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Sample records for ath5 neurogenic network

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

    PubMed Central

    2013-01-01

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

  2. Neurogenic Bladder

    PubMed Central

    Dorsher, Peter T.; McIntosh, Peter M.

    2012-01-01

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

  3. [Neurogenic shock].

    PubMed

    Meister, Rafael; Pasquier, Mathieu; Clerc, David; Carron, Pierre-Nicolas

    2014-08-13

    The neurogenic shock is a common complication of spinal cord injury, especially when localized at the cervical level. Characterized by a vasoplegia (hypotension) and bradycardia, the neurogenic shock is secondary to the damage of the sympathetic nervous system. The clinical presentation often includes tetraplegia, with or without respiratory failure. Early treatment aims to minimize the occurrence of secondary spinal cord lesions resulting from systemic ischemic injuries. Medical management consists in a standardized ABCDE approach, in order to stabilize vital functions and immobilize the spine. The hospital care includes performing imaging, further measures of neuro-resuscitation, and coordinated surgical assessment and treatment of any other injury. PMID:25199226

  4. 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

  5. Neurogenic heterotopic ossification.

    PubMed

    Jensen, L L; Halar, E; Little, J W; Brooke, M M

    1987-12-01

    Neurogenic heterotopic ossification is a potential sequela of neurological disorders, especially spinal cord injury and head injury. The etiology is unknown. Clinical, radiologic, and bone scan findings are typical. Complications may threaten function. The differential diagnosis is crucial in its early stages. Treatment options include diphosphonates, non-steroidal anti-inflammatory drugs, and surgery. This article has reviewed the literature on neurogenic heterotopic ossification (HO), soft tissue ossification of neurologic disease, including pathogenesis, histology, presentation, diagnosis, natural history, complications, and current treatments. PMID:3124630

  6. [Neurogenic erectile dysfunction].

    PubMed

    Ramos, Antonio Sánchez; Durán, Juan Antonio Godino; Oliviero, Antonio

    2010-10-01

    Neurogenic erectile dysfunction is a consequence of alterations in neural pathways, autonomic, somatic, the combination of both or brain components that induce erection. This review aims to explain the physiopathological mechanisms of the most frequent neurological alterations causing erectile dysfunction and sexual disorders. PMID:20978292

  7. 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. PMID:25673127

  8. 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

  9. [Traumatic neurogenic shock].

    PubMed

    Maurin, O; de Régloix, S; Caballé, D; Arvis, A-M; Perrochon, J-C; Tourtier, J-P

    2013-05-01

    Traumatic neurogenic shock is a rare but serious complication of spinal cord injury. It associates bradycardia and hypotension caused by a medullary trauma. It is life-threatening for the patient and it aggravates the neurological deficit. Strict immobilization and a quick assessment of the gravity of cord injury are necessary as soon as prehospital care has begun. Initial treatment requires vasopressors associated with fluid resuscitation. Steroids are not recommended. Early decompression is recommended for incomplete deficit seen in the first 6 hours. We relate the case of secondary spinal shock to a luxation C6/C7 treated in prehospital care. PMID:23566590

  10. Augmentation cystoplasty in neurogenic bladder.

    PubMed

    Çetinel, Bülent; Kocjancic, Ervin; Demirdağ, Çetin

    2016-09-01

    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

  11. 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

  12. Neutral endopeptidase modulates neurogenic inflammation.

    PubMed

    Nadel, J A

    1991-06-01

    A noncholinergic, nonadrenergic nervous system has been described, involving the sensory nerves in the airways. Chemicals, dusts and other irritants stimulate these sensory nerves to release substance P and related neuropeptides. These neuropeptides have the remarkable ability to affect multiple cells in the airways and to provoke many responses including cough, mucus secretion, smooth muscle contraction, plasma extravasation and neutrophil adhesion. This series of effects is termed "neurogenic inflammation." An enzyme exists on the surfaces of all lung cells that contain receptors for these neuropeptides. This enzyme, neutral endopeptidase (NEP), by cleaving and thus inactivating the neuropeptides, limits the concentration of the neuropeptide that reaches the receptor on the cell surface. Thus, neurogenic inflammatory responses are normally mild and presumably protective in nature. However, when NEP is inhibited pharmacologically (with NEP inhibitors) or by cigarette smoke, respiratory viral infection, or by inhalation of the industrial pollutant toluene diisocyanate, neurogenic inflammatory responses are exaggerated. Delivery of exogenous human recombinant NEP inhibits neurogenic inflammation. Finally, evidence is provided that corticosteroids suppress neurogenic plasma extravasation and that this drug can upregulate NEP in human airway tissue. Neutral endopeptidase cleaves multiple peptides. Thus, its selectivity resides, at least in part, on its fixed location on the surfaces of specific cells where it can modulate effects of peptides exposed to the cells' surfaces. PMID:1889501

  13. 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. PMID:25900825

  14. 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. PMID:27048686

  15. Bibliometric profile of neurogenic bladder in the literature: a 20-year bibliometric analysis

    PubMed Central

    Gao, Yuan; Qu, Bo; Shen, Yan; Su, Xiao-jing; Dong, Xiao-yan; Chen, Xue-mei; Zhou, Yu-hong; Pi, Hong-ying

    2015-01-01

    Neurogenic bladder is a dysfunction of the lower urinary tract caused by nervous system disorder. We investigated the trends in publication of articles under the topic “neurogenic bladder” using bibliometric analysis. Articles on neurogenic bladder, published between 1995 and 2014, were retrieved from the ISI Web of Science citation database. We analyzed the search results for authors, countries, institutions, journals, and top-cited papers. A total of 1,904 articles were retrieved. There was a small increase in the number of articles on neurogenic bladder from 1995 (n = 43) to 2014 (n = 117). The USA was the leading country in the total number of articles (n = 598). However, the number of publications from China has rapidly increased, and China was ranked second in 2014. Emmanuel Chartier-Kastler (n = 65) was the most productive author, and University of Paris VI (Paris 6) (n = 61) was the most productive institution. The Journal of Urology published the greatest number of articles on this topic (n = 285). Articles on neurogenic bladder were often published in a professional journal under the category Urology & Nephrology, Neurosciences & Neurology, or Rehabilitation. Visualization analysis based on co-citation networks was conducted using CiteSpace III. Visualization analysis revealed that the hot spots in neurogenic bladder were botulinum toxin-A, prazosin, bethanechol, and afferent pathways. These findings provide new insight into the publication trends and hot spots in neurogenic bladder. PMID:26109957

  16. 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

  17. 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

  18. Understanding migraine: Potential role of neurogenic inflammation.

    PubMed

    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

  19. Droxidopa in neurogenic orthostatic hypotension.

    PubMed

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

    2015-01-01

    Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure (BP) 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 (MSA), pure autonomic failure (PAF), 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 BP by acting at the neurovascular junction to increase vascular tone. This article summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials. PMID:26092297

  20. 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

  1. 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. PMID:22071315

  2. The role of histamine in neurogenic inflammation

    PubMed Central

    Rosa, A C; Fantozzi, R

    2013-01-01

    The term ‘neurogenic inflammation’ has been adopted to describe the local release of inflammatory mediators, such as substance P and calcitonin gene-related peptide, from neurons. Once released, these neuropeptides induce the release of histamine from adjacent mast cells. In turn, histamine evokes the release of substance P and calcitonin gene-related peptide; thus, a bidirectional link between histamine and neuropeptides in neurogenic inflammation is established. The aim of this review is to summarize the most recent findings on the role of histamine in neurogenic inflammation, with particular regard to nociceptive pain, as well as neurogenic inflammation in the skin, airways and bladder. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 PMID:23734637

  3. 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

  4. Optimizing therapy and management of neurogenic bladder.

    PubMed

    Ginsberg, David

    2013-01-01

    Clinicians managing patients with neurogenic bladder (NGB) and neurogenic detrusor overactivity (NDO) are faced with a myriad of complex choices when deciding on appropriate medical and/or surgical interventions to relieve bothersome symptoms associated with NGB and NDO, especially urinary incontinence. Therapies must provide maximum benefits while minimizing patients' risk for adverse events. A thorough knowledge and understanding of available and emerging medical and surgical treatment options for NGB/NDO is vital to assist clinicians in choosing appropriate treatment pathways and optimize response to therapy and individual outcomes. PMID:24495241

  5. Droxidopa for neurogenic orthostatic hypotension

    PubMed Central

    Freeman, Roy; Biaggioni, Italo; Low, Phillip; Pedder, Simon; Hewitt, L. Arthur; Mauney, Joe; Feirtag, Michael; Mathias, Christopher J.

    2014-01-01

    Objective: To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH). Methods: Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100–600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities. Results: From randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units (p = 0.010), with maximum change in “dizziness/lightheadedness.” Improvement in symptom-impact subscore favored droxidopa by 1.06 units (p = 0.003), with maximum change for “standing a long time.” Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events. Conclusions: In patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated. Classification of evidence: This study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days. PMID:24944260

  6. 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…

  7. [Neurogenic pulmonary edema. Report of 2 cases].

    PubMed

    Dragosavac, D; Falcão, A L; Araújo, S; Terzi, R G

    1997-06-01

    Neurogenic pulmonary edema is a rare and serious complication in patients with head injury. It also may develop after a variety of cerebral insults such as subarachnoid hemorrhage, brain tumors and after epileptic seizures. Thirty six patients with severe head injury and four patients with cerebrovascular insults treated in Intensive Care Unit of HC-UNICAMP from January to September 1995 were evaluated. In this period there were two patients with neurogenic pulmonary edema, one with head injury and other with intracerebral hemorrhage. Diagnosis was made by rapid onset of pulmonary edema, severe hypoxemia, decrease of pulmonary complacence and diffuse pulmonary infiltrations, without previous history of tracheal aspiration or any other risk factor for development of adult respiratory distress syndrome. In the first case, with severe head trauma, neurogenic pulmonary edema was diagnosed at admission one hour after trauma, associated with severe systemic inflammatory reaction, and good outcome in three days. The second case, with hemorrhagic vascular insult, developed neurogenic pulmonary edema the fourth day after drainage of intracerebral hematoma and died. PMID:9629392

  8. 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. PMID:26657764

  9. UTIs in patients with neurogenic bladder.

    PubMed

    Jahromi, Mona S; Mure, Amanda; Gomez, Christopher S

    2014-09-01

    Urinary tract infections (UTI) remain one of the most prevalent and frustrating morbidities for neurogenic bladder patients, and death attributed to urosepsis in the spinal cord injury (SCI) patient is higher when compared to the general population. Risk factors include urinary stasis, high bladder pressures, bladder stones, and catheter use. While classic symptoms of UTI include dysuria, increased frequency and urgency, neurogenic bladder patients present differently with increased spasticity, autonomic dysreflexia, urinary incontinence, and vague pains. Multiple modalities have been assessed for prevention including catheter type, oral supplements, bladder irrigation, detrusor injections and prophylactic antimicrobials. Of these, bladder inoculation with E. coli HU2117, irrigation with iAluRil(®), detrusor injections, and weekly prophylaxis with alternating antibiotics appear to have a positive reduction in UTI but require further study. Ultimately, treatment for symptomatic UTI should account for the varied flora and possible antibiotic resistances including relying on urine cultures to guide antibiotic therapy. PMID:25113150

  10. Neurogenic stress cardiomyopathy associated with subarachnoid hemorrhage.

    PubMed

    Pinnamaneni, Sowmya; Dutta, Tanya; Melcer, Joshua; Aronow, Wilbert S

    2015-01-01

    Cardiac manifestations are recognized complications of subarachnoid hemorrhage. Neurogenic stress cardiomyopathy is one complication that is seen in acute subarachnoid hemorrhage. It can present as transient diffuse left ventricular dysfunction or as transient regional wall motion abnormalities. It occurs more frequently with neurologically severe-grade subarachnoid hemorrhage and is associated with increased morbidity and poor clinical outcomes. Managing this subset of patients is challenging. Early identification followed by a multidisciplinary team approach can potentially improve outcomes. PMID:25606704

  11. Neurogenic fibrosarcoma following radiation therapy for seminoma

    SciTech Connect

    O'Brien, W.M.; Abbondanzo, S.L.; Chun, B.K.; Manz, H.J.; Maxted, W.C.

    1989-05-01

    We report a case of radiation-induced neurogenic fibrosarcoma that developed in a patient who received radiation therapy for seminoma. The sarcoma developed within the irradiated field after a latency period of nineteen years. Although the occurrence of a secondary neoplasm is unusual, this possibility should be included in the differential diagnosis of patients who present with tumor growth after a long interval following radiation therapy.

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

    PubMed

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

    2016-01-01

    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. Finally, we discuss the pathophysiology of neurogenic stunned myocardium, as well as its implications for anesthesiologists caring for neurosurgical patients. PMID:26462162

  13. 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. PMID:26475949

  14. 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

  15. 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

  16. 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. PMID:17234174

  17. It Takes a Village: Constructing the Neurogenic Niche

    PubMed Central

    Bjornsson, Christopher S.; Apostolopoulou, Maria; Tian, Yangzi; Temple, Sally

    2016-01-01

    While many features of neurogenesis during development and in the adult are intrinsic to the neurogenic cells themselves, the role of the microenvironment is irrefutable. The neurogenic niche is a melting pot of cells and factors that influence CNS development. How do the diverse elements assemble, and when? How does the niche change structurally and functionally during embryogenesis and into adulthood? In this review, we focus on the impact of non-neural cells that participate in the neurogenic niche, highlighting how cells of different embryonic origins influence this critical germinal space. PMID:25710530

  18. Ureteral reimplantation in children with neurogenic bladder.

    PubMed

    Belloli, G P; Musi, L; Campobasso, P; Cattaneo, A

    1979-04-01

    The treatment of urologic complications from myelomeningocele and especially of vesico-renal reflux is a controversial problem. A series of 26 reimplanted ureters in 17 children, with good results in more than 85%, is reported. Ureteroneocystostomy, carried out with a few technical innovation, may represent a useful method for the treatment of vesico-renal reflux and obstruction of the uretero-vesical junction in neurogenic bladder associated with myelomeningocele. This surgical approach leads to the disappearance of the reflux, decrease of dilatation of the upper urinary tract and preservation of renal function in most cases; moreover, infection can be more easily controlled. Ureteral reimplantation should be preceded by periodic urethral dilatation, external transurethral sphincterotomy, and pharmacologic regulation in order to attempt to decrease urethral resistance. After successful surgery, it is possible to try to reeducate the bladder. Reimplantation should be preferred to permanent urinary diversion even if there is gross reflux. PMID:458534

  19. Neurogenic dysphagia resulting from Chiari malformations.

    PubMed

    Pollack, I F; Pang, D; Kocoshis, S; Putnam, P

    1992-05-01

    Between 1980 and 1989, 15 of 46 patients (11 children, 4 adults) who underwent suboccipital craniectomy and cervical laminectomy for symptomatic Chiari malformations presented with manifestations of neurogenic dysphagia. Each of these patients had normal swallowing function before the development of dysphagic symptoms. Dysphagia was progressive in all 15 and, in most cases, preceded the onset of other severe brain stem signs. The rate of symptom progression varied depending on the age of the patient. Whereas the six infants (all Chiari II) deteriorated rapidly after the onset of initial symptoms, the five older children (two Chiari I, three Chiari II) and four adults (all Chiari I) showed a more gradual deterioration. In 11 patients with severe dysphagia, barium video esophagograms, pharyngoesophageal motility studies, continuous esophageal pH monitoring, and appropriate scintigraphic studies were useful in defining the scope of the swallowing impairment and determining whether perioperative nasogastric or gastrostomy feedings, gastric fundoplication, and/or tracheostomy were needed to maintain adequate nutrition and avoid aspiration. These patients all had widespread dysfunction of the swallowing mechanism, with a combination of diffuse pharyngoesophageal dysmotility, cricopharyngeal achalasia, nasal regurgitation, tracheal aspiration, and gastroesophageal reflux. The pathophysiology of these swallowing impairments and their relation to the hindbrain malformation is discussed. Postoperative outcome with regard to swallowing function correlated with the severity of preoperative symptoms. The four patients with mild dysphagia showed rapid improvement in swallowing function after surgery. Seven patients with more severe impairment but without other signs of severe brain stem compromise, such as central apnea or complete bilateral vocal cord paralysis, also improved, albeit more slowly. In contrast, the outcome in the four patients who developed other signs of severe

  20. 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. PMID:26904414

  1. [Sacral neuromodulation for neurogenic bladder dysfunction].

    PubMed

    Kessler, T M; Wöllner, J; Kozomara, M; Mordasini, L; Mehnert, U

    2012-02-01

    Sacral neuromodulation (SNM) represents a promising option for managing treatment-refractory neurogenic bladder dysfunction. It remains to be seen, however, which types of neurogenic bladder dysfunction and which underlying neurological disorders best respond to SNM. Constant improvements in SNM have been achieved and it is now a minimally invasive approach performed under local anesthesia which should be considered before undertaking larger reconstructive procedures. An electrode is implanted in the S3 or S4 sacral foramen and during a test phase lasting for days to weeks the patient keeps a bladder diary to determine whether SNM has provided a relevant benefit. If the results of the test phase are positive, a neuromodulator is implanted in the gluteal area (or more rarely in the abdominal wall).The mechanism of action of SNM has not been completely clarified, but the afferent nerves most likely play a key role. It appears that SNM produces a modulation of medullary reflexes and brain centers by peripheral afferents. The implanted neuromodulation system does not lead to limitation of the patient's activities. However, it should be noted that high-frequency diathermy and unipolar electrocauterization are contraindicated in patients with neuromodulators, that during extracorporeal shock wave lithotripsy the focal point should not be in the direct vicinity of the neuromodulator or the electrode, that ultrasound and radiotherapy in the region of the implanted components should be avoided, that the neuromodulation should be discontinued in pregnancy, and that MRI examinations should only be conducted when urgently indicated and the neuromodulator is turned off. PMID:22269992

  2. 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

  3. Management options for sphincteric deficiency in adults with neurogenic bladder

    PubMed Central

    Mayer, Erik N.; Lenherr, Sara

    2016-01-01

    Neurogenic bladder is a very broad disease definition that encompasses varied disease and injury states affecting the bladder. The majority of patients with neurogenic bladder dysfunction do not have concomitant intrinsic sphincteric deficiency (ISD), but when this occurs the challenges of management of urinary incontinence from neurogenic bladder are compounded. There are no guidelines for surgical correction of ISD in adults and most of the literature on treatment of the problem comes from treatment of children with congenital diseases, such as myelomeningocele. Our goal, in this review, is to present some of the common surgical options for ISD [including artificial urinary sphincters, bladder slings, bladder neck reconstruction (BNR) and urethral bulking agents] and the evidence underlying these treatments in adults with neurogenic bladder. PMID:26904420

  4. 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. PMID:26056339

  5. Botulinum Toxin in Neurogenic Detrusor Overactivity

    PubMed Central

    Ferreira, Rúiter Silva; Rassi, Mauricio Carneiro

    2012-01-01

    Purpose To evaluate the effects of botulinum toxin on urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity. Methods Thirty four adult patients with spinal cord injury and detrusor overactivity were selected. The patients received 300 units of botulinum toxin type A. The endpoints evaluated with the episodes of urinary incontinence and measured the maximum cystometric capacity, maximum amplitude of detrusor pressure and bladder compliance at the beginning and end of the study (24 weeks) and evaluated the quality of life by applying the Qualiveen questionnaire. Results A significant decrease in the episodes of urinary incontinence was observed. All urodynamic parameters presented a significant improvement. The same was observed in the quality of life index and the specific impact of urinary problems scores from the Qualiveen questionnaire. Six patients did not complete the study, two due to incomplete follow-up, and four violated protocol and were excluded from the analyses. No systemic adverse events of botulinum toxin type A were reported. Conclusions A botulinum toxin type A showed a significantly improved response in urodynamics parameters and specific and general quality of life. PMID:23094220

  6. Discerning Neurogenic vs. Non-Neurogenic Postnatal Lateral Ventricular Astrocytes via Activity-Dependent Input

    PubMed Central

    Adlaf, Elena W.; Mitchell-Dick, Aaron; Kuo, Chay T.

