whilst ciliary epithelium has been thought to constitute a source of neural stem cells, a population of Müller glia in the neural retina has also been shown to exhibit neurogenic characteristics. This study aimed to compare the neurogenic and proliferative abilities between these two major cell populations. It also examined whether differences exist between the pigmented and non-pigmented ciliary epithelium (CE) from the adult human eye. On this basis, Müller glia with stem cell characteristics and pigmented and non-pigmented CE were isolated from human neural retina and ciliary epithelium respectively. Expression of glial, epithelial and neural progenitor markers was examined in these cells following culture under adherent and non-adherent conditions and treatments to induce neural differentiation. Unlike pigmented CE which did not proliferate, non-pigmented CE cells exhibited limited proliferation in vitro, unless epidermal growth factor (EGF) was present in the culture medium to prolong their survival. In contrast, Müller glial stem cells (MSC) cultured as adherent monolayers reached confluence within a few weeks and continued to proliferative indefinitely in the absence of EGF. Both MSC and non-pigmented CE expressed markers of neural progenitors, including SOX2, PAX6, CHX10 and NOTCH. Nestin, a neural stem cell marker, was only expressed by MSC. Non-pigmented CE displayed epithelial morphology, limited photoreceptor gene expression and stained strongly for pigmented epithelial markers upon culture with neural differentiation factors. In contrast, MSC adopted neural morphology and expressed markers of retinal ganglion cells and photoreceptors when cultured under similar conditions. This study provides the first demonstration that pigmented CE possess different proliferative abilities from non-pigmented CE. It also showed that although non-pigmented CE express genes

  4. Botulinum Toxin Is Effective in the Management of Neurogenic Dysphagia. Clinical-Electrophysiological Findings and Tips on Safety in Different Neurological Disorders

    PubMed Central

    Alfonsi, Enrico; Restivo, Domenico A.; Cosentino, Giuseppe; De Icco, Roberto; Bertino, Giulia; Schindler, Antonio; Todisco, Massimiliano; Fresia, Mauro; Cortese, Andrea; Prunetti, Paolo; Ramusino, Matteo C.; Moglia, Arrigo; Sandrini, Giorgio; Tassorelli, Cristina

    2017-01-01

    Background and Aims: Neurogenic dysphagia linked to failed relaxation of the upper esophageal sphincter (UES) can be treated by injecting botulinum toxin (BTX) into the cricopharyngeal (CP) muscle. We compared the effects of this treatment in different neurological disorders with dysphagia, to evaluate its efficacy over time including the response to a second injection. Materials and Methods: Sixty-seven patients with neurogenic dysphagia associated with incomplete or absent opening of the UES (24 with brainstem or hemispheric stroke, 21 with parkinsonian syndromes, 12 with multiple sclerosis, and 10 with spastic-dystonic syndromes secondary to post-traumatic encephalopathy) were treated with the injection of IncobotulinumtoxinA (dose 15–20 U) into the CP muscle under electromyographic guidance. The patients were assessed at baseline and after the first and second treatment through clinical evaluation and fiberoptic endoscopy of swallowing, while their dysphagia was quantified using the Dysphagia Outcome and Severity Scale (DOSS). An electrokinesiographic/electromyographic study of swallowing was performed at baseline. Results: Most patients responded to the first BTX treatment: 35 patients (52.2%) were classified as high responders (DOSS score increase >2 levels), while other 19 patients (28.4%) were low responders (DOSS score increase of ≤2 levels). The effect of the first treatment usually lasted longer than 4 months (67%), and in some cases up to a year. The treatment efficacy remained high also after the second injection: 31 patients (46.3%) qualified as high responders and other 22 patients (32.8%) showed a low response. Only in the parkinsonian syndromes group we observed a reduction in the percentage of high responders as compared with the first treatment. Side effects were mostly mild and reported in non-responders following the first injection. A severe side effect, consisting of ingestion pneumonia, was observed following the second BTX injection in

  5. Stimulation of large-conductance calcium-activated potassium channels inhibits neurogenic contraction of human bladder from patients with urinary symptoms and reverses acetic acid-induced bladder hyperactivity in rats.

    PubMed

    La Fuente, José M; Fernández, Argentina; Cuevas, Pedro; González-Corrochano, Rocío; Chen, Mao Xiang; Angulo, Javier

    2014-07-15

    We have analysed the effects of large-conductance calcium-activated potassium channel (BK) stimulation on neurogenic and myogenic contraction of human bladder from healthy subjects and patients with urinary symptoms and evaluated the efficacy of activating BK to relief bladder hyperactivity in rats. Bladder specimens were obtained from organ donors and from men with benign prostatic hyperplasia (BPH). Contractions elicited by electrical field stimulation (EFS) and carbachol (CCh) were evaluated in isolated bladder strips. in vivo cystometric recordings were obtained in anesthetized rats under control and acetic acid-induced hyperactive conditions. Neurogenic contractions of human bladder were potentiated by blockade of BK and small-conductance calcium-activated potassium channels (SK) but were unaffected by the blockade of intermediate calcium-activated potassium channels (IK). EFS-induced contractions were inhibited by BK stimulation with NS-8 or NS1619 or by SK/IK stimulation with NS309 (3µM). CCh-induced contractions were not modified by blockade or stimulation of BK, IK or SK. The anti-cholinergic agent, oxybutynin (0.3µM) inhibited either neurogenic or CCh-induced contractions. Neurogenic contractions of bladders from BPH patients were less sensitive to BK inhibition and more sensitive to BK activation than healthy bladders. The BK activator, NS-8 (5mg/kg; i.v.), reversed bladder hyperactivity induced by acetic acid in rats, while oxybutynin was ineffective. NS-8 did not significantly impact blood pressure or heart rate. BK stimulation specifically inhibits neurogenic contractions in patients with urinary symptoms and relieves bladder hyperactivity in vivo without compromising bladder contractile capacity or cardiovascular safety, supporting its potential therapeutic use for relieving bladder overactivity.

  6. Unexpected Rapid Improvement and Neurogenic Stunned Myocardium in a Patient With Acute Motor Axonal Neuropathy: A Case Report and Literature Review.

    PubMed

    Magid-Bernstein, Jessica; Al-Mufti, Fawaz; Merkler, Alexander E; Roh, David; Patel, Sweta; May, Teresa L; Agarwal, Sachin; Claassen, Jan; Park, Soojin

    2016-03-01

    Acute Motor Axonal Neuropathy-type Guillain-Barré Syndrome (GBS) is a subset of GBS with either a rapidly improving or protracted course that was first described in China. We describe a 27-year-old previously healthy woman with weakness that progressed to complete tetraplegia and areflexia within 2 weeks after an upper respiratory illness. A lumbar puncture performed 4 days after onset of neurologic symptoms was inconclusive for GBS, and electromyography revealed complete motor axonal neuropathy. The patient had Mycoplasma pneumoniae in her nares and blood, and several antiganglioside antibodies in her blood. She was treated with plasmapheresis, antibiotics, and physical therapy. Her motor function and reflexes improved rapidly with treatment, and she was able to ambulate within 3 weeks. She also experienced cardiomyopathy, which improved with plasmapheresis. We report a rare case of Mycoplasma pneumonia-associated acute motor axonal neuropathy-type GBS presenting with complete tetraplegia, areflexia, and neurogenic stunned myocardium that rapidly improved with plasmapheresis.

  7. Retrograde pyelonephritis and lumbar spondylitis as a result of Salmonella typhi in a type 2 diabetes patient with neurogenic bladder.

    PubMed

    Fukuda, Tatsuya; Bouchi, Ryotaro; Minami, Isao; Ohara, Norihiko; Nakano, Yujiro; Nishitani, Rie; Murakami, Masanori; Takeuchi, Takato; Akihisa, Momoko; Fujita, Masamichi; Izumiyama, Hajime; Hashimoto, Koshi; Yoshimoto, Takanobu; Ogawa, Yoshihiro

    2016-05-01

    We present a case of a 62-year-old diabetic woman with acute pyelonephritis and spondylitis caused by Salmonella typhi. She was admitted to Tokyo Medical Dental University Hospital, Tokyo, Japan, because of unconsciousness and was diagnosed with sepsis by retrograde pyelonephritis as a result of Salmonella typhi. Antibiotics treatment was immediately started; however, she subsequently developed lumbar spondylitis, and long-term conservative treatment with antibiotics and a fixing device were required. This is the first report of a diabetic patient who developed retrograde urinary tract infection with Salmonella typhi, followed by sepsis and spondylitis. The infection could be a result of diabetic neuropathy, presenting neurogenic bladder and hydronephrosis. The patient was successfully treated with antibiotics and became asymptomatic with normal inflammatory marker levels, and no clinical sign of recurrence was observed in the kidney and spine at 4 months.

  8. Neurogenic Potential Assessment and Pharmacological Characterization of 6-Methoxy-1,2,3,4-tetrahydro-β-carboline (Pinoline) and Melatonin-Pinoline Hybrids.

    PubMed

    de la Fuente Revenga, Mario; Pérez, Concepción; Morales-García, José A; Alonso-Gil, Sandra; Pérez-Castillo, Ana; Caignard, Daniel-Henri; Yáñez, Matilde; Gamo, Ana M; Rodríguez-Franco, María Isabel

    2015-05-20

    6-Methoxy-1,2,3,4-tetrahydro-β-carboline (pinoline) and N-acetyl-5-methoxytryptamine (melatonin) are both structurally related to 5-hydroxytryptamine (serotonin). Here we describe the design, synthesis, and characterization of a series of melatonin rigid analogues resulting from the hybridization of both pinoline and melatonin structures. The pharmacological evaluation of melatonin-pinoline hybrids comprises serotonergic and melatonergic receptors, metabolic enzymes (monoamine oxidases), antioxidant potential, the in vitro blood-brain barrier permeability, and neurogenic studies. Pinoline at trace concentrations and 2-acetyl-6-methoxy-1,2,3,4-tetrahydro-β-carboline (2) were able to stimulate early neurogenesis and neuronal maturation in an in vitro model of neural stem cells isolated from the adult rat subventricular zone. Such effects are presumably mediated via serotonergic and melatonergic stimulation, respectively.

  9. Hyperthermic potentiation of doxorubicin and 4'-EPI-doxorubicin in a transplantable neurogenic rat tumor (BT/sub 4/A) in BD IX rats

    SciTech Connect

    Dahl, O.

    1983-02-01

    The combined effect of hyperthermia and doxorubicin on the neurogenic rat cell line BT/sub 4/C was found to be synergistic in vitro. The present investigation was initiated to study if this synergistic effect also could be obtained in vivo. An enhanced effect occurred when doxorubicin and 4'-epi-doxorubicin 7 mg/kg body weight were given 30 minutes prior to local water bath hyperthermia (one hour at 44.0 degrees C). The local side effects of the combined treatment did not increase above that of hyperthermia alone. Therefore, local hyperthermia may become a useful modality for enhancement of the effect of anthracyclines on tumors with marginal drug sensitivity or bulky tumors with poor drug penetration.

  10. The in vivo pharmacological profile of a 5-HT1 receptor agonist, CP-122,288, a selective inhibitor of neurogenic inflammation.

    PubMed

    Gupta, P; Brown, D; Butler, P; Ellis, P; Grayson, K L; Land, G C; Macor, J E; Robson, S F; Wythes, M J; Shepperson, N B

    1995-11-01

    1. The aim of the present study was to investigate the in vivo pharmacological profile of CP-122,288, an indole-derivative with a conformationally restricted N-methylpyrrolidinyl basic side chain in the C-3 position. This C-3 substituent structurally differentiates CP-122,288 from the 5-HT1D receptor agonist sumatriptan, which possesses an N,N-dimethylaminoethyl group. [Formula: see text] 2. When administered prior to electrical stimulation of the trigeminal ganglion, CP-122,288 (0.3-300 ng kg-1, i.v.) produced a dose-related inhibition of plasma protein extravasation in rat dura mater (minimum effective dose, MED, 3 ng kg-1 i.v., P < 0.05; maximal inhibition of plasma extravasation at 30 ng kg-1 i.v., P < 0.01). Sumatriptan produced a similar inhibition of plasma leakage in the dura, but at much higher dose levels (MED, 100 micrograms kg-1 i.v., P < 0.05). Thus, CP-122,288 is of the order of 10(4) fold more potent than sumatriptan. 3. At all doses tested, CP-122,288 did not inhibit plasma protein extravasation measured in extracranial tissues such as the lower lip, eyelid, and conjunctiva. 4. In a separate series of studies in the anaesthetized rat, CP-122,288 (0.003-3 micrograms kg-1 i.v.) produced no change in either heart rate or mean arterial blood pressure, thus demonstrating that doses of CP-122,288 which inhibit plasma protein leakage in rat dura, are devoid of hemodynamic effects. 5. Following a 5 min period of electrical stimulation of the trigeminal ganglion, a 20 min period of sustained neurogenically-driven plasma extravasation, occurring in the absence of electrical stimulation, was initiated. By administration of the compound 5 min after completing the phase of electrical stimulation, this protocol permitted the evaluation of the activity of CP-122,288 on an ongoing and established inflammatory event. CP-122,288 (30 and 300 ng kg-1, i.v., P < 0.01 and P < 0.05, respectively) produced a complete inhibition of plasma protein leakage which was

  11. Deletion of protein tyrosine phosphatase 1b in proopiomelanocortin neurons reduces neurogenic control of blood pressure and protects mice from leptin- and sympatho-mediated hypertension.

    PubMed

    Bruder-Nascimento, Thiago; Butler, Benjamin R; Herren, David J; Brands, Michael W; Bence, Kendra K; Belin de Chantemèle, Eric J

    2015-12-01

    Protein tyrosine phosphatase 1b (Ptp1b), which represses leptin signaling, is a promising therapeutic target for obesity. Genome wide deletion of Ptp1b, increases leptin sensitivity, protects mice from obesity and diabetes, but alters cardiovascular function by increasing blood pressure (BP). Leptin-control of metabolism is centrally mediated and involves proopiomelanocortin (POMC) neurons. Whether these neurons contribute to leptin-mediated increases in BP remain unclear. We hypothesized that increasing leptin signaling in POMC neurons with Ptp1b deletion will sensitize the cardiovascular system to leptin and enhance neurogenic control of BP. We analyzed the cardiovascular phenotype of Ptp1b+/+ and POMC-Ptp1b-/- mice, at baseline and after 7 days of leptin infusion or sympatho-activation with phenylephrine. POMCPtp1b deletion did not alter baseline cardiovascular hemodynamics (BP, heart rate) but reduced BP response to ganglionic blockade and plasma catecholamine levels that suggests a decreased neurogenic control of BP. In contrast, POMC-Ptp1b deletion increased vascular adrenergic reactivity and aortic α-adrenergic receptors expression. Chronic leptin treatment reduced vascular adrenergic reactivity and blunted diastolic and mean BP increases in POMC-Ptp1b-/- mice only. Similarly POMC-Ptp1b-/- mice exhibited a blunted increased in diastolic and mean BP accompanied by a gradual reduction in adrenergic reactivity in response to chronic vascular sympatho-activation with phenylephrine. Together these data rule out our hypothesis but suggest that deletion of Ptp1b in POMC neurons protects from leptin- and sympatho-mediated increases in BP. Vascular adrenergic desensitization appears as a protective mechanism against hypertension, and POMC-Ptp1b as a key therapeutic target for the treatment of metabolic and cardiovascular dysfunctions associated with obesity.

  12. Antinociceptive activity of transient receptor potential channel TRPV1, TRPA1, and TRPM8 antagonists in neurogenic and neuropathic pain models in mice.

    PubMed

    Sałat, Kinga; Filipek, Barbara

    2015-03-01

    The aim of this research was to assess the antinociceptive activity of the transient receptor potential (TRP) channel TRPV1, TRPM8, and TRPA1 antagonists in neurogenic, tonic, and neuropathic pain models in mice. For this purpose, TRP channel antagonists were administered into the dorsal surface of a hind paw 15 min before capsaicin, allyl isothiocyanate (AITC), or formalin. Their antiallodynic and antihyperalgesic efficacies after intraperitoneal administration were also assessed in a paclitaxel-induced neuropathic pain model. Motor coordination of paclitaxel-treated mice that received these TRP channel antagonists was investigated using the rotarod test. TRPV1 antagonists, capsazepine and SB-366791, attenuated capsaicin-induced nociceptive reaction in a concentration-dependent manner. At 8 µg/20 µl, this effect was 51% (P<0.001) for capsazepine and 37% (P<0.05) for SB-366791. A TRPA1 antagonist, A-967079, reduced pain reaction by 48% (P<0.05) in the AITC test and by 54% (P<0.001) in the early phase of the formalin test. The test compounds had no influence on the late phase of the formalin test. In paclitaxel-treated mice, they did not attenuate heat hyperalgesia but N-(3-aminopropyl)-2-{[(3-methylphenyl)methyl]oxy}-N-(2-thienylmethyl) benzamide hydrochloride salt (AMTB), a TRPM8 antagonist, reduced cold hyperalgesia and tactile allodynia by 31% (P<0.05) and 51% (P<0.01), respectively. HC-030031, a TRPA1 channel antagonist, attenuated tactile allodynia in the von Frey test (62%; P<0.001). In conclusion, distinct members of TRP channel family are involved in different pain models in mice. Antagonists of TRP channels attenuate nocifensive responses of neurogenic, tonic, and neuropathic pain, but their efficacies strongly depend on the pain model used.

  13. The Felix-trial. Double-blind randomization of interspinous implant or bony decompression for treatment of spinal stenosis related intermittent neurogenic claudication

    PubMed Central

    2010-01-01

    Background Decompressive laminotomy is the standard surgical procedure in the treatment of patients with canal stenosis related intermittent neurogenic claudication. New techniques, such as interspinous process implants, claim a shorter hospital stay, less post-operative pain and equal long-term functional outcome. A comparative (cost-) effectiveness study has not been performed yet. This protocol describes the design of a randomized controlled trial (RCT) on (cost-) effectiveness of the use of interspinous process implants versus conventional decompression surgery in patients with lumbar spinal stenosis. Methods/Design Patients (age 40-85) presenting with intermittent neurogenic claudication due to lumbar spinal stenosis lasting more than 3 months refractory to conservative treatment, are included. Randomization into interspinous implant surgery versus bony decompression surgery will take place in the operating room after induction of anesthesia. The primary outcome measure is the functional assessment of the patient measured by the Zurich Claudication Questionnaire (ZCQ), at 8 weeks and 1 year after surgery. Other outcome parameters include perceived recovery, leg and back pain, incidence of re-operations, complications, quality of life, medical consumption, absenteeism and costs. The study is a randomized multi-institutional trial, in which two surgical techniques are compared in a parallel group design. Patients and research nurses are kept blinded of the allocated treatment during the follow-up period of 1 year. Discussion Currently decompressive laminotomy is the golden standard in the surgical treatment of lumbar spinal stenosis. Whether surgery with interspinous implants is a reasonable alternative can be determined by this trial. Trial register Dutch Trial register number: NTR1307 PMID:20507568

  14. Pneumonia and in-hospital mortality in the context of neurogenic oropharyngeal dysphagia (NOD) in stroke and a new NOD step-wise concept.

    PubMed

    Ickenstein, G W; Riecker, A; Höhlig, C; Müller, R; Becker, U; Reichmann, H; Prosiegel, M

    2010-09-01

    The aim of our work was to develop a step-wise concept for investigating neurogenic oropharyngeal dysphagia (NOD) that could be used by both trained nursing staff as well as swallowing therapists and physicians to identify patients with NOD at an early stage and so enable an appropriate therapy to be started. To achieve this objective, we assessed uniform terminology and standard operating procedures (SOP) in a new NOD step-wise concept. In-house stroke mortality rates and rates of pneumonia were measured over time (2003-2009) in order to show improvements in quality of care. In addition, outcome measures in a stroke-unit monitoring system were studied after neurorehabilitation (day 90) assessing quality of life (QL) and patient feedback. An investigation that was carried out in the context of internal and external quality assurance stroke projects revealed a significant correlation between the NOD step-wise concept and low rates of pneumonia and in-house mortality. The quality of life measures show a delta value that can contribute to "post-stroke" depression. The NOD step-wise concept (NSC) should, on the one hand, be capable of being routinely used in clinical care and, on the other, being able to fulfil the requirements of being scientifically based for investigating different stages of swallowing disorders. The value of our NSC relates to the effective management of clinical resources and the provision of adequate diagnostic and therapeutic options for different grades of dysphagia. We anticipate that our concept will provide substantial support to physicians, as well as swallowing therapists, in clinical settings and rehabilitation facilities, thereby promoting better guidance and understanding of neurogenic dysphagia as a concept in acute and rehabilitation care, especially stroke-unit settings.

  15. Chronic treatment with taurine ameliorates diabetes-induced dysfunction of nitric oxide-mediated neurogenic and endothelium-dependent corpus cavernosum relaxation in rats.

    PubMed

    Dalaklioglu, Selvinaz; Kuscu, Nilay; Celik-Ozenci, Ciler; Bayram, Zeliha; Nacitarhan, Cahit; Ozdem, Sadi Satilmis

    2014-08-01

    This study was aimed to examine the effect of chronic taurine treatment on corpus cavernosum dysfunction in diabetic rats and to investigate possible underlying mechanisms. Thirty male rats were randomized to three groups of 10 each, including control, diabetic, and taurine-treated diabetic. Diabetes was induced in rats by streptozotocin (STZ, single intraperitoneal dose of 50 mg/kg body weight). Taurine was administered orally for 12 weeks (1% w/v in drinking water) from the day on which STZ was injected. At the end of the 12th week, strips of corpus cavernosum were suspended in an organ bath system for functional studies. Nitric oxide (NO)-mediated endothelium-dependent and neurogenic corpus cavernosum relaxation were evaluated by acetylcholine (ACh, 0.1-100 μm) and electrical field stimulation (EFS, 30 V, 5 ms, 2-32 Hz), respectively. The expressions of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (Ser-1177), neuronal nitric oxide synthase (nNOS), NADPH oxidase subunit gp91(phox) , Rho A, and Rho kinase in corpus cavernosum were semi-quantitatively assessed by immunohistochemistry. Induction of diabetes resulted in significant inhibition of NO-mediated endothelium-dependent and neurogenic corpus cavernosum relaxation. Furthermore, eNOS, p-eNOS, and nNOS expressions decreased significantly in diabetic rats compared to controls, while gp91(phox) , RhoA and Rho kinase expressions increased significantly. The diminished relaxation response to ACh and EFS as well as diabetes-related changes in expressions of these proteins in corpus cavernosum of diabetic rats was significantly improved by taurine. Taurine treatment improves NO-mediated relaxations of corpus cavernosum in diabetic rats probably by inhibiting NADPH oxidase/Rho kinase pathways.

