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Sample records for ath5 neurogenic network

  1. Uncoupling neurogenic gene networks in the Drosophila embryo.

    PubMed

    Rogers, William A; Goyal, Yogesh; Yamaya, Kei; Shvartsman, Stanislav Y; Levine, Michael S

    2017-04-01

    The EGF signaling pathway specifies neuronal identities in the Drosophila embryo by regulating developmental patterning genes such as intermediate neuroblasts defective (ind). EGFR is activated in the ventral midline and neurogenic ectoderm by the Spitz ligand, which is processed by the Rhomboid protease. CRISPR/Cas9 was used to delete defined rhomboid enhancers mediating expression at each site of Spitz processing. Surprisingly, the neurogenic ectoderm, not the ventral midline, was found to be the dominant source of EGF patterning activity. We suggest that Drosophila is undergoing an evolutionary transition in central nervous system (CNS)-organizing activity from the ventral midline to the neurogenic ectoderm. © 2017 Rogers et al.; Published by Cold Spring Harbor Laboratory Press.

  2. 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

  3. Essential role of BAF complex interacting with Pax6 in establishment of a core cross-regulatory neurogenic network

    PubMed Central

    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

    2014-01-01

    The molecular mechanisms of neurogenic fate determination are of particular importance in light of the need to regenerate neurons. Here we define the mechanisms of installing neurogenic fate by the transcription factor Pax6 acting together with the Brg1-containing BAF chromatin remodeling complex. We show that Pax6 physically interacts with Brg1-containing BAF complex and genetic deletion of either Pax6 or Brg1, in the neural stem cells in the adult mouse subependymal zone results in a strikingly similar fate conversion from neuronal progenitors to glia. The Pax6-BAF complex drives neurogenesis by directly activating transcription factors Sox11, Nfib and Pou3f4, which form a cross-regulatory network that maintains neurogenic fate downstream of the Pax6-BAF complex in neuroblasts. Our work identifies a novel concept of stratification in neural fate commitment with a strikingly specific role of the Pax6-BAF complex in initiating a cross-regulatory network essential for maintenance of the neurogenic lineage in the adult brain. PMID:23933087

  4. 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

  5. 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.

  6. [Neurogenic Dysphagia].

    PubMed

    Prosiegel, M

    2007-10-01

    Neurogenic dysphagia occurs in many diseases, the most frequent cause being stroke. Diagnostic approaches include neurologic examination and fiberoptic and videofluoroscopic evaluations of swallowing, which are complementary. The pivotal aim of therapeutic interventions is the prevention of aspiration and aspiration pneumonia. Proof of the effectivity of some restitutional, compensatory, and adaptive methods is given.

  7. 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.

  8. 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

  9. [Holoprosencephaly with neurogenic hypernatremia].

    PubMed

    Cuisset, J M; Cuvellier, J C; Vallée, L; Ryckewäert, P; Soto-Ares, G; Nuyts, J P

    1999-01-01

    Semi-lobar holoprosencephalies can be seldom complicated by neurogenic hypernatremia, which must be distinguished from other causes of hypernatremia. In two admitted children with semi-lobar holoprosencephaly, 7 months and 4 years old, biological data revealed chronic hypernatremia and hyperosmolarity without clinical signs of dehydration, which were finally attributed to a neurogenic hypernatremia. Neurogenic hypernatremia must be clearly differentiated from other causes of hypernatremia since it never causes specific complications.

  10. Efficacy and Tolerability of Propiverine Hydrochloride in Patients With Neurogenic Detrusor Overactivity

    ClinicalTrials.gov

    2012-02-09

    Neurogenic Urinary Bladder Disorder; Urinary Bladder, Neurogenic; Bladder Disorder, Neurogenic; Urinary Bladder Disorder, Neurogenic; Neurogenic Bladder Disorder; Urinary Bladder Neurogenic Dysfunction; Urologic Diseases; Overactive Detrusor Function; Urinary Incontinence

  11. [Neurogenic senile vertebral spondylopathy].

    PubMed

    Meneghello, A

    1993-01-01

    Neurogenic spinal arthropathy is quite frequent a finding in elderly patients. Peripheral neuropathy underlies this complication. As a matter of fact, impaired proprioception and sensitivity, which are often associated with lesions of the motor nerves, prevent the joint or bone segment submitted to repeated traumas from perceiving alarm sensations, especially pain. Thus, bone lesions follow, which present as bone erosions, fractures, and even more severe bone destruction. At first, tabetic neuropathy was held responsible for this condition. Then, neurogenic arthropathy was observed in diabetes, syringomyelia, and sometimes trauma. However, in the elderly patient, other conditions can cause peripheral neuropathy, which accounts for the high incidence of this disorder. The radiologic findings of the lumbar spine of 23 of 4,922 patients examined in our department 1989 to 1991 were suggestive of neurogenic spinal arthropathy. Clinical, laboratory and electromyographic findings confirmed the presence of neuropathy. Besides the neurogenic lesions described in 7 diabetic patients, these lesions are reported for the first time in 4 cases of multiple myeloma, in a case of Waldenström's macroglobulinemia, in 2 cases of vincristine-treated lymphoma, and finally in an alcohol abuser. Analgesic abuse was observed in 2 patients. In the extant cases, the pathogenesis of neuropathy remained unknown, even though "elderly neuropathy" is known to exist and to be underlain by vascular or degenerative conditions.

  12. Neurogenic neuroprotection: clinical perspectives

    PubMed Central

    Mandel, Mauricio; Fonoff, Erich Talamoni; Bor-Seng-Shu, Edson; Teixeira, Manoel Jacobsen; Chadi, Gerson

    2012-01-01

    Summary Neurogenic neuroprotection is a promising approach for treating patients with ischemic brain lesions. In rats, stimulation of the deep brain nuclei has been shown to reduce the volume of focal infarction. In this context, protection of neural tissue can be a rapid intervention that has a relatively long-lasting effect, making fastigial nucleus stimulation (FNS) a potentially valuable method for clinical application. Although the mechanisms of neuroprotection induced by FNS remain partially unclear, important data have been presented in the last two decades. A 1-h electrical FNS reduced, by 59%, infarctions triggered by permanent occlusion of the middle cerebral artery in Fisher rats. The acute effect of electrical FNS is likely mediated by a prolonged opening of potassium channels, and the sustained effect appears to be linked to inhibition of the apoptotic cascade. A better understanding of the neuronal circuitry underlying neurogenic neuroprotection may contribute to improving neurological outcomes in ischemic brain insults. PMID:23597434

  13. Neurogenic voiding dysfunction.

    PubMed

    Georgopoulos, Petros; Apostolidis, Apostolos

    2017-05-01

    This review aims to analyze and discuss all recently published articles associated with neurogenic voiding discussion providing readers with the most updated knowledge and trigger for further research. They include the proposal of a novel classification system for the pathophysiology of neurogenic lower urinary tract dysfunction (NLUTD) which combines neurological defect in a distinct anatomic location, and data on bowel dysfunction, autonomic dysreflexia and urine biomarkers; review of patient-reported outcome measures in NLUTD; review of the criteria for the diagnosis of clinically significant urinary infections; novel research findings on the pathophysiology of NLUTD; and review of data on minimally and more invasive treatments. Despite the extended evidence base on NLUTD, there is a paucity of high-quality new research concerning voiding dysfunction as opposed to storage problems. The update aims to inform clinicians about new developments in clinical practice, as well as ignite discussion for further clinical and basic research in the aforementioned areas of NLUTD.

  14. 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.

  15. Neurogenic muscle hypertrophy.

    PubMed

    Charlot-Lambrecht, Isabelle; Brochot, Pascal; Noblet, Hervé; Varoquier, Coralie; Eschard, Jean-Paul

    2009-07-01

    We report the case of a 48-year-old man who presented with left calf hypertrophy 6 years after an episode of left S1 sciatica related to a herniated disk. Magnetic resonance imaging disclosed muscle hypertrophy. Electromyography showed left S1 radiculopathy with abnormal spontaneous muscle activity. Neurogenic muscle hypertrophy is a rare phenomenon that is chiefly seen when denervation occurs slowly and gradually. The typical patient is a middle-aged man who has a history of S1 radiculopathy. The soleus muscle is the main site of involvement. The pathophysiology is unclear but may involve type I fiber hypertrophy in response to the complex repetitive discharges recorded by electromyography. The natural history of neurogenic muscle hypertrophy is incompletely understood.

  16. 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

  17. 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

  18. 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

  19. [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.

  20. [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.

  1. Stars from the darkest night: unlocking the neurogenic potential of astrocytes in different brain regions.

    PubMed

    Magnusson, Jens P; Frisén, Jonas

    2016-04-01

    In a few regions of the adult brain, specialized astrocytes act as neural stem cells capable of sustaining life-long neurogenesis. In other, typically non-neurogenic regions, some astrocytes have an intrinsic capacity to produce neurons when provoked by particular conditions but do not use this ability to replace neurons completely after injury or disease. Why do astrocytes display regional differences and why do they not use their neurogenic capacity for brain repair to a greater extent? In this Review, we discuss the neurogenic potential of astrocytes in different brain regions and ask what stimulates this potential in some regions but not in others. We discuss the transcriptional networks and environmental cues that govern cell identity, and consider how the activation of neurogenic properties in astrocytes can be understood as the de-repression of a latent neurogenic transcriptional program. © 2016. Published by The Company of Biologists Ltd.

  2. 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.

  3. Cough responsiveness in neurogenic dysphagia.

    PubMed

    Smith, P E; Wiles, C M

    1998-03-01

    In neurogenic dysphagia a good cough is important for airway protection. If triggering of cough, or its effectiveness, is impaired this might result in an increased aspiration risk. Capsaicin, an agent which induces cough through sensory nerve stimulation, was used to test cough sensitivity in groups of patients with and without neurogenic dysphagia. On the basis of swallowing speed (ml/s) in a validated water test 28 alert neurological inpatients (16 women, aged 22-71 years) were classified into 13 with abnormal and 15 with normal swallowing (median swallowing speed 23% and 99%, median volume/swallow 43% and 106% of that predicted for age and sex respectively: p<0.001). Capsaicin nebulised on air in saline was inhaled via a low resistance valve using a mouthpiece and noseclip. Up to seven incremental concentrations of capsaicin ranging from 0.07-20.0 x 10(-4) mol/l were each inhaled for up to a minute. A pneumotachograph connected to the expiratory limb gave a paper recording of expiratory air flow. Coughs were recorded as high flow expirations of short duration. Capsaicin concentrations at first cough (threshold) were recorded; concentrations at frequencies of 10 and 20 coughs/minute were interpolated from the dose-response curve. Cough threshold tended to be lower in those with abnormal swallowing (non-significant): the (log) concentration of capsaicin producing 10 or 20 coughs/ minute also tended to be lower (p=0.12 and 0.07 respectively) in those with abnormal swallowing. Contrary to expectation, these results suggest that cough responsiveness is enhanced in alert patients with neurogenic dysphagia even after allowing for diagnostic category, the possible presence of a bulbar upper motor neuron lesion, or voluntary respiratory capacity. It is concluded that these patients with neurogenic dysphagia do not have a reduced sensitivity of cough triggering.

  4. Electrodiagnostic methods for neurogenic dysphagia.

    PubMed

    Ertekin, C; Aydogdu, I; Yüceyar, N; Tarlaci, S; Kiylioglu, N; Pehlivan, M; Celebi, G

    1998-08-01

    Swallowing mechanisms and neurogenic dysphagia have not been systematically studied by the EMG technique. It is desirable to evaluate neurogenic dysphagia for diagnostic and possibly for therapeutic purposes using electrophysiological methods. The following methods were described: mechanical upward/downward movements of the larynx were detected using a piezoelectric sensor, while submental integrated EMG activity was recorded during dry and wet swallowing. The EMG activity of cricopharyngeal muscle of the upper oesophageal sphincter was also recorded in some normal subjects and patients. Piecemeal deglutition and the dysphagia limit were determined in all patients to detect dysphagia objectively. In this study 75 normal subjects and 177 neurological patients with various degrees of dysphagia were investigated. Voluntarily triggered oropharyngeal swallowing was commonly pathological in the majority of patients, with or without overt dysphagia. The dysphagia limit appeared to be an objective measure of the degree of dysphagia in more than 90% of patients. Pathophysiological mechanisms were different in at least three groups of patients with neurogenic dysphagia. In the group of patients with muscular disorders, laryngeal elevators were involved while the CP-sphincter was intact. The second group included patients with the clinical signs of corticobulbar fibre involvement such as amyotrophic lateral sclerosis and pseudobulbar palsy. In these patients, there was incoordination between paretic laryngeal elevators and hyperreflexic CP-sphincter. In the third group (patients with Parkinson's disease), the swallowing reflex was delayed and prolonged. EMG methods described in the present study are very useful for the diagnosis of neurogenic dysphagia, objectively and quickly. They are important to understand the physiological mechanisms for deglutition and its disorders.

  5. Patient reported outcome measures in neurogenic bladder

    PubMed Central

    Clark, Roderick

    2016-01-01

    Many interventions for neurogenic bladder patients are directed towards improving quality of life (QOL). Patient reported outcome measures (PROMs) are the primary method of evaluating QOL, and they provide an important quantification of symptoms which can’t be measured objectively. Our goal was to review general measurement principles, and identify and discuss PROMs relevant to neurogenic bladder patients. We identify two recent reviews of the state of the literature and updated the results with an additional Medline search up to September 1, 2015. Using the previous identified reviews, and our updated literature review, we identified 16 PROMs which are used for the assessment of QOL and symptoms in neurogenic bladder patients. Several are specifically designed for neurogenic bladder patients, such as the Qualiveen (for neurogenic bladder related QOL), and the Neurogenic Bladder Symptom Score (NBSS) (for neurogenic bladder symptoms). We also highlight general QOL measures for patients with multiple sclerosis (MS) and spinal cord injury (SCI) which include questions about bladder symptoms, and incontinence PROMs which are commonly used, but not specifically designed for neurogenic bladder patients. It is essential for clinicians and researchers with an interest in neurogenic bladder to be aware of the current PROMs, and to have a basic understanding of the principals of measurement in order to select the most appropriate one for their purpose. PMID:26904409

  6. 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

  7. [Videofluoroscopy study of swallowing in neurogenic dysphagia].

    PubMed

    Avdiunina, I A; Popova, L M; Dokuchaeva, N V; Bragina, L K; Dokuchaeva, N F

    2000-01-01

    Videofluoroscopy (VFS) was for the first time used for examining swallowing in 49 patients with nervous diseases. Disturbances in each phase of swallowing act are analyzed with evaluation of the time parameters and defects, causes of aspiration in neurogenic dysphagia are discussed, and cricopharyngeal insufficiency is described. Neurogenic dysphagia is characterized by a combination of disorders which determine the degree of dysphagia. The most severe swallowing disorders were observed in patients with multiple foci in the brain stem and in diphtheritic polyneuropathies. The authors conclude that VFS is the optimal method for the diagnosis of neurogenic dysphagia.

  8. Treatment of neurogenic diabetes insipidus.

    PubMed

    Chanson, Philippe; Salenave, Sylvie

    2011-12-01

    Central or neurogenic diabetes insipidus results from a deficiency in antidiuretic hormone (ADH) or arginine-vasopressin (AVP). Treatment is based on replacement therapy with the hormone analog desmopressin (d-DAVP). d-DAVP can be administered subcutaneously to infants or patients with postoperative or posttraumatic brain injury being monitored for transient diabetes insipidus. Intranasal and oral forms are also available. The recently introduced lyophilisate, which melts under the tongue, has replaced the tablet form (recently withdrawn from the market in France) and provides better bioavailability. Irrespective of the mode of administration, it is usually the patient who finds the effective minimal dose necessary for a normal life, i.e. without excessive polyuria, particularly at night. Patient education is necessary to avoid the risk of water intoxication and hyponatremia. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  9. 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

  10. [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.

  11. The neurogenic bladder: medical treatment

    PubMed Central

    Buyse, Gunnar M.

    2007-01-01

    Neurogenic bladder sphincter dysfunction (NBSD) can cause severe and irreversible renal damage and bladder-wall destruction years before incontinence becomes an issue. Therefore, the first step in adequate management is to recognize early the bladder at risk for upper- and lower-tract deterioration and to start adequate medical treatment proactively. Clean intermittent catheterization combined with anticholinergics (oral or intravesical) is the standard therapy for NBSD. Early institution of such treatment can prevent both renal damage and secondary bladder-wall changes, thereby potentially improving long-term outcomes. In children with severe side effects or with insufficient suppression of detrusor overactivity despite maximal dosage of oral oxybutynin, intravesical instillation is an effective alternative. Intravesical instillation eliminates systemic side effects by reducing the first-pass metabolism and, compared with oral oxybutynin, intravesical oxybutynin is a more potent and long-acting detrusor suppressor. There is growing evidence that with early adequate treatment, kidneys are saved and normal bladder growth can be achieved in children so they will no longer need surgical bladder augmentation to achieve safe urinary continence in adolescence and adulthood. PMID:18095004

  12. 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

  13. Oropharyngeal Dysphagia: neurogenic etiology and manifestation.

    PubMed

    Sebastian, Swapna; Nair, Prem G; Thomas, Philip; Tyagi, Amit Kumar

    2015-03-01

    To determine the type, severity and manifestation of dysphagia in patients with neurogenic etiology. Clinical documentation was done on the different etiologies, its manifestation, assessment findings and management strategies taken for patients with neurogenic oropharyngeal dysphagia who were referred for assessment and management of dysphagia over a period of three months in a tertiary care teaching hospital. Flexible endoscopic examination was done in all the patients. The severity of dysphagia in these patients were graded based on Gugging Swallowing Screen (GUSS). A total of 53 patients with neurogenic oropharyngeal dysphagia were evaluated by an otolaryngologist and a speech language pathologist over a period of three months. The grading of severity based on GUSS for these patients were done. There were 30 patients with recurrent laryngeal nerve injury due to various etiologies, one patient with Neurofibroma-vestibular schwanoma who underwent surgical excision, 16 patients with stroke, two patients with traumatic brain injury, two patients with Parkinsonism and two patients with myasthenia gravis. The manifestation of dysphagia was mainly in the form of prolonged masticatory time, oral transit time, and increased number of swallows required for each bolus, cricopharyngeal spasms and aspiration. Among the dysphagia patients with neurogenic etiology, dysphagia is manifested with a gradual onset and is found to have a progressive course in degenerative disorders. Morbidity and mortality may be reduced with early identification and management of neurogenic dysphagia.

  14. Multiple sclerosis and the neurogenic bladder.

    PubMed

    Rashid, T M; Hollander, J B

    1998-08-01

    Most patients with progressive MS will develop voiding dysfunction. In order to properly manage these patients, it is imperative to have a basic understanding of normal and abnormal bladder function. Based on history, physical examination, urinalysis, and renal function, diagnostic evaluation can be tailored to the individual. Empiric therapy without urologic consultation may be appropriate in some patients. In others, referral for full urodynamic evaluation will be necessary to best manage neurogenic voiding dysfunctions. Although there are many treatment options for patients with neurogenic bladders, it is imperative that therapy remain conservative and initially reversible because symptoms from MS tend to wax and wane over time. Long-term follow-up for patients with MS and neurogenic bladders is required to preserve renal function and avoid infections. A urologic program should be designed to promote continent, low-pressure bladder storage and controlled emptying while minimizing symptoms in a manner that promotes improved quality of life and self-esteem.

  15. 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

  16. 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. © 2016. Published by The Company of Biologists Ltd.

  17. 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…

  18. 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…

  19. 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.

  20. Neurogenic sarcomas of the neck in neurofibromatosis.

    PubMed

    Martin, G; Kleinsasser, O

    1981-01-01

    Based on two observations and a review of the literature, the pathological and clinical findings in sarcomas of the neck in patients with neurofibromatosis are described. Histologically these neurogenic tumours show a manifold picture; in addition to spindle-cell sarcomas pleomorphic structures are to be found, which can be similar to rhabdomyo-, lipo-, chondro-, angio-, or osteogenic sarcomas so that a histological diagnosis of a neurogenic sarcoma cannot always be made without clinical details. Up to the present surgical treatment is preferred; the value of cytostatic therapy and irradiation is controversial. The results of treating these tumours are unsatisfactory. Of 29 cases reported in the literature, only two could be found in which the patient survived without a recurrence for more than five years.

  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 Inflammation – The Peripheral Nervous System’s Role in Host Defense and Immunopathology

    PubMed Central

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

    2012-01-01

    The peripheral nervous and immune systems are traditionally thought of as serving separate functions. This line 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 for rapid local and systemic neurogenic modulation of immunity. Peripheral neurons also appear to play a significant role in 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. PMID:22837035

  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. Neurogenic plasma leakage in mouse airways

    PubMed Central

    Baluk, Peter; Thurston, Gavin; Murphy, Thomas J; Bunnett, Nigel W; McDonald, Donald M

    1999-01-01

    This study sought to determine whether neurogenic inflammation occurs in the airways by examining the effects of capsaicin or substance P on microvascular plasma leakage in the trachea and lungs of male pathogen-free C57BL/6 mice. Single bolus intravenous injections of capsaicin (0.5 and 1 μmol kg−1, i.v.) or substance P (1, 10 and 37 nmol kg−1, i.v.) failed to induce significant leakage in the trachea, assessed as extravasation of Evans blue dye, but did induce leakage in the urinary bladder and skin. Pretreatment with captopril (2.5 mg kg−1, i.v.), a selective inhibitor of angiotensin converting enzyme (ACE), either alone or in combination with phosphoramidon (2.5 mg kg−1, i.v.), a selective inhibitor of neutral endopeptidase (NEP), increased baseline leakage of Evans blue in the absence of any exogenous inflammatory mediator. The increase was reversed by the bradykinin B2 receptor antagonist Hoe 140 (0.1 mg kg−1, i.v.). After pretreatment with phosphoramidon and captopril, capsaicin increased the Evans blue leakage above the baseline in the trachea, but not in the lung. This increase was reversed by the tachykinin (NK1) receptor antagonist SR 140333 (0.7 mg kg−1, i.v.), but not by the NK2 receptor antagonist SR 48968 (1 mg kg−1, i.v.). Experiments using Monastral blue pigment as a tracer localized the leakage to postcapillary venules in the trachea and intrapulmonary bronchi, although the labelled vessels were less numerous in mice than in comparably treated rats. Blood vessels of the pulmonary circulation were not labelled. We conclude that neurogenic inflammation can occur in airways of pathogen-free mice, but only after the inhibition of enzymes that normally degrade inflammatory peptides. Neurogenic inflammation does not involve the pulmonary microvasculature. PMID:10077247

  6. [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.

  7. Urinary Tract Infection and Neurogenic Bladder.

    PubMed

    McKibben, Maxim J; Seed, Patrick; Ross, Sherry S; Borawski, Kristy M

    2015-11-01

    Urinary tract infections (UTIs) are frequent, recurrent, and lifelong for patients with neurogenic bladder and present challenges in diagnosis and treatment. Patients often present without classic symptoms of UTI but with abdominal or back pain, increased spasticity, and urinary incontinence. Failure to recognize and treat infections can quickly lead to life-threatening autonomic dysreflexia or sepsis, whereas overtreatment contributes to antibiotic resistance, thus limiting future treatment options. Multiple prevention methods are used but evidence-based practices are few. Prevention and treatment of symptomatic UTI requires a multimodal approach that focuses on bladder management as well as accurate diagnosis and appropriate antibiotic treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. 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.

  9. 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

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

    PubMed Central

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

    2016-01-01

    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. PMID:17234174

  11. 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.

  12. Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility.

    PubMed

    Neuberger, Eric J; Swietek, Bogumila; Corrubia, Lucas; Prasanna, Anagha; Santhakumar, Vijayalakshmi

    2017-09-12

    Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. 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.

  14. Management of oropharyngeal neurogenic dysphagia in adults.

    PubMed

    Miles, Anna; Allen, Jacqui E

    2015-12-01

    This article reviews recent literature in the management of neurogenic oropharyngeal dysphagia (OPD) including assessment processes and treatments, with a specific focus on OPD as a result of stroke and Parkinson's disease. A large number of high-quality systematic reviews were published that provide an excellent summary of current evidence across assessment and treatment of swallowing disorders. There is building interest and knowledge in technology in both the understanding and treatment of OPD including functional MRI, manometry, and noninvasive brain stimulation. Neurologic disorders demonstrate a high prevalence of OPD resulting in significant decrement to health and healthcare costs. Novel technologies were reported in assessment and tracking of dysphagia as well as emerging innovative therapeutic options.

  15. 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

  16. 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.

  17. 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.

  18. Pyridostigmine treatment trial in neurogenic orthostatic hypotension.

    PubMed

    Singer, Wolfgang; Sandroni, Paola; Opfer-Gehrking, Tonette L; Suarez, Guillermo A; Klein, Caroline M; Hines, Stacy; O'Brien, Peter C; Slezak, Jeffrey; Low, Phillip A

    2006-04-01

    Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension. By enhancing ganglionic transmission, pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension. To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide, alone or in combination with a subthreshold (2.5 mg) or suprathreshold (5 mg) dose of midodrine hydrochloride, compared with placebo. We report a double-blind, randomized, 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH. A total of 58 patients with neurogenic OH were enrolled. After 1 day of baseline measurements, patients were given 4 treatments (3 active treatments [60 mg of pyridostigmine bromide; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride] and a placebo) in random order on successive days. Blood pressure (BP) and heart rate were measured, both supine and standing, immediately before treatment and hourly for 6 hours after the treatment was given. No significant differences were seen in the supine BP, either systolic (P = .36) or diastolic (P = .85). In contrast, the primary end point of the fall in standing diastolic BP was significantly reduced (P = .02) with treatment. Pairwise comparison showed significant reduction by pyridostigmine alone (BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo; P = .04) and pyridostigmine and 5 mg of midodrine hydrochloride (BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo; P = .002). Standing BP improvement significantly regressed with improvement in OH symptoms. Pyridostigmine significantly improves standing BP in patients with OH without worsening supine hypertension. The greatest effect is on diastolic BP, suggesting that the improvement is due to increased total peripheral resistance.

  19. Arthrogryposis Multiplex Congenita: Neurogenic Type with Autosomal Recessive Inheritance

    PubMed Central

    Rosenmann, A.; Arad, I.

    1974-01-01

    An infant affected by severe arthrogryposis multiplex congenita leading to death in infancy due to neurogenic atrophy is described. Six other sibs were similarly affected. An autosomal recessive mode of inheritance is suggested. Images PMID:4837288

  20. 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.

  1. 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.

  2. [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.

  3. [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

  4. Investigation into neurogenic bladder in arthrogryposis multiplex congenita.

    PubMed

    Arantes de Araújo, Liubiana; Ferraz de Arruda Musegante, André; de Oliveira Damasceno, Edjane; Barroso, Ubirajara; Badaro, Roberto

    2013-12-01

    During the follow-up of children who had been diagnosed with arthrogryposis multiplex congenita (AMC), it was noted that some were experiencing dysfunctional voiding. Further investigation into these cases led to a diagnosis of neurogenic bladder. Few studies have investigated the relationship between AMC and neurogenic bladder, this being the first to describe the clinical characteristics of neurogenic bladder among these patients. A series of 26 cases were obtained from the electronic medical records of patients with AMC who were admitted to Hospital Sarah in Salvador between 1994 and 2007. The patients had all been diagnosed with neurogenic bladder through clinical symptoms, lower urinary tract exams, and urodynamic findings. There was urinary incontinence in 21 patients (81%), and 50% had a history of urinary tract infections. Renal function was altered in 4 patients (15%) and normal in 22 (85%). In the urodynamic study, 14 patients (64%) had detrusor overactivity and 6 (27%) had underactivity. Patients with AMC may show changes in the urinary tract, including neurogenic bladder. It is mandatory to study these symptomatic children with urinary disorders. Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  5. 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)

  6. Treatment of Neurogenic Cough with Tramadol: A Pilot Study.

    PubMed

    Dion, Gregory R; Teng, Stephanie E; Achlatis, Efstratios; Fang, Yixin; Amin, Milan R

    2017-07-01

    This study employs validated cough assessment tools to prospectively determine the impact of tramadol on cough severity and quality of life in subjects with neurogenic cough. The study was a prospective case series with planned data collection at a tertiary care academic medical center laryngology practice. Sixteen consecutive collected subjects with neurogenic cough prospectively completed pre- and posttreatment validated cough assessment tools, the cough severity index (CSI) and Leicester Cough Questionnaire (LCQ). All subjects in the study reported at least some improvement in their cough symptoms. In a Wilcoxon signed rank test that compared paired results, CSI scores improved from 23 to 14 and LCQ scores improved from 74 to 103 ( P = .003 and P = .005, respectively). This small preliminary assessment suggests that tramadol warrants additional evaluation as a treatment for neurogenic cough.

  7. A practical guide to the treatment of neurogenic orthostatic hypotension.

    PubMed

    Berger, Michael J; Kimpinski, Kurt

    2014-03-01

    Neurogenic orthostatic hypotension (NOH) is a debilitating condition associated with many central and peripheral neurological disorders. It has a complex pathophysiology and variable clinical presentation, which makes diagnosis and treatment difficult. Neurogenic orthostatic hypotension is often confused with other disorders of orthostatic intolerance, hypovolemic states and systemic conditions. Diagnosis is usually made by an autonomic specialist following characteristic responses to head-up tilt. Symptom control can be achieved through a combination of patient education, nonpharmacologic and pharmacologic therapy. The purpose of this review is to provide the clinician with a practical approach to the diagnosis and management of NOH.

  8. 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 ...

  9. 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.

  10. 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.

  11. 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 ...

  12. 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

  13. [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. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. 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

  15. 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

  16. [Neurogenic communication disorders: how effective are relaxation therapy and acupuncture?].

    PubMed

    Ptok, M

    2008-12-01

    Not only neurologists but also ENT-physicians and phoniatricians have to prescribe speech and language therapy for patients with communication disorders. Complementary and alternative medicine (CAM) has gained increasing popularity among patients. Many studies have investigated these procedures and positive effects on certain physical e. g., chronic pain and anxiety disorders could be validated. Unfortunately only few empirical investigations have targeted the use of CAM to treat neurogenic disorders of communication or cognition. In this review we provide an overview over general therapeutical principals of two widely used approaches, relaxation therapy and acupuncture. Then we survey the literature and summarize existent research literature regarding the effects of the treatment of neurogenic disorders including dementia.

  17. 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

  18. 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.

  19. Preemptive analgesia: the prevention of neurogenous orofacial pain.

    PubMed Central

    Foreman, P. A.

    1995-01-01

    Chronic neurogenous pain is often an extremely difficult condition to manage. In the orofacial region, trauma from injury or dental procedures may lead to the development of severe neuralgic pains and major distress to the patient. Clinical and experimental evidence suggests that the use of adequate preemptive regional anesthesia, systemic analgesia, and the avoidance of repeated, painful stimuli may reduce the incidence of this problem. PMID:8934952

  20. Primary intrapulmonary neurogenic sarcoma with hypertrophic pulmonary osteoarthropathy and asbestosis

    PubMed Central

    Caves, P. K.; Jacques, J.

    1971-01-01

    A case of primary intrapulmonary neurogenic sarcoma with hypertrophic pulmonary osteoarthropathy and asbestosis is described. The essential histological features of this rare tumour are detailed, and the five authentic cases previously reported are reviewed. The pathogenesis of hypertrophic pulmonary osteoarthropathy and its occurrence in this case are discussed. After surgical removal of the tumour recurrence appeared in the chest within six months. It responded poorly to radiotherapy, and death from metastases occurred 16 months after operation. Images PMID:5576539

  1. 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

  2. Medical management of neurogenic bladder with oral therapy.

    PubMed

    Cameron, Anne P

    2016-02-01

    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.

  3. The pre-vertebrate origins of neurogenic placodes.

    PubMed

    Abitua, Philip Barron; Gainous, T Blair; Kaczmarczyk, Angela N; Winchell, Christopher J; Hudson, Clare; Kamata, Kaori; Nakagawa, Masashi; Tsuda, Motoyuki; Kusakabe, Takehiro G; Levine, Michael

    2015-08-27

    The sudden appearance of the neural crest and neurogenic placodes in early branching vertebrates has puzzled biologists for over a century. These embryonic tissues contribute to the development of the cranium and associated sensory organs, which were crucial for the evolution of the vertebrate "new head". A previous study suggests that rudimentary neural crest cells existed in ancestral chordates. However, the evolutionary origins of neurogenic placodes have remained obscure owing to a paucity of embryonic data from tunicates, the closest living relatives to those early vertebrates. Here we show that the tunicate Ciona intestinalis exhibits a proto-placodal ectoderm (PPE) that requires inhibition of bone morphogenetic protein (BMP) and expresses the key regulatory determinant Six1/2 and its co-factor Eya, a developmental process conserved across vertebrates. The Ciona PPE is shown to produce ciliated neurons that express genes for gonadotropin-releasing hormone (GnRH), a G-protein-coupled receptor for relaxin-3 (RXFP3) and a functional cyclic nucleotide-gated channel (CNGA), which suggests dual chemosensory and neurosecretory activities. These observations provide evidence that Ciona has a neurogenic proto-placode, which forms neurons that appear to be related to those derived from the olfactory placode and hypothalamic neurons of vertebrates. We discuss the possibility that the PPE-derived GnRH neurons of Ciona resemble an ancestral cell type, a progenitor to the complex neuronal circuit that integrates sensory information and neuroendocrine functions in vertebrates.

  4. 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.

  5. [Alterations in blood circulation of vesicourethral segment in men with neurogenic and non-neurogenic lower urinary tract symptoms].

    PubMed

    Alayev, Yu G; Esilevskiy, Yu M; Shmidt, T E; Demidko, Yu L; Fiev, D N; Kazantsev, K Yu

    2016-12-01

    To specify the pathogenetic link between blood supply of the bladder neck and lower urinary tract symptoms (LUTS). The study involved 78 men aged 26 to 50 years, including 19 patients with multiple sclerosis (MS) and LUTS, 29 patients with chronic prostatitis category IIIB with LUTS and 30 patients with chronic prostatitis category IIIB without LUTS (control group). All the patients underwent Doppler ultrasonography of prostatic arteries and selective study of blood flow in the neck of the bladder. Pharmacological test using combinations of 1-blockers (1-AB) with m-anticholinergics (m-CB) and phosphodiesterase type 5 inhibitors (PDEI-5). The changes in the blood circulation of VUS were found to correlate with LUTS. The response of blood flow depended not only on the type of pharmacological agents, but also on the degree of vascular changes and neurological deficit in VUS. The findings of VUS vascular pharmacological tests with PDEI-5 and 1-AB + m-CB were comparable in chronic prostatitis with non-neurogenic LUTS and in MS with neurogenic LUTS. Vascular reaction in VUS depends on the presence of neurological deficit. The combination of (1-AB+ m-CB) increases the blood circulation of the bladder neck and prostate and reduces the LUTS. PDEI-5 reduces LUTS due to the positive effect on the blood circulation of the prostate and VUS. Circulatory abnormalities (=hypoxia) in VUS is an important pathogenetic mechanism of neurogenic and non-neurogenic LUTS and the way to compensate them using a combination of (1-AB+ m-CB) or PDEI-5. Therefore, one of the mechanisms of LUTS is associated with impaired blood flow in the bladder neck and VUS.