    2016-01-01

    Throughout development, neural stem cells (NSCs) give rise to differentiated neurons, astrocytes, and oligodendrocytes which together modulate perception, memory, and behavior in the adult nervous system. To understand how NSCs contribute to postnatal/adult brain remodeling and repair after injury, the lateral ventricular (LV) neurogenic niche in the rodent postnatal brain serves as an excellent model system. It is a specialized area containing self-renewing GFAP+ astrocytes functioning as NSCs generating new neurons throughout life. In addition to this now well-studied regenerative process, the LV niche also generates differentiated astrocytes, playing an important role for glial scar formation after cortical injury. While LV NSCs can be clearly distinguished from their neuroblast and oligodendrocyte progeny via molecular markers, the astrocytic identity of NSCs has complicated their distinction from terminally-differentiated astrocytes in the niche. Our current models of postnatal/adult LV neurogenesis do not take into account local astrogenesis, or the possibility that cellular markers may be similar between non-dividing GFAP+ NSCs and their differentiated astrocyte daughters. Postnatal LV neurogenesis is regulated by NSC-intrinsic mechanisms interacting with extracellular/niche-driven cues. It is generally believed that these local effects are responsible for sustaining neurogenesis, though behavioral paradigms and disease states have suggested possibilities for neural circuit-level modulation. With recent experimental findings that neuronal stimulation can directly evoke responses in LV NSCs, it is possible that this exciting property will add a new dimension to identifying postnatal/adult NSCs. Here, we put forth a notion that neural circuit-level input can be a distinct characteristic defining postnatal/adult NSCs from non-neurogenic astroglia. PMID:27047330

  7. Role of Neurogenic Inflammation in Pancreatitis and Pancreatic Pain

    PubMed Central

    Vera-Portocarrero, Louis; Westlund, Karin N.

    2009-01-01

    Pain arising from pancreatic diseases can become chronic and difficult to treat. There is a paucity of knowledge regarding the mechanisms that sensitize neural pathways that transmit noxious information from visceral organs. In this review, neurogenic inflammation is presented as a possible amplifier of the noxious signal from peripheral organs including the pancreas. The nerve pathways that transmit pancreatic pain are also reviewed as a conduit of the amplified signals. It is likely that components of these visceral pain pathways can also be sensitized after neurogenic inflammation. PMID:16215298

  8. 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. PMID:24534025

  9. Unconventional Neurogenic Niches and Neurogenesis Modulation by Vitamins

    PubMed Central

    Oyarce, Karina; Bongarzone, Ernesto R.; Nualart, Francisco

    2015-01-01

    Although the generation of new neurons occurs in adult mammals, it has been classically described in two defined regions of the brain denominated neurogenic niches: the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus. In these regions, neural stem cells give rise to new neurons and glia, which functionally integrate into the existing circuits under physiological conditions. However, accumulating evidence indicates the presence of neurogenic potential in other brain regions, from which multipotent precursors can be isolated and differentiated in vitro. In some of these regions, neuron generation occurs at low levels; however, the addition of growth factors, hormones or other signaling molecules increases the proliferation and differentiation of precursor cells. In addition, vitamins, which are micronutrients necessary for normal brain development, and whose deficiency produces neurological impairments, have a regulatory effect on neural stem cells in vitro and in vivo. In the present review, we will describe the progress that has been achieved in determining the neurogenic potential in other regions, known as unconventional niches, as well as the characteristics of the neural stem cells described for each region. Finally, we will revisit the roles of commonly known vitamins as modulators of precursor cell proliferation and differentiation, and their role in the complex and tight molecular signaling that impacts these neurogenic niches. PMID:26203401

  10. NEUROGENIC RESPONSES OF RAT LUNG TO DIESEL EXHAUST

    EPA Science Inventory

    The investigators are among the first researchers to investigate neurogenic inflammation in the lungs of rats exposed to whole diesel exhaust. After exposure to both concentrations of diesel exhaust, consistently higher levels of plasma leakage and lower activity of the enz...

  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 thoracic outlet and pectoralis minor syndromes in children.

    PubMed

    Sanders, Richard J; Annest, Stephen J; Goldson, Edward

    2013-07-01

    Brachial plexus compression (BPC) occurs above the clavicle as neurogenic thoracic outlet syndrome (NTOS) and below as neurogenic pectoralis minor syndrome (NPMS). It was recently noted that 75% of the adults seen for NTOS also had NPMS and in some this was the only diagnosis. This is also true in children but has not yet been reported. Because surgical treatment of NPMS is a minimum risk operation for pectoralis minor tenotomy (PMT), recognition of NPMS and distinguishing it from NTOS becomes important. In this study, 40 operations, 20 PMT and 20 NTOS procedures, were performed. Success rate for PMT was 85% and for thoracic outlet decompression was 70%. It was concluded that in children, as in adults, BPC is more often due to combined NTOS and NPMS. Surgical PMT should be considered first as the treatment of choice for children with NPMS. Thoracic outlet decompression is available if PMT is unsuccessful. PMID:23503361

  14. 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

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

    PubMed

    Shridharani, Anand N; Brant, William O

    2016-02-01

    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. Slipped capital femoral epiphysis caused by neurogenic heterotopic ossification.

    PubMed

    Chang, Sam Yeol; Yoo, Won Joon; Park, Moon Seok; Chung, Chin Youb; Choi, In Ho; Cho, Tae-Joon

    2013-11-01

    Slipped capital femoral epiphysis (SCFE) is rare in nonambulatory patients, as mechanical factors play important roles in the development of the disease. We report a case of SCFE, which occurred in a 12-year-old girl with a nonambulatory status after cerebral infarction. SCFE occurred after she received passive range of motion exercise and extracorporeal shock wave treatment for neurogenic heterotopic ossification around the hip joint. The patient was successfully managed by a stepwise approach, with radiological and clinical improvements. PMID:23969564

  17. 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

  18. 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

  19. In silico Therapeutics for Neurogenic Hypertension and Vasovagal Syncope.

    PubMed

    Bojić, Tijana; Perović, Vladimir R; Glišić, Sanja

    2015-01-01

    Neurocardiovascular diseases (NCVD) are the leading cause of death in the developed world and will remain so till 2020. In these diseases the pathologically changed nervous control of cardiovascular system has the central role. The actual NCV syndromes are neurogenic hypertension, representing the sympathetically mediated disorder, and vasovagal syncope, which is the vagally mediated disorders. Vasovagal syncope, the disease far from its etiological treatment, could benefit from recruiting and application of antimuscarinic drugs used in other parasympathetic disorders. The informational spectrum method (ISM), a method widely applied for the characterization of protein-protein interactions in the field of immunology, endocrinology and anti HIV drug discovery, was applied for the first time in the analysis of neurogenic hypertension and vasovagal syncope therapeutic targets. In silico analysis revealed the potential involvement of apelin in neurogenic hypertension. Applying the EIIP/ISM bioinformatics concept in investigation of drugs for treatment of vasovagal syncope suggests that 78% of tested antimuscarinic drugs could have anti vasovagal syncope effect. The presented results confirm that ISM is a promissing method for investigation of molecular mechanisms underlying pathophysiological proceses of NCV syndromes and discovery of therapeutics targets for their treatment. PMID:26834545

  20. 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. PMID:26258298

  1. In silico Therapeutics for Neurogenic Hypertension and Vasovagal Syncope

    PubMed Central

    Bojić, Tijana; Perović, Vladimir R.; Glišić, Sanja

    2016-01-01

    Neurocardiovascular diseases (NCVD) are the leading cause of death in the developed world and will remain so till 2020. In these diseases the pathologically changed nervous control of cardiovascular system has the central role. The actual NCV syndromes are neurogenic hypertension, representing the sympathetically mediated disorder, and vasovagal syncope, which is the vagally mediated disorders. Vasovagal syncope, the disease far from its etiological treatment, could benefit from recruiting and application of antimuscarinic drugs used in other parasympathetic disorders. The informational spectrum method (ISM), a method widely applied for the characterization of protein-protein interactions in the field of immunology, endocrinology and anti HIV drug discovery, was applied for the first time in the analysis of neurogenic hypertension and vasovagal syncope therapeutic targets. In silico analysis revealed the potential involvement of apelin in neurogenic hypertension. Applying the EIIP/ISM bioinformatics concept in investigation of drugs for treatment of vasovagal syncope suggests that 78% of tested antimuscarinic drugs could have anti vasovagal syncope effect. The presented results confirm that ISM is a promissing method for investigation of molecular mechanisms underlying pathophysiological proceses of NCV syndromes and discovery of therapeutics targets for their treatment. PMID:26834545

  2. Regulation of airway neurogenic inflammation by neutral endopeptidase.

    PubMed

    Di Maria, G U; Bellofiore, S; Geppetti, P

    1998-12-01

    Airway neurogenic inflammation is caused by tachykinins released from peripheral nerve endings of sensory neurons within the airways, and is characterized by plasma protein extravasation, airway smooth muscle contraction and increased secretion of mucus. Tachykinins are degraded and inactivated by neutral endopeptidase (NEP), a membrane-bound metallopeptidase, which is located mainly at the surface of airway epithelial cells, but is also present in airway smooth muscle cells, submucosal gland cells and fibroblasts. The key role of NEP in limiting and regulating the neurogenic inflammation provoked by different stimuli has been demonstrated in a large series of studies published in recent years. It has also been shown that a variety of factors, which are relevant for airway diseases, including viral infections, allergen exposure, inhalation of cigarette smoke and other respiratory irritants, is able to reduce NEP activity, thus enhancing the effects of tachykinins within the airways. On the basis of these observations, the reduction of neutral endopeptidase activity may be regarded as a factor that switches neurogenic airway responses from their physiological and protective functions to a detrimental role that increases and perpetuates airway inflammation. However, further studies are needed to assess the role of neutral endopeptidase down regulation in the pathogenesis of asthma and other inflammatory airway diseases. PMID:9877509

  3. 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

  4. Adult Neurogenesis: Ultrastructure of a Neurogenic Niche and Neurovascular Relationships

    PubMed Central

    Chaves da Silva, Paula Grazielle; Benton, Jeanne L.; Beltz, Barbara S.; Allodi, Silvana

    2012-01-01

    The first-generation precursors producing adult-born neurons in the crayfish (Procambarus clarkii) brain reside in a specialized niche located on the ventral surface of the brain. In the present work, we have explored the organization and ultrastructure of this neurogenic niche, using light-level, confocal and electron microscopic approaches. Our goals were to define characteristics of the niche microenvironment, examine the morphological relationships between the niche and the vasculature and observe specializations at the boundary between the vascular cavity located centrally in the niche. Our results show that the niche is almost fully encapsulated by blood vessels, and that cells in the vasculature come into contact with the niche. This analysis also characterizes the ultrastructure of the cell types in the niche. The Type I niche cells are by far the most numerous, and are the only cell type present superficially in the most ventral cell layers of the niche. More dorsally, Type I cells are intermingled with Types II, III and IV cells, which are observed far less frequently. Type I cells have microvilli on their apical cell surfaces facing the vascular cavity, as well as junctional complexes between adjacent cells, suggesting a role in regulating transport from the blood into the niche cells. These studies demonstrate a close relationship between the neurogenic niche and vascular system in P. clarkii. Furthermore, the specializations of niche cells contacting the vascular cavity are also typical of the interface between the blood/cerebrospinal fluid (CSF)-brain barriers of vertebrates, including cells of the subventricular zone (SVZ) producing new olfactory interneurons in mammals. These data indicate that tissues involved in producing adult-born neurons in the crayfish brain use strategies that may reflect fundamental mechanisms preserved in an evolutionarily broad range of species, as proposed previously. The studies described here extend our understanding of

  5. Neurogenic stunned myocardium and cardiac transplantation: a case report.

    PubMed

    Hernández-Caballero, C; Martín-Bermúdez, R; Revuelto-Rey, J; Aguilar-Cabello, M; Villar-Gallardo, J

    2012-09-01

    We present the case of a 46-year-old woman referred to our center for urgent heart transplantation assessment, initially diagnosed as having cardiogenic shock of uncertain etiology. Some hours before she had suffered syncope without regaining consciousness. When she arrived at our hospital, the objective examination revealed bilateral unreactive mydriasis and absent brain-stem reflexes, and echocardiography showed global left ventricle wall hypokinesis sparing the apex. An urgent computed tomography (CT) imaging of the head was performed, which showed a massive subarachnoid hemorrhage and extensive cerebral edema. In the following hours, she fulfilled the criteria of brain-stem death and indeed became a multiorgan donor. The heart was rejected for transplantation because of the existence of left ventricle wall motion abnormalities associated with neurogenic stunned myocardium. Neurogenic stunned myocardium is a stress-related cardiomyopathy that occurs after an acute brain injury. It is especially frequent in subarachnoid hemorrhage, where it reaches an incidence of up to 40% of patients. It is characterized by acute electrocardiographic changes and regional hypokinesis of the left ventricle wall not consistent with the coronary artery distribution, and is thought to be a transient condition. For this reason it should not constitute an absolute contraindication to cardiac donation in young donors with no previous cardiac disease. In our hospital during the last year one third of the potential heart donors had regional left ventricle wall motion abnormalities compatible with neurogenic stunned myocardium. With the aim of improving the number of cardiac donors, several strategies have been described to try to demonstrate the reversibility of this entity, such as dobutamine stress echocardiography. PMID:22974925

  6. Neurogenic orthostatic hypotension and supine hypertension in Parkinson's disease and related synucleinopathies: prioritisation of treatment targets.

    PubMed

    Espay, Alberto J; LeWitt, Peter A; Hauser, Robert A; Merola, Aristide; Masellis, Mario; Lang, Anthony E

    2016-08-01

    Neurogenic orthostatic hypotension and supine hypertension are common manifestations of cardiovascular dysautonomia in Parkinson's disease and related synucleinopathies. Because these disorders are haemodynamic opposites, improvement in one might be achieved at the expense of worsening of the other. Thus, management decisions necessitate assessment of the individual risks for patients with coexistent neurogenic orthostatic hypotension and supine hypertension. Whereas neurogenic orthostatic hypotension poses risks for falls and can be associated with cognitive impairment in the short term, chronic supine hypertension can be associated with stroke and myocardial infarction in the long term. Because few clinical trial data exist for outcomes in patients with coexistent neurogenic orthostatic hypotension and supine hypertension, clinicians need to balance, on the basis of comorbidities and disease staging, the potential immediate benefits of treatment for neurogenic orthostatic hypotension and the long-term risks of supine hypertension treatment in each patient. Future research needs to focus on ascertaining a safe degree of supine hypertension when treating neurogenic orthostatic hypotension; the effectiveness of nocturnal antihypertensive therapy in patients with coexistent neurogenic orthostatic hypotension and supine hypertension; and the prevalence, scope, and therapeutic requirements for managing neurogenic orthostatic hypotension that manifests with falls or cognitive impairment, but without postural lightheadedness or near syncope. PMID:27478953

  7. 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…

  8. From blood to brain: the neurogenic niche of the crayfish brain.

    PubMed

    Hartenstein, Volker

    2014-08-11

    Adult neurogenic niches are present in both vertebrates and invertebrates. Where do stem cells populating these niches originate, and what are the mechanisms maintaining their self-renewal? In this issue of Developmental Cell, Benton et al. (2014) show that in crayfish, hemolymph-derived cells enter a neurogenic niche to replenish neural progenitors. PMID:25117680

  9. Neurogenic effect of VEGF is related to increase of astrocytes transdifferentiation into new mature neurons in rat brains after stroke.

    PubMed

    Shen, Shu-Wen; Duan, Chun-Ling; Chen, Xian-Hua; Wang, Yong-Quan; Sun, Xiao; Zhang, Qiu-Wan; Cui, Hui-Ru; Sun, Feng-Yan

    2016-09-01

    To study the cellular mechanism of vascular endothelial growth factor (VEGF)-enhanced neurogenesis in ischemic brain injury, we used middle cerebral artery occlusion (MCAO) model to induce transient focal ischemic brain injury. The results showed that ischemic injury significantly increased glial fibrillary acidic protein immunopositive (GFAP(+)) and nestin(+) cells in ipsilateral striatum 3 days following MCAO. Most GFAP(+) cells colocalized with nestin (GFAP(+)-nestin(+)), Pax6 (GFAP(+)-Pax6(+)), or Olig2 (GFAP(+)-Olig2(+)). VEGF further increased GFAP(+)-nestin(+) and GFAP(+)-Pax6(+) cells, and decreased GFAP(+)-Olig2(+) cells. We used striatal injection of GFAP targeted enhanced green fluorescence protein (pGfa2-EGFP) vectors combined with multiple immunofluorescent staining to trace the neural fates of EGFP-expressing (GFP(+)) reactive astrocytes. The results showed that MCAO-induced striatal reactive astrocytes differentiated into neural stem cells (GFP(+)-nestin(+) cells) at 3 days after MCAO, immature (GFP(+)-Tuj-1(+) cells) at 1 week and mature neurons (GFP(+)-MAP-2(+) or GFP(+)-NeuN(+) cells) at 2 weeks. VEGF increased GFP(+)-NeuN(+) and BrdU(+)-MAP-2(+) newborn neurons after MCAO. Fluorocitrate, an astrocytic inhibitor, significantly decreased GFAP and nestin expression in ischemic brains, and also reduced VEGF-enhanced neurogenic effects. This study is the first time to report that VEGF-mediated increase of newly generated neurons is dependent on the presence of reactive astrocytes. The results also illustrate cellular mechanism of VEGF-enhanced neural repair and functional plasticity in the brains after ischemic injury. We concluded that neurogenic effect of VEGF is related to increase of striatal astrocytes transdifferentiation into new mature neurons, which should be very important for the reconstruction of neurovascular units/networks in non-neurogenic regions of the mammalian brain. PMID:26603138

  10. 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

  11. 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. PMID:21834782

  12. [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. PMID:27156505

  13. 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. PMID:26592100

  14. Outcomes of bowel program in spinal cord injury patients with neurogenic bowel dysfunction

    PubMed Central

    Ozisler, Zuhal; Koklu, Kurtulus; Ozel, Sumru; Unsal-Delialioglu, Sibel

    2015-01-01

    In this study, we aimed to determine gastrointestinal problems associated with neurogenic bowel dysfunction in spinal cord injury patients and to assess the efficacy of bowel program on gastrointestinal problems and the severity of neurogenic bowel dysfunction. Fifty-five spinal cord injury patients were included in this study. A bowel program according to the characteristics of neurogenic bowel dysfunction was performed for each patient. Before and after bowel program, gastrointestinal problems (constipation, difficult intestinal evacuation, incontinence, abdominal pain, abdominal distension, loss of appetite, hemorrhoids, rectal bleeding and gastrointestinal induced autonomic dysreflexia) and bowel evacuation methods (digital stimulation, oral medication, suppositories, abdominal massage, Valsalva maneuver and manual evacuation) were determined. Neurogenic bowel dysfunction score was used to assess the severity of neurogenic bowel dysfunction. At least one gastrointestinal problem was identified in 44 (80%) of the 55 patients before bowel program. Constipation (56%, 31/55) and incontinence (42%, 23/55) were the most common gastrointestinal problems. Digital rectal stimulation was the most common method for bowel evacuation, both before (76%, 42/55) and after (73%, 40/55) bowel program. Oral medication, enema and manual evacuation application rates were significantly decreased and constipation, difficult intestinal evacuation, abdominal distention, and abdominal pain rates were significantly reduced after bowel program. In addition, mean neurogenic bowel dysfunction score was decreased after bowel program. An effective bowel program decreases the severity of neurogenic bowel dysfunction and reduces associated gastrointestinal problems in patients with spinal cord injury. PMID:26330842