  16. Long-term follow-up after botulinum toxin A (BTX-A) injection into the detrusor for treatment of neurogenic detrusor hyperactivity in children

    PubMed Central

    Becker, Tanja; Koen, Mark; Berger, Christoph; Riccabona, Marcus

    2012-01-01

    Purpose To prove the long-term efficacy of BTX-A injection in the management of children with neurogenic detrusor hyperactivity. Materials and methods 28 out of 145 children with neurogenic bladder (15 male and 13 female, mean age 10.7 years) who were treated between 2002 and 2010 and became non-responders to conservative treatment were included into the retrospective study. We injected 10-12 U/kg of BTX-A (Botox®) into the detrusor at 20-30 sites, sparing the trigone. The mean follow-up was 48 months (range 6-84 months). Results Group 1. 14 patients had a single injection of BTX-A. Five of them were successful. Mean bladder reflex volume increased (from 62.9 to 117.5 ml), maximum detrusor pressure decreased (from 59 to 37.5 cm H2O), detrusor compliance increased (from 4.8 to 9.5 ml/cm H2O), and leak-point-pressure decreased (from 46.5 to 24.2 cm H2O). Four patients did not respond and were treated by ileocystoplasty. Another five were lost to follow-up. Group 2. 14 patients had repeated (mean 2.5) injections of BTX-A with a mean interval of 13.7 months. In thirteen patients, urodynamic parameters of the first and last injection were similar to those obtained in Group 1, showing a good response. One patient received an ileocystoplasty. Conclusion BTX-A is a safe alternative in the treatment of detrusor hyperactivity in children with myelomeningocele (MMC). The efficacy lasted a mean of 12 months and urodynamic response was unchanged even after several injections. In our series, 21.7% of children with severe low-compliance bladders were non-responders. PMID:24578954

  17. Development of the larval anterior neurogenic domains of Terebratalia transversa (Brachiopoda) provides insights into the diversification of larval apical organs and the spiralian nervous system

    PubMed Central

    2012-01-01

    Background Larval features such as the apical organ, apical ciliary tuft, and ciliated bands often complicate the evaluation of hypotheses regarding the origin of the adult bilaterian nervous system. Understanding how neurogenic domains form within the bilaterian head and larval apical organ requires expression data from animals that exhibit aspects of both centralized and diffuse nervous systems at different life history stages. Here, we describe the expression of eight neural-related genes during the larval development of the brachiopod, Terebratalia transversa. Results Radially symmetric gastrulae broadly express Tt-Six3/6 and Tt-hbn in the animal cap ectoderm. Tt-NK2.1 and Tt-otp are restricted to a central subset of these cells, and Tt-fez and Tt-FoxQ2 expression domains are already asymmetric at this stage. As gastrulation proceeds, the spatial expression of these genes is split between two anterior ectodermal domains, a more dorsal region comprised of Tt-Six3/6, Tt-fez, Tt-FoxQ2, and Tt-otp expression domains, and an anterior ventral domain demarcated by Tt-hbn and Tt-NK2.1 expression. More posteriorly, the latter domains are bordered by Tt-FoxG expression in the region of the transverse ciliated band. Tt-synaptotagmin 1 is expressed throughout the anterior neural ectoderm. All genes are expressed late into larval development. The basiepithelial larval nervous system includes three neurogenic domains comprised of the more dorsal apical organ and a ventral cell cluster in the apical lobe as well as a mid-ventral band of neurons in the mantle lobe. Tt-otp is the only gene expressed in numerous flask-shaped cells of the apical organ and in a subset of neurons in the mantle lobe. Conclusions Our expression data for Tt-Six3/6, Tt-FoxQ2, and Tt-otp confirm some aspects of bilaterian-wide conservation of spatial partitioning within anterior neurogenic domains and also suggest a common origin for central otp-positive cell types within the larval apical organs of

  18. Network Science

    NASA Astrophysics Data System (ADS)

    Barabási, Albert-László

    2016-07-01

    Preface; Personal introduction; 1. Introduction; 2. Graph theory; 3. Random networks; 4. The scale-free property; 5. The Barabási-Albert model; 6. Evolving networks; 7. Degree correlation; 8. Network robustness; 9. Communities; 10. Spreading phenomena; Index.

  19. Role of PiCCO monitoring for the integrated management of neurogenic pulmonary edema following traumatic brain injury: A case report and literature review.

    PubMed

    Lin, Xiaoping; Xu, Zhijun; Wang, Pengfei; Xu, Yan; Zhang, Gensheng

    2016-10-01

    Neurogenic pulmonary edema (NPE) is occasionally observed in patients with traumatic brain injury (TBI); however, this condition is often underappreciated. NPE is frequently misdiagnosed due to its atypical clinical performance, thus delaying appropriate treatment. A comprehensive management protocol of NPE in patients with TBI has yet to be established. The current study reported the case of a 67-year-old man with severe TBI who was transferred to our intensive care unit (ICU). On day 7 after hospitalization, the patient suddenly suffered tachypnea, tachycardia, systemic hypertension and hypoxemia during lumbar cistern drainage. Intravenous diuretics, tranquilizer and glucocorticoid were administered due to suspected left heart failure attack. Chest radiography examination supported the diagnosis of pulmonary edema; however, hypotension and hypovolemia were subsequently observed. Pulse index continuous cardiac output (PiCCO) hemodynamic monitoring and bedside echocardiography were performed, which excluded the diagnosis of cardiac pulmonary edema, and thus the diagnosis of NPE was confirmed. Goal-directed therapy by dynamic PiCCO monitoring was then implemented. In addition, levosimendan, an inotropic agent, was introduced to improve cardiac output. The patient had complete recovered from pulmonary edema and regained consciousness on day 11 of hospitalization. The current case demonstrated that PiCCO monitoring may serve a central role in the integrated management of NPE in patients with TBI. Levosimendan may be a potential medicine in treating cardiac dysfunction, along with its benefit from improving neurological function in NPE patients.

  20. Role of PiCCO monitoring for the integrated management of neurogenic pulmonary edema following traumatic brain injury: A case report and literature review

    PubMed Central

    Lin, Xiaoping; Xu, Zhijun; Wang, Pengfei; Xu, Yan; Zhang, Gensheng

    2016-01-01

    Neurogenic pulmonary edema (NPE) is occasionally observed in patients with traumatic brain injury (TBI); however, this condition is often underappreciated. NPE is frequently misdiagnosed due to its atypical clinical performance, thus delaying appropriate treatment. A comprehensive management protocol of NPE in patients with TBI has yet to be established. The current study reported the case of a 67-year-old man with severe TBI who was transferred to our intensive care unit (ICU). On day 7 after hospitalization, the patient suddenly suffered tachypnea, tachycardia, systemic hypertension and hypoxemia during lumbar cistern drainage. Intravenous diuretics, tranquilizer and glucocorticoid were administered due to suspected left heart failure attack. Chest radiography examination supported the diagnosis of pulmonary edema; however, hypotension and hypovolemia were subsequently observed. Pulse index continuous cardiac output (PiCCO) hemodynamic monitoring and bedside echocardiography were performed, which excluded the diagnosis of cardiac pulmonary edema, and thus the diagnosis of NPE was confirmed. Goal-directed therapy by dynamic PiCCO monitoring was then implemented. In addition, levosimendan, an inotropic agent, was introduced to improve cardiac output. The patient had complete recovered from pulmonary edema and regained consciousness on day 11 of hospitalization. The current case demonstrated that PiCCO monitoring may serve a central role in the integrated management of NPE in patients with TBI. Levosimendan may be a potential medicine in treating cardiac dysfunction, along with its benefit from improving neurological function in NPE patients. PMID:27698733

  1. TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization.

    PubMed

    Gouin, Olivier; L'Herondelle, Killian; Lebonvallet, Nicolas; Le Gall-Ianotto, Christelle; Sakka, Mehdi; Buhé, Virginie; Plée-Gautier, Emmanuelle; Carré, Jean-Luc; Lefeuvre, Luc; Misery, Laurent; Le Garrec, Raphaele

    2017-03-31

    Cutaneous neurogenic inflammation (CNI) is inflammation that is induced (or enhanced) in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli. It is now clear that the expression of both channels also extends far beyond the sensory nerves in the skin, occuring also in keratinocytes, mast cells, dendritic cells, and endothelial cells. In these non-neuronal cells, TRPV1 and TRPA1 also act as nociceptive sensors and potentiate the inflammatory process. This review discusses the role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells. In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI.

  2. Inhibition of Adult Neurogenesis by Inducible and Targeted Deletion of ERK5 MAP Kinase Specifically in Adult Neurogenic Regions Impairs Contextual Fear Memory Extinction and Remote Fear Memory

    PubMed Central

    Pan, Yung-Wei; Chan, Guy C.K.; Kuo, Chay T.; Storm, Daniel R.; Xia, Zhengui

    2012-01-01

    Although there is evidence suggesting that adult neurogenesis may contribute to hippocampus-dependent memory, signaling mechanisms responsible for adult hippocampal neurogenesis are not well characterized. Here we report that ERK5 MAP kinase is specifically expressed in the neurogenic regions of the adult mouse brain. The inducible and conditional knockout (icKO) of erk5 specifically in neural progenitors of the adult mouse brain attenuated adult hippocampal neurogenesis. It also caused deficits in several forms of hippocampus-dependent memory including contextual fear conditioning generated by a weak foot shock. The ERK5 icKO mice were also deficient in extinction of contextual fear memory and reversal of Morris water maze spatial learning and memory, suggesting that adult neurogenesis is important for learning that requires active forgetting of a prior memory. Furthermore, our data suggest a critical role for ERK5-mediated adult neurogenesis in pattern separation, a form of dentate gyrus-dependent spatial learning and memory. Moreover, ERK5 icKO mice have no memory 21 days post-training in the passive avoidance test, suggesting a pivotal role for adult hippocampal neurogenesis in the expression of remote memory. Together, our results implicate ERK5 as a novel signaling molecule regulating adult neurogenesis and provide strong evidence that adult neurogenesis is critical for several forms of hippocampus-dependent memory formation including memory extinction, and for the expression of remote memory. PMID:22573667

  3. Cellular basis of neurogenesis in the brain of crayfish, Procambarus clarkii: Neurogenic complex in the olfactory midbrain from hatchlings to adults.

    PubMed

    Song, Cha-Kyong; Johnstone, Laurel M; Edwards, Donald H; Derby, Charles D; Schmidt, Manfred

    2009-07-01

    Neurogenesis in the central olfactory pathway of decapod crustaceans persists throughout life. Here we describe the structural basis of neurogenesis within the olfactory deutocerebrum of the crayfish Procambarus clarkii from hatchlings to adults. Using a proliferation marker and immunostaining, we found that throughout development each hemibrain contains a neurogenic complex consisting of five parts: two proliferation zones, each within the neuronal soma clusters containing local or projection interneurons, a tail of proliferating cells extending from each proliferation zone, and an elongated clump of cells where the two tails meet. The clump of cells comprises two subdivisions joined at a nucleus-free central area. Each subdivision consists of a dense group of clump cells with small, spindle-shaped nuclei and is connected to one of the proliferation zones by a strand of fibrous material encompassing the tail of proliferating cells extending from it. We identify one proliferating cell with a large nucleus in each subdivision as a putative neuroblast. Its daughter cells migrate through the strands to the associated proliferation zones, but in the strand leading to the soma cluster of local interneurons this is masked by local proliferation. We conclude that neurogenesis in the olfactory deutocerebrum of juvenile and adult P. clarkii is based on a few neuroblasts that are associated with unique clumps of cells likely representing stem cell niches.

  4. Limited Ca2+ and PKA-pathway dependent neurogenic differentiation of human adult mesenchymal stem cells as compared to fetal neuronal stem cells.

    PubMed

    Lepski, Guilherme; Jannes, Cinthia Elim; Maciaczyk, Jaroslaw; Papazoglou, Anna; Mehlhorn, Alexander T; Kaiser, Stefan; Teixeira, Manoel Jacobsen; Marie, Suely K N; Bischofberger, Josef; Nikkhah, Guido

    2010-01-15

    The ability of mesenchymal stem cells to generate functional neurons in culture is still a matter of controversy. In order to assess this issue, we performed a functional comparison between neuronal differentiation of human MSCs and fetal-derived neural stem cells (NSCs) based on morphological, immunocytochemical, and electrophysiological criteria. Furthermore, possible biochemical mechanisms involved in this process were presented. NF200 immunostaining was used to quantify the yield of differentiated cells after exposure to cAMP. The addition of a PKA inhibitor and Ca(2+) blockers to the differentiation medium significantly reduced the yield of differentiated cells. Activation of CREB was also observed on MSCs during maturation. Na(+)-, K(+)-, and Ca(2+)-voltage-dependent currents were recorded from MSCs-derived cells. In contrast, significantly larger Na(+) currents, firing activity, and spontaneous synaptic currents were recorded from NSCs. Our results indicate that the initial neuronal differentiation of MSCs is induced by cAMP and seems to be dependent upon Ca(2+) and the PKA pathway. However, compared to fetal neural stem cells, adult mesenchymal counterparts are limited in their neurogenic potential. Despite the similar yield of neuronal cells, NSCs achieved a more mature functional state. Description of the underlying mechanisms that govern MSCs' differentiation toward a stable neuronal phenotype and their limitations provides a unique opportunity to enhance our understanding of stem cell plasticity.

  5. Antibiotic prophylaxis may not be necessary in patients with asymptomatic bacteriuria undergoing intradetrusor onabotulinumtoxinA injections for neurogenic detrusor overactivity

    PubMed Central

    Leitner, Lorenz; Sammer, Ulla; Walter, Matthias; Knüpfer, Stephanie C.; Schneider, Marc P.; Seifert, Burkhardt; Tornic, Jure; Mehnert, Ulrich; Kessler, Thomas M.

    2016-01-01

    Many of the patients undergoing intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity (NDO) present with chronic bacteriuria. In these patients, antibiotic prophylaxis has been widely recommended since bacteriuria might impair treatment efficacy and cause urinary tract infections (UTI) but the evidence is limited. The aim of this study was to evaluate if an antibiotic prophylaxis is needed in patients with asymptomatic bacteriuria undergoing intradetrusor onabotulinumtoxinA injections. Between 06/2012 and 12/2014, a consecutive series of 154 patients undergoing a total of 273 treatment cycles were prospectively evaluated. Before treatment urine samples were collected, patients with no clinical signs for UTI underwent onabotulinumtoxinA injections, no antibiotic prophylaxis was given. Asymptomatic bacteriuria was found in 73% (200/273 treatments). Following treatment, UTI occurred in 5% (9/200) and 7% (5/73) of patients with and without bacteriuria, respectively. Intradetrusor onabotulinumtoxinA injections were clinically and urodynamically successful in 70% (192/273). There was no association between bacteriuria and treatment-related adverse events (odds ratio 0.64, 95% CI 0.23–1.81, p = 0.4) nor between bacteriuria and therapy failure (odds ratio 0.78, 95% CI 0.43–1.43, p = 0.4). Thus, we conclude that antibiotic prophylaxis needs to be critically reconsidered in patients undergoing intradetrusor onabotulinumtoxinA injections, especially taking into account the alarming antibiotic resistance worldwide. PMID:27616488

  6. Mcidas and GemC1 are key regulators for the generation of multiciliated ependymal cells in the adult neurogenic niche.

    PubMed

    Kyrousi, Christina; Arbi, Marina; Pilz, Gregor-Alexander; Pefani, Dafni-Eleftheria; Lalioti, Maria-Eleni; Ninkovic, Jovica; Götz, Magdalena; Lygerou, Zoi; Taraviras, Stavros

    2015-11-01

    Multiciliated cells are abundant in the epithelial surface of different tissues, including cells lining the walls of the lateral ventricles in the brain and the airway epithelium. Their main role is to control fluid flow and defects in their differentiation are implicated in many human disorders, such as hydrocephalus, accompanied by defects in adult neurogenesis and mucociliary disorder in the airway system. Here we show that Mcidas, which is mutated in human mucociliary clearance disorder, and GemC1 (Gmnc or Lynkeas), previously implicated in cell cycle progression, are key regulators of multiciliated ependymal cell generation in the mouse brain. Overexpression and knockdown experiments show that Mcidas and GemC1 are sufficient and necessary for cell fate commitment and differentiation of radial glial cells to multiciliated ependymal cells. Furthermore, we show that GemC1 and Mcidas operate in hierarchical order, upstream of Foxj1 and c-Myb transcription factors, which are known regulators of ependymal cell generation, and that Notch signaling inhibits GemC1 and Mcidas function. Our results suggest that Mcidas and GemC1 are key players in the generation of multiciliated ependymal cells of the adult neurogenic niche.

  7. Does Reduction of Number of Intradetrusor Injection Sites of aboBoNTA (Dysport®) Impact Efficacy and Safety in a Rat Model of Neurogenic Detrusor Overactivity?

    PubMed Central

    Huynh Le Maux, Amélie; Pignol, Bernadette; Behr-Roussel, Delphine; Blachon, Jean-Luc; Chabrier, Pierre-Etienne; Compagnie, Sandrine; Picaut, Philippe; Bernabé, Jacques; Giuliano, François; Denys, Pierre

    2015-01-01

    Intradetrusor injections of Botulinum toxin A—currently onabotulinumtoxinA—is registered as a second-line treatment to treat neurogenic detrusor overactivity (NDO). The common clinical practice is 30 × 1 mL injections in the detrusor; however, protocols remain variable and standardization is warranted. The effect of reducing the number of injection sites of Dysport® abobotulinumtoxinA (aboBoNTA) was assessed in the spinal cord-injured rat (SCI). Nineteen days post-spinalization, female rats received intradetrusor injections of saline or aboBoNTA 22.5 U distributed among four or eight sites. Two days after injection, continuous cystometry was performed in conscious rats. Efficacy of aboBoNTA 22.5 U was assessed versus aggregated saline groups on clinically-relevant parameters: maximal pressure, bladder capacity, compliance, voiding efficiency, as well as amplitude, frequency, and volume threshold for nonvoiding contractions (NVC). AboBoNTA 22.5 U significantly decreased maximal pressure, without affecting voiding efficiency. Injected in four sites, aboBoNTA significantly increased bladder capacity and compliance while only the latter when in eight sites. AboBoNTA significantly reduced NVC frequency and amplitude. This preclinical investigation showed similar inhibiting effects of aboBoNTA despite the number of sites reduction. Further studies are warranted to optimize dosing schemes to improve the risk-benefit ratio of BoNTA-based treatment modalities for NDO and further idiopathic overactive bladder. PMID:26694464

  8. Effects of Physiotherapy in the Treatment of Neurogenic Bladder in Patients Infected with Human T-Lymphotropic Virus 1 (HTLV-1)

    PubMed Central

    Andrade, Rosana C.P.; Neto, José A.; Andrade, Luciana; Oliveira, Tatiane S. S.; Santos, Dislene N.; Oliveira, Cassius J.V.; Prado, Márcio J.; Carvalho, Edgar M.

    2016-01-01

    Objective To evaluate the efficacy of physiotherapy for urinary manifestations in patients with HTLV-1-associated lower urinary tract dysfunction. Methods Open clinical trial with 21 patients attending the physiotherapy clinic of the Hospital Universitário, Bahia, Brazil. Combinations of behavioral therapy, perineal exercises and intravaginal/intra-anal electrical stimulation were used. Results The mean age was 54±12 years and 67% were female. After treatment, there was an improvement in symptoms of urinary urgency, frequency, incontinence, nocturia and in the sensation of incomplete emptying (p<0.001). There was also a reduction in the overactive bladder symptom score from 10±4 to 6±3 (p<0.001) and an increasing in the perineal muscle strength (p<0.001). The urodynamic parameters improved, with reduction in the frequency of patients with detrusor hyperactivity from 57.9% to 42.1%; detrusor-sphincter dyssynergia (DSD) from 31.6% to 5.3%; detrusor hypocontractility from 15.8% to 0% and detrusor areflexia from 10.5% to 0%, with positive repercussions in the quality of life in all patients. Conclusion Physiotherapy was effective in cases of HTLV-1-associated neurogenic bladder, reducing symptoms, increasing perineal muscle strength, improving urodynamic parameters and quality of life. PMID:26724409

  9. Network Cosmology

    PubMed Central

    Krioukov, Dmitri; Kitsak, Maksim; Sinkovits, Robert S.; Rideout, David; Meyer, David; Boguñá, Marián

    2012-01-01

    Prediction and control of the dynamics of complex networks is a central problem in network science. Structural and dynamical similarities of different real networks suggest that some universal laws might accurately describe the dynamics of these networks, albeit the nature and common origin of such laws remain elusive. Here we show that the causal network representing the large-scale structure of spacetime in our accelerating universe is a power-law graph with strong clustering, similar to many complex networks such as the Internet, social, or biological networks. We prove that this structural similarity is a consequence of the asymptotic equivalence between the large-scale growth dynamics of complex networks and causal networks. This equivalence suggests that unexpectedly similar laws govern the dynamics of complex networks and spacetime in the universe, with implications to network science and cosmology. PMID:23162688

  10. Network cosmology.

    PubMed

    Krioukov, Dmitri; Kitsak, Maksim; Sinkovits, Robert S; Rideout, David; Meyer, David; Boguñá, Marián

    2012-01-01

    Prediction and control of the dynamics of complex networks is a central problem in network science. Structural and dynamical similarities of different real networks suggest that some universal laws might accurately describe the dynamics of these networks, albeit the nature and common origin of such laws remain elusive. Here we show that the causal network representing the large-scale structure of spacetime in our accelerating universe is a power-law graph with strong clustering, similar to many complex networks such as the Internet, social, or biological networks. We prove that this structural similarity is a consequence of the asymptotic equivalence between the large-scale growth dynamics of complex networks and causal networks. This equivalence suggests that unexpectedly similar laws govern the dynamics of complex networks and spacetime in the universe, with implications to network science and cosmology.

  11. Network Kits.

    ERIC Educational Resources Information Center

    Falk, Howard

    1999-01-01

    Describes interconnection methods, speed, and comparative equipment costs of networking starter kits. These kits supply network-connection devices that plug into or connect to each computer that is part of a network; they may also provide interconnection cables and installation software needed to set up a network. Reviews 20 kits that use a…

  12. Network Solutions.

    ERIC Educational Resources Information Center

    Vietzke, Robert; And Others

    1996-01-01

    This special section explains the latest developments in networking technologies, profiles school districts benefiting from successful implementations, and reviews new products for building networks. Highlights include ATM (asynchronous transfer mode), cable modems, networking switches, Internet screening software, file servers, network management…

  13. Networking standards

    NASA Technical Reports Server (NTRS)

    Davies, Mark

    1991-01-01

    The enterprise network is currently a multivendor environment consisting of many defacto and proprietary standards. During the 1990s, these networks will evolve towards networks which are based on international standards in both Local Area Network (LAN) and Wide Area Network (WAN) space. Also, you can expect to see the higher level functions and applications begin the same transition. Additional information is given in viewgraph form.

  14. Semantic Networks and Social Networks

    ERIC Educational Resources Information Center

    Downes, Stephen

    2005-01-01

    Purpose: To illustrate the need for social network metadata within semantic metadata. Design/methodology/approach: Surveys properties of social networks and the semantic web, suggests that social network analysis applies to semantic content, argues that semantic content is more searchable if social network metadata is merged with semantic web…

  15. Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke.

    PubMed

    Gustafsson, Elin; Andsberg, Gunnar; Darsalia, Vladimer; Mohapel, Paul; Mandel, Ronald J; Kirik, Deniz; Lindvall, Olle; Kokaia, Zaal

    2003-06-01

    To explore the role of brain-derived neurotrophic factor for survival and generation of striatal neurons after stroke, recombinant adeno-associated viral vectors carrying brain-derived neurotrophic factor or green fluorescent protein genes were injected into right rat substantia nigra 4-5 weeks prior to 30 min ipsilateral of middle cerebral artery occlusion. The brain-derived neurotrophic factor-recombinant adeno-associated viral transduction markedly increased the production of brain-derived neurotrophic factor protein by nigral cells. Brain-derived neurotrophic factor was transported anterogradely to the striatum and released in biologically active form, as revealed by the hypertrophic response of striatal neuropeptide Y-positive interneurons. Animals transduced with brain-derived neurotrophic factor-recombinant adeno-associated virus also exhibited abnormalities in body posture and movements, including tilted body to the right, choreiform movements of left forelimb and head, and spontaneous, so-called 'barrel' rotation along their long axis. The continuous delivery of brain-derived neurotrophic factor had no effect on the survival of striatal projection neurons after stroke, but exaggerated the loss of cholinergic, and parvalbumin- and neuropeptide Y-positive, gamma-aminobutyric acid-ergic interneurons. The high brain-derived neurotrophic factor levels in the animals subjected to stroke also gave rise to an increased number of striatal cells expressing doublecortin, a marker for migrating neuroblasts, and cells double-labelled with the mitotic marker, 5-bromo-2'-deoxyuridine-5'monophosphate, and early neuronal (Hu) or striatal neuronal (Meis2) markers. Our findings indicate that long-term anterograde delivery of high levels of brain-derived neurotrophic factor increases the vulnerability of striatal interneurons to stroke-induced damage. Concomitantly, brain-derived neurotrophic factor potentiates the stroke-induced neurogenic response, at least at early stages.

  16. Acute neurogenic airway plasma exudation and edema induced by inhaled wood smoke in guinea pigs: role of tachykinins and hydroxyl radical.