  6. 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

  7. 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

  8. 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

  9. Survey of spinal cord injury-induced neurogenic bladder studies using the Web of Science.

    PubMed

    Zou, Benjing; Zhang, Yongli; Li, Yucheng; Wang, Zantao; Zhang, Ping; Zhang, Xiyin; Wang, Bingdong; Long, Zhixin; Wang, Feng; Song, Guo; Wang, Yan

    2012-08-15

    To identify global trends in research on spinal cord injury-induced neurogenic bladder, through a bibliometric analysis using the Web of Science. We performed a bibliometric analysis of studies on spinal cord injury-induced neurogenic bladder using the Web of Science. Data retrieval was performed using key words "spinal cord injury", "spinal injury", "neurogenic bladder", "neuropathic bladder", "neurogenic lower urinary tract dysfunction", "neurogenic voiding dysfunction", "neurogenic urination disorder" and "neurogenic vesicourethral dysfunction". (a) published peer-reviewed articles on spinal cord injury-induced neurogenic bladder indexed in the Web of Science; (b) type of articles: original research articles and reviews; (c) year of publication: no limitation. (a) articles that required manual searching or telephone access; (b) Corrected papers and book chapters. (1) Annual publication output; (2) distribution according to journals; (3) distribution according to subject areas; (4) distribution according to country; (5) distribution according to institution; and (6) top cited publications. There were 646 research articles addressing spinal cord injury-induced neurogenic bladder in the Web of Science. Research on spinal cord injury-induced neurogenic bladder was found in the Science Citation Index-Expanded as of 1946. The United States, Ireland and Switzerland were the three major countries contributing to studies in spinal cord injury-induced neurogenic bladder in the 1970s. However, in the 1990s, the United States, the United Kingdom, the Netherlands, Germany and Japan published more papers on spinal cord injury-induced neurogenic bladder than Switzerland, and Ireland fell off the top ten countries list. In this century, the United States ranks first in spinal cord injury-induced neurogenic bladder studies, followed by France, the United Kingdom, Germany, Switzerland and Japan. Subject categories including urology, nephrology and clinical neurology, as well as

  10. Neurogenic mucosal bicarbonate secretion in guinea pig duodenum

    PubMed Central

    Fei, G; Fang, X; Wang, GD; Liu, S; Wang, XY; Xia, Y; Wood, JD

    2013-01-01

    Background and Purpose To test a hypothesis that: (i) duodenal pH and osmolarity are individually controlled at constant set points by negative feedback control centred in the enteric nervous system (ENS); (ii) the purinergic P2Y1 receptor subtype is expressed by non-cholinergic secretomotor/vasodilator neurons, which represent the final common excitatory pathway from the ENS to the bicarbonate secretory glands. Experimental Approach Ussing chamber and pH-stat methods investigated involvement of the P2Y1 receptor in neurogenic stimulation of mucosal bicarbonate (HCO3−) secretion in guinea pig duodenum. Key Results ATP increased HCO3− secretion with an EC50 of 160 nM. MRS2179, a selective P2Y1 purinergic receptor antagonist, suppressed ATP-evoked HCO3− secretion by 47% and Cl− secretion by 63%. Enteric neuronal blockade by tetrodotoxin or exposure to a selective vasoactive intestinal peptide (VIP, VPAC1) receptor antagonist suppressed ATP-evoked HCO3− secretion by 61 and 41%, respectively, and Cl- by 97 and 70% respectively. Pretreatment with the muscarinic antagonist, scopolamine did not alter ATP-evoked HCO3− or Cl− secretion. Conclusion and Implications Whereas acid directly stimulates the mucosa to release ATP and stimulate HCO3− secretion in a cytoprotective manner, neurogenically evoked HCO3− secretion accounts for feedback control of optimal luminal pH for digestion. ATP stimulates duodenal HCO3− secretion through an excitatory action at purinergic P2Y1 receptors on neurons in the submucosal division of the ENS. Stimulation of the VIPergic non-cholinergic secretomotor/vasodilator neurons, which are one of three classes of secretomotor neurons, accounts for most, if not all, of the neurogenic secretory response evoked by ATP. PMID:22994306

  11. 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

  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. 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.

  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. [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.

  16. 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.

  17. Bladder augmentation and urinary diversion for neurogenic LUTS: current indications.

    PubMed

    Sajadi, Kamran P; Goldman, Howard B

    2012-10-01

    Augmentation cystoplasty and urinary diversion are no longer commonplace in the management of patients with neurogenic bladder, but remain an important surgical treatment for those with refractory LUTS who have failed neuromodulation and onabotulinum toxin treatment or who are not candidates for those treatments. Augmentation is an option in patients who can perform intermittent catheterization and is usually performed with ileum or large intestine. Some patients benefit from continent cutaneous catherizable channels. Supravesical urinary diversion may be necessary in more severe cases. Ileovesicostomies are being supplanted by indwelling suprapubic catheters, and when catheters fail conduits may be a better option. When feasible, the diverted bladder should be excised to avoid pyocystis.

  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. 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…

  20. 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

  1. A clinician survey of speech and non-speech characteristics of neurogenic stuttering.

    PubMed

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

    2008-03-01

    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 these four etiology groups. Results suggested possible group differences, including site of lesion and influence of speech conditions on stuttering. Other characteristics, such as within-word localization of disfluencies and presence of secondary behaviors were comparable across the etiology groups. The implications of our results for the diagnosis of neurogenic stuttering will be discussed. After reading this article, the reader will be able to: (1) provide a concise overview of the main literature on neurogenic stuttering; (2) discuss the speech and non-speech characteristics of neurogenic stuttering; (3) provide an overview of current clinical practices for intervention with neurogenic stuttering patients and their perceived outcome.

  2. 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. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  3. 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

  4. 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

  5. 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

  6. [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.

  7. Analysis of carbonated thin liquids in pediatric neurogenic dysphagia.

    PubMed

    Lundine, Jennifer P; Bates, D Gregory; Bates, David G; Yin, Han

    2015-08-01

    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. This pilot study examined whether carbonated thin liquids (CARB) improved swallowing compared to non-carbonated thin liquids (NOCARB) for children with neurogenic dysphagia. 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. 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). 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.

  8. Rehabilitation of neurogenic dysphagia with percutaneous endoscopic gastrostomy.

    PubMed

    Klor, B M; Milianti, F J

    1999-01-01

    Neurogenic oropharyngeal dysphagia is common in nursing home populations, and the risk of aspiration is sufficient to indicate the need for percutaneous endoscopid gastrostomy (PEG) feedings. Although intake provided through the PEG may meet the nutritional and hydration requirements for this group of patients, the risk of complication, e.g., aspiration of reflux, skin breakdown at the site of insertion, potential for infection, digestive difficulties, higher risk of rehospitalization, pneumonia, prolonged nursing home stay, and greater morbidity than for those without PEG tubes, may compromise the gains accrued from the ease of feeding. In an attempt to reduce these complications and return individuals to per orum (PO) diets, a program was developed to treat the dysphagia. Sixteen male nursing home patients were enrolled in a treatment program based on videofluoroscopic examination. Interventions included combinations of dietary consistency modifications, compensatory techniques, and direct swallow retraining. Results indicated such an approach reintroduced successful oral feeding in all patients, improved dietary consistency, resulted in a mean weight gain of 5.1 pounds, yielded a mean albumin increase of 0.5 g/dl, and allowed PEG tubes to be removed in 10 of the 16 patients. As a result of intervention, these findings suggest significant benefits in both quality of life issues and health care savings for this neurogenically based population.

  9. Neurogenic ejaculatory disorders: focus on current and future treatments.

    PubMed

    Calabrò, Rocco S; Polimeni, Giovanni; Ciurleo, Rosella; Casella, Carmela; Bramanti, Placido

    2011-09-01

    Ejaculation is a complex and still poorly understood neurological mechanism, at both spinal and cerebral levels as it is closely associated with orgasm. Physiologically, ejaculation is defined as the expulsion of seminal fluid from the urethral meatus and consists of two phases, namely emission and expulsion. Ejaculation is mediated by a spinal control center, referred to as a spinal pattern generator that coordinates sympathetic, parasympathetic and motor (somatic) outflows, integrating the latter with the inputs from the supraspinal sites in brainstem, hypothalamus and preoptic area. Premature ejaculation (PE) is the most common sexual dysfunction among young men, and it has been considered mostly psychogenic in origin, although it can be associated to diverse urological and neurological diseases. On the contrary, retrograde ejaculation and anejaculation are predominantly related to organic causes, particularly to neurogenic ones. Since ejaculation is mostly a spinal reflex, it is comprehensible that ejaculatory disorders are more frequent in spinal cord injury than in other neurological disorders. Over the past decades, research has focused on PE, and evidence from clinical studies showed a beneficial effect of antidepressants for the treatment of men with PE. Other ejaculatory disorders, especially painful ejaculation, have been less investigated and the proper therapy is still controversial. Aim of this review is to provide a comprehensive description of both currently available treatments and most promising future therapies, including assigned patents, for the neurogenic ejaculatory disorders.

  10. 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.

  11. 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.

  12. Neurogenic claudication secondary to degenerative spondylolisthesis: is fusion always necessary?

    PubMed

    Kitchen, W J; Mohamed, Mohamed; Bhojak, Manesh; Wilby, Martin

    2016-12-01

    This study examines the efficacy and long-term safety of a midline sparing decompression for patients with degenerative spondylolisthesis (DS). We specifically looked at the rate of re-operation with a lumbar fusion. Of the patients that did require a secondary fusion procedure, we examined retrospectively any risk factors (both clinical and radiological) that could have been identified pre-operatively to predict the necessity of a primary fusion procedure. Data was collected prospectively within a single surgeon practice at our institution. All patients had a diagnosis of neurogenic claudication secondary to DS. Radiological and clinical risk factors that could have predicted the requirement of a fusion procedure were retrospectively analysed. This is a study of 70 patients (46F:24M). The median age at surgery was 68 years. All patients had a diagnosis of neurogenic claudication and were treated with a mid-line sparing decompression. Following the primary procedure, patients' VAS and ODI scores for both leg and back pain improved significantly both at short-term follow-up (mean seven months) and sustained at long-term follow-up (range 16-57 months, mean 33 months; p < 0.0001 Wilcoxon matched pair ranks). Eight (11%) patients had symptom progression and required a further fusion procedure. We found that if on the pre-operative MRI, the patient had a facet joint angle of greater than 60°, and a preserved disc height (greater than 7 mm) this would increase the likelihood of the requirement for fusion. Of the patients that required a secondary fusion procedure, 6/8 patients (75%) had sagittal facets, hyperlordosis and a preserved disc height pre-operatively. A primary decompression using a midline sparing osteotomy is an effective procedure for the treatment of neurogenic claudication caused by DS. The second message is that on inspection of the pre-operative imaging, sagittally placed facet joints, a hyperlordosis and a preserved disc height then a fusion

  13. 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.

  14. Neurogenic claudication without spinal stenosis arising as a result of lumbar epidural varices.

    PubMed

    Dabasia, H; Rahim, N; Marshall, R

    2012-09-01

    Neurogenic claudication is most frequently observed in patients with degenerative lumbar spinal stenosis. We describe a patient with lumbar epidural varices secondary to obstruction of the inferior vena cava by pathological lymph nodes presenting with this syndrome. Following a diagnosis of follicular lymphoma, successful chemotherapy led to the resolution of the varices and the symptoms of neurogenic claudication. The lumbar epidural venous plexus may have an important role in the pathogenesis of spinal stenosis. Although rare, epidural venous engorgement can induce neurogenic claudication without spinal stenosis. Further investigations should be directed at identifying an underlying cause.

  15. 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.

  16. 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.

  17. 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.

  18. Neurogenic lower urinary tract dysfunction: evaluation and management.

    PubMed

    Tudor, Katarina Ivana; Sakakibara, Ryuji; Panicker, Jalesh N

    2016-12-01

    The lower urinary tract (LUT) in health is regulated by coordinated multi-level neurological inputs which require an intact central and peripheral nervous system. Lower urinary tract dysfunction is, therefore, a common sequelae of neurological disease and the patterns of bladder storage and voiding dysfunction depend upon the level of neurological lesion. Evaluation includes history taking, bladder diary, urological examination when relevant, ultrasonography and urodynamic testing when indicated. Antimuscarinic agents are the first line treatment for patients with storage dysfunction. Alternative treatments include intradetrusor injection of onabotulinumtoxinA, which has been shown to be of benefit in patients with neurogenic detrusor overactivity (NDO), and neuromodulation. Intermittent catheterization remains the option of choice in patients with significant voiding dysfunction resulting in high post-void residual volumes.

  19. A portable device for experimental treatment of neurogenic detrusor overactivity.

    PubMed

    Fjorback, M V; Hansen, J; Dalmose, A L; Rijkhoff, N J M; Sinkjaer, T

    2003-07-01

    The objective of this study was to evaluate the effect of automatic event-driven electrical stimulation on the dorsal penile/clitoral nerve for management of neurogenic detrusor overactivity in spinal cord injured subjects. In order to reach the objectives it was necessary to design and realize a portable device for ambulatory urodynamic studies which was able to activate an electrical stimulator when the detrusor pressure exceeded a certain threshold. The developed device was repeatedly tested in a healthy subject and subsequently tested in a spinal cord injured subject. In testing the automatic event-driven system in the spinal cord injured subject, detrusor contractions were successfully inhibited until a certain bladder volume was reached and no incontinence episodes were observed prior to disabling the system. The preliminary results indicate that automatic event-driven electrical stimulation on the dorsal penile/clitoral nerve can inhibit involuntary detrusor contractions in spinal cord injured subjects and hereby restore continence and increase bladder capacity.

  20. 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

  1. 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.

  2. 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

  3. Diuresis and urinary saturation in patients with neurogenic bladder.

    PubMed

    Burr, R G; Nuseibeh, I

    1981-03-01

    The effects of variation in fluid intake, of hard or softened drinking water, and of dietary calcium restriction on urinary relative saturation with calcium phosphates and magnesium ammonium phosphate were studied in 36 patients with neruogenic bladder. The relationship between urine volume and brushite saturation was statistically significant in 25 patients. For 8, an output of at least 4 liters per day should provide effective antistone therapy. For 17, an impossibly large volume (up to 11 liters daily) would be required. In two patients brushite saturation was significantly reduced in response to substitution of softened water for hard drinking, and in another two soft water combined with dietary calcium restriction had a similar effect. Unless urinary pH can be controlled, limitation of calcium intake is of no value in the majority of patients with neurogenic bladder and calculous disease.

  4. [PROSPECTS FOR THE TREATMENT OF IDIOPATHIC AND NEUROGENIC OVERACTIVE BLADDER].

    PubMed

    Kamalov, A A; Korshunova, E S; Popov, G R; Khodyreva, L A; Dudareva, A A; Nizov, A N

    2015-01-01

    Overactive bladder (OAB) is a common problem in modern population. The main line of medical treatment of this condition is the use of M-cholinoblockers. Solifenacin has shown high selectivity for the bladder in preclinical studies. Data on the efficacy and safety of high-dose (10 mg/day) of solifenacin are insufficient. The study was aimed to the comparative evaluation of the effectiveness and safety of solifenacin at a dose of 5 and 10 mg/day. The study included 28 patients (17 women and 11 men), mean age was 41.3±6.7 years. All patients were divided into two groups. In Group 1 included 12 patients with idiopathic overactive bladder, the Group 2 (n=16) - with neurogenic overactive bladder. Depending on the effect obtained, in some patients the dose was increased to 10 mg/day 1 month after starting treatment. The duration of treatment was 12 weeks. Application of solifenacin at a dose of 5 mg in patients with overactive bladder significantly reduces the severity of symptoms. Increasing the dose was required in 3 (25%) patients with idiopathic OAB and in 10 (62.5%) - with neurogenic OAB. Patients unsatisfied by therapy with solifenacin 5 mg/ day initially had more severe symptoms of the disease - significantly more urgency frequency, incontinence episodes, and nocturia. The use of high doses of solifenacin increased the effectiveness of treatment. Statistical significance was achieved for all parameters evaluated. Against the background of increasing doses, the number ofadverse effects may increase, but within a month of therapy in most cases they are reduced.

  5. [Validity of schintigraphy in the study of neurogenic dysphagia].

    PubMed

    Galli, J; Valenza, V; D'Alatri, L; Gajate Samanes, A M; Reale, F; La Mura, F

    2000-08-01

    The purpose of the present study was to verify the validity and potential application of oropharyngealesophageal scintigraphy in the analysis of neurogenic dysphagia. Scintigraphy was used on 36 patients divided into 2 groups: Group 1 (control) comprised 17 healthy volunteers; Group 2 included 19 patients suffering from various neurological and neuromuscular pathologies (myasthenia gravis, Parkinson's disease, polymyositis, stroke, paralysis of the last cranial nerves). In group 1 scintigraphy provided normal results both for mode of swallowing and transit, and for the values of the various parameters studied. On the other hand, scintigraphy showed that in group 2 all oral, pharyngeal and esophageal phases of swallowing were altered vs the controls with a statistically significant increase in the average values for the oral transit time (OTT) (1.45 sec., p = 0.0005), pharyngeal transit time (OTT) (3.23 sec., p = 0.044), esophageal transit time (ETT) e19.87 sec., p = 0.005) as well as in the corresponding bolus retention indexes ORU (12.95%, p = 0.0003), FIR (15.05%, p = 0.0003) and ERI (28.63%, p = 0.002). Moreover, the quality and means of swallowing also proved altered while tracheobronchial aspiration was only seen in 6 of the 19 patients (maximum value: 90%, average value; 7.66%) with a marked prevalence in the stroke subgroup (4/8). In light of these results and considering the low dose of radiation (0.00043 Gy), the lack of invasiveness and excellent tolerability, scintigraphy has confirmed its clinical validity in the functional, objective and quali-quantitative study of deglutition, even in patients suffering from neurogenic dysphagia.

  6. 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.

  7. 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.

  8. Neurogenic potential of dental pulp stem cells isolated from murine incisors

    PubMed Central

    2014-01-01

    Introduction Interest in the use of dental pulp stem cells (DPSC) to enhance neurological recovery following stroke and traumatic injury is increasing following successful pre-clinical studies. A murine model of autologous neural stem cell transplantation would be useful for further pre-clinical investigation of the underlying mechanisms. However, while human-derived DPSC have been well characterised, the neurogenic potential of murine DPSC (mDPSC) has been largely neglected. In this study we demonstrate neuronal differentiation of DPSC from murine incisors in vitro. Methods mDPSC were cultured under neuroinductive conditions and assessed for neuronal and glial markers and electrophysiological functional maturation. Results mDPSC developed a neuronal morphology and high expression of neural markers nestin, ßIII-tubulin and GFAP. Neurofilament M and S100 were found in lower abundance. Differentiated cells also expressed protein markers for cholinergic, GABAergic and glutaminergic neurons, indicating a mixture of central and peripheral nervous system cell types. Intracellular electrophysiological analysis revealed the presence of voltage-gated L-type Ca2+ channels in a majority of cells with neuronal morphology. No voltage-gated Na+ or K+ currents were found and the cultures did not support spontaneous action potentials. Neuronal-like networks expressed the gap junction protein, connexin 43 but this was not associated with dye coupling between adjacent cells after injection of the low-molecular weight tracers Lucifer yellow or Neurobiotin. This indicated that the connexin proteins were not forming traditional gap junction channels. Conclusions The data presented support the differentiation of mDPSC into immature neuronal-like networks. PMID:24572146

  9. 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.

  10. 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

  11. Neurogenic pulmonary edema following Cryptococcal meningoencephalitis associated with HIV infection.

    PubMed

    Kondo, Reiichiro; Sugita, Yasuo; Arakawa, Kenji; Nakashima, Shinji; Umeno, Yumi; Todoroki, Keita; Yoshida, Tomoko; Takase, Yorihiko; Kage, Masayoshi; Oshima, Koichi; Yano, Hirohisa

    2015-08-01

    Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant central nervous system insult. Only a few cases of NPE after Cryptococcal meningitis have been reported. We report a case of NPE following Cryptococcal meningoencephalitis. A 40-year-old man with no medical history was hospitalized for disturbance of consciousness. Blood glucose level was 124 mg/dL. Non-contrast head computed tomography showed no abnormalities. Lumbar puncture revealed a pressure of over 300 mm H2 O and cerebrospinal fluid (CSF) confirmed a white blood cell count of 65/mm(3) . The CSF glucose level was 0 mg/dL. The patient was empirically started on treatment for presumptive bacterial and viral meningitis. Four days after, the patient died in a sudden severe pulmonary edema. Autopsy was performed. We found at autopsy a brain edema with small hemorrhage of the right basal ganglia, severe pulmonary edema and mild cardiomegaly. Histologically, dilated Virchow-Robin spaces, crowded with Cryptococci were observed. In the right basal ganglia, Virchow-Robin spaces were destroyed with hemorrhage and Cryptococci spread to parenchyma of the brain. No inflammatory reaction of the lung was seen. Finally, acute pulmonary edema in this case was diagnosed as NPE following Cryptococcal meningoencephalitis. After autopsy, we found that he was positive for serum antibodies to human immunodeficiency virus. © 2015 Japanese Society of Neuropathology.

  12. 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.

  13. Neurogenic factors in the impaired healing of diabetic foot ulcers.

    PubMed

    Galkowska, Hanna; Olszewski, Waldemar L; Wojewodzka, Urszula; Rosinski, Grzegorz; Karnafel, Waldemar

    2006-08-01

    We hypothesize that the reduced innervation of skin can be observed both in clinically neuropathic and non-neuropathic diabetic foot ulcers and can contribute to low inflammatory cell infiltration. Twenty patients with type 2 diabetes and active foot ulcers, without clinical evidence of peripheral sensory neuropathy (n = 12) and with sensory neuropathy (n = 8) were involved in this study. Biopsies from ulcer margin were examined immunohistochemically. Studies revealed presence of protein gene product 9.5 (PGP9.5)+ nerve endings only in reticular dermis in 3 of 12 non-neuropathic subjects, however, regenerating GAP-43+ endings were seen in dermis of almost all specimens. Lack of substance P+ nerve endings was characteristic for both groups. The reduced distribution of calcitonin gene-related peptide+ nerves in epidermis and dermis was seen mainly in neuropathic group. In neo-epidermis lack of nerve growth factor expression was observed in both groups, whereas neurotrophin 3 immunostaining was characteristic for neuropathic specimens (P < 0.03). Expression of trkA and trkC receptors did not differ significantly between groups. Low inflammatory cell infiltration and moderate presence of fibroblasts was characteristic for all studied specimens. The observed reduction of foot skin innervation and neurogenic factors expression can be correlated with low inflammatory cell accumulation and subsequently leads to the observed chronicity of diabetic foot ulcer healing process in both neuropathic and non-neuropathic patients.

  14. Immunological regulation of neurogenic niches in the adult brain

    PubMed Central

    Gonzalez-Perez, Oscar; Gutierrez-Fernandez, Fernando; Lopez-Virgen, Veronica; Collas-Aguilar, Jorge; Quinones-Hinojosa, Alfredo; Garcia-Verdugo, Jose M.

    2012-01-01

    In mammals, neurogenesis and oligodendrogenesis are germinal processes that occur in the adult brain throughout life. The subventricular (SVZ) and subgranular (SGZ) zones are the main neurogenic regions in adult brain. Therein, it resides a subpopulation of astrocytes that act as neural stem cells. Increasing evidence indicates that pro-inflammatory and other immunological mediators are important regulators of neural precursors into the SVZ and the SGZ. There are a number of inflammatory cytokines that regulate the function of neural stem cells. Some of the most studied include: interleukin-1, interleukin-6, tumor necrosis factor-alpha, insulin-like growth factor-1, growth-regulated oncogene-alpha, leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha. This plethora of immunological mediators can control the migration, proliferation, quiescence, cell-fate choices and survival of neural stem cells and their progeny. Thus, systemic or local inflammatory processes represent important regulators of germinal niches in the adult brain. In this review, we summarized the current evidence regarding the effects of pro-inflammatory cytokines involved in the regulation of adult neural stem cells under in vitro and in vivo conditions. Additionally, we described the role of proinflammatory cytokines in neurodegenerative diseases and some therapeutical approaches for the immunomodulation of neural progenitor cells. PMID:22986164

  15. Evaluation of neurogenic dysphagia in Iraqi patients with acute stroke.

    PubMed

    Hasan, Zeki N; Al-Shimmery, Ehsan K; Taha, Mufeed A

    2010-04-01

    To clinically assess neurogenic dysphagia, and to correlate its presence with demographic features, different stroke risk factors, anatomical arterial territorial stroke types, and pathological stroke types. Seventy-two stroke inpatients were studied between July 2007 and February 2008, at the Departments of Medicine and Neurology at Al-Yarmouk Teaching Hospital, Baghdad, and Rizgary Teaching Hospital, Erbil, Iraq. All patients were assessed using the Mann Assessment of Swallowing Ability score (MASA), Modified Rankin Scale, and the Stroke Risk Scorecard. All patients were reassessed after one month. There were 40 males and 32 females. Sixty-eight patients had ischemic stroke, and 4 had primary intracerebral hemorrhage (ICH). According to the MASA score, 55% of anterior circulation stroke (ACS) cases were associated with dysphasia, and 91% of lateral medullary syndrome cases were associated with dysphagia. Fifty-six percent of ACS dysphagic cases improved within the first month. Forty percent of dysphagic patients died in the one month follow up period, and in most, death was caused by aspiration pneumonia. We observed no significant differences regarding demographic features of dysphagia. Dysphagia can be an indicator of the severity of stroke causing higher mortality and morbidity in affected patients. It was not related to the stroke risk factors and the type of stroke. It is essential from a prognostic point of view to assess swallowing, and to treat its complications early.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. Neurogenic claudication, a delayed complication of a retained bullet.

    PubMed

    Kuijlen, J M; Herpers, M J; Beuls, E A

    1997-04-15

    A case report is presented of a 31-year-old man who visited the authors' neurosurgical department in 1993, complaining of neurogenic claudication. History revealed a gunshot incident 11 years ago, with a bullet left in situ. To determine whether to operate on patients who have a bullet in situ near the spinal cord without initial neurologic deficits. In the literature, only four publications report an epidural chronic inflammatory mass as a reaction to a retained bullet, thereby causing delayed neurologic symptoms. Previous to this report, only one case is described of a patient with a bullet lodged in the paravertebral musculature. Clinically, the patient had pain radiating from his lower back to both his thighs, provoked by walking, standing, and the Valsalva maneuver. Comparison of radiographs made in 1990 and in 1993 showed the lead bullet still completely intact in 1990, whereas in 1993, a partial disintegration and displacement of the bullet, causing a chronic inflammatory reaction (extraspinal and intraspinal), as well as cyst formation, was seen. Particularly notable was the radiographic feature of a sort of "fallen leaf sign" at the level of L5-S1. The preoperative complaints were still absent 1 year after surgery. It is argued that with regard to a retained bullet in the vicinity of the spinal canal, the presence or absence of neurologic symptoms should be the guide for further diagnostic procedures. Only if a neurologic deficit develops, which is possible after many years, should surgical intervention be considered, depending on the severity and type of the deficit, as presented in this case report.

  1. [Total agenesis of the sacrum and neurogenic bladder dysfunction].

    PubMed

    Capitanucci, M L; Silveri, M; Nappo, S; Mosiello, G; Capozza, N; De Gennaro, M

    1997-01-01

    Total Sacral Agenesis (TSA) is a rare congenital anomaly of the lower vertebral column, frequently associated with bladder dysfunction. The diagnosis is often delayed until the evidence of neurological disorders addresses at neuro-radiological examination. In the last 9 years we observed 7 children, 3 males and 4 females, with TSA. The average age at diagnosis was 8 years (range: 1-15 years). Maternal diabetes was present only in one case. In 5 patients, urological ones have been the symptoms of presentation. In one case, TSA has been discovered because of the presence of a sacral mass (lipoma) and the subsequent development of club-foot. The neurological screening, performed in all patients with anorectal anomalies, led to the diagnosis of total sacral agenesis in a child with anteriorized anus. All patients have been evaluated by means of Magnetic Resonance Imaging, renal ultrasound, voiding cystography, renal nuclear scan and urodynamics. The functional evaluation of the lower urinary tract has shown a pattern of neurogenic bladder dysfunction in all children, while bilateral vesico-ureteral reflux has been detected in 2 cases. Intermittent clean catheterization (ICC) has been instituted at the diagnosis in all children. Surgery for continence and protection of upper urinary tract (bladder augmentation and bilateral ureteral reimplantation) has been performed in one patient. At a medium follow-up of 3 years (range: 1-5 years) 2 patients have been lost, normal renal function and urinary continence have been achieved in 4 and one child is continent but has renal failure. An early diagnosis and a correct neuro-urological evaluation and treatment are necessary to prevent urinary tract damage and achieve urinary continence in these patients. Symptoms, clinical findings and relationship with maternal diabetes are discussed. The diagnosis can be enough early if physicians pay attention to maternal diabetes, subtle neurological symptoms (voiding disturbance

  2. 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.

  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. 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

  6. The multiple phenotypes of arthrogryposis multiplex congenita with reference to the neurogenic variant.

    PubMed

    Ambegaonkar, Gautam; Manzur, Adnan Y; Robb, Stephanie A; Kinali, Maria; Muntoni, Francesco

    2011-07-01

    Arthrogryposis can occur in isolation or as part of a syndrome. Amyoplasia, the commonest type of arthrogryposis, has been well described in literature, but neurogenic arthrogryposis, a rarer but significantly heterogeneous variant, has not. We conducted a single-centre, 10-year retrospective study of all children with arthrogryposis at the Dubowitz Neuromuscular Centre, London, UK to describe the various phenotypes of arthrogryposis with special reference to the neurogenic variant including presentation, associated features and long-term outcome. Twenty-seven children with arthrogryposis were identified (13 males) and 25 survivors followed-up for 6.4 ± 2.32 yrs. Perinatal history, presenting clinical features, investigations, final diagnosis and long-term outcomes were recorded. All four limbs were involved in 19 (ankles>wrists>elbows) whilst 8 had isolated upper (UL) or lower limb (LL) involvement. Twelve children had neurogenic arthrogryposis confirmed by a combination of clinical examination, EMG and/or muscle pathology. CK was normal in all children with neurogenic arthrogryposis. Three children in this cohort had abnormal brain MRIs and global developmental delay. Long-term follow up did not show deterioration of muscle power in any of our 12 children with neurogenic arthrogryposis, although contractures lead to temporary worsening of function ability in some (n = 3). Most children improved with physiotherapy and well-fitted orthoses. Our study suggests that neurogenic arthrogryposis is usually a non-progressive disorder and in the absence of concomitant brain abnormalities, allows the clinician to offer an optimistic prognosis to the family. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  7. 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.

  8. 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)

  9. Is There Still a Role for Interspinous Spacers in the Management of Neurogenic Claudication?

    PubMed

    Ravindra, Vijay M; Ghogawala, Zoher

    2017-07-01

    Lumbar spinal stenosis with neurogenic claudication is prevalent in the elderly population. Decompression for this condition is the operation most commonly used to treat older patients. Because of the risks associated with open decompression procedures, particularly in older patients with comorbidities, minimally invasive procedures with implantation of interspinous process devices have been developed. This article reviews the current role of interspinous spacers in the treatment of lumbar spinal stenosis with neurogenic claudication and discusses the body of literature surrounding this treatment alternative. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. [Effects of octreotide on experimental orthostatic neurogenic hypotension].

    PubMed

    Verwaerde, P; Bordet, R; Portolan, G; Tran, M A; Marques, M A; Montastruc, J L; Sénard, J M

    1996-08-01

    The synthetic somatostatin analogue, octreotide, has recently been proposed for the treatment of both postprandial and orthostatic hypotension (OH) in humans with autonomic failure related to multiple system atrophy (MSA) or diabetes mellitus. However, pharmacodynamic data are not still available in experimental models of orthostatic hypotension. We investigated in a model of neurogenic orthostatic hypotension, obtained by chronic sinoaortic denervation (SAD) in chloralose-anaesthetized dogs, the effects of octreotide (0.1 mg/kg, subcutaneous route) during a double-blind cross-over study vs placebo. Blood pressure (BP) and heart rate (HR) average values, SBP and HR short-term variabilities (using fast Fourier transformation) in both low (LF: 50-150 mHz) and high frequency range (respiratory rate +/- 50 mHz) and plasma noradrenaline (NA) levels (HPLC) were measured in supine position and during head-up tilt test (HUT: 80 degrees, 10 min) before and 45 min after drug administration. In controls, as expected, head-up tilt test induced a significant increase in DBP (+14 +/- 8 mmHg), HR (+36 +/- 21 beat/min), NA (296 +/- 118 vs 141 +/- 63 pg/ml), SBP-LF (25 +/- 5 vs 14 +/- 3%) whereas HR-HF significantly decreased. The changes during head-up tilt test were not modified after placebo or octreotide administration. In SAD dogs, head-up tilt test elicited a dramatic fall in SBP (-74 +/- 39 mmHg), DBP (-20 +/- 15 mmHg) without any significant change in HR (-5 +/- 12 beat/min), NA (708 +/- 213 vs 606 +/- 331 pg/ml), SBP-LF (16 +/- 3 vs 16 +/- 3%), HR-HF (8 +/- 2 vs 7 +/- 1%). Octreotide or placebo failed to significantly modify any of the measured parameters during head-up tilt test performed 45 min after drug administration. At the dose used, octreotide elicited a 80% decrease in insulin plasma levels after 45 min in both normal and SAD dogs. These results suggest that 1) this experimental model of orthostatic hypotension in SAD dogs is reproductible and can be used to

  11. Neurogenic obesity and systemic inflammation following spinal cord injury: a review.

    PubMed

    Farkas, Gary J; Gater, David R

    2017-07-30

    Content Spinal Cord Injury (SCI) results in physiological changes that markedly reduces whole-body metabolism, resulting in neurogenic obesity via adipose tissue accumulation. Adipose tissue has been implicated in the release of proinflammatory adipokines that lead to chronic, systemic inflammation, and evidence suggests these adipokines contribute to the pathogeneses of metabolic diseases that often accompany obesity. In this review, we propose the concept of neurogenic obesity through paralysis-induced adiposity as the primary source of systemic inflammation and metabolic dysfunction reported in chronic SCI. We also briefly discuss how exercise in SCI can attenuate the negative consequences of obesity-induced inflammation and its comorbidities. Methods A MEDLINE, PubMed, Google Scholar, and ClinicalKey search was performed using the following search terms: obesity, adiposity, adipose tissue, proinflammatory adipokines, proinflammatory cytokines, metabolic dysfunction, exercise, physical activity, and spinal cord injury. All papers identified were full-text, English language papers. The reference list of identified papers was also searched for additional papers. Results Research suggests that obesity in SCI results in a state of chronic, systemic inflammation primarily through proinflammatory adipokines secreted from excess adipose tissue. The reduction of adipose tissue through the use of diet and exercise demonstrates promise to combat neurogenic obesity, inflammation, and cardiometabolic dysfunction in SCI. Conclusion Proinflammatory adipokines may serve as biomarkers for the development of obesity-related complication in SCI. Mechanistic and interventional studies on neurogenic obesity-induced inflammation in chronic SCI are warranted.