  15. Lumbosacral perineural cysts as a cause for neurogenic muscular hypertrophy.

    PubMed

    Amoiridis, G; Wöhrle, J; Heye, N; Przuntek, H

    1997-08-01

    We report the case of a 40 year-old man with a severe lesion of the anterior rami of the left spinal nerves L5 and S1 who showed hypertrophy of the leg and atrophy of the intrinsic foot and gluteal muscles. In the biopsy of the hypertrophied gastrocnemius muscle, perivascular inflammatory infiltrates were observed, apart from atrophied and hypertrophied muscle fibres. Electromyography revealed no pathologic spontaneous activity but chronic neurogenic changes. The precise site of the lesion was predicted by electrophysiologic investigations. The lesion was caused by two perineural cysts in the region of the upper sacral plexus, as demonstrated by MRI and CT of the small pelvis and confirmed at operation. Three years earlier, when almost only L5 muscles were affected, an intervertebral disc prolapse L5/S1 had been suspected on myelography and CT but could not have been confirmed at operation. PMID:9298339

  16. Discriminating neurogenic from myopathic disease via measurement of muscle anisotropy.

    PubMed

    Garmirian, Lindsay P; Chin, Anne B; Rutkove, Seward B

    2009-01-01

    Skeletal muscle is electrically anisotropic, with a tendency for applied electrical current to flow more readily along muscle fibers than across them. In this study, we assessed a method for non-invasive measurement of anisotropy to determine its potential to serve as a new technique for distinguishing neurogenic from myopathic disease. Measurements were made on the biceps brachii and tibialis anterior muscles in 15 normal subjects and 12 patients with neuromuscular disease (6 with amyotrophic lateral sclerosis and 6 with various myopathies) using 50 kHZ applied current. Consistent multi-angle anisotropic patterns were found for reactance and phase in both muscles in normal subjects. Normalized anisotropy differences for each subject were defined, and group average values identified. The amyotrophic lateral sclerosis (ALS) patients demonstrated increased and distorted anisotropy patterns, whereas myopathic patients demonstrated normal or reduced anisotropy. These results suggest that non-invasive measurement of muscle anisotropy has potential for diagnosis of neuromuscular diseases. PMID:19058193

  17. The Neurogenic Potential of Astrocytes Is Regulated by Inflammatory Signals.

    PubMed

    Michelucci, Alessandro; Bithell, Angela; Burney, Matthew J; Johnston, Caroline E; Wong, Kee-Yew; Teng, Siaw-Wei; Desai, Jyaysi; Gumbleton, Nigel; Anderson, Gregory; Stanton, Lawrence W; Williams, Brenda P; Buckley, Noel J

    2016-08-01

    Although the adult brain contains neural stem cells (NSCs) that generate new neurons throughout life, these astrocyte-like populations are restricted to two discrete niches. Despite their terminally differentiated phenotype, adult parenchymal astrocytes can re-acquire NSC-like characteristics following injury, and as such, these 'reactive' astrocytes offer an alternative source of cells for central nervous system (CNS) repair following injury or disease. At present, the mechanisms that regulate the potential of different types of astrocytes are poorly understood. We used in vitro and ex vivo astrocytes to identify candidate pathways important for regulation of astrocyte potential. Using in vitro neural progenitor cell (NPC)-derived astrocytes, we found that exposure of more lineage-restricted astrocytes to either tumor necrosis factor alpha (TNF-α) (via nuclear factor-κB (NFκB)) or the bone morphogenetic protein (BMP) inhibitor, noggin, led to re-acquisition of NPC properties accompanied by transcriptomic and epigenetic changes consistent with a more neurogenic, NPC-like state. Comparative analyses of microarray data from in vitro-derived and ex vivo postnatal parenchymal astrocytes identified several common pathways and upstream regulators associated with inflammation (including transforming growth factor (TGF)-β1 and peroxisome proliferator-activated receptor gamma (PPARγ)) and cell cycle control (including TP53) as candidate regulators of astrocyte phenotype and potential. We propose that inflammatory signalling may control the normal, progressive restriction in potential of differentiating astrocytes as well as under reactive conditions and represent future targets for therapies to harness the latent neurogenic capacity of parenchymal astrocytes. PMID:26138449

  18. A novel natural product inspired scaffold with robust neurotrophic, neurogenic and neuroprotective action.

    PubMed

    Chakravarty, Sumana; Maitra, Swati; Reddy, R Gajendra; Das, Tapatee; Jhelum, Priya; Kootar, Scherazad; Rajan, Wenson D; Samanta, Anumita; Samineni, Ramesh; Pabbaraja, Srihari; Kernie, Steven G; Mehta, Goverdhan; Kumar, Arvind

    2015-01-01

    In search for drugs to treat neuropsychiatric disorders wherein neurotrophic and neurogenic properties are affected, two neurotrophically active small molecules specially crafted following natural product leads based on 2-oxa-spiro[5.5]-undecane scaffold, have been thoroughly evaluated for their neurotrophic, neurogenic and neuroprotective potential in ex vivo primary culture and in vivo zebrafish and mouse models. The outcome of in vivo investigations suggest that one of these molecules is more neurotrophic than neurogenic while the other one is more neurogenic than neurotrophic and the former exhibits remarkable neuroprotection in a mouse acute ischemic stroke model. The molecular mechanisms of action of these compounds appear to be through the TrkB-MEK-ERK-CREB-BDNF pathway as pre-treatment with neurotrophin receptor TrkB inhibitor ANA-12 and MEK inhibitor PD98059 attenuates the neurotrophic action of compounds. PMID:26388493

  19. A novel natural product inspired scaffold with robust neurotrophic, neurogenic and neuroprotective action

    PubMed Central

    Chakravarty, Sumana; Maitra, Swati; Reddy, R Gajendra; Das, Tapatee; Jhelum, Priya; Kootar, Scherazad; Rajan, Wenson D.; Samanta, Anumita; Samineni, Ramesh; Pabbaraja, Srihari; Kernie, Steven G.; Mehta, Goverdhan; Kumar, Arvind

    2015-01-01

    In search for drugs to treat neuropsychiatric disorders wherein neurotrophic and neurogenic properties are affected, two neurotrophically active small molecules specially crafted following natural product leads based on 2-oxa-spiro[5.5]-undecane scaffold, have been thoroughly evaluated for their neurotrophic, neurogenic and neuroprotective potential in ex vivo primary culture and in vivo zebrafish and mouse models. The outcome of in vivo investigations suggest that one of these molecules is more neurotrophic than neurogenic while the other one is more neurogenic than neurotrophic and the former exhibits remarkable neuroprotection in a mouse acute ischemic stroke model. The molecular mechanisms of action of these compounds appear to be through the TrkB-MEK-ERK-CREB-BDNF pathway as pre-treatment with neurotrophin receptor TrkB inhibitor ANA-12 and MEK inhibitor PD98059 attenuates the neurotrophic action of compounds. PMID:26388493

  20. Is Melanoma a stem cell tumor? Identification of neurogenic proteins in trans-differentiated cells

    PubMed Central

    Rasheed, Suraiya; Mao, Zisu; Chan, Jane MC; Chan, Linda S

    2005-01-01

    proteins that halt the tumorigenic potential of melanoma cells and drive them toward neurogenerative pathways involved in early neurogenesis. A better understanding of these proteins in a well-coordinated signaling network would also help in developing novel approaches for suppression of highly malignant tumors that arise from stem-like embryonic cells. PMID:15784142

  1. 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. PMID:26238098

  2. Preventing kidney injury in children with neurogenic bladder dysfunction.

    PubMed

    Larijani, Faezeh Javadi; Moghtaderi, Mastaneh; Hajizadeh, Nilofar; Assadi, Farahnak

    2013-12-01

    The most common cause of neurogenic bladder dysfunction (NBD) in newborn infants is myelomeningocele. The pathophysiology almost always involves the bladder detrusor sphincter dyssynergy (DSD), which if untreated can cause severe and irreversible damage to the upper and lower urinary tracts. Early diagnosis and adequate management of NBD is critical to prevent both renal damage and bladder dysfunction and to reduce chances for the future surgeries. Initial investigation of the affected newborn infant includes a renal and bladder ultrasound, measurement of urine residual, determination of serum creatinine level, and urodynamics study. Voiding cystogram is indicated when either hydronephrosis or DSD is present. The main goal of treatment is prevention of urinary tract deterioration and achievement of continuance at an appropriate age. Clean intermittent catheterization (CIC) in combination with anticholinergic (oxybutynin) and antibiotics are instituted in those with high filling and voiding pressures, DSD and/or high grade reflux immediately after the myelomeningocele is repaired. Botulium toxin-A injection into detrusor is a safe alternative in patients with insufficient response or significant side effects to anticholinergic (oral or intravesical instillation) therapy. Surgery is an effective alternative in patients with persistent detrusor hyperactivity and/or dyssynergic detrusor sphincter despites of the CIC and maximum dosage of anticholinergic therapy. Children with NBD require care from a multidisciplinary team approach consisting of pediatricians, neurosurgeon, urologist, nephrologists, orthopedic surgeon, and other allied medical specialists. PMID:24498490

  3. 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

  4. The role of botulinum toxin A in treating neurogenic bladder.

    PubMed

    Weckx, Filip; Tutolo, Manuela; De Ridder, Dirk; Van der Aa, Frank

    2016-02-01

    Neurogenic detrusor overactivity (NDO) can result in lower and upper urinary tract complications and eventually even in end-stage kidney failure. Since the driving force of this clinical cascade is high bladder pressure, controlling intravesical pressure in NDO patients improves both quality of life and life-expectancy in these patients. Botulinum toxin A (BTX-A) has proven its efficacy in reducing intravesical pressure and in reducing incontinence episodes. BTX-A also improves quality of life in patients with NDO. Both onabotulinumtoxinA (Botox(®), Allergan, Irvine, USA) and abobotulinumtoxinA (Dysport(®), Ipsen, Paris, France) have a level A recommendation for NDO-treatment. The recommended dose for intradetrusor injections in NDO patients is 200 U of onabotulinumtoxinA or 500 U of abobotulinumtoxinA. The drug is generally administered extratrigonal in the detrusor muscle, via cystoscopic guided injection at 20 sites in 1 mL injections. Intradetrusor BTX-A injections are safe, with mostly local complications such as urinary tract infection and high post-void residual or retention. The effect of the toxin lasts for approximately 9 months. Repeat injections can be performed without loss of efficacy. Different injection techniques, novel ways of BTX-A administration, eliminating the need for injection or new BTX-A types with better/longer response rates could change the field in the future. PMID:26904413

  5. The role of botulinum toxin A in treating neurogenic bladder

    PubMed Central

    Weckx, Filip; Tutolo, Manuela; De Ridder, Dirk

    2016-01-01

    Neurogenic detrusor overactivity (NDO) can result in lower and upper urinary tract complications and eventually even in end-stage kidney failure. Since the driving force of this clinical cascade is high bladder pressure, controlling intravesical pressure in NDO patients improves both quality of life and life-expectancy in these patients. Botulinum toxin A (BTX-A) has proven its efficacy in reducing intravesical pressure and in reducing incontinence episodes. BTX-A also improves quality of life in patients with NDO. Both onabotulinumtoxinA (Botox®, Allergan, Irvine, USA) and abobotulinumtoxinA (Dysport®, Ipsen, Paris, France) have a level A recommendation for NDO-treatment. The recommended dose for intradetrusor injections in NDO patients is 200 U of onabotulinumtoxinA or 500 U of abobotulinumtoxinA. The drug is generally administered extratrigonal in the detrusor muscle, via cystoscopic guided injection at 20 sites in 1 mL injections. Intradetrusor BTX-A injections are safe, with mostly local complications such as urinary tract infection and high post-void residual or retention. The effect of the toxin lasts for approximately 9 months. Repeat injections can be performed without loss of efficacy. Different injection techniques, novel ways of BTX-A administration, eliminating the need for injection or new BTX-A types with better/longer response rates could change the field in the future. PMID:26904413

  6. 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

  7. Management of detrusor external sphincter dyssynergia in neurogenic bladder.

    PubMed

    Mahfouz, W; Corcos, J

    2011-12-01

    Spinal cord injury (SCI) affects 11.5 to 53.4 individuals per million of the population in developed countries each year. SCI is caused by trauma, although it can also result from myelopathy, myelitis, vascular disease or arteriovenous malformations and multiple sclerosis. Patients with complete lesions of the spinal cord between spinal cord level T6 and S2, after they recover from spinal shock, generally exhibit involuntary bladder contractions without sensation, smooth sphincter synergy, but with detrusor striated sphincter dyssynergia (DESD). Those with lesions above spinal cord level T6 may experience, in addition, smooth sphincter dyssynergia and autonomic hyperreflexia. DESD is a debilitating problem in patients with SCI. It carries a high risk of complications, and even life expectancy can be affected. Nearly half of the patients with untreated DESD will develop deleterious urologic complications, due to high intravesical pressures, resulting in urolithiasis, urinary tract infection (UTI), vesicoureteral reflux (VUR), hydronephrosis, obstructive uropathy, and renal failure. The mainstay of treatment is the use of antimuscarinics and catheterization, but in those for whom this is not possible external sphincterotomy has been a last resort option. External sphincterotomy is associated with significant risks, including haemorrhage; erectile dysfunction and the possibility of redo procedures. Over the last decade alternatives have been investigated, such as urethral stents and intrasphincteric botulinum toxin injection. In this review, we will cover neurogenic DESD, with emphasis on definition, classifications, diagnosis and different therapeutic options available. PMID:22081065

  8. Early versus Late Surgical Treatment for Neurogenic Thoracic Outlet Syndrome

    PubMed Central

    Al-Hashel, Jasem Yousef; El Shorbgy, Ashraf Ali M. A.; Elshereef, Rawhia R.

    2013-01-01

    Objectives. To compare the outcome of early surgical intervention versus late surgical treatment in cases of neurogenic thoracic outlet syndrome (NTOS). Design. Prospective study. Settings. Secondary care (Al-Minia University Hospital, Egypt) from 2007 to 2010. Participants. Thirty-five patients of NTOS (25 women and 10 men, aged 20–52 years), were classified into 2 groups. First group (20 patients) was operated within 3 months of the onset and the second group (15 patients) was operated 6 months after physiotherapy. Interventions. All patients were operated via supraclavicular surgical approach. Outcomes Measures. Both groups were evaluated clinically and, neurophysiologically and answered the disabilities of the arm, shoulder, and hand (DASH) questionnaire preoperatively and 6 months after the surgery. Results. Paraesthesia, pain, and sensory nerve action potential (SNAP) of ulnar nerve were significantly improved in group one. Muscle weakness and denervation in electromyography EMG were less frequent in group one. The postoperative DASH score improved in both groups but it was less significant in group two (P < .001 in group 1 and P < .05 in group 2). Conclusions. Surgical treatment of NTOS improves functional disability and stop degeneration of the nerves. Early surgical treatment decreases the occurrence of muscle wasting and denervation of nerves compared to late surgery. PMID:24109518

  9. 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

  10. Replication-deficient adenoviral vector for gene transfer potentiates airway neurogenic inflammation.

    PubMed

    Piedimonte, G; Pickles, R J; Lehmann, J R; McCarty, D; Costa, D L; Boucher, R C

    1997-03-01

    Human trials for the treatment of cystic fibrosis lung disease with adenoviral vectors have been complicated by acute inflammatory reactions of unknown etiology. Because replicating respiratory viruses can potentiate tachykinin-mediated neurogenic inflammatory responses in airways, we studied whether the endotracheal administration of a replication-deficient adenoviral vector potentiated this response. The vector Ad5CMVLacZ was administered endotracheally to rats and the leakage of Evans blue dye was used to measure the capsaicin-induced neurogenic albumin extravasation. These studies show that neurogenic albumin extravasation is significantly potentiated in the airways of rats after administration of Ad5CMVLacZ. This inflammatory response can be blocked by selective antagonists of the substance P receptor or by glucocorticoids. Therefore, (1) the acute airway inflammation observed in patients after exposure to adenoviral vectors may exhibit a neurogenic component, which can be blocked pharmacologically, and (2) preclinical adenoviral vector safety studies of other organs innervated by the tachykinin system, e.g., coronary arteries and gastrointestinal tract, should include assessment of neurogenic inflammation. PMID:9070609

  11. New developments in the management of neurogenic orthostatic hypotension.

    PubMed

    Biaggioni, Italo

    2014-11-01

    Orthostatic hypotension (OH) is defined as a sustained reduction of ≥ 20 mmHg systolic blood pressure or ≥ 10 mmHg diastolic blood pressure upon standing for ≤ 3 min. Orthostatic hypotension is commonly associated with hypertension, and its prevalence is highest in those with uncontrolled hypertension compared to those with controlled hypertension or normotensive community elderly subjects. Orthostatic hypotension can cause significant disability, with patients experiencing dizziness, lightheadedness or syncope, and other problems that potentially have a profound negative impact on activities of daily living that require standing or walking. Furthermore, OH increases the risk of falls and, importantly, is an independent risk factor of mortality. Despite its importance, there is a paucity of treatment options for this condition. Most of the advances in treatment options have relied on small studies of repurposed drugs done in patients with severe OH due to rare neurodegenerative conditions. Midodrine, an oral prodrug converted to the selective α1-adrenoceptor agonist desglymidodrine, was approved by the FDA for the treatment of OH in 1996. For almost two decades, no other pharmacotherapy was developed specifically for the treatment of OH until 2014, when droxidopa was approved by the FDA for the treatment of neurogenic OH associated with primary autonomic neuropathies including Parkinson disease, multiple system atrophy, and pure autonomic failure. These are neurodegenerative diseases ultimately characterized by failure of the autonomic nervous system to generate norepinephrine responses appropriate to postural challenge. Droxidopa is a synthetic amino acid that is converted to norepinephrine by dopa-decarboxylase, the same enzyme that converts levodopa into dopamine in the treatment of Parkinson disease. We will review this and other advances in the treatment of OH in an attempt to provide a practical guide to its management. PMID:25303896

  12. Blocking Neurogenic Inflammation for the Treatment of Acute Disorders of the Central Nervous System

    PubMed Central

    Lewis, Kate Marie; Turner, Renée Jade

    2013-01-01

    Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis. PMID:23819099

  13. 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

  14. 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. PMID:26991819

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

    PubMed

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

    2015-09-01

    Neurogenic detrusor overactivity (NDO) is a lower urinary tract dysfunction commonly seen in rehabilitation settings. The emotional, medical, and financial consequences of NDO can be substantial and management typically requires a multidisciplinary team approach. Physiatrists need to be able to identify patients who require referral to specialists for diagnostic testing or higher-tiered treatment and need to engender open lines of communication between their patients and all treating clinicians. This requires an understanding of the evaluation, diagnosis, and treatment of neurogenic lower urinary tract dysfunctions. PMID:26318392

  16. 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

  17. Comprehensive expression map of transcription regulators in the adult zebrafish telencephalon reveals distinct neurogenic niches.