    PubMed

    Lin, Y S; Kou, Y R

    2000-04-07

    We studied the mechanisms underlying the wood smoke-induced acute airway injury in 120 anaesthetized guinea pigs. Five minutes after airway exposure, various doses of wood smoke produced a dose-dependent increase in Evans blue dye contents at all airway levels measured. Additionally, inhaled wood smoke produced submucosal edema of the trachea and bronchus, and peribronchial edema. These acute airway responses were nearly abolished by pretreatment with CP-96,345 alone [a tachykinin NK(1) receptor antagonist; (2S, 3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-azabicyc lo( 2.2.2.)-octan-3-amine] or with a combination of CP-96,345 and dimethylthiourea (a hydroxyl radical scavenger), and were attenuated by pretreatment with dimethylthiourea alone, yet were not affected by pretreatment with SR-48,968 [a tachykinin NK(2) receptor antagonist; (S)-N-methyl-N(4-(4-acetylamino-4-phenylpiperidino)-2-(3, 4-dichlorophenyl)-butyl)benzamide], with a combination of CP-96,344 and SR-48,965 (inactive enantiomers), with MK-886 [a leukotriene biosynthesis inhibitor; L-663, 536(3-(1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl)-2, 2-dimethylpropanoic acid], with indomethacin (a cyclooxygenase inhibitor), or with N(G)-nitro-L-arginine methyl ester (a nitric oxide (NO) synthase inhibitor). The activity of airway neutral endopeptidase (an enzyme for tachykinin degradation) was not influenced by wood smoke at 5-min post-exposure. We conclude that both endogenous tachykinins and hydroxyl radical play an important role in producing smoke-induced acute airway plasma exudation and airway edema in guinea pigs. The contribution of tachykinins to these neurogenic responses is mediated via the activation of tachykinin NK(1) receptors and partly via a hydroxyl radical mechanism, and is not associated with inactivation of neutral endopeptidase.

  17. Feedback From Peripheral Musculature to Central Pattern Generator in the Neurogenic Heart of the Crab Callinectes sapidus: Role of Mechanosensitive Dendrites

    PubMed Central

    García-Crescioni, Keyla; Fort, Timothy J.; Stern, Estee; Brezina, Vladimir

    2010-01-01

    The neurogenic heart of decapod crustaceans is a very simple, self-contained, model central pattern generator (CPG)-effector system. The CPG, the nine-neuron cardiac ganglion (CG), is embedded in the myocardium itself; it generates bursts of spikes that are transmitted by the CG's five motor neurons to the periphery of the system, the myocardium, to produce its contractions. Considerable evidence suggests that a CPG-peripheral loop is completed by a return feedback pathway through which the contractions modify, in turn, the CG motor pattern. One likely pathway is provided by dendrites, presumably mechanosensitive, that the CG neurons project into the adjacent myocardial muscle. Here we have tested the role of this pathway in the heart of the blue crab, Callinectes sapidus. We performed “de-efferentation” experiments in which we cut the motor neuron axons to the myocardium and “de-afferentation” experiments in which we cut or ligated the dendrites. In the isolated CG, these manipulations had no effect on the CG motor pattern. When the CG remained embedded in the myocardium, however, these manipulations, interrupting either the efferent or afferent limb of the CPG-peripheral loop, decreased contraction amplitude, increased the frequency of the CG motor neuron spike bursts, and decreased the number of spikes per burst and burst duration. Finally, passive stretches of the myocardium likewise modulated the spike bursts, an effect that disappeared when the dendrites were cut. We conclude that feedback through the dendrites indeed operates in this system and suggest that it completes a loop through which the system self-regulates its activity. PMID:19828726

  18. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

    PubMed Central

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

  19. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.

    PubMed

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.

  20. Neurogenic detrusor overactivity is associated with decreased expression and function of the large conductance voltage- and Ca(2+)-activated K(+) channels.

    PubMed

    Hristov, Kiril L; Afeli, Serge A Y; Parajuli, Shankar P; Cheng, Qiuping; Rovner, Eric S; Petkov, Georgi V

    2013-01-01

    Patients suffering from a variety of neurological diseases such as spinal cord injury, Parkinson's disease, and multiple sclerosis often develop neurogenic detrusor overactivity (NDO), which currently lacks a universally effective therapy. Here, we tested the hypothesis that NDO is associated with changes in detrusor smooth muscle (DSM) large conductance Ca(2+)-activated K(+) (BK) channel expression and function. DSM tissue samples from 33 patients were obtained during open bladder surgeries. NDO patients were clinically characterized preoperatively with pressure-flow urodynamics demonstrating detrusor overactivity, in the setting of a clinically relevant neurological condition. Control patients did not have overactive bladder and did not have a clinically relevant neurological disease. We conducted quantitative polymerase chain reactions (qPCR), perforated patch-clamp electrophysiology on freshly-isolated DSM cells, and functional studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO patients showed decreased BK channel mRNA expression in comparison to controls. Patch-clamp experiments demonstrated reduced whole cell and transient BK currents (TBKCs) in freshly-isolated DSM cells from NDO patients. Functional studies on DSM contractility showed that spontaneous phasic contractions had a decreased sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips isolated from NDO patients. These results reveal the novel finding that NDO is associated with decreased DSM BK channel expression and function leading to increased DSM excitability and contractility. BK channel openers or BK channel gene transfer could be an alternative strategy to control NDO. Future clinical trials are needed to evaluate the value of BK channel opening drugs or gene therapies for NDO treatment and to identify any possible adverse effects.

  1. The use of autologous neurogenically-induced bone marrow-derived mesenchymal stem cells for the treatment of paraplegic dogs without nociception due to spinal trauma

    PubMed Central

    BESALTI, Omer; AKTAS, Zeynep; CAN, Pinar; AKPINAR, Eylul; ELCIN, Ayse Eser; ELCIN, Yasar Murat

    2016-01-01

    The aim of this study was to investigate the effects of percutaneous transplanted autologous neurogenically-induced bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to external spinal trauma. Thirteen client owned dogs that had failed in improvement neurologically at least 42 days after conservative management, decompression and decompression-stabilization were included in the study. Each dog received two doses of autologous 5.0 × 106 NIBM-MSCs suspension, which were positive to 2′,3′-Cyclic-nucleotide-3′-phosphodiesterase (CNPase) and Microtubule-associated protein 2 (MAP-2), as well as to Glial fibrillary acidic protein (GFAP) and beta III tubulin. The cells were injected into the spinal cord through the hemilaminectomy or laminectomy defects percutaneously with 21 days interval for 2 times. The results were evaluated using Texas Spinal Cord Injury Scale (TSCIS), somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) at the admission time, cell transplantation procedures and during 2, 5, 7 and 12th months after the second cell transplantation. Improvement after cell transplantation in gait, nociception, proprioception, SEP and MEP results was observed in just 2 cases, and only gait score improvement was seen in 6 cases, and no improvement was recorded in 5 cases. All progresses were observed until 2nd month after the second cell transplantation, however, there was no improvement after this period. In conclusion, percutaneous transplantation of autologous NIBM-MSCs is a promising candidate modality for cases with spinal cord injury after spinal trauma and poor prognosis. PMID:27301583

  2. ALCAR Exerts Neuroprotective and Pro-Neurogenic Effects by Inhibition of Glial Activation and Oxidative Stress via Activation of the Wnt/β-Catenin Signaling in Parkinsonian Rats.

    PubMed

    Singh, Sonu; Mishra, Akanksha; Shukla, Shubha

    2016-09-01

    Oxidative stress and neuroinflammation are known causative factors in progressive degeneration of dopaminergic (DAergic) neurons in Parkinson's disease (PD). Neural stem cells (NSCs) contribute in maintaining brain plasticity; therefore, survival of NSCs and neuroblasts during neurodegenerative process becomes important in replenishing the pool of mature neuronal population. Acetyl-L-carnitine (ALCAR), present in almost all body cells, increases endogenous antioxidants and regulates bioenergetics. Currently, no information is available about the putative mechanism and neuroprotective effects of ALCAR in 6-hydroxydopamine (6-OHDA)-induced rat model of PD-like phenotypes. Herein, we investigated the effect of ALCAR on death/survival of DAergic neurons, neuroblasts and NSCs and associates mechanism of neuroprotection in 6-OHDA-induced rat model of PD-like phenotypes. ALCAR (100 mg/kg/day, intraperitoneal (i.p.)) treatment started 3 days prior to 6-OHDA lesioning and continued for another 14 day post-lesioning. We found that ALCAR pretreatment in 6-OHDA-lesioned rats increased expression of neurogenic and the Wnt pathway genes in the striatum and substantia nigra pars compacta (SNpc) region. It suppressed the glial cell activation, improved antioxidant status, increased NSC/neuroblast population and rescued the DAergic neurons in nigrostriatal pathway. ALCAR pretreatment in 6-OHDA-lesioned rats decreased GSK-3β activation and increased nuclear translocation of β-catenin. Functional deficits were restored following ALCAR pretreatment in 6-OHDA-lesioned rats as demonstrated by improved motor coordination and rotational behaviour, confirming protection of DAergic innervations in lesioned striatum. These results indicate that ALCAR exerts neuroprotective effects through the activation of Wnt/β-catenin pathway, suggesting its therapeutic use to treat neurodegenerative diseases by enhancing regenerative capacity.

  3. A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients

    PubMed Central

    Fava, M; Johe, K; Ereshefsky, L; Gertsik, L G; English, B A; Bilello, J A; Thurmond, L M; Johnstone, J; Dickerson, B C; Makris, N; Hoeppner, B B; Flynn, M; Mischoulon, D; Kinrys, G; Freeman, M P

    2016-01-01

    We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg b.i.d. (n=6) or placebo (n=2), and the third cohort 40 mg t.i.d. (n=6) or placebo (n=2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4–20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions—Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort. PMID:26643541

  4. Remote Control of Respiratory Neural Network by Spinal Locomotor Generators

    PubMed Central

    Le Gal, Jean-Patrick; Juvin, Laurent; Cardoit, Laura; Thoby-Brisson, Muriel; Morin, Didier

    2014-01-01

    During exercise and locomotion, breathing rate rapidly increases to meet the suddenly enhanced oxygen demand. The extent to which direct central interactions between the spinal networks controlling locomotion and the brainstem networks controlling breathing are involved in this rhythm modulation remains unknown. Here, we show that in isolated neonatal rat brainstem-spinal cord preparations, the increase in respiratory rate observed during fictive locomotion is associated with an increase in the excitability of pre-inspiratory neurons of the parafacial respiratory group (pFRG/Pre-I). In addition, this locomotion-induced respiratory rhythm modulation is prevented both by bilateral lesion of the pFRG region and by blockade of neurokinin 1 receptors in the brainstem. Thus, our results assign pFRG/Pre-I neurons a new role as elements of a previously undescribed pathway involved in the functional interaction between respiratory and locomotor networks, an interaction that also involves a substance P-dependent modulating mechanism requiring the activation of neurokinin 1 receptors. This neurogenic mechanism may take an active part in the increased respiratory rhythmicity produced at the onset and during episodes of locomotion in mammals. PMID:24586951

  5. Network Basics.

    ERIC Educational Resources Information Center

    Tennant, Roy

    1992-01-01

    Explains how users can find and access information resources available on the Internet. Highlights include network information centers (NICs); lists, both formal and informal; computer networking protocols, including international standards; electronic mail; remote log-in; and file transfer. (LRW)

  6. Network neuroscience.

    PubMed

    Bassett, Danielle S; Sporns, Olaf

    2017-02-23

    Despite substantial recent progress, our understanding of the principles and mechanisms underlying complex brain function and cognition remains incomplete. Network neuroscience proposes to tackle these enduring challenges. Approaching brain structure and function from an explicitly integrative perspective, network neuroscience pursues new ways to map, record, analyze and model the elements and interactions of neurobiological systems. Two parallel trends drive the approach: the availability of new empirical tools to create comprehensive maps and record dynamic patterns among molecules, neurons, brain areas and social systems; and the theoretical framework and computational tools of modern network science. The convergence of empirical and computational advances opens new frontiers of scientific inquiry, including network dynamics, manipulation and control of brain networks, and integration of network processes across spatiotemporal domains. We review emerging trends in network neuroscience and attempt to chart a path toward a better understanding of the brain as a multiscale networked system.

  7. Network science.

    PubMed

    Barabási, Albert-László

    2013-03-28

    Professor Barabási's talk described how the tools of network science can help understand the Web's structure, development and weaknesses. The Web is an information network, in which the nodes are documents (at the time of writing over one trillion of them), connected by links. Other well-known network structures include the Internet, a physical network where the nodes are routers and the links are physical connections, and organizations, where the nodes are people and the links represent communications.

  8. Integrated Networks.

    ERIC Educational Resources Information Center

    Robinovitz, Stewart

    1987-01-01

    A strategy for integrated data and voice networks implemented at the University of Michigan is described. These networks often use multi-technologies, multi-vendors, and multi-transmission media that will be fused into a single integrated network. Transmission media include twisted-pair wire, coaxial cable, fiber optics, and microwave. (Author/MLW)

  9. Superelastic networks

    SciTech Connect

    Obukhov, S.P.; Rubinstein, M.; Colby, R.H.

    1993-12-31

    This paper discusses the elastic modulus, swelling, and deswelling behavior of networks as a function of their concentration and the preparation state. Based on these results, the authors expect that networks prepared by crosslinking long chains at low concentration, followed by removal of solvent, will have superelastic properties - the deswollen networks will have low modulus and will be capable of stretching by enormous amounts without breaking. This is because deswelling introduces only temporary entanglements. These temporary entanglements change the static configuration of the network strands. The authors discuss the non-Gaussian nature of these strands and the linear viscoelastic response of the superelastic networks.

  10. Networking computers.

    PubMed

    McBride, D C

    1997-03-01

    This decade the role of the personal computer has shifted dramatically from a desktop device designed to increase individual productivity and efficiency to an instrument of communication linking people and machines in different places with one another. A computer in one city can communicate with another that may be thousands of miles away. Networking is how this is accomplished. Just like the voice network used by the telephone, computer networks transmit data and other information via modems over these same telephone lines. A network can be created over both short and long distances. Networks can be established within a hospital or medical building or over many hospitals or buildings covering many geographic areas. Those confined to one location are called LANs, local area networks. Those that link computers in one building to those at other locations are known as WANs, or wide area networks. The ultimate wide area network is the one we've all been hearing so much about these days--the Internet, and its World Wide Web. Setting up a network is a process that requires careful planning and commitment. To avoid potential pitfalls and to make certain the network you establish meets your needs today and several years down the road, several steps need to be followed. This article reviews the initial steps involved in getting ready to network.

  11. Vulnerability of network of networks

    NASA Astrophysics Data System (ADS)

    Havlin, S.; Kenett, D. Y.; Bashan, A.; Gao, J.; Stanley, H. E.

    2014-10-01

    Our dependence on networks - be they infrastructure, economic, social or others - leaves us prone to crises caused by the vulnerabilities of these networks. There is a great need to develop new methods to protect infrastructure networks and prevent cascade of failures (especially in cases of coupled networks). Terrorist attacks on transportation networks have traumatized modern societies. With a single blast, it has become possible to paralyze airline traffic, electric power supply, ground transportation or Internet communication. How, and at which cost can one restructure the network such that it will become more robust against malicious attacks? The gradual increase in attacks on the networks society depends on - Internet, mobile phone, transportation, air travel, banking, etc. - emphasize the need to develop new strategies to protect and defend these crucial networks of communication and infrastructure networks. One example is the threat of liquid explosives a few years ago, which completely shut down air travel for days, and has created extreme changes in regulations. Such threats and dangers warrant the need for new tools and strategies to defend critical infrastructure. In this paper we review recent advances in the theoretical understanding of the vulnerabilities of interdependent networks with and without spatial embedding, attack strategies and their affect on such networks of networks as well as recently developed strategies to optimize and repair failures caused by such attacks.

  12. Lack of transient receptor potential vanilloid 1 channel modulates the development of neurogenic bladder dysfunction induced by cross-sensitization in afferent pathways

    PubMed Central

    2013-01-01

    Background Bladder pain of unknown etiology has been associated with co-morbid conditions and functional abnormalities in neighboring pelvic organs. Mechanisms underlying pain co-morbidities include cross-sensitization, which occurs predominantly via convergent neural pathways connecting distinct pelvic organs. Our previous results showed that colonic inflammation caused detrusor instability via activation of transient receptor potential vanilloid 1 (TRPV1) signaling pathways, therefore, we aimed to determine whether neurogenic bladder dysfunction can develop in the absence of TRPV1 receptors. Methods Adult male C57BL/6 wild-type (WT) and TRPV1−/− (knockout) mice were used in this study. Colonic inflammation was induced by intracolonic trinitrobenzene sulfonic acid (TNBS). The effects of transient colitis on abdominal sensitivity and function of the urinary bladder were evaluated by cystometry, contractility and relaxation of detrusor smooth muscle (DSM) in vitro to various stimuli, gene and protein expression of voltage-gated sodium channels in bladder sensory neurons, and pelvic responses to mechanical stimulation. Results Knockout of TRPV1 gene did not eliminate the development of cross-sensitization between the colon and urinary bladder. However, TRPV1−/− mice had prolonged intermicturition interval and increased number of non-voiding contractions at baseline followed by reduced urodynamic responses during active colitis. Contractility of DSM was up-regulated in response to KCl in TRPV1−/− mice with inflamed colon. Application of Rho-kinase inhibitor caused relaxation of DSM in WT but not in TRPV1−/− mice during colonic inflammation. TRPV1−/− mice demonstrated blunted effects of TNBS-induced colitis on expression and function of voltage-gated sodium channels in bladder sensory neurons, and delayed development of abdominal hypersensitivity upon colon-bladder cross-talk in genetically modified animals. Conclusions The lack of TRPV1 receptors

  13. The role of hypoxia and neurogenic genes (Mash-1 and Prox-1) in the developmental programming and maturation of pulmonary neuroendocrine cells in fetal mouse lung.

    PubMed

    McGovern, Suzanne; Pan, Jie; Oliver, Guillermo; Cutz, Ernest; Yeger, Herman

    2010-02-01

    Pulmonary neuroendocrine cells (PNECs) are the first cell type to differentiate within the primitive airway epithelium, suggesting a possible role in lung development. The differentiation of PNECs in fetal lung is governed by proneural genes such as the mammalian homolog of the achaete-scute complex (Mash-1) and a related transcription factor, hairy and enhancer of split1 (Hes-1). We examined the expression of Mash-1 and a downstream transcription factor Prox-1 in the developing mouse lung of wild-type and respective knockout mouse models. During early stages (embryonic day 12, E12) of development, only some PNECs expressed Mash-1 and Prox-1, but by E15, all PNECs coexpressed both transcription factors. PNECs failed to develop in Mash-1 but not in Prox-1-null mice, indicating that Mash-1 is essential for the initiation of the PNEC phenotype, whereas Prox-1 is associated with the development of this phenotype. As lung develops within a low O(2) environment (fetal euoxia, pO(2) approximately 20 to 30 mm Hg), we examined the effects of hypoxia on PNEC differentiation. Organ cultures of fetal mouse lungs at E12 and E16 were maintained under either 20% O(2) (normoxia, Nox) or 5% O(2) (hypoxia, Hox) and were examined every 24 h for up to 6 days in culture. In E12 explants, Hox enhanced branching morphogenesis and increased cell proliferation, but PNEC numbers and Mash-1 expression were significantly reduced. This effect could be reversed by switching the explants back to Nox. In contrast, Hox had no apparent effect on Hes-1 expression. Similarly, Hox had no effect on airway branching, PNEC numbers, or Mash-1 expression in E16 explants, indicating locked-in developmental programming. We suggest that during early stages of lung development, pO(2) concentration in concert with neurogenic gene expression modulates PNEC phenotype. Thus, disturbances in intrauterine pO(2) homeostasis could alter the functional maturation of the PNEC system and hence be involved in the

  14. An Intronic cis-Regulatory Element Is Crucial for the Alpha Tubulin Pl-Tuba1a Gene Activation in the Ciliary Band and Animal Pole Neurogenic Domains during Sea Urchin Development

    PubMed Central

    Cuttitta, Angela; Gianguzza, Fabrizio; Ragusa, Maria Antonietta

    2017-01-01

    In sea urchin development, structures derived from neurogenic territory control the swimming and feeding responses of the pluteus as well as the process of metamorphosis. We have previously isolated an alpha tubulin family member of Paracentrotus lividus (Pl-Tuba1a, formerly known as Pl-Talpha2) that is specifically expressed in the ciliary band and animal pole neurogenic domains of the sea urchin embryo. In order to identify cis-regulatory elements controlling its spatio-temporal expression, we conducted gene transfer experiments, transgene deletions and site specific mutagenesis. Thus, a genomic region of about 2.6 Kb of Pl-Tuba1a, containing four Interspecifically Conserved Regions (ICRs), was identified as responsible for proper gene expression. An enhancer role was ascribed to ICR1 and ICR2, while ICR3 exerted a pivotal role in basal expression, restricting Tuba1a expression to the proper territories of the embryo. Additionally, the mutation of the forkhead box consensus sequence binding site in ICR3 prevented Pl-Tuba1a expression. PMID:28141828

  15. Neural Networks

    DTIC Science & Technology

    1990-01-01

    FUNDING NUMBERS PROGRAM PROJECT TASK WORK UNIT ELEMENT NO. NO. NO. ACCESSION NO 11 TITLE (Include Security Classification) NEURAL NETWORKS 12. PERSONAL...SUB-GROUP Neural Networks Optical Architectures Nonlinear Optics Adaptation 19. ABSTRACT (Continue on reverse if necessary and identify by block number...341i Y C-odes , lo iii/(iv blank) 1. INTRODUCTION Neural networks are a type of distributed processing system [1

  16. Network reliability

    NASA Technical Reports Server (NTRS)

    Johnson, Marjory J.

    1985-01-01

    Network control (or network management) functions are essential for efficient and reliable operation of a network. Some control functions are currently included as part of the Open System Interconnection model. For local area networks, it is widely recognized that there is a need for additional control functions, including fault isolation functions, monitoring functions, and configuration functions. These functions can be implemented in either a central or distributed manner. The Fiber Distributed Data Interface Medium Access Control and Station Management protocols provide an example of distributed implementation. Relative information is presented here in outline form.

  17. Innovation Networks

    NASA Astrophysics Data System (ADS)

    Pyka, Andreas; Scharnhorst, Andrea

    The idea for this book started when we organized a topical workshop entitled "Innovation Networks - New Approaches in Modeling and Analyzing" (held in Augsburg, Germany in October 2005), under the auspices of Exystence, a network of excellence funded in the European Union's Fifth Framework Program. Unlike other conferences on innovation and networks, however, this workshop brought together scientists from economics, sociology, communication science, science and technology studies, and physics. With this book we aim to build further on a bridge connecting the bodies of knowledge on networks in economics, the social sciences and, more recently, statistical physics.

  18. Neurogenic bladder: etiology and assessment

    PubMed Central

    2008-01-01

    A review of the various causes of neurologic impairment to the lower urinary tract in children was the aim of this presentation. The emphasis was on diagnosis, pathophysiology, and treatment that strive to maintain as normal a function as possible in order to achieve eventual urinary continence and health of the upper urinary tract. The latest principles based on the most up to date evidence are promulgated but with an eye towards historical prospective. The reader should gain an adequate understanding of various disorders that comprise this condition and feel comfortable with proposing options for management when faced with the responsibility of caring for an affected child. PMID:18270749

  19. Infantile amnesia: a neurogenic hypothesis.

    PubMed

    Josselyn, Sheena A; Frankland, Paul W

    2012-08-16

    In the late 19th Century, Sigmund Freud described the phenomenon in which people are unable to recall events from early childhood as infantile amnesia. Although universally observed, infantile amnesia is a paradox; adults have surprisingly few memories of early childhood despite the seemingly exuberant learning capacity of young children. How can these findings be reconciled? The mechanisms underlying this form of amnesia are the subject of much debate. Psychological/cognitive theories assert that the ability to maintain detailed, declarative-like memories in the long term correlates with the development of language, theory of mind, and/or sense of "self." However, the finding that experimental animals also show infantile amnesia suggests that this phenomenon cannot be explained fully in purely human terms. Biological explanations of infantile amnesia suggest that protracted postnatal development of key brain regions important for memory interferes with stable long-term memory storage, yet they do not clearly specify which particular aspects of brain maturation are causally related to infantile amnesia. Here, we propose a hypothesis of infantile amnesia that focuses on one specific aspect of postnatal brain development--the continued addition of new neurons to the hippocampus. Infants (humans, nonhuman primates, and rodents) exhibit high levels of hippocampal neurogenesis and an inability to form lasting memories. Interestingly, the decline of postnatal neurogenesis levels corresponds to the emergence of the ability to form stable long-term memory. We propose that high neurogenesis levels negatively regulate the ability to form enduring memories, most likely by replacing synaptic connections in preexisting hippocampal memory circuits.