  12. 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

  13. 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

  14. 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…

  15. Neurogenic pulmonary edema due to ventriculo-atrial shunt dysfunction: a case report.

    PubMed

    Cruz, Ana Sofia; Menezes, Sónia; Silva, Maria

    2016-01-01

    Pulmonary edema is caused by the accumulation of fluid within the air spaces and the interstitium of the lung. Neurogenic pulmonary edema is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant central nervous system insult. It may be a less-recognized consequence of raised intracranial pressure due to obstructive hydrocephalus by blocked ventricular shunts. It usually appears within minutes to hours after the injury and has a high mortality rate if not recognized and treated appropriately. We report a patient with acute obstructive hydrocephalus due to ventriculo-atrial shunt dysfunction, proposed to urgent surgery for placement of external ventricular drainage, who presented with neurogenic pulmonary edema preoperatively. She was anesthetized and supportive treatment was instituted. At the end of the procedure the patient showed no clinical signs of respiratory distress, as prompt reduction in intracranial pressure facilitated the regression of the pulmonary edema. This report addresses the importance of recognition of neurogenic pulmonary edema as a possible perioperative complication resulting from an increase in intracranial pressure. If not recognized and treated appropriately, neurogenic pulmonary edema can lead to acute cardiopulmonary failure with global hypoperfusion and hypoxia. Therefore, awareness of and knowledge about the occurrence, clinical presentation and treatment are essential. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  16. Acupuncture for neurogenic bladder due to spinal cord injury: a systematic review protocol

    PubMed Central

    Zhang, Tao; Liu, Huilin; Liu, Zhishun; Wang, Linpeng

    2014-01-01

    Introduction Neurogenic bladder is one of the most common complications following spinal cord injury (SCI). In China, acupuncture therapy is a common treatment for neurogenic bladder due to SCI, but its effects and safety remain uncertain. A protocol is described for a systematic review to investigate the beneficial effects and safety of acupuncture for neurogenic bladder due to SCI. Methods and analysis Eight databases will be searched from their inception: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, the China National Knowledge Infrastructure (CNKI), the VIP database, the Wanfang database, the China Doctoral Dissertations Full-text Database (CDFD) and the China Master's Theses Full-text Database (CMFD). Any clinical randomised controlled trials (RCTs) and the first period of randomised cross-over studies related to acupuncture for neurogenic bladder due to SCI will be included. Outcomes will include change in urinary symptoms, urodynamic tests, clinical assessment and quality of life (QoL). The incidence of adverse events will be assessed as the safety outcome. Study selection, data extraction and quality assessment will be performed independently by two reviewers. Assessment of risk of bias, data synthesis and subgroup analysis will be carried out using Review Manager software. Ethics and dissemination Ethics approval is not required as this is a protocol for a systematic review. The findings of this systematic review will be disseminated via peer-reviewed publications and conference presentations. Trial registration number PROSPERO (CRD42014010448). PMID:25208851

  17. 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…

  18. 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…

  19. 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…

  20. Therapeutic effects of acupuncture for neurogenic dysphagia--a randomized controlled trial.

    PubMed

    Chan, Sze-Ling; Or, Ka-Hang; Sun, Wai-Zhu; Ng, Kwan-Yee; Lo, See-Kit; Lee, Yuet-Sheung

    2012-03-01

    To evaluate the therapeutic effects and long-term efficacy of acupuncture for neurogenic dysphagia. Subjects with neurogenic dysphagia undergoing routine swallowing management were randomized to receive either 20 sessions of true acupuncture (experimental group) or sham acupuncture (control group 1) for approximately one and a half months. A third group (control group 2) comprised of non-randomized subjects with neurogenic dysphagia who received routine care were recruited from separate wards. The outcomes were assessed by the Royal Brisbane Hospital Outcome Measure for Swallowing (RBHOMS), as well as by the consistencies of ingested food and fluid. A total of 87 subjects (experimental group, n = 20; control group 1, n = 19; control group 2, n = 48) were recruited into the trial. The average RBHOMS score showed a greater improvement in the experimental group and in control group 1 than in control group 2. The average levels of food and fluid consistencies displayed greater improvement in the experimental group than in the two control groups. This study demonstrates that acupuncture may have therapeutic effects and long-term efficacy for neurogenic dysphagia. However, due to an insufficient sample size and the lack of follow-up for control group 2, multi-centre trials employing a larger sample size may be required to draw concrete conclusions.

  1. 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

  2. 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

  3. 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

  4. Anal sphincteric neurogenic injury in asymptomatic nulliparous women and fecal incontinence.

    PubMed

    Bharucha, Adil E; Daube, Jasper; Litchy, William; Traue, Julia; Edge, Jessica; Enck, Paul; Zinsmeister, Alan R

    2012-07-15

    While anal sphincter neurogenic injury documented by needle electromyography (EMG) has been implicated to cause fecal incontinence (FI), most studies have been uncontrolled. Normal values and the effects of age on anal sphincter motor unit potentials (MUP) are ill defined. The functional significance of anal sphincter neurogenic injury in FI is unclear. Anal pressures and EMG were assessed in 20 asymptomatic nulliparous women (age, 38 ± 5 yr; mean ± SE) and 20 women with FI (54 ± 3 yr). A computerized program quantified MUP duration and phases. These parameters and MUP recruitment were also semiquantitatively assessed by experienced electromyographers in real time. Increasing age was associated with longer and more polyphasic MUP in nulliparous women by quantitative analysis. A higher proportion of FI patients had prolonged (1 control, 7 patients, P = 0.04) and polyphasic MUP (2 controls, 9 patients, P = 0.03) at rest but not during squeeze. Semiquantitative analyses identified neurogenic or muscle injury in the anal sphincter (11 patients) and other lumbosacral muscles (4 patients). There was substantial agreement between quantitative and semiquantitative analyses (κ statistic 0.63 ± 95% CI: 0.32-0.96). Anal resting and squeeze pressures were lower (P ≤ 0.01) in FI than controls. Anal sphincter neurogenic or muscle injury assessed by needle EMG was associated (P = 0.01) with weaker squeeze pressures (83 ± 10 mmHg vs. 154 ± 30 mmHg) and explained 19% (P = 0.01) of the variation in squeeze pressure. Anal sphincter MUP are longer and more polyphasic in older than younger nulliparous women. Women with FI have more severe neurogenic or muscle anal sphincter injury, which is associated with lower squeeze pressures.

  5. Anal sphincteric neurogenic injury in asymptomatic nulliparous women and fecal incontinence

    PubMed Central

    Daube, Jasper; Litchy, William; Traue, Julia; Edge, Jessica; Enck, Paul; Zinsmeister, Alan R.

    2012-01-01

    While anal sphincter neurogenic injury documented by needle electromyography (EMG) has been implicated to cause fecal incontinence (FI), most studies have been uncontrolled. Normal values and the effects of age on anal sphincter motor unit potentials (MUP) are ill defined. The functional significance of anal sphincter neurogenic injury in FI is unclear. Anal pressures and EMG were assessed in 20 asymptomatic nulliparous women (age, 38 ± 5 yr; mean ± SE) and 20 women with FI (54 ± 3 yr). A computerized program quantified MUP duration and phases. These parameters and MUP recruitment were also semiquantitatively assessed by experienced electromyographers in real time. Increasing age was associated with longer and more polyphasic MUP in nulliparous women by quantitative analysis. A higher proportion of FI patients had prolonged (1 control, 7 patients, P = 0.04) and polyphasic MUP (2 controls, 9 patients, P = 0.03) at rest but not during squeeze. Semiquantitative analyses identified neurogenic or muscle injury in the anal sphincter (11 patients) and other lumbosacral muscles (4 patients). There was substantial agreement between quantitative and semiquantitative analyses (κ statistic 0.63 ± 95% CI: 0.32–0.96). Anal resting and squeeze pressures were lower (P ≤ 0.01) in FI than controls. Anal sphincter neurogenic or muscle injury assessed by needle EMG was associated (P = 0.01) with weaker squeeze pressures (83 ± 10 mmHg vs. 154 ± 30 mmHg) and explained 19% (P = 0.01) of the variation in squeeze pressure. Anal sphincter MUP are longer and more polyphasic in older than younger nulliparous women. Women with FI have more severe neurogenic or muscle anal sphincter injury, which is associated with lower squeeze pressures. PMID:22575218

  6. 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…

  7. 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

  8. 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

  9. 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.

  10. Identifying and classifying quality of life tools for neurogenic bladder function after spinal cord injury: A systematic review.

    PubMed

    Best, Krista L; Ethans, Karen; Craven, B Catharine; Noreau, Luc; Hitzig, Sander L

    2017-09-01

    To identify and classify quality of life (QoL) tools for assessing the influence of neurogenic bladder after spinal cord injury/disease (SCI). Systematic Review Methods: Medline/Pubmed, CINAHL, and PsycInfo were searched using terms related to SCI, neurogenic bladder and QoL. Studies that assessed the influence neurogenic bladder on QoL (or related construct) in samples consisting of ≥50% individuals with SCI were included. Two independent reviewers screened titles and abstracts of 368 identified references; 118 full-text articles were assessed for eligibility, and 42 studies were included. Two reviewers independently classified outcomes as objective (societal viewpoint) or subjective (patient perspective) using a QoL framework. Ten objective QoL measures were identified, with the Medical Outcomes Short Form (SF-36/SF-12) used most frequently. Fourteen subjective QoL measures were identified; 8 were specific to neurogenic bladder. Psychometric evidence for SCI-specific neurogenic bladder QoL tools was reported for the Quality of Life Index (QLI), Qualiveen, Bladder Complications Scale, Spinal Cord Injury-Quality of Life (SCI-QOL) Bladder Management Difficulties, and the SCI-QOL Bladder Management Difficulties-Short Form. The QLI and Qualiveen showed sensitivity to neurogenic bladder in experimental designs. Several objective and subjective tools exist to assess the influence of neurogenic bladder on QoL in SCI. The QLI and Qualiveen, both subjective tools, were the only validated SCI-specific tools that showed sensitivity to neurogenic bladder. Further validation of existing subjective SCI-specific outcomes is needed. Research to validate objective measures of QoL would be useful for informing practice and policy related to resource allocation for bladder care post-SCI.

  11. 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

  12. A systematic review and comparison of questionnaires in the management of spinal cord injury, multiple sclerosis and the neurogenic bladder.

    PubMed

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

    2016-03-01

    Validated questionnaires are increasingly the preferred method used to obtain historical information. Specialized questionnaires exist validated for patients with neurogenic disease including neurogenic bladder. Those currently available are systematically reviewed and their potential for clinical and research use are described. A systematic search via Medline and PubMed using the key terms questionnaire(s) crossed with Multiple Sclerosis (MS) and Spinal Cord Injury (SCI) for the years 1946 to January 22, 2014 inclusive. Additional articles were selected from review of references in the publications identified. Only peer reviewed articles published in English were included. 18 questionnaires exist validated for patients with neurogenic bladder; 14 related to MS, 3 for SCI, and 1 for neurogenic bladder in general; with 4 cross-validated in both MS and SCI. All 18 are validated for both male and female patients; 59% are available only in English. The domains of psychological impact and physical function are represented in 71% and 76% of questionnaires, respectively. None for the female population included elements to measure symptoms of prolapse. The last decade has seen an expansion of validated questionnaires to document bladder symptoms in neurogenic disease. Disease specific instruments are available for incorporation into the clinical setting for MS and SCI patients with neurogenic bladder. The availability of caregiver and interview options enhances suitability in clinical practice as they can be adapted to various extents of disability. Future developments should include expanded language validation to the top 10 global languages reported by the World Health Organization. © 2015 Wiley Periodicals, Inc.

  13. 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

  14. 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

  15. [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.

  16. 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

  17. 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

  18. [Maintenance of logopedic orientation in a patient with oropharyngeal dysphagia of neurogenic origin].

    PubMed

    Zambran-Toledo, N

    Speech therapy treatment on patients who have a neurogenically induced dysphagia begins at hospital, in the intensive rehabilitation units. This study shows some of the difficulties found dealing with and orienting the family and the patient from a therapy point of view, mainly during his return to home surroundings. To better understand the dysphagic situation, normal swallowing steps (oral, pharyngeal and esophageal) steps have been described. These were then related to the dysphagic problems, with their evaluation, classification and characteristics. Under dysphagia rehabilitation the therapeutic guidance should be lead by the appropriate nutritional demands, and prevent aspirations. Some of the therapeutic procedures for treating and controlling neurogenic dysphagia have been described (head posture control, tactile and thermal stimuli, etc.). The author questions the difficulties found controlling orientation and maintaining conduct outside the hospital environment, principally with patients at risk from aspirations.

  19. Kinematic analysis of laryngeal movements in patients with neurogenic dysphagia before and after swallowing rehabilitation.

    PubMed

    Prosiegel, M; Heintze, M; Sonntag, E W; Schenk, T; Yassouridis, A

    2000-01-01

    To examine whether kinematic analysis of laryngeal movements (which are closely linked to pharyngeal swallowing) can differentiate between normal and disturbed swallowing, we used a three-dimensional ultrasound movement recording system to measure the movements of the larynx during swallowing in 32 patients with neurogenic dysphagia caused by central nervous system lesions and in 32 age- and sex-matched healthy individuals. At the beginning of an inpatient rehabilitation swallowing program, laryngeal movements in 24 patients were highly disturbed in terms of velocity curve irregularities. After rehabilitation, the majority of patients with hitherto irregular velocity profiles exhibited laryngeal kinematics that were indistinguishable from those of 32 healthy subjects. Kinematic analysis of laryngeal movements, therefore, is suitable for monitoring motor recovery of swallowing disturbances in patients with neurogenic dysphagia while undergoing swallowing rehabilitation.

  20. The influence of tracheotomy tubes on the swallowing frequency in neurogenic dysphagia.

    PubMed

    Seidl, Rainer O; Nusser-Müller-Busch, Ricki; Ernst, Arne

    2005-03-01

    To compare the swallowing frequency in patients with neurogenic dysphagia with or without tracheotomy tubes (TT) to assess the underlying mechanisms of dysphagia to improve rehabilitation strategies. Prospective study, 10 patients (64 +/- 7 years) with neurogenic dysphagia. Glasgow Coma Scale (GCS) less than 8 points, tracheotomy due to the dysphagia 2 weeks before the examination. The swallowing frequency (1 or less over 5 min) was assessed over 5 consecutive days with or without TT. The swallowing frequency increased after removal of the TT. These findings did not influence the GCS or the Coma Remission Scale. Over a 5-day period, the frequency of swallowing was increased. TTs decisively influence the swallowing behavior of vegetative patients. This phenomenon could be based on an improved sensitivity under re-established physiological expiration. We strongly favor removing the TT or deflating the cuff of the TT under therapeutic conditions in a rehabilitation therapy setting.

  1. Progressive neurogenic muscle atrophy with fasciculation in mice treated with IDPN.

    PubMed

    Uebayashi, Y; Yano, I; Yase, Y

    1987-03-01

    Spontaneous discharges recorded on the EMG appeared in experimental mice given repeated doses of IDPN according to a time schedule. Spontaneous discharges showing a polyphasic pattern and duration of over 10 ms were considered to be fasciculations. One group of mice, treated with IDPN for 4 weeks became active with an increase in muscle volume 2 months after initiation of experiment; spontaneous discharges were recorded in this group at 3-4 weeks after first IDPN injection and disappeared at 4 months. Histologically, neurogenic muscle atrophy, in terms of group atrophy of muscles, was seen in muscles of mice exhibiting spontaneous discharge patterns. Peripheral nerves showed marked atrophy with degeneration. Dissociation of neurofilaments and other organelles was observed. Axonal swellings, filled with numerous maloriented neurofilaments, were confirmed in the lumbar cord. IDPN given repeatedly to mice at a certain dose causes degeneration of the peripheral nerves and results in neurogenic muscle atrophy.

  2. 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.

  3. Buccally Administered Intranasal Desmopressin Acetate for the Treatment of Neurogenic Diabetes Insipidus in Infancy.

    PubMed

    Smego, Allison R; Backeljauw, Philippe; Gutmark-Little, Iris

    2016-05-01

    The treatment of neurogenic diabetes insipidus (DI) in infancy is challenging and complicated by fluid overload and dehydration. Therapy with subcutaneous (SC), intranasal (IN), or oral tablet desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]) remains difficult to titrate in infants. Assess the efficacy and safety of buccally administered IN DDAVP for the management of infants with neurogenic DI. Retrospective review of clinical and laboratory data of 15 infants (mean age, 4.5 mo) with neurogenic DI treated at a tertiary care center. Treatment was with diluted IN DDAVP formulation (10 mcg/mL) administered buccally via a tuberculin syringe to the buccal mucosa. After initial DDAVP titration of 2-3 days, IN DDAVP doses ranged from 1 to 5 mcg twice daily given buccally. Mean serum sodium concentration at DI diagnosis was 159 ± 6.6 mmol/L (range, 151-178) and improved to 142 ± 3.5 mmol/L (range, 137-147) with the buccally administered IN DDAVP. Normal sodium concentrations were established without major fluctuations. Serum sodium was then maintained in the outpatient setting at a mean of 145.7 ± 4.8 mmol/L (mean duration of follow-up, 11 mo). Buccally administered IN formulation of DDAVP provides a practical and safe treatment alternative for neurogenic DI in infancy. Our approach avoided severe hypo- and hypernatremia during DDAVP titration and ongoing outpatient management of DI. The possibility for smaller dosage increments and ease of administration make IN DDAVP administered buccally preferable over other DDAVP treatment options in infants.

  4. 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

  5. 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.

  6. A role for transient receptor potential vanilloid 4 in tonicity-induced neurogenic inflammation.

    PubMed

    Vergnolle, N; Cenac, N; Altier, C; Cellars, L; Chapman, K; Zamponi, G W; Materazzi, S; Nassini, R; Liedtke, W; Cattaruzza, F; Grady, E F; Geppetti, P; Bunnett, N W

    2010-03-01

    Changes in extracellular fluid osmolarity, which occur after tissue damage and disease, cause inflammation and maintain chronic inflammatory states by unknown mechanisms. Here, we investigated whether the osmosensitive channel, transient receptor potential vanilloid 4 (TRPV4), mediates inflammation to hypotonic stimuli by a neurogenic mechanism. TRPV4 was localized in dorsal root ganglia (DRG) by immunofluorescence. The effects of TRPV4 agonists on release of pro-inflammatory neuropeptides from peripheral tissues and on inflammation were examined. Immunoreactive TRPV4 was detected in DRG neurones innervating the mouse hindpaw, where it was co-expressed in some neurones with CGRP and substance P, mediators of neurogenic inflammation. Hypotonic solutions and 4alpha-phorbol 12,13-didecanoate, which activate TRPV4, stimulated neuropeptide release in urinary bladder and airways, sites of neurogenic inflammation. Intraplantar injection of hypotonic solutions and 4alpha-phorbol 12,13-didecanoate caused oedema and granulocyte recruitment. These effects were inhibited by a desensitizing dose of the neurotoxin capsaicin, antagonists of CGRP and substance P receptors, and TRPV4 gene knockdown or deletion. In contrast, antagonism of neuropeptide receptors and disruption of TRPV4 did not prevent this oedema. TRPV4 gene knockdown or deletion also markedly reduced oedema and granulocyte infiltration induced by intraplantar injection of formalin. Activation of TRPV4 stimulates neuropeptide release from afferent nerves and induces neurogenic inflammation. This mechanism may mediate the generation and maintenance of inflammation after injury and during diseases, in which there are changes in extracellular osmolarity. Antagonism of TRPV4 may offer a therapeutic approach for inflammatory hyperalgesia and chronic inflammation.

  7. 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

  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. 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

  10. 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.

  11. Notch receptor expression in neurogenic regions of the adult zebrafish brain.

    PubMed

    de Oliveira-Carlos, Vanessa; Ganz, Julia; Hans, Stefan; Kaslin, Jan; Brand, Michael

    2013-01-01

    The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 [Formula: see text] of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA [Formula: see text] cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA [Formula: see text] cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches.

  12. Notch Receptor Expression in Neurogenic Regions of the Adult Zebrafish Brain

    PubMed Central

    de Oliveira-Carlos, Vanessa; Ganz, Julia; Hans, Stefan; Kaslin, Jan; Brand, Michael

    2013-01-01

    The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches. PMID:24039926

  13. A new complication of hypothyroid coma: neurogenic dysphagia: presentation, diagnosis, and treatment.

    PubMed

    Urquhart, A D; Rea, I M; Lawson, L T; Skipper, M

    2001-06-01

    We report the case of a patient with severe hypothyroid coma in whom hypothyroid-related neurogenic oropharyngeal dysphagia was suspected, videoscopically confirmed, and successfully treated. This complication has not previously been described, and may have contributed to the historically high mortality associated with severe cases of hypothyroid coma. In the future, the early detection and aggressive treatment of this complication and its sequelae should ensure a further reduction in mortality from hypothyroid coma.

  14. Early treatment improves urodynamic prognosis in neurogenic voiding dysfunction: 20 years of experience.

    PubMed

    Costa Monteiro, Lucia M; Cruz, Glaura O; Fontes, Juliana M; Vieira, Eliane T R C; Santos, Eloá N; Araújo, Grace F; Ramos, Eloane G

    To evaluate the association between early treatment and urodynamic improvement in pediatric and adolescent patients with neurogenic bladder. Retrospective longitudinal and observational study (between 1990 and 2013) including patients with neurogenic bladder and myelomeningocele treated based on urodynamic results. The authors evaluated the urodynamic follow-up (bladder compliance and maximum bladder capacity and pressure) considering the first urodynamic improvement in two years as the outcome variable and early referral as the exposure variable, using a descriptive and multivariate analysis with logistic regression model. Among 230 patients included, 52% had an early referral. The majority were diagnosed as overactive bladder with high bladder pressure (≥40cm H2O) and low bladder compliance (3mL/cmH2O) and were treated with oxybutynin and intermittent catheterization. Urodynamic follow-up results showed 68% of improvement at the second urodynamic examination decreasing bladder pressure and increasing bladder capacity and compliance. The percentage of incontinence and urinary tract infections decreased over treatment. Early referral (one-year old or less) increased by 3.5 the probability of urodynamic improvement in two years (95% CI: 1.81-6.77). Treatment onset within the first year of life improves urodynamic prognosis in patients with neurogenic bladder and triplicates the probability of urodynamic improvement in two years. The role of neonatologists and pediatricians in early referral is extremely important. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  15. Antidepressant responsiveness in adulthood is permanently impaired after neonatal destruction of the neurogenic pool

    PubMed Central

    Yu, S; Zutshi, I; Stoffel, R; Zhang, J; Ventura-Silva, A P; Sousa, N; Costa, P S; Holsboer, F; Patchev, A; Almeida, O F X

    2017-01-01

    The dynamic turnover of hippocampal neurons is implicated in the regulation of cognitive and affective behavior. Extending our previous demonstration that administration of dexamethasone (ND) to neonatal rats depletes the resident population of neural precursor cells (NPC) and restrains the size of the neurogenic regions, we now show that the adverse effects of ND persist into adulthood. Specifically, ND impairs repletion of the neurogenic pool and neurogenesis; ND also compromises cognitive performance, the ability to actively adapt to an acute stressor and, the efficacy of glucocorticoid (GC) negative feedback. Interestingly, although ND depletes the neurogenic pool, it does not permanently abolish the proliferative machinery of the residual NPC population; however, ND increases the susceptibility of hippocampal granule neurons to apoptosis. Although the antidepressant fluoxetine (FLX) reverses the latter phenomenon, it does not replenish the NPC pool. Treatment of ND-treated adult rats with FLX also improves GC negative feedback, albeit without rescuing the deleterious effects of ND on behavior. In summary, ND leads to protracted disruption of mental functions, some of which are resistant to antidepressant interventions. We conclude that manipulation of the NPC pool during early life may jeopardize the therapeutic potential of antidepressants in adulthood. PMID:28045461

  16. Long-term efficacy and safety of tolterodine in children with neurogenic detrusor overactivity.

    PubMed

    Reddy, Pramod P; Borgstein, Niels G; Nijman, Rien J M; Ellsworth, Pamela I

    2008-12-01

    We evaluated long-term (> or =12 months) efficacy and safety of tolterodine in children with neurogenic detrusor overactivity. Subjects successfully completed one of three 12-week, open-label studies and had stable neurologic disease and urodynamic evidence of neurogenic detrusor overactivity requiring intermittent catheterization. Drug formulation and dosing were based on age (4 months-4 years, tolterodine oral solution 0.2-2mg twice daily; 5-10 years, tolterodine oral solution 0.5-4 mg twice daily; 11-16 years, tolterodine extended-release capsules 2, 4, or 6 mg once daily). Daily doses were individualized for each subject. Efficacy was evaluated urodynamically and using parent-completed 3-day bladder diaries. Thirty subjects were enrolled. Functional bladder capacity (volume at first leakage, first sensation of bladder fullness or 40 cm H(2)O pressure) increased by month 12 in the younger age groups but not in the oldest subjects. Volume to first detrusor contraction >10 cm H(2)O pressure and detrusor leak point pressure did not change in any age group. The number of incontinence episodes per 24h decreased in all subjects, as did the number of catheterizations per 24h. Mean volume per catheterization increased in all subjects. Seven treatment-related adverse events were reported. Both tolterodine formulations were effective and well tolerated in children with neurogenic detrusor overactivity.

  17. 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

  18. 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

  19. Complications of untreated and ineffectively treated neurogenic bladder dysfunctions in children: our own practical classification.

    PubMed

    Kroll, P; Zachwieja, J

    2016-04-01

    The neurogenic dysfunctions of the detrusor and the sphincter are caused by either a known congenital defect of the nervous system or by acquired damage to the nervous system. In patients with idiopathic bladder dysfunctions neurological examinations fail to reveal any pathology in the nervous system. The treatment strategy for the patient with detrusor-sphincter dysfunction should be based on a comprehensive functional and morphological evaluation. Clean Intermittent Catheterization is mandatory if voiding is ineffective. Reduced bladder capacity related to detrusor overactivity and decreased bladder walls compliance is successfully managed conservatively with oral anticholinergics. Conservative treatment prevents complications in the majority of patients. However, despite proper conservative treatment, some patients still develop complications. We propose our own practical classification of complications characteristic for the bladder and sphincter dysfunctions: 1. Urinary tract infections; 2. Urolithiasis; 3. Anatomic changes in the lower urinary tract; 4. Anatomic changes in the upper urinary tract; 5. Functional disturbances of kidneys parenchyma; 6. Urinary incontinence. Proposed practical classification of complications of bladder and sphincter dysfunctions is clear and simple. This classification can be used both in children with neurogenic and non-neurogenic dysfunctions. It is helpful in planning follow-up procedures and evaluation of treatment results.

  20. Experience with glycerin for antegrade continence enema in patients with neurogenic bowel.

    PubMed

    Chu, David I; Balsara, Zarine R; Routh, Jonathan C; Ross, Sherry S; Wiener, John S

    2013-02-01

    Malone antegrade continence enemas are used in the management of neurogenic bowel to attain fecal continence. Several different irrigation solutions have been described but glycerin, an osmotic laxative that promotes peristalsis, has rarely been mentioned or studied. We assessed clinical outcomes in our patients with a Malone antegrade continence enema using glycerin based irrigation. We retrospectively reviewed patients with neurogenic bowel who underwent a Malone antegrade continence enema procedure between 1997 and 2011. Glycerin diluted with tap water followed by a tap water flush is our preferred irrigation protocol. Bowel regimen outcomes examined included fecal continence, emptying time, leakage from stoma, enema volume, frequency and independence. Of the 23 patients with followup greater than 6 months 19 used glycerin based irrigation. Average age at surgery was 8.8 years. Patients using glycerin instilled a median of 30 ml (mean 29) glycerin and 50 ml (131) tap water. Fecal continence rate was 95% and stoma leakage rate was 16%, and only 16% of patients required daily irrigation. Glycerin is a viable and effective alternative irrigant for antegrade enemas of neurogenic bowel, with an excellent fecal continence rate. The volume of irrigant needed is typically less than 90 ml, which is much less than in published reports using tap water alone. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  1. 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.

  2. 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.

  3. 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.

  4. Experience with Glycerin for Antegrade Continence Enema in Patients with Neurogenic Bowel

    PubMed Central

    Chu, David I.; Balsara, Zarine R.; Routh, Jonathan C.; Ross, Sherry S.; Wiener, John S.

    2017-01-01

    Purpose Malone antegrade continence enemas are used in the management of neurogenic bowel to attain fecal continence. Several different irrigation solutions have been described but glycerin, an osmotic laxative that promotes peristalsis, has rarely been mentioned or studied. We assessed clinical outcomes in our patients with a Malone antegrade continence enema using glycerin based irrigation. Materials and Methods We retrospectively reviewed patients with neurogenic bowel who underwent a Malone antegrade continence enema procedure between 1997 and 2011. Glycerin diluted with tap water followed by a tap water flush is our preferred irrigation protocol. Bowel regimen outcomes examined included fecal continence, emptying time, leakage from stoma, enema volume, frequency and independence. Results Of the 23 patients with followup greater than 6 months 19 used glycerin based irrigation. Average age at surgery was 8.8 years. Patients using glycerin instilled a median of 30 ml (mean 29) glycerin and 50 ml (131) tap water. Fecal continence rate was 95% and stoma leakage rate was 16%, and only 16% of patients required daily irrigation. Conclusions Glycerin is a viable and effective alternative irrigant for antegrade enemas of neurogenic bowel, with an excellent fecal continence rate. The volume of irrigant needed is typically less than 90 ml, which is much less than in published reports using tap water alone. PMID:22986031

  5. Neurogenic Shock Immediately following Posterior Lumbar Interbody Fusion: Report of Two Cases

    PubMed Central

    Matsumoto, Tomiya; Okuda, Shinya; Haku, Takamitsu; Maeda, Kazuya; Maeno, Takafumi; Yamashita, Tomoya; Yamasaki, Ryoji; Kuratsu, Shigeyuki; Iwasaki, Motoki

    2014-01-01

    Study Design Case report. Objective To present two cases of neurogenic shock that occurred immediately following posterior lumbar interbody fusion (PLIF) and that appeared to have been caused by the vasovagal reflex after dural injury and incarceration of the cauda equina. Case Report We present two cases of neurogenic shock that occurred immediately following PLIF. One patient had bradycardia, and the other developed cardiac arrest just after closing the surgical incision and opening the drainage tube. Cardiopulmonary resuscitation was performed immediately, and the patients recovered successfully, but they showed severe motor loss after awakening. The results of laboratory data, chest X-ray, electrocardiogram, computed tomography, and echocardiography ruled out pulmonary embolism, hemorrhagic shock, and cardiogenic shock. Although the reasons for the postoperative shock were obscure, reoperation was performed to explore the cause of paralysis. At reoperation, a cerebrospinal fluid collection and the incarceration of multiple cauda equina rootlets through a small dural tear were observed. The incarcerated cauda equina rootlets were reduced, and the dural defect was closed. In both cases, the reoperation was uneventful. From the intraoperative findings at reoperation, it was thought that the pathology was neurogenic shock via the vasovagal reflex. Conclusion Incarceration of multiple cauda equina rootlets following the accidental dural tear by suction drainage caused a sudden decrease of cerebrospinal fluid pressure and traction of the cauda equina, which may have led to the vasovagal reflex. PMID:26225287

  6. Neurogenic Shock Immediately following Posterior Lumbar Interbody Fusion: Report of Two Cases.

    PubMed

    Matsumoto, Tomiya; Okuda, Shinya; Haku, Takamitsu; Maeda, Kazuya; Maeno, Takafumi; Yamashita, Tomoya; Yamasaki, Ryoji; Kuratsu, Shigeyuki; Iwasaki, Motoki

    2015-08-01

    Study Design Case report. Objective To present two cases of neurogenic shock that occurred immediately following posterior lumbar interbody fusion (PLIF) and that appeared to have been caused by the vasovagal reflex after dural injury and incarceration of the cauda equina. Case Report We present two cases of neurogenic shock that occurred immediately following PLIF. One patient had bradycardia, and the other developed cardiac arrest just after closing the surgical incision and opening the drainage tube. Cardiopulmonary resuscitation was performed immediately, and the patients recovered successfully, but they showed severe motor loss after awakening. The results of laboratory data, chest X-ray, electrocardiogram, computed tomography, and echocardiography ruled out pulmonary embolism, hemorrhagic shock, and cardiogenic shock. Although the reasons for the postoperative shock were obscure, reoperation was performed to explore the cause of paralysis. At reoperation, a cerebrospinal fluid collection and the incarceration of multiple cauda equina rootlets through a small dural tear were observed. The incarcerated cauda equina rootlets were reduced, and the dural defect was closed. In both cases, the reoperation was uneventful. From the intraoperative findings at reoperation, it was thought that the pathology was neurogenic shock via the vasovagal reflex. Conclusion Incarceration of multiple cauda equina rootlets following the accidental dural tear by suction drainage caused a sudden decrease of cerebrospinal fluid pressure and traction of the cauda equina, which may have led to the vasovagal reflex.

  7. Neurogenic heterotopic ossification: epidemiology and morphology on conventional radiographs in an early neurological rehabilitation population.

    PubMed

    Seipel, R; Langner, S; Platz, T; Lippa, M; Kuehn, J P; Hosten, N

    2012-01-01

    To retrospectively evaluate neurogenic heterotopic ossification in an early neurological rehabilitation population (phases B and C) with respect to epidemiology and morphology on conventional radiographs. Over a 4-year period, 1,463 patients treated at a clinic for early neurological rehabilitation were evaluated for clinical symptoms of neurogenic heterotopic ossification. In case of clinical suspicion, plain radiographs of the expected sites were obtained. If heterotopic ossification was detected, the initial and subsequent radiographs were retrospectively analyzed for sites, size, and morphology. Immature lesions were categorized as small (<10 mm) or large (10-100 mm). The prevalence rate of neurogenic heterotopic ossification was 2.05%. The condition was most common in young male adults. The hip was the most common site accounting for more than half of the cases. Two or more ossifications were seen in 56.7% of the affected patients with approximately two-thirds showing bilateral symmetric involvement of corresponding joint regions. The size of ossifications strongly varied interindividually. Small immature lesions demonstrated less progression in size than large lesions during maturation (P < 0.05). Standard radiographs, as a fast and inexpensive technique, allow the expected size progression of heterotopic ossifications during maturation to be estimated, which is relevant in terms of therapeutic decisions, patient mobilization, and neurological rehabilitation.

  8. Ventral midbrain neural stem cells have delayed neurogenic potential in vitro.

    PubMed

    Hegarty, Shane V; Spitere, Katie; Sullivan, Aideen M; O'Keeffe, Gerard W

    2014-01-24

    Neural stem cells (NSCs) have been the focus of an intensive effort to direct their differentiation in vitro towards desired neuronal phenotypes for cell replacement therapies. It is thought that NSCs derived from older embryos have limited neurogenic capacity and are restricted towards an astroglial fate. This idea is largely based on studies that typically analysed NSC-derived progeny following one week of in vitro differentiation. In this report, the neurogenic capacity of older ventral midbrain (VM) NSCs was assessed. When the older NSCs were differentiated for three weeks, there were significant increases in the numbers of newly born neurons at 14 and 21 days, as assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation. Therefore this study demonstrates that older NSCs retain significantly more neurogenic potential than was previously thought. These data have implications for NSC preparatory protocols and the choice of donor age for cell transplantation studies, and contributes to the understanding of NSC behaviour in vitro. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Hepatogenic and neurogenic differentiation of bone marrow mesenchymal stem cells from abattoir-derived bovine fetuses

    PubMed Central

    2014-01-01

    Background Mesenchymal stem cells (MSC) are multipotent progenitor cells characterized by their ability to both self-renew and differentiate into tissues of mesodermal origin. The plasticity or transdifferentiation potential of MSC is not limited to mesodermal derivatives, since under appropriate cell culture conditions and stimulation by bioactive factors, MSC have also been differentiated into endodermal (hepatocytes) and neuroectodermal (neurons) cells. The potential of MSC for hepatogenic and neurogenic differentiation has been well documented in different animal models; however, few reports are currently available on large animal models. In the present study we sought to characterize the hepatogenic and neurogenic differentiation and multipotent potential of bovine MSC (bMSC) isolated from bone marrow (BM) of abattoir-derived fetuses. Results Plastic-adherent bMSC isolated from fetal BM maintained a fibroblast-like morphology under monolayer culture conditions. Flow cytometric analysis demonstrated that bMSC populations were positive for MSC markers CD29 and CD73 and pluripotency markers OCT4 and NANOG; whereas, were negative for hematopoietic markers CD34 and CD45. Levels of mRNA of hepatic genes α-fetoprotein (AFP), albumin (ALB), alpha1 antitrypsin (α1AT), connexin 32 (CNX32), tyrosine aminotransferase (TAT) and cytochrome P450 (CYP3A4) were up-regulated in bMSC during a 28-Day period of hepatogenic differentiation. Functional analyses in differentiated bMSC cultures evidenced an increase (P < 0.05) in albumin and urea production and glycogen storage. bMSC cultured under neurogenic conditions expressed NESTIN and MAP2 proteins at 24 h of culture; whereas, at 144 h also expressed TRKA and PrPC. Levels of MAP2 and TRKA mRNA were up-regulated at the end of the differentiation period. Conversely, bMSC expressed lower levels of NANOG mRNA during both hepatogenic and neurogenic differentiation processes. Conclusion The expression patterns of linage

  10. 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.