    PubMed

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

    2015-06-01

    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. PMID:25556858

  18. 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…

  19. Ruptured spinal arteriovenous malformation: Presenting as stunned myocardium and neurogenic shock

    PubMed Central

    Mehesry, Tasneem H.; Shaikh, Nissar; Malmstrom, Mohammad F.; Marcus, Marco A. E.; Khan, Adnan

    2015-01-01

    Background: Neurogenic pulmonary edema (NPE) is a clinical syndrome usually defined as an acute pulmonary edema occurring shortly after a central neurologic insult. NPE was identified 100 years ago, but it is still underappreciated in the clinical setup. NPE usually appears within minutes to hours after the injury. It has a high mortality rate if not recognized early and treated appropriately. Similarly, neurogenic shock is a known complication of spinal cord injury reported incidence is more than 20% in isolated upper cervical spinal injury. But NPE is rare to occur, and stunned myocardium (SM) is not reported in spinal arteriovenous malformation (AVM) rupture. SM is a reversible cardiomyopathy resulting in transient left ventricular dysfunction which has been described to occur in the setting of catecholamine release during situations of physiologic stress. We report a case of high spinal AVM rupture presenting as SM, NPE, and neurogenic shock. Case Description: A 32-year-old male who presented with sudden onset of pain and weakness in upper limbs. Imaging studies showed AVM rupture by imaging techniques. Initially, the patient had severe hypertension, respiratory distress requiring intubation and ventilation, then he developed hypotension, bradycardia, and asystole, which required immediate cardiopulmonary resuscitation and atropine. He remained with quadriplegia and suffered from frequent episodes of bradycardia and asystole. Conclusions: Spinal AVM rupture can present as neurogenic shock, stunned myocardium, and pulmonary edema. Early recognition of AVM rupture and prompt surgical intervention, as well as aggressive treatment of shock, may enhance recovery and decrease the long-term morbidity. PMID:26539315

  20. 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

  1. 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…

  2. miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction

    PubMed Central

    Woodbury, Maya E.; Freilich, Robert W.; Cheng, Christopher J.; Asai, Hirohide; Ikezu, Seiko; Boucher, Jonathan D.; Slack, Frank

    2015-01-01

    Peripheral and CNS inflammation leads to aberrations in developmental and postnatal neurogenesis, yet little is known about the mechanism linking inflammation to neurogenic abnormalities. Specific miRs regulate peripheral and CNS inflammatory responses. miR-155 is the most significantly upregulated miR in primary murine microglia stimulated with lipopolysaccharide (LPS), a proinflammatory Toll-Like Receptor 4 ligand. Here, we demonstrate that miR-155 is essential for robust IL6 gene induction in microglia under LPS stimulation in vitro. LPS-stimulated microglia enhance astrogliogenesis of cocultured neural stem cells (NSCs), whereas blockade of IL6 or genetic ablation of microglial miR-155 restores neural differentiation. miR-155 knock-out mice show reversal of LPS-induced neurogenic deficits and microglial activation in vivo. Moreover, mice with transgenic elevated expression of miR-155 in nestin-positive neural and hematopoietic stem cells, including microglia, show increased cell proliferation and ectopically localized doublecortin-positive immature neurons and radial glia-like cells in the hippocampal dentate gyrus (DG) granular cell layer. Microglia have proliferative and neurogenic effects on NSCs, which are significantly altered by microglial miR-155 overexpression. In addition, miR-155 elevation leads to increased microglial numbers and amoeboid morphology in the DG. Our study demonstrates that miR-155 is essential for inflammation-induced neurogenic deficits via microglial activation and induction of IL6 and is sufficient for disrupting normal hippocampal development. PMID:26134658

  3. 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

  4. Focal Ligamentum Flavum Hypertrophy with Ochronotic Deposits: An Unusual Cause for Neurogenic Claudication in Alkaptonuria

    PubMed Central

    Vijayasaradhi, Mudumba; Biswal, Debabrat

    2012-01-01

    Neurogenic claudication resulting from focal hypertrophy of the ligamentum flavum in the lumbar spine due to ochronotic deposits has not been reported till date. The authors discuss one such case highlighting the pathogenesis, histological and radiological features. Salient features of management are also emphasized upon. PMID:22708021

  5. 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

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

    PubMed

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

    2016-02-01

    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

  7. 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

  8. Endogenous neurogenic cell response in the mature mammalian brain following traumatic injury.

    PubMed

    Sun, Dong

    2016-01-01

    In the mature mammalian brain, new neurons are generated throughout life in the neurogenic regions of the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus. Over the past two decades, extensive studies have examined the extent of adult neurogenesis in the SVZ and DG, the role of the adult generated new neurons in normal brain function and the underlying mechanisms regulating the process of adult neurogenesis. The extent and the function of adult neurogenesis under neuropathological conditions have also been explored in varying types of disease models in animals. Increasing evidence has indicated that these endogenous neural stem/progenitor cells may play regenerative and reparative roles in response to CNS injuries or diseases. This review will discuss the potential functions of adult neurogenesis in the injured brain and will describe the recent development of strategies aimed at harnessing this neurogenic capacity in order to repopulate and repair the injured brain following trauma. PMID:25936874

  9. Acute intraoperative neurogenic myocardial stunning during intracranial endoscopic fenestration and shunt revision in a pediatric patient.

    PubMed

    Dragan, Kristen Elizabeth; Patten, William D; Elzamzamy, Osama M; Attaallah, Ahmed Fikry

    2016-02-01

    Neurogenic stunned myocardium (NSM) is syndrome of myocardial dysfunction following an acute neurological insult. We report a case of NSM that occurred intraoperatively in a pediatric patient undergoing endoscopic fenestration and shunt revision. Accidental outflow occlusion of irrigation fluid and ventricular distension resulted in an acute increase in heart rate and arterial blood pressure. Subsequently, the patient developed stunned myocardium with global myocardial hypokinesia and pulmonary edema. She was promptly treated intraoperatively then admitted to the pediatric intensive care unit with resolution of her symptoms within 12 h. She was later discharged to home on the fourth postoperative day. In the current endoscopic era, this report highlights the possibility of intraoperative NSM and neurogenic pulmonary edema in the pediatric population. Early detection and treatment with a team approach help to achieve optimal control of this life-threatening condition and improve the outcome. PMID:26314948

  10. Topical acetyl salicylate and dipyrone attenuate neurogenic protein extravasation in rat skin in vivo.

    PubMed

    Schmelz, M; Weber, S; Kress, M

    2000-08-18

    The effect of topically applied acetyl salicylic acid (ASA) and dipyrone on capsaicin-evoked protein extravasation was investigated by dermal microdialysis in rat. After a baseline of 75 min, capsaicin (1%) was applied epicutaneously under occlusion for 75 min above the capillaries. Topical capsaicin stimulation induced neurogenic protein extravasation with a mean increase of protein concentration in the perfusate of 165+/-27% (mean+/-SEM; n=15), whereas in sham-stimulated sites protein concentration decreased to 73+/-7% of the prestimulation value (n=6). ASA (2-200 mg/ml) and dipyrone (3-300 mg/ml) dose-dependently reduced the capsaicin induced protein extravasation to 118+/-23% (ASA, 200 mg/ml; n=8) and 72+/-9% (dipyrone, 300 mg/ml; n=8) of the prestimulation value. ASA and dipyrone antagonized the excitatory effects of capsaicin on skin nociceptors and thus suppressed the neurogenic protein extravasation. PMID:10925174

  11. 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

  12. 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

  13. Neurogenic stunned myocardium as a manifestation of encephalitis involving cerebellar tonsils.

    PubMed

    Lin, Wen-Sou; Sung, Yueh-Feng

    2012-11-01

    Neurogenic stunned myocardium is defined as a myocardial injury or dysfunction after neurological insults. It is most commonly reported in patients with subarachnoid hemorrhage, and the presenting symptoms may mimic an acute myocardial infarction or myocarditis. In severe cases, cardiogenic shock and acute pulmonary edema may occur and lead to a devastating event. Therefore, it requires prompt recognition and proper intervention. We herein report the case of a 25-year-old woman who presented to our hospital with the symptoms of acute pulmonary edema, shock, and consciousness disturbance. The diagnosis of encephalitis of cerebellar tonsils complicated with acute hydrocephalus and neurogenic stunned myocardium was made. Detailed neurologic examinations, neuroimaging studies, and characteristic echocardiographic changes expedite the correct diagnosis and treatment. PMID:22205010

  14. 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

  15. A simple assessment model to quantifying the dynamic hippocampal neurogenic process in the adult mammalian brain.

    PubMed

    Choi, Minee L; Begeti, Faye; Barker, Roger A; Kim, Namho

    2016-04-01

    Adult hippocampal neurogenesis is a highly dynamic process in which new cells are born, but only some of which survive. Of late it has become clear that these surviving newborn neurons have functional roles, most notably in certain forms of memory. Conventional methods to look at adult neurogenesis are based on the quantification of the number of newly born neurons using a simple cell counting methodology. However, this type of approach fails to capture the dynamic aspects of the neurogenic process, where neural proliferation, death and differentiation take place continuously and simultaneously. In this paper, we propose a simple mathematical approach to better understand the adult neurogenic process in the hippocampus which in turn will allow for a better analysis of this process in disease states and following drug therapies. © 2015 Wiley Periodicals, Inc. PMID:26443687

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

    PubMed

    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. 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

  18. Dynamic changes of the neurogenic potential in the rat cochlear nucleus during post-natal development.

    PubMed

    Rak, Kristen; Völker, Johannes; Frenz, Silke; Scherzed, Agmal; Radeloff, Andreas; Hagen, Rudolf; Mlynski, Robert

    2013-05-01

    Neuronal stem cells have been described in the post-natal cochlear nucleus recently. The aim of the study was to analyse the neurogenic potential in the cochlear nucleus from the early post-natal days until adulthood. Cochlear nuclei from Sprague-Dawley rats from post-natal day P3 up to P40 were examined. Neurosphere assays showed persistent neurosphere formation from the early post-natal days until adulthood. The numbers of generated neurospheres were fewer in older ages. Neurospheres were smaller, but displayed the same pattern of neuronal stem cell markers. The markers GFAP, MBP and ß-III Tubulin showed differentiation of dissociated cells from the neurospheres in all cells of the neuronal lineage. BrdU incorporation could be detected, in an age-dependent decrease, in whole-mount experiments of the cochlear nucleus on all examined days. BrdU co-labelled with Atoh1 and ß-III Tubulin. In addition, gene expression and cellular distribution studies of the neuronal stem cell markers displayed an age-dependent reduction in both quantity and numbers. The presented results display a possible neurogenic potential until adulthood in the cochlear nucleus by in vitro and in vivo experiments. The fact that this potential is highest at a critical period of development reveals possible functional importance for the development of the cochlear nucleus and the auditory function. The persistent neurogenic potential displayed until adulthood could be a neurogenic niche in the adult cochlear nucleus, which might be used for potential therapeutic strategies. PMID:23455726

  19. 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

  20. 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. PMID:12512793

  1. Pathophysiological and Therapeutic Considerations for Non-Neurogenic Lower Urinary Tract Dysfunction in Children.

    PubMed

    Kakizaki, Hidehiro; Kita, Masafumi; Watanabe, Masaki; Wada, Naoki

    2016-05-01

    Non-neurogenic lower urinary tract dysfunction (LUTD) in children is very common in clinical practice and is important as an underlying cause of lower urinary tract symptoms, urinary tract infection and vesicoureteral reflux in affected children. LUTD in children is caused by multiple factors and might be related with a delay in functional maturation of the lower urinary tract. Behavioral and psychological problems often co-exist in children with LUTD and bowel dysfunction. Recent findings in functional brain imaging suggest that bladder bowel dysfunction and behavioral and psychiatric disorders in children might share common pathophysiological factors in the brain. Children with suspected LUTD should be evaluated properly by detailed history taking, validated questionnaire on voiding and defecation, voiding and bowel diary, urinalysis, screening ultrasound, uroflowmetry and post-void residual measurement. Invasive urodynamic study such as videourodynamics should be reserved for children in whom standard treatment fails. Initial treatment of non-neurogenic LUTD is standard urotherapy comprising education of the child and family, regular optimal voiding regimens and bowel programs. Pelvic floor muscle awareness, biofeedback and neuromodulation can be used as a supplementary purpose. Antimuscarinics and α-blockers are safely used for overactive bladder and dysfunctional voiding, respectively. For refractory cases, botulinum toxin A injection is a viable treatment option. Prudent use of urotherapy and pharmacotherapy for non-neurogenic LUTD should have a better chance to cure various problems and improve self-esteem and quality of life in affected children. PMID:27111618

  2. Congenital neurogenic muscular atrophy in megaconial myopathy due to a mutation in CHKB gene.

    PubMed

    Castro-Gago, Manuel; Dacruz-Alvarez, David; Pintos-Martínez, Elena; Beiras-Iglesias, Andrés; Arenas, Joaquín; Martín, Miguel Ángel; Martínez-Azorín, Francisco

    2016-01-01

    Choline kinase beta gene (CHKB) mutations have been identified in Megaconial Congenital Muscular Dystrophy (MDCMC) patients, a very rare inborn error of metabolism with 21 cases reported worldwide. We report the case of a Spanish boy of Caucasian origin who presented a generalized congenital muscular hypotonia, more intense at lower limb muscles, mildly elevated creatine kinase (CK), serum aspartate transaminase (AST) and lactate. Electromyography (EMG) showed neurogenic potentials in the proximal muscles. Histological studies of a muscle biopsy showed neurogenic atrophy with enlarged mitochondria in the periphery of the fibers, and complex I deficiency. Finally, genetic analysis showed the presence of a homozygous mutation in the gene for choline kinase beta (CHKB: NM_005198.4:c.810T>A, p.Tyr270(∗)). We describe here the second Spanish patient whit mutation in CHKB gene, who despite having the same mutation, presented an atypical aspect: congenital neurogenic muscular atrophy progressing to a combined neuropathic and myopathic phenotype (mixed pattern). PMID:26006750

  3. 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. PMID:26225287

  4. 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

  5. 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

  6. 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

  7. 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. PMID:27097940

  8. Protocol for a prospective magnetic resonance imaging study on supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity

    PubMed Central

    2014-01-01

    resonance imaging analysis. Discussion This study will identify structural and functional alterations in supraspinal networks of lower urinary tract control in spinal cord injury patients with neurogenic detrusor overactivity compared to healthy controls. Post-treatment magnetic resonance imaging measurements in spinal cord injury patients will provide further insights into the mechanism of action of treatments such as intradetrusor onabotulinumtoxinA injections and the effect on supraspinal lower urinary tract control. Trial registration ClinicalTrials.gov NCT01768910. PMID:25132340

  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. Loss of capsaicin-induced meningeal neurogenic sensory vasodilatation in diabetic rats.

    PubMed

    Dux, M; Rosta, J; Pintér, S; Sántha, P; Jancsó, G

    2007-11-30

    Neuropathic alterations of sensory nerves involved in the mediation of neurogenic inflammation of the meninges may contribute to the increased incidence of headaches in diabetics. In the rat, activation of capsaicin-sensitive nociceptors, which express the transient receptor potential vanilloid type 1 (TRPV1) receptor, induces meningeal vasodilatation, a significant component of neurogenic inflammation, through the release of calcitonin gene-related peptide (CGRP). This study examines the effects of streptozotocin-induced diabetes on TRPV1 receptor-mediated neurogenic sensory vasodilatation, CGRP release and nerve fiber density in the rat dura mater. In a cranial window preparation, epidural application of capsaicin (10(-7) M) produced distinct vasodilatory responses in control animals as measured by laser Doppler flowmetry. In diabetic rats, capsaicin-induced vasodilatation was reduced or even abolished 6, but not 2 or 4 weeks after diabetes induction. In contrast, vasoconstriction, a non-neurogenic response to capsaicin at a higher concentration (10(-5) M), was not altered in diabetic rats. The vasodilatory effects of histamine (10(-5) M), acetylcholine (10(-4) M) and CGRP (10(-5) M) were similar in control, diabetic and insulin-treated diabetic animals. In diabetic rats, a significant decrease in the capsaicin-evoked release of CGRP and reduction in the density of TRPV1-immunoreactive (IR) nerves were demonstrated. Treatment of the diabetic rats with insulin restored both the vasodilatory response and the capsaicin-induced CGRP release toward control values. In conclusion, this study revealed a marked impairment of meningeal TRPV1-IR nerves in streptozotocin diabetic rats by showing reduced neurogenic sensory vasodilatation, decreased capsaicin-evoked CGRP release and reduction in the number of TRPV1-IR nerve fibers of the dura mater. The findings suggest that capsaicin-sensitive afferents may play an important role in meningeal nociceptor function and their

  11. 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)

  12. Epistatic Partners of Neurogenic Genes Modulate Drosophila Olfactory Behavior

    PubMed Central

    St. Armour, Genevieve E.; Mackay, Trudy F. C.; Anholt, Robert R. H.

    2016-01-01

    The extent to which epistasis affects the genetic architecture of complex traits is difficult to quantify, and identifying variants in natural populations with epistatic interactions is challenging. Previous studies in Drosophila implicated extensive epistasis between variants in genes that affect neural connectivity and contribute to natural variation in olfactory response to benzaldehyde. Here, we implemented a powerful screen to quantify the magnitude of epistasis as well as identify candidate interacting variants using 203 inbred wild-derived lines with sequenced genomes of the Drosophila melanogaster Genetic Reference Panel (DGRP). We crossed the DGRP lines to P[GT1]-element insertion mutants in Sema-5c and neuralized (neur), two neurodevelopmental loci which affect olfactory behavior, and to their co-isogenic wild type control. We observed significant variation in olfactory responses to benzaldehyde among F1 genotypes and for the DGRP line by mutant genotype interactions for both loci, revealing extensive non-additive genetic variation. We performed genome-wide association analyses to identify the candidate modifier loci. None of these polymorphisms were in or near the focal genes; therefore, epistasis is the cause of the non-additive genetic variance. The candidate epistatic partners form interaction networks enriched for functions in neural development. Analyses of mutants of candidate epistatic partners with neur (merry-go-round (mgr), prospero (pros), CG10098, Alhambra (Alh) and CG12535) and Sema-5c (CG42540 and bruchpilot (brp)) showed aberrant olfactory responses compared to co-isogenic controls. Thus, integrating genome-wide analyses of natural variants with mutations at defined genomic locations in a common co-isogenic background can unmask specific epistatic modifiers of behavioral phenotypes. PMID:26678546

  13. 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…

  14. 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. PMID:27013951

  15. 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

  16. Role of opioid receptors in neurogenic dural vasodilation and sensitization of trigeminal neurones in anaesthetized rats

    PubMed Central

    Williamson, D J; Shepheard, S L; Cook, D A; Hargreaves, R J; Hill, R G; Cumberbatch, M J

    2001-01-01

    Migraine headache is thought to be caused by a distension of meningeal blood vessels, the activation of trigeminal sensory neurones and the the development of a central sensitization within the trigeminal nucleus caudalis (TNC). It has been proposed that clinically effective 5-HT1B/1D agonists act peripherally to inhibit the release of calcitonin gene-related peptide (CGRP) and neurogenic dural vasodilation, and to attenuate nociceptive neurotransmission within the TNC. Since opioids are also effective anti-migraine agents the present studies investigated the role of opioids within the trigemino-vascular system in anaesthetised rats. Electrical stimulation of the dura mater evoked neurogenic dural vasodilation which was significantly inhibited by morphine (1 mg kg−1) the selective μ-opioid agonist DAGO (10 μg kg−1) and the mixed agonist/antagonist butorphanol (1 mg kg−1) but not by the κ- and δ-opioid agonists (±) U50488H (100 μg kg−1) and DPDPE (1 mg kg−1). Morphine had no effect on CGRP-evoked dural vasodilation. In electrophysiological studies morphine (1 – 10 mg kg−1) significantly attenuated brainstem neuronal activity in response to electrical stimulation of the dura by 65% at 10 mg kg−1. Morphine (3 mg kg−1) also inhibited the TNC neuronal sensitization following CGRP-evoked dilation. The present studies have demonstrated that opioids block the nociceptive neurotransmission within the trigeminal nucleus caudalis and in addition inhibit neurogenic dural vasodilation via an action on μ-opioid receptors located on trigeminal sensory fibres innervating dural blood vessels. These peripheral and central actions are similar to those of the ‘triptan' 5-HT1B/1D agonists and could account for the anti-migraine actions of opioids. PMID:11454653

  17. Double-blind, randomized, controlled, crossover trial of pregabalin for neurogenic claudication

    PubMed Central

    Frazer, Maria E.; Rast, Shirley A.; McDermott, Michael P.; Gewandter, Jennifer S.; Chowdhry, Amit K.; Czerniecka, Kate; Pilcher, Webster H.; Simon, Lee S.; Dworkin, Robert H.