  20. Network Flows

    DTIC Science & Technology

    1988-12-01

    Researchers have suggested other solution strategies, using ideas from nonlinear progamming for solving this general separable convex cost flow problems. Some...plane methods and branch and bound procedures of integer programming, primal-dual methods of linear and nonlinear programming, and polyhedral methods...Combinatorial Optimization: Networks and Matroids), Bazaraa and Jarvis [1978] (Linear Programming and Network Flows), Minieka [1978] (Optimization Algorithms for

  1. Temporal networks

    NASA Astrophysics Data System (ADS)

    Holme, Petter; Saramäki, Jari

    2012-10-01

    A great variety of systems in nature, society and technology-from the web of sexual contacts to the Internet, from the nervous system to power grids-can be modeled as graphs of vertices coupled by edges. The network structure, describing how the graph is wired, helps us understand, predict and optimize the behavior of dynamical systems. In many cases, however, the edges are not continuously active. As an example, in networks of communication via e-mail, text messages, or phone calls, edges represent sequences of instantaneous or practically instantaneous contacts. In some cases, edges are active for non-negligible periods of time: e.g., the proximity patterns of inpatients at hospitals can be represented by a graph where an edge between two individuals is on throughout the time they are at the same ward. Like network topology, the temporal structure of edge activations can affect dynamics of systems interacting through the network, from disease contagion on the network of patients to information diffusion over an e-mail network. In this review, we present the emergent field of temporal networks, and discuss methods for analyzing topological and temporal structure and models for elucidating their relation to the behavior of dynamical systems. In the light of traditional network theory, one can see this framework as moving the information of when things happen from the dynamical system on the network, to the network itself. Since fundamental properties, such as the transitivity of edges, do not necessarily hold in temporal networks, many of these methods need to be quite different from those for static networks. The study of temporal networks is very interdisciplinary in nature. Reflecting this, even the object of study has many names-temporal graphs, evolving graphs, time-varying graphs, time-aggregated graphs, time-stamped graphs, dynamic networks, dynamic graphs, dynamical graphs, and so on. This review covers different fields where temporal graphs are considered

  2. Technological Networks

    NASA Astrophysics Data System (ADS)

    Mitra, Bivas

    The study of networks in the form of mathematical graph theory is one of the fundamental pillars of discrete mathematics. However, recent years have witnessed a substantial new movement in network research. The focus of the research is shifting away from the analysis of small graphs and the properties of individual vertices or edges to consideration of statistical properties of large scale networks. This new approach has been driven largely by the availability of technological networks like the Internet [12], World Wide Web network [2], etc. that allow us to gather and analyze data on a scale far larger than previously possible. At the same time, technological networks have evolved as a socio-technological system, as the concepts of social systems that are based on self-organization theory have become unified in technological networks [13]. In today’s society, we have a simple and universal access to great amounts of information and services. These information services are based upon the infrastructure of the Internet and the World Wide Web. The Internet is the system composed of ‘computers’ connected by cables or some other form of physical connections. Over this physical network, it is possible to exchange e-mails, transfer files, etc. On the other hand, the World Wide Web (commonly shortened to the Web) is a system of interlinked hypertext documents accessed via the Internet where nodes represent web pages and links represent hyperlinks between the pages. Peer-to-peer (P2P) networks [26] also have recently become a popular medium through which huge amounts of data can be shared. P2P file sharing systems, where files are searched and downloaded among peers without the help of central servers, have emerged as a major component of Internet traffic. An important advantage in P2P networks is that all clients provide resources, including bandwidth, storage space, and computing power. In this chapter, we discuss these technological networks in detail. The review

  3. Innovation network

    PubMed Central

    Acemoglu, Daron; Akcigit, Ufuk; Kerr, William R.

    2016-01-01

    Technological progress builds upon itself, with the expansion of invention in one domain propelling future work in linked fields. Our analysis uses 1.8 million US patents and their citation properties to map the innovation network and its strength. Past innovation network structures are calculated using citation patterns across technology classes during 1975–1994. The interaction of this preexisting network structure with patent growth in upstream technology fields has strong predictive power on future innovation after 1995. This pattern is consistent with the idea that when there is more past upstream innovation for a particular technology class to build on, then that technology class innovates more. PMID:27681628

  4. Innovation network.

    PubMed

    Acemoglu, Daron; Akcigit, Ufuk; Kerr, William R

    2016-10-11

    Technological progress builds upon itself, with the expansion of invention in one domain propelling future work in linked fields. Our analysis uses 1.8 million US patents and their citation properties to map the innovation network and its strength. Past innovation network structures are calculated using citation patterns across technology classes during 1975-1994. The interaction of this preexisting network structure with patent growth in upstream technology fields has strong predictive power on future innovation after 1995. This pattern is consistent with the idea that when there is more past upstream innovation for a particular technology class to build on, then that technology class innovates more.

  5. Sentinel Network

    Cancer.gov

    The Sentinel Network is an integrated, electronic, national medical product safety initiative that compiles information about the safe and effective use of medical products accessible to patients and healthcare practitioners.

  6. Exchange Network

    EPA Pesticide Factsheets

    The Environmental Information Exchange Network (EIEN) is an Internet-based system used by state, tribal and territorial partners to securely share environmental and health information with one another and EPA.

  7. Surgical therapy of neurogenic detrusor overactivity (hyperreflexia) in paraplegic patients by sacral deafferentation and implant driven micturition by sacral anterior root stimulation: methods, indications, results, complications, and future prospects.

    PubMed

    Kutzenberger, J

    2007-01-01

    Spinal cord injured patients with a suprasacral lesion usually develop a spastic bladder. The neurogenic detrusor overactivity (NDO) and the overactive external sphincter cause incontinence and threaten these patients with recurrent urinary tract infections (UTI), renal failure and autonomic dysreflexia. All of these severe disturbances may be well managed by sacral deafferentation (SDAF) and implantation of a sacral anterior root stimulator (SARS). Since September 1986 to December 2002, 464 paraplegic patients (220 females, 244 males) received a SDAF-SARS. The SDAF was done intradurally in almost all cases, which means that we used a single operation field to do a two-stages procedure (SDAF and SARS). The results include data on 440 patients with a mean follow-up of 8.6 years (18 months to 18 years) until December 2004. The complete deafferentation was successful in 95.2%. Of these patients, 420 paraplegics use the SARS for voiding, (frequency 4.7 per day) and 401 for defecation (frequency 4.7 per week). Continence was achieved in 364 patients (83%). UTIs decreased from 6.3 per year preoperatively to 1.2 per year postoperatively. Kidney function remained stable. Early complications were 6 CSF leaks and 5 implant infections. Late compli cations included receiver or cable failures and required surgical repair in 44 patients. A step-by-step program for trouble-shooting distinguishes implant failure from myogenic or neurogenic failure. SDAF is able to restore the reservoir function of urinary bladder and makes the patient achieve continence. Autonomic dysreflexia disappeared in most cases. By accurate adjustment of stimulation parameters, it is possible for the patient to have a low resistance micturition. The microsurgical technique requires intensive education. In addition, the therapist should be able to manage late complications.

  8. Redox-Sensitive Oxidation and Phosphorylation of PTEN Contribute to Enhanced Activation of PI3K/Akt Signaling in Rostral Ventrolateral Medulla and Neurogenic Hypertension in Spontaneously Hypertensive Rats

    PubMed Central

    Wu, Kay L.H.; Wu, Chiung-Ai; Wu, Chih-Wei; Chan, Samuel H.H.; Chang, Alice Y.W.

    2013-01-01

    Abstract Aims: The activity of phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (Akt) is enhanced under hypertension. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of PI3K signaling, and its activity is redox-sensitive. In the rostral ventrolateral medulla (RVLM), which is responsible for the maintenance of blood pressure, oxidative stress plays a pivotal role in neurogenic hypertension. The present study evaluated the hypothesis that redox-sensitive inactivation of PTEN results in enhanced PI3K/Akt signaling in RVLM, leading to neurogenic hypertension. Results: Compared to age-matched normotensive Wistar-Kyoto (WKY) rats, PTEN inactivation in the form of oxidation and phosphorylation were greater in RVLM of spontaneously hypertensive rats (SHR). PTEN inactivation was accompanied by augmented PI3K activity and PI3K/Akt signaling, as reflected by the increase in phosphorylation of Akt and mammalian target of rapamycin. Intracisternal infusion of tempol or microinjection into the bilateral RVLM of adenovirus encoding superoxide dismutase significantly antagonized the PTEN inactivation and blunted the enhanced PI3K/Akt signaling in SHR. Gene transfer of PTEN to RVLM in SHR also abrogated the enhanced Akt activation and promoted antihypertension. Silencing PTEN expression in RVLM with small-interfering RNA, on the other hand, augmented PI3K/Akt signaling and promoted long-term pressor response in normotensive WKY rats. Innovation: The present study demonstrated for the first time that the redox-sensitive check-and-balance process between PTEN and PI3K/Akt signaling is engaged in the pathogenesis of hypertension. Conclusion: We conclude that an aberrant interplay between the redox-sensitive PTEN and PI3k/Akt signaling in RVLM underpins neural mechanism of hypertension. Antioxid. Redox Signal. 18, 36–50. PMID:22746319

  9. Developer Network

    SciTech Connect

    2012-08-21

    NREL's Developer Network, developer.nrel.gov, provides data that users can access to provide data to their own analyses, mobile and web applications. Developers can retrieve the data through a Web services API (application programming interface). The Developer Network handles overhead of serving up web services such as key management, authentication, analytics, reporting, documentation standards, and throttling in a common architecture, while allowing web services and APIs to be maintained and managed independently.

  10. Sentient networks

    SciTech Connect

    Chapline, G.

    1998-03-01

    The engineering problems of constructing autonomous networks of sensors and data processors that can provide alerts for dangerous situations provide a new context for debating the question whether man-made systems can emulate the cognitive capabilities of the mammalian brain. In this paper we consider the question whether a distributed network of sensors and data processors can form ``perceptions`` based on sensory data. Because sensory data can have exponentially many explanations, the use of a central data processor to analyze the outputs from a large ensemble of sensors will in general introduce unacceptable latencies for responding to dangerous situations. A better idea is to use a distributed ``Helmholtz machine`` architecture in which the sensors are connected to a network of simple processors, and the collective state of the network as a whole provides an explanation for the sensory data. In general communication within such a network will require time division multiplexing, which opens the door to the possibility that with certain refinements to the Helmholtz machine architecture it may be possible to build sensor networks that exhibit a form of artificial consciousness.

  11. Neural Networks

    SciTech Connect

    Smith, Patrick I.

    2003-09-23

    Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing

  12. Network motif identification in stochastic networks

    NASA Astrophysics Data System (ADS)

    Jiang, Rui; Tu, Zhidong; Chen, Ting; Sun, Fengzhu

    2006-06-01

    Network motifs have been identified in a wide range of networks across many scientific disciplines and are suggested to be the basic building blocks of most complex networks. Nonetheless, many networks come with intrinsic and/or experimental uncertainties and should be treated as stochastic networks. The building blocks in these networks thus may also have stochastic properties. In this article, we study stochastic network motifs derived from families of mutually similar but not necessarily identical patterns of interconnections. We establish a finite mixture model for stochastic networks and develop an expectation-maximization algorithm for identifying stochastic network motifs. We apply this approach to the transcriptional regulatory networks of Escherichia coli and Saccharomyces cerevisiae, as well as the protein-protein interaction networks of seven species, and identify several stochastic network motifs that are consistent with current biological knowledge. expectation-maximization algorithm | mixture model | transcriptional regulatory network | protein-protein interaction network

  13. Metabolic Networks

    NASA Astrophysics Data System (ADS)

    Palumbo, Maria Concetta; Farina, Lorenzo; Colosimo, Alfredo; Giuliani, Alessandro

    The use of the term `network' is more and more widespread in all fields of biology. It evokes a systemic approach to biological problems able to overcome the evident limitations of the strict reductionism of the past twenty years. The expectations produced by taking into considerations not only the single elements but even the intermingled `web' of links connecting different parts of biological entities, are huge. Nevertheless, we believe that the lack of consciousness that networks, beside their biological `likelihood', are modeling tools and not real entities, could be detrimental to the exploitation of the full potential of this paradigm. Like any modeling tool the network paradigm has a range of application going from situations in which it is particularly fit to situations in which its application can be largely misleading. In this chapter we deal with an aspect of biological entities that is particularly fit for the network approach: the intermediate metabolism. This fit derives both from the existence of a privileged formalization in which the relative role of nodes (metabolites) and arches (enzymes) is immediately suggested by the system architecture. Here we will discuss some applications of both graph theory based analysis and multidimensional statistics method to metabolic network studies with the emphasis on the derivation of biologically meaningful information.

  14. Network dismantling

    PubMed Central

    Braunstein, Alfredo; Dall’Asta, Luca; Semerjian, Guilhem; Zdeborová, Lenka

    2016-01-01

    We study the network dismantling problem, which consists of determining a minimal set of vertices in which removal leaves the network broken into connected components of subextensive size. For a large class of random graphs, this problem is tightly connected to the decycling problem (the removal of vertices, leaving the graph acyclic). Exploiting this connection and recent works on epidemic spreading, we present precise predictions for the minimal size of a dismantling set in a large random graph with a prescribed (light-tailed) degree distribution. Building on the statistical mechanics perspective, we propose a three-stage Min-Sum algorithm for efficiently dismantling networks, including heavy-tailed ones for which the dismantling and decycling problems are not equivalent. We also provide additional insights into the dismantling problem, concluding that it is an intrinsically collective problem and that optimal dismantling sets cannot be viewed as a collection of individually well-performing nodes. PMID:27791075

  15. Rapid Network Design

    DTIC Science & Technology

    2013-09-01

    packet- switched networks are extremely prone to human design faults, which can adversely affect the reliability of the network. This thesis proposes an...network devices and create a functioning packet- switch network. network design , network topology, packet- switching networks, routing protocols, data... switched networks are extremely prone to human design faults, which can adversely affect the reliability of the network. This thesis proposes an

  16. Network Physiology: Mapping Interactions Between Networks of Physiologic Networks

    NASA Astrophysics Data System (ADS)

    Ivanov, Plamen Ch.; Bartsch, Ronny P.

    The human organism is an integrated network of interconnected and interacting organ systems, each representing a separate regulatory network. The behavior of one physiological system (network) may affect the dynamics of all other systems in the network of physiologic networks. Due to these interactions, failure of one system can trigger a cascade of failures throughout the entire network. We introduce a systematic method to identify a network of interactions between diverse physiologic organ systems, to quantify the hierarchical structure and dynamics of this network, and to track its evolution under different physiologic states. We find a robust relation between network structure and physiologic states: every state is characterized by specific network topology, node connectivity and links strength. Further, we find that transitions from one physiologic state to another trigger a markedly fast reorganization in the network of physiologic interactions on time scales of just a few minutes, indicating high network flexibility in response to perturbations. This reorganization in network topology occurs simultaneously and globally in the entire network as well as at the level of individual physiological systems, while preserving a hierarchical order in the strength of network links. Our findings highlight the need of an integrated network approach to understand physiologic function, since the framework we develop provides new information which can not be obtained by studying individual systems. The proposed system-wide integrative approach may facilitate the development of a new field, Network Physiology.

  17. Gradient networks

    NASA Astrophysics Data System (ADS)

    Toroczkai, Zoltán; Kozma, Balázs; Bassler, Kevin E.; Hengartner, N. W.; Korniss, G.

    2008-04-01

    Gradient networks are defined (Toroczkai and Bassler 2004 Nature 428 716) as directed graphs formed by local gradients of a scalar field distributed on the nodes of a substrate network G. We present the derivation for some of the general properties of gradient graphs and give an exact expression for the in-degree distribution R(l) of the gradient network when the substrate is a binomial (Erd{\\;\\kern -0.10em \\raise -0.35ex \\{{^{^{\\prime\\prime}}}}\\kern -0.57em \\o} s-Rényi) random graph, G_{N,p} , and the scalars are independent identically distributed (i.i.d.) random variables. We show that in the limit N \\to \\infty, p \\to 0, z = pN = \\mbox{const} \\gg 1, R(l)\\propto l^{-1} for l < l_c = z , i.e., gradient networks become scale-free graphs up to a cut-off degree. This paper presents the detailed derivation of the results announced in Toroczkai and Bassler (2004 Nature 428 716).

  18. Network Views

    ERIC Educational Resources Information Center

    Alexander, Louis

    2010-01-01

    The world changed in 2008. The financial crisis brought with it a deepening sense of insecurity, and the desire to be connected to a network increased. Throughout the summer and fall of 2008, events were unfolding with alarming rapidity. The Massachusetts Institute of Technology (MIT) Alumni Association wanted to respond to this change in the…

  19. Resistive Networks.

    ERIC Educational Resources Information Center

    Balabanian, Norman

    This programed text on resistive networks was developed under contract with the United States Office of Education as part of a series of materials for use in an electrical engineering sequence. It is to be used in conjunction with other materials and with other short texts in the series, this one being Number 3. (DH)

  20. Beyond Networking.

    ERIC Educational Resources Information Center

    Carmel, Michael

    1981-01-01

    Discusses the new relationships between libraries and their users with reference to the worldwide medical information networks which have developed through the influence of the U.S. National Library of Medicine. Consideration is given to the new roles librarians will have to assume. (Author/LLS)

  1. Knowledge Networks

    ERIC Educational Resources Information Center

    McLeod, Scott

    2008-01-01

    The blogosphere and the Internet are both examples of complex, self-organizing networks. So too is the world of academic publishing. Some faculty members are prolific article and book writers. Their publications often are hubs, or even superhubs, in the scholarly literature, cited regularly by others. Some scholars might just be nodes, with…

  2. Global Networking.

    ERIC Educational Resources Information Center

    Lynch, Clifford

    1997-01-01

    Discusses the state of the Internet. Highlights include the magnitude of the infrastructure, costs, its increasing pace, constraints in international links, provision of network capacity to homes and small businesses, cable television modems, political and cultural problems, the digital library concept, search engines, the failure of personal…

  3. Modeling the Citation Network by Network Cosmology

    PubMed Central

    Xie, Zheng; Ouyang, Zhenzheng; Zhang, Pengyuan; Yi, Dongyun; Kong, Dexing

    2015-01-01

    Citation between papers can be treated as a causal relationship. In addition, some citation networks have a number of similarities to the causal networks in network cosmology, e.g., the similar in-and out-degree distributions. Hence, it is possible to model the citation network using network cosmology. The casual network models built on homogenous spacetimes have some restrictions when describing some phenomena in citation networks, e.g., the hot papers receive more citations than other simultaneously published papers. We propose an inhomogenous causal network model to model the citation network, the connection mechanism of which well expresses some features of citation. The node growth trend and degree distributions of the generated networks also fit those of some citation networks well. PMID:25807397

  4. Modeling the citation network by network cosmology.

    PubMed

    Xie, Zheng; Ouyang, Zhenzheng; Zhang, Pengyuan; Yi, Dongyun; Kong, Dexing

    2015-01-01

    Citation between papers can be treated as a causal relationship. In addition, some citation networks have a number of similarities to the causal networks in network cosmology, e.g., the similar in-and out-degree distributions. Hence, it is possible to model the citation network using network cosmology. The casual network models built on homogenous spacetimes have some restrictions when describing some phenomena in citation networks, e.g., the hot papers receive more citations than other simultaneously published papers. We propose an inhomogenous causal network model to model the citation network, the connection mechanism of which well expresses some features of citation. The node growth trend and degree distributions of the generated networks also fit those of some citation networks well.

  5. Neural Networks

    NASA Astrophysics Data System (ADS)

    Schwindling, Jerome

    2010-04-01

    This course presents an overview of the concepts of the neural networks and their aplication in the framework of High energy physics analyses. After a brief introduction on the concept of neural networks, the concept is explained in the frame of neuro-biology, introducing the concept of multi-layer perceptron, learning and their use as data classifer. The concept is then presented in a second part using in more details the mathematical approach focussing on typical use cases faced in particle physics. Finally, the last part presents the best way to use such statistical tools in view of event classifers, putting the emphasis on the setup of the multi-layer perceptron. The full article (15 p.) corresponding to this lecture is written in french and is provided in the proceedings of the book SOS 2008.

  6. Network gravity

    NASA Astrophysics Data System (ADS)

    Lombard, John

    2017-01-01

    We introduce the construction of a new framework for probing discrete emergent geometry and boundary-boundary observables based on a fundamentally a-dimensional underlying network structure. Using a gravitationally motivated action with Forman weighted combinatorial curvatures and simplicial volumes relying on a decomposition of an abstract simplicial complex into realized embeddings of proper skeletons, we demonstrate properties such as a minimal volume-scale cutoff, the necessity of a term playing the role of a positive definite cosmological constant as a regulator for nondegenerate geometries, and naturally emergent simplicial structures from Metropolis network evolution simulations with no restrictions on attachment rules or regular building blocks. We see emergent properties which echo results from both the spinfoam formalism and causal dynamical triangulations in quantum gravity, and provide analytical and numerical results to support the analogy. We conclude with a summary of open questions and intent for future work in developing the program.

  7. NASA Network

    NASA Technical Reports Server (NTRS)

    Carter, David; Wetzel, Scott

    2000-01-01

    The NASA Network includes nine NASA operated and partner operated stations covering North America, the west coast of South America, the Pacific, and Western Australia . A new station is presently being setup in South Africa and discussions are underway to add another station in Argentina. NASA SLR operations are supported by Honeywell Technical Solutions, Inc (HTSI), formally AlliedSignal Technical Services, The University of Texas, the University of Hawaii and Universidad Nacional de San Agustin.

  8. Why Network? Theoretical Perspectives on Networking

    ERIC Educational Resources Information Center

    Muijs, Daniel; West, Mel; Ainscow, Mel

    2010-01-01

    In recent years, networking and collaboration have become increasingly popular in education. However, there is at present a lack of attention to the theoretical basis of networking, which could illuminate when and when not to network and under what conditions networks are likely to be successful. In this paper, we will attempt to sketch the…

  9. Neural Network Function Classifier

    DTIC Science & Technology

    2003-02-07

    neural network sets. Each of the neural networks in a particular set is trained to recognize a particular data set type. The best function representation of the data set is determined from the neural network output. The system comprises sets of trained neural networks having neural networks trained to identify different types of data. The number of neural networks within each neural network set will depend on the number of function types that are represented. The system further comprises

  10. [Networks in cognitive research].

    PubMed

    Pléh, Csaba

    2012-01-01

    This review paper starts from discussing two models of network research: one starting from general networks, the other starting from the Ego. Ego based researches are characterized starting form the model of Dunbar as presenting networks of different size and intimacy, both in real and virtual networks. Researches into the personality determinants of networks mainly shows the effects of extroversion. The future of network research indicates a trend towards relating personal, conceptual, and neural networks.

  11. Communications Network

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The Multi-Compatible Network Interface Unit (MCNIU) is intended to connect the space station's communications and tracking, guidance and navigation, life support, electric power, payload data, hand controls, display consoles and other systems, and also communicate with diverse processors. Honeywell is now marketing MCNIU commercially. It has applicability in certain military operations or civil control centers. It has nongovernment utility among large companies, universities and research organizations that transfer large amounts of data among workstations and computers. *This product is no longer commercially available.

  12. TELECOM 1 multiservices network

    NASA Astrophysics Data System (ADS)

    Lombard, D.; Ramat, P.; Rancy, F.