  11. 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. Copyright © 2013 Wiley Periodicals, Inc.

  12. 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

  13. Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation.

    PubMed

    Corrigan, Frances; Mander, Kimberley A; Leonard, Anna V; Vink, Robert

    2016-10-11

    The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.

  14. 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

  15. 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.

  16. 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

  17. Atrial fibrillation detected after acute ischemic stroke: evidence supporting the neurogenic hypothesis.

    PubMed

    González Toledo, María E; Klein, Francisco R; Riccio, Patricia M; Cassará, Fátima Pagani; Muñoz Giacomelli, Francisco; Racosta, Juan M; Roberts, Eleanor S; Sposato, Luciano A

    2013-11-01

    It is unknown whether atrial fibrillation (AF) detected after acute ischemic stroke is caused by neurogenic or cardiogenic mechanisms. Based on the potential damage to the autonomic nervous system, neurogenic mechanisms could be implicated in the pathophysiology of newly diagnosed AF. To test this hypothesis, we developed a mechanistic approach by comparing a prespecified set of indicators in acute ischemic stroke patients with newly diagnosed AF, known AF, and sinus rhythm. We prospectively assessed every acute ischemic stroke patient undergoing continuous electrocardiographic monitoring from 2008 through 2011. We compared newly diagnosed AF, known AF, and sinus rhythm patients by using 20 indicators grouped in 4 domains: vascular risk factors, underlying cardiac disease, burden of neurological injury, and in-hospital outcome. We studied 275 acute ischemic stroke patients, 23 with newly diagnosed AF, 64 with known AF, and 188 with sinus rhythm. Patients with newly diagnosed AF had a lower proportion of left atrial enlargement (60.9% versus 91.2%, P=.001), a smaller left atrial area (22.0 versus 26.0 cm2, P=.021), and a higher frequency of insular involvement (30.4% versus 9.5%, P=.017) than participants with known AF. Compared with patients in sinus rhythm, those with newly diagnosed AF had a higher proportion of brain infarcts of 15 mm or more (60.9% versus 37.2%, P=.029) and a higher frequency of insular involvement (30.4% versus 7.3%, P<.001). The low frequency of underlying cardiac disease and the strikingly high proportion of concurrent strategic insular infarctions in patients with newly diagnosed AF provide additional evidence supporting the role of neurogenic mechanisms in a subset of AF detected after acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  18. [Urodynamic changes after bladder augmentation surgery in paediatric patients with myelomeningocele due to neurogenic bladder].

    PubMed

    Zaragoza Torres, Raúl Ignacio; Galarza-Flores, Mario Eduardo; Gómez-Castellanos, Julio Cesar; Barrera-de León, Juan Carlos

    2016-01-01

    Augmentation cystoplasty is a successful surgical procedure for the management of neurogenic bladder in children in order to improve urodynamic parameters. The aim of this article is to describe urodynamic changes after augmentation cystoplasty in children with myelomeningocele. A descriptive cross-sectional study including children aged 8-16 years with a myelomeningocele operated on for augmentation cystoplasty surgery with sigmoid colon segments due to a neurogenic bladder from the years 2003-2013. A urodynamic study was conducted before and after the surgical procedure. Non-probabilistic sample of consecutive cases. Descriptive statistics with frequencies and percentages, medians, and ranges. Inferential intra-group comparison with the Wilcoxon test and inter-group with Mann-Whitney U. SPSS 20.0 statistical package. The study included 50 patients, of whom 25 were male and 25 were female, with a median age of 12 years (range, 6-15 years). Bladder capacity improved from 52.8% to 95.9% (p<0.001), uninhibited contractions 1.4-1.8, contraction intensity 47-8.5 (p<0.001), mean pre-surgical and post-surgical filling pressure 40.8cm H2O and 11.0cm H2O, respectively (p<0.001), mean emptying pressure 48.5 vs. 3.6cm H2O (p<0.001), and bladder accommodation 4.6 vs. 41.3cm H2O (p<0.001). Augmentation cystoplasty with sigmoid colon significantly improved urodynamic parameters, such as bladder accommodation and filling pressure in children with myelomeningocele-associated neurogenic bladder. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  19. Positional changes in voiding dynamics of children with non-neurogenic bladder dysfunction.

    PubMed

    Uluocak, Nihat; Oktar, Tayfun; Acar, Omer; Incesu, Olga; Ziylan, Orhan; Erkorkmaz, Unal

    2008-09-01

    To investigate the effect of certain positions on voiding dynamics in children with non-neurogenic bladder dysfunction. A total of 29 patients (10 male, 19 female) with non-neurogenic overactive bladder were enrolled. None of the patients had voiding phase dysfunction. Male patients were told to urinate in three positions (sitting, squatting, standing). Female patients did not void while standing. During voiding, maximum urinary flow rate (Qmax), detrusor pressure at maximal flow (Pdet-Qmax), and intra-abdominal pressure at maximal flow (Pabd-Qmax) were recorded. After voiding in one position, the bladder was re-distended. The same procedures were repeated for the three different positions. Then patients were told to perform three drinking-voiding cycles without the catheter in place. After recording Qmax, residual urine was measured with ultrasonography. The differences between these parameters were analyzed. The mean (+/- standard deviation) patient age was 11.10 +/- 2.94 years (range, 6-16 years). In girls, the mean Pdet-Qmax value in the sitting and squatting positions was 43.11 +/- 16.74 cm H(2)O and 35.21 +/- 10.67 cm H(2)O, respectively (P = .028). Girls voided with a significantly higher Qmax in sitting and squatting positions than boys, regardless of the presence of a catheter. The mean Pdet-Qmax value in the squatting position was 59.20 +/- 20.45 cm H(2)O in boys and 35.21 +/- 10.67 cm H(2)O in girls. The presence of a catheter significantly lowered mean maximal urinary flow rates in sitting and squatting positions. This is the first study to demonstrate the effect of voiding positions on pressure flow study results in children. Our results show that voiding dynamics are influenced by different voiding positions in children with non-neurogenic bladder dysfunction.

  20. 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

  1. Neurogenic Lower Urinary Tract Dysfunction in Adults with Cerebral Palsy: Outcomes following a Conservative Management Approach.

    PubMed

    Goldfarb, Robert A; Pisansky, Andrew; Fleck, Joseph; Hoversten, Patrick; Cotter, Katherine J; Katorski, Jenna; Liberman, Daniel; Elliott, Sean P

    2016-04-01

    Cerebral palsy is characterized by motor impairment following injury to the developing brain. Neurogenic lower urinary tract dysfunction is estimated to affect at least a third of children with cerebral palsy. However there are limited data as patients transition to adulthood. We sought to describe the symptoms, sequelae and management of neurogenic lower urinary tract dysfunction in adults with cerebral palsy. We retrospectively reviewed the charts of adult patients with cerebral palsy between 2011 and 2014. Patients with prior bladder reconstruction or catheterization based bladder drainage were excluded from study. Cerebral palsy severity was determined using GMFCS (Gross Motor Function Classification System). A conservative evaluation and treatment paradigm was used. Noninvasive treatments were encouraged. Specifically clean intermittent catheterization, which is often not feasible, is avoided unless urinary retention, hydronephrosis or refractory lower urinary tract symptoms develop. There were 121 patients included in final analysis. Median age was 25 and 61 patients (50%) had GMFCS level V. Noninvasive management failed in 28 of 121 patients (23%) as defined by hydronephrosis in 9, persistent urinary retention in 10 and refractory lower urinary tract symptoms/incontinence in 9. Urethral clean intermittent catheterization was poorly tolerated. Of all patients 25% showed evidence of urolithiasis during the study period. Surgical intervention was rare and associated with significant morbidity. Adults with cerebral palsy may present with variable signs and symptoms of neurogenic lower urinary tract dysfunction. Conservative treatment was successful in more than 75% of patients. Clean intermittent catheterization was poorly tolerated in patients in whom conservative treatment failed. Surgical intervention was rarely indicated and it should be reserved for select individuals. Copyright © 2016 American Urological Association Education and Research, Inc

  2. 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

  3. 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

  4. 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

  5. New Frontiers of Basic Science Research in Neurogenic Lower Urinary Tract Dysfunction.

    PubMed

    Miyazato, Minoru; Kadekawa, Katsumi; Kitta, Takeya; Wada, Naoki; Shimizu, Nobutaka; de Groat, William C; Birder, Lori A; Kanai, Anthony J; Saito, Seiichi; Yoshimura, Naoki

    2017-08-01

    The lower urinary tract's main functions are storage and elimination. The micturition reflex pathway is modulated by the spinobulbospinal reflex pathway as well as higher brain centers involved in the voluntary micturition control. Micturition is sensitive to numerous injuries, resulting in various types of dysfunction. Animal studies indicate that lower urinary tract dysfunction partly depends on plasticity of the neural pathways. Reflex plasticity is associated with changes in ion channels, receptors, and numerous mediators. Animal models may aid in understanding the mechanisms leading to pathologic conditions and the plasticity in reflex pathways to the lower urinary tract after neurogenic lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Choosing Surgery for Neurogenic TOS: The Roles of Physical Exam, Physical Therapy, and Imaging.

    PubMed

    Kuwayama, David P; Lund, Jason R; Brantigan, Charles O; Glebova, Natalia O

    2017-06-23

    Neurogenic thoracic outlet syndrome (nTOS) is characterized by arm and hand pain, paresthesias, and sometimes weakness resulting from compression of the brachial plexus within the thoracic outlet. While it is the most common subtype of TOS, nTOS can be difficult to diagnose. Furthermore, patient selection for surgical treatment can be challenging as symptoms may be vague and ambiguous, and diagnostic studies may be equivocal. Herein, we describe some approaches to aid in identifying patients who would be expected to benefit from surgical intervention for nTOS. We describe the role of physical examination, physical therapy, and imaging in the evaluation and diagnosis of nTOS.

  7. [Endoscopic augmentation of neurogenic bladder with botulinum-A toxin in children].

    PubMed

    Kroll, Paweł; Jankowski, Andrzej; Zachwieja, Jacek; Zaniew, Marcin; Mańkowski, Przemysław; Harasymczuk, Jerzy; Antczak, Andrzej; Murias, Marek

    2008-01-01

    To present our experience with endoscopic intradetrusor injections of botulinum-A toxin. Endoscopic treatment was proposed for children in which no improvement or side effects were observed. Botulinum-A toxin was injected in 25 children 3 to 7 years old. All children were evaluated with voiding-charts, in all of them urodynamic investigations were also performed in the pre and post-procedure period. Increased bladder volume was found in 18 patients, in 5 children bladder volume decreased. No major side effects were noted post BTX injections. Botulinum-A toxin in useful in children with neurogenic bladder overactivity.

  8. 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.

  9. Choosing Surgery for Neurogenic TOS: The Roles of Physical Exam, Physical Therapy, and Imaging

    PubMed Central

    P. Kuwayama, David; R. Lund, Jason; O. Brantigan, Charles; O. Glebova, Natalia

    2017-01-01

    Neurogenic thoracic outlet syndrome (nTOS) is characterized by arm and hand pain, paresthesias, and sometimes weakness resulting from compression of the brachial plexus within the thoracic outlet. While it is the most common subtype of TOS, nTOS can be difficult to diagnose. Furthermore, patient selection for surgical treatment can be challenging as symptoms may be vague and ambiguous, and diagnostic studies may be equivocal. Herein, we describe some approaches to aid in identifying patients who would be expected to benefit from surgical intervention for nTOS. We describe the role of physical examination, physical therapy, and imaging in the evaluation and diagnosis of nTOS. PMID:28644402

  10. Subgemmal neurogenous plaque of the tongue: a report of three cases.

    PubMed

    Gonzaga, Amanda Katarinny Goes; Moreira, Deborah Gondim Lambert; Sena, Dáurea Adília Cóbe; Lopes, Maria Luiza Diniz de Sousa; de Souza, Lélia Batista; Queiroz, Lélia Maria Guedes

    2017-05-10

    Subgemmal neurogenous plaque (SNP) is a biphasic neural structure associated with the taste buds. Clinically, SNP usually presents as an asymptomatic, normally colored, papule located in the posterior lateral border of the tongue. Accurate diagnosis is based only on histopathological examination, which shows a superficial neurofibroma-like pattern and a neuroma-like in the deep zone. Appropriate recognition of clinical and morphological aspects of SNPs can avoid their misdiagnosis as neural neoplasms. We report three cases of SNP with detailed clinical, histopathological, and immunohistochemical features.

  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. 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.

  13. Transcutaneous Electrical Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.

    PubMed

    Gross, Tobias; Schneider, Marc P; Bachmann, Lucas M; Blok, Bertil F M; Groen, Jan; Hoen, Lisette A 't; Castro-Diaz, David; Padilla Fernández, Bárbara; Del Popolo, Giulio; Musco, Stefania; Hamid, Rizwan; Ecclestone, Hazel; Karsenty, Gilles; Phé, Véronique; Pannek, Jürgen; Kessler, Thomas M

    2016-06-01

    Transcutaneous electrical nerve stimulation (TENS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option in patients with an underlying neurological disorder. We systematically reviewed all available evidence on the efficacy and safety of TENS for treating neurogenic lower urinary tract dysfunction. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. After screening 1943 articles, 22 studies (two randomised controlled trials, 14 prospective cohort studies, five retrospective case series, and one case report) enrolling 450 patients were included. Eleven studies reported on acute TENS and 11 on chronic TENS. In acute TENS and chronic TENS, the mean increase of maximum cystometric capacity ranged from 69ml to 163ml and from 4ml to 156ml, the mean change of bladder volume at first detrusor overactivity from a decrease of 13ml to an increase of 175ml and from an increase of 10ml to 120ml, a mean decrease of maximum detrusor pressure at first detrusor overactivity from 18 cmH20 to 72 cmH20 and 8 cmH20, and a mean decrease of maximum storage detrusor pressure from 20 cmH20 to 58 cmH2O and from 3 cmH20 to 8 cmH2O, respectively. In chronic TENS, a mean decrease in the number of voids and leakages per 24h ranged from 1 to 3 and from 0 to 4, a mean increase of maximum flow rate from 2ml/s to 7ml/s, and a mean change of postvoid residual from an increase of 26ml to a decrease of 85ml. No TENS-related serious adverse events have been reported. Risk of bias and confounding was high in most studies. Although preliminary data suggest TENS might be effective and safe for treating neurogenic lower urinary tract dysfunction, the evidence base is poor and more reliable data from well-designed randomised controlled trials are needed to make definitive conclusions. Early data suggest that transcutaneous electrical nerve stimulation might be effective and safe for

  14. 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

  15. Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension.

    PubMed

    Braga, V A; Medeiros, I A; Ribeiro, T P; França-Silva, M S; Botelho-Ono, M S; Guimarães, D D

    2011-09-01

    Neurogenic hypertension has been the subject of extensive research worldwide. This review is based on the premise that some forms of neurogenic hypertension are caused in part by the formation of angiotensin-II (Ang-II)-induced reactive oxygen species along the subfornical organ-paraventricular nucleus of the hypothalamus-rostral ventrolateral medulla pathway (SFO-PVN-RVLM pathway). We will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the SFO (an important circumventricular organ) are activated by Ang-II, how the SFO communicates with two other important areas involved in sympathetic activity regulation (PVN and RVLM) and how Ang-II-induced reactive oxygen species participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension.

  16. Neurogenic function in rats with unilateral hippocampal sclerosis that experienced early-life status epilepticus

    PubMed Central

    Dunleavy, Mark; Schindler, Clara K; Shinoda, Sachiko; Crilly, Shane; Henshall, David C

    2014-01-01

    Status epilepticus in the adult brain invariably causes an increase in hippocampal neurogenesis and the appearance of ectopic cells and this has been implicated as a causal factor in epileptogenesis. The effect of status epilepticus on neurogenesis in the developing brain is less well characterized and models of early-life seizures typically do not reproduce the hippocampal damage common to human mesial temporal sclerosis. We recently reported that evoking status epilepticus by intra-amygdala microinjection of kainic acid in post-natal (P) day 10 rats caused substantial acute neuronal death within the ipsilateral hippocampus and rats later developed unilateral hippocampal sclerosis and spontaneous recurrent seizures. Here, we examined the expression of a selection of genes associated with neurogenesis and assessed neurogenic function in this model. Protein levels of several markers of neurogenesis including polysialic acid neural cell adhesion molecule, neuroD and doublecortin were reduced in the hippocampus three days after status epilepticus in P10 rats. In contrast, protein levels of neurogenesis markers were similar to control in rats at P55. Pulse-chase experiments using thymidine analogues suggested there was a reduction in new neurons at 72 h after status epilepticus in P10 rats, whereas numbers of new neurons labelled in epileptic rats at P55 with hippocampal sclerosis were similar to controls. The present study suggests that status epilepticus in the immature brain suppresses neurogenesis but the neurogenic potential is retained in animals that later develop hippocampal sclerosis. PMID:25755841

  17. [Dysphagia caused by neurogenic deglutition disorders and diffuse idiopathic skeletal hyperostosis (DISH)].

    PubMed

    Bremke, M; Wagner, H-J; Folz, B J

    2006-09-01

    Diffuse idiopathic skeletal hyperostosis (DISH) may lead to dysphagia caused by osteophytes of the cervical spine. Osteophytes can be resected transorally or transcervically, but operative ablation should not be indicated generously because of the threat of severe complications. A fifty-year-old man with dysphagia and loss of weight of 15 kg in the last three months is presented. He also suffered from a brain damage during infancy which caused grand-mal-seizures. One seizure lead to cardiac arrest which required cardio-pulmonary resuscitation and subsequent tracheostomy. A spheric tumor of the posterior pharyngeal wall could be seen endoscopically, it appeared radiologically as an osteophytic formation of the segments C (3) - C (5). Ossification of the anterior longitudinal ligament was also seen. Diagnosis of DISH was made on the basis of these results. Contrast imaging of the esophagus and videofluoroscopy showed aspiration in terms of neurogenic disorders. The patient received a percutaneous gastrostomy after his case was discussed with neurologic and orthopaedic colleagues, because a causal therapy of the combined disease seemed to be impossible. Dysphagia in the presented case was caused by a combination of neurogenic deglutition disorders and oropharyngeal obstruction through osteophytes. Surgical removal of the osteophytes was not indicated because it would have put the patient at a certain risk, but only a part of the underlying problem would have been removed. Symptomatic therapy with a gastrostomy secures normocaloric diet. The patient's weight remained stable and he can follow his habitual daily routine.

  18. Pharmacokinetics and effects of intravesical oxybutynin on the paediatric neurogenic bladder.

    PubMed

    Amark, P; Eksborg, S; Juneskans, O; Bussman, G; Palm, C

    1998-12-01

    To evaluate the pharmacokinetics of both oxybutynin and its active metabolite, N-desethyl oxybutynin (NDO), when the drug is instilled directly into the bladder in children with myelodysplasia and neurogenic bladder disturbance, in whom it may improve continence and decrease the risk of upper urinary tract deterioration. The study comprised 13 children (five girls and eight boys, mean age 9.3 years, range 1-15) with neurogenic bladders who were treated using clean intermittent catheterization and intravesical instillation of a sterile, pharmacy-produced solution of oxybutynin. Steady-state minimum plasma levels of oxybutynin and NDO, together with their effect on urodynamic variables and incontinence, were evaluated. The dose (0.04-0.17 mg/kg, mean 0.1 mg/kg) was instilled twice daily. The effects of the drug on incontinence and urodynamic variables were pronounced, improving both in most cases. Minimum plasma levels were < 0.3-7.2 ng/mL for oxybutynin and 0.8-14 ng/mL for NDO. The ratio of oxybutynin to NDO was 0.29-0.83 (mean 0.47). There was no clear relationship between minimum plasma levels of the drug or NDO and their clinical effects; however, the combination of oxybutynin and NDO seemed to be more strongly correlated with the clinical effects.

  19. 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).

  20. 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.

  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. Evaluation of 3 Methods of Bladder Irrigation to Treat Bacteriuria in Persons With Neurogenic Bladder

    PubMed Central

    Waites, Ken B; Canupp, Kay C; Roper, James F; Camp, Susan M; Chen, Yuying

    2006-01-01

    Background/Objective: We conducted a randomized, double-blind comparison of twice daily bladder irrigation using 1 of 3 different solutions in community-residing persons with neurogenic bladder who used indwelling catheters to evaluate efficacy in treatment of bacteriuria. Methods: Eighty-nine persons with bacteriuria were randomized to irrigate their bladders twice daily for 8 weeks with 30 mL of (a) sterile saline, (b) acetic acid, or (c) neomycin-polymyxin solution. Urinalysis, cultures, and antimicrobial susceptibility tests were performed at baseline and weeks 2, 4, and 8 to determine the extent to which each of the solutions affected numbers and types of bacteria, urinary pH, urinary leukocytes, and generation of antimicrobial-resistant organisms. Results: Bladder irrigation was well tolerated with the exception of 3 participants who had bladder spasms. None of the 3 irrigants had a detectable effect on the degree of bacteriuria or pyuria in 52 persons who completed the study protocol. A significant increase in urinary pH occurred in all 3 groups. No significant development of resistance to oral antimicrobials beyond what was observed at baseline was detected. Conclusions: Bladder irrigation was generally well tolerated for 8 weeks. No advantages were detected for neomycin-polymyxin or acetic acid over saline in terms of reducing the urinary bacterial load and inflammation. We cannot recommend bladder irrigation as a means of treatment for bacteriuria in persons with neurogenic bladder. PMID:16859225

  3. Effect of onabotulinumtoxinA treatment on symptoms and urodynamic findings in pediatric neurogenic bladder.

    PubMed

    Kask, M; Rintala, R; Taskinen, S

    2014-04-01

    To evaluate clinical and urodynamic efficiency of onabotulinumtoxinA (Botox) treatment in pediatric patients with urinary incontinence due to neurogenic overactive bladder. Seventeen patients aged from 6 to 17 years (median 11 years) were treated with Botox injections. Clinical response to incontinence, duration of the response, and urodynamic results before and 1-3 months after treatment were evaluated. Mean incontinence frequency decreased significantly (p = 0.036); six of 17 patients had >90% reduction, and a further three patients had a 50-90% reduction in incontinence episodes. Median duration of the response was 15 months (range 3-42 months). Mean bladder volume changed from 380 ± 148 ml to 453 ± 147 (p = 0.078), maximal detrusor pressure decreased from 45 ± 31 cmH2O to 32 ± 21 cmH2O (p = 0.030), and the number of patients with detrusor contractions during filling decreased from 12 to three (p = 0.005) after the treatment. The patients with poor bladder compliance had either no response or a short duration of response. At follow-up eight patients had undergone bladder augmentation because of persistent incontinence. About one third of pediatric patients with neurogenic bladder had a good response to Botox treatment. In many patients, the clinical response was longer than expected. The patients who initially had poor bladder compliance had a poor response to the treatment. Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  4. Boundary Caps Give Rise to Neurogenic Stem Cells and Terminal Glia in the Skin.

    PubMed

    Gresset, Aurélie; Coulpier, Fanny; Gerschenfeld, Gaspard; Jourdon, Alexandre; Matesic, Graziella; Richard, Laurence; Vallat, Jean-Michel; Charnay, Patrick; Topilko, Piotr

    2015-08-11

    While neurogenic stem cells have been identified in rodent and human skin, their manipulation and further characterization are hampered by a lack of specific markers. Here, we perform genetic tracing of the progeny of boundary cap (BC) cells, a neural-crest-derived cell population localized at peripheral nerve entry/exit points. We show that BC derivatives migrate along peripheral nerves to reach the skin, where they give rise to terminal glia associated with dermal nerve endings. Dermal BC derivatives also include cells that self-renew in sphere culture and have broad in vitro differentiation potential. Upon transplantation into adult mouse dorsal root ganglia, skin BC derivatives efficiently differentiate into various types of mature sensory neurons. Together, this work establishes the embryonic origin, pathway of migration, and in vivo neurogenic potential of a major component of skin stem-like cells. It provides genetic tools to study and manipulate this population of high interest for medical applications. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications

    PubMed Central

    Capilla-Gonzalez, Vivian; Hernandez-Rabaza, Vicente

    2011-01-01

    The capacity of the brain to generate new adult neurons is a recent discovery that challenges the old theory of an immutable adult brain. A new and fascinating field of research now focuses on this regenerative process. The two brain systems that constantly produce new adult neurons, known as the adult neurogenic systems, are the dentate gyrus (DG) of the hippocampus and the lateral ventricules/olfactory bulb system. Both systems are involved in memory and learning processes. Different drugs of abuse, such as cocaine and MDMA, have been shown to produce cellular and molecular changes that affect adult neurogenesis. This review summarizes the effects that these drugs have on the adult neurogenic systems. The functional relevance of adult neurogenesis is obscured by the functions of the systems that integrate adult neurons. Therefore, we explore the effects that cocaine and MDMA produce not only on adult neurogenesis, but also on the DG and olfactory bulbs. Finally, we discuss the possible role of new adult neurons in cocaine- and MDMA-induced impairments. We conclude that, although harmful drug effects are produced at multiple physiological and anatomical levels, the specific consequences of reduced hippocampus neurogenesis are unclear and require further exploration.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

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

    PubMed

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

    2015-01-01

    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 re?ex (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.

  12. 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.

  13. 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

  14. 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.

  15. Stress-Induced Neurogenic Inflammation in Murine Skin Skews Dendritic Cells Towards Maturation and Migration

    PubMed Central

    Joachim, Ricarda Alcira; Handjiski, Bori; Blois, Sandra Maria; Hagen, Evelin; Paus, Ralf; Arck, Petra Clara

    2008-01-01

    The skin continuously serves as a biosensor of multiple exogenous stressors and integrates the resulting responses with an individual’s central and peripheral endogenous response systems to perceived stress; it also acts to protect against external challenges such as wounding and infection. We have previously shown in mice that stress induces nerve growth factor- and substance P-dependent neurogenic inflammation, which includes the prominent clustering of MHC class II+ cells. Because the contribution of dendritic cells (DCs) in response to stress is not well understood, we examined the role of DCs in neurogenic inflammation in murine skin using a well-established murine stress model. We show that sound stress increases the number of intradermal langerin+ and CD11c+ DCs and induces DC maturation, as indicated by the up-regulated expression of CD11c, MHC class II, and intercellular adhesion molecule-1 (ICAM-1). Blocking of ICAM-1/leukocyte function-associated antigen-1 interactions significantly abrogated the stress-induced numeric increase, maturation, and migration of dermal DCs in vivo and also reduced stress-induced keratinocyte apoptosis and endothelial cell expression of ICAM-1. In conclusion, stress exposure causes a state of immune alertness in the skin. Such adaptation processes may ensure protection from possible infections on wounding by stressors, such as attack by predators. However, present-day stressors have changed and such adaptations appear redundant and may overrun skin homeostasis by inducing immune dermatoses. PMID:18832583

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

    PubMed

    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.

  17. Differential vascular permeability along the forebrain ventricular neurogenic niche in the adult murine brain.

    PubMed

    Colín-Castelán, Dannia; Ramírez-Santos, Jesús; Gutiérrez-Ospina, Gabriel

    2016-02-01

    Adult neurogenesis is influenced by blood-borne factors. In this context, greater or lesser vascular permeability along neurogenic niches would expose differentially neural stem cells (NSCs), transit amplifying cells (TACs), and neuroblasts to such factors. Here we evaluate endothelial cell morphology and vascular permeability along the forebrain neurogenic niche in the adult brain. Our results confirm that the subventricular zone (SVZ) contains highly permeable, discontinuous blood vessels, some of which allow the extravasation of molecules larger than those previously reported. In contrast, the rostral migratory stream (RMS) and the olfactory bulb core (OBc) display mostly impermeable, continuous blood vessels. These results imply that NSCs, TACs, and neuroblasts located within the SVZ are exposed more readily to blood-borne molecules, including those with very high molecular weights, than those positioned along the RMS and the OBc, subregions in which every stage of neurogenesis also takes place. These observations suggest that the existence of specialized vascular niches is not a precondition for neurogenesis to occur; specialized vascular beds might be essential for keeping high rates of proliferation and/or differential differentiation of neural precursors located at distinct domains. © 2015 Wiley Periodicals, Inc.

  18. Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain

    PubMed Central

    Moszczynska, Anna; Flack, Amanda; Qiu, Ping; Muotri, Alysson R.; Killinger, Bryan A.

    2015-01-01

    Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum. PMID:26463126

  19. Selecting for neurogenic potential as an alternative for Alzheimer's disease drug discovery.

    PubMed

    Prior, Marguerite; Goldberg, Joshua; Chiruta, Chandramouli; Farrokhi, Catherine; Kopynets, Mariya; Roberts, Amanda J; Schubert, David

    2016-06-01

    Neurons die in Alzheimer's disease (AD) and are not effectively replaced. An alternative approach to maintain nerve cell number is to identify compounds that stimulate the proliferation of endogenous neural stem cells in old individuals to replace lost neurons. However, unless a neurogenic drug is also neuroprotective, the replacement of lost neurons will not be sufficient to stop disease progression. The neuroprotective AD drug candidate J147 is shown to enhance memory, improve dendritic structure, and stimulate cell division in germinal regions of the brains of very old mice. Based on the potential neurogenic potential of J147, a neuronal stem cell screening assay was developed to optimize derivatives of J147 for human neurogenesis. The best derivative of J147, CAD-031, maintains the neuroprotective and memory enhancing properties of J147, yet is more active in the human neural stem cell assays. The combined properties of neuroprotection, neurogenesis, and memory enhancement in a single drug are more likely to be effective for the treatment of age-associated neurodegenerative disorders than any individual activity alone. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  20. 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

  1. Repeated injections of intradetrusor onabotulinumtoxinA as adjunctive treatment of children with neurogenic bladder.

    PubMed

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

    2014-01-01

    To evaluate the effects of repeated injections of onabotulinumtoxinA in children with neurogenic bladders refractory to conventional treatment. A total of 26 children with neurogenic bladder were prospectively studied. Some patients received up to four repeat injections. Patients were reinjected if they showed improvement in voiding diary, score of urinary incontinence and/or urodynamic studies; otherwise, augmentation cystoplasty was indicated. Of the 26 patients, 12 were reinjected a second time, 6 patients were reinjected a third time and 2 patients received a repeat injection for the fourth time. Six months after the first, second and third injection, the urinary incontinence score 0 (dry) was 50, 77 and 75 %, respectively. After each injection, the mean bladder capacity in voiding diary and the mean maximum cystometric capacity increased. The mean detrusor pressure at the end of filling decreased. Only compliance after the first injection improved significantly. Detrusor overactivity (n: 4), improved during 3 months and reappeared in three children after the first injection, but at greater cystometric volumes. In the fourth case, it reappeared 11 months after the third injection. Five patients underwent cystoplasty. After treatment with onabotulinumtoxinA, urinary continence achieved was 50-77 %. There were favorable changes in urodynamic variables, but they were insufficient. Detrusor overactivity was attenuated, but did not disappear completely.

  2. Effects of carbonated liquids on oropharyngeal swallowing measures in people with neurogenic dysphagia.

    PubMed

    Sdravou, Katerina; Walshe, Margaret; Dagdilelis, Lukas

    2012-06-01

    Aspiration is common in adults with neurogenic dysphagia and pharyngeal delay. This can lead to dehydration, malnutrition, and aspiration pneumonia. Diet modifications aimed at reducing thin liquid aspiration are partially successful or unpalatable or both. Carbonated liquids show some potential in influencing swallowing behavior. However, there is a paucity of evidence to support this intervention. This study compares the effects of carbonated thin liquids (CTL) with that of noncarbonated thin liquids (NCTL) on oropharyngeal swallowing in adults with neurogenic dysphagia and examines the palatability of the CTL stimulus. Seventeen people with pharyngeal delay attended for videofluoroscopy (VFSS). Outcome measures were oral transit time (OTT), pharyngeal transit time (PTT), stage transition duration (STD), initiation of the pharyngeal swallow (IPS), penetration-aspiration scale (PENASP), and pharyngeal retention (PR). A modification of Quartermaster Hedonic Scale (AQHS) was employed to assess palatability of the CTL. CTL vs. NCTL significantly decreased penetration and aspiration on 5-ml (P = 0.028) and 10-ml (P = 0.037) swallows. CTL had no significant effect on OTT, PTT, IPS, and PR for any volume of bolus. Only one participant disliked the CTL stimulus. These findings support the hypothesis that oropharyngeal swallowing can be modulated in response to sensory stimuli. Implications for research and clinical practice are discussed.

  3. The effect of bolus viscosity on swallowing function in neurogenic dysphagia.

    PubMed

    Clavé, P; de Kraa, M; Arreola, V; Girvent, M; Farré, R; Palomera, E; Serra-Prat, M

    2006-11-01

    To assess the pathophysiology and treatment of neurogenic dysphagia. 46 patients with brain damage, 46 with neurodegenerative diseases and eight healthy volunteers were studied by videofluoroscopy while swallowing 3-20 mL liquid (20.4 mPa s), nectar (274.4 mPa s) and pudding (3931.2 mPa s) boluses. Volunteers presented a safe and efficacious swallow, short swallow response (< or =740 ms), fast laryngeal closure (< or =160 ms) and strong bolus propulsion (> or =0.33 mJ). Brain damage patients presented: (i) 21.6% aspiration of liquids, reduced by nectar (10.5%) and pudding (5.3%) viscosity (P < 0.05) and (ii) 39.5% oropharyngeal residue. Neurodegenerative patients presented: (i) 16.2% aspiration of liquids, reduced by nectar (8.3%) and pudding (2.9%) viscosity (P < 0.05) and (ii) 44.4% oropharyngeal residue. Both group of patients presented prolonged swallow response (> or =806 ms) with a delay in laryngeal closure (> or =245 ms), and weak bolus propulsion forces (< or =0.20 mJ). Increasing viscosity did not affect timing of swallow response or bolus kinetic energy. Patients with neurogenic dysphagia presented high prevalence of videofluoroscopic signs of impaired safety and efficacy of swallow, and were at high risk of respiratory and nutritional complications. Impaired safety is associated with slow oropharyngeal reconfiguration and impaired efficacy with low bolus propulsion. Increasing bolus viscosity greatly improves swallowing function in neurological patients.

  4. Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain.

    PubMed

    Moszczynska, Anna; Flack, Amanda; Qiu, Ping; Muotri, Alysson R; Killinger, Bryan A

    2015-10-14

    Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum.