    2015-01-01

    Objectives: To test the effects of pregabalin on the induction of neurogenic claudication. Methods: This study was a randomized, double-blind, active placebo-controlled, 2-period, crossover trial. Twenty-nine subjects were randomized to receive pregabalin followed by active placebo (i.e., diphenhydramine) or active placebo followed by pregabalin. Each treatment period lasted 10 days, including a 2-step titration. Periods were separated by a 10-day washout period, including a 3-day taper phase after the first period. The primary outcome variable was the time to first moderate pain symptom (Numeric Rating Scale score ≥4) during a 15-minute treadmill test (Tfirst). Secondary outcome measures included pain intensity at rest, pain intensity at the end of the treadmill test, distance walked, and validated self-report measures of pain and functional limitation including the Roland-Morris Disability Questionnaire, modified Brief Pain Inventory–Short Form, Oswestry Disability Index, and Swiss Spinal Stenosis Questionnaire. Results: No significant difference was found between pregabalin and active placebo for the time to first moderate pain symptom (difference in median Tfirst = −1.08 [95% confidence interval −2.25 to 0.08], p = 0.61). In addition, none of the secondary outcome measures of pain or functional limitation were significantly improved by pregabalin compared with active placebo. Conclusions: Pregabalin was not more effective than active placebo in reducing painful symptoms or functional limitations in patients with neurogenic claudication associated with lumbar spinal stenosis. Classification of evidence: This study provides Class I evidence that for patients with neurogenic claudication, compared with diphenhydramine, pregabalin does not increase the time to moderate pain during a treadmill test. PMID:25503625

  18. Mesenchymal stem cells expressing neural antigens instruct a neurogenic cell fate on neural stem cells.

    PubMed

    Croft, Adam P; Przyborski, Stefan A

    2009-04-01

    The neurogenic response to injury in the postnatal brain is limited and insufficient for restoration of function. Recent evidence suggests that transplantation of mesenchymal stem cells (MSCs) into the injured brain is associated with improved functional recovery, mediated in part through amplification in the endogenous neurogenic response to injury. In the current study we investigate the interactions between bone marrow-derived MSCs and embryonic neural stem cells (NSCs) plus their differentiated progeny using an in vitro co-culture system. Two populations of MSCs were used, MSCs induced to express neural antigens (nestin+, Tuj-1+, GFAP+) and neural antigen negative MSCs. Following co-culture of induced MSCs with differentiating NSC/progenitor cells a significant increase in Tuj-1+ neurons was detected compared to co-cultures of non-induced MSCs in which an increase in astrocyte (GFAP+) differentiation was observed. The effect was mediated by soluble interactions between the two cell populations and was independent of any effect on cell death and proliferation. Induced and non-induced MSCs also promoted the survival of Tuj-1+ cell progeny in long-term cultures and both promoted axonal growth, an effect also seen in differentiating neuroblastoma cells. Therefore, MSCs provide instructive signals that are able to direct the differentiation of NSCs and promote axonal development in neuronal progeny. The data indicates that the nature of MSC derived signals is dependent not only on their microenvironment but on the developmental status of the MSCs. Pre-manipulation of MSCs prior to transplantation in vivo may be an effective means of enhancing the endogenous neurogenic response to injury. PMID:19159625

  19. Furosemide modifies heart hypertrophy and glycosaminoglycan myocardium content in a rat model of neurogenic hypertension.

    PubMed

    Pourzitaki, Chryssa; Tsaousi, Georgia; Manthou, Maria Eleni; Karakiulakis, Georgios; Kouvelas, Dimitrios; Papakonstantinou, Eleni

    2016-08-01

    Hypertension is a major risk factor for atherogenesis and heart hypertrophy, both of which are associated with specific morphological and functional changes of the myocardium. Glycosaminoglycans (GAGs) are complex molecules involved both in tissue morphology and function. In the present study, we investigated the effects of neurogenic hypertension and subsequent antihypertensive treatment with furosemide, on heart hypertrophy and the content of GAGs in the myocardium. Neurogenic hypertension was achieved in male Wistar rats by bilateral aortic denervation (bAD). At days 2, 7 and 15 after surgery, animals were sacrificed and the hearts were dissected away, weighted, and homogenized. Total GAGs were assessed by measuring the uronic acid content colorimetrically and individual GAGs were isolated and characterized by enzymatic treatment, with GAG-degrading enzymes, using electrophoresis on polyacrylamide gradient gels and cellulose acetate membranes. In bAD-animals blood pressure, blood pressure lability, heart rate and heart weight were significantly increased 15 days postoperatively. These effects were prevented by treatment with furosemide. Major GAGs identified in the heart were chondroitin sulphates, heparin (H), heparan sulphate (HS) and hyaluronic acid. The content of uronic and the relative content of H and HS in the heart in bAD animals significantly decreased from day 2 to day 15 postoperatively. Furosemide prevented the bAD induced decrease in GAG content. Considering that H and HS are potent inhibitors of cardiomyocyte hypertrophy, our results indicate that heart hypertrophy induced by neurogenic hypertension may be associated with decreases in the relative content of heparin and heparan sulphate in the heart. PMID:27221775

  20. Blockade of hyperalgesia and neurogenic oedema by topical application of nitroglycerin.

    PubMed

    Ferreira, S H; Lorenzetti, B B; Faccioli, L H

    1992-07-01

    Surprisingly, a single topical application of a nitroglycerin (NTG) gel in humans has been shown to cause analgesia and to reduce oedema in thrombophlebitis. In the present investigation, we showed that the NTG gel reduces prostaglandin E2-induced hyperalgesia and blocks neurogenic inflammation induced in rat skin by antidromic electrical stimulation of the saphenous nerve. These results offer an explanation for the effects of topical application of NTG observed in thrombophlebitis, which may be common to other cutaneous pathologies. The data also support the development of nitrates the effects of which are restricted to the site of application. PMID:1425939

  1. 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

  2. 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

  3. 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

  4. [The treatment of neurogenic hyperreflexic bladder dysfunctions in girls with low-intensity laser radiation].

    PubMed

    Kosilov, K V; Itskovich, A I; Orekhov, V R

    1995-01-01

    120 girls were investigated for the efficacy of three methods of treatment: conventional, infrared laser radiation on the projection of the bladder plus He-Ne laser radiation on biologically active points (BAP), red He-Ne laser BAP radiation. All the patients suffered from neurogenic hyperreflexic dysfunctions of the bladder, 99.8% had the diagnosis of vegetovascular dystonia, 94.9% had sympathetic-tonic or mixed patterns. The combined laser exposure brought about the greatest response rate-90.0%. PMID:7785111

  5. Neurogenic lower urinary tract dysfunction: how, when, and with which patients do we use urodynamics?

    PubMed

    Danforth, Teresa L; Ginsberg, David A

    2014-08-01

    Neurogenic lower urinary tract dysfunction (NLUTD) affects many patients and requires close monitoring. Initial studies establishing patients at risk for upper tract disease revealed that high detrusor leak point pressures were predictive of upper tract disease. Urodynamics in patients with NLUTD have specific challenges. Initial studies in patients after an acute injury should be delayed until after the spinal shock phase. In children with spinal dysraphism, studies should be done early to established potential risk. The goals are maintaining low bladder pressures, decreasing risk of infection, and maintaining continence. PMID:25063601

  6. 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

  7. The novel anti-migraine agent rizatriptan inhibits neurogenic dural vasodilation and extravasation.

    PubMed

    Williamson, D J; Shepheard, S L; Hill, R G; Hargreaves, R J

    1997-06-01

    These studies in anaesthetised rats showed, using intravital microscopy, that the novel anti-migraine agent, rizatriptan, significantly reduced electrically stimulated dural vasodilation but had no effect on increases in dural vessel diameter produced by exogenous substance P or calcitonin gene-related peptide (CGRP). Rizatriptan also significantly inhibited dural plasma protein extravasation produced by high intensity electrical stimulation of the trigeminal ganglion. We suggest that rizatriptan inhibits the release of sensory neuropeptides from perivascular trigeminal nerves to prevent neurogenic vasodilation and extravasation in the dura mater. These prejunctional inhibitory effects may be involved in the anti-migraine action of rizatriptan. PMID:9203569

  8. Bioimpedance based monitoring system for people with neurogenic dysfunction of the urinary bladder.

    PubMed

    Palla, Alessandro; Rossi, Stefano; Fanucci, Luca

    2015-01-01

    Patients with impaired bladder volume sensation have the necessity to monitor bladder level in order to avoid urinary tract infections and urinary reflux that can lead to renal failure. In this paper the the effectiveness of an embedded and wearable solution for bladder volume monitoring using the bioimpedance measurement is tested. Data are streamed real-time using Bluetooth wireless technology. The bioimpedance measurements on a healthy subject prove the effectiveness of the proposed solution. In the future the system will be evaluated in real world scenarios with patients affected by spinal paralysis and bladder neurogenic dysfunction. PMID:26294580

  9. Multipotent neurogenic fate of mesenchymal stem cell is determined by Cdk4-mediated hypophosphorylation of Smad-STAT3.

    PubMed

    Kim, Dong-Young; Lee, Janet; Kang, Dongrim; Lee, Do-Hyeong; Kim, Yoon-Ja; Hwang, Sang-Gu; Kim, Dong-Ik; Lee, Chang-Woo; Lee, Kyung-Hoon

    2016-07-01

    Cyclin-dependent kinase (Cdk) in complex with a corresponding cyclin plays a pivotal role in neurogenic differentiation. In particular, Cdk4 activity acts as a signaling switch to direct human mesenchymal stem cells (MSCs) to neural transdifferentiation. However, the molecular evidence of how Cdk4 activity converts MSCs to neurogenic lineage remains unknown. Here, we found that Cdk4 inhibition in human MSCs enriches the populations of neural stem and progenitor pools rather than differentiated glial and neuronal cell pools. Interestingly, Cdk4 inhibition directly inactivates Smads and subsequently STAT3 signaling by hypophosphorylation, and both Cdk4 and Smads levels are linked during the processes of neural transdifferentiation and differentiation. In summary, our results provide novel molecular evidence in which Cdk4 inhibition leads to directing human MSCs to a multipotent neurogenic fate by inactivating Smads-STAT3 signaling. PMID:27192561

  10. 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. PMID:26482843

  11. 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. PMID:26492830

  12. 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

    2016-01-01

    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). PMID:27598108

  13. Neurogenic airway inflammation induced by repeated intra-esophageal instillation of HCl in guinea pigs.

    PubMed

    Liu, Chunli; Chen, Ruchong; Luo, Wei; Lai, Kefang; Zhong, Nanshan

    2013-04-01

    This study was conducted to investigate if repeated intra-esophageal acid administrations may induce neurogenic inflammation in the airways and nodose ganglion in a guinea pig model. Guinea pigs were sedated and perfused with 0.1 N HCl in the distal esophagus via a nasoesophageal catheter for 14 consecutive days. Substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and calcitonin gene-related peptide concentration were measured by ELISA or radioimmunoassay. Neuropeptide expression in the airways and nodose ganglion was detected by immunohistochemistry and assessed semi-quantitatively. Inflammation was found in the trachea and bronchi. There was a threefold increase in substance P concentration in the trachea, main bronchi, and lung homogenate and a twofold increase in NKA and NKB concentration in the main bronchi, lung homogenate, and bronchial alveolus lavage fluid, respectively. The SP and NKA expressions in the airways and nodose ganglion were also significantly increased. Chronic intra-esophageal acid instillation induces significant neurogenic inflammation in the airways and nodose ganglion in the vagus nerve in guinea pigs. PMID:23225164

  14. 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. PMID:26407702

  15. Electrically evoked neuropeptide release and neurogenic inflammation differ between rat and human skin.

    PubMed

    Sauerstein, K; Klede, M; Hilliges, M; Schmelz, M

    2000-12-15

    Protein extravasation and vasodilatation can be induced by neuropeptides released from nociceptive afferents (neurogenic inflammation). We measured electrically evoked neuropeptide release and concomitant protein extravasation in human and rat skin using intradermal microdialysis. Plasmapheresis capillaries were inserted intradermally at a length of 1.5 cm in the volar forearm of human subjects or abdominal skin of rats. Capillaries were perfused with Ringer solution at a flow rate of 2.5 or 1.6 microl min(-1). After a baseline period of 60 min capillaries were stimulated electrically (1 Hz, 80 mA, 0.5 ms or 4 Hz, 30 mA, 0.5 ms) for 30 min using a surface electrode directly above the capillaries and a stainless-steel wire inserted in the capillaries. Total protein concentration was assessed photometrically and calcitonin gene-related peptide (CGRP) and substance P (SP) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). In rat skin, electrical stimulation increased CGRP and total protein concentration in the dialysate. SP measurements showed a larger variance but only for the 1 Hz stimulation was the increased release significant. In human skin, electrical stimulation provoked a large flare reaction and at a frequency of 4 Hz both CGRP and SP concentrations increased significantly. In spite of the large flare reactions no protein extravasation was induced, which suggests major species differences. It will be of interest to investigate whether the lack of neurogenic protein extravasation is also valid under pathophysiological conditions. PMID:11118507

  16. 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

  17. Electrically evoked neuropeptide release and neurogenic inflammation differ between rat and human skin

    PubMed Central

    Sauerstein, Katja; Klede, Monika; Hilliges, Marita; Schmelz, Martin

    2000-01-01

    Protein extravasation and vasodilatation can be induced by neuropeptides released from nociceptive afferents (neurogenic inflammation). We measured electrically evoked neuropeptide release and concomitant protein extravasation in human and rat skin using intradermal microdialysis. Plasmapheresis capillaries were inserted intradermally at a length of 1.5 cm in the volar forearm of human subjects or abdominal skin of rats. Capillaries were perfused with Ringer solution at a flow rate of 2.5 or 1.6 μl min−1. After a baseline period of 60 min capillaries were stimulated electrically (1 Hz, 80 mA, 0.5 ms or 4 Hz, 30 mA, 0.5 ms) for 30 min using a surface electrode directly above the capillaries and a stainless-steel wire inserted in the capillaries. Total protein concentration was assessed photometrically and calcitonin gene-related peptide (CGRP) and substance P (SP) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). In rat skin, electrical stimulation increased CGRP and total protein concentration in the dialysate. SP measurements showed a larger variance but only for the 1 Hz stimulation was the increased release significant. In human skin, electrical stimulation provoked a large flare reaction and at a frequency of 4 Hz both CGRP and SP concentrations increased significantly. In spite of the large flare reactions no protein extravasation was induced, which suggests major species differences. It will be of interest to investigate whether the lack of neurogenic protein extravasation is also valid under pathophysiological conditions. PMID:11118507

  18. A case of hypokalemic paralysis in a patient with neurogenic diabetes insipidus.

    PubMed

    Nguyen, Frederic N; Kar, Jitesh K; Verduzco-Gutierrez, Monica; Zakaria, Asma

    2014-04-01

    Acute hypokalemic paralysis is characterized by muscle weakness or paralysis secondary to low serum potassium levels. Neurogenic diabetes insipidus (DI) is a condition where the patient excretes large volume of dilute urine due to low levels of antidiuretic hormone. Here, we describe a patient with neurogenic DI who developed hypokalemic paralysis without a prior history of periodic paralysis. A 30-year-old right-handed Hispanic male was admitted for refractory seizures and acute DI after developing a dental abscess. He had a history of pituitary adenoma resection at the age of 13 with subsequent pan-hypopituitarism and was noncompliant with hormonal supplementation. On hospital day 3, he developed sudden onset of quadriplegia with motor strength of 0 of 5 in the upper extremities bilaterally and 1 of 5 in both lower extremities with absent deep tendon reflexes. His routine laboratory studies revealed severe hypokalemia of 1.6 mEq/dL. Nerve Conduction Study (NCS) revealed absent compound motor action potentials (CMAPs) with normal sensory potentials. Electromyography (EMG) did not reveal any abnormal insertional or spontaneous activity. He regained full strength within 36 hours following aggressive correction of the hypokalemia. Repeat NCS showed return of CMAPs in all nerves tested and EMG revealed normal motor units and normal recruitment without myotonic discharges. In patients with central DI with polyuria, hypokalemia can result in sudden paralysis. Hypokalemic paralysis remains an important differential in an acute case of paralysis and early recognition and appropriate management is key. PMID:24707338

  19. 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

  20. The subependymal zone neurogenic niche: a beating heart in the centre of the brain

    PubMed Central

    2009-01-01

    The mammalian brain is a remarkably complex organ comprising millions of neurons, glia and various other cell types. Its impressive cytoarchitecture led to the long standing belief that it is a structurally static organ and thus very sensitive to injury. However, an area of striking structural flexibility has been recently described at the centre of the brain. It is the subependymal zone of the lateral wall of the lateral ventricles. The subependymal zone—like a beating heart—continuously sends new cells to different areas of the brain: neurons to the olfactory bulbs and glial cells to the cortex and the corpus callosum. Interestingly, the generation and flow of cells changes in response to signals from anatomically remote areas of the brain or even from the external environment of the organism, therefore indicating that subependymal neurogenesis—as a system—is integrated in the overall homeostatic function of the brain. In this review, it will be attempted to describe the fundamental structural and functional characteristics of the subependymal neurogenic niche and to summarize the available evidence regarding its plasticity. Special focus is given on issues such as whether adult neural stem cells are activated after neurodegeneration, whether defects in neurogenesis contribute to neuropathological conditions and whether monitoring changes in neurogenic activity can have a diagnostic value. PMID:19773354

  1. Neurogenically mediated contractions of dog basilar artery involve the release of a thromboxane-like substance.

    PubMed

    Connor, H E; Edwards, L A; Feniuk, W

    1989-12-19

    Electrical field stimulation of dog isolated basilar artery produced neurogenically mediated contractions which were unaffected by phentolamine (1 microM), atropine (1 microM), ketanserin (1 microM) or methiothepin (0.1 microM). Responses were abolished by GR32191 (1-10 nM), BM 13.177 (0.1-10 microM) or flurbiprofen (0.5 microM) and markedly attenuated by dazoxiben (1-10 microM). Removal of the endothelium by Triton X-100-perfusion did not modify the magnitude of contractions to electrical stimulation and GR32191 still abolished the responses. GR32191 (1-10 nM) did not modify neurogenically mediated contraction of rabbit ear artery or potassium chloride-induced contraction of dog basilar artery. The results suggest that electrical field stimulation of dog basilar artery causes contractions which are mediated via a cyclo-oxygenase product with characteristics similar to thromboxane. This thromboxane-like substance is not endothelial in origin, nor released by contraction of the cerebrovascular smooth muscle per se and is therefore derived from a subendothelial, possibly neuronal, source. PMID:2483549

  2. Neurogenic Stuttering

    MedlinePlus

    ... Facts FAQ Basic Research Resources Brochures Free E-Books Free Videos Webinars Blog Referral Lists Newsletters Check your Library Books on Stuttering Product LIst Links Translations Podcasts Press ...