    The main objectives of the TELECOM 1 French domestic satellite project are to set up a business communication network which is to carry a wide range of digital services including data, voice, and pictures between a number of small earth stations located on the subscribers' premises. The parallel development of terrestrial specialized services networks has enabled the fitting of the TELECOM 1 network with high interworking capabilities with these networks. It has also allowed TELECOM 1 to be designed as the basis of the Future Integrated Services Digital Network. The TELECOM 1 network consists of the terrestrial network, the satellite network, and the maintenance network. Various elements which include the terrestrial network; the satellite network, and its modulation, TDMA frame and terminals; the System Management Center; the signalling system; and the demand assignment operation which are involved in the operation of the multiservices network are presented. The TELECOM 1 network evolution until 1990 through the rapid development of the ISDN is discussed.

  13. Robustness of a Network of Networks

    NASA Astrophysics Data System (ADS)

    Gao, Jianxi; Buldyrev, Sergey V.; Stanley, H. Eugene; Havlin, Shlomo

    2012-02-01

    Network research has been focused on studying the properties of a single isolated network, which rarely exists. We develop a general analytical framework for studying percolation of n interdependent networks. We illustrate our analytical solutions for three examples: (i) For any tree of n fully dependent Erdos-R'enyi (ER) networks, each of average degree k, we find that the giant component P∞=p[1-(-kP∞)]^n where 1 - p is the initial fraction of removed nodes. This general result coincides for n = 1 with the known second-order phase transition for a single network. For any n>1 cascading failures occur and the percolation becomes an abrupt first-order transition. (ii) For a starlike network of n partially interdependent ER networks, P∞ depends also on the topology--in contrast to case (i). (iii) For a looplike network formed by n partially dependent ER networks, P∞ is independent of n.

  14. Interconnection networks

    DOEpatents

    Faber, V.; Moore, J.W.

    1988-06-20

    A network of interconnected processors is formed from a vertex symmetric graph selected from graphs GAMMA/sub d/(k) with degree d, diameter k, and (d + 1)exclamation/ (d /minus/ k + 1)exclamation processors for each d greater than or equal to k and GAMMA/sub d/(k, /minus/1) with degree d /minus/ 1, diameter k + 1, and (d + 1)exclamation/(d /minus/ k + 1)exclamation processors for each d greater than or equal to k greater than or equal to 4. Each processor has an address formed by one of the permutations from a predetermined sequence of letters chosen a selected number of letters at a time, and an extended address formed by appending to the address the remaining ones of the predetermined sequence of letters. A plurality of transmission channels is provided from each of the processors, where each processor has one less channel than the selected number of letters forming the sequence. Where a network GAMMA/sub d/(k, /minus/1) is provided, no processor has a channel connected to form an edge in a direction delta/sub 1/. Each of the channels has an identification number selected from the sequence of letters and connected from a first processor having a first extended address to a second processor having a second address formed from a second extended address defined by moving to the front of the first extended address the letter found in the position within the first extended address defined by the channel identification number. The second address is then formed by selecting the first elements of the second extended address corresponding to the selected number used to form the address permutations. 9 figs.

  15. Animal transportation networks

    PubMed Central

    Perna, Andrea; Latty, Tanya

    2014-01-01

    Many group-living animals construct transportation networks of trails, galleries and burrows by modifying the environment to facilitate faster, safer or more efficient movement. Animal transportation networks can have direct influences on the fitness of individuals, whereas the shape and structure of transportation networks can influence community dynamics by facilitating contacts between different individuals and species. In this review, we discuss three key areas in the study of animal transportation networks: the topological properties of networks, network morphogenesis and growth, and the behaviour of network users. We present a brief primer on elements of network theory, and then discuss the different ways in which animal groups deal with the fundamental trade-off between the competing network properties of travel efficiency, robustness and infrastructure cost. We consider how the behaviour of network users can impact network efficiency, and call for studies that integrate both network topology and user behaviour. We finish with a prospectus for future research. PMID:25165598

  16. Air Traffic Network Project

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The high level requirement of the Air Traffic Network (ATN) project is to provide a mechanism for evaluating the impact of router scheduling modifications on a networks efficiency, without implementing the modifications in the live network.

  17. The deep space network

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Presented is Deep Space Network (DSN) progress in flight project support, tracking and data acquisition (TDA) research and technology, network engineering, hardware and software implementation, and operations.

  18. The deep space network

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Summaries are given of Deep Space Network progress in flight project support, tracking and data acquisition research and technology, network engineering, hardware and software implementation, and operations.

  19. Computer Networks and Networking: A Primer.

    ERIC Educational Resources Information Center

    Collins, Mauri P.

    1993-01-01

    Provides a basic introduction to computer networks and networking terminology. Topics addressed include modems; the Internet; TCP/IP (Transmission Control Protocol/Internet Protocol); transmission lines; Internet Protocol numbers; network traffic; Fidonet; file transfer protocol (FTP); TELNET; electronic mail; discussion groups; LISTSERV; USENET;…

  20. Robustness of Interdependent Networks

    NASA Astrophysics Data System (ADS)

    Havlin, Shlomo

    2011-03-01

    In interdependent networks, when nodes in one network fail, they cause dependent nodes in other networks to also fail. This may happen recursively and can lead to a cascade of failures. In fact, a failure of a very small fraction of nodes in one network may lead to the complete fragmentation of a system of many interdependent networks. We will present a framework for understanding the robustness of interacting networks subject to such cascading failures and provide a basic analytic approach that may be useful in future studies. We present exact analytical solutions for the critical fraction of nodes that upon removal will lead to a failure cascade and to a complete fragmentation of two interdependent networks in a first order transition. Surprisingly, analyzing complex systems as a set of interdependent networks may alter a basic assumption that network theory has relied on: while for a single network a broader degree distribution of the network nodes results in the network being more robust to random failures, for interdependent networks, the broader the distribution is, the more vulnerable the networks become to random failure. We also show that reducing the coupling between the networks leads to a change from a first order percolation phase transition to a second order percolation transition at a critical point. These findings pose a significant challenge to the future design of robust networks that need to consider the unique properties of interdependent networks.

  1. Network Plus

    NASA Astrophysics Data System (ADS)

    Bender, Walter; Chesnais, Pascal

    1988-05-01

    Over the past several years, the Electronic Publishing Group at the MIT Media Laboratory has been conducting a family of media experiments which explore a new kind of broadcast: the distribution of data and computer programs rather than pre-packaged material. This broadcast is not directed to a human recipient, but to a local computational agent acting on his behalf. In response to instructions from both the broadcaster and the reader, this agent selects from the incoming data and presents it in a manner suggestive of traditional media. The embodiment of these media experiments is a news retrieval system where the news editor has been replaced by the personal computer. A variety of both local and remote databases which operate passively as well as interac-tively are accessed by "reporters." These "reporters" are actually software interfaces, which are programmed to gather news. Ideally, they are "broadcatching" that is to say, watching all broadcast television channels, listening to all radio transmissions, and reading all newspapers, magazines, and journals. 1 A possible consequence of the synthesis of media through active processing is the merger of newspapers and television (figure 1). The result is either a newspaper with illustrations which move 2 or, conversely, print as television output. The latter is the theme of Network Plus.

  2. Data center networks and network architecture

    NASA Astrophysics Data System (ADS)

    Esaki, Hiroshi

    2014-02-01

    This paper discusses and proposes the architectural framework, which is for data center networks. The data center networks require new technical challenges, and it would be good opportunity to change the functions, which are not need in current and future networks. Based on the observation and consideration on data center networks, this paper proposes; (i) Broadcast-free layer 2 network (i.e., emulation of broadcast at the end-node), (ii) Full-mesh point-to-point pipes, and (iii) IRIDES (Invitation Routing aDvertisement for path Engineering System).

  3. Network epidemiology and plant trade networks

    PubMed Central

    Pautasso, Marco; Jeger, Mike J.

    2014-01-01

    Models of epidemics in complex networks are improving our predictive understanding of infectious disease outbreaks. Nonetheless, applying network theory to plant pathology is still a challenge. This overview summarizes some key developments in network epidemiology that are likely to facilitate its application in the study and management of plant diseases. Recent surveys have provided much-needed datasets on contact patterns and human mobility in social networks, but plant trade networks are still understudied. Human (and plant) mobility levels across the planet are unprecedented—there is thus much potential in the use of network theory by plant health authorities and researchers. Given the directed and hierarchical nature of plant trade networks, there is a need for plant epidemiologists to further develop models based on undirected and homogeneous networks. More realistic plant health scenarios would also be obtained by developing epidemic models in dynamic, rather than static, networks. For plant diseases spread by the horticultural and ornamental trade, there is the challenge of developing spatio-temporal epidemic simulations integrating network data. The use of network theory in plant epidemiology is a promising avenue and could contribute to anticipating and preventing plant health emergencies such as European ash dieback. PMID:24790128

  4. Neural Network Studies

    DTIC Science & Technology

    1993-07-01

    basic useful theorems and general rules which apply to neural networks (in ’Overview of Neural Network Theory’), studies of training time as the...The Neural Network , Bayes- Gaussian, and k-Nearest Neighbor Classifiers’), an analysis of fuzzy logic and its relationship to neural network (in ’Fuzzy

  5. Damselfly Network Simulator

    SciTech Connect

    2014-04-01

    Damselfly is a model-based parallel network simulator. It can simulate communication patterns of High Performance Computing applications on different network topologies. It outputs steady-state network traffic for a communication pattern, which can help in studying network congestion and its impact on performance.

  6. Engineering technology for networks

    NASA Technical Reports Server (NTRS)

    Paul, Arthur S.; Benjamin, Norman

    1991-01-01

    Space Network (SN) modeling and evaluation are presented. The following tasks are included: Network Modeling (developing measures and metrics for SN, modeling of the Network Control Center (NCC), using knowledge acquired from the NCC to model the SNC, and modeling the SN); and Space Network Resource scheduling.

  7. Designing Secure Library Networks.

    ERIC Educational Resources Information Center

    Breeding, Michael

    1997-01-01

    Focuses on designing a library network to maximize security. Discusses UNIX and file servers; connectivity to campus, corporate networks and the Internet; separation of staff from public servers; controlling traffic; the threat of network sniffers; hubs that eliminate eavesdropping; dividing the network into subnets; Switched Ethernet;…

  8. Energy Efficient Digital Networks

    SciTech Connect

    Lanzisera, Steven; Brown, Richard

    2013-01-01

    Digital networks are the foundation of the information services, and play an expanding and indispensable role in our lives, via the Internet, email, mobile phones, etc. However, these networks consume energy, both through the direct energy use of the network interfaces and equipment that comprise the network, and in the effect they have on the operating patterns of devices connected to the network. The purpose of this research was to investigate a variety of technology and policy issues related to the energy use caused by digital networks, and to further develop several energy-efficiency technologies targeted at networks.

  9. Epidemics on interconnected networks

    NASA Astrophysics Data System (ADS)

    Dickison, Mark; Havlin, S.; Stanley, H. E.

    2012-06-01

    Populations are seldom completely isolated from their environment. Individuals in a particular geographic or social region may be considered a distinct network due to strong local ties but will also interact with individuals in other networks. We study the susceptible-infected-recovered process on interconnected network systems and find two distinct regimes. In strongly coupled network systems, epidemics occur simultaneously across the entire system at a critical infection strength βc, below which the disease does not spread. In contrast, in weakly coupled network systems, a mixed phase exists below βc of the coupled network system, where an epidemic occurs in one network but does not spread to the coupled network. We derive an expression for the network and disease parameters that allow this mixed phase and verify it numerically. Public health implications of communities comprising these two classes of network systems are also mentioned.

  10. Networks in Cell Biology

    NASA Astrophysics Data System (ADS)

    Buchanan, Mark; Caldarelli, Guido; De Los Rios, Paolo; Rao, Francesco; Vendruscolo, Michele

    2010-05-01

    Introduction; 1. Network views of the cell Paolo De Los Rios and Michele Vendruscolo; 2. Transcriptional regulatory networks Sarath Chandra Janga and M. Madan Babu; 3. Transcription factors and gene regulatory networks Matteo Brilli, Elissa Calistri and Pietro Lió; 4. Experimental methods for protein interaction identification Peter Uetz, Björn Titz, Seesandra V. Rajagopala and Gerard Cagney; 5. Modeling protein interaction networks Francesco Rao; 6. Dynamics and evolution of metabolic networks Daniel Segré; 7. Hierarchical modularity in biological networks: the case of metabolic networks Erzsébet Ravasz Regan; 8. Signalling networks Gian Paolo Rossini; Appendix 1. Complex networks: from local to global properties D. Garlaschelli and G. Caldarelli; Appendix 2. Modelling the local structure of networks D. Garlaschelli and G. Caldarelli; Appendix 3. Higher-order topological properties S. Ahnert, T. Fink and G. Caldarelli; Appendix 4. Elementary mathematical concepts A. Gabrielli and G. Caldarelli; References.

  11. Electronic Neural Networks

    NASA Technical Reports Server (NTRS)

    Thakoor, Anil

    1990-01-01

    Viewgraphs on electronic neural networks for space station are presented. Topics covered include: electronic neural networks; electronic implementations; VLSI/thin film hybrid hardware for neurocomputing; computations with analog parallel processing; features of neuroprocessors; applications of neuroprocessors; neural network hardware for terrain trafficability determination; a dedicated processor for path planning; neural network system interface; neural network for robotic control; error backpropagation algorithm for learning; resource allocation matrix; global optimization neuroprocessor; and electrically programmable read only thin-film synaptic array.

  12. Network Science Experimentation Vision

    DTIC Science & Technology

    2015-09-01

    is referred to here as a multi-genre composite network . Given that the term “ network ” is used in a multiplicity of ways in a variety of contexts...expertise, models, and tools in multiple domains. These areas of expertise include, but are not limited to, the following: • networks and network ...composite networks are there to support multiple missions. While this report focuses on experiments that involve a single mission, extending them to

  13. Percolation of a general network of networks.

    PubMed

    Gao, Jianxi; Buldyrev, Sergey V; Stanley, H Eugene; Xu, Xiaoming; Havlin, Shlomo

    2013-12-01

    Percolation theory is an approach to study the vulnerability of a system. We develop an analytical framework and analyze the percolation properties of a network composed of interdependent networks (NetONet). Typically, percolation of a single network shows that the damage in the network due to a failure is a continuous function of the size of the failure, i.e., the fraction of failed nodes. In sharp contrast, in NetONet, due to the cascading failures, the percolation transition may be discontinuous and even a single node failure may lead to an abrupt collapse of the system. We demonstrate our general framework for a NetONet composed of n classic Erdős-Rényi (ER) networks, where each network depends on the same number m of other networks, i.e., for a random regular network (RR) formed of interdependent ER networks. The dependency between nodes of different networks is taken as one-to-one correspondence, i.e., a node in one network can depend only on one node in the other network (no-feedback condition). In contrast to a treelike NetONet in which the size of the largest connected cluster (mutual component) depends on n, the loops in the RR NetONet cause the largest connected cluster to depend only on m and the topology of each network but not on n. We also analyzed the extremely vulnerable feedback condition of coupling, where the coupling between nodes of different networks is not one-to-one correspondence. In the case of NetONet formed of ER networks, percolation only exhibits two phases, a second order phase transition and collapse, and no first order percolation transition regime is found in the case of the no-feedback condition. In the case of NetONet composed of RR networks, there exists a first order phase transition when the coupling strength q (fraction of interdependency links) is large and a second order phase transition when q is small. Our insight on the resilience of coupled networks might help in designing robust interdependent systems.

  14. Percolation of a general network of networks

    NASA Astrophysics Data System (ADS)

    Gao, Jianxi; Buldyrev, Sergey V.; Stanley, H. Eugene; Xu, Xiaoming; Havlin, Shlomo

    2013-12-01

    Percolation theory is an approach to study the vulnerability of a system. We develop an analytical framework and analyze the percolation properties of a network composed of interdependent networks (NetONet). Typically, percolation of a single network shows that the damage in the network due to a failure is a continuous function of the size of the failure, i.e., the fraction of failed nodes. In sharp contrast, in NetONet, due to the cascading failures, the percolation transition may be discontinuous and even a single node failure may lead to an abrupt collapse of the system. We demonstrate our general framework for a NetONet composed of n classic Erdős-Rényi (ER) networks, where each network depends on the same number m of other networks, i.e., for a random regular network (RR) formed of interdependent ER networks. The dependency between nodes of different networks is taken as one-to-one correspondence, i.e., a node in one network can depend only on one node in the other network (no-feedback condition). In contrast to a treelike NetONet in which the size of the largest connected cluster (mutual component) depends on n, the loops in the RR NetONet cause the largest connected cluster to depend only on m and the topology of each network but not on n. We also analyzed the extremely vulnerable feedback condition of coupling, where the coupling between nodes of different networks is not one-to-one correspondence. In the case of NetONet formed of ER networks, percolation only exhibits two phases, a second order phase transition and collapse, and no first order percolation transition regime is found in the case of the no-feedback condition. In the case of NetONet composed of RR networks, there exists a first order phase transition when the coupling strength q (fraction of interdependency links) is large and a second order phase transition when q is small. Our insight on the resilience of coupled networks might help in designing robust interdependent systems.

  15. Minimal Increase Network Coding for Dynamic Networks.

    PubMed

    Zhang, Guoyin; Fan, Xu; Wu, Yanxia

    2016-01-01

    Because of the mobility, computing power and changeable topology of dynamic networks, it is difficult for random linear network coding (RLNC) in static networks to satisfy the requirements of dynamic networks. To alleviate this problem, a minimal increase network coding (MINC) algorithm is proposed. By identifying the nonzero elements of an encoding vector, it selects blocks to be encoded on the basis of relationship between the nonzero elements that the controls changes in the degrees of the blocks; then, the encoding time is shortened in a dynamic network. The results of simulations show that, compared with existing encoding algorithms, the MINC algorithm provides reduced computational complexity of encoding and an increased probability of delivery.

  16. Minimal Increase Network Coding for Dynamic Networks

    PubMed Central

    Wu, Yanxia

    2016-01-01

    Because of the mobility, computing power and changeable topology of dynamic networks, it is difficult for random linear network coding (RLNC) in static networks to satisfy the requirements of dynamic networks. To alleviate this problem, a minimal increase network coding (MINC) algorithm is proposed. By identifying the nonzero elements of an encoding vector, it selects blocks to be encoded on the basis of relationship between the nonzero elements that the controls changes in the degrees of the blocks; then, the encoding time is shortened in a dynamic network. The results of simulations show that, compared with existing encoding algorithms, the MINC algorithm provides reduced computational complexity of encoding and an increased probability of delivery. PMID:26867211

  17. Networking: challenges for network centric operations

    NASA Astrophysics Data System (ADS)

    Stotts, Larry B.; Allen, John G.

    2004-11-01

    This paper examines some of the challenges facing the community in providing radio communications to enable information systems for military operations. We believe that much of the on-going/completed work is necessary, but not sufficient, to provide the military Network Centric Operations, which integrates military"s network centric enterprise with network centric warfare. Additional issues need to be addressed to better support battle commanders as well as decider-sensor-effecter linkages. We discuss a possible way ahead.

  18. Robustness of a Network of Networks

    NASA Astrophysics Data System (ADS)

    Gao, Jianxi; Buldyrev, Sergey V.; Havlin, Shlomo; Stanley, H. Eugene

    2011-11-01

    Network research has been focused on studying the properties of a single isolated network, which rarely exists. We develop a general analytical framework for studying percolation of n interdependent networks. We illustrate our analytical solutions for three examples: (i) For any tree of n fully dependent Erdős-Rényi (ER) networks, each of average degree k¯, we find that the giant component is P∞=p[1-exp⁡(-k¯P∞)]n where 1-p is the initial fraction of removed nodes. This general result coincides for n=1 with the known second-order phase transition for a single network. For any n>1 cascading failures occur and the percolation becomes an abrupt first-order transition. (ii) For a starlike network of n partially interdependent ER networks, P∞ depends also on the topology—in contrast to case (i). (iii) For a looplike network formed by n partially dependent ER networks, P∞ is independent of n.

  19. Weighted projected networks: Mapping hypergraphs to networks

    NASA Astrophysics Data System (ADS)

    López, Eduardo

    2013-05-01

    Many natural, technological, and social systems incorporate multiway interactions, yet are characterized and measured on the basis of weighted pairwise interactions. In this article, I propose a family of models in which pairwise interactions originate from multiway interactions, by starting from ensembles of hypergraphs and applying projections that generate ensembles of weighted projected networks. I calculate analytically the statistical properties of weighted projected networks, and suggest ways these could be used beyond theoretical studies. Weighted projected networks typically exhibit weight disorder along links even for very simple generating hypergraph ensembles. Also, as the size of a hypergraph changes, a signature of multiway interaction emerges on the link weights of weighted projected networks that distinguishes them from fundamentally weighted pairwise networks. This signature could be used to search for hidden multiway interactions in weighted network data. I find the percolation threshold and size of the largest component for hypergraphs of arbitrary uniform rank, translate the results into projected networks, and show that the transition is second order. This general approach to network formation has the potential to shed new light on our understanding of weighted networks.

  20. Improving network utilization over heterogeneous airborne networks

    NASA Astrophysics Data System (ADS)

    Griffin, Peter H.; Rickenbach, Brent L.; Rush, Jason A.

    2011-06-01

    Existing and future military networks vary widely in bandwidth and other network characteristics, potentially challenging deployment of services and applications across heterogeneous data links. To address this challenge, General Dynamics and Naval Research Laboratory created network services to allow applications to use wireless data links more efficiently. The basis for the network services are hooks into the data links and transport protocols providing status about the airborne networking environment. The network service can monitor heterogeneous data links on a platform and report on link availability and parameters such as latency and bandwidth. The network service then presents the network characteristics to other services and applications. These services and applications are then able to tune parameters and content based on network parameters. The technology has been demonstrated in several live-flight experiments sponsored by the United States Air Force and United States Navy. The technology was housed on several aircraft with a variety of data links ranging from directional, high-bandwidth systems to omnidirectional, medium-bandwidth systems to stable but low-bandwidth satellite systems. In each of these experiments, image and video data was successfully delivered over tactical data links that varied greatly in bandwidth and delay.

  1. Translated chemical reaction networks.

    PubMed

    Johnston, Matthew D

    2014-05-01

    Many biochemical and industrial applications involve complicated networks of simultaneously occurring chemical reactions. Under the assumption of mass action kinetics, the dynamics of these chemical reaction networks are governed by systems of polynomial ordinary differential equations. The steady states of these mass action systems have been analyzed via a variety of techniques, including stoichiometric network analysis, deficiency theory, and algebraic techniques (e.g., Gröbner bases). In this paper, we present a novel method for characterizing the steady states of mass action systems. Our method explicitly links a network's capacity to permit a particular class of steady states, called toric steady states, to topological properties of a generalized network called a translated chemical reaction network. These networks share their reaction vectors with their source network but are permitted to have different complex stoichiometries and different network topologies. We apply the results to examples drawn from the biochemical literature.

  2. Wayfinding in Social Networks

    NASA Astrophysics Data System (ADS)

    Liben-Nowell, David

    With the recent explosion of popularity of commercial social-networking sites like Facebook and MySpace, the size of social networks that can be studied scientifically has passed from the scale traditionally studied by sociologists and anthropologists to the scale of networks more typically studied by computer scientists. In this chapter, I will highlight a recent line of computational research into the modeling and analysis of the small-world phenomenon - the observation that typical pairs of people in a social network are connected by very short chains of intermediate friends - and the ability of members of a large social network to collectively find efficient routes to reach individuals in the network. I will survey several recent mathematical models of social networks that account for these phenomena, with an emphasis on both the provable properties of these social-network models and the empirical validation of the models against real large-scale social-network data.

  3. Network connectivity value.

    PubMed

    Dragicevic, Arnaud; Boulanger, Vincent; Bruciamacchie, Max; Chauchard, Sandrine; Dupouey, Jean-Luc; Stenger, Anne

    2017-02-23

    In order to unveil the value of network connectivity, we formalize the construction of ecological networks in forest environments as an optimal control dynamic graph-theoretic problem. The network is based on a set of bioreserves and patches linked by ecological corridors. The node dynamics, built upon the consensus protocol, form a time evolutive Mahalanobis distance weighted by the opportunity costs of timber production. We consider a case of complete graph, where the ecological network is fully connected, and a case of incomplete graph, where the ecological network is partially connected. The results show that the network equilibrium depends on the size of the reception zone, while the network connectivity depends on the environmental compatibility between the ecological areas. Through shadow prices, we find that securing connectivity in partially connected networks is more expensive than in fully connected networks, but should be undertaken when the opportunity costs are significant.