  5. NFIX Regulates Proliferation and Migration Within the Murine SVZ Neurogenic Niche

    PubMed Central

    Heng, Yee Hsieh Evelyn; Zhou, Bo; Harris, Lachlan; Harvey, Tracey; Smith, Aaron; Horne, Elise; Martynoga, Ben; Andersen, Jimena; Achimastou, Angeliki; Cato, Kathleen; Richards, Linda J.; Gronostajski, Richard M.; Yeo, Giles S.; Guillemot, François; Bailey, Timothy L.; Piper, Michael

    2015-01-01

    Transcription factors of the nuclear factor one (NFI) family play a pivotal role in the development of the nervous system. One member, NFIX, regulates the development of the neocortex, hippocampus, and cerebellum. Postnatal Nfix−/− mice also display abnormalities within the subventricular zone (SVZ) lining the lateral ventricles, a region of the brain comprising a neurogenic niche that provides ongoing neurogenesis throughout life. Specifically, Nfix−/− mice exhibit more PAX6-expressing progenitor cells within the SVZ. However, the mechanism underlying the development of this phenotype remains undefined. Here, we reveal that NFIX contributes to multiple facets of SVZ development. Postnatal Nfix−/− mice exhibit increased levels of proliferation within the SVZ, both in vivo and in vitro as assessed by a neurosphere assay. Furthermore, we show that the migration of SVZ-derived neuroblasts to the olfactory bulb is impaired, and that the olfactory bulbs of postnatal Nfix−/− mice are smaller. We also demonstrate that gliogenesis within the rostral migratory stream is delayed in the absence of Nfix, and reveal that Gdnf (glial-derived neurotrophic factor), a known attractant for SVZ-derived neuroblasts, is a target for transcriptional activation by NFIX. Collectively, these findings suggest that NFIX regulates both proliferation and migration during the development of the SVZ neurogenic niche. PMID:25331604

  6. 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.

  7. Factors implicated in pathogenesis of urinary tract infections in neurogenic bladders: some revered, few forgotten, others ignored.

    PubMed

    Vasudeva, Pawan; Madersbacher, Helmut

    2014-01-01

    To comprehensively review factors implicated in the pathogenesis of urinary tract infection in patients with neurogenic bladders, and to stimulate research, especially in the somewhat ignored and forgotten areas of this important clinical subject. In addition to reviewing relevant articles on pubmed, some important articles from previous times which were not available online were also procured and reviewed. Intrinsic defence mechanisms including protective flora, anti-adherence mechanisms, urothelial, and immunological responses to bacterial binding and the blood supply to the urinary bladder may be impaired in patients with neurogenic bladders. Further, bacterial washout mechanisms may be compromised as a result of inefficient voiding, reflux, and altered hydrokinetics. Finally, catheterization itself contributes to urinary tract infection in patients with neurogenic bladders. In order to address the issue of urinary tract infection in patients with neurogenic bladders, multiple factors need to be looked into and corrected. Further research is required, especially in the area of compromised host defence mechanisms. An individualized approach, which attempts to optimize each factor is recommended. © 2013 Wiley Periodicals, Inc.

  8. Endoscopic gastrostomy for enteral nutrition in neurogenic dysphagia: Application of a nasogastric tube or percutaneous endoscopic gastrostomy.

    PubMed

    Maitines, Gennaro; Ugenti, Ippazio; Memeo, Riccardo; Clemente, Nicola; Iambrenghi, Onofrio Caputi

    2009-01-01

    Enteral nutrition can be administered via a nasogastric tube or, in selected patients, via a percutaneous endoscopic gastrostomy. In patients with neurogenic dysphagia, the choice of nutritional administration, and above all the timing, are crucial. Our aim was to retrospectively assess the impact of new guidelines for percutaneous endoscopic gastrostomy insertion adopted since January 2002 and compare them with our previous experience. From January 1992 to June 2007, 285 gastrostomies (168 M, 117 F) were positioned in our institute. We analysed 232 patients (139 M, 93 F) in whom a percutaneous endoscopic gastrostomy was applied for neurogenic dysphagia: Group A (from January 1992 to December 2001) consisting of 174 patients; Group B (from January 2002 to June 2007) consisting of 58 patients. The percutaneous endoscopic gastrostomy was positioned in all the cases with neurogenic dysphagia after a period of not less than 3 weeks of nutrition by nasogastric tube. A total of 6 major complications (2.3 %) occurred, almost all in group A. The mortality rate (3 patients, 2%) correlated with the complications in group A. In cases of neurogenic dysphagia we believe that greater methodological rigour in the multidisciplinary decision-making process, and a period of about 6-8 weeks' nutrition by nasogastric tube after the acute neurological damage may be useful to ensure a better prognostic evaluation of the patient and hence of the indications for percutaneous endoscopic gastrostomy.

  9. 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

  10. [Giant prostatic calculus with neurogenic bladder disease and prostate diverticulum: a case report and review of the literature].

    PubMed

    Li, Xiao-Shi; Quan, Chang-Yi; Li, Gang; Cai, Qi-Liang; Hu, Bin; Wang, Jiu-Wei; Niu, Yuan-Jie

    2013-02-01

    To study the etiology, clinical manifestation, diagnosis and treatment of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum. We retrospectively analyzed the clinical data of a case of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum and reviewed the relevant literature. The patient was a 37-year-old man, with urinary incontinence for 22 years and intermittent dysuria with frequent micturition for 9 years, aggravated in the past 3 months. He had received surgery for spina bifida and giant vesico-prostatic calculus. The results of preoperative routine urinary examination were as follows: WBC 17 -20/HPF, RBC 12 - 15/HPF. KUB, IVU and pelvic CT revealed spina bifida occulta, neurogenic bladder and giant prostatic calculus. The patient underwent TURP and transurethral lithotripsy with holmium-YAG laser. The prostatic calculus was carbonate apatite in composition. Urinary dynamic images at 2 weeks after surgery exhibited significant improvement in the highest urine flow rate and residual urine volume. Seventeen months of postoperative follow-up showed dramatically improved urinary incontinence and thicker urine stream. Prostate diverticulum with prostatic giant calculus is very rare, and neurogenic bladder may play a role in its etiology. Cystoscopy is an accurate screening method for its diagnosis. For the young patients and those who wish to retain sexual function, TURP combined with holmium laser lithotripsy can be employed, and intraoperative rectal examination should be taken to ensure complete removal of calculi.

  11. Neurogenic bladder

    MedlinePlus

    ... cause skin to break down and lead to pressure sores Kidney damage if the bladder becomes too full, ... dysfunction; NBSD Patient Instructions Multiple sclerosis - discharge Preventing pressure ulcers Images Voiding cystourethrogram References Chapple CR, Osman NI. ...

  12. Neurogenic Stuttering

    MedlinePlus

    ... may vary widely across individuals depending on the nature of the neurologic injury or disease. Can other ... of other communication and cognitive disorders and the nature of the individual’s underlying neurological condition. If other ...

  13. [Neurogenic dysphagia].

    PubMed

    Wirth, R; Dziewas, R

    2017-02-01

    Approximately half of neurological and geriatric inpatients suffer from oropharyngeal dysphagia. This often leads to pneumonia, malnutrition and dehydration; however, the underlying dysphagia is frequently not diagnosed and treated. This is particularly the case for patients with so-called silent aspiration. Knowledge on the physiology of swallowing, including the central nervous system control of swallowing and the therapeutic options have achieved considerable progress in recent years. In particular, the increasing implementation of flexible endoscopic evaluation of swallowing (FEES) has significantly contributed to this knowledge. It provides the ability to identify the individual pattern of oropharyngeal dysphagia leading to a suitable selection of therapeutic and compensatory strategies for individual patients. The various therapeutic options range from modification of the consistency of the diet, over diverse logopedic strategies and stimulation techniques up to interventional procedures.

  14. Semiconditional electrical stimulation of pudendal nerve afferents stimulation to manage neurogenic detrusor overactivity in patients with spinal cord injury.

    PubMed

    Lee, Young-Hee; Kim, Jung Moon; Im, Hyung Tae; Lee, Kye-Wook; Kim, Sung Hoon; Hur, Dong Min

    2011-10-01

    To evaluate the effect of semiconditional electrical stimulation of the pudendal nerve afferents for the neurogenic detrusor overactivity in patients with spinal cord injury. Forty patients (36 males, 4 males) with spinal cord injury who had urinary incontinence and frequency, as well as felt bladder contraction with bladder filling sense or autonomic dysreflexic symptom participated in this study. Patients with neurogenic detrusor overactivity were subdivided into complete injury and incomplete injury groups by ASIA classification and subdivided into tetraplegia and paraplegia groups by neurologic level of injury. Bladder function, such as bladder volumes infused to the bladder until the first occurrence of neurogenic detrusor overactivity (V(ini)) and the last contraction suppressed by electrical stimulation (V(max)) was measured by water cystometry (CMG) and compared with the results of each subgroup. Among the 40 subjects, 35 patients showed neurogenic detrusor overactivity in the CMG study. Among these 35 patients, detrusor overactivity was suppressed effectively by pudendal nerve afferent electrical stimulation in 32 patients. The infusion volume until the occurrence of the first reflex contraction (V(ini)) was 99.4±80.3 ml. The volume of saline infused to the bladder until the last contraction suppressed by semiconditional pudendal nerve stimulation (V(max)) was 274.3±93.2 ml, which was significantly greater than V(ini). In patients with good response to the pudendal nerve afferent stimulation, the bladder volume significantly increased by stimulation in all the patients. In this study, semiconditional electrical stimulation on the dorsal penile afferent nerve could effectively inhibit neurogenic detrusor overactivity and increase bladder volume in patients with spinal cord injury.

  15. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Effect of citric acid and citric acid-sucrose mixtures on swallowing in neurogenic oropharyngeal dysphagia.

    PubMed

    Pelletier, Cathy A; Lawless, Harry T

    2003-01-01

    The ability of sour and sweet-sour mixtures to improve swallowing in 11 nursing home residents with neurogenic oropharyngeal dysphagia was investigated using fiberoptic endoscopic evaluation of swallowing. Citric acid (2.7%) significantly reduced aspiration and penetration compared with water. Teaspoon delivery of liquids significantly reduced aspiration and penetration compared with natural cup drinking. Subjects tended to appropriately self-regulate the cup volume they consumed after the first trial. A significant increase in spontaneous dry swallows was observed after both taste stimuli. The mechanisms for improved swallowing due to citric acid are not understood but may be due to increased gustatory and trigeminal stimulation of acid to the brainstem in neurologically impaired subjects.

  7. Haemodynamic instability during thyroid surgery: a baroreflex-mediated neurogenic phenomenon?

    PubMed

    Nouraei, S A R; Davies, M R; Obholzer, R; Sandhu, G S; Porter, F

    2006-03-01

    We present a case of marked intra-operative blood pressure instability in a euthyroid, fit 33-year-old female undergoing elective hemithyroidectomy. This led to significant haemodynamic compromise, cardiac failure and end-organ damage. There was no evidence of a vasoactive endocrine cause, and the nature and timing of the event strongly pointed towards baroreflex-mediated neurogenic sympathetic dysfunction. This can occur during carotid surgery and neck dissection. Although haemodynamic fluctuations may happen during thyroid surgery, their severity in this case was unusual. We believe this could have been a rebound phenomenon in response to acute decompression of the carotid artery which had been compressed by an enlarging cyst. We suggest that in similar cases blockade of the carotid sinus could attenuate such responses.

  8. The physical and psychological impact of neurogenic claudication: the patients’ perspectives

    PubMed Central

    Ammendolia, Carlo; Schneider, Michael; Williams, Kelly; Zickmund, Susan; Hamm, Megan; Stuber, Kent; Tomkins-Lane, Christy; Rampersaud, Y Raja

    2017-01-01

    Background: The patient perspective regarding the impact of neurogenic claudication (NC) has not been well studied. The objectives of this study were to determine what is most bothersome among patients with NC and how it impacts their lives and expectations with surgical and non-surgical treatment. Methods: Semi-structured telephone interviews were conducted, audio recorded and transcribed verbatim. A thematic analysis categorized key findings based on relative importance and impact on participants. Results: Twenty-eight individuals participated in this study. Participants were most bothered by the pain of NC, which dramatically impacted their lives. Inability to walk was the dominant functional limitation and this impacted the ability to engage in recreational and social activities. The most surprising finding was how frequently participants reported significant emotional effects of NC. Conclusions: From a patients’ perspective NC has a significant multidimensional effects with pain, limited walking ability and emotional effects being most impactful to their lives. PMID:28413220

  9. 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

  10. 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.

  11. A randomized trial of clitoral vacuum suction versus vibratory stimulation in neurogenic female orgasmic dysfunction.

    PubMed

    Alexander, Marcalee; Bashir, Khurram; Alexander, Craig; Marson, Lesley; Rosen, Raymond

    2017-09-09

    To examine safety and efficacy of use of a clitoral vacuum suction device (CVSD) versus vibratory stimulation (V) to treat orgasmic dysfunction in women with MS or SCI. Randomized clinical trial. Two academic medical centers. Thirty-one women including 20 with MS and 11 with SCI. A 12-week trial of the use of a CVSD versus V MAIN OUTCOME MEASURES: Female Sexual Function Inventory (FSFI) and Female Sexual Distress Scale (FSDS). 23 women (18 MS; 5 SCI) completed the study including 13/16 randomized to CVSD and 10/15 randomized to V. There was a statistically significant increase in total FSFI score (p=.011), desire (p=. 009), arousal (p=.009), lubrication (p=.008), orgasm (p=.012), and satisfaction (p=.049) and a significant decrease in distress as measured by FSDS (p=.020) in subjects using the CVSD. In subjects who used V, there was a statistically significant increase in the orgasm subscale of the FSFI (p=.028). Subjects using the CVSD maintained improvements 4 weeks after treatment. CVSD is safe and overall efficacious to treat female neurogenic sexual dysfunction related to MS and SCI. V is also safe and efficacious to female neurogenic orgasmic dysfunction; however, results were limited to the active treatment period. Due to ease of access and cost, clinicians can consider use of V for women with MS or SCI with orgasmic dysfunction. CVSD is recommended for women with multiple sexual dysfunctions or for whom V is ineffective. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  12. 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.

  13. Use of botulinum toxin in individuals with neurogenic detrusor overactivity: State of the art review

    PubMed Central

    Linsenmeyer, Todd A.

    2013-01-01

    Background Botulinum neurotoxin (BoNT) injection into the bladder wall has been shown to be an effective alternative to anticholinergic (antimuscarinic) medications and more invasive surgery in those with multiple sclerosis and spinal cord injury with neurogenic detrusor overactivity (NDO) and urinary incontinence who are not tolerating anticholinergic medications. In August 2011, Botox® (onabotulinumtoxinA) received Food and Drug Administration (FDA) approval for this use. Clinically, intradetrusor injection of BoNT has been found to decrease urinary incontinence and improve quality of life. Its impact on urodynamic parameters is an increase in the maximum cystometric (bladder) capacity and decrease in the maximum detrusor pressures. The most common side effects are urinary tract infections and urinary retention. There have been rare reports and a black box warning of distant spread of BoNT. BoNT has gained popularity because of its effectiveness and long duration of action, relative ease of administration, easy learning curve, reproducibility of results on repeated administration, and low incidence of complications. Objective To discuss the structure and function, mechanisms of action, clinical and urodynamic studies, injection technique, potential beneficial and adverse effects, and potential areas of research of BoNT. Methods Literature search focused on botulinum toxin in MEDLINE/PubMed. Search terms included botulinum toxin, neurogenic bladder, NDO, botox bladder, botox spinal cord injury, botox, FDA, botox side effects. All papers identified were English language, full-text papers. In addition, English abstracts of non-English papers were noted. The reference list of identified articles was also searched for further papers. Conclusion Botulinum toxin is an alternative treatment for individuals with NDO who fail to tolerate anticholinergic medications. Its popularity has increased because of the literature, which has supported its effectiveness, safety, easy

  14. Stroke increases neural stem cells and angiogenesis in the neurogenic niche of the adult mouse.

    PubMed

    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.

  15. 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

  16. Oxygen Tension Within the Neurogenic Niche Regulates Dopaminergic Neurogenesis in the Developing Midbrain

    PubMed Central

    Wagenführ, Lisa; Meyer, Anne Karen; Marrone, Lara

    2016-01-01

    Oxygen tension is an important factor controlling stem cell proliferation and maintenance in various stem cell populations with a particular relevance in midbrain dopaminergic progenitors. Further studies have shown that the oxygen-dependent transcription factor hypoxia-inducible factor 1α (HIF-1α) is involved in these processes. However, all available studies on oxygen effects in dopaminergic neuroprogenitors were performed in vitro and thus it remains unclear whether tissue oxygen tension in the embryonic midbrain is also relevant for the regulation of dopaminergic neurogenesis in vivo. We thus dissect here the effects of oxygen tension in combination with HIF-1α conditional knockout on dopaminergic neurogenesis by using a novel experimental design allowing for the control of oxygen tension within the microenvironment of the neurogenic niche of the murine fetal midbrain in vivo. The microenvironment of the midbrain dopaminergic neurogenic niche was detected as hypoxic with oxygen tensions below 1.1%. Maternal oxygen treatment of 10%, 21%, and 75% atmospheric oxygen tension for 48 h translates into robust changes in fetal midbrain oxygenation. Fetal midbrain hypoxia hampered the generation of dopaminergic neurons and is accompanied with restricted fetal midbrain development. In contrast, induced hyperoxia stimulated proliferation and differentiation of dopaminergic progenitors during early and late embryogenesis. Oxygen effects were not directly mediated through HIF-1α signaling. These data—in agreement with in vitro data—indicate that oxygen is a crucial regulator of developmental dopaminergic neurogenesis. Our study provides the initial framework for future studies on molecular mechanisms mediating oxygen regulation of dopaminergic neurogenesis within the fetal midbrain as its natural environment. PMID:26577812

  17. 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

  18. Characteristics of neurogenic bowel in spinal cord injury and perceived quality of life.

    PubMed

    Pardee, Connie; Bricker, Diedre; Rundquist, Jeanine; MacRae, Christi; Tebben, Cherisse

    2012-01-01

    To investigate the association between characteristics of individuals with spinal cord injury and neurogenic bowel and their perceived quality of life. The study design is an exploratory, descriptive correlational design. To measure the variables of the study the Quality of Life Survey developed by Randell et al. (2001) was used to measure perceived quality of life related to bowel management. Individual bowel management preferences and subjective costs and benefits of the preferences were gathered through the Neurogenic Bowel Characteristics Survey. PARTICIPANTS/METHOD: Data were collected from a random half of the individuals who met the inclusion criteria from the patient database (n=1193). Two hundred and forty one surveys were analyzed for this study. More than half of the sample (n=134) provided their own bowel management consisting of digital stimulation, suppositories, and other aids; 8% (n=19) had a colostomy. Regardless of the bowel management program 54% (n=127) were satisfied with current methods. Although time reported to complete bowel programs ranged from 1 to 120 minutes, there was no difference in rating of satisfaction with time. There was a statistically significant difference between those satisfied and dissatisfied with current bowel management and quality of life; those satisfied demonstrated a higher quality of life on three subscales, work function (p= .021), bowel problems (p< .001), and social function (p< .001). Those dissatisfied with their bowel program perceived a lower quality of life and indicated problems of time (p= .001), pain or discomfort (p= .033), and poor results (p< .001). Research data provide the patient's perspective on bowel management characteristics, complications, satisfaction, and their perceived quality of life. Results of this research will be incorporated into bowel management education and possible modification of the current inpatient bowel management program. © 2012 Association of Rehabilitation Nurses.

  19. 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.

  20. Recurrent neurogenic thoracic outlet syndrome stressing the importance of pectoralis minor syndrome.

    PubMed

    Sanders, Richard J

    2011-01-01

    Although first described over 60 years ago, neurogenic pectoralis minor syndrome (NPMS) has only recently been noted to be present in over half the patients with a clinical diagnosis of neurogenic thoracic outlet syndrome (NTOS). Similarly, NPMS has also been observed in the majority of patients with recurrent NTOS. This study explores the role of pectoralis minor tenotomy (PMT) in patients with recurrent NTOS. A total of 86 patients with symptoms of recurrent NTOS, who had failed to improve on conservative management, were evaluated by history and physical examination for both NPMS and NTOS. Diagnostic tests included pectoralis minor muscle (PMM) blocks, scalene muscle blocks, and medial antebrachial cutaneous nerve (MAC) measurements. Surgery was either PMT alone or PMT plus brachial plexus decompression (BPD). Follow-up was 1 to 3 years. All patients had multiple symptoms of pain, weakness, and paresthesia. Patients who qualified for PMT alone had slightly fewer symptoms than those who required PMT plus BPD. There was essentially no difference in physical findings between the 2 groups. It was the response to PMM blocks and scalene muscle blocks that determined which of the 2 operations was performed. Pectoralis minor tenotomy alone gave 69% good results in 65 operations, with 8% fair and 23% failures. Pectoralis minor tenotomy plus BPD in 39 operations gave 58% good improvement, 20% fair and 22% failures. All patients with recurrent NTOS should be evaluated clinically for NPMS. If patients complain of pain or tenderness in the anterior chest wall and axilla, a diagnostic PMM block should be performed. A good response to the block suggests that consideration be given to performing PMT alone as it a simple, low-risk outpatient procedure. If unsuccessful, BPD can be performed at a later date. If there is a poor response to the PMM block, BPD is indicated along with PMT, provided there were some symptoms of NPMS.

  1. 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

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

    PubMed

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

    2015-01-01

    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). 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. 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. 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' understanding of their condition.

  3. 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

  4. A framework for transitioning patients from pediatric to adult health settings for patients with neurogenic bladder.

    PubMed

    Lewis, Jennifer; Frimberger, Dominic; Haddad, Emily; Slobodov, Gennady

    2017-04-01

    Adolescents with neurogenic bladder are a vulnerable population that severely lacks consistent transitional care from pediatric to adult urology settings. Our practice determined that 100 patients with spina bifida and other neurogenic bladder conditions were not appropriately transferred to the adult setting once reaching adulthood. We initiated a transitional program to establish a dedicated and formal process for adolescent patients to transition to adult urology. The REACH clinic implements a formalized staging framework to facilitate migration of adolescents and young adults to the adult health setting. A social worker was incorporated to act as a patient advocate, behavioral health consultant, and resource specialist. To date 45 patients have been enrolled in the transition program. We have identified and categorized according to the appropriate stage. The REACH clinic has appropriately outlined the goals and mission of the program and resources utilized are financially practical and feasible by conducting a monthly combined clinic. The program has been instrumental in improving tracking and monitoring of these patients through their transition period. Through the efforts of the pediatric and adult urology teams, the REACH program is a dedicated framework that provides structure for transition of the adolescent patient. The addition of a social worker has resulted in enriched rapport and will likely result in improved compliance. This program allows for surveillance and evaluation of patient outcome indicators in this patient population. We believe that early introduction and frequent encounters with the adult urologic team is crucial to successful transitions. Neurourol. Urodynam. 36:973-978, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. 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

  6. 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.

  7. Oxygen Tension Within the Neurogenic Niche Regulates Dopaminergic Neurogenesis in the Developing Midbrain.

    PubMed

    Wagenführ, Lisa; Meyer, Anne Karen; Marrone, Lara; Storch, Alexander

    2016-02-01

    Oxygen tension is an important factor controlling stem cell proliferation and maintenance in various stem cell populations with a particular relevance in midbrain dopaminergic progenitors. Further studies have shown that the oxygen-dependent transcription factor hypoxia-inducible factor 1α (HIF-1α) is involved in these processes. However, all available studies on oxygen effects in dopaminergic neuroprogenitors were performed in vitro and thus it remains unclear whether tissue oxygen tension in the embryonic midbrain is also relevant for the regulation of dopaminergic neurogenesis in vivo. We thus dissect here the effects of oxygen tension in combination with HIF-1α conditional knockout on dopaminergic neurogenesis by using a novel experimental design allowing for the control of oxygen tension within the microenvironment of the neurogenic niche of the murine fetal midbrain in vivo. The microenvironment of the midbrain dopaminergic neurogenic niche was detected as hypoxic with oxygen tensions below 1.1%. Maternal oxygen treatment of 10%, 21%, and 75% atmospheric oxygen tension for 48 h translates into robust changes in fetal midbrain oxygenation. Fetal midbrain hypoxia hampered the generation of dopaminergic neurons and is accompanied with restricted fetal midbrain development. In contrast, induced hyperoxia stimulated proliferation and differentiation of dopaminergic progenitors during early and late embryogenesis. Oxygen effects were not directly mediated through HIF-1α signaling. These data--in agreement with in vitro data-indicate that oxygen is a crucial regulator of developmental dopaminergic neurogenesis. Our study provides the initial framework for future studies on molecular mechanisms mediating oxygen regulation of dopaminergic neurogenesis within the fetal midbrain as its natural environment.

  8. 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

  9. Development of hydronephrosis secondary to poorly managed neurogenic bowel requiring surgical disimpaction in a patient with spinal cord injury: A case report

    PubMed Central

    Downs, Jairon; Wolfe, Tracy; Walker, Heather

    2014-01-01

    Context Case of an adult patient with paraplegia managing neurogenic bladder with intermittent catheterization who was not performing a standard bowel program for management of neurogenic bowel. Findings Patient presented with increasing spasticity, fecal incontinence, and abdominal pain and ultimately was hospitalized for management. Imaging revealed massive fecal impaction, resulting in ureteral obstruction and hydronephrosis. Despite repeated aggressive bowel regimens, serial abdominal X-rays showed continued large stool burden. Ultimately surgical intervention was required to evacuate the colon and subsequently the hydronephrosis resolved. Conclusion/Clinical relevance This case illustrates the importance of proper management of neurogenic bowel, as significant medical complications, such as hydronephrosis can occur with poorly managed neurogenic bowel. PMID:24617444

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Early Endovascular Treatment of Aneurysmal Subarachnoid Hemorrhage Complicated by Neurogenic Pulmonary Edema and Takotsubo-Like Cardiomyopathy

    PubMed Central

    Manto, Andrea; De Gennaro, Angela; Manzo, Gaetana; Serino, Antonietta; Quaranta, Gaetano; Cancella, Claudia

    2014-01-01

    Summary Aneurysmal subarachnoid hemorrhage (SAH) may be associated with acute cardiopulmonary complications, like neurogenic pulmonary edema (NPE) and Takotsubo-like cardiomyopathy (TCM). These dysfunctions seem to result from a neurogenically induced overstimulation of the sympathetic nervous system through the brain-heart connection and often complicate poor grade aneurysmal SAH. The optimal treatment modality and timing of intervention in this clinical setting have not been established yet. Early endovascular therapy seems to be the fitting treatment in this particular group of patients, in which surgical clipping is often contraindicated due to the added risk of craniotomy. Herein we describe the case of a woman admitted to the emergency department with aneurysmal SAH complicated by NPE-TCM, in which early endovascular coiling was successfully performed. Our case, characterized by a favorable outcome, further supports the evidence that early endovascular treatment should be preferred in this peculiar clinical scenario. PMID:24976204

  16. Early endovascular treatment of aneurysmal subarachnoid hemorrhage complicated by neurogenic pulmonary edema and Takotsubo-like cardiomyopathy.

    PubMed

    Manto, Andrea; De Gennaro, Angela; Manzo, Gaetana; Serino, Antonietta; Quaranta, Gaetano; Cancella, Claudia

    2014-06-01

    Aneurysmal subarachnoid hemorrhage (SAH) may be associated with acute cardiopulmonary complications, like neurogenic pulmonary edema (NPE) and Takotsubo-like cardiomyopathy (TCM). These dysfunctions seem to result from a neurogenically induced overstimulation of the sympathetic nervous system through the brain-heart connection and often complicate poor grade aneurysmal SAH. The optimal treatment modality and timing of intervention in this clinical setting have not been established yet. Early endovascular therapy seems to be the fitting treatment in this particular group of patients, in which surgical clipping is often contraindicated due to the added risk of craniotomy. Herein we describe the case of a woman admitted to the emergency department with aneurysmal SAH complicated by NPE-TCM, in which early endovascular coiling was successfully performed. Our case, characterized by a favorable outcome, further supports the evidence that early endovascular treatment should be preferred in this peculiar clinical scenario.

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

    PubMed

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

    2016-12-01

    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.

  18. [FEES for neurogenic dysphagia: training curriculum of the German Society of Neurology and the German Stroke Society].

    PubMed

    Dziewas, R; Glahn, J; Helfer, C; Ickenstein, G; Keller, J; Lapa, S; Ledl, C; Lindner-Pfleghar, B; Nabavi, D; Prosiegel, M; Riecker, A; Stanschus, S; Warnecke, T; Busse, O

    2014-08-01

    Neurogenic dysphagia is one of the most frequent and prognostically relevant neurological deficits in a variety of disorders, such as stroke, parkinsonism and advanced neuromuscular diseases. Flexible endoscopic evaluation of swallowing (FEES) is now probably the most frequently used tool for objective dysphagia assessment in Germany. It allows evaluation of the efficacy and safety of swallowing, determination of appropriate feeding strategies and assessment of the efficacy of different swallowing manoeuvres. The literature furthermore indicates that FEES is a safe and well-tolerated procedure. In spite of the huge demand for qualified dysphagia diagnostics in neurology, a systematic FEES education has yet not been established. The structured training curriculum presented in this article aims to close this gap and intends to enforce a robust and qualified FEES service. As management of neurogenic dysphagia is not confined to neurologists, this educational program is applicable to other clinicians and speech language therapists with expertise in dysphagia as well.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1

    PubMed Central

    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

    2007-01-01

    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 α,β-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. PMID:17684094

  4. 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

  5. New scenarios for neuronal structural plasticity in non-neurogenic brain parenchyma: the case of cortical layer II immature neurons.

    PubMed

    Bonfanti, Luca; Nacher, Juan

    2012-07-01

    The mammalian central nervous system, due to its interaction with the environment, must be endowed with plasticity. Conversely, the nervous tissue must be substantially static to ensure connectional invariability. Structural plasticity can be viewed as a compromise between these requirements. In adult mammals, brain structural plasticity is strongly reduced with respect to other animal groups in the phylogenetic tree. It persists under different forms, which mainly consist of remodeling of neuronal shape and connectivity, and, to a lesser extent, the production of new neurons. Adult neurogenesis is mainly restricted within two neurogenic niches, yet some gliogenic and neurogenic processes also occur in the so-called non-neurogenic tissue, starting from parenchymal progenitors. In this review we focus on a population of immature, non-newly generated neurons in layer II of the cerebral cortex, which were previously thought to be newly generated since they heavily express the polysialylated form of the neural cell adhesion molecule and doublecortin. These unusual neurons exhibit characteristics defining an additional type of structural plasticity, different from either synaptic plasticity or adult neurogenesis. Evidences concerning their morphology, antigenic features, ultrastructure, phenotype, origin, fate, and reaction to different kind of stimulations are gathered and analyzed. Their possible role is discussed in the context of an enriched complexity and heterogeneity of mammalian brain structural plasticity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. 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.

  7. [The Effectiveness of Abdominal Massage on Neurogenic Bowel Dysfunction in Patients With Spinal Cord Injury: A Systematic Review].

    PubMed

    Wu, Tzu-Jung; Lin, Chiu-Chu; Wang, Hsiu-Hung

    2017-02-01

    Neurogenic bowel dysfunction is a common comorbidity in spinal cord injury patients that may result in fecal incontinence. Abdominal massage is one intestinal training method that is used to improve bowel movement and defecation. To review the effectiveness of abdominal massage on neurogenic bowel dysfunction in patients with spinal cord injury. A systematic review of Chinese and English-language articles was performed in six databases using the following key words: spinal cord injury, abdominal massage, neurogenic bowel dysfunction, and bowel training. Relevant studies published prior to June 2016 that met the inclusion and exclusion criteria were selected. The Downs and Black scale was used to appraise the quality of each of the included studies. Eight studies were included in the final analysis. Four of these studies indicated that abdominal massage significantly improved bowel functions and the regularity and frequency of bowel movements. Although two of the studies indicated that abdominal massage significantly reduced the use of glycerin and laxatives, the remaining six did not. The eight studies earned respective quality scores ranging between 13 and 25. The current literature lacks consensus on the efficacy of abdominal massage in terms of improving bowel dysfunction in patients with spinal cord injuries. Future studies should use more stringent experimental designs such as randomized controlled studies to explore the correlations among massage time and frequency and bowel function improvements in order to provide guidelines for clinical care applications.

  8. 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.

  9. 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.

  10. Noninvasive Evaluation of Cellular Proliferative Activity in Brain Neurogenic Regions in Rats under Depression and Treatment by Enhanced [18F]FLT-PET Imaging.

    PubMed

    Tamura, Yasuhisa; Takahashi, Kayo; Takata, Kumi; Eguchi, Asami; Yamato, Masanori; Kume, Satoshi; Nakano, Masayuki; Watanabe, Yasuyoshi; Kataoka, Yosky

    2016-08-03

    Neural stem cells in two neurogenic regions, the subventricular zone and the subgranular zone (SGZ) of the hippocampal dentate gyrus, can divide and produce new neurons throughout life. Hippocampal neurogenesis is related to emotions, including depression/anxiety, and the therapeutic effects of antidepressants, as well as learning and memory. The establishment of in vivo imaging for proliferative activity of neural stem cells in the SGZ might be used to diagnose depression and to monitor the therapeutic efficacy of antidepressants. Positron emission tomography (PET) imaging with 3'-deoxy-3'-[(18)F]fluoro-l-thymidine ([(18)F]FLT) has been studied to allow visualization of proliferative activity in two neurogenic regions of adult mammals; however, the PET imaging has not been widely used because of lower accumulation of [(18)F]FLT, which does not allow quantitative assessment of the decline in cellular proliferative activity in the SGZ under the condition of depression. We report the establishment of an enhanced PET imaging method with [(18)F]FLT combined with probenecid, an inhibitor of drug transporters at the blood-brain barrier, which can allow the quantitative visualization of neurogenic activity in rats. Enhanced PET imaging allowed us to evaluate reduced cell proliferation in the SGZ of rats with corticosterone-induced depression, and further the recovery of proliferative activity in rats under treatment with antidepressants. This enhanced [(18)F]FLT-PET imaging technique with probenecid can be used to assess the dynamic alteration of neurogenic activity in the adult mammalian brain and may also provide a means for objective diagnosis of depression and monitoring of the therapeutic effect of antidepressant treatment. Adult hippocampal neurogenesis may play a role in major depression and antidepressant therapy. Establishment of in vivo imaging for hippocampal neurogenic activity may be useful to diagnose depression and monitor the therapeutic efficacy of

  11. Drug development for pediatric neurogenic bladder dysfunction: dosing, endpoints, and study design.

    PubMed

    Momper, Jeremiah D; Karesh, Alyson; Green, Dionna J; Hirsch, Mark; Khurana, Mona; Lee, Jinoo; Kim, Myong-Jin; Mulugeta, Yeruk; Sachs, Hari C; Yao, Lynne; Burckart, Gilbert J

    2014-11-01

    Pediatric drug development is challenging when a product is studied for a pediatric disease that has a different underlying etiology and pathophysiology compared to the adult disease. Neurogenic bladder dysfunction (NBD) is such a therapeutic area with multiple unsuccessful development programs. The objective of this study was to critically evaluate clinical trial design elements that may have contributed to unsuccessful drug development programs for pediatric NBD. Trial design elements of drugs tested for pediatric NBD were identified from trials submitted to the U.S. Food and Drug Administration. Data were extracted from publically available FDA reviews and labeling and included trial design, primary endpoints, enrollment eligibilities, and pharmacokinetic data. A total of four products were identified. Although all four programs potentially provided clinically useful information, only one drug (oxybutynin) demonstrated efficacy in children with NBD. The lack of demonstrable efficacy for the remainder of the products illustrates that future trials should give careful attention to testing a range of doses, using objectively measured, clinically meaningful endpoints, and selecting clinical trial designs that are both interpretable and feasible. Compiling the drug development experience with pediatric NBD will facilitate an improved approach for future drug development for this, and perhaps other, therapeutic areas. © 2014, The American College of Clinical Pharmacology.