  3. Neurogenic bladder

    MedlinePlus

    ... on the cause. They often include symptoms of urinary incontinence . Symptoms of overactive bladder: Having to urinate too ... If you are having urinary incontinence, organizations are available for further information and support.

  4. AB200. Treatment effect of TURP plus urethral sphincter botox A injection on male neurogenic micturition dysfunction

    PubMed Central

    Huang, Xiao; Jiang, Hai; Shen, Yuehong

    2016-01-01

    Objective To investigate the treatment effect of TURP plus urethral sphincter botox A injection on male neurogenic micturition dysfunction. Methods Sixteen cases of male neurogenic bladder dysfunction patients. Age from 50 to 68 years old. Average 56 years old. All patients have dysuria symptom with normal bladder capacity. Detrusor underactivity 15 cases. Normal detrusor contractility 1 case. Reasons for neurogenic bladder: spinal cord injury 8 cases, spinal cord tumor 3 cases, postencephalitic 1 case, unknown reasons 4 cases, re-injection 1 case. Residual urine from 80 to 220 mL. Different degrees of prostatic hyperplasia were verified by ultrasound in 15 cases. Routine TURP were administrated under plasma cystoscopy. 100u botox A was injected into urethral sphincter muscle in 10 spots evenly. Symptom scores and ultrasound residual urine were recorded before and 4 weeks after surgery. Results were analyzed for treatment effect estimation. Results The average residual urine volume reduced from 154.8sidua to 57.3erage mL (P<0.01). Three cases stress urinary incontinence were observed, and reduced or recovered after 2–3 months pelvic floor muscle training. All patients were satisfied with the treatment results. The treatment effect lasted more than 15 months. Conclusions TURP plus urethral sphincter botox A injection is an effective and economic treatment on male neurogenic micturition dysfunction.

  5. Development of the adult neurogenic niche in the hippocampus of mice

    PubMed Central

    Nicola, Zeina; Fabel, Klaus; Kempermann, Gerd

    2015-01-01

    When does adult hippocampal neurogenesis begin? We describe the development of the neurogenic niche in the subgranular zone (SGZ) of the hippocampal dentate gyrus. We did so from the perspective of the situation in the adult. Ontogeny of the dentate gyrus is complex and results in an ectopic neurogenic niche that lifelong generates new granule cells. Neurogenesis during the fetal and early postnatal periods builds the dentate gyrus and gives way to activity-dependent “adult” neurogenesis. We used markers most relevant to adult neurogenesis research to describe this transition: Nestin, Sox2, BLBP, GFAP, Tbr2, Doublecortin (DCX), NeuroD1 and Prox1. We found that massive changes and a local condensation of proliferating precursor cells occurs between postnatal day 7 (P7), near the peak in proliferation, and P14. Before and around P7, the spatial distribution of cells and the co-localization of markers were distinct from the situation in the adult. Unlike the adult SGZ, the marker pair Nestin/Sox2 and the radial glial marker BLBP were not overlapping during embryonic development, presumably indicating different types of radial glia-like cells. Before P7 GFAP-positive cells in the hilus lacked the radial orientation that is characteristic of the adult type-1 cells. DCX, which is concentrated in type-2b and type-3 progenitor cells and early postmitotic neurons in the adult, showed diffuse expression before P7. Intermediate progenitor cell marker Tbr2 became restricted to the SGZ but was found in the granule cell layer (GCL) and hilus before. Lineage markers NeuroD1 and Prox1 confirmed this pattern. We conclude that the neurogenic niche of adult neurogenesis is in place well before true adulthood. This might indicate that consistent with the hypothesized function of adult neurogenesis in activity-dependent plasticity, the early transition from postnatal neurogenesis to adult neurogenesis coincides with the time, when the young mice start to become active themselves

  6. Alpha 1-adrenoceptors and calcium sources in adrenergic neurogenic contractions of rat vas deferens.

    PubMed Central

    Bültmann, R.; Kurz, A. K.; Starke, K.

    1994-01-01

    1. The involvement of alpha 1-adrenoceptor subtypes in adrenergic neurogenic contractions of different type was studied in epididymal and prostatic portions of the rat vas deferens. 2. The adrenergic component of neurogenic contractions was isolated by suramin (300 microM). Twitch-like and tonic contractions were elicited by appropriate pulse patterns of electrical field stimulation, and contractions relying on intracellular calcium mobilization and calcium entry were isolated by means of nifedipine (10 microM) and ryanodine (20 microM), respectively. Increasing concentrations of 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)- amino)-propyl)benzeneacetonitrile (HV 723), prazosin and 5-methylurapidil progressively, monophasically and with potency decreasing in that order reduced and finally abolished all types of contraction, with one exception: concentration-effect curves of 5-methylurapidil in epididymal segments in the presence of ryanodine levelled off at about 75% inhibition. In the presence of both nifedipine (10 microM) and ryanodine (20 microM), contractions were abolished. 3. Contractions elicited by exogenous noradrenaline were also studied in the presence of either nifedipine 10 microM (prostatic segments) or ryanodine 20 microM (epididymal segments). Increasing concentrations of tamsulosin, WB 4101, benoxathian, HV 723, prazosin, 5-methylurapidil and urapidil progressively, monophasically and with potency decreasing in that order reduced and eventually abolished both kinds of contraction, with two exceptions: in epididymal segments in the presence of ryanodine, the concentration-effect curve of 5-methylurapidil was biphasic and the curve of urapidil levelled off at only partial inhibition. 4. In slices prepared from the prostatic end and preincubated with [3H]-noradrenaline, WB 4101, HV 723, prazosin and 5-methylurapidil, at the highest concentrations tested against

  7. 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.

  8. 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.

  9. 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

  10. Slow negative evoked potentials in the rhesus monkey (Macaca mulatta): myogenic versus neurogenic influences.

    PubMed

    Fria, T J; Saad, M M; Doyle, W J; Cantekin, E I

    1984-02-01

    The influence of myogenic activity on the generation of slow negative evoked potentials (SN10) to octave, toneburst stimuli (0.5-2 Hz) was investigated in 5 rhesus monkeys (M. mulatta) by comparing responses obtained prior to and during total paralysis induced with curare. The SN10 could be easily elicited during paralysis, regardless of stimulus intensity, rate, or frequency. During paralysis, there were no systematic changes in either response latency or amplitude; variability in latency was less than 10% and changes in response amplitude were within 30%. These findings suggest that the myogenic contribution to the SN10 response is negligible and that this response is of neurogenic origin in the rhesus monkey. PMID:6198169

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

    PubMed

    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

  12. Neurogenic radial glial cells in reptile, rodent and human: from mitosis to migration.

    PubMed

    Weissman, Tamily; Noctor, Stephen C; Clinton, Brian K; Honig, Lawrence S; Kriegstein, Arnold R

    2003-06-01

    Radial glial cells play at least two crucial roles in cortical development: neuronal production in the ventricular zone (VZ) and the subsequent guidance of neuronal migration. There is evidence that radial glia-like cells are present not only during development but in the adult mammalian brain as well. In addition, radial glial cells appear to be neurogenic in the central nervous system of a number of vertebrate species. We demonstrate here that most dividing progenitor cells in the embryonic human VZ express radial glial proteins. Furthermore, we provide evidence that radial glial cells maintain a vimentin-positive radial fiber throughout each stage of cell division. Asymmetric inheritance of this fiber may be an important factor in determining how neuronal progeny will migrate into the developing cortical plate. Although radial glial cells have traditionally been characterized by their role in guiding migration, their role as neuronal progenitors may represent their defining characteristic throughout the vertebrate CNS. PMID:12764028

  13. NTOS symptoms and mobility: a case study on neurogenic thoracic outlet syndrome involving massage therapy.

    PubMed

    Streit, Robin S

    2014-01-01

    Neurogenic thoracic outlet syndrome (NTOS) is a neuromuscular condition affecting brachial plexus functionality. NTOS is characterized by paresthesia, pain, muscle fatigue, and restricted mobility in the upper extremity. This study quantified massage therapy's possible contribution to treatment of NTOS. A 24-year-old female with NTOS received eight treatments over 35 days. Treatment included myofascial release, trigger point therapy, cross fiber friction, muscle stripping, and gentle passive stretching. Abduction and lateral rotation at the glenohumeral (GH joint) assessments measured range of motion (ROM). A resisted muscle test evaluated upper extremity strength. The client rated symptoms daily via a visual analog scale (VAS). Findings showed improvement in ROM at the GH joint. VAS ratings revealed a reduction in muscle weakness, pain, numbness, and 'paresthesia'. Results suggest massage may be useful as part of a broad approach to managing NTOS symptoms and improving mobility. PMID:24411148

  14. 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

  15. Do changes in the coupling between respiratory and sympathetic activities contribute to neurogenic hypertension?

    PubMed

    Zoccal, Daniel B; Paton, Julian F R; Machado, Benedito H

    2009-12-01

    1. It is well known that respiration markedly modulates the sympathetic nervous system. Interactions between pontine and medullary neurons involved in the control of sympathetic and respiratory functions are the main mechanism underlying the respiratory related oscillations in sympathetic nerve activity. 2. Recently, in rats treated with chronic intermittent hypoxia, we demonstrated that alterations in respiratory pattern may drive increased sympathetic outflow and hence the development of systemic hypertension. These experiments, performed in the in situ working heart-brain stem preparation, raise the possibility that enhanced central coupling between respiratory and sympathetic activities could be a potential mechanism underpinning the development and/or the maintenance of neurogenic hypertension. 3. In the present review, we discuss the neural basis of the enhanced entrainment between respiratory and sympathetic neurons in the brain stem that can be induced by chronic intermittent hypoxia and the possible implications of these mechanisms in the genesis of sympathetic overactivity and, consequently, hypertension. PMID:19413588

  16. 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. PMID:26323825

  17. Transpulmonary Thermodilution-Based Management of Neurogenic Pulmonary Edema After Subarachnoid Hemorrhage.

    PubMed

    Mutoh, Tatsushi; Kazumata, Ken; Ueyama-Mutoh, Tomoko; Taki, Yasuyuki; Ishikawa, Tatsuya

    2015-11-01

    Neurogenic pulmonary edema (NPE) is a potentially catastrophic but treatable systemic event after subarachnoid hemorrhage (SAH). The development of NPE most frequently occurs immediately after SAH, and the severity is usually self-limiting. Despite extensive research efforts and a breadth of collective clinical experience, accurate diagnosis of NPE can be difficult, and effective hemodynamic treatment options are limited. Recently, a bedside transpulmonary thermodilution device has been introduced that traces physiological patterns consistent with current theories regarding the mechanism (hydrostatic or permeability PE) of NPE. This article provides an overview of the clinical usefulness of the advanced technique for use in the neurointensive care unit for the diagnosis and management of post-SAH NPE. PMID:26517502

  18. Neurogenic Astrocytes and Their Glycoconjugates: Not Just “Glue” Anymore

    PubMed Central

    Steindler, Dennis A.

    2015-01-01

    Cells with certain attributes of very immature astroglial cells and their radial precursors can act as stem and/or progenitor cells during developmental and persistent neurogenesis. Neural stem/progenitor cells both express and are affected by a variety of developmentally regulated macromolecules and growth factors, and such signaling or recognition molecules are being uncovered through extensive genomic and proteomic studies, as well as tested using in vitro/in vivo cell growth bioassays. Glycosylated molecules are appreciated as distinct signaling molecules during morphogenesis in a variety of tissues and organs, with glycoconjugates (glycoproteins, glycolipids, and glycosaminoglycans) serving as mediators for the interactions of cells with each other and their substrates, to confer growth and differentiation cues to precursor cells in search of identity. Neurogenic astrocytes and associated glycoconjugates, especially extracellular matrix molecules, are discussed in the context of neurogenesis and stem/progenitor cell growth, fate choice, and differentiation. PMID:22144297

  19. Anatomical variations in the brachial plexus roots: implications for diagnosis of neurogenic thoracic outlet syndrome.

    PubMed

    Leonhard, Vanessa; Smith, Riley; Caldwell, Gregory; Smith, Heather F

    2016-07-01

    Neurogenic thoracic outlet syndrome (NTOS) is the most common type of TOS. Typically it results from impingement of the neurovasculature as it passes between the anterior and middle scalene muscles; this classic anatomical relationship being the foundation of clinical diagnosis. Positional testing relies on vascular compromise occurring when the subclavian artery is compressed in this space. This study describes several anatomical variations observed in this relationship. Sixty-five cadavers (35m/30f) were assessed to determine the frequency and extent of brachial plexus branching variants. A total of thirty-one variations from "classic" anatomy were observed (47.7%). In two specimens (3.1%), the entire superior trunk coursed completely anterior to the anterior scalene in a position of relative vulnerability. In 27 instances, a portion of or the entire superior trunk pierced the anterior scalene muscle, and in two, the middle trunk also pierced the muscle belly. Interestingly, while two bilateral branching variations were observed, the majority occurred unilaterally, and almost exclusively on the left side. There were no sex differences in frequency. The high frequency of these variations and their potential to predispose patients to neurogenic TOS suggest that current diagnostic methods may be insufficient in clinical diagnosis. Due to lack of vascular compromise, patients with the piercing variant would not display positive signs on the traditional positional tests. The use of ultrasound to determine the route of the brachial plexus could determine whether this variation is present in patients who suffer from TOS symptoms but lack a diagnosis based on traditional positional testing. PMID:27133185

  20. Expression of neurotransmitters and neurotrophins in neurogenic inflammation of the rat retina.

    PubMed

    Bronzetti, Elena; Artico, M; Kovacs, I; Felici, L M; Magliulo, G; Vignone, D; D'Ambrosio, A; Forte, F; Di Liddo, R; Feher, J

    2007-01-01

    Antidromic stimulation of the rat trigeminal ganglion triggers the release of substance P (SP) and calcitonin gene-related peptide (CGRP) from sensory nerve terminals of the capsaicin sensitive C-fibers. These pro-inflammatory neuropeptides produce a marked hyperemia in the anterior segment of the eye, accompanied by increased intraocular pressure, breakdown of the blood-aqueous barrier and myosis. To assess the effects of neurogenic inflammation on the retina, specifically on the immunostaining of neurotransmitters and neurotrophins, as well as on the expression of neurotrophin receptors in the retina. RT-PCR was also accomplished in control and stimulated animals to confirm the immunohistochemical results. In the electrically stimulated eyes, immunostaining for SP, CGRP, VIP and nNOS demonstrated a marked increase in the RPE/POS (Retinal Pigment Epithelium/Photoreceptor Outer Segments), in the inner and outer granular layers and in the ganglion cells in comparison to the control eyes. CGRP and SP were found increased in stimulated animals and this result has been confirmed by RT- PCR. Changes in neurotrophin immunostaining and in receptor expression were also observed after electric stimulation of trigeminal ganglia. Decrease of BDNF and NT4 in the outer and inner layers and in ganglion cells was particularly marked. In stimulated rat retinas immunostaining and RT-PCR showed a NGF expression increase. Neurotrophin receptors remained substantially unchanged. These studies demonstrated, for the first time, that antidromic stimulation of the trigeminal ganglion and subsequent neurogenic inflammation affect immunostaining of retinal cell neurotransmitter/neuropeptides and neurotrophins as well as the expression of neurotrophin receptors. PMID:18162454

  1. 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

    2015-08-01

    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. PMID:25784603

  2. Clinically Relevant Progestins Regulate Neurogenic and Neuroprotective Responses in Vitro and in Vivo

    PubMed Central

    Liu, Lifei; Zhao, Liqin; She, Hongyun; Chen, Shuhua; Wang, Jun Ming; Wong, Charisse; McClure, Kelsey; Sitruk-Ware, Regine; Brinton, Roberta Diaz

    2010-01-01

    Previously, we demonstrated that progesterone (P4) promoted adult rat neural progenitor cell (rNPC) proliferation with concomitant regulation of cell-cycle gene expression via the P4 receptor membrane component/ERK pathway. Here, we report the efficacy of seven clinically relevant progestins alone or in combination with 17β-estradiol (E2) on adult rNPC proliferation and hippocampal cell viability in vitro and in vivo. In vitro analyses indicated that P4, norgestimate, Nestorone, norethynodrel, norethindrone, and levonorgestrel (LNG) significantly increased in rNPC proliferation, whereas norethindrone acetate was without effect, and medroxyprogesterone acetate (MPA) inhibited rNPC proliferation. Proliferative progestins in vitro were also neuroprotective. Acute in vivo exposure to P4 and Nestorone significantly increased proliferating cell nuclear antigen and cell division cycle 2 expression and total number of hippocampal 5-bromo-2-deoxyuridine (BrdU)-positive cells, whereas LNG and MPA were without effect. Mechanistically, neurogenic progestins required activation of MAPK to promote proliferation. P4, Nestorone, and LNG significantly increased ATP synthase subunit α (complex V, subunit α) expression, whereas MPA was without effect. In combination with E2, P4, Nestorone, LNG, and MPA significantly increased BrdU incorporation. However, BrdU incorporation induced by E2 plus LNG or MPA was paralleled by a significant increase in apoptosis. A rise in Bax/Bcl-2 ratio paralleled apoptosis induced by LNG and MPA. With the exception of P4, clinical progestins antagonized E2-induced rise in complex V, subunit α. These preclinical translational findings indicate that the neurogenic response to clinical progestins varies dramatically. Progestin impact on the regenerative capacity of the brain has clinical implications for contraceptive and hormone therapy formulations prescribed for pre- and postmenopausal women. PMID:20943809

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

    PubMed Central

    Johnson, E. U.; Singh, Gurpreet

    2013-01-01

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

  4. A novel CGRP-neutralizing Spiegelmer attenuates neurogenic plasma protein extravasation

    PubMed Central

    Hoehlig, K; Johnson, K W; Pryazhnikov, E; Maasch, C; Clemens-Smith, A; Purschke, W G; Vauléon, S; Buchner, K; Jarosch, F; Khiroug, L; Vater, A; Klussmann, S

    2015-01-01

    Background and Purpose Calcitonin gene-related peptide (CGRP) plays an important role in the pathology of migraine, and recent clinical trials suggest the inhibition of CGRP-mediated processes as a new therapeutic option in migraine. In this study, we describe the generation of NOX-L41, a CGRP-neutralizing mirror-image (l-)aptamer (Spiegelmer) and investigate its in vitro and in vivo function. Experimental Approach A CGRP-binding Spiegelmer was identified by in vitro selection. Binding studies were performed using surface plasmon resonance (SPR), and the inhibitory activity was determined in cell-based assays. The pharmacokinetic profile comparing i.v. and s.c. dosing was analysed in rats. Intravital two-photon microscopy was employed to follow extravasation from meningeal vessels. Finally, in vivo efficacy was tested in a model of electrically evoked meningeal plasma protein extravasation (PPE) in rats. Key Results We identified NOX-L41, a novel CGRP-neutralizing Spiegelmer. SPR studies showed that NOX-L41 binds to human and rat/mouse CGRP with sub-nanomolar affinities and is highly selective against related peptides such as amylin. In vitro, NOX-L41 effectively inhibited CGRP-induced cAMP formation in SK-N-MC cells. In rats, NOX-L41 had a plasma half-life of 8 h. Pharmacodynamic studies showed that NOX-L41 extravasates from blood vessels in the dura mater and inhibits neurogenic meningeal PPE for at least 18 h after single dosing. Conclusions and Implications This is the first description of the CGRP-neutralizing Spiegelmer NOX-L41. Preclinical studies confirmed a role for CGRP in neurogenic PPE and provided proof-of-concept for the potential use of this new drug candidate for the treatment or prevention of migraine. PMID:25659966

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    2012-01-01

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

  7. 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

  8. 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

  9. Bladder neck closure and suprapubic catheter placement as definitive management of neurogenic bladder

    PubMed Central

    Colli, Janet; Lloyd, L. Keith

    2011-01-01

    Objective Surgical management for neurogenic bladder may require abandonment of the native urethra due to intractable urinary incontinence, irreparable urethral erosion, severe scarring from previous transurethral procedures, or urethrocutaneous fistula. In these patients, bladder neck closure (BNC) excludes the native urethra and provides continence while preserving the antireflux mechanism of the native ureters. This procedure is commonly combined with ileovesicostomy or continent catheterizable stoma, with or without augmentation enterocystoplasty. Alternatively, BNC can be paired with suprapubic catheter diversion. This strategy does not require a bowel segment, resulting in shorter operative times and less opportunity for bowel-related morbidity. The study purpose is to examine preoperative characteristics, indications, complications, and long-term maintenance of renal function of BNC patients. Methods A retrospective review of medical records of 35 patients who underwent BNC with suprapubic catheter placement from 1998 to 2007 by a single surgeon (LKL) was completed. Results Neurogenic bladder was attributable to spinal cord injury in 71%, 23% had multiple sclerosis, and 9% had cerebrovascular accident. Indications for BNC included severe urethral erosion in 80%, decubitus ulcer exacerbated by urinary incontinence in 34%, urethrocutaneous fistula in 11%, and other indications in 9%. The overall complication rate was 17%. All but two patients were continent at follow-up. Forty-nine per cent of patients had imaging available for review, none of which showed deterioration of the upper tracts. Conclusions Our results suggest that BNC in conjunction with suprapubic catheter diversion provides an excellent chance at urethral continence with a reasonable complication rate. PMID:21756565

  10. 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.