  4. Ascl1 as a novel player in the Ptf1a transcriptional network for GABAergic cell specification in the retina.

    PubMed

    Mazurier, Nicolas; Parain, Karine; Parlier, Damien; Pretto, Silvia; Hamdache, Johanna; Vernier, Philippe; Locker, Morgane; Bellefroid, Eric; Perron, Muriel

    2014-01-01

    In contrast with the wealth of data involving bHLH and homeodomain transcription factors in retinal cell type determination, the molecular bases underlying neurotransmitter subtype specification is far less understood. Using both gain and loss of function analyses in Xenopus, we investigated the putative implication of the bHLH factor Ascl1 in this process. We found that in addition to its previously characterized proneural function, Ascl1 also contributes to the specification of the GABAergic phenotype. We showed that it is necessary for retinal GABAergic cell genesis and sufficient in overexpression experiments to bias a subset of retinal precursor cells towards a GABAergic fate. We also analysed the relationships between Ascl1 and a set of other bHLH factors using an in vivo ectopic neurogenic assay. We demonstrated that Ascl1 has unique features as a GABAergic inducer and is epistatic over factors endowed with glutamatergic potentialities such as Neurog2, NeuroD1 or Atoh7. This functional specificity is conferred by the basic DNA binding domain of Ascl1 and involves a specific genetic network, distinct from that underlying its previously demonstrated effects on catecholaminergic differentiation. Our data show that GABAergic inducing activity of Ascl1 requires the direct transcriptional regulation of Ptf1a, providing therefore a new piece of the network governing neurotransmitter subtype specification during retinogenesis.

  5. Sympathetic network drive during water deprivation does not increase respiratory or cardiac rhythmic sympathetic nerve activity.

    PubMed

    Holbein, Walter W; Toney, Glenn M

    2013-06-15

    Effects of water deprivation on rhythmic bursting of sympathetic nerve activity (SNA) were investigated in anesthetized, bilaterally vagotomized, euhydrated (control) and 48-h water-deprived (WD) rats (n = 8/group). Control and WD rats had similar baseline values of mean arterial pressure, heart rate, end-tidal CO2, and central respiratory drive. Although integrated splanchnic SNA (sSNA) was greater in WD rats than controls (P < 0.01), analysis of respiratory rhythmic bursting of sSNA revealed that inspiratory rhythmic burst amplitude was actually smaller (P < 0.005) in WD rats (+68 ± 6%) than controls (+208 ± 20%), and amplitudes of the early expiratory (postinspiratory) trough and late expiratory burst of sSNA were not different between groups. Further analysis revealed that water deprivation had no effect on either the amplitude or periodicity of the cardiac rhythmic oscillation of sSNA. Collectively, these data indicate that the increase of sSNA produced by water deprivation is not attributable to either increased respiratory or cardiac rhythmic burst discharge. Thus the sympathetic network response to acute water deprivation appears to differ from that of chronic sympathoexcitation in neurogenic forms of arterial hypertension, where increased respiratory rhythmic bursting of SNA and baroreflex adaptations have been reported.

  6. Satellite networks for education

    NASA Technical Reports Server (NTRS)

    Singh, J. P.; Morgan, R. P.; Rosenbaum, F. J.

    1972-01-01

    Satellite based educational networking is discussed with particular attention given to the potential uses of communications satellites to help meet educational needs in the United states. Four major subject areas were covered; (1) characteristics and structure of networks, (2) definition of pressures within educational establishment that provide motivation for various types of networks, (3) examination of current educational networking status for educational radio and television, instructional television fixed services, inter- and intra-state educational communication networks, computer networks, and cable television for education, and (4) identification of possible satellite based educational telecommunication services and three alternatives for implementing educational satellite systems.

  7. Parental Social Network and Child's Friendship Network.

    ERIC Educational Resources Information Center

    Uhlendorff, Harald; Oswald, Hans

    This study analyzed the relation between the friendship networks of parents and the peer networks of their children. Subjects were 255 second- through fifth-grade children of an inner-city primary school in the western part of Berlin, Germany, who were interviewed about friends. In the interview, children were asked to name other children with…

  8. Local area networking: Ames centerwide network

    NASA Technical Reports Server (NTRS)

    Price, Edwin

    1988-01-01

    A computer network can benefit the user by making his/her work quicker and easier. A computer network is made up of seven different layers with the lowest being the hardware, the top being the user, and the middle being the software. These layers are discussed.

  9. The deep space network

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Progress is reported in flight project support, tracking and data acquisition research and technology, network engineering, hardware and software implementation, and operations. The functions and facilities of the Deep Space Network are emphasized.

  10. The Merit Computer Network

    ERIC Educational Resources Information Center

    Aupperle, Eric M.; Davis, Donna L.

    1978-01-01

    The successful Merit Computer Network is examined in terms of both technology and operational management. The network is fully operational and has a significant and rapidly increasing usage, with three major institutions currently sharing computer resources. (Author/CMV)

  11. The deep space network

    NASA Technical Reports Server (NTRS)

    1980-01-01

    The functions and facilities of the Deep Space Network are considered. Progress in flight project support, tracking and data acquisition research and technology, network engineering, hardware and software implementation, and operations is reported.

  12. Virtualized Network Control (VNC)

    SciTech Connect

    Lehman, Thomas; Guok, Chin; Ghani, Nasir

    2013-01-31

    The focus of this project was on the development of a "Network Service Plane" as an abstraction model for the control and provisioning of multi-layer networks. The primary motivation for this work were the requirements of next generation networked applications which will need to access advanced networking as a first class resource at the same level as compute and storage resources. A new class of "Intelligent Network Services" were defined in order to facilitate the integration of advanced network services into application specific workflows. This new class of network services are intended to enable real-time interaction between the application co-scheduling algorithms and the network for the purposes of workflow planning, real-time resource availability identification, scheduling, and provisioning actions.

  13. Class network routing

    DOEpatents

    Bhanot, Gyan; Blumrich, Matthias A.; Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E.; Heidelberger, Philip; Steinmacher-Burow, Burkhard D.; Takken, Todd E.; Vranas, Pavlos M.

    2009-09-08

    Class network routing is implemented in a network such as a computer network comprising a plurality of parallel compute processors at nodes thereof. Class network routing allows a compute processor to broadcast a message to a range (one or more) of other compute processors in the computer network, such as processors in a column or a row. Normally this type of operation requires a separate message to be sent to each processor. With class network routing pursuant to the invention, a single message is sufficient, which generally reduces the total number of messages in the network as well as the latency to do a broadcast. Class network routing is also applied to dense matrix inversion algorithms on distributed memory parallel supercomputers with hardware class function (multicast) capability. This is achieved by exploiting the fact that the communication patterns of dense matrix inversion can be served by hardware class functions, which results in faster execution times.

  14. The deep space network

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The facilities, programming system, and monitor and control system for the deep space network are described. Ongoing planetary and interplanetary flight projects are reviewed, along with tracking and ground-based navigation, communications, and network and facility engineering.

  15. The deep space network

    NASA Technical Reports Server (NTRS)

    1979-01-01

    A report is given of the Deep Space Networks progress in (1) flight project support, (2) tracking and data acquisition research and technology, (3) network engineering, (4) hardware and software implementation, and (5) operations.

  16. The deep space network

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A Deep Space Network progress report is presented dealing with in flight project support, tracking and data acquisition research and technology, network engineering, hardware and software implementation, and operations.

  17. Wireless Mesh Networks

    NASA Astrophysics Data System (ADS)

    Ishmael, Johnathan; Race, Nicholas

    Wireless Mesh Networks have emerged as an important technology in building next-generation networks. They are seen to have a range of benefits over traditional wired and wireless networks including low deployment costs, high scalability and resiliency to faults. Moreover, Wireless Mesh Networks (WMNs) are often described as being autonomic with self-* (healing and configuration) properties and their popularity has grown both as a research platform and as a commercially exploitable technology.

  18. Automatic Microwave Network Analysis.

    DTIC Science & Technology

    A program and procedure are developed for the automatic measurement of microwave networks using a Hewlett-Packard network analyzer and programmable calculator . The program and procedure are used in the measurement of a simple microwave two port network. These measurements are evaluated by comparing with measurements on the same network using other techniques. The programs...in the programmable calculator are listed in Appendix 1. The step by step procedure used is listed in Appendix 2. (Author)

  19. Generalized classifier neural network.

    PubMed

    Ozyildirim, Buse Melis; Avci, Mutlu

    2013-03-01

    In this work a new radial basis function based classification neural network named as generalized classifier neural network, is proposed. The proposed generalized classifier neural network has five layers, unlike other radial basis function based neural networks such as generalized regression neural network and probabilistic neural network. They are input, pattern, summation, normalization and output layers. In addition to topological difference, the proposed neural network has gradient descent based optimization of smoothing parameter approach and diverge effect term added calculation improvements. Diverge effect term is an improvement on summation layer calculation to supply additional separation ability and flexibility. Performance of generalized classifier neural network is compared with that of the probabilistic neural network, multilayer perceptron algorithm and radial basis function neural network on 9 different data sets and with that of generalized regression neural network on 3 different data sets include only two classes in MATLAB environment. Better classification performance up to %89 is observed. Improved classification performances proved the effectivity of the proposed neural network.

  20. CD-ROM Networking.

    ERIC Educational Resources Information Center

    Akeroyd, John

    1992-01-01

    Provides an overview of CD-ROM networks. Highlights include network technology, including local area networks; an example of an installation at the South Bank Polytechnic (United Kingdom) library; interface issues, including standardization; possible future developments; licensing arrangements; and acquiring data in formats other than CD-ROM.…

  1. Reactive Sensor Networks (RSN)

    DTIC Science & Technology

    2003-10-01

    Networks,” Distributed Autonomous Robotic Systems DARS 2000, pp. 471-472, Springer Verlag, Tokyo. R. R. Brooks. “Stigmergy an intelligence metric...Paper, March 2003. • R. Brooks, et al. “Reactive Sensor Networks: Mobile Code Support for Autonomous Sensor Networks,” Distributed Autonomous Robotic Systems DARS

  2. OSI Network Management.

    ERIC Educational Resources Information Center

    Harris, Ethan

    1990-01-01

    Management of heterogeneous networks is complicated by the persistence of proprietary management schemes. The need for integration of network management capabilities is pressing. The International Organization for Standardization is developing standards for managing networks as part of the Open Systems Interconnection (OSI) effort. OSI management…

  3. Spanish Museum Libraries Network.

    ERIC Educational Resources Information Center

    Lopez de Prado, Rosario

    This paper describes the creation of an automated network of museum libraries in Spain. The only way in which the specialized libraries in the world today can continue to be active and to offer valid information is to automate the service they offer, and create network libraries with cooperative plans. The network can be configured with different…

  4. Real Time Network Assessment

    DTIC Science & Technology

    2013-07-12

    Demonstrate a simple system Conduct a feasibility assessment of data storage, maintenance, and integration requirements Test a web-based data feed...Real Time Network Assessment Prototype We demonstrated the feasibility of linking near real time network analytics to mashups and web- based...combining similar concepts into single node) Stemmers Thesauri application Network position Statistical common patterns Pronoun identification

  5. Information network architectures

    NASA Technical Reports Server (NTRS)

    Murray, N. D.

    1985-01-01

    Graphs, charts, diagrams and outlines of information relative to information network architectures for advanced aerospace missions, such as the Space Station, are presented. Local area information networks are considered a likely technology solution. The principle needs for the network are listed.

  6. Networking Brown University.

    ERIC Educational Resources Information Center

    Beckham, Bonnie

    1989-01-01

    Assesses BRUNET, a campuswide network that links more than 100 academic and administrative buildings and 40 dormitories. Notes a key element is hierarchical network management and support. Discusses the deployment, security, and use of four networking spheres in the system. (MVL)

  7. Security of Complex Networks

    DTIC Science & Technology

    2010-02-18

    social network (DS), (8) network of American football games among colleges (AFC), (9) social network of friendships of a karate club (FKC), (10...Ax2 = 12 book karate football ’•■ electronic circuit dolphins a C. Elegans 102 Figure 8: For Universal scaling law for six real-world

  8. Advanced Network Security Project

    DTIC Science & Technology

    2005-12-01

    network. The network observed was the Abilene network of the University Consortium for Advanced Internet Development (UCAID), often known as “ Internet2 ...for Advanced Internet Development (UCAID), often known as “ Internet2 .” This contract was heavily operational in nature, as opposed to a contract

  9. Emergent Network Defense

    ERIC Educational Resources Information Center

    Crane, Earl Newell

    2013-01-01

    The research problem that inspired this effort is the challenge of managing the security of systems in large-scale heterogeneous networked environments. Human intervention is slow and limited: humans operate at much slower speeds than networked computer communications and there are few humans associated with each network. Enabling each node in the…

  10. Computer Networking for Educators.

    ERIC Educational Resources Information Center

    McCain, Ted D. E.; Ekelund, Mark

    This book is intended to introduce the basic concepts of connecting computers together and to equip individuals with the technical background necessary to begin constructing small networks. For those already experienced with creating and maintaining computer networks, the book can help in considering the creation of a schoolwide network. The book…

  11. Metallic nanowire networks

    DOEpatents

    Song, Yujiang; Shelnutt, John A.

    2012-11-06

    A metallic nanowire network synthesized using chemical reduction of a metal ion source by a reducing agent in the presence of a soft template comprising a tubular inverse micellar network. The network of interconnected polycrystalline nanowires has a very high surface-area/volume ratio, which makes it highly suitable for use in catalytic applications.

  12. Probabilistic Analysis of Neural Networks

    DTIC Science & Technology

    1990-11-26

    provide an understanding of the basic mechanisms of learning and recognition in neural networks . The main areas of progress were analysis of neural ... networks models, study of network connectivity, and investigation of computer network theory.

  13. Directed network discovery with dynamic network modelling.

    PubMed

    Anzellotti, Stefano; Kliemann, Dorit; Jacoby, Nir; Saxe, Rebecca

    2017-02-16

    Cognitive tasks recruit multiple brain regions. Understanding how these regions influence each other (the network structure) is an important step to characterize the neural basis of cognitive processes. Often, limited evidence is available to restrict the range of hypotheses a priori, and techniques that sift efficiently through a large number of possible network structures are needed (network discovery). This article introduces a novel modelling technique for network discovery (Dynamic Network Modelling or DNM) that builds on ideas from Granger Causality and Dynamic Causal Modelling introducing three key changes: (1) efficient network discovery is implemented with statistical tests on the consistency of model parameters across participants, (2) the tests take into account the magnitude and sign of each influence, and (3) variance explained in independent data is used as an absolute (rather than relative) measure of the quality of the network model. In this article, we outline the functioning of DNM, we validate DNM in simulated data for which the ground truth is known, and we report an example of its application to the investigation of influences between regions during emotion recognition, revealing top-down influences from brain regions encoding abstract representations of emotions (medial prefrontal cortex and superior temporal sulcus) onto regions engaged in the perceptual analysis of facial expressions (occipital face area and fusiform face area) when participants are asked to switch between reporting the emotional valence and the age of a face.

  14. Characteristics on hub networks of urban rail transit networks

    NASA Astrophysics Data System (ADS)

    Zhang, Jianhua; Wang, Shuliang; Zhang, Zhaojun; Zou, Kuansheng; Shu, Zhan

    2016-04-01

    This paper proposes an approach to extract the hub networks from urban rail transit networks, and analyzes the characteristics of the hub networks. Minsk metro and Shanghai metro networks are given to illustrate the feasibility and effectiveness of the presented method in this paper. By simulations, we discover that the hub networks of urban rail transit networks possess small-world property and scale-free property. Meanwhile, this paper shows that the hub networks are completely different from the corresponding metro networks. Moreover, we find that the hub network is a hierarchical network, and the root of hub network corresponds to the transfer station of metro network which is passed by the most lines in metro network, and the root controls the main characteristics of hub network. In other words, the transfer station corresponding to this root plays the most important role in the urban rail transit networks.

  15. Network Characterization Service (NCS)

    SciTech Connect

    Jin, Guojun; Yang, George; Crowley, Brian; Agarwal, Deborah

    2001-06-06

    Distributed applications require information to effectively utilize the network. Some of the information they require is the current and maximum bandwidth, current and minimum latency, bottlenecks, burst frequency, and congestion extent. This type of information allows applications to determine parameters like optimal TCP buffer size. In this paper, we present a cooperative information-gathering tool called the network characterization service (NCS). NCS runs in user space and is used to acquire network information. Its protocol is designed for scalable and distributed deployment, similar to DNS. Its algorithms provide efficient, speedy and accurate detection of bottlenecks, especially dynamic bottlenecks. On current and future networks, dynamic bottlenecks do and will affect network performance dramatically.

  16. Studies in Neural Networks

    DTIC Science & Technology

    1991-01-01

    N00014-87-K-0377 TITLE: "Studies in Neural Networks " fl.U Q l~~izie JUL 021991 "" " F.: L9’CO37 "I! c-1(.d Contract No.: N00014-87-K-0377 Final...34) have been very useful, both in understanding the dynamics of neural networks and in engineering networks to perform particular tasks. We have noted...understanding more complex network computation. Interest in applying ideas from biological neural networks to real problems of engineering raises the issues of

  17. NASA's unique networking environment

    NASA Technical Reports Server (NTRS)

    Johnson, Marjory J.

    1988-01-01

    Networking is an infrastructure technology; it is a tool for NASA to support its space and aeronautics missions. Some of NASA's networking problems are shared by the commercial and/or military communities, and can be solved by working with these communities. However, some of NASA's networking problems are unique and will not be addressed by these other communities. Individual characteristics of NASA's space-mission networking enviroment are examined, the combination of all these characteristics that distinguish NASA's networking systems from either commercial or military systems is explained, and some research areas that are important for NASA to pursue are outlined.

  18. Networks Technology Conference

    NASA Technical Reports Server (NTRS)

    Tasaki, Keiji K. (Editor)

    1993-01-01

    The papers included in these proceedings represent the most interesting and current topics being pursued by personnel at GSFC's Networks Division and supporting contractors involved in Space, Ground, and Deep Space Network (DSN) technical work. Although 29 papers are represented in the proceedings, only 12 were presented at the conference because of space and time limitations. The proceedings are organized according to five principal technical areas of interest to the Networks Division: Project Management; Network Operations; Network Control, Scheduling, and Monitoring; Modeling and Simulation; and Telecommunications Engineering.

  19. Groundwater data network interoperability

    USGS Publications Warehouse

    Brodaric, Boyan; Booth, Nathaniel; Boisvert, Eric; Lucido, Jessica M.

    2016-01-01

    Water data networks are increasingly being integrated to answer complex scientific questions that often span large geographical areas and cross political borders. Data heterogeneity is a major obstacle that impedes interoperability within and between such networks. It is resolved here for groundwater data at five levels of interoperability, within a Spatial Data Infrastructure architecture. The result is a pair of distinct national groundwater data networks for the United States and Canada, and a combined data network in which they are interoperable. This combined data network enables, for the first time, transparent public access to harmonized groundwater data from both sides of the shared international border.

  20. Neurogenic Effects of Ghrelin on the Hippocampus

    PubMed Central

    Kim, Chanyang; Kim, Sehee; Park, Seungjoon

    2017-01-01

    Mammalian neurogenesis continues throughout adulthood in the subventricular zone of the lateral ventricle and in the subgranular zone of the dentate gyrus in the hippocampus. It is well known that hippocampal neurogenesis is essential in mediating hippocampus-dependent learning and memory. Ghrelin, a peptide hormone mainly synthesized in the stomach, has been shown to play a major role in the regulation of energy metabolism. A plethora of evidence indicates that ghrelin can also exert important effects on neurogenesis in the hippocampus of the adult brain. The aim of this review is to discuss the current role of ghrelin on the in vivo and in vitro regulation of neurogenesis in the adult hippocampus. We will also discuss the possible role of ghrelin in dietary restriction-induced hippocampal neurogenesis and the link between ghrelin-induced hippocampal neurogenesis and cognitive functions. PMID:28282857

  1. Neurogenic Effects of Ghrelin on the Hippocampus.

    PubMed

    Kim, Chanyang; Kim, Sehee; Park, Seungjoon

    2017-03-08

    Mammalian neurogenesis continues throughout adulthood in the subventricular zone of the lateral ventricle and in the subgranular zone of the dentate gyrus in the hippocampus. It is well known that hippocampal neurogenesis is essential in mediating hippocampus-dependent learning and memory. Ghrelin, a peptide hormone mainly synthesized in the stomach, has been shown to play a major role in the regulation of energy metabolism. A plethora of evidence indicates that ghrelin can also exert important effects on neurogenesis in the hippocampus of the adult brain. The aim of this review is to discuss the current role of ghrelin on the in vivo and in vitro regulation of neurogenesis in the adult hippocampus. We will also discuss the possible role of ghrelin in dietary restriction-induced hippocampal neurogenesis and the link between ghrelin-induced hippocampal neurogenesis and cognitive functions.

  2. Intonation in Neurogenic Foreign Accent Syndrome

    ERIC Educational Resources Information Center

    Kuschmann, Anja; Lowit, Anja; Miller, Nick; Mennen, Ineke

    2012-01-01

    Foreign accent syndrome (FAS) is a motor speech disorder in which changes to segmental as well as suprasegmental aspects lead to the perception of a foreign accent in speech. This paper focuses on one suprasegmental aspect, namely that of intonation. It provides an in-depth analysis of the intonation system of four speakers with FAS with the aim…

  3. Emergent Complex Network Geometry

    PubMed Central

    Wu, Zhihao; Menichetti, Giulia; Rahmede, Christoph; Bianconi, Ginestra

    2015-01-01

    Networks are mathematical structures that are universally used to describe a large variety of complex systems such as the brain or the Internet. Characterizing the geometrical properties of these networks has become increasingly relevant for routing problems, inference and data mining. In real growing networks, topological, structural and geometrical properties emerge spontaneously from their dynamical rules. Nevertheless we still miss a model in which networks develop an emergent complex geometry. Here we show that a single two parameter network model, the growing geometrical network, can generate complex network geometries with non-trivial distribution of curvatures, combining exponential growth and small-world properties with finite spectral dimensionality. In one limit, the non-equilibrium dynamical rules of these networks can generate scale-free networks with clustering and communities, in another limit planar random geometries with non-trivial modularity. Finally we find that these properties of the geometrical growing networks are present in a large set of real networks describing biological, social and technological systems. PMID:25985280

  4. Satellite networks for education.

    NASA Technical Reports Server (NTRS)

    Singh, J. P.; Morgan, R. P.; Rosenbaum, F. J.

    1972-01-01

    Consideration of satellite-based educational networking. The characteristics and structure of networks are reviewed, and pressures within the educational establishment that are providing motivation for various types of networks are discussed. A number of studies are cited in which networking needs for educational sectors and services are defined. The current status of educational networking for educational radio and television, instructional television fixed services, inter- and intrastate educational communication networks, computer networks, cable television for education, and continuing and proposed educational experiments using NASA's Applications Technology Satellites is reviewed. Possible satellite-based educational telecommunication services and three alternatives for implementing educational satellite systems are described. Some remarks are made concerning public policy aspects of future educational satellite system development.

  5. Percolation on Sparse Networks

    NASA Astrophysics Data System (ADS)

    Karrer, Brian; Newman, M. E. J.; Zdeborová, Lenka

    2014-11-01

    We study percolation on networks, which is used as a model of the resilience of networked systems such as the Internet to attack or failure and as a simple model of the spread of disease over human contact networks. We reformulate percolation as a message passing process and demonstrate how the resulting equations can be used to calculate, among other things, the size of the percolating cluster and the average cluster size. The calculations are exact for sparse networks when the number of short loops in the network is small, but even on networks with many short loops we find them to be highly accurate when compared with direct numerical simulations. By considering the fixed points of the message passing process, we also show that the percolation threshold on a network with few loops is given by the inverse of the leading eigenvalue of the so-called nonbacktracking matrix.

  6. Internet protocol network mapper

    DOEpatents

    Youd, David W.; Colon III, Domingo R.; Seidl, Edward T.