  12. 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.

  13. 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

  14. 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

  15. ECG abnormalities predict neurogenic pulmonary edema in patients with subarachnoid hemorrhage.

    PubMed

    Chen, Wei-Lung; Huang, Chi-Hung; Chen, Jiann-Hwa; Tai, Henry Chih-Hung; Chang, Su-Hen; Wang, Yung-Cheng

    2016-01-01

    The study aims to assess if electrocardiographic (ECG) abnormalities could predict the development of neurogenic pulmonary edema (NPE) within 24 hours in cases of spontaneous subarachnoid hemorrhage (SAH). We studied prospectively a cohort of 269 adult patients with nontraumatic SAH in an emergency department of a university-affiliated medical center. A 12-lead ECG was taken for these patients. The patients were stratified into NPE and non-NPE based on serially clinical and radiologic findings. The ECG abnormalities were compared between these 2 groups of patients. Compared with the non-NPE (n = 229), the NPE (n = 40) had significantly higher World Federation of Neurological Surgeons class (P < .001), higher Hunt-Hess scale (P < .001), and higher prevalence of diabetes mellitus (P = .033). In addition, the percentage of ECG morphological abnormality was significantly higher in NPE, in which nonspecific ST- or T-wave changes (NSSTTCs) are significantly higher. Multiple logistic regression model identified World Federation of Neurological Surgeons class (95% confidence interval [CI], 2.6-13.3; P < .001), abnormal Q or QS wave (95% CI, 1.1-9.1; P = .038), and NSSTTCs (95% CI, 1.2-7.5; P = .016) as the significant variables associated with NPE. Electrocardiographic abnormalities, especially abnormal Q or QS wave and NSSTTCs, may predict the development of NPE within 24 hours in adult patients with spontaneous SAH. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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

  17. Optimal treatment for severe neurogenic bowel dysfunction after chronic spinal cord injury: a decision analysis.

    PubMed

    Furlan, J C; Urbach, D R; Fehlings, M G

    2007-09-01

    When conservative management fails in patients with chronic spinal cord injury (SCI) and neurogenic bowel dysfunction, clinicians have to choose from a variety of treatment options which include colostomy, ileostomy, Malone anterograde continence enema (MACE) and sacral anterior root stimulator (SARS) implantation. This study employed a decision analysis to examine the optimal treatment for bowel management of young individuals with chronic refractory constipation in the setting of chronic SCI. A decision analysis was created to compare the four surgical strategies using baseline analysis, one-way and two-way sensitivity analyses, 'worst scenario' and 'best scenario' sensitivity analyses, and probabilistic sensitivity analyses. Quality-adjusted life expectancy (QALE) was the primary outcome. The baseline analysis indicated that patients who underwent the MACE procedure had the highest QALE value compared with the other interventions. Sensitivity analyses showed that these results were robust. The MACE procedure may provide the best long-term outcome in terms of the probability of improving bowel function, reducing complication rates and the incidence of autonomic dysreflexia, and being congruent with patients' preferences. The analysis was sensitive to changes in assumptions about quality of life/utility, and thus the results could change if more specific estimates of utility became available. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  18. 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

  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. 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

  1. Submental sensitive transcutaneous electrical stimulation (SSTES) at home in neurogenic oropharyngeal dysphagia: a pilot study.

    PubMed

    Verin, E; Maltete, D; Ouahchi, Y; Marie, J-P; Hannequin, D; Massardier, E Guegan; Leroi, A-M

    2011-09-01

    Oropharyngeal dysphagia is frequent in chronic neurological disorders and increases mortality, mainly due to pulmonary complications. Our aim was to show that submental sensitive transcutaneous electrical stimulation (SSTES) applied during swallowing at home can improve swallowing function in patients with chronic neurological disorders. Thirteen patients were recruited for the study (4 f, 68 ± 12 years). They all suffered from neurogenic oropharyngeal dysphagia. We first compared the swallowing of paste and liquid with and without SSTES. Thereafter, the patients were asked to perform SSTES at home with each meal. Swallowing was evaluated before and after six weeks of SSTES using the SWAL-QoL questionnaire. With the stimulator switch turned on, swallowing coordination improved, with a decrease in swallow reaction time for the liquid (P<0.05) and paste boluses (P<0.01). Aspiration scores also decreased significantly with the electrical stimulations (P<0.05), with no change in stasis. At-home compliance was excellent and most patients tolerated the electrical stimulations with no discomfort. A comparison of the SWAL-QoL questionnaires after 6 weeks revealed an improvement in the burden (P=0.001), fatigue (P<0.05), and pharyngeal symptom (P<0.001) scales. The present study demonstrated that SSTES is easy to use at home and improves oropharyngeal dysphagia quality of life. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  2. 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

  3. Lamivudine/telbivudine-associated neuromyopathy: neurogenic damage, mitochondrial dysfunction and mitochondrial DNA depletion

    PubMed Central

    Xu, Hongliang; Wang, Zhaoxia; Zheng, Lemin; Zhang, Wei; Lv, He; Jin, Suqin; Yuan, Yun

    2014-01-01

    Aims Myopathy or neuropathy has been associated with lamivudine/telbivudine therapy in hepatitis B patients. We aim to describe the pathological changes of lamivudine/telbivudine-associated neuromyopathy. Methods We retrospectively recruited six patients who were diagnosed with nucleotide analogues-associated myopathy or neuropathy. Muscle and nerve biopsy were performed, and the specimens were prepared for the light microscopy and electron microscopy. Genomic DNA was extracted from frozen muscle specimens, and the mitochondrial DNA (mtDNA) content was quantified by real-time PCR. Results Recovery of the myopathy can be achieved after the discontinuation or changing the drugs to entecavir. Muscle and nerve biopsy revealed similar changes under either the light or electronic microscopy in all the subjects. Quantitative real-time PCR revealed decrease of mtDNA content in the affected muscle. Conclusions MtDNA depletion results in mitochondrial dysfunction in the lamivudine/telbivudine-associated neuromyopathy. Myopathy was characterised by mitochondrial dysfunction accompanied with neurogenic damage due to axonal neuropathy. Ultrastructure changes of mitochondria included vacuolisation, simplification of the cristae and homogenised matrix. PMID:25190818

  4. 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

  5. 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

  6. 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

  7. Facial vein in the rabbit. Neurogenic vasodilation mediated by beta-adrenergic receptors.

    PubMed

    Pegram, B L; Bevan, R D; Bevan, J A

    1976-12-01

    A segment of the facial vein of the rabbit, that opposite the buccal cavity, responds to norepinephrine (NE) and opposite the buccal cavity, responds to norepinephrine (NE) and transmural nerve stimulation (TNS) by a brisk biphasic dilation. The dilation in response to both procedures is reveresed by prior exposure to propranolol (10(-6)M). Pretreatment with phenoxybenzamine (10(-5)M) increases the size of the neurogenic response and displaces the NE dose-relaxation curve to the left. Histamine causes a constrictor response exclusively. Sympathetic stimulation of a segment of the facial vein proximal to this buccal segment, and also of the external jugular vein, results in constriction. Light microscopy showed no fequtres which can account for the dilation, and fluorescence histochemistry using a modified Flack technique showed a dense adrenergic nerve plexus extending throughout the thickness of the media. We found that frequency-response characteristics and neuronal uptake of 3H-NE were consistent with findings for a blood vessel with a heavy medial innervation. Also, monoamine oxidase and catechol O-methyltransferase activities were similar to those found in other rabbit veins. Furthermore, these results are consistent with an adrenergic neuroeffector organization in which there is a predominance of beta- over alpha-adrenergic receptors. In conclusion, the presence of a dilator response in this buccal segment of the facial vein may be related to its location in the wall of the cheek, where it may be subjected to considerable stretch.

  8. Compilation of a preliminary checklist for the differential diagnosis of neurogenic stuttering.

    PubMed

    Lundie, Mariska; Erasmus, Zandria; Zsilavecz, Ursula; Van der Linde, Jeannie

    2014-06-27

    Neurogenic stuttering (NS) is the most frequently occurring acquired form of stuttering in children and adults. This form of stuttering is primarily caused by neurological incidents. Owing to controversies with regard to similarities between developmental stuttering (DS) and NS symptomatology, differential diagnosis is problematic. Differential diagnosis will guide the appropriate management of persons who stutter (PWS). The aim of this study was to describe and highlight the characteristics of NS in order to compile a preliminary checklist for accurate diagnosis and intervention. An explorative, applied mixed method, multiple case study research design was followed. Purposive sampling was used to select four participants. A comprehensive assessment battery was compiled for data collection. The results revealed a distinct pattern of core stuttering behaviours in NS, although discrepancies existed regarding stuttering severity and frequency. It was also found that DS and NS can co-occur. The case history and the core stuttering pattern are important considerations during differential diagnosis, as these are the only consistent characteristics in people with NS. It is unlikely that all the symptoms of NS are present in an individual. The researchers scrutinised the findings of this study and the findings of previous literature to compile a potentially workable checklist.

  9. 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.

  10. 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

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

    PubMed Central

    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. PMID:24445575

  12. Novel genetic and neuropathological insights in neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP).

    PubMed

    Claeys, Kristl G; Abicht, Angela; Häusler, Martin; Kleinle, Stephanie; Wiesmann, Martin; Schulz, Jörg B; Horvath, Rita; Weis, Joachim

    2016-08-01

    Neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) is caused by m.8993T>G/C mutations in the mitochondrial adenosine triphosphate synthase subunit 6 gene (MT-ATP6). Traditionally, heteroplasmy levels between 70% and 90% lead to NARP, and >90% result in Leigh syndrome. In this study we report a 30-year-old man with NARP and m.8993T>G in MT-ATP6. Although the patient carried the mutation in homoplasmic state in blood with similarly high levels in urine (94%) and buccal swab (92%), he presented with NARP and not the expected, more severe Leigh phenotype. The mutation could not be detected in any of the 3 analyzed tissues of the mother, indicating a large genetic shift between mother and offspring. Nerve biopsy revealed peculiar endoneurial Schwann cell nuclear accumulations, clusters of concentrically arranged Schwann cells devoid of myelinated axons, and degenerated mitochondria. We emphasize the phenotypic variability of the m.8993T>G MT-ATP6 mutation and the need for caution in predictive counseling in such patients. Muscle Nerve 54: 328-333, 2016. © 2016 Wiley Periodicals, Inc.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24952232

  14. 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.

  15. Therapeutic and protective effect of environmental enrichment against psychogenic and neurogenic stress.

    PubMed

    Fox, Cosette; Merali, Zul; Harrison, Catherine

    2006-11-25

    Environmental enrichment (EE) has beneficial neurobiological, physiological and behavioral effects. The purpose of the present paper is to review the animal research literature pertaining to the impact of EE on altering physiological and behavioral anxiety outcomes. Evidence supports the view that EE attenuates responses to certain anxiety provoking situations, and that these effects persist over time. Specifically, EE attenuates behavioral anxiety-type responses and endocrine responses mediated via the hypothalamic-pituitary-adrenal (HPA) axis evoked by psychogenic and/or neurogenic stressors. EE is not only able to protect from excessive anxiety in response to a present stressor, but also attenuates the enduring or persistent effects engendered by past psychogenic stressor(s) such as prenatal stress or neonatal maternal separation. It is noteworthy that the protective effects of EE are particularly apparent in animals that are highly anxious or when the task is highly challenging for the subject. Various mechanisms of action of EE have been proposed, ranging from behavioral/cognitive to cellular/molecular processes. A pronounced variability in the enrichment protocols used by different investigators may account for some of the inconsistencies noted in the effect of EE on behavioral (e.g. anxiety) and endocrine (e.g. plasma corticosterone) responses. Although the occasional inconsistencies highlight the need for further research, a preponderance of the animal research data indicates that EE exerts therapeutic and protective (anxiolytic) effects against (a) impending threat, (b) enduring effects of past stressor(s) and (c) subsequent stressors.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. The Intensive Dysphagia Rehabilitation Approach Applied to Patients With Neurogenic Dysphagia: A Case Series Design Study.

    PubMed

    Malandraki, Georgia A; Rajappa, Akila; Kantarcigil, Cagla; Wagner, Elise; Ivey, Chandra; Youse, Kathleen

    2016-04-01

    To examine the effects of the Intensive Dysphagia Rehabilitation approach on physiological and functional swallowing outcomes in adults with neurogenic dysphagia. Intervention study; before-after trial with 4-week follow-up through an online survey. Outpatient university clinics. A consecutive sample of subjects (N=10) recruited from outpatient university clinics. All subjects were diagnosed with adult-onset neurologic injury or disease. Dysphagia diagnosis was confirmed through clinical and endoscopic swallowing evaluations. No subjects withdrew from the study. Participants completed the 4-week Intensive Dysphagia Rehabilitation protocol, including 2 oropharyngeal exercise regimens, a targeted swallowing routine using salient stimuli, and caregiver participation. Treatment included hourly sessions twice per week and home practice for approximately 45 min/d. Outcome measures assessed pre- and posttreatment included airway safety using an 8-point Penetration Aspiration Scale, lingual isometric pressures, self-reported swallowing-related quality of life (QOL), and level of oral intake. Also, patients were monitored for adverse dysphagia-related effects. QOL and adverse effects were also assessed at the 4-week follow-up (online survey). The Intensive Dysphagia Rehabilitation approach was effective in improving maximum and mean Penetration Aspiration Scale scores (P<.05, η(2)=.8146 and P<.05, η(2)=.799708, respectively) and level of oral intake (P<.005, Cohen d=-1.387). Of the 5 patients who were feeding tube dependent initially, 2 progressed to total oral nutrition, and 2 progressed to partial oral nutrition. One patient remained tube dependent. QOL was significantly improved at the 4-week follow-up (95% confidence interval, 6.38-14.5; P<.00), but not at the posttreatment. No adverse effects were observed/reported. The Intensive Dysphagia Rehabilitation approach was safe and improved physiological and some functional swallowing outcomes in our sample; however

  3. Diagnostic value of "dysphagia limit" for neurogenic dysphagia: 17 years of experience in 1278 adults.

    PubMed

    Aydogdu, Ibrahim; Kiylioglu, Nefati; Tarlaci, Sultan; Tanriverdi, Zeynep; Alpaydin, Sezin; Acarer, Ahmet; Baysal, Leyla; Arpaci, Esra; Yuceyar, Nur; Secil, Yaprak; Ozdemirkiran, Tolga; Ertekin, Cumhur

    2015-03-01

    Neurogenic dysphagia (ND) is a prevalent condition that accounts for significant mortality and morbidity worldwide. Screening and follow-up are critical for early diagnosis and management which can mitigate its complications and be cost-saving. The aims of this study are to provide a comprehensive investigation of the dysphagia limit (DL) in a large diverse cohort and to provide a longitudinal assessment of dysphagia in a subset of subjects. We developed a quantitative and noninvasive method for objective assessment of dysphagia by using laryngeal sensor and submental electromyography. DL is the volume at which second or more swallows become necessary to swallow the whole amount of bolus. This study represents 17 years experience with the DL approach in assessing ND in a cohort of 1278 adult subjects consisting of 292 healthy controls, 784 patients with dysphagia, and 202 patients without dysphagia. A total of 192 of all patients were also reevaluated longitudinally over a period of 1-19 months. DL has 92% sensitivity, 91% specificity, 94% positive predictive value, and 88% negative predictive value with an accuracy of 0.92. Patients with ALS, stroke, and movement disorders have the highest sensitivity (85-97%) and positive predictive value (90-99%). The clinical severity of dysphagia has significant negative correlation with DL (r=-0.67, p<0.0001). We propose the DL as a reliable, quick, noninvasive, quantitative test to detect and follow both clinical and subclinical dysphagia and it can be performed in an EMG laboratory. Our study provides specific quantitative features of DL test that can be readily utilized by the neurologic community and nominates DL as an objective and robust method to evaluate dysphagia in a wide range of neurologic conditions. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  4. Parents of children with neurogenic bowel dysfunction: their experiences of using transanal irrigation with their child.

    PubMed

    Sanders, C; Bray, L; Driver, C; Harris, V

    2014-11-01

    Neurogenic bowel dysfunction in children is a lifelong condition often resulting in the need for active bowel management programmes, such as transanal irrigation. Parents are central in the decision-making process to initiate and carry out treatments until such a time their child becomes independent. Minimal research has focussed on examining parents' experiences of undertaking transanal irrigation with their child. This study aimed to explore parents' experiences of learning about and using irrigation with their child and how parents motivated their children to become independent. Semi-structured telephone interviews were conducted with parents with experience of using transanal irrigation with their child. Interviews were undertaken by a parent researcher. Data were analysed using qualitative content analysis. Eighteen telephone interviews (16 mothers, 1 father and 1 carer) were conducted. Parents shared how they had negotiated getting started and using transanal irrigation with their child. They discussed a sense of success derived from their confidence in using and mastering irrigation, the process of making decisions to continue or stop using irrigation and how they motivated themselves and their child to continue with the irrigation regime. Challenges included minimizing their child's distress during the irrigation procedure and how they negotiated and moved towards their child becoming independent. Despite the emotional difficulty parents experienced as a result of the invasive nature of transanal irrigation most parents reported an improvement in their child's faecal continence which positively impacted on the child and family's lives. The child's physical ability and emotional readiness to develop independent irrigation skills in the future concerned some parents. The experiences shared by parents in this study has the capacity to inform transanal irrigation nursing and medical care. © 2013 John Wiley & Sons Ltd.

  5. 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.

  6. OnabotulinumtoxinA for neurogenic detrusor overactivity and dose differences: a systematic review

    PubMed Central

    Zhang, Rui; Xu, Yongteng; Yang, Shengping; Liang, Hui; Zhang, Yunxin; Liu, Yali

    2015-01-01

    Purpose To evaluate the efficacy and safety of onabotulinumtoxinA for patients with neurogenic detrusor overactivity (NDO). Materials and Methods We searched the Cochrane Library, PUBMED, EMBASE, Chinese Bio-medicine database, China Journal Full-text Database, VIP database, Wanfang database for randomized controlled trials (from inception to September 2012). Two authors independently selected studies, extracted data and assessed the methodological and evidence quality using the Cochrane Risk of Bias Table and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) respectively. Data analysis was performed by RevMan 5.1 and descriptive analysis was employed if necessary. Results Eight studies were selected (n=1879 participants). OnabotulinumtoxinA was more related to urinary tract infection (UTI) (200U: OR 1.72, CI: 1.18-2.52; 300U: OR 1.88, CI: 1.31-2.69) versus placebo. Also, OnabotulinumtoxinA was superior to placebo in improving maximum cystometric capacity (MCC) (200U: OR 138.80, CI: 112.45-165.15; 300U: OR 152.09, CI: 125.25-178.93) and decreasing maximum detrusor pressure (MDP) (200U: MD -29.61, CI: -36.52--22.69; 300U: MD-28.92, CI: -39.59--18.25). However, there were no statistical differences between 200U and 300U onabotulinumtoxinA in UTI (OR 0.84, CI: 0.58-1.22), MCC (OR-12.72, CI: -43.36-17.92) and MDP (MD 2.21, CI: -6.80-11.22). Conclusions OnabotulinumtoxinA may provide superior clinical and urodynamic benefit for populations with NDO. High-quality studies are required for evaluating the optimal dose, long-term application and when to perform repeated injections. PMID:26005961

  7. Neurogenic pulmonary edema in patients with nontraumatic intracerebral hemorrhage: predictors and association with outcome.

    PubMed

    Junttila, Eija; Ala-Kokko, Tero; Ohtonen, Pasi; Vaarala, Anne; Karttunen, Ari; Vuolteenaho, Olli; Salo, Tuula; Sutinen, Meeri; Karhu, Toni; Herzig, Karl-Heinz; Koskenkari, Juha

    2013-04-01

    Neurogenic pulmonary edema (NPE) is a well-recognized phenomenon after intracranial insult. In this study, we evaluated the predictors for NPE and its association with outcome in patients with intensive care unit-treated nontraumatic intracranial hemorrhage. This was a prospective, observational clinical study in a university-level intensive care unit. Clinical characteristics, level of consciousness, and Acute Physiology and Chronic Health Evaluation (APACHE) II score were recorded on admission and the findings of primary head computed tomography were reviewed. A chest radiograph and arterial blood gas analysis were taken serially and NPE was determined as acute bilateral infiltrates in chest radiograph and hypoxemia. Echocardiography and cardiac and inflammatory markers were recorded. The 1-year outcome was assessed using the Glasgow Outcome Scale. NPE developed in 38 (35%) of the 108 patients included. Predictors for NPE were higher APACHE II score (≥20, odds ratio 6.17, P = 0.003) and higher interleukin-6 plasma concentration (>40 pg/mL, odds ratio 5.62, P = 0.003). Of patients with 0, 1, or 2 predictors mentioned above, 4%, 37%, and 65% had NPE, respectively. NPE was associated with a higher 1-year mortality (37% vs 14%, P = 0.007, respectively), but with an unchanged functional outcome after 1 year (Glasgow Outcome Scale score 1-3, 53% vs 51%, P > 0.9). Predictors for NPE are the severity of disease defined by APACHE II scores and higher levels of systemic inflammatory mediators. NPE is associated with a higher 1-year mortality, but not with a poorer 1-year functional outcome.

  8. An electrophysiological approach to the diagnosis of neurogenic dysphagia: implications for botulinum toxin treatment.

    PubMed

    Alfonsi, E; Merlo, I M; Ponzio, M; Montomoli, C; Tassorelli, C; Biancardi, C; Lozza, A; Martignoni, E

    2010-01-01

    Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle has been proposed for the treatment of neurogenic dysphagia due to CP hyperactivity. The aim was to determine whether an electrophysiological method exploring oropharyngeal swallowing could guide treatment and discriminate responders from non-responders, based on the association of CP dysfunction with other electrophysiological abnormalities of swallowing. Patients with different neurological disorders were examined: Parkinson disease, progressive supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system atrophy cerebellar variant, stroke, multiple sclerosis and ataxia telangiectasia. All patients presented with clinical dysphagia, and with complete absence of CP muscle inhibition during the hypopharyngeal phase of swallowing. Each patient underwent clinical and electrophysiological investigations before and after treatment with BTX into the CP muscle of one side (15 units of Botox). Clinical and electrophysiological procedures were performed in a blind manner by two different investigators. The following electrophysiological measures were analysed: (1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); (2) duration of laryngopharyngeal mechanogram (LPM-D); (3) duration of the inhibition of the CP muscle EMG activity (CPEMG-ID); and (4) interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngopharyngeal mechanogram (I-SHEMG-LPM). Two months after treatment, 50% of patients showed a significant improvement. Patients with prolonged or reduced SHEMG-D values and prolonged I-SHEMG-LPM values did not respond to BTX. Therefore, values for which BTX had no effect (warning values) were identified. This electrophysiological method can recognise swallowing abnormalities which may affect the outcome of the therapeutic approach to dysphagia with BTX treatment.

  9. Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado.

    PubMed

    Miller, M J; Vergnolle, N; McKnight, W; Musah, R A; Davison, C A; Trentacosti, A M; Thompson, J H; Sandoval, M; Wallace, J L

    2001-09-01

    This study was designed to determine if the Amazonian medicinal sangre de grado, confers benefit by suppressing the activation of sensory afferent nerves. (i) vasorelaxation of rat mesenteric arteries in response to calcitonin gene-related peptide; (ii) rat paw edema in response to protease- activating peptide receptor 2-activating peptide; (iii) rat paw hyperalgesia in response to low-dose protease-activating peptide receptor 2-activating peptide or prostaglandin E2; (iv) gastric hyperemia in response luminal capsaicin; (v) a clinical trial of a sangre de grado balm in pest control workers. The parent botanical was fractionated for evaluation of potential active components. In preconstricted rat mesenteric arteries, highly diluted sangre de grado (1:10,000) caused a shift to the right of the calcitonin gene-related peptide dose-response curve (p < 0.01). Paw edema in response to protease-activating peptide receptor 2-activating peptide (500 microg) was reduced by as single topical administration sangre de grado balm (1% concentration, p < 0.01) for at least 6 h. Hyperalgesia induced by either low-dose protease-activating peptide receptor 2-activating peptide (50 microg) or prostaglandin E2 was prevented by sangre de grado balm. A fraction possessing analgesic and capsaicin antagonistic properties was isolated and high-performance liquid chromatography and gas chromatography-mass spectrometry analysis indicated that it was a proanthocyandin oligomer. In pest control workers, sangre de grado balm (Zangrado) was preferred over placebo, for the relief of itching, pain, discomfort, edema, and redness in response to wasps, fire ants, mosquitoes, bees, cuts, abrasions, and plant reactions. Subjects reported relief within minutes. We conclude that sangre de grado is a potent inhibitor of sensory afferent nerve mechanisms and supports its ethnomedical use for disorders characterized by neurogenic inflammation.

  10. The expression of neurogenic markers after neuronal induction of chorion-derived mesenchymal stromal cells.

    PubMed

    Manochantr, Sirikul; Marupanthorn, Kulisara; Tantrawatpan, Chairat; Kheolamai, Pakpoom

    2015-06-01

    Chorion is a tissue of early embryologic period that is discarded after delivery. It might be the potential source of mesenchymal stromal cells (MSCs) that can be used for research and eventually for therapeutic studies. At present, the biological properties and the differentiation capacity of chorion-derived MSCs are still poorly characterised. The objective of this study is to characterise and explore the differentiating potential of chorion-derived MSCs towards the neuronal lineages. Chorionic membrane was digested with enzyme and cultured in Dulbecco's Modified Eagle's medium supplemented with 10% fetal bovine serum. The expression of MSC markers was examined using flow cytometry. The adipogenic, osteogenic and neurogenic differentiation were examined by culturing in appropriate induction media. The expression of neuronal markers was determined by immunofluorescence and quantitative real time-PCR. Chorion-derived MSCs were easily expanded up to 20 passages. They were positive for MSC markers (CD73, CD90 and CD105), and negative for haematopoietic markers (CD34 and CD45). Chorion-derived MSCs could differentiate into several mesodermal-lineages including adipocytes and osteoblasts. Moreover, chorion-derived MSCs could differentiate into neuronal-like cells as characterised by cell morphology and the presence of neural markers including MAP-2, glial fibrillary acidic protein (GFAP) and beta-tubulin III. Chorion-derived MSCs can be readily obtained and expanded in culture. These cells also have transdifferentiation capacity as evidenced by their neuronal differentiation potential. Therefore, chorion can be used as an alternative source of MSCs for stem cell therapy in nervous system disorders.

  11. 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.

  12. Selective Deletion of the Brain-Specific Isoform of Renin Causes Neurogenic Hypertension.

    PubMed

    Shinohara, Keisuke; Liu, Xuebo; Morgan, Donald A; Davis, Deborah R; Sequeira-Lopez, Maria Luisa S; Cassell, Martin D; Grobe, Justin L; Rahmouni, Kamal; Sigmund, Curt D

    2016-12-01

    The renin-angiotensin system (RAS) in the brain is a critical determinant of blood pressure, but the mechanisms regulating RAS activity in the brain remain unclear. Expression of brain renin (renin-b) occurs from an alternative promoter-first exon. The predicted translation product is a nonsecreted enzymatically active renin whose function is unknown. We generated a unique mouse model by selectively ablating the brain-specific isoform of renin (renin-b) while preserving the expression and function of the classical isoform expressed in the kidney (renin-a). Preservation of renal renin was confirmed by measurements of renin gene expression and immunohistochemistry. Surprisingly, renin-b-deficient mice exhibited hypertension, increased sympathetic nerve activity to the kidney and heart, and impaired baroreflex sensitivity. Whereas these mice displayed decreased circulating RAS activity, there was a paradoxical increase in brain RAS activity. Physiologically, renin-b-deficient mice exhibited an exaggerated depressor response to intracerebroventricular administration of losartan, captopril, or aliskiren. At the molecular level, renin-b-deficient mice exhibited increased expression of angiotensin-II type 1 receptor in the paraventricular nucleus, which correlated with an increased renal sympathetic nerve response to leptin, which was dependent on angiotensin-II type 1 receptor activity. Interestingly, despite an ablation of renin-b expression, expression of renin-a was significantly increased in rostral ventrolateral medulla. These data support a new paradigm for the genetic control of RAS activity in the brain by a coordinated regulation of the renin isoforms, with expression of renin-b tonically inhibiting expression of renin-a under baseline conditions. Impairment of this control mechanism causes neurogenic hypertension. © 2016 American Heart Association, Inc.

  13. 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.

  14. 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

  15. A sphingosine 1-phosphate 1 receptor agonist modulates brain death-induced neurogenic pulmonary injury.

    PubMed

    Sammani, Saad; Park, Ki-Sung; Zaidi, Syed R; Mathew, Biji; Wang, Ting; Huang, Yong; Zhou, Tong; Lussier, Yves A; Husain, Aliya N; Moreno-Vinasco, Liliana; Vigneswaran, Wickii T; Garcia, Joe G N

    2011-11-01

    Lung transplantation remains the only viable therapy for patients with end-stage lung disease. However, the full utilization of this strategy is severely compromised by a lack of donor lung availability. The vast majority of donor lungs available for transplantation are from individuals after brain death (BD). Unfortunately, the early autonomic storm that accompanies BD often results in neurogenic pulmonary edema (NPE), producing varying degrees of lung injury or leading to primary graft dysfunction after transplantation. We demonstrated that sphingosine 1-phosphate (S1P)/analogues, which are major barrier-enhancing agents, reduce vascular permeability via the S1P1 receptor, S1PR1. Because primary lung graft dysfunction is induced by lung vascular endothelial cell barrier dysfunction, we hypothesized that the S1PR1 agonist, SEW-2871, may attenuate NPE when administered to the donor shortly after BD. Significant lung injury was observed after BD, with increases of approximately 60% in bronchoalveolar lavage (BAL) total protein, cell counts, and lung tissue wet/dry (W/D) weight ratios. In contrast, rats receiving SEW-2871 (0.1 mg/kg) 15 minutes after BD and assessed after 4 hours exhibited significant lung protection (∼ 50% reduction, P = 0.01), as reflected by reduced BAL protein/albumin, cytokines, cellularity, and lung tissue wet/dry weight ratio. Microarray analysis at 4 hours revealed a global impact of both BD and SEW on lung gene expression, with a differential gene expression of enriched immune-response/inflammation pathways across all groups. Overall, SEW served to attenuate the BD-mediated up-regulation of gene expression. Two potential biomarkers, TNF and chemokine CC motif receptor-like 2, exhibited gene array dysregulation. We conclude that SEW-2871 significantly attenuates BD-induced lung injury, and may serve as a potential candidate to improve human donor availability.

  16. Factors that influence the urodynamic results of botulinum toxin in the treatment of neurogenic hyperactivity.

    PubMed

    Gutiérrez-Martín, P; Vírseda-Chamorro, M; Salinas Casado, J; Gómez-Rodríguez, A; Esteban-Fuertes, M

    2015-05-01

    To determine the urodynamic efficacy and factors that influence the urodynamic results of treatment of neurogenic detrusor hyperactivity with intradetrusor injection of botulinum toxin type A (BTX-A) in patients with spinal cord injury (SCI). A retrospective study was conducted with a cohort of 70 patients composed of 40 men and 30 women with stable SCI (mean age, 39 ± 13.3 years) who underwent an intradetrusor injection of 300 IUs of BTX-A. A urodynamic study was conducted prior to the injection and 6 ± 4.3 months after the treatment. New urodynamic studies were subsequently performed up to an interval of 16 ± 12.2 months. The BTX-A significantly increased (p < .05) the cystomanometric bladder capacity, the bladder volume of the first involuntary contraction of the detrusor and the postvoid residue. We observed a decrease that tended towards statistical significance (p < .1) of the maximum detrusor pressure and the maximum urine flow. Neither the bladder accommodation nor the urethral resistance index (bladder outlet obstruction index) varied significantly. The increase in vesical capacity was maintained in 50% of the sample for more than 32 months. Age, sex, anticholinergic treatment and lesion age showed no influence in terms of the increase in bladder capacity. The indwelling urinary catheter (IUC) was the only statistically significant negative factor. The urodynamic effect of BTX-A is maintained for a considerable time interval. The IUC negatively influences the result of the treatment. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. 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

  18. Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin.

    PubMed

    Peyronnet, Benoit; Castel-Lacanal, Evelyne; Manunta, Andréa; Roumiguié, Mathieu; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

    2015-12-01

    To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results. © 2015 The Japanese Urological Association.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Button Cystostomy: Is it Really a Safe and Effective Therapeutic Option in Pediatric Patients With Neurogenic Bladder?

    PubMed

    Mosiello, Giovanni; Lopes Mendes, Ana Ludy; Capitanucci, Maria Luisa; Zaccara, Antonio Maria; De Gennaro, Mario

    2017-03-01

    To define safety and effectiveness of cystostomy button in the management of bladder drainage in pediatric patients with neurogenic bladder, and report our personalized surgical technique. This study is a retrospective analysis of patients undergoing cystostomy button placement for bladder drainage from October 2009 to December 2015. Endoscopic and open surgical techniques and medium-term complication were analyzed and indications were recorded. Thirty-five patients, 16 (45.7%) females and 19 (54.3%) males, underwent cystostomy button placement for bladder drainage with a mean age of 8.6 ± 4.8 years (standard deviation) and a mean follow-up time of 37 months. There were 91.4% of patients who had a neurogenic bladder; a nonobstructive urinary retention was diagnosed in the remainder of cases. A medium-term complication was mostly represented by urinary tract infection observed in 10 of 35 patients that was the most representative cause of button removal (4 of 35). Other observed complications were button leakage (n = 2), decubitus (n = 1), and bladder stone (n = 1). No postoperative complication was observed and no differences were found in terms of complications in the two surgical approaches performed. Cystostomy button is a safe and effective treatment for bladder drainage in neurogenic pediatric patients and it is also well accepted by patients and caregivers. Cystostomy button, which may avoid mechanical concerns and most of the social discomfort, should be considered an alternative method to other bladder drainage modalities. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. EAU Guidelines on the Assessment of Non-neurogenic Male Lower Urinary Tract Symptoms including Benign Prostatic Obstruction.

    PubMed

    Gratzke, Christian; Bachmann, Alexander; Descazeaud, Aurelien; Drake, Marcus J; Madersbacher, Stephan; Mamoulakis, Charalampos; Oelke, Matthias; Tikkinen, Kari A O; Gravas, Stavros

    2015-06-01

    Lower urinary tract symptoms (LUTS) represent one of the most common clinical complaints in adult men and have multifactorial aetiology. To develop European Association of Urology (EAU) guidelines on the assessment of men with non-neurogenic LUTS. A structured literature search on the assessment of non-neurogenic male LUTS was conducted. Articles with the highest available level of evidence were selected. The Delphi technique consensus approach was used to develop the recommendations. As a routine part of the initial assessment of male LUTS, a medical history must be taken, a validated symptom score questionnaire with quality-of-life question(s) should be completed, a physical examination including digital rectal examination should be performed, urinalysis must be ordered, post-void residual urine (PVR) should be measured, and uroflowmetry may be performed. Micturition frequency-volume charts or bladder diaries should be used to assess male LUTS with a prominent storage component or nocturia. Prostate-specific antigen (PSA) should be measured only if a diagnosis of prostate cancer will change the management or if PSA can assist in decision-making for patients at risk of symptom progression and complications. Renal function must be assessed if renal impairment is suspected from the history and clinical examination, if the patient has hydronephrosis, or when considering surgical treatment for male LUTS. Uroflowmetry should be performed before any treatment. Imaging of the upper urinary tract in men with LUTS should be performed in patients with large PVR, haematuria, or a history of urolithiasis. Imaging of the prostate should be performed if this assists in choosing the appropriate drug and when considering surgical treatment. Urethrocystoscopy should only be performed in men with LUTS to exclude suspected bladder or urethral pathology and/or before minimally invasive/surgical therapies if the findings may change treatment. Pressure-flow studies should be performed

  7. 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.