  11. The indirect role of fibroblast growth factor-8 in defining neurogenic niches of the olfactory/GnRH systems.

    PubMed

    Forni, Paolo Emanuele; Bharti, Kapil; Flannery, Ellen M; Shimogori, Tomomi; Wray, Susan

    2013-12-11

    Bone morphogenic protein-4 (BMP4) and fibroblast growth factor-8 (FGF8) are thought to have opposite roles in defining epithelial versus neurogenic fate in the developing olfactory/vomeronasal system. In particular, FGF8 has been implicated in specification of olfactory and gonadotropin releasing hormone-1 (GnRH) neurons, as well as in controlling olfactory stem cell survival. Using different knock-in mouse lines and Cre-lox-mediated lineage tracing, Fgf8 expression and cell lineage was analyzed in the developing nose in relation to the expression of Bmp4 and its antagonist Noggin (Nog). FGF8 is expressed by cells that acquire an epidermal, respiratory cell fate and not by stem cells that acquire neuronal olfactory or vomeronasal cell fate. Ectodermal and mesenchymal sources of BMP4 control the expression of BMP/TGFβ antagonist Nog, whereas mesenchymal sources of Nog define the neurogenic borders of the olfactory pit. Fgf8 hypomorph mouse models, Fgf8(neo/neo) and Fgf8(neo/null), displayed severe craniofacial defects together with overlapping defects in the olfactory pit including (1) lack of neuronal formation ventrally, where GnRH neurons normally form, and (2) altered expression of Bmp4 and Nog, with Nog ectopically expressed in the nasal mesenchyme and no longer defining the GnRH and vomeronasal neurogenic border. Together our data show that (1) FGF8 is not sufficient to induce ectodermal progenitors of the olfactory pit to acquire neural fate and (2) altered neurogenesis and lack of GnRH neuron specification after chronically reduced Fgf8 expression reflected dysgenesis of the nasal region and loss of a specific neurogenic permissive milieu that was defined by mesenchymal signals. PMID:24336726

  12. Pre-operative embolization facilitating a posterior approach for the surgical resection of giant sacral neurogenic tumors.

    PubMed

    Chen, Kangwu; Zhou, Ming; Yang, Huilin; Qian, Zhonglai; Wang, Genlin; Wu, Guizhong; Zhu, Xiaoyu; Sun, Zhiyong

    2013-07-01

    The present study aimed to assess a posterior approach for the surgical resection of giant sacral neurogenic tumors, and to evaluate the oncological and functional outcomes. A total of 16 patients with giant sacral neurogenic tumors underwent pre-operative embolization and subsequent posterior sacral resection between January 2000 and June 2010. Benign tumors were identified in 12 cases, while four cases exhibited malignant peripheral nerve sheath tumors (MPNSTs). An evaluation of the operative techniques used, the level of blood loss, any complications and the functional and oncological outcomes was performed. All tumor masses were removed completely without intra-operative shock or fatalities. The mean tumor size was 17.5 cm (range, 11.5-28 cm) at the greatest diameter. The average level of intra-operative blood loss was 1,293 ml (range, 400-4,500 ml). Wound complications occurred in four patients (25%), including three cases of cutaneous necrosis and one wound infection. The mean follow-up time was 59 months (range, 24-110 months). Tumor recurrence or patient mortality as a result of the disease did not occur in any of the patients with benign sacral neurogenic tumors. The survival rate of the patients with malignant lesions was 75% (3/4 patients) since 25 % (1/4 patients) had multiple local recurrences and succumbed to the disease. The patients with benign tumors scored an average of 92.8% on the Musculoskeletal Tumor Society (MSTS) score functional evaluation, while the patients with malignant tumors scored an average of 60.3%. A posterior approach for the surgical resection of giant sacral neurogenic tumors, combined with pre-operative embolization may be safely conducted with satisfactory oncological and functional outcomes. PMID:23946813

  13. VSX2 and ASCL1 Are Indicators of Neurogenic Competence in Human Retinal Progenitor Cultures.

    PubMed

    Wright, Lynda S; Pinilla, Isabel; Saha, Jishnu; Clermont, Joshua M; Lien, Jessica S; Borys, Katarzyna D; Capowski, Elizabeth E; Phillips, M Joseph; Gamm, David M

    2015-01-01

    Three dimensional (3D) culture techniques are frequently used for CNS tissue modeling and organoid production, including generation of retina-like tissues. A proposed advantage of these 3D systems is their potential to more closely approximate in vivo cellular microenvironments, which could translate into improved manufacture and/or maintenance of neuronal populations. Visual System Homeobox 2 (VSX2) labels all multipotent retinal progenitor cells (RPCs) and is known to play important roles in retinal development. In contrast, the proneural transcription factor Acheate scute-like 1 (ASCL1) is expressed transiently in a subset of RPCs, but is required for the production of most retinal neurons. Therefore, we asked whether the presence of VSX2 and ASCL1 could gauge neurogenic potential in 3D retinal cultures derived from human prenatal tissue or ES cells (hESCs). Short term prenatal 3D retinal cultures displayed multiple characteristics of human RPCs (hRPCs) found in situ, including robust expression of VSX2. Upon initiation of hRPC differentiation, there was a small increase in co-labeling of VSX2+ cells with ASCL1, along with a modest increase in the number of PKCα+ neurons. However, 3D prenatal retinal cultures lost expression of VSX2 and ASCL1 over time while concurrently becoming refractory to neuronal differentiation. Conversely, 3D optic vesicles derived from hESCs (hESC-OVs) maintained a robust VSX2+ hRPC population that could spontaneously co-express ASCL1 and generate photoreceptors and other retinal neurons for an extended period of time. These results show that VSX2 and ASCL1 can serve as markers for neurogenic potential in cultured hRPCs. Furthermore, unlike hESC-OVs, maintenance of 3D structure does not independently convey an advantage in the culture of prenatal hRPCs, further illustrating differences in the survival and differentiation requirements of hRPCs extracted from native tissue vs. those generated entirely in vitro. PMID:26292211

  14. The various types of neurogenic bladder dysfunction: an update of current therapeutic concepts.

    PubMed

    Madersbacher, H

    1990-05-01

    weak reflex detrusor contractions are present. (3) With the combination of an areflexive or hyporeflexive detrusor and a flaccid pelvic floor, passive voiding by abdominal straining or by the Credé manoeuvre is usually recommended, but should be replaced by CIC if this mechanism of bladder emptying creates unphysiological high and dangerous intravesical pressures, or if vesico-uretero-renal reflux is present. Neurogenic urinary stress incontinence is usually associated with this type of lesion and can be successfully treated by the implantation of an artificial urinary sphincter (Scott). However in two thirds of the patients with neurogenic bladder dysfunction, additional, usually operative treatment is necessary to meet the criteria for implantation. Moreover, a 30% rate of repair operations must be accepted by patients, but is becoming less frequently required with an improved design of the device.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2235029

  15. [The role of enkephalinase (neutral endopeptidase) in neurogenic inflammation of the respiratory tract].

    PubMed

    Djokić, T D

    1992-01-01

    In addition to the cholinergic and adrenergic nervous systems, a new noncholinergic and nonadrenergic nervous system has recently been described, involving the afferent sensory nerves in the airways. Many irritants (dusts, chemicals) stimulate these sensory nerves to release neuropeptides. Among these neuropeptides, the "tachykinins" exist in sensory nerves of airways (substance P, neurokinin A). These tachykinins have the ability to affect multiple cells in the airways and to provoke many responses including smooth muscle contraction, mucus secretion, plasma extravasation and neutrophil adhesion. This series of effects is termed "neurogenic inflammation". Using the respiratory tract as experimental model, it has been shown that: a) substance P (SP) is widely distributed in afferent fibers in the vagus, b) SP-immunoreactivity has been demonstrated in the epithelium, in airway smooth muscle, near blood vessels and submucosal glands, c) substance P and other tachykinins are released from sensory nerve terminals during stimulation electrically and by capsaicin, d) local administration of substance P mimics the effect of sensory nerve stimulation, e) smooth muscle contraction, gland secretion and plasma leakage, normally induced by nerve stimulation or noxious stimulus, are absent in tissues pretreated with the substance P depleting agent capsaicin or with tachykinin antagonists. These findings indicate that peptidergic nerve fibers are involved in the local regulation of tone of smooth muscle, regulation of blood flow, vascular permeability, and mucus secretion. We released that degradative mechanisms could play an important role in modulating tachykinin effects, just as acetylcholinesterase modulates effects of acetylcholine released from nerve terminals. We discovered that a membrane-bound enzyme called enkephalinase (also called neutral endopeptidase, EC 3, 4, 24, 11), located on specific cells that contain tachykinin receptors, modulate the action of tachykinins

  16. The multifaceted subventricular zone astrocyte: From a metabolic and pro-neurogenic role to acting as a neural stem cell.

    PubMed

    Platel, J C; Bordey, A

    2016-05-26

    A few decades ago it was discovered that two regions of the adult brain retain the ability to generate new neurons. These regions include the subgranular zone of the hippocampal dentate gyrus and the ventricular-subventricular zone (V-SVZ) located at the border of the lateral ventricle. In the V-SVZ, it was discovered that neural progenitor cells (NPCs) share many features of mature astrocytes and are often referred as V-SVZ astrocytes. We will first describe the markers, the morphology, and the neurophysiological characteristics of the mouse V-SVZ astrocytes. We will then discuss the fact that V-SVZ astrocytes constitute a mixed population with respect to their neurogenic properties, e.g., quiescent versus activated state, neurogenic fate, and transcription factors expression. Finally, we will describe two functions of V-SVZ astrocytes, their metabolic coupling to blood vessels and their neurogenic-supportive role consisting of providing guidance and survival cues to migrating newborn neurons. PMID:26546469

  17. 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

  18. Analysis of adult neurogenesis: evidence for a prominent "non-neurogenic" DCX-protein pool in rodent brain.

    PubMed

    Kremer, Thomas; Jagasia, Ravi; Herrmann, Annika; Matile, Hugues; Borroni, Edilio; Francis, Fiona; Kuhn, Hans Georg; Czech, Christian

    2013-01-01

    Here, we have developed a highly sensitive immunoassay for Dcx to characterize expression in brain and cerebrospinal fluid (CSF) of rodents. We demonstrate that Dcx is widely expressed during development in various brain regions and as well can be detected in cerebrospinal fluid of rats (up to 30 days postnatal). While Dcx protein level decline in adulthood and were detectable in neurogenic regions of the adult rodent brain, similar levels were also detectable in brain regions expected to bear no neurogenesis including the cerebral cortex and CA1/CA3 enriched hippocampus. We monitored DCX protein levels after paradigms to increase or severely decrease adult hippocampal neurogenesis, namely physical activity and cranial radiation, respectively. In both paradigms, Dcx protein- and mRNA-levels clearly reflected changes in neurogenesis in the hippocampus. However, basal Dcx-levels are unaffected in non-neurogenic regions (e.g. CA1/CA3 enriched hippocampus, cortex). These data suggest that there is a substantial "non-neurogenic" pool of Dcx- protein, whose regulation can be uncoupled from adult neurogenesis suggesting caution for the interpretation of such studies. PMID:23690918

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

    PubMed

    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. MDM2 inhibition rescues neurogenic and cognitive deficits in a mouse model of fragile X syndrome.

    PubMed

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

    2016-04-27

    Fragile X syndrome, the most common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein (FMRP). However, the mechanism remains unclear, and effective treatment is lacking. We show that loss of FMRP leads to activation of adult mouse neural stem cells (NSCs) and a subsequent reduction in the production of neurons. We identified the ubiquitin ligase mouse double minute 2 homolog (MDM2) as a target of FMRP. FMRP regulates Mdm2 mRNA stability, and loss of FMRP resulted in elevated MDM2 mRNA and protein. Further, we found that increased MDM2 expression led to reduced P53 expression in adult mouse NSCs, leading to alterations in NSC proliferation and differentiation. Treatment with Nutlin-3, a small molecule undergoing clinical trials for treating cancer, specifically inhibited the interaction of MDM2 with P53, and rescued neurogenic and cognitive deficits in FMRP-deficient mice. Our data reveal a potential regulatory role for FMRP in the balance between adult NSC activation and quiescence, and identify a potential new treatment for fragile X syndrome. PMID:27122614

  1. The anatomical basis and prevention of neurogenic voiding dysfunction following radical hysterectomy.

    PubMed

    Tong, X K; Huo, R J

    1991-01-01

    The disorder of neurogenic dysfunction is one of the most important complications of radical hysterectomy. In order to prevent this potential complication, the authors have studied the composition and layers of the pelvic paravisceral structures. The nerve branching and distribution of the pelvic plexus of 12 adult female cadavers were analyzed. From lateral to medial the pelvic paravisceral structure is made up of three layers. The lateral layer is the pelvic visceral fascia, the middle, a vascular layer, and the medial one, a nervous one which consists of the pelvic plexus and subsidiary plexuses. The pelvic plexus and subsidiary plexuses are laid closely to the lateral walls of pelvic organs. The ischial spine was taken as the central point and two perpendicular lines penetrating through the ischial spine were used as the longitudinal axis and transverse axis. According to these landmarks, the pelvic plexus could be divided into three parts: behind the longitudinal axis are the roots of the pelvic plexus, near the longitudinal axis is the uterovaginal plexus, and in front of the longitudinal axis are the branches distributed to bladder and urethra. The pelvic plexus and the uterosacral and cardinal ligaments are closely related. The pelvic and subsidiary plexuses can be damaged in radical hysterectomy and voiding dysfunction may then develop. Some anatomic bases are provided to explain and hopefully prevent this from happening. PMID:1925917

  2. Bladder wall thickness in the assessment of neurogenic bladder: a translational discussion of current clinical applications.

    PubMed

    Sturm, Renea M; Cheng, Earl Y

    2016-01-01

    The prospective trial by Kim et al. "Can Bladder Wall Thickness Predict Videourodynamic Findings in Children with Spina Bifida?" published in Journal of Urology investigated the measurement of bladder wall thickness (BWT) as a non-invasive assessment tool for lower urinary tract changes in neurogenic bladder (NGB). In this study, no significant association was observed between BWT and high-risk urodynamic parameters. This editorial discusses the basic science of bladder wall thickening as well as prior studies relating wall thickness to clinical parameters. Although Kim et al. provide a unique literature contribution in terms of assessment of BWT at defined percent cystometric capacity, specific aspects of study methodology and population may have contributed to a lack of correlation with high-risk urodynamic findings. The application of non-invasive modalities to lower urinary tract assessment of NGB remains a promising and relevant area of future research to prevent progression to end stage lower urinary tract changes for all individuals with spina bifida. PMID:26889485

  3. 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

  4. 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

  5. Diazoxide enhances excitotoxicity-induced neurogenesis and attenuates neurodegeneration in the rat non-neurogenic hippocampus.

    PubMed

    Martínez-Moreno, M; Batlle, M; Ortega, F J; Gimeno-Bayón, J; Andrade, C; Mahy, N; Rodríguez, M J

    2016-10-01

    Diazoxide, a well-known mitochondrial KATP channel opener with neuroprotective effects, has been proposed for the effective and safe treatment of neuroinflammation. To test whether diazoxide affects the neurogenesis associated with excitotoxicity in brain injury, we induced lesions by injecting excitotoxic N-methyl-d-aspartate (NMDA) into the rat hippocampus and analyzed the effects of a daily oral administration of diazoxide on the induced lesion. Specific glial and neuronal staining showed that NMDA elicited a strong glial reaction associated with progressive neuronal loss in the whole hippocampal formation. Doublecortin immunohistochemistry and bromo-deoxyuridine (BrdU)-NeuN double immunohistochemistry revealed that NMDA also induced cell proliferation and neurogenesis in the lesioned non-neurogenic hippocampus. Furthermore, glial fibrillary acidic protein (GFAP)-positive cells in the injured hippocampus expressed transcription factor Sp8 indicating that the excitotoxic lesion elicited the migration of progenitors from the subventricular zone and/or the reprograming of reactive astrocytes. Diazoxide treatment attenuated the NMDA-induced hippocampal injury in rats, as demonstrated by decreases in the size of the lesion, neuronal loss and microglial reaction. Diazoxide also increased the number of BrdU/NeuN double-stained cells and elevated the number of Sp8-positive cells in the lesioned hippocampus. These results indicate a role for KATP channel activation in regulating excitotoxicity-induced neurogenesis in brain injury. PMID:27471195

  6. 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

  7. 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

  8. 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

  9. Neurogenic plasticity of mesenchymal stem cell, an alluring cellular replacement for traumatic brain injury.

    PubMed

    Pati, Soumya; Muthuraju, Sangu; Hadi, Raisah Ab; Huat, Tee Jong; Singh, Shailja; Maletic-Savatic, Mirjana; Abdullah, Jafri Malin; Jaafar, Hasnan

    2016-01-01

    Traumatic brain injury (TBI) imposes horrendous neurophysiological alterations leading to most devastating forms of neuro-disability. Which includes impaired cognition, distorted locomotors activity and psychosomatic disability in both youths and adults. Emerging evidence from recent studies has identified mesenchymal stem cells (MSCs) as one of the promising category of stem cells having excellent neuroregenerative capability in TBI victims. Some of the clinical and animal studies reported that MSCs transplantation could cure neuronal damage as well as improve cognitive and locomotors behaviors in TBI. However, mechanism behind their broad spectrum neuroregenerative potential in TBI has not been reviewed yet. Therefore, in the present article, we present a comprehensive data on the important attributes of MSCs, such as neurotransdifferentiation, neuroprotection, axonal repair and plasticity, maintenance of blood-brain integrity, reduction of reactive oxygen species (ROS) and immunomodulation. We have reviewed in detail the crucial neurogenic capabilities of MSCs in vivo and provided consolidated knowledge regarding their cellular remodeling in TBI for future therapeutic implications. PMID:26763886