    2016-02-23

    A network mapper for performing tasks on targets is provided. The mapper generates a map of a network that specifies the overall configuration of the network. The mapper inputs a procedure that defines how the network is to be mapped. The procedure specifies what, when, and in what order the tasks are to be performed. Each task specifies processing that is to be performed for a target to produce results. The procedure may also specify input parameters for a task. The mapper inputs initial targets that specify a range of network addresses to be mapped. The mapper maps the network by, for each target, executing the procedure to perform the tasks on the target. The results of the tasks represent the mapping of the network defined by the initial targets.

  7. Network topology analysis.

    SciTech Connect

    Kalb, Jeffrey L.; Lee, David S.

    2008-01-01

    Emerging high-bandwidth, low-latency network technology has made network-based architectures both feasible and potentially desirable for use in satellite payload architectures. The selection of network topology is a critical component when developing these multi-node or multi-point architectures. This study examines network topologies and their effect on overall network performance. Numerous topologies were reviewed against a number of performance, reliability, and cost metrics. This document identifies a handful of good network topologies for satellite applications and the metrics used to justify them as such. Since often multiple topologies will meet the requirements of the satellite payload architecture under development, the choice of network topology is not easy, and in the end the choice of topology is influenced by both the design characteristics and requirements of the overall system and the experience of the developer.

  8. Dim Networks: The Utility of Social Network Analysis for Illuminating Partner Security Force Networks

    DTIC Science & Technology

    2015-12-01

    use of social network analysis (SNA) has allowed the military to map dark networks of terrorist organizations and selectively target key elements...data to improve SC. 14. SUBJECT TERMS social network analysis, dark networks, light networks, dim networks, security cooperation, Southeast Asia...task may already exist. Recently, the use of social network analysis (SNA) has allowed the military to map dark networks of terrorist organizations

  9. Organization of complex networks

    NASA Astrophysics Data System (ADS)

    Kitsak, Maksim

    Many large complex systems can be successfully analyzed using the language of graphs and networks. Interactions between the objects in a network are treated as links connecting nodes. This approach to understanding the structure of networks is an important step toward understanding the way corresponding complex systems function. Using the tools of statistical physics, we analyze the structure of networks as they are found in complex systems such as the Internet, the World Wide Web, and numerous industrial and social networks. In the first chapter we apply the concept of self-similarity to the study of transport properties in complex networks. Self-similar or fractal networks, unlike non-fractal networks, exhibit similarity on a range of scales. We find that these fractal networks have transport properties that differ from those of non-fractal networks. In non-fractal networks, transport flows primarily through the hubs. In fractal networks, the self-similar structure requires any transport to also flow through nodes that have only a few connections. We also study, in models and in real networks, the crossover from fractal to non-fractal networks that occurs when a small number of random interactions are added by means of scaling techniques. In the second chapter we use k-core techniques to study dynamic processes in networks. The k-core of a network is the network's largest component that, within itself, exhibits all nodes with at least k connections. We use this k-core analysis to estimate the relative leadership positions of firms in the Life Science (LS) and Information and Communication Technology (ICT) sectors of industry. We study the differences in the k-core structure between the LS and the ICT sectors. We find that the lead segment (highest k-core) of the LS sector, unlike that of the ICT sector, is remarkably stable over time: once a particular firm enters the lead segment, it is likely to remain there for many years. In the third chapter we study how

  10. Network planning under uncertainties

    NASA Astrophysics Data System (ADS)

    Ho, Kwok Shing; Cheung, Kwok Wai

    2008-11-01

    One of the main focuses for network planning is on the optimization of network resources required to build a network under certain traffic demand projection. Traditionally, the inputs to this type of network planning problems are treated as deterministic. In reality, the varying traffic requirements and fluctuations in network resources can cause uncertainties in the decision models. The failure to include the uncertainties in the network design process can severely affect the feasibility and economics of the network. Therefore, it is essential to find a solution that can be insensitive to the uncertain conditions during the network planning process. As early as in the 1960's, a network planning problem with varying traffic requirements over time had been studied. Up to now, this kind of network planning problems is still being active researched, especially for the VPN network design. Another kind of network planning problems under uncertainties that has been studied actively in the past decade addresses the fluctuations in network resources. One such hotly pursued research topic is survivable network planning. It considers the design of a network under uncertainties brought by the fluctuations in topology to meet the requirement that the network remains intact up to a certain number of faults occurring anywhere in the network. Recently, the authors proposed a new planning methodology called Generalized Survivable Network that tackles the network design problem under both varying traffic requirements and fluctuations of topology. Although all the above network planning problems handle various kinds of uncertainties, it is hard to find a generic framework under more general uncertainty conditions that allows a more systematic way to solve the problems. With a unified framework, the seemingly diverse models and algorithms can be intimately related and possibly more insights and improvements can be brought out for solving the problem. This motivates us to seek a

  11. Patterns in randomly evolving networks: Idiotypic networks

    NASA Astrophysics Data System (ADS)

    Brede, Markus; Behn, Ulrich

    2003-03-01

    We present a model for the evolution of networks of occupied sites on undirected regular graphs. At every iteration step in a parallel update, I randomly chosen empty sites are occupied and occupied sites having occupied neighbor degree outside of a given interval (tl,tu) are set empty. Depending on the influx I and the values of both lower threshold and upper threshold of the occupied neighbor degree, different kinds of behavior can be observed. In certain regimes stable long-living patterns appear. We distinguish two types of patterns: static patterns arising on graphs with low connectivity and dynamic patterns found on high connectivity graphs. Increasing I patterns become unstable and transitions between almost stable patterns, interrupted by disordered phases, occur. For still larger I the lifetime of occupied sites becomes very small and network structures are dominated by randomness. We develop methods to analyze the nature and dynamics of these network patterns, give a statistical description of defects and fluctuations around them, and elucidate the transitions between different patterns. Results and methods presented can be applied to a variety of problems in different fields and a broad class of graphs. Aiming chiefly at the modeling of functional networks of interacting antibodies and B cells of the immune system (idiotypic networks), we focus on a class of graphs constructed by bit chains. The biological relevance of the patterns and possible operational modes of idiotypic networks are discussed.

  12. Optical Access Networks

    NASA Astrophysics Data System (ADS)

    Zheng, Jun; Ansari, Nirwan

    2005-05-01

    Call for Papers: Optical Access Networks With the wide deployment of fiber-optic technology over the past two decades, we have witnessed a tremendous growth of bandwidth capacity in the backbone networks of today's telecommunications infrastructure. However, access networks, which cover the "last-mile" areas and serve numerous residential and small business users, have not been scaled up commensurately. The local subscriber lines for telephone and cable television are still using twisted pairs and coaxial cables. Most residential connections to the Internet are still through dial-up modems operating at a low speed on twisted pairs. As the demand for access bandwidth increases with emerging high-bandwidth applications, such as distance learning, high-definition television (HDTV), and video on demand (VoD), the last-mile access networks have become a bandwidth bottleneck in today's telecommunications infrastructure. To ease this bottleneck, it is imperative to provide sufficient bandwidth capacity in the access networks to open the bottleneck and thus present more opportunities for the provisioning of multiservices. Optical access solutions promise huge bandwidth to service providers and low-cost high-bandwidth services to end users and are therefore widely considered the technology of choice for next-generation access networks. To realize the vision of optical access networks, however, many key issues still need to be addressed, such as network architectures, signaling protocols, and implementation standards. The major challenges lie in the fact that an optical solution must be not only robust, scalable, and flexible, but also implemented at a low cost comparable to that of existing access solutions in order to increase the economic viability of many potential high-bandwidth applications. In recent years, optical access networks have been receiving tremendous attention from both academia and industry. A large number of research activities have been carried out or

  13. Optical Access Networks

    NASA Astrophysics Data System (ADS)

    Zheng, Jun; Ansari, Nirwan; Jersey Inst Ansari, New; Jersey Inst, New

    2005-04-01

    Call for Papers: Optical Access Networks With the wide deployment of fiber-optic technology over the past two decades, we have witnessed a tremendous growth of bandwidth capacity in the backbone networks of today's telecommunications infrastructure. However, access networks, which cover the "last-mile" areas and serve numerous residential and small business users, have not been scaled up commensurately. The local subscriber lines for telephone and cable television are still using twisted pairs and coaxial cables. Most residential connections to the Internet are still through dial-up modems operating at a low speed on twisted pairs. As the demand for access bandwidth increases with emerging high-bandwidth applications, such as distance learning, high-definition television (HDTV), and video on demand (VoD), the last-mile access networks have become a bandwidth bottleneck in today's telecommunications infrastructure. To ease this bottleneck, it is imperative to provide sufficient bandwidth capacity in the access networks to open the bottleneck and thus present more opportunities for the provisioning of multiservices. Optical access solutions promise huge bandwidth to service providers and low-cost high-bandwidth services to end users and are therefore widely considered the technology of choice for next-generation access networks. To realize the vision of optical access networks, however, many key issues still need to be addressed, such as network architectures, signaling protocols, and implementation standards. The major challenges lie in the fact that an optical solution must be not only robust, scalable, and flexible, but also implemented at a low cost comparable to that of existing access solutions in order to increase the economic viability of many potential high-bandwidth applications. In recent years, optical access networks have been receiving tremendous attention from both academia and industry. A large number of research activities have been carried out or

  14. Optical Access Networks

    NASA Astrophysics Data System (ADS)

    Zheng, Jun; Ansari, Nirwan

    2005-06-01

    Call for Papers: Optical Access Networks With the wide deployment of fiber-optic technology over the past two decades, we have witnessed a tremendous growth of bandwidth capacity in the backbone networks of today's telecommunications infrastructure. However, access networks, which cover the "last-mile" areas and serve numerous residential and small business users, have not been scaled up commensurately. The local subscriber lines for telephone and cable television are still using twisted pairs and coaxial cables. Most residential connections to the Internet are still through dial-up modems operating at a low speed on twisted pairs. As the demand for access bandwidth increases with emerging high-bandwidth applications, such as distance learning, high-definition television (HDTV), and video on demand (VoD), the last-mile access networks have become a bandwidth bottleneck in today's telecommunications infrastructure. To ease this bottleneck, it is imperative to provide sufficient bandwidth capacity in the access networks to open the bottleneck and thus present more opportunities for the provisioning of multiservices. Optical access solutions promise huge bandwidth to service providers and low-cost high-bandwidth services to end users and are therefore widely considered the technology of choice for next-generation access networks. To realize the vision of optical access networks, however, many key issues still need to be addressed, such as network architectures, signaling protocols, and implementation standards. The major challenges lie in the fact that an optical solution must be not only robust, scalable, and flexible, but also implemented at a low cost comparable to that of existing access solutions in order to increase the economic viability of many potential high-bandwidth applications. In recent years, optical access networks have been receiving tremendous attention from both academia and industry. A large number of research activities have been carried out or

  15. Cognitive Network Neuroscience

    PubMed Central

    Medaglia, John D.; Lynall, Mary-Ellen; Bassett, Danielle S.

    2016-01-01

    Network science provides theoretical, computational, and empirical tools that can be used to understand the structure and function of the human brain in novel ways using simple concepts and mathematical representations. Network neuroscience is a rapidly growing field that is providing considerable insight into human structural connectivity, functional connectivity while at rest, changes in functional networks over time (dynamics), and how these properties differ in clinical populations. In addition, a number of studies have begun to quantify network characteristics in a variety of cognitive processes and provide a context for understanding cognition from a network perspective. In this review, we outline the contributions of network science to cognitive neuroscience. We describe the methodology of network science as applied to the particular case of neuroimaging data and review its uses in investigating a range of cognitive functions including sensory processing, language, emotion, attention, cognitive control, learning, and memory. In conclusion, we discuss current frontiers and the specific challenges that must be overcome to integrate these complementary disciplines of network science and cognitive neuroscience. Increased communication between cognitive neuroscientists and network scientists could lead to significant discoveries under an emerging scientific intersection known as cognitive network neuroscience. PMID:25803596

  16. Branching toughens fibrous networks.

    PubMed

    Koh, C T; Oyen, M L

    2012-08-01

    Fibrous collagenous networks are not only stiff but also tough, due to their complex microstructures. This stiff yet tough behavior is desirable for both medical and military applications but it is difficult to reproduce in engineering materials. While the nonlinear hyperelastic behavior of fibrous networks has been extensively studied, the understanding of toughness is still incomplete. Here, we identify a microstructure mimicking the branched bundles of a natural type I collagen network, in which partially cross-linked long fibers give rise to novel combinations of stiffness and toughness. Finite element analysis shows that the stiffness of fully cross-linked fibrous networks is amplified by increasing the fibril length and cross-link density. However, a trade-off of such stiff networks is reduced toughness. By having partially cross-linked networks with long fibrils, the networks have comparable stiffness and improved toughness as compared to the fully cross-linked networks. Further, the partially cross-linked networks avoid the formation of kinks, which cause fibril rupture during deformation. As a result, the branching allows the networks to have stiff yet tough behavior.

  17. Serial Network Flow Monitor

    NASA Technical Reports Server (NTRS)

    Robinson, Julie A.; Tate-Brown, Judy M.

    2009-01-01

    Using a commercial software CD and minimal up-mass, SNFM monitors the Payload local area network (LAN) to analyze and troubleshoot LAN data traffic. Validating LAN traffic models may allow for faster and more reliable computer networks to sustain systems and science on future space missions. Research Summary: This experiment studies the function of the computer network onboard the ISS. On-orbit packet statistics are captured and used to validate ground based medium rate data link models and enhance the way that the local area network (LAN) is monitored. This information will allow monitoring and improvement in the data transfer capabilities of on-orbit computer networks. The Serial Network Flow Monitor (SNFM) experiment attempts to characterize the network equivalent of traffic jams on board ISS. The SNFM team is able to specifically target historical problem areas including the SAMS (Space Acceleration Measurement System) communication issues, data transmissions from the ISS to the ground teams, and multiple users on the network at the same time. By looking at how various users interact with each other on the network, conflicts can be identified and work can begin on solutions. SNFM is comprised of a commercial off the shelf software package that monitors packet traffic through the payload Ethernet LANs (local area networks) on board ISS.

  18. Collaborative learning in networks.

    PubMed

    Mason, Winter; Watts, Duncan J

    2012-01-17

    Complex problems in science, business, and engineering typically require some tradeoff between exploitation of known solutions and exploration for novel ones, where, in many cases, information about known solutions can also disseminate among individual problem solvers through formal or informal networks. Prior research on complex problem solving by collectives has found the counterintuitive result that inefficient networks, meaning networks that disseminate information relatively slowly, can perform better than efficient networks for problems that require extended exploration. In this paper, we report on a series of 256 Web-based experiments in which groups of 16 individuals collectively solved a complex problem and shared information through different communication networks. As expected, we found that collective exploration improved average success over independent exploration because good solutions could diffuse through the network. In contrast to prior work, however, we found that efficient networks outperformed inefficient networks, even in a problem space with qualitative properties thought to favor inefficient networks. We explain this result in terms of individual-level explore-exploit decisions, which we find were influenced by the network structure as well as by strategic considerations and the relative payoff between maxima. We conclude by discussing implications for real-world problem solving and possible extensions.

  19. Computer network programming

    SciTech Connect

    Hsu, J.Y.

    1996-12-31

    The programs running on a computer network can be divided into two parts, the Network Operating System and the user applications. Any high level language translator, such as C, JAVA, BASIC, FORTRAN, or COBOL, runs under NOS as a programming tool to produce network application programs or software. Each application program while running on the network provides the human user with network application services, such as remote data base search, retrieval, etc. The Network Operating System should provide a simple and elegant system interface to all the network application programs. This programming interface may request the Transport layer services on behalf of a network application program. The primary goals are to achieve programming convenience, and to avoid complexity. In a 5-layer network model, the system interface is comprised of a group of system calls which are collectively known as the session layer with its own Session Protocol Data Units. This is a position paper discussing the basic system primitives which reside between a network application program and the Transport layer, and a programming example of using such primitives.

  20. Cognitive network neuroscience.

    PubMed

    Medaglia, John D; Lynall, Mary-Ellen; Bassett, Danielle S

    2015-08-01

    Network science provides theoretical, computational, and empirical tools that can be used to understand the structure and function of the human brain in novel ways using simple concepts and mathematical representations. Network neuroscience is a rapidly growing field that is providing considerable insight into human structural connectivity, functional connectivity while at rest, changes in functional networks over time (dynamics), and how these properties differ in clinical populations. In addition, a number of studies have begun to quantify network characteristics in a variety of cognitive processes and provide a context for understanding cognition from a network perspective. In this review, we outline the contributions of network science to cognitive neuroscience. We describe the methodology of network science as applied to the particular case of neuroimaging data and review its uses in investigating a range of cognitive functions including sensory processing, language, emotion, attention, cognitive control, learning, and memory. In conclusion, we discuss current frontiers and the specific challenges that must be overcome to integrate these complementary disciplines of network science and cognitive neuroscience. Increased communication between cognitive neuroscientists and network scientists could lead to significant discoveries under an emerging scientific intersection known as cognitive network neuroscience.

  1. Weighted Multiplex Networks

    PubMed Central

    Menichetti, Giulia; Remondini, Daniel; Panzarasa, Pietro; Mondragón, Raúl J.; Bianconi, Ginestra

    2014-01-01

    One of the most important challenges in network science is to quantify the information encoded in complex network structures. Disentangling randomness from organizational principles is even more demanding when networks have a multiplex nature. Multiplex networks are multilayer systems of nodes that can be linked in multiple interacting and co-evolving layers. In these networks, relevant information might not be captured if the single layers were analyzed separately. Here we demonstrate that such partial analysis of layers fails to capture significant correlations between weights and topology of complex multiplex networks. To this end, we study two weighted multiplex co-authorship and citation networks involving the authors included in the American Physical Society. We show that in these networks weights are strongly correlated with multiplex structure, and provide empirical evidence in favor of the advantage of studying weighted measures of multiplex networks, such as multistrength and the inverse multiparticipation ratio. Finally, we introduce a theoretical framework based on the entropy of multiplex ensembles to quantify the information stored in multiplex networks that would remain undetected if the single layers were analyzed in isolation. PMID:24906003

  2. NASA Communications Augmentation network

    NASA Technical Reports Server (NTRS)

    Omidyar, Guy C.; Butler, Thomas E.; Laios, Straton C.

    1990-01-01

    The NASA Communications (Nascom) Division of the Mission Operations and Data Systems Directorate (MO&DSD) is to undertake a major initiative to develop the Nascom Augmentation (NAUG) network to achieve its long-range service objectives for operational data transport to support the Space Station Freedom Program, the Earth Observing System (EOS), and other projects. The NAUG is the Nascom ground communications network being developed to accommodate the operational traffic of the mid-1990s and beyond. The NAUG network development will be based on the Open Systems Interconnection Reference Model (OSI-RM). This paper describes the NAUG network architecture, subsystems, topology, and services; addresses issues of internetworking the Nascom network with other elements of the Space Station Information System (SSIS); discusses the operations environment. This paper also notes the areas of related research and presents the current conception of how the network will provide broadband services in 1998.

  3. Expert networks in CLIPS

    NASA Technical Reports Server (NTRS)

    Hruska, S. I.; Dalke, A.; Ferguson, J. J.; Lacher, R. C.

    1991-01-01

    Rule-based expert systems may be structurally and functionally mapped onto a special class of neural networks called expert networks. This mapping lends itself to adaptation of connectionist learning strategies for the expert networks. A parsing algorithm to translate C Language Integrated Production System (CLIPS) rules into a network of interconnected assertion and operation nodes has been developed. The translation of CLIPS rules to an expert network and back again is illustrated. Measures of uncertainty similar to those rules in MYCIN-like systems are introduced into the CLIPS system and techniques for combining and hiring nodes in the network based on rule-firing with these certainty factors in the expert system are presented. Several learning algorithms are under study which automate the process of attaching certainty factors to rules.

  4. Distributed network scheduling

    NASA Technical Reports Server (NTRS)

    Clement, Bradley J.; Schaffer, Steven R.

    2004-01-01

    Distributed Network Scheduling is the scheduling of future communications of a network by nodes in the network. This report details software for doing this onboard spacecraft in a remote network. While prior work on distributed scheduling has been applied to remote spacecraft networks, the software reported here focuses on modeling communication activities in greater detail and including quality of service constraints. Our main results are based on a Mars network of spacecraft and include identifying a maximum opportunity of improving traverse exploration rate a factor of three; a simulation showing reduction in one-way delivery times from a rover to Earth from as much as 5 to 1.5 hours; simulated response to unexpected events averaging under an hour onboard; and ground schedule generation ranging from seconds to 50 minutes for 15 to 100 communication goals.

  5. Compressive Network Analysis

    PubMed Central

    Jiang, Xiaoye; Yao, Yuan; Liu, Han; Guibas, Leonidas

    2014-01-01

    Modern data acquisition routinely produces massive amounts of network data. Though many methods and models have been proposed to analyze such data, the research of network data is largely disconnected with the classical theory of statistical learning and signal processing. In this paper, we present a new framework for modeling network data, which connects two seemingly different areas: network data analysis and compressed sensing. From a nonparametric perspective, we model an observed network using a large dictionary. In particular, we consider the network clique detection problem and show connections between our formulation with a new algebraic tool, namely Randon basis pursuit in homogeneous spaces. Such a connection allows us to identify rigorous recovery conditions for clique detection problems. Though this paper is mainly conceptual, we also develop practical approximation algorithms for solving empirical problems and demonstrate their usefulness on real-world datasets. PMID:25620806

  6. Professional social networking.

    PubMed

    Rowley, Robert D

    2014-12-01

    We review the current state of social communication between healthcare professionals, the role of consumer social networking, and some emerging technologies to address the gaps. In particular, the review covers (1) the current state of loose social networking for continuing medical education (CME) and other broadcast information dissemination; (2) social networking for business promotion; (3) social networking for peer collaboration, including simple communication as well as more robust data-centered collaboration around patient care; and (4) engaging patients on social platforms, including integrating consumer-originated data into the mix of healthcare data. We will see how, as the nature of healthcare delivery moves from the institution-centric way of tradition to a more social and networked ambulatory pattern that we see emerging today, the nature of health IT has also moved from enterprise-centric systems to more socially networked, cloud-based options.

  7. Compressive Network Analysis.

    PubMed

    Jiang, Xiaoye; Yao, Yuan; Liu, Han; Guibas, Leonidas

    2014-11-01

    Modern data acquisition routinely produces massive amounts of network data. Though many methods and models have been proposed to analyze such data, the research of network data is largely disconnected with the classical theory of statistical learning and signal processing. In this paper, we present a new framework for modeling network data, which connects two seemingly different areas: network data analysis and compressed sensing. From a nonparametric perspective, we model an observed network using a large dictionary. In particular, we consider the network clique detection problem and show connections between our formulation with a new algebraic tool, namely Randon basis pursuit in homogeneous spaces. Such a connection allows us to identify rigorous recovery conditions for clique detection problems. Though this paper is mainly conceptual, we also develop practical approximation algorithms for solving empirical problems and demonstrate their usefulness on real-world datasets.

  8. Reconfigureable network node

    DOEpatents

    Vanderveen, Keith B.; Talbot, Edward B.; Mayer, Laurence E.

    2008-04-08

    Nodes in a network having a plurality of nodes establish communication links with other nodes using available transmission media, as the ability to establish such links becomes available and desirable. The nodes predict when existing communications links will fail, become overloaded or otherwise degrade network effectiveness and act to establish substitute or additional links before the node's ability to communicate with the other nodes on the network is adversely affected. A node stores network topology information and programmed link establishment rules and criteria. The node evaluates characteristics that predict existing links with other nodes becoming unavailable or degraded. The node then determines whether it can form a communication link with a substitute node, in order to maintain connectivity with the network. When changing its communication links, a node broadcasts that information to the network. Other nodes update their stored topology information and consider the updated topology when establishing new communications links for themselves.