  8. Aspiration in children and adolescents with neurogenic dysphagia: comparison of clinical judgment and fiberoptic endoscopic evaluation of swallowing.

    PubMed

    Beer, Sabrina; Hartlieb, Till; Müller, Arnd; Granel, Michael; Staudt, Martin

    2014-12-01

    A total of 30 children and adolescents with dysphagia due to various chronic neurological disorders were assessed for their risk of aspiration. This assessment was performed clinically by experienced speech and swallowing therapists, and verified thereafter by fiberoptic endoscopy. We found the clinical judgment to be correct in only 70% (for aspiration of saliva), 55% (of puree), and 67% (of thin liquids). We conclude that, because of this unacceptably high error rate of clinical assessment, a fiberoptic evaluation of swallowing is a necessary diagnostic step both for the planning of therapy and for the development of feeding strategies in children and adolescents with neurogenic dysphagia. Georg Thieme Verlag KG Stuttgart · New York.

  9. Effect of Alpha-1-Adrenergic Agonist, Midodrine for the Management of Long-Standing Neurogenic Shock in Patient with Cervical Spinal Cord Injury: A Case Report

    PubMed Central

    Kim, Taikwan

    2015-01-01

    We report a rare case of a 71-year-old male patient who had suffered from long-lasting neurogenic shock for 13 weeks after cervical spinal cord injury (SCI) caused by a bicycle accident. The neurogenic shock was resolved dramatically 2 weeks after the administration of alpha-1-adrenergic agonist, midodrine hydrochloride. In usual cases, neurogenic shock tends to improve between 2 and 6 weeks after SCI; however, in a few cases, the shock lasts for several months. In our case, spinal shock lasted for 13 weeks and exhibited very sensitive decline of blood pressure for even a slight decrease of dopamine despite recovered bulbospongiosus reflex. Three days after midodrine hydrochloride was added, hypotension improved dramatically. We discuss our rare case with pertinent literatures. PMID:27169082

  10. Long-term anodal block stimulation at sacral anterior roots promoted recovery of neurogenic bladder function in a rabbit model of complete spinal cord injury☆

    PubMed Central

    Wang, Xiaoran; Gao, Qi; Yang, Xiaoyu; Wang, Weihua; Gu, Xinquan; Liu, Guifeng; Yan, Peng; Gao, Ge; Yu, Xin; Wang, Yongjie; Lian, Jihu; Shi, Chaoling; Wang, Yao; Fan, Li

    2012-01-01

    A complete spinal cord injury model was established in experimental rabbits using the spinal cord clip compression method. Urodynamic examination was performed 2 weeks later to determine neurogenic bladder status. The rabbits were treated with anodal block stimulation at sacral anterior roots for 4 weeks. Electrical stimulation of sacral anterior roots improved urodynamic parameters of neurogenic bladder in rabbit models of complete spinal cord injury, effectively promoted urinary function, and relieved urinary retention. Immunohistochemistry results showed that a balance was achieved among expression of muscarinic receptor subunits M2, M3, ATP-gated ion channel P2X3 receptors, and β2-adrenergic receptor, and nerve growth factor expression decreased. These results suggested that long-term sacral anterior root stimulation of anodal block could be used to treat neurogenic bladder in a rabbit model of complete spinal cord injury. PMID:25774174

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

    PubMed

    Wang, Ye; Wang, Desheng; Guo, Dawen

    2016-01-01

    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). 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. 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. 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.

  12. 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

  13. Treatment of facet cysts associated with neurogenic intermittent claudication with x-stop.

    PubMed

    Abrams, Joshua; Hsu, Ken; Kondrashov, Dimitri; McDermott, Tim; Zucherman, James

    2013-06-01

    Facet degeneration often leads to the formation of synovial facet cysts. As facet cysts invade the spinal canal, they become a contributing factor to spinal stenosis. Previous studies have demonstrated successful treatment of neurogenic intermittent claudication (NIC), a major symptom of spinal stenosis, with an interspinous process device. To compare clinical outcomes of patients with and without synovial facet cysts treated with an interspinous process device. Retrospective review of prospective data of consecutive patients undergoing the X-Stop procedure at an institution. Visual Analog Scale; Oswestry Disability Index; sitting, standing, and walking tolerances; and satisfaction survey. Review of all patients from 2006 to 2010 undergoing X-Stop procedure at an institution. Imaging studies were used to identify the presence and measure the size of the facet cysts in 285 patients with a minimum of 6-month follow-up. Comparative clinical outcomes determined if X-Stop is a successful treatment option for patients with NIC in conjunction with synovial facet cysts (<3 mm, ≥3 mm). Fifty-eight of 285 patients (20.4%) were determined to have a synovial cyst as a contributing component of spinal stenosis. Twelve of 58 patients were noted to have a cyst ≥3 mm. The mean follow-up time for patients with and without a facet cyst was 21 months (6-55±12 mo) and 22 months (6-61±12 mo), respectively. The age of the patient at the time of the operation with and without facet cysts was 73 (±10 y). Patients without synovial cysts, with synovial cysts, and cysts ≥3 mm had an average change in Oswestry Disability Index of 15.6, 15.8, and 16.2, respectively. Visual Analog Scale scores were 2.3, 1.8, and 2.3, respectively. In addition, on satisfaction surveys 72.4%, 82.0%, and 77.8% were either very or somewhat satisfied, respectively. Overall complications included 4 spinous process fracture, 4 hematomas, 1 wound infection, and 1 implant migration. No statistical difference

  14. OnabotulinumtoxinA improves quality of life in patients with neurogenic detrusor overactivity

    PubMed Central

    Patel, Vaishali; Leng, Wendy W.; Shenot, Patrick J.; Lam, Wayne; Globe, Denise R.; Loeb, Alex L.; Chapple, Christopher R.

    2013-01-01

    Objective: To evaluate the effects of onabotulinumtoxinA on patient-reported outcomes including health-related quality of life (HRQOL), treatment satisfaction, and treatment goal attainment in patients with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO). Methods: In this multicenter, double-blind, randomized, placebo-controlled, phase III, 52-week study (ClinicalTrials.gov NCT00311376), patients with UI due to NDO who were not adequately managed with anticholinergic therapy were treated with intradetrusor injections of onabotulinumtoxinA (200 or 300 U) or placebo (0.9% saline). HRQOL measures included the Incontinence Quality of Life (I-QOL) Questionnaire total score, and the 3 domain scores (avoidance and limiting behavior, psychosocial, and social embarrassment), the modified Overactive Bladder Patient Satisfaction with Treatment Questionnaire (OAB-PSTQ), and Patient Global Assessment. Assessments were made at baseline, posttreatment week 6 (primary time point), week 12, and at 12-week intervals. Results: Patients (mean age of 46 years with 30.5 weekly UI episodes at baseline) were randomized to receive placebo (n = 149) or onabotulinumtoxinA (200 U [n = 135] or 300 U [n = 132]). At week 6, improvements from baseline in I-QOL Questionnaire total score were greater (p < 0.001) in both onabotulinumtoxinA-treated groups vs placebo. Responses to the OAB-PSTQ also demonstrated greater mean improvements from baseline (p < 0.001) in both onabotulinumtoxinA-treated groups vs placebo at week 6. Patients who received onabotulinumtoxinA also reported greater improvement in the Patient Global Assessment than those in the placebo group (p ≤ 0.001 vs placebo). Conclusions: Patients with UI due to NDO reported greater improvement in HRQOL and treatment satisfaction with onabotulinumtoxinA than with placebo consistently across several patient-reported outcome instruments. Classification of evidence: This study provides Class I evidence that

  15. Minimal effective dose of dysport and botox in a rat model of neurogenic detrusor overactivity.

    PubMed

    Behr-Roussel, Delphine; Oger, Stéphanie; Pignol, Bernadette; Pham, Emmanuel; Le Maux, Amélie; Chabrier, Pierre-Etienne; Caisey, Stéphanie; Compagnie, Sandrine; Picaut, Philippe; Bernabé, Jacques; Alexandre, Laurent; Giuliano, François; Denys, Pierre

    2012-05-01

    Two botulinum toxins A have been evaluated for the treatment of refractory neurogenic detrusor overactivity (NDO) in humans: Dysport (abobotulinumtoxinA) and Botox (onabotulinumtoxinA). However, these two distinct commercialized products have different potency units and are not interchangeable. Assessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord-injured (SCI) rats with NDO. Female, adult, Sprague-Dawley rats (n=98) underwent T8-T9 spinal cord transection. Nineteen days after spinal cord injury, rats received intradetrusor injections (25μl injected, eight sites) of vehicle (V); Dysport 2, 5, 7.5, 10, and 12.5 U; and Botox 0.8, 2, 5, 7.5, and 10 U. Two days after injection, continuous cystometry was performed in conscious rats. Voiding contractions (VC) were assessed by duration of VC, intercontraction interval, voided volume, maximal pressure, pressure threshold change, and intravesical baseline pressure (BP), while nonvoiding contractions (NVC) were evaluated by amplitude, frequency, and volume threshold to elicit NVC. MEDs for Dysport and Botox were determined by analysis of variance step-down trend test. MEDs for Dysport and Botox were 10 U and 7.5 U, respectively. Regarding VC, only BP significantly decreased after 10 U Dysport and 7.5 U Botox compared to V (from 3.7±0.6 to 1.5±0.1 and 1.4±0.3mm Hg, respectively; p<0.01 and p<0.001, respectively). Dysport (10 U) and Botox (7.5 U) significantly inhibited NVC by decreasing their amplitude (from 7.4±1.1 to 5.8±0.5 and 5.4±0.6mm Hg, respectively; p<0.05); frequency (from 2.2±0.4 to 1.5±0.2 and 1.3±0.3 NVC per minute, respectively; p<0.01); and increasing volume threshold to elicit NVC (from 29.8±3.7 to 47.6±6.9 and 47.7±6.3%, respectively; p<0.05 and p<0.001, respectively). This is the first preclinical dose-ranging study with Dysport and Botox under standardized conditions showing similar inhibiting effects on NDO, albeit at different

  16. Inhibitory effect of neurogenic and immune stressors on testosterone secretion in rats.

    PubMed

    Rivier, Catherine

    2002-01-01

    We investigated the ability of foot shocks, endotoxemia and turpentine-induced tissue injury, to interfere with luteinizing hormone (LH) and testosterone (T) secretion, and the putative role of beta-adrenergic, opiate- and corticotropin-releasing factor (CRF) receptors in these responses. Adult male rats were exposed to mild intermittent foot shocks for 1 h, administered endotoxin [lipopolysaccharide (LPS)] intravenously (i.v., 5 microg/kg), or injected with turpentine intradermally (i.m., 400 microl/kg), prior to injection with human chorionic gonadotropin (hCG, 1 U/kg i.v.). In some cases, antagonists to CRF, adrenergic or opiate receptors, or their vehicle were administered prior to the stressors. Levels of LH, T, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), adrenocorticotropin (ACTH) and/or corticosterone were measured in serial blood samples. All three challenges significantly lowered basal LH and T levels and blunted the T response to hCG, though the magnitude of this inhibition was significantly (p < 0.01) smaller in shocked rats (42%), compared to animals injected with LPS (92%) or turpentine (78%). Shocks, LPS and turpentine all significantly stimulated ACTH and corticosterone release, and the magnitude and time course of these responses were also stressor specific. While turpentine only increased circulating IL-6 concentrations, shocks and LPS both significantly increased circulating TNF-alpha and IL-6 levels, but the effect of shocks was markedly smaller. Pretreatment with propranolol did not restore T responses, while naloxone produced small and inconsistent effects. However, the CRF antagonist Astressin B, which significantly prevented stressor-induced increase in circulating levels of ACTH and corticosterone, partially reversed the inhibitory effect of LPS on hCG-induced T release. (1) Both neurogenic and systemic stressors lower basal plasma LH and T levels and blunt the T response to hCG. (2) LPS, whose ability to release ACTH and

  17. Supraclavicular decompression for neurogenic thoracic outlet syndrome in adolescent and adult populations.

    PubMed

    Caputo, Francis J; Wittenberg, Anna M; Vemuri, Chandu; Driskill, Matthew R; Earley, Jeanne A; Rastogi, Rahul; Emery, Valerie B; Thompson, Robert W

    2013-01-01

    This study was conducted to better define clinical results and understand factors determining responsiveness to surgical treatment for neurogenic thoracic outlet syndrome (NTOS) in adolescent and adult populations. A retrospective review was conducted for 189 patients with disabling NTOS who underwent primary supraclavicular decompression (scalenectomy, brachial plexus neurolysis and first rib resection, with or without pectoralis minor tenotomy) from April 2008 to December 2010. Clinical characteristics were compared between 35 adolescent patients (aged<21 years) and 154 adults (aged>21 years). Functional outcome measures were assessed before surgery and at 3- and 6-month follow-up using a composite NTOS Index combining the Disabilities of the Arm, Shoulder and Hand (DASH) survey, the Cervical-Brachial Symptom Questionnaire (CBSQ), and a 10-point visual analog scale (VAS) for pain. Adolescent and adult patients were not significantly different with respect to sex (overall 72.5% female), side affected (58.7% right, 60.3% dominant limb), bony anomalies (23.3%), previous injury (55.6%), coexisting pain disorders (11.1%), and positive responses to scalene muscle anesthetic blocks (95.6%). Compared with adults, adolescent patients had a significantly (P<.05) lower incidence of depression (11.4% vs 41.6%), motor vehicle injury (5.7% vs 20.1%), previous operations (11.4% vs 29.9%), preoperative use of opiate medications (17.1% vs 44.8%), and symptom duration>2 years (24.2% vs 50.0%). Mean preoperative NTOS Index (scale 0-100) was significantly lower in adolescent vs adult patients (46.5±3.6 vs 58.5±1.7; P=.009), and hospital length of stay was 4.4±0.2 vs 4.9±0.1 days (P=.03), but the rate of postoperative complications was no different (overall, 4.2%). Although both groups exhibited significant improvement in functional outcome measures at 3 and 6 months, adolescent patients had significantly lower NTOS Index (10.4±3.1 vs 39.3±3.3; P<.001) and use of opiate

  18. Performance Metrics in Professional Baseball Pitchers before and after Surgical Treatment for Neurogenic Thoracic Outlet Syndrome.

    PubMed

    Thompson, Robert W; Dawkins, Corey; Vemuri, Chandu; Mulholland, Michael W; Hadzinsky, Tyler D; Pearl, Gregory J

    2017-02-01

    High-performance throwing athletes may be susceptible to the development of neurogenic thoracic outlet syndrome (NTOS). This condition can be career-threatening but the outcomes of treatment for NTOS in elite athletes have not been well characterized. The purpose of this study was to utilize objective performance metrics to evaluate the impact of surgical treatment for NTOS in Major League Baseball (MLB) pitchers. Thirteen established MLB pitchers underwent operations for NTOS between July 2001 and July 2014. For those returning to MLB, traditional and advanced (PitchF/x) MLB performance metrics were acquired from public databases for various time-period scenarios before and after surgery, with comparisons made using paired t-tests, Wilcoxon matched-pair signed-rank tests, and Kruskal-Wallis analysis of variance. Ten of 13 pitchers (77%) achieved a sustained return to MLB, with a mean age of 30.2 ± 1.4 years at the time of surgery and 10.8 ± 1.5 months of postoperative rehabilitation before the return to MLB. Pre- and postoperative career data revealed no significant differences for 15 traditional pitching metrics, including earned run average (ERA), fielding independent pitching, walks plus hits per inning pitched (WHIP), walks per 9 innings, and strikeouts to walk ratio (SO/BB). There were also no significant differences between the 3 years before and the 3 years after surgical treatment. Using PitchF/x data for 72 advanced metrics and 25 different time-period scenarios, the highest number of significant relationships (n = 18) was observed for the 8 weeks before/12 weeks after scenario. In this analysis, 54 (75%) measures were unchanged (including ERA, WHIP, and SO/BB) and 14 (19%) were significantly improved, while only 4 (6%) were significantly decreased (including hard pitch maximal velocity 93.1 ± 1.0 vs. 92.5 ± 0.9 miles/hr, P = 0.047). Six pitchers remained active in MLB during the study period, while the other 4 had retired due to

  19. Anticholinergic drugs for adult neurogenic detrusor overactivity: a systematic review and meta-analysis.

    PubMed

    Madhuvrata, Priya; Singh, Manju; Hasafa, Zaid; Abdel-Fattah, Mohamed

    2012-11-01

    There is a lack of evidence about the efficacy and safety of anticholinergic drugs and about the optimal anticholinergic drug, if any, for the treatment of adult neurogenic detrusor overactivity (NDO). Review the current evidence on the efficacy, safety, and tolerability of anticholinergic drugs in the treatment of adult NDO. A literature search was conducted from 1966 to May 2011. Meta-analysis of all published randomised controlled trials (RCTs) comparing anticholinergic drugs with placebo and comparing different types, doses, and routes of administration of anticholinergic drugs, in adults with NDO, was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The primary outcome was patient-reported cure/improvement of overactive bladder symptoms. Secondary outcomes were quality of life (QoL) changes, bladder diary events, urodynamic outcomes, adverse events, and costs to health services. A total of 960 patients from 16 RCTs with mean follow-up of 3.8 wk were included. Anticholinergic drugs were associated with statistically significantly better patient-reported cure/improvement (risk ratio: 2.80; 95% confidence interval [CI], 1.64 to 4.77), higher maximum cystometric capacity (weighted mean difference [WMD]: 49.49; 95% CI, 15.38 to 84.20), higher volume at first contraction (WMD: 49.92; 95% CI, 20.06 to 79.78), and lower maximum detrusor pressure (WMD: -38.30; 95% CI, -53.17 to -23.43) when compared with placebo. The dry-mouth rates were statistically significantly higher with anticholinergics, with no difference in withdrawals because of adverse events. There was no statistically significant difference in any of the outcomes between oxybutynin and other anticholinergics or among different doses and preparations of anticholinergic drugs. No study reported QoL changes or costs to health services. Compared with placebo, anticholinergic treatment in patients with NDO is associated with better patient

  20. [Definition of botulinum toxin failure in neurogenic detrusor overactivity: Preliminary results of the DETOX survey].

    PubMed

    Peyronnet, B; Sanson, S; Amarenco, G; Castel-Lacanal, E; Chartier-Kastler, E; Charvier, K; Damphousse, M; Denys, P; de Seze, M; Egon, G; Even, A; Forin, V; Karsenty, G; Kerdraon, J; le Normand, L; Loche, C-M; Manunta, A; Mouracade, P; Phe, V; Previnaire, J-G; Ruffion, A; Saussine, C; Schurch, B; Game, X

    2015-12-01

    There is currently no guideline regarding the management of neurogenic detrusor overactivity (NDO) refractory to intra-detrusor botulinum toxin injections. The primary objective of the present study was to find a consensus definition of failure of botulinum toxin intra-detrusor injections for NDO. The secondary objective was to report current trends in the managment of NDO refractory to botulinum toxin. A survey was created, based on data drawn from current literature, and sent via e-mail to all the experts form the Group for research in neurourology in french language (GENULF) and from the comittee of neurourology of the French urological association (AFU). The experts who did not answer to the first e-mail were contacted again twice. Main results from the survey are presented and expressed as numbers and proportions. Out of the 42 experts contacted, 21 responded to the survey. Nineteen participants considered that the definition of failure should be a combination of clinical and urodynamics criteria. Among the urodynamics criteria, the persistence of a maximum detrusor pressure>40 cm H2O was the most supported by the experts (18/21, 85%). According to the vast majority of participants (19/21, 90.5%), the impact of injections on urinary incontinence should be included in the definition of failure. Regarding the management, most experts considered that the first line treatment in case of failure of a first intra-detrusor injection of Botox(®) 200 U should be a repeat injection of Botox(®) at a higher dosage (300 U) (15/20, 75%), regardless of the presence or not of urodynamics risk factors of upper tract damage (16/20, 80%). This work has provided a first overview of the definition of failure of intra-detrusor injections of botulinum toxin in the management of NDO. For 90.5% of the experts involved, the definition of failure should be clinical and urodynamic and most participants (75%) considered that, in case of failure of a first injection of Botox(®) 200 U

  1. Assessing erectile neurogenic dysfunction from heart rate variability through a Generalized Linear Mixed Model framework.

    PubMed

    Fernández, Elmer Andrés; Souza Neto, E P; Abry, P; Macchiavelli, R; Balzarini, M; Cuzin, B; Baude, C; Frutoso, J; Gharib, C

    2010-07-01

    The low (LF) vs. high (HF) frequency energy ratio, computed from the spectral decomposition of heart beat intervals, has become a major tool in cardiac autonomic system control and sympatho-vagal balance studies. The (statistical) distributions of response variables designed from ratios of two quantities, such as the LF/HF ratio, are likely to non-normal, hence preventing e.g., from a relevant use of the t-test. Even using a non-parametric formulation, the solution may be not appropriate as the test statistics do not account for correlation and heteroskedasticity, such as those that can be observed when several measures are taken from the same patient. The analyses for such type of data require the application of statistical models which do not assume a priori independence. In this spirit, the present contribution proposes the use of the Generalized Linear Mixed Models (GLMMs) framework to assess differences between groups of measures performed over classes of patients. Statistical linear mixed models allow the inclusion of at least one random effect, besides the error term, which induces correlation between observations from the same subject. Moreover, by using GLMM, practitioners could assume any probability distribution, within the exponential family, for the data, and naturally model heteroskedasticity. Here, the sympatho-vagal balance expressed as LF/HF ratio of patients suffering neurogenic erectile dysfunction under three different body positions was analyzed in a case-control protocol by means of a GLMM under gamma and Gaussian distributed responses assumptions. The gamma GLMM model was compared with the normal linear mixed model (LMM) approach conducted using raw and log transformed data. Both raw GLMM gamma and log transformed LMM allow better inference for factor effects, including correlations between observations from the same patient under different body position compared to the raw LMM. The gamma GLMM provides a more natural distribution assumption

  2. [Rehabilitation of oro-pharyngeal dysphagia of neurogenic etiology using radiological examination: preliminary results].

    PubMed

    Ruoppolo, G; Virdia, P; Romualdi, P; Formisano, R; Amitrano, A; Benvegnù, B; Fanucci, A; Cerro, P; Ietto, F; Metastasio, F

    1992-01-01

    Dysphagia is more frequently observed in patients with neurologic diseases (stroke, bulbar or pseudo-bulbar syndrome, amyotrophic lateral sclerosis, cranial trauma). Furthermore, the presence of this pathology is obviously more frequently noted in the light of the increase in the length of the human life span. It has become evident that alternative feeding procedures such as the nasogastric tube or gastrostomy may bring about complications and deprive patients of the oral phase of deglutition which plays a leading role in stimulating digestive functions. The Authors report a systematic research on the rehabilitation aspects of neurogenous dysphagia. All the patients studied underwent a neurological examination and oropharyngeal functional evaluation using echo-videorecording of the oral phase of deglutition and fluoro-videorecording of the pharyngeal phase. The data obtained allowed for the selection of five patients considered suitable for the rehabilitation program. One of them had a multi-infarct encephalopathy, two a spastic hemiplegia f.b.c., a fourth a cerebellar syndrome and the last a sequela of meningioma removal of the ponto-cerebellar angle with peripheral paralysis of the right VII, IX, X, XI cranial nerves. This last patient also underwent a crico-pharyngeal myotomy. Therapy consisted in making the patient sensitive to swallowing movements and in training them to assume a compensatory posture as well as functional rehabilitation of the organs involved in deglutition. The first datum emerging from the study is the lack of etiological homogeneity found in the cases treated with evident variability in different deglutition organ impairment, even though there was the common denominator of the dysphagia symptom. With regard to the results obtained, there was a complete resolution in one patient, while in the other four there was such an improvement as to allow the patients a safe autonomous oral assumption of food. The positive results obtained are not only

  3. 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

  4. OnabotulinumtoxinA improves quality of life in patients with neurogenic detrusor overactivity.

    PubMed

    Chancellor, Michael B; Patel, Vaishali; Leng, Wendy W; Shenot, Patrick J; Lam, Wayne; Globe, Denise R; Loeb, Alex L; Chapple, Christopher R

    2013-08-27

    To evaluate the effects of onabotulinumtoxinA on patient-reported outcomes including health-related quality of life (HRQOL), treatment satisfaction, and treatment goal attainment in patients with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO). In this multicenter, double-blind, randomized, placebo-controlled, phase III, 52-week study (ClinicalTrials.gov NCT00311376), patients with UI due to NDO who were not adequately managed with anticholinergic therapy were treated with intradetrusor injections of onabotulinumtoxinA (200 or 300 U) or placebo (0.9% saline). HRQOL measures included the Incontinence Quality of Life (I-QOL) Questionnaire total score, and the 3 domain scores (avoidance and limiting behavior, psychosocial, and social embarrassment), the modified Overactive Bladder Patient Satisfaction with Treatment Questionnaire (OAB-PSTQ), and Patient Global Assessment. Assessments were made at baseline, posttreatment week 6 (primary time point), week 12, and at 12-week intervals. Patients (mean age of 46 years with 30.5 weekly UI episodes at baseline) were randomized to receive placebo (n = 149) or onabotulinumtoxinA (200 U [n = 135] or 300 U [n = 132]). At week 6, improvements from baseline in I-QOL Questionnaire total score were greater (p < 0.001) in both onabotulinumtoxinA-treated groups vs placebo. Responses to the OAB-PSTQ also demonstrated greater mean improvements from baseline (p < 0.001) in both onabotulinumtoxinA-treated groups vs placebo at week 6. Patients who received onabotulinumtoxinA also reported greater improvement in the Patient Global Assessment than those in the placebo group (p ≤ 0.001 vs placebo). Patients with UI due to NDO reported greater improvement in HRQOL and treatment satisfaction with onabotulinumtoxinA than with placebo consistently across several patient-reported outcome instruments. This study provides Class I evidence that onabotulinumtoxinA intradetrusor injections (200 or 300 U) can improve quality of

  5. Prediction of outcome in neurogenic oropharyngeal dysphagia within 72 hours of acute stroke.

    PubMed

    Ickenstein, Guntram W; Höhlig, Carolin; Prosiegel, Mario; Koch, Horst; Dziewas, Rainer; Bodechtel, Ulf; Müller, Rainer; Reichmann, Heinz; Riecker, Axel

    2012-10-01

    Stroke is the most frequent cause of neurogenic oropharyngeal dysphagia (NOD). In the acute phase of stroke, the frequency of NOD is greater than 50% and, half of this patient population return to good swallowing within 14 days while the other half develop chronic dysphagia. Because dysphagia leads to aspiration pneumonia, malnutrition, and in-hospital mortality, it is important to pay attention to swallowing problems. The question arises if a prediction of severe chronic dysphagia is possible within the first 72 hours of acute stroke. On admission to the stroke unit, all stroke patients were screened for swallowing problems by the nursing staff within 2 hours. Patients showing signs of aspiration were included in the study (n = 114) and were given a clinical swallowing examination (CSE) by the swallowing/speech therapist within 24 hours and a swallowing endoscopy within 72 hours by the physician. The primary outcome of the study was the functional communication measure (FCM) of swallowing (score 1-3, tube feeding dependency) on day 90. The grading system with the FCM swallowing and the penetration-aspiration scale (PAS) in the first 72 hours was tested in a multivariate analysis for its predictive value for tube feeding-dependency on day 90. For the FCM level 1 to 3 (P < .0022) and PAS level 5 to 8 (P < .00001), the area under the curve (AUC) was 72.8% and showed an odds ratio of 11.8 (P < .00001; 95% confidence interval 0.036-0.096), achieving for the patient a 12 times less chance of being orally fed on day 90 and therefore still being tube feeding-dependent. We conclude that signs of aspiration in the first 72 hours of acute stroke can predict severe swallowing problems on day 90. Consequently, patients should be tested on admission to a stroke unit and evaluated with established dysphagia scales to prevent aspiration pneumonia and malnutrition. A dysphagia program can lead to better communication within the stroke unit team to initiate the appropriate

  6. 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

  7. 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.

  8. Neurogenic inflammation in the upper digestive tract of the mule duck: effect of a chemical algogen and force-feeding.

    PubMed

    Servière, J; Carriere, M; Duvaux-Ponter, C; Guy, G; Roussel, S

    2011-12-01

    1.The objectives were to quantify the presence of neurogenic inflammation in 4 regions of the upper digestive tract of anaesthetised ducks (post-pharynx, pseudo-crop, transition between the pseudo-crop and the proventriculus, and proventriculus) after application of HCl stimulation of up to 4 M in the pseudo-crop. 2.The second objective was to quantify the presence of neurogenic inflammation in the same digestive tract regions as mentioned above during 4 feeding periods of foie gras production (rearing, preparation to force-feeding, and second and last meals of the force-feeding period). 3. Extravasation increased above a HCl stimulation threshold of 2 M. Furthermore, more extravasation was observed in the proventriculus compared to the other regions (P < 0·001). 4.Highest extravasation responses were observed in the proventriculus and the pseudo-crop at the end of the preparation period, and in the proventriculus after the second forced meal, compared with the rearing period (P < 0·01), with a return to rearing level at the end of force-feeding. 5.Such a kinetic could be indicative of a relative mildness of the irritant components associated with this feeding practice.

  9. [Bacterial ecology and resistance to antibiotics in patients with neurogenic overactive bladder treated with intravesical botulinum toxin injections].

    PubMed

    Levy, J; Le Breton, F; Jousse, M; Haddad, R; Verollet, D; Guinet-Lacoste, A; Amarenco, G

    2014-10-01

    For the last ten years, botulinum neurotoxin type A has become the gold standard for the treatment of neurogenic overactive detrusor. Bacterial colonization is common for these patients using clean intermittent self-catheterization, and toxin injections are at risk of urinary tract infections. The aim of our study was to determine the prevalence of different germs and their resistance to antibiotics in patients with neurogenic bladder, treated with intravesical botulinum toxin injections. This epidemiologic study took place from September to October 2012 in a urodynamic and neurourology unit in a teaching hospital in Paris, France. Eighty patients with a valid urine culture according to our protocol, were included. Fourty-four culture were positive with 45 bacteria. We found an Escherichia coli in 42.5%, a Klebsiella pneumoniae in 7.5%, a Citrobacter freundii and an enterococcus in 2.5%, and a Staphylococcus aureus in 1.25%. Penicillin resistance were found in 51.11%, 3rd generation cephalosporins in 8.89%, quinolones in 28.89% and sulfamids in 24.44%. None were resistant to fosfomycin. E. coli was the most frequent bacterium. No resistance to fosfomycin was found. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. 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

  11. Nerve growth factor combined with vascular endothelial growth factor enhances regeneration of bladder acellular matrix graft in spinal cord injury-induced neurogenic rat bladder.

    PubMed

    Kikuno, Nobuyuki; Kawamoto, Ken; Hirata, Hiroshi; Vejdani, Kaveh; Kawakami, Kazumori; Fandel, Thomas; Nunes, Lora; Urakami, Shinji; Shiina, Hiroaki; Igawa, Mikio; Tanagho, Emil; Dahiya, Rajvir

    2009-05-01

    To determine the combined effects of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) on regeneration of the bladder acellular matrix graft (BAMG) in spinal cord injury (SCI)-mediated neurogenic bladder in rats. In all, 40 female Sprague-Dawley rats were used. At 8 weeks after spinalization surgery (neurogenic bladder), they were divided into five groups consisting of untreated controls and those whose bladders were injected with either no growth factor, NGF (2 microg/rat), VEGF (2 microg/rat) or both at partial BAMG replacement surgery. After 8 weeks, bladder function was assessed by urodynamic studies and the bladders were harvested for histological examination. Smooth muscle induction, collagen and nerve fibre regeneration were assessed immunohistochemically using antibodies to smooth muscle actin (alpha-actin), Masson's trichrome and protein gene product 9.5, respectively. Bladder capacity and compliance were significantly increased in all BAMG groups 8 weeks after surgery compared with that before bladder replacement surgery. Bladder capacity and compliance were much higher in the VEGF and NGF combined group than in the control, or NGF and VEGF alone groups. There was no significant difference in the residual volume ratio among all groups. This is the first report showing that NGF has a significant synergistic effect on the development, differentiation and functional restoration of the BAMG when administered with VEGF in neurogenic bladder. Our results indicate that NGF may be a useful cytokine for enhancing the regeneration of a functional bladder following acellular matrix grafting in a neurogenic rat model.

  12. 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

  13. An Evaluation of the Efficacy of Selective Alpha-Blockers in the Treatment of Children with Neurogenic Bladder Dysfunction--Preliminary Findings.

    PubMed

    Kroll, Paweł; Gajewska, Ewa; Zachwieja, Jacek; Sobieska, Magdalena; Mańkowski, Przemysław

    2016-03-15

    The aim of this study was to assess the usefulness of selective α1-blockers in children with neurogenic urinary tract dysfunctions and increased leak point pressure (LPP). 14 children from age 6 to 16 years with neurogenic urinary tract dysfunctions (neurogenic bladder) and LPP > 40 cm H₂O were enrolled in the study. All patients received a selective α1-blocker (doxazosin) for 6-8 weeks with an initial dosage of 0.03 mg/kg. During the observation period the continuation of oral anticholinergics, Clean Intermittent Catheterization (CIC), observation of "urinary dryness" and urinary incontinence periods were recommended. Patients were scheduled for a follow-up visit and urodynamic investigation after 6-8 weeks after the doxazosin therapy was started. In 4 patients, urine leakage occurred at lower pressures; in 9 patients, no significant changes in urine leak point pressures were detected; in 3 patients, there was a significant increase in the bladder capacity; in one patient, deterioration in continence was noted. The differences both in LPP and LPV before and after the treatment were not statistically significant. Our observations are consistent with the conclusions from other studies and showed no evident efficacy of doxazosin in children with neurogenic bladder.

  14. An Evaluation of the Efficacy of Selective Alpha-Blockers in the Treatment of Children with Neurogenic Bladder Dysfunction—Preliminary Findings

    PubMed Central

    Kroll, Paweł; Gajewska, Ewa; Zachwieja, Jacek; Sobieska, Magdalena; Mańkowski, Przemysław

    2016-01-01

    The aim of this study was to assess the usefulness of selective α1-blockers in children with neurogenic urinary tract dysfunctions and increased leak point pressure (LPP). 14 children from age 6 to 16 years with neurogenic urinary tract dysfunctions (neurogenic bladder) and LPP > 40 cm H2O were enrolled in the study. All patients received a selective α1-blocker (doxazosin) for 6–8 weeks with an initial dosage of 0.03 mg/kg. During the observation period the continuation of oral anticholinergics, Clean Intermittent Catheterization (CIC), observation of “urinary dryness” and urinary incontinence periods were recommended. Patients were scheduled for a follow-up visit and urodynamic investigation after 6–8 weeks after the doxazosin therapy was started. In 4 patients, urine leakage occurred at lower pressures; in 9 patients, no significant changes in urine leak point pressures were detected; in 3 patients, there was a significant increase in the bladder capacity; in one patient, deterioration in continence was noted. The differences both in LPP and LPV before and after the treatment were not statistically significant. Our observations are consistent with the conclusions from other studies and showed no evident efficacy of doxazosin in children with neurogenic bladder. PMID:26999168

  15. Complete Genome Sequence of a Paenalcaligenes hominis Strain Isolated from a Paraplegic Patient with Neurogenic Bladder Using Single-Molecule Real-Time Sequencing Technology.

    PubMed

    Mukhopadhyay, Rituparna; Joaquin, Joselita; Hogue, Robin; Kilaru, Austin; Jospin, Guillaume; Mars, Kristin; Eisen, Jonathan A; Chaturvedi, Vishnu

    2017-04-27

    The genome of Paenalcaligenes hominis, isolated from a paraplegic patient with neurogenic bladder, was sequenced with the Pacific Biosciences RSII platform. The genome size is 2.68 Mb and includes 3,096 annotated coding sequences, including genes associated with quinone cofactors, which play crucial roles in the virulence of Gram-negative bacteria. Copyright © 2017 Mukhopadhyay et al.

  16. 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

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

    PubMed

    Al Taweel, Waleed; Alzyoud, Khalil Mohammed

    2015-01-01

    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. 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. 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 (2.5-21) months. Intradetrusor

  18. 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

  19. State-of-the-Art lecture: influence of exercise training on neurogenic control of blood pressure in spontaneously hypertensive rats.

    PubMed

    Krieger, E M; Brum, P C; Negrão, C E

    1999-10-01

    Exercise training plays an important role in the reduction of high blood pressure. In this review, we discuss the effect of distinct intensities of exercise training on the reduction of high blood pressure in spontaneously hypertensive rats (SHR). In addition, we present some hemodynamic mechanisms and associated neural controls by which exercise training attenuates hypertension in SHR. Low-intensity exercise training is more effective in reducing high blood pressure than is high-intensity exercise training in SHR. The decrease in blood pressure is due to resting bradycardia, and in consequence, lower cardiac output. Sympathetic attenuation to the heart is the major explanation for the resting bradycardia. Recovery of the sensitivity of baroreflex control of heart rate, which is usually impaired in SHR, is an important neurogenic component involved in the benefits elicited by exercise training.

  20. 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

  1. 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

  2. Laparoscopic excision of mesenteric duplication enteric cyst embedded in sigmoid mesocolon mimicking retroperitoneal neurogenic tumor in adults.

    PubMed

    Wang, Jui-Ho; Lin, Jen-Tai; Hsu, Chao-Wen

    2012-10-01

    Mesenteric cysts are rare abdominal tumors with an incidence of 1/105,000 to 250,000 hospitalized adult surgical patients. These cysts may occur in every part of the mesentery, from duodenum to rectum. Most frequently, cysts are localized in small bowel mesentery. They usually present during the first decade of life, mostly occurring in pediatric patients. These lesions characteristically arise from the mesenteric border of the bowel. The majority are asymptomatic and, if found, are discovered incidentally during abdominal exploration or radiologic examination. Traditionally, the treatment of mesenteric cyst is surgical excision by laparotomy. However, in 1993, Mackenzie described the first laparoscopic excision of a mesenteric cyst. Since then, several cases have been reported but mainly in small intestine. Here, we reported an adult patient of a mesenteric duplication enteric cyst embedded in sigmoid mesocolon mimicking retroperitoneal neurogenic tumor, which was completely excised using the laparoscopic approach (Supplemental Digital Content 1, http://links.lww.com/SLE/A73).

  3. Expanding the Phenotype Associated With the NEFL Mutation Neuromuscular Disease in a Family with Overlapping Myopathic and Neurogenic Findings

    PubMed Central

    Agrawal, Pankaj B.; Joshi, Mugdha; Marinakis, Nicholas S.; Schmitz-Abe, Klaus; Ciarlini, Pedro D. S. C.; Sargent, Jane C.; Markianos, Kyriacos; De Girolami, Umberto; Chad, David A.; Beggs, Alan H.

    2014-01-01

    Importance Newer sequencing technologies in combination with traditional gene mapping techniques, such as linkage analysis, can help identify the genetic basis of disease for patients with rare disorders of uncertain etiology. This approach may expand the phenotypic spectrum of disease associated with those genetic mutations. Objective To elucidate the molecular cause of a neuromuscular disease among a family in which 4 members, a mother and her 3 sons, were affected. Design, Setting, and Participants Two of 4 affected members manifested nemaline myopathy, a common subtype of congenital myopathy, while the other 2 had a nonspecific myopathy. Single-nucleotide polymorphism–based linkage analysis was performed on DNA samples from the 4 affected family members, and whole-genome sequencing was performed in the proband. Real-time quantitative reverse transcription–polymerase chain reaction, immunofluorescence, and Western blot analysis were performed on muscle biopsy specimens. Main outcomes and Measures Whole-genome sequencing and linkage analysis identified a variant in a gene that explains the phenotype. Results We identified a novel neurofilament light polypeptide (NEFL) nonsense mutation in all affected members. NEFL mutations have been previously linked to Charcot-Marie-Tooth disease in humans. This led us to reevaluate the diagnosis, and we recognized that several of the findings, especially those related to the muscle biopsy specimens and electromyography, were consistent with a neurogenic disease. Conclusions and Relevance NEFL mutations are known to cause Charcot-Marie-Tooth disease in humans and motor neuron disease in mice. We report the identification of an NEFL mutation in a family clinically manifesting congenital myopathy. We also describe potential overlap between myopathic and neurogenic findings in this family. These findings expand the phenotypic spectrum of diseases associated with NEFL mutations. This study is an example of the power of genomic

  4. EP₃ receptor-mediated contraction of human pulmonary arteries and inhibition of neurogenic tachycardia in pithed rats.

    PubMed

    Kozłowska, Hanna; Baranowska-Kuczko, Marta; Schlicker, Eberhard; Kozłowski, Mirosław; Zakrzeska, Agnieszka; Grzęda, Emilia; Malinowska, Barbara

    2012-01-01

    The aim of our study was (1) the pharmacological characterization of EP(3) receptors in human pulmonary arteries and (2) the examination of the potential involvement of these receptors in the regulation of neurogenic tachycardia in pithed rats. L-826266 served as the EP(3) receptor antagonist. Experiments were performed on isolated human pulmonary arteries and pithed rats. The prostanoid EP(1)/EP(3) receptor agonist sulprostone (1 nM - 100 μM) concentration-dependently contracted isolated human pulmonary arteries (pEC50, 6.88 ± 0.10). The EP(1) receptor antagonist SC 19920 (100 μM) did not affect the vasoconstriction induced by sulprostone, the TP receptor antagonist sulotroban (10 μM) only slightly attenuated the effects elicited by sulprostone >3 μM, whereas L-826266 (10 μM) shifted its concentration-response curve to the right (apparent pA(2) value 6.18; incubation time 0.5 h). In rings exposed to L-826266 (0.1, 1 or 10 μM) for 3 h, a concentration-dependent inhibitory effect against the sulprostone-induced vasoconstriction was obtained, yielding a Schild plot-based pA(2) value of 7.39. In pithed rats, sulprostone (10 - 1,000 nmol/kg), but not the IP/EP(1) receptor agonist iloprost (1-100 nmol/kg), inhibited the electrically evoked increase in heart rate (HR) dose-dependently, maximally by at least 80%. L-826266 (3 μmol/kg) did not affect basal HR and diastolic blood pressure, but reduced the inhibitory effect of sulprostone 1,000 nmol/kg by about 20%. EP(3) receptors (1) located postsynaptically strongly contract human pulmonary arteries and (2) located presynaptically on sympathetic nerve fibers supplying the heart of pithed rats strongly inhibit the neurogenic tachycardia.

  5. 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.

  6. Leptin Induces Mitosis and Activates the Canonical Wnt/β-Catenin Signaling Pathway in Neurogenic Regions of Xenopus Tadpole Brain

    PubMed Central

    Bender, Melissa Cui; Sifuentes, Christopher J.; Denver, Robert J.

    2017-01-01

    In addition to its well-known role as an adipostat in adult mammals, leptin has diverse physiological and developmental actions in vertebrates. Leptin has been shown to promote development of hypothalamic circuits and to induce mitosis in different brain areas of mammals. We investigated the ontogeny of leptin mRNA, leptin actions on cell proliferation in the brain, and gene expression in the preoptic area/hypothalamus of tadpoles of Xenopus laevis. The level of leptin mRNA was low in premetamorphic tadpoles, but increased strongly at the beginning of metamorphosis and peaked at metamorphic climax. This increase in leptin mRNA at the onset of metamorphosis correlated with increased cell proliferation in the neurogenic zones of tadpole brain. We found that intracerebroventricular (i.c.v.) injection of recombinant Xenopus leptin (rxLeptin) in premetamorphic tadpoles strongly increased cell proliferation in neurogenic zones throughout the tadpole brain. We conducted gene expression profiling of genes induced at 2 h following i.c.v. injection of rxLeptin. This analysis identified 2,322 genes induced and 1,493 genes repressed by rxLeptin. The most enriched Kyoto Encyclopedia of Genes and Genomes term was the canonical Wnt/β-catenin pathway. Using electroporation-mediated gene transfer into tadpole brain of a reporter vector responsive to the canonical Wnt/β-catenin signaling pathway, we found that i.c.v. rxLeptin injection activated Wnt/β-catenin-dependent transcriptional activity. Our findings show that leptin acts on the premetamorphic tadpole brain to induce cell proliferation, possibly acting via the Wnt/β-catenin signaling pathway. PMID:28533765

  7. 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

  8. [Assessment of severity of neurogenic bowel dysfunction in chronic patients with a simple 1-item questionnaire (PGI-S)].

    PubMed

    Prévinaire, J G; Soler, J M; Bordji, H; Fiolet, M C; Navaux, M A; Mortier, P E

    2016-09-01

    Bowel symptoms (constipation and incontinence) are frequent in patients with a neurologic disease, but rarely assessed in rehabilitation centres. To study the prevalence of neurogenic bowel dysfunction (NBD) in those patients, and to assess its severity with the Patient Global Impression of Severity (PGI-S). Prospective study by questionnaires, with the Neurogenic Bowel Dysfunction Score (0-47) and the PGI-S, a 1-item questionnaire (absent, mild, moderate, severe) for the severity of the bowel symptoms, and the Bristol Stool Chart for stool consistency. All patients presenting a chronic (>2months) neurological disease were included. Inclusion of 169 patients, 97 with spinal cord injury, 42 with multiple sclerosis and 30 with hemiplegia. In each population, prevalence of constipation was 67 %, 45 % and 17 %, of pelvic floor dyssynergia 82 %, 45 % and 27 %, and leakages (gas or stools) de 74 %, 48 % and 43 %, respectively. Moderate to severe bowel symptoms were seen in 61 % of spinal cord injury, 43 % of multiple sclerosis and 23 % of hemiplegic patients, with NBD scores of 11.9±6.5, 5.7±4.9 and 3.7±4.2, respectively (P<0.01). There was a significant relation between PGI-S and NBD score (P<0.01). Significant lower NBD scores were associated with normal stool consistency (Bristol type 3 or 4) (P<0.01). In case of severe bowel symptoms, the use of transanal irrigation was hampered by patients' motivation and acceptation, and their autonomy. PGI-S and Bristol Stool Chart are reliable tools to assess the presence of bowel symptoms in clinical practice. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Measurement of electrochemical conductance of penile skin using Sudoscan(®): A new tool to assess neurogenic impotence.

    PubMed

    Lefaucheur, Jean-Pascal

    2017-06-01

    To investigate the value of electrochemical skin conductance (ESC) measurement at penile level using Sudoscan(®) for the diagnosis of neurogenic impotence in diabetics. The following neurophysiological parameters were assessed in 25 male diabetics who complained of impotence and 25 age-matched normal male subjects without erectile dysfunction (age range: 29-70 years): ESC, sympathetic skin responses (SSR), warm detection thresholds (WDT), and cold detection thresholds (CDT) for the penis and the feet, vibration detection thresholds (VDT) for the penis, and sensory nerve conduction study of the dorsal nerve of the penis (DNP) with sensory nerve action potential (SNAP) recording. Diabetic patients with impotence differed from controls with regard to most neurophysiological results at both penile and foot levels. Among penile innervation variables in the group of impotent diabetics, penile ESC was found to be the most frequently abnormal (80% of patients), followed by penile WDT, CDT, and DNP-SNAP amplitude (52% of patients), and then penile SSR amplitude and VDT (44% of patients). Various combinations of abnormalities were observed: penile ESC was the only abnormal test in 2 patients, while all tests were abnormal in 2 patients and remained normal in only one patient. Erectile dysfunction is common in diabetic men, but the diagnosis of a neurogenic origin is challenging. This study showed that ESC measurement using Sudoscan(®) is feasible and more sensitive than SSR recordings to show penile sympathetic innervation impairment. This new test should be further studied to better define its diagnostic accuracy and clinical correlates. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  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. Effect of opioid receptor subtype-selective agonists on purinergic and adrenergic components of neurogenic contractions of mouse vas deferens.

    PubMed Central

    Driessen, B.; Bültmann, R.; von Kügelgen, I.; Starke, K.

    1993-01-01

    1. Effects of opioid agonists on the purinergic and adrenergic components of neurogenic contractions and in some experiments on transmitter overflow were studied in the mouse isolated vas deferens. 2. When the vas deferens was stimulated every 2 min by pairs of pulses 2 s apart in the presence of prazosin 0.3 microM (to isolate the purinergic component) or alpha,beta-methylene-ATP 3 microM (to isolate the adrenergic component), each pulse elicited a separate twitch. The opioid agonists [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO, mu-receptor-selective), [D-Pen2,D-Pen5]enkephalin (DPDPE, delta-selective) and trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide (U-50488, kappa-selective) concentration-dependently reduced both purinergic and adrenergic contractions. For each agonist, maximal effects and concentrations causing half-maximal effects were very similar for inhibition of the purinergic component on the one hand and for inhibition of the adrenergic component on the other hand, although the adrenergic component was inhibited with a slight preference. Moreover, effects on contractions elicited by the first and the second pulse of the pairs were very similar. 3. When vasa deferentia preincubated with [3H]-noradrenaline were stimulated with trains of 100 pulses delivered at 20 Hz, morphine 10 microM reduced significantly both evoked tritium overflow and evoked contractions. Its effect was antagonized by naloxone. 4. It is concluded that, in contrast to drugs acting at some other presynaptic receptors, opioid mu-, delta- and kappa-agonists inhibit purinergic and adrenergic neurogenic contractions of the mouse vas deferens in a similar manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8383564

  12. Women's experiences of living with neurogenic bladder and bowel after spinal cord injury: life controlled by bladder and bowel.

    PubMed

    Nevedal, Andrea; Kratz, Anna L; Tate, Denise G

    2016-01-01

    Neurogenic bladder and bowel (NBB) is a chronic condition hindering the functioning and quality of life (QOL) of people with spinal cord injury (SCI). NBB research has focused on men with SCI leaving unanswered questions about women's experiences of living with NBB. The purpose of this study was to identify and describe women's experiences of living with SCI and NBB. Secondary analysis of semi-structured interviews from a larger qualitative study of women with SCI (N = 50) was carried out. Transcripts were coded for bowel and bladder content. Pile-sorting techniques were used to identify emergent themes related to NBB. Meta-themes were categorized under the International Classification of Functioning, Disability and Health. Bladder and bowel topics were spontaneously discussed by 46 out of 50 study participants suggesting the salience of this issue for women with SCI. We identified 6 meta-themes: life controlled by bladder and bowel, bladder and bowel accidents, women's specific challenges, life course disruption, bladder and bowel medical management, and finding independence. Findings describe concerns, strategies, and the detrimental impact of NBB in the lives of women with SCI. Findings inform policy makers, health care and rehabilitation professionals to improve accessibility and quality of life for women with NBB. Women with spinal cord injury (SCI) reported gender specific challenges to living with neurogenic bladder and bowel (NBB). Interventions designed for women with SCI can address these problems and provide recommendations for prevention and treatment. Women described the detrimental impact of NBB on life course expectations, emotional, social, physical health, and quality of life domains. Psychosocial and educational programs can be developed to address these challenges and improve overall quality of life. Recommendations for special treatment and policy considerations are needed to maximize women's independence and health while living with NBB

  13. Neurogenic bowel dysfunction in patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson’s disease

    PubMed Central

    Awad, Richard A

    2011-01-01

    Exciting new features have been described concerning neurogenic bowel dysfunction, including interactions between the central nervous system, the enteric nervous system, axonal injury, neuronal loss, neurotransmission of noxious and non-noxious stimuli, and the fields of gastroenterology and neurology. Patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson’s disease present with serious upper and lower bowel dysfunctions characterized by constipation, incontinence, gastrointestinal motor dysfunction and altered visceral sensitivity. Spinal cord injury is associated with severe autonomic dysfunction, and bowel dysfunction is a major physical and psychological burden for these patients. An adult myelomeningocele patient commonly has multiple problems reflecting the multisystemic nature of the disease. Multiple sclerosis is a neurodegenerative disorder in which axonal injury, neuronal loss, and atrophy of the central nervous system can lead to permanent neurological damage and clinical disability. Parkinson's disease is a multisystem disorder involving dopaminergic, noradrenergic, serotoninergic and cholinergic systems, characterized by motor and non-motor symptoms. Parkinson's disease affects several neuronal structures outside the substantia nigra, among which is the enteric nervous system. Recent reports have shown that the lesions in the enteric nervous system occur in very early stages of the disease, even before the involvement of the central nervous system. This has led to the postulation that the enteric nervous system could be critical in the pathophysiology of Parkinson's disease, as it could represent the point of entry for a putative environmental factor to initiate the pathological process. This review covers the data related to the etiology, epidemiology, clinical expression, pathophysiology, genetic aspects, gastrointestinal motor dysfunction, visceral sensitivity, management, prevention and prognosis of neurogenic bowel

  14. 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

  15. 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

    PubMed Central

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

    2012-01-01

    The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial 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. PMID:22814253

  16. 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.

  17. 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

  18. Novel therapeutic approach for neurogenic erectile dysfunction: effect of neurotrophic tyrosine kinase receptor type 1 monoclonal antibody.

    PubMed

    Lin, Guiting; Li, Huixi; Zhang, Xiaoyu; Wang, Jianwen; Zaid, Uwais; Sanford, Melissa T; Tu, Victor; Wu, Alex; Wang, Lin; Tian, Fei; Kotanides, Helen; Krishnan, Venkatesh; Wang, Guifang; Ning, Hongxiu; Banie, Lia; Lin, Ching-Shwun; Deng, Gary G; Lue, Tom F

    2015-04-01

    Erectile dysfunction (ED) is a major health issue in aged populations, and neurogenic ED is particularly difficult to treat. Novel therapeutic approaches are needed for treatment of neurogenic ED of peripheral origin. To investigate the therapeutic effects of a neurotrophic tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb) on erectile function and sexual behavior in a rat model of cavernous nerve injury (CNI). In one experiment, 84 male rats were randomly assigned to seven groups. The groups underwent either CNI or sham surgery, subsequent injection into the major pelvic ganglion (IMPG) of phosphate-buffered saline (PBS), an immunoglobulin G (IgG) control, or TrkA-mAb, and then intracavernosal (IC) injection of either PBS or varying TrkA-mAb concentrations immediately after surgery and then 1 wk later. Erectile function was assessed and histologic/molecular analyses were performed at 6 wk after surgery. In a second experiment, 36 male rats were randomly divided into three groups. The groups underwent CNI or sham surgery and then IC injection of PBS, IgG, or TrkA-mAb immediately after surgery and for 5 wk thereafter. At 6 wk after surgery, the performance of the rats in sexual behavior tests was videotaped. CNI or sham surgery; IMPG of PBS, IgG, or TrkA-mAb; IC injection of PBS or TrkA-mAb. The intracavernous pressure response to cavernous nerve electrostimulation was measured and midpenile cross-sections were histologically examined. Western blotting (WB) of cavernous tissue protein was performed. Rats were assessed for chasing, mounting, intromission, and ejaculation behaviors during sexual behavior tests. The data were analyzed using one-way analysis of variance followed by the Tukey-Kramer t test. Recovery of erectile function of varying degrees was observed in the TrkA-mAb groups. TrkA-mAb treatment significantly suppressed tyrosine hydroxylase-positive nerve fibers in the corpus cavernosum and enhanced neuronal nitric oxide synthase

  19. 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.

  20. Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure.

    PubMed

    Luo, Yu-long; Li, Pei-bo; Zhang, Chen-chen; Zheng, Yan-fang; Wang, Sheng; Nie, Yi-chu; Zhang, Ke-jian; Su, Wei-wei

    2013-12-01

    The effects of four antitussives, including codeine phosphate (CP), moguisteine, levodropropizine (LVDP) and naringin, on airway neurogenic inflammation and enhanced cough were investigated in guinea pig model of chronic cough. Guinea pigs were exposed to CS for 8 weeks. At the 7th and 8th week, the animals were treated with vehicle, CP (4.8 mg/kg), moguisteine (24 mg/kg), LVDP (14 mg/kg) and naringin (18.4 mg/kg) respectively. Then the cough and the time-enhanced pause area under the curve (Penh-AUC) during capsaicin challenge were recorded. The substance P (SP) content, NK-1 receptor expression and neutral endopeptidase (NEP) activity in lung were determined. Chronic CS exposure induced a bi-phase time course of cough responsiveness to capsaicin. Eight weeks of CS exposure significantly enhanced the airway neurogenic inflammation and cough response in guinea pigs. Two weeks of treatment with CP, moguisteine, LVDP or naringin effectively attenuated the chronic CS-exposure enhanced cough. Only naringin exerted significant effect on inhibiting Penh-AUC, SP content and NK-1 receptor expression, as well as preventing the declining of NEP activity in lung. Chronic CS-exposed guinea pig is suitable for studying chronic pathological cough, in which naringin is effective on inhibiting both airway neurogenic inflammation and enhanced cough.

  1. Can adult neural stem cells create new brains? Plasticity in the adult mammalian neurogenic niches: realities and expectations in the era of regenerative biology.

    PubMed

    Kazanis, Ilias

    2012-02-01

    Since the first experimental reports showing the persistence of neurogenic activity in the adult mammalian brain, this field of neurosciences has expanded significantly. It is now widely accepted that neural stem and precursor cells survive during adulthood and are able to respond to various endogenous and exogenous cues by altering their proliferation and differentiation activity. Nevertheless, the pathway to therapeutic applications still seems to be long. This review attempts to summarize and revisit the available data regarding the plasticity potential of adult neural stem cells and of their normal microenvironment, the neurogenic niche. Recent data have demonstrated that adult neural stem cells retain a high level of pluripotency and that adult neurogenic systems can switch the balance between neurogenesis and gliogenesis and can generate a range of cell types with an efficiency that was not initially expected. Moreover, adult neural stem and precursor cells seem to be able to self-regulate their interaction with the microenvironment and even to contribute to its synthesis, altogether revealing a high level of plasticity potential. The next important step will be to elucidate the factors that limit this plasticity in vivo, and such a restrictive role for the microenvironment is discussed in more details.

  2. 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.

  3. 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.

  4. 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

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

    PubMed

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

    2016-05-01

    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. Copyright© Ferrata Storti Foundation.

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

    PubMed

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

    2015-09-01

    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. Copyright © 2015 the American Physiological Society.

  7. 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.

  8. 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

  9. 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

  10. Intra-articular injection of Botulinum toxin A reduces neurogenic inflammation in CFA-induced arthritic rat model.

    PubMed

    Wang, Lin; Wang, Kaile; Chu, Xiao; Li, Tieshan; Shen, Nana; Fan, Chenglei; Niu, Zhenyuan; Zhang, Xiaochen; Hu, Luoman

    2017-02-01

    Currently, administration of Botulinum toxin Type A (BoNT/A) to treat arthritic pain has promising efficacy in clinical research. However, the mechanisms underlying anti-neurogenic inflammation mediated by BoNT/A remains unclear. The aim of this study was to demonstrate the effectiveness in macro and micro levels and to explore the causal mechanism of BoNT/A. Wistar rats (n = 60) were injected with 50ul complete Freund's adjuvant (CFA) in the left ankle joint capsule to establish a model of chronic monoarthritis. Pain behaviour (Evoked pain assessment) and infrared thermal imaging testing were performed at the macroscopic level to assess the effectiveness of analgesia and anti-inflammation. Western blotting and immunofluorescence staining were used at the microscopic level in an attempt to determine the mechanisms of anti-nociceptive or anti-inflammatory effects of BoNT/A. Additionally, hematoxylin-eosin staining was also used to visualise the cartilage and the synovial degenerative conditions of arthritis. By comparing the outcome of the evoked pain test and immunofluorescence staining, there was a significant improvement in BoNT/A compared with the normal saline (NS) injected control group. In addition, thermal variations showed that the temperature of ipsilateral ankle joint increased between 1 and 2 weeks following injection of CFA, but decreased after 3 weeks (still above the contralateral side). However, the temperature showed no difference between the BoNT/A group and NS group after treatment. The expression of IL-1β or TNF-α in the ankle synovial tissue was significantly decreased in the BoNT/A group compared to the NS group (p < 0.05). Based on the HE assessment, cartilage degeneration and infiltration of inflammatory cells in the BoNT/A group was alleviated compared to the NS group after treatment. In conclusion, we proposed the hypothesis that intra-articular BoNT/A administration does play an important role in anti-neurogenic inflammation. The

  11. 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

  12. Onabotulinumtoxin A for Treating Overactive/Poor Compliant Bladders in Children and Adolescents with Neurogenic Bladder Secondary to Myelomeningocele

    PubMed Central

    Marte, Antonio

    2012-01-01

    This retrospective study was performed to verify the efficacy and safety of Onabotulinumtoxin A (BTX-A) in treating children with neurogenic bladder (NB) secondary to myelomeningocele (MMC) with detrusor overactivity/low compliance. From January 2002 to June 2011, 47 patients out of 68 with neuropathic bladder were selected (22 females, 25 males, age range 5–17 years; mean age 10.7 years at first injection). They presented overactive/poor compliant neurogenic bladders on clean intermittent catheterization, and were resistant or non compliant to pharmacological therapy. Ten patients presented second to fourth grade concomitant monolateral/bilateral vesicoureteral reflux (VUR). All patients were incontinent despite catheterization. In the majority of patients Botulinum-A toxin was administered under general/local anesthesia by the injection of 200 IU of toxin, without exceeding the dosage of 12IU/kg body weight, diluted in 20 cc of saline solution in 20 sites, except in the periureteral areas. Follow-up included clinical and ultrasound examination, urodynamics performed at 6, 12 and 24 weeks, and annually thereafter. Seven patients remained stable, 21 patients required a second injection after 6–9 months and 19 a third injection. VUR was corrected, when necessary, in the same session after the BT-A injection, by 1–3 cc of subureteral Deflux®. Urodynamic parameters considered were leak point pressure (LPP), leak point volume (LPV) and specific volume at 20 cm H2O pressure. The results were analyzed using the Wilcoxon test. All patients experienced a significant 66.45% average increase of LPV (Wilcoxon paired rank test = 7169 × 10 −10) and a significant 118.57% average increase of SC 20 (Wilcoxon paired rank test = 2.466 × 10 −12). The difference between preoperative and postoperative LPP resulted not significant (Wilcoxon paired rank test = 0.8858) No patient presented severe systemic complications; 38/47 patients presented slight hematuria for 2–3 days

  13. 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

  14. 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.

  15. Calcium-sensing receptor-mediated osteogenic and early-stage neurogenic differentiation in umbilical cord matrix mesenchymal stem cells from a large animal model.

    PubMed

    Martino, Nicola Antonio; Reshkin, Stephan Joel; Ciani, Elena; Dell'Aquila, Maria Elena

    2014-01-01

    Umbilical cord matrix mesenchymal stem cells (UCM-MSCs) present a wide range of potential therapeutical applications. The extracellular calcium-sensing receptor (CaSR) regulates physiological and pathological processes. We investigated, in a large animal model, the involvement of CaSR in triggering osteogenic and neurogenic differentiation of two size-sieved UCM-MSC lines, by using AMG641, a novel potent research calcimimetic acting as CaSR agonist. Large (>8 µm in diameter) and small (<8 µm) equine UCM-MSC lines were cultured in medium with high calcium (Ca2+) concentration ([Ca2+]o; 2.87 mM) and dose-response effects of AMG641 (0.01 to 3µM) on cell proliferation were evaluated. Both cell lines were then cultured in osteogenic or neurogenic differentiation medium containing: 1) low [Ca2+]o (0.37 mM); 2) high [Ca2+]o (2.87 mM); 3) AMG641 (0.05, 0.1 or 1 µM) with high [Ca2+]o and 4) the CaSR antagonist NPS2390 (10 mM for 30 min) followed by incubation with AMG641 in high [Ca2+]o. Expression of osteogenic or neurogenic differentiation biomarkers was compared among groups. In both cell lines, AMG641 dose-dependently increased cell proliferation (up to P<0.001). Osteogenic molecular markers expression was differentially regulated by AMG641, with stimulatory (OPN up-regulation) in large or inhibitory (RUNX2 and OPN down-regulation) effects in small cells, respectively. AMG641 significantly increased alkaline phosphatase activity and calcium phosphate deposition in both cell lines. Following treatment with AMG641 during osteogenic differentiation, in both cell lines CaSR expression was inversely related to that of osteogenic markers and inhibition of CaSR by NPS2390 blocked AMG641-dependent responses. Early-stage neurogenic differentiation was promoted/triggered by AMG641 in both cell lines, as Nestin and CaSR mRNA transcription up-regulation were observed. Calcium- and AMG641-induced CaSR stimulation promoted in vitro proliferation and osteogenic and early

  16. Calcium-Sensing Receptor-Mediated Osteogenic and Early-Stage Neurogenic Differentiation in Umbilical Cord Matrix Mesenchymal Stem Cells from a Large Animal Model

    PubMed Central

    Martino, Nicola Antonio; Reshkin, Stephan Joel; Ciani, Elena; Dell'Aquila, Maria Elena

    2014-01-01

    Background Umbilical cord matrix mesenchymal stem cells (UCM-MSCs) present a wide range of potential therapeutical applications. The extracellular calcium-sensing receptor (CaSR) regulates physiological and pathological processes. We investigated, in a large animal model, the involvement of CaSR in triggering osteogenic and neurogenic differentiation of two size-sieved UCM-MSC lines, by using AMG641, a novel potent research calcimimetic acting as CaSR agonist. Methodology/Principal Findings Large (>8µm in diameter) and small (<8µm) equine UCM-MSC lines were cultured in medium with high calcium (Ca2+) concentration ([Ca2+]o; 2.87 mM) and dose-response effects of AMG641 (0.01 to 3µM) on cell proliferation were evaluated. Both cell lines were then cultured in osteogenic or neurogenic differentiation medium containing: 1) low [Ca2+]o (0.37 mM); 2) high [Ca2+]o (2.87 mM); 3) AMG641 (0.05, 0.1 or 1 µM) with high [Ca2+]o and 4) the CaSR antagonist NPS2390 (10 mM for 30 min) followed by incubation with AMG641 in high [Ca2+]o. Expression of osteogenic or neurogenic differentiation biomarkers was compared among groups. In both cell lines, AMG641 dose-dependently increased cell proliferation (up to P<0.001). Osteogenic molecular markers expression was differentially regulated by AMG641, with stimulatory (OPN up-regulation) in large or inhibitory (RUNX2 and OPN down-regulation) effects in small cells, respectively. AMG641 significantly increased alkaline phosphatase activity and calcium phosphate deposition in both cell lines. Following treatment with AMG641 during osteogenic differentiation, in both cell lines CaSR expression was inversely related to that of osteogenic markers and inhibition of CaSR by NPS2390 blocked AMG641-dependent responses. Early-stage neurogenic differentiation was promoted/triggered by AMG641 in both cell lines, as Nestin and CaSR mRNA transcription up-regulation were observed. Conclusions/Significance Calcium- and AMG641-induced CaSR stimulation

  17. 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. © 2015 The Authors.

  18. 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

  19. 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.

  20. 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.

  1. A systematic review of the diagnosis and treatment of patients with neurogenic hyperactivity of the detrusor muscle.

    PubMed

    Borau, A; Adot, J M; Allué, M; Arlandis, S; Castro, D; Esteban, M; Salinas, J

    2017-04-13

    Neurogenic detrusor hyperactivity (NDH) is a urodynamic observation characterised by involuntary detrusor contractions during the filling phase that are caused by an underlying neurological disease. The common and severe complications that can result from NDH warrant the preparation of healthcare protocols for the proper management of patients with NDH. The aim of this study is to standardise the criteria for the decision-making process in the management of patients with diagnosed or suspected NDH, providing personalised medical care. We performed a systematic noncomprehensive literature review on the aspects of the diagnosis and treatment of NDH. Based on the review, recommendations were issued by nominal consensus of a group of urology specialists. In general, the diagnosis of NDH is arrived at by a proper review of the medical history, physical examination and voiding diary before performing any diagnostic study. The main treatment objectives are to protect the upper urinary tract, restore function of the lower tract and improve these patients' continence and quality of life. The treatment consists of several steps aimed at obtaining proper bladder storage that allows for sufficiently spaced voidings. The follow-up should be personalised based on each patient's needs. The identification and management of NDH is important for positively redirecting the function of the lower urinary tract, in terms of filling and voiding, thereby improving the patients' quality of life. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  2. 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.

  3. Severe muscle symptoms with lipid-lowering agents may be confused with neurogenic claudication associated with spinal canal stenosis.

    PubMed

    Savage, Ruth L; Star, Kristina; Hill, Richard

    2012-01-01

    Screening of the WHO global individual case safety report database (VigiBase) has recently identified case reports with HMG CoA reductase inhibitors and muscle symptoms co-reported with spinal stenosis. In some reports spinal stenosis appears to have been listed as a coincidental finding. To assess reports with sufficient information to ascertain if they suggested that there may have been diagnostic confusion between muscle symptoms attributable to HMG CoA reductase inhibitors with or without ezetimibe and symptoms of spinal stenosis. Reports were examined for patient demographics, past history, clinical and investigational findings, co-prescribed medicines and outcomes. Three case histories recorded details suggestive of diagnostic confusion between severe and disabling muscle symptoms affecting the lower limbs attributable to an HMG CoA reductase inhibitor with and without ezetimbe and symptoms of neurogenic claudication due to spinal stenosis. The statins were not discontinued promptly leading to prolonged morbidity. Serum creatine kinase levels (CK) were normal in two patients and not recorded for the third. The reports include two safety issues, firstly the need to consider HMG CoA reductase inhibitors as a cause of severe lower limb muscle symptoms even in the presence of spinal stenosis and normal CK levels and the second, the need to measure serum creatine kinase when these symptoms occur to detect progression of myopathy and potentially serious outcomes.

  4. What do we know about neurogenic bladder prevalence and management in developing countries and emerging regions of the world?

    PubMed

    Przydacz, Mikolaj; Denys, Pierre; Corcos, Jacques

    2017-09-01

    To summarize information on Neurogenic Bladder (NB) epidemiology, management and access to patient treatment in developing countries and emerging regions of the world in order to propose future interventions and help governmental as well as non-governmental organizations design their action plans. Different search methods were used to gather the maximum available data. They included strategic searches; reference checks; grey literature searches (reports, working papers, government documents, civil society information); contacting professional societies, registries, and authors; requesting unpublished data from organizations; and browsing related websites and journals. The incidence and prevalence rates of NB in developing countries are difficult to establish because epidemiological reports are few and far between. The frequency of bladder dysfunction in neurologically impaired populations can be approximately estimated in some of these countries. Similar information paucity affects diagnostic and therapeutic approaches to NB patients living in less-developed regions of the world. The assessment and management of NB seems to vary markedly between countries, and care of patients from emerging regions of the world is often inadequate. Strong concerted efforts are needed on the part of international scientific societies, non-governmental organizations and local governments to work together to change the prognosis for these patients and to improve their quality of life. Copyright © 2017. Published by Elsevier Masson SAS.

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