  9. Oscillations of complex networks

    NASA Astrophysics Data System (ADS)

    Wang, Xingang; Lai, Ying-Cheng; Lai, Choy Heng

    2006-12-01

    A complex network processing information or physical flows is usually characterized by a number of macroscopic quantities such as the diameter and the betweenness centrality. An issue of significant theoretical and practical interest is how such quantities respond to sudden changes caused by attacks or disturbances in recoverable networks, i.e., functions of the affected nodes are only temporarily disabled or partially limited. By introducing a model to address this issue, we find that, for a finite-capacity network, perturbations can cause the network to oscillate persistently in the sense that the characterizing quantities vary periodically or randomly with time. We provide a theoretical estimate of the critical capacity-parameter value for the onset of the network oscillation. The finding is expected to have broad implications as it suggests that complex networks may be structurally highly dynamic.

  10. Seven Deadliest Network Attacks

    SciTech Connect

    Prowell, Stacy J; Borkin, Michael; Kraus, Robert

    2010-05-01

    Do you need to keep up with the latest hacks, attacks, and exploits effecting networks? Then you need "Seven Deadliest Network Attacks". This book pinpoints the most dangerous hacks and exploits specific to networks, laying out the anatomy of these attacks including how to make your system more secure. You will discover the best ways to defend against these vicious hacks with step-by-step instruction and learn techniques to make your computer and network impenetrable. Attacks detailed in this book include: Denial of Service; War Dialing; Penetration 'Testing'; Protocol Tunneling; Spanning Tree Attacks; Man-in-the-Middle; and, Password Replay. Knowledge is power, find out about the most dominant attacks currently waging war on computers and networks globally. Discover the best ways to defend against these vicious attacks; step-by-step instruction shows you how. Institute countermeasures, don't be caught defenseless again, learn techniques to make your computer and network impenetrable.

  11. The optimation of random network coding in wireless MESH networks

    NASA Astrophysics Data System (ADS)

    Pang, Chunjiang; Pan, Xikun

    2013-03-01

    In order to improve the efficiency of wireless mesh network transmission, this paper focused on the network coding technology. Using network coding can significantly increase the wireless mesh network's throughput, but it will inevitably increase the computational complexity to the network, and the traditional linear network coding algorithm requires the aware of the whole network topology, which is impossible in the ever-changing topology of wireless mesh networks. In this paper, we use a distributed network coding strategy: random network coding, which don't need to know the whole topology of the network. In order to decrease the computation complexity, this paper suggests an improved strategy for random network coding: Do not code the packets which bring no good to the whole transmission. In this paper, we list several situations which coding is not necessary. Simulation results show that applying these strategies can improve the efficiency of wireless mesh network transmission.

  12. The deep space network

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The objectives, functions, and organization of the Deep Space Network are summarized along with deep space station, ground communication, and network operations control capabilities. Mission support of ongoing planetary/interplanetary flight projects is discussed with emphasis on Viking orbiter radio frequency compatibility tests, the Pioneer Venus orbiter mission, and Helios-1 mission status and operations. Progress is also reported in tracking and data acquisition research and technology, network engineering, hardware and software implementation, and operations.

  13. Tomography using neural networks

    NASA Astrophysics Data System (ADS)

    Demeter, G.

    1997-03-01

    We have utilized neural networks for fast evaluation of tomographic data on the MT-1M tokamak. The networks have proven useful in providing the parameters of a nonlinear fit to experimental data, producing results in a fraction of the time required for performing the nonlinear fit. Time required for training the networks makes the method worth applying only if a substantial amount of data are to be evaluated.

  14. Nonlinear Neural Network Oscillator.

    DTIC Science & Technology

    A nonlinear oscillator (10) includes a neural network (12) having at least one output (12a) for outputting a one dimensional vector. The neural ... neural network and the input of the input layer for modifying a magnitude and/or a polarity of the one dimensional output vector prior to the sample of...first or a second direction. Connection weights of the neural network are trained on a deterministic sequence of data from a chaotic source or may be a

  15. Neural Network Hurricane Tracker

    DTIC Science & Technology

    1998-05-27

    data about the hurricane and supplying the data to a trained neural network for yielding a predicted path for the hurricane. The system further includes...a device for displaying the predicted path of the hurricane. A method for using and training the neural network in the system is described. In the...method, the neural network is trained using information about hurricanes in a specific geographical area maintained in a database. The training involves

  16. Albuquerque Basin seismic network

    USGS Publications Warehouse

    Jaksha, Lawrence H.; Locke, Jerry; Thompson, J.B.; Garcia, Alvin

    1977-01-01

    The U.S. Geological Survey has recently completed the installation of a seismic network around the Albuquerque Basin in New Mexico. The network consists of two seismometer arrays, a thirteen-station array monitoring an area of approximately 28,000 km 2 and an eight-element array monitoring the area immediately adjacent to the Albuquerque Seismological Laboratory. This report describes the instrumentation deployed in the network.

  17. Networks of Markovian Queues.

    DTIC Science & Technology

    1987-05-01

    8217There is a recognized need to make the subject of queueing network theory less esoteric.’ The engineer who is faced with an application often does not...112 5.3.2 Local Balance ..... a. ................................ 114 5.3.3 An Application of an Open Queueing Network ...Rate Case ....................... 125 5.3.2 Closed Networks ...................................... 127 * 5.4.3 An Application of Closed Queueing

  18. Network problem threshold

    NASA Technical Reports Server (NTRS)

    Gejji, Raghvendra, R.

    1992-01-01

    Network transmission errors such as collisions, CRC errors, misalignment, etc. are statistical in nature. Although errors can vary randomly, a high level of errors does indicate specific network problems, e.g. equipment failure. In this project, we have studied the random nature of collisions theoretically as well as by gathering statistics, and established a numerical threshold above which a network problem is indicated with high probability.

  19. NASA Integrated Network COOP

    NASA Technical Reports Server (NTRS)

    Anderson, Michael L.; Wright, Nathaniel; Tai, Wallace

    2012-01-01

    Natural disasters, terrorist attacks, civil unrest, and other events have the potential of disrupting mission-essential operations in any space communications network. NASA's Space Communications and Navigation office (SCaN) is in the process of studying options for integrating the three existing NASA network elements, the Deep Space Network, the Near Earth Network, and the Space Network, into a single integrated network with common services and interfaces. The need to maintain Continuity of Operations (COOP) after a disastrous event has a direct impact on the future network design and operations concepts. The SCaN Integrated Network will provide support to a variety of user missions. The missions have diverse requirements and include anything from earth based platforms to planetary missions and rovers. It is presumed that an integrated network, with common interfaces and processes, provides an inherent advantage to COOP in that multiple elements and networks can provide cross-support in a seamless manner. The results of trade studies support this assumption but also show that centralization as a means of achieving integration can result in single points of failure that must be mitigated. The cost to provide this mitigation can be substantial. In support of this effort, the team evaluated the current approaches to COOP, developed multiple potential approaches to COOP in a future integrated network, evaluated the interdependencies of the various approaches to the various network control and operations options, and did a best value assessment of the options. The paper will describe the trade space, the study methods, and results of the study.

  20. The Deep Space Network

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The objectives, functions, and organization, of the Deep Space Network are summarized. Deep Space stations, ground communications, and network operations control capabilities are described. The network is designed for two-way communications with unmanned spacecraft traveling approximately 1600 km from earth to the farthest planets in the solar system. It has provided tracking and data acquisition support for the following projects: Ranger, Surveyor, Mariner, Pioneer, Apollo, Helios, Viking, and the Lunar Orbiter.

  1. The Unesco/UIE Literacy Network: A Network of Networks.

    ERIC Educational Resources Information Center

    Giere, Ursula

    In order to achieve significant results, crucial criteria for stabilizing a network's capacity for dialog are high levels of commitment to offer high quality knowledge, two-way translation from research knowledge to practitioners and from practice to researchers, a maximum size, face-to-face communication, infrastructure, and funds for…

  2. Network of Networks and the Climate System

    NASA Astrophysics Data System (ADS)

    Kurths, Jürgen; Boers, Niklas; Bookhagen, Bodo; Donges, Jonathan; Donner, Reik; Malik, Nishant; Marwan, Norbert; Stolbova, Veronika

    2013-04-01

    Network of networks is a new direction in complex systems science. One can find such networks in various fields, such as infrastructure (power grids etc.), human brain or Earth system. Basic properties and new characteristics, such as cross-degree, or cross-betweenness will be discussed. This allows us to quantify the structural role of single vertices or whole sub-networks with respect to the interaction of a pair of subnetworks on local, mesoscopic, and global topological scales. Next, we consider an inverse problem: Is there a backbone-like structure underlying the climate system? For this we propose a method to reconstruct and analyze a complex network from data generated by a spatio-temporal dynamical system. This technique is then applied to 3-dimensional data of the climate system. We interpret different heights in the atmosphere as different networks and the whole as a network of networks. This approach enables us to uncover relations to global circulation patterns in oceans and atmosphere. The global scale view on climate networks offers promising new perspectives for detecting dynamical structures based on nonlinear physical processes in the climate system. This concept is applied to Indian Monsoon data in order to characterize the regional occurrence of strong rain events and its impact on predictability. References: Arenas, A., A. Diaz-Guilera, J. Kurths, Y. Moreno, and C. Zhou, Phys. Reports 2008, 469, 93. Donges, J., Y. Zou, N. Marwan, and J. Kurths, Europhys. Lett. 2009, 87, 48007. Donner, R., Y. Zou, J. Donges, N. Marwan, and J. Kurths, Phys. Rev. E 2010, 81, 015101(R ). Mokhov, I. I., D. A. Smirnov, P. I. Nakonechny, S. S. Kozlenko, E. P. Seleznev, and J. Kurths, Geophys. Res. Lett. 2011, 38, L00F04. Malik, N., B. Bookhagen, N. Marwan, and J. Kurths, Climate Dynamics, 2012, 39, 971. Donges, J., H. Schultz, N. Marwan, Y. Zou, J. Kurths, Eur. J. Phys. B 2011, 84, 635-651. Donges, J., R. Donner, M. Trauth, N. Marwan, H.J. Schellnhuber, and J. Kurths

  3. Optical network democratization.

    PubMed

    Nejabati, Reza; Peng, Shuping; Simeonidou, Dimitra

    2016-03-06

    The current Internet infrastructure is not able to support independent evolution and innovation at physical and network layer functionalities, protocols and services, while at same time supporting the increasing bandwidth demands of evolving and heterogeneous applications. This paper addresses this problem by proposing a completely democratized optical network infrastructure. It introduces the novel concepts of the optical white box and bare metal optical switch as key technology enablers for democratizing optical networks. These are programmable optical switches whose hardware is loosely connected internally and is completely separated from their control software. To alleviate their complexity, a multi-dimensional abstraction mechanism using software-defined network technology is proposed. It creates a universal model of the proposed switches without exposing their technological details. It also enables a conventional network programmer to develop network applications for control of the optical network without specific technical knowledge of the physical layer. Furthermore, a novel optical network virtualization mechanism is proposed, enabling the composition and operation of multiple coexisting and application-specific virtual optical networks sharing the same physical infrastructure. Finally, the optical white box and the abstraction mechanism are experimentally evaluated, while the virtualization mechanism is evaluated with simulation.

  4. Celestial data routing network

    NASA Astrophysics Data System (ADS)

    Bordetsky, Alex

    2000-11-01

    Imagine that information processing human-machine network is threatened in a particular part of the world. Suppose that an anticipated threat of physical attacks could lead to disruption of telecommunications network management infrastructure and access capabilities for small geographically distributed groups engaged in collaborative operations. Suppose that small group of astronauts are exploring the solar planet and need to quickly configure orbital information network to support their collaborative work and local communications. The critical need in both scenarios would be a set of low-cost means of small team celestial networking. To the geographically distributed mobile collaborating groups such means would allow to maintain collaborative multipoint work, set up orbital local area network, and provide orbital intranet communications. This would be accomplished by dynamically assembling the network enabling infrastructure of the small satellite based router, satellite based Codec, and set of satellite based intelligent management agents. Cooperating single function pico satellites, acting as agents and personal switching devices together would represent self-organizing intelligent orbital network of cooperating mobile management nodes. Cooperative behavior of the pico satellite based agents would be achieved by comprising a small orbital artificial neural network capable of learning and restructing the networking resources in response to the anticipated threat.

  5. Mobile Virtual Private Networking

    NASA Astrophysics Data System (ADS)

    Pulkkis, Göran; Grahn, Kaj; Mårtens, Mathias; Mattsson, Jonny

    Mobile Virtual Private Networking (VPN) solutions based on the Internet Security Protocol (IPSec), Transport Layer Security/Secure Socket Layer (SSL/TLS), Secure Shell (SSH), 3G/GPRS cellular networks, Mobile IP, and the presently experimental Host Identity Protocol (HIP) are described, compared and evaluated. Mobile VPN solutions based on HIP are recommended for future networking because of superior processing efficiency and network capacity demand features. Mobile VPN implementation issues associated with the IP protocol versions IPv4 and IPv6 are also evaluated. Mobile VPN implementation experiences are presented and discussed.

  6. Generalized Communities in Networks

    NASA Astrophysics Data System (ADS)

    Newman, M. E. J.; Peixoto, Tiago P.

    2015-08-01

    A substantial volume of research is devoted to studies of community structure in networks, but communities are not the only possible form of large-scale network structure. Here, we describe a broad extension of community structure that encompasses traditional communities but includes a wide range of generalized structural patterns as well. We describe a principled method for detecting this generalized structure in empirical network data and demonstrate with real-world examples how it can be used to learn new things about the shape and meaning of networks.

  7. Mixing navigation on networks

    NASA Astrophysics Data System (ADS)

    Zhou, Tao

    2008-05-01

    In this article, we propose a mixing navigation mechanism, which interpolates between random-walk and shortest-path protocol. The navigation efficiency can be remarkably enhanced via a few routers. Some advanced strategies are also designed: For non-geographical scale-free networks, the targeted strategy with a tiny fraction of routers can guarantee an efficient navigation with low and stable delivery time almost independent of network size. For geographical localized networks, the clustering strategy can simultaneously increase efficiency and reduce the communication cost. The present mixing navigation mechanism is of significance especially for information organization of wireless sensor networks and distributed autonomous robotic systems.

  8. Mission Critical Networking

    SciTech Connect

    Eltoweissy, Mohamed Y.; Du, David H.C.; Gerla, Mario; Giordano, Silvia; Gouda, Mohamed; Schulzrinne, Henning; Youssef, Moustafa

    2010-06-01

    Mission-Critical Networking (MCN) refers to networking for application domains where life or livelihood may be at risk. Typical application domains for MCN include critical infrastructure protection and operation, emergency and crisis intervention, healthcare services, and military operations. Such networking is essential for safety, security and economic vitality in our complex world characterized by uncertainty, heterogeneity, emergent behaviors, and the need for reliable and timely response. MCN comprise networking technology, infrastructures and services that may alleviate the risk and directly enable and enhance connectivity for mission-critical information exchange among diverse, widely dispersed, mobile users.

  9. Future Optical Networks

    NASA Astrophysics Data System (ADS)

    O'Mahony, Michael J.; Politi, Christina; Klonidis, Dimitrios; Nejabati, Reza; Simeonidou, Dimitra

    2006-12-01

    This paper presents views on the future of optical networking. A historical look at the emergence of optical networking is first taken, followed by a discussion on the drivers pushing for a new and pervasive network, which is based on photonics and can satisfy the needs of a broadening base of residential, business, and scientific users. Regional plans and targets for optical networking are reviewed to understand which current approaches are judged important. Today, two thrusts are driving separate optical network infrastructure models, namely 1) the need by nations to provide a ubiquitous network infrastructure to support all the future services and telecommunication needs of residential and business users and 2) increasing demands by the scientific community for networks to support their requirements with respect to large-scale data transport and processing. This paper discusses these network models together with the key enabling technologies currently being considered for future implementation, including optical circuit, burst and packet switching, and optical code-division multiplexing. Critical subsystem functionalities are also reviewed. The discussion considers how these separate models might eventually merge to form a global optical network infrastructure.

  10. Entangled networks, synchronization, and optimal network topology.

    PubMed

    Donetti, Luca; Hurtado, Pablo I; Muñoz, Miguel A

    2005-10-28

    A new family of graphs, entangled networks, with optimal properties in many respects, is introduced. By definition, their topology is such that it optimizes synchronizability for many dynamical processes. These networks are shown to have an extremely homogeneous structure: degree, node distance, betweenness, and loop distributions are all very narrow. Also, they are characterized by a very interwoven (entangled) structure with short average distances, large loops, and no well-defined community structure. This family of nets exhibits an excellent performance with respect to other flow properties such as robustness against errors and attacks, minimal first-passage time of random walks, efficient communication, etc. These remarkable features convert entangled networks in a useful concept, optimal or almost optimal in many senses, and with plenty of potential applications in computer science or neuroscience.

  11. The Benefits of Grid Networks

    ERIC Educational Resources Information Center

    Tennant, Roy

    2005-01-01

    In the article, the author talks about the benefits of grid networks. In speaking of grid networks the author is referring to both networks of computers and networks of humans connected together in a grid topology. Examples are provided of how grid networks are beneficial today and the ways in which they have been used.

  12. Local Area Networks: Part II.

    ERIC Educational Resources Information Center

    Dessy, Raymond E., Ed.

    1982-01-01

    Discusses five approaches used by industry/colleges to provide local area network (LAN) capabilities in the analytical laboratory: (1) mixed baseband bus network coupled to a star net; (2) broadband bus network; (3) ring network; (4) star network coupled to broadband net; and (5) simple multiprocessor center. Part I (September issue) focused on…

  13. An approach for modeling vulnerability of the network of networks

    NASA Astrophysics Data System (ADS)

    Zhang, Jianhua; Song, Bo; Zhang, Zhaojun; Liu, Haikuan

    2014-10-01

    In this paper, a framework is given to model the network of networks and to investigate the vulnerability of the network of networks subjected to failures. Because there are several redundant systems in infrastructure systems, the dependent intensity between two networks is introduced and adopted to discuss the vulnerability of the interdependent infrastructure networks subjected to failures. Shanghai electrified rail transit network is used to illustrate the feasibility and effectiveness of the proposed framework. Because the rail network is dependent on the power grid and communication network, the corresponding power grid and communication network are also included in this system. Meanwhile the failures to the power grid and communication network are utilized to investigate the vulnerability of the rail network. The results show that the rail network strongly depends on the power grid and weakly depends on the communication network, and the transport functionality loss of the rail network increases with the increase of dependent intensity. Meanwhile the highest betweenness node-based attack to the power grid and the largest degree node-based attack to the communication network can result in the most functionality losses to the rail network. Moreover, the functionality loss of the rail network has the smallest value when the tolerance parameter of the power grid equals 0.75 and the critical nodes of the power grid and communication network can be obtained by simulations.

  14. Cascading Failures and Recovery in Networks of Networks

    NASA Astrophysics Data System (ADS)

    Havlin, Shlomo

    Network science have been focused on the properties of a single isolated network that does not interact or depends on other networks. In reality, many real-networks, such as power grids, transportation and communication infrastructures interact and depend on other networks. I will present a framework for studying the vulnerability and the recovery of networks of interdependent networks. In interdependent networks, when nodes in one network fail, they cause dependent nodes in other networks to also fail. This is also the case when some nodes like certain locations play a role in two networks -multiplex. This may happen recursively and can lead to a cascade of failures and to a sudden fragmentation of the system. I will present analytical solutions for the critical threshold and the giant component of a network of n interdependent networks. I will show, that the general theory has many novel features that are not present in the classical network theory. When recovery of components is possible global spontaneous recovery of the networks and hysteresis phenomena occur and the theory suggests an optimal repairing strategy of system of systems. I will also show that interdependent networks embedded in space are significantly more vulnerable compared to non embedded networks. In particular, small localized attacks may lead to cascading failures and catastrophic consequences.Thus, analyzing data of real network of networks is highly required to understand the system vulnerability. DTRA, ONR, Israel Science Foundation.

  15. Better sales networks.

    PubMed

    Ustüner, Tuba; Godes, David

    2006-01-01

    Anyone in sales will tell you that social networks are critical. The more contacts you have, the more leads you'll generate, and, ultimately, the more sales you'll make. But that's a vast oversimplification. Different configurations of networks produce different results, and the salesperson who develops a nuanced understanding of social networks will outshine competitors. The salesperson's job changes over the course of the selling process. Different abilities are required in each stage of the sale: identifying prospects, gaining buy-in from potential customers, creating solutions, and closing the deal. Success in the first stage, for instance, depends on the salesperson acquiring precise and timely information about opportunities from contacts in the marketplace. Closing the deal requires the salesperson to mobilize contacts from prior sales to act as references. Managers often view sales networks only in terms of direct contacts. But someone who knows lots of people doesn't necessarily have an effective network because networks often pay off most handsomely through indirect contacts. Moreover, the density of the connections in a network is important. Do a salesperson's contacts know all the same people, or are their associates widely dispersed? Sparse networks are better, for example, at generating unique information. Managers can use three levers--sales force structure, compensation, and skills development--to encourage salespeople to adopt a network-based view and make the best possible use of social webs. For example, the sales force can be restructured to decouple lead generation from other tasks because some people are very good at building diverse ties but not so good at maintaining other kinds of networks. Companies that take steps of this kind to help their sales teams build better networks will reap tremendous advantages.

  16. Identification of Topological Network Modules in Perturbed Protein Interaction Networks

    PubMed Central

    Sardiu, Mihaela E.; Gilmore, Joshua M.; Groppe, Brad; Florens, Laurence; Washburn, Michael P.

    2017-01-01

    Biological networks consist of functional modules, however detecting and characterizing such modules in networks remains challenging. Perturbing networks is one strategy for identifying modules. Here we used an advanced mathematical approach named topological data analysis (TDA) to interrogate two perturbed networks. In one, we disrupted the S. cerevisiae INO80 protein interaction network by isolating complexes after protein complex components were deleted from the genome. In the second, we reanalyzed previously published data demonstrating the disruption of the human Sin3 network with a histone deacetylase inhibitor. Here we show that disrupted networks contained topological network modules (TNMs) with shared properties that mapped onto distinct locations in networks. We define TMNs as proteins that occupy close network positions depending on their coordinates in a topological space. TNMs provide new insight into networks by capturing proteins from different categories including proteins within a complex, proteins with shared biological functions, and proteins disrupted across networks. PMID:28272416

  17. Identification of Topological Network Modules in Perturbed Protein Interaction Networks.

    PubMed

    Sardiu, Mihaela E; Gilmore, Joshua M; Groppe, Brad; Florens, Laurence; Washburn, Michael P

    2017-03-08

    Biological networks consist of functional modules, however detecting and characterizing such modules in networks remains challenging. Perturbing networks is one strategy for identifying modules. Here we used an advanced mathematical approach named topological data analysis (TDA) to interrogate two perturbed networks. In one, we disrupted the S. cerevisiae INO80 protein interaction network by isolating complexes after protein complex components were deleted from the genome. In the second, we reanalyzed previously published data demonstrating the disruption of the human Sin3 network with a histone deacetylase inhibitor. Here we show that disrupted networks contained topological network modules (TNMs) with shared properties that mapped onto distinct locations in networks. We define TMNs as proteins that occupy close network positions depending on their coordinates in a topological space. TNMs provide new insight into networks by capturing proteins from different categories including proteins within a complex, proteins with shared biological functions, and proteins disrupted across networks.

  18. Programming neural networks

    SciTech Connect

    Anderson, J.A.; Markman, A.B.; Viscuso, S.R.; Wisniewski, E.J.

    1988-09-01

    Neural networks ''compute'' though not in the way that traditional computers do. One must accept their weaknesses to use their strengths. The authors present several applications of a particular non-linear network (the BSB model) to illustrate some of the peculiarities inherent in this architecture.

  19. Network Difficulties: Stand By.

    ERIC Educational Resources Information Center

    Oborn, Richard L.

    This document traces the development of Federal Communications Commission (FCC) network regulations from their beginning in 1941 with the "Report on Chain Broadcasting." The eight rules defined by the report were aimed at correcting network abuses and were intended to maintain community broadcasting in the public interest. The document…

  20. Telecommunications network optimization

    NASA Technical Reports Server (NTRS)

    Lee, J.

    1979-01-01

    Analysis discusses STACOM (state criminal justic communication) network topology program used to design and evaluate digital telecommunications networks STACOM employs ESAU-WILLIAMS technique to search for direct links between system terminations and regional switching center. Inputs include traffic data, terminal locations, and functional requirements.