  10. A step-wise approach to sperm retrieval in men with neurogenic anejaculation.

    PubMed

    Fode, Mikkel; Ohl, Dana A; Sønksen, Jens

    2015-11-01

    Normal fertility is dependent on intravaginal delivery of semen through ejaculation. This process is highly dependent on an intact ejaculatory reflex arc, which can be disrupted through any type of trauma or disease causing damage to the CNS and/or peripheral nerves. Neurogenic anejaculation is most commonly associated with spinal cord injury. This aetiology is especially relevant because most men with spinal cord injuries are injured at reproductive age. Assisted ejaculation in the form of penile vibratory stimulation is the first choice for sperm retrieval in such patients because it is noninvasive and inexpensive. In patients in whom vibratory stimulation fails, electroejaculation is almost always successful. When both methods of assisted ejaculation are unsuccessful, sperm retrieval by aspiration from either the vas deferens or the epididymis, or by testicular biopsy or surgery are reasonable options. In such cases the most inexpensive and least invasive methods should be considered first. The obtained semen can be used for intravaginal or intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection. PMID:26481575

  11. Permanent neonatal diabetes with arthrogryposis multiplex congenita and neurogenic bladder - a new syndrome?

    PubMed

    Goksen, Damla; Darcan, Sukran; Coker, Mahmut; Aksu, Güzide; Yildiz, Basak; Kara, Sinan; Kültürsay, Nilgün

    2006-10-01

    Neonatal diabetes mellitus is a rare (1/400 000 newborns) but potentially devastating condition, which may be transient or permanent; typical symptoms occur within the first 4 wk of life. The transient form is a developmental insulin production disorder that resolves postnatally. Fifty to 60% of cases can be seen as transient form. Cases that require lifelong insulin therapy can be described as permanent condition. This fraction of cases is less common than the transient form. There are no clinical features that can predict whether a neonate with diabetes mellitus but no other dysmorphology will eventually have permanent neonatal diabetes mellitus (PNDM) or transient neonatal diabetes mellitus. Some metabolic or genetic defects such as complete deficiency of glucokinase or heterozygous activating mutations of KCNJ11, encoding Kir6.2, were found in patients with PNDM. A preterm female infant with a gestational age of 36 wk was admitted to the neonatal intensive care unit in the first hours of life due to prematurity and intra-uterine growth retardation. She was diagnosed as having arthrogryposis multiplex congenita on the first day. Hyperglycemia was detected on the third day of life, and she required insulin treatment. The patient is now 6 yr old with PNDM, arthrogryposis multiplex, neurogenic bladder, immune deficiency, constipation, and ichthyosis. Is this a new form of neonatal diabetes mellitus? PMID:17054450

  12. CIT, a gene involved in neurogenic cytokinesis, is mutated in human primary microcephaly.

    PubMed

    Basit, Sulman; Al-Harbi, Khalid M; Alhijji, Sabri A M; Albalawi, Alia M; Alharby, Essa; Eldardear, Amr; Samman, Mohammed I

    2016-10-01

    Autosomal recessive primary microcephaly (MCPH) is a static neurodevelopmental disorder characterized by congenital small head circumference and non-progressive intellectual disability without additional severe brain malformations. MCPH is a genetically heterogeneous disorder. Sixteen genes (MCPH1-MCPH16) have been discovered so far, mutations thereof lead to autosomal recessive primary microcephaly. In a family, segregating MCPH in an autosomal recessive manner, genome-wide homozygosity mapping mapped a disease locus to 16.9-Mb region on chromosome 12q24.11-q24.32. Following this, exome sequencing in three affected individuals of the family discovered a splice site variant (c.753+3A>T) in citron kinase (CIT) gene, segregating with the disorder in the family. CIT co-localizes to the midbody ring during cytokinesis, and its loss of expression results in defects in neurogenic cytokinesis in both humans and mice. Splice site variant in CIT, identified in this study, is predicted to abolish splice donor site. cDNA sequence of an affected individual showed retention of an intron next to the splice donor site. The study, presented here, revealed the first variant in the CIT causing MCPH in the family. PMID:27519304

  13. Do We Need Surveillance Urethro-Cystoscopy in Patients with Neurogenic Lower Urinary Tract Dysfunction?

    PubMed Central

    Knüpfer, Stephanie C.; Mehnert, Ulrich; Bode-Lesniewska, Beata; Kessler, Thomas M.

    2015-01-01

    Purpose To examine the value of surveillance urethro-cystoscopy in patients with neurogenic lower urinary tract dysfunction (NLUTD) in regard to the conflicting literature as it is generally agreed that patients with NLUTD are at increased risk for bladder cancer. Materials and Methods In a cross-sectional study, a consecutive series of 129 patients (50 females, 79 males, mean age 51, range 18–88) suffering from NLUTD for at least 5 years was prospectively investigated using urethro-cystoscopy and bladder washing cytology at a single university spinal cord injury (SCI) center. Results Due to suspicious urethro-cystoscopy and/or bladder washing cytology findings, 13 (10%) of 129 patients underwent transurethral resection of the bladder lesion and/or random bladder biopsies. Overall, 9 relevant histological findings were found in 5% (7/129) of our patients: bladder melanosis (n = 1), nephrogenic adenoma (n = 3), keratinizing squamous metaplasia (n = 1), intestinal metaplasia (n = 3), and muscle-invasive adenocarcinoma of the bladder (n = 1). Conclusions Using surveillance urethro-cystoscopy, we found relevant histological findings in 5% of our patients suffering from NLUTD for at least 5 years. Thus, surveillance urethro-cystoscopy might be warranted, although the ideal starting point and frequency remain to be determined in further prospective studies. PMID:26513149

  14. Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche.

    PubMed Central

    Kuo, Chay T.; Mirzadeh, Zaman; Soriano-Navarro, Mario; Rašin, Mladen; Wang, Denan; Shen, Jie; Šestan, Nenad; Garcia-Verdugo, Jose; Alvarez-Buylla, Arturo; Jan, Lily Y.; Jan, Yuh-Nung

    2007-01-01

    SUMMARY Neural stem cells are retained in the postnatal subventricular zone (SVZ), a specialized neurogenic niche with unique cytoarchitecture and cell-cell contacts. Although the SVZ stem cells continuously regenerate, how they and the niche respond to local changes is unclear. Here we generated nestin-creERtm transgenic mice with inducible Cre recombinase in the SVZ, and removed Numb/Numblike, key regulators of embryonic neurogenesis from postnatal SVZ progenitors and ependymal cells. This resulted in severe damage to brain lateral ventricle integrity, and identified previously unknown roles for Numb/Numblike in regulating ependymal wall integrity and SVZ neuroblast survival. Surprisingly, the ventricular damage was eventually repaired: SVZ reconstitution and ventricular wall remodeling were mediated by progenitors that escaped Numb deletion. Our results show a self-repair mechanism in the mammalian brain, and may have implications for niche plasticity in other areas of stem cell biology, and for the therapeutic use of neural stem cells in neurodegenerative diseases. PMID:17174898

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

    PubMed

    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

  16. Two pediatric cases of variant neurogenic stress cardiomyopathy after intracranial hemorrhage.

    PubMed

    Wittekind, Samuel G; Yanay, Ofer; Johnson, Erin M; Gibbons, Edward F

    2014-10-01

    Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy, is an acquired form of left ventricular systolic dysfunction seen in the setting of physiologic stress and the absence of coronary artery disease. It is thought to be caused by excessive sympathetic stimulation. It is well described in the adult literature associated with subarachnoid hemorrhage where it is known as neurogenic stress cardiomyopathy (NSC), but few such pediatric cases have been reported. We describe our experience with 2 children (13- and 10-year-old girls) who presented with spontaneous intracranial hemorrhage followed by pulmonary edema and shock. Echocardiography revealed similar patterns of left ventricular wall motion abnormalities consistent with NSC, inverted Takotsubo variant. One child progressed to death, whereas the other made a remarkable recovery, including significant improvement in cardiac function over the course of 1 week. We argue that at least 1 of these cases represents true stress-induced cardiomyopathy. This report will alert pediatricians to this transient cardiomyopathy that is likely underdiagnosed in pediatric intensive care. We also highlight the challenges of managing both shock and elevated intracranial pressure in the setting of NSC. PMID:25201800

  17. Infective rhomboencephalitis and inverted Takotsubo: neurogenic-stunned myocardium or myocarditis?

    PubMed

    Ruggieri, Francesco; Cerri, Marco; Beretta, Luigi

    2014-02-01

    Here we originally describe the clinical scenario of a young immune-competent patient affected by acute rhomboencephalitis with severe parenchymal edema and acute hydrocephalus who developed sudden life-threatening cardiac derangement. Hemodynamic and perfusion parameters revealed cardiogenic shock, so intensive circulatory support with epinephrine infusion and intra-aortic balloon pump was needed to restore organ perfusion. Transesophageal echocardiographic examination showed severe left ventricular dysfunction (ejection fraction as low as 20%) with wall motion abnormalities resembling a pattern of Takotsubo-inverted cardiomyopathy. Cultural investigations revealed infection by Listeria monocytogenes. Nevertheless, her conditions rapidly improved, and she had full cardiac recovery within few days. Acute cerebral damage, pattern of echocardiographic wall motion abnormalities, and clinical course may suggest neurogenic stunned as pathological mechanism responsible for cardiac dysfunction, but differential diagnosis with acute myocarditis is to be considered too. Acute cardiogenic shock during the course of rhomboencephalitis by L monocytogenes has not been yet reported; prompt clinical suspicion and intensive care are needed to manage this life-threatening condition. PMID:24079984

  18. 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

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

    PubMed

    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

  20. Optimal bladder diary duration for patients with suprapontine neurogenic lower urinary tract dysfunction

    PubMed Central

    Konstantinidis, Charalampos; Kratiras, Zisis; Samarinas, Michael; Skriapas, Konstantinos

    2016-01-01

    ABSTRACT Purpose: To identify the minimum bladder diary's length required to furnish reliable documentation of LUTS in a specific cohort of patients suffering from neurogenic urinary dysfunction secondary to suprapontine pathology. Materials and Methods: From January 2008 to January 2014, patients suffering from suprapontine pathology and LUTS were requested to prospectively complete a bladder diary form for 7 consecutive days. Micturitions per day, excreta per micturition, urgency and incontinence episodes and voided volume per day were evaluated from the completed diaries. We compared the averaged records of consecutive days (2-6 days) to the total 7 days records for each patient's diary, seeking the minimum diary's length that could provide records comparable to the 7 days average, the reference point in terms of reliability. Results: From 285 subjects, 94 male and 69 female patients enrolled in the study. The records of day 1 were significantly different from the average of the 7 days records in every parameter, showing relatively small correlation and providing insufficient documentation. Correlations gradually increased along the increase in diary's duration. According to our results a 3-day duration bladder diary is efficient and can provide results comparable to a 7 day length for four of our evaluated parameters. Regarding incontinence episodes, 3 days seems inadequate to furnish comparable results, showing a borderline difference. Conclusions: A 3-day diary can be used, as its reliability is efficient regarding number of micturition per day, excreta per micturition, episodes of urgency and voided volume per day. PMID:27564288

  1. 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

  2. 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

  3. 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

  4. Caspase-1 inhibitor Prevents Neurogenic Pulmonary Edema after Subarachnoid Hemorrhage in Mice

    PubMed Central

    Suzuki, Hidenori; Sozen, Takumi; Hasegawa, Yu; Chen, Wanqiu; Zhang, John H.

    2009-01-01

    Background and Purpose We examined the effects of a caspase-1 inhibitor, N-Ac-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-CMK), on neurogenic pulmonary edema (NPE) in the endovascular perforation model of subarachnoid hemorrhage (SAH) in mice. Methods Ninety-seven mice were assigned to sham, SAH+vehicle, SAH+Ac-YVAD-CMK (6 or 10mg/kg) and SAH+Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK, 6mg/kg) groups. Drugs were intraperitoneally injected 1 hour post-SAH. Pulmonary edema measurements, Western blot for interleukin-1β, interleukin-18, myeloperoxidase, matrix metalloproteinase (MMP)-2, MMP-9, cleaved caspase-3 and zona occludens (ZO)-1, MMP zymography, TUNEL staining and immunostaining were performed on the lung at 24 hours post-SAH. Results Ten- but not 6-mg/kg of Ac-YVAD-CMK significantly inhibited a post-SAH increase in the activation of interleukin-1β and caspase-3 and the number of TUNEL-positive pulmonary endothelial cells, preventing NPE. Another antiapoptotic drug Z-VAD-FMK also reduced NPE. SAH did not change interleukin-18, myeloperoxidase, MMP-2, MMP-9, ZO-1 levels and MMP activity. Conclusions We report for the first time that Ac-YVAD-CMK prevents lung cell apoptosis and NPE after SAH in mice. PMID:19875734

  5. A Patient With Focal Dystonia That Occurred Secondary to a Peripheral Neurogenic Tumor: A Case Report

    PubMed Central

    Park, Minho; Lee, Jong Ha; Yun, Dong Hwan; Chon, Jinmann; Han, Yoo Jin

    2015-01-01

    Dystonia is a movement disorder characterized by involuntary muscle contractions. Patients with dystonia may experience uncontrollable twisting, repetitive movements, or abnormal posture. A 55-year-old man presented with an involuntary left forearm supination, which he had experienced for five years. There was no history of antecedent trauma to the wrist or elbow. Although conventional therapeutic modalities had been performed, the symptoms persisted. When he visited our hospital, electromyography was performed. Reduced conduction velocity was evident at the elbow-axilla segment of the left median nerve. We suspected that there was a problem on the median nerve between the elbow and the axilla. For this reason, we performed an ultrasonography and magnetic resonance imaging study. A spindle-shaped soft tissue mass was observed at the left median nerve that suggested the possibility of neurofibroma. Dystonia caused by traumatic or compressive peripheral nerve injury has often been reported, but focal dystonia due to a neurogenic tumor is extremely rare. Here, we report our case with a review of the literature. PMID:26361606

  6. Potential neurogenic and vascular roles of nitric oxide in migraine headache and aura.

    PubMed

    Myers, D E

    1999-02-01

    It has long been known that nitrate and nitrite medications consistently cause significant headache as a side effect. Classical research has shown that cerebral vasodilation accompanies the use of these medications. More modern studies suggest that these vasodilators exert their action on blood vessels via nitric oxide and its second messenger, cyclic guanosine monophosphate. This paper reviews research studies and theoretical articles which address the concept that nitric oxide plays a major role in the vasodilation associated with the headache phase of migraine with aura. A brief discussion of nitric oxide biochemistry and pharmacology follows. In addition, there is a review of evidence examining the possible contributions of nitric oxide to the neurogenic and vascular events associated with spreading cortical depression, an animal model of migraine aura. The paradoxical hypotheses that nitric oxide may contribute to both the propagation of spreading cortical depression and its limitation are presented. Finally, a rationale for the experimental use of nitric oxide agonists and antagonists in the abortion of migraine aura is introduced. PMID:15613204

  7. Bladder wall thickness in the assessment of neurogenic bladder: a translational discussion of current clinical applications

    PubMed Central

    Sturm, Renea M.

    2016-01-01

    The prospective trial by Kim et al. “Can Bladder Wall Thickness Predict Videourodynamic Findings in Children with Spina Bifida?” published in Journal of Urology investigated the measurement of bladder wall thickness (BWT) as a non-invasive assessment tool for lower urinary tract changes in neurogenic bladder (NGB). In this study, no significant association was observed between BWT and high-risk urodynamic parameters. This editorial discusses the basic science of bladder wall thickening as well as prior studies relating wall thickness to clinical parameters. Although Kim et al. provide a unique literature contribution in terms of assessment of BWT at defined percent cystometric capacity, specific aspects of study methodology and population may have contributed to a lack of correlation with high-risk urodynamic findings. The application of non-invasive modalities to lower urinary tract assessment of NGB remains a promising and relevant area of future research to prevent progression to end stage lower urinary tract changes for all individuals with spina bifida. PMID:26889485

  8. Successful lung salvage by ex vivo reconditioning of neurogenic pulmonary edema: case report.

    PubMed

    Sanchez, P G; Iacono, A T; Rajagopal, K; Griffith, B P

    2014-09-01

    Liberalization in donor selection criteria allowed centers to increase the number of lung transplants, yet less than 25% of all donors had lungs utilized for transplantation in the United States in 2013. Less than 5% of all transplanted donors deviate 3 or more criteria from the ideal donor. Ex vivo lung perfusion (EVLP) provides the opportunity to increase the percentage of used donors by acting on modifiable selection criteria such as oxygenation, contusion and pulmonary infiltrates. We report the pre-transplant use of EVLP in the salvage of lungs from a donor that developed neurogenic pulmonary edema -PaO2 188 mmHg-. The recipient had a lung allocation score of 69.3. The post-operative course was excellent and was discharged home after 15 days. He is alive and doing well 780 days after transplant. In this report the pre-transplant use of EVLP led not only to transplanting lungs that otherwise would not have been used by many centers, but also to a very short and typical period of post-operative mechanical ventilation and hospital stay. PMID:25242800

  9. Osteogenic and Neurogenic Stem Cells in Their Own Place: Unraveling Differences and Similarities Between Niches

    PubMed Central

    Lattanzi, Wanda; Parolisi, Roberta; Barba, Marta; Bonfanti, Luca

    2015-01-01

    Although therapeutic use of stem cells (SCs) is already available in some tissues (cornea, blood, and skin), in most organs we are far from reaching the translational goal of regenerative medicine. In the nervous system, due to intrinsic features which make it refractory to regeneration/repair, it is very hard to obtain functionally integrated regenerative outcomes, even starting from its own SCs (the neural stem cells; NSCs). Besides NSCs, mesenchymal stem cells (MSCs) have also been proposed for therapeutic purposes in neurological diseases. Yet, direct (regenerative) and indirect (bystander) effects are often confused, as are MSCs and bone marrow-derived (stromal, osteogenic) stem cells (BMSCs), whose plasticity is actually overestimated (i.e., trans-differentiation along non-mesodermal lineages, including neural fates). In order to better understand failure in the “regenerative” use of SCs for neurological disorders, it could be helpful to understand how NSCs and BMSCs have adapted to their respective organ niches. In this perspective, here the adult osteogenic and neurogenic niches are considered and compared within their in vivo environment. PMID:26635534

  10. Spinal Burkitt's Lymphoma Mimicking Dumbbell Shape Neurogenic Tumor: A Case Report and Review of the Literature

    PubMed Central

    Kim, You-Sub; Choi, Ki-Young; Jang, Jae-Won

    2015-01-01

    Non-Hodgkin's lymphoma (NHL), a disease which may involve the spine, is frequently associated with advanced disease. Radiculopathy caused by spinal root compression as the initial presentation in patients with NHL is very rare and thought to occur in less than 5% of cases. A 69-year-old woman complained of a history of low back pain with right sciatica for 1 month prior to admission. Computed tomography and magnetic resonance imaging of the lumbar spine showed a dumbbell-shape epidural mass lesion extending from L2 to L3, which was suggestive of a neurogenic tumor. After paraspinal approach and L2 lower half partial hemilaminectomy, total excision of the tumor was achieved, followed by rapid improvement of back pain and radiating pain. The lesion was confirmed to be Burkitt's lymphoma by histopathological examination. We then checked whole-body PET-CT, which showed multifocal malignant lesions in the intestine, liver, bone and left supraclavicular lymph node. Although a rare situation, Burkitt's lymphoma should be considered in the differential diagnosis for patients presenting with back and lumbar radicular pain without a prior history of malignancy. Burkitt's lymphoma could be the cause of dumbbell-shape spinal tumor. PMID:26512290

  11. [Posttraumatic stress disorder in patients with neurogenic amnesia for the traumatic event].

    PubMed

    Podoll, K; Kunert, H J; Sass, H

    2000-10-01

    The development of symptoms of posttraumatic stress disorder (PTSD) in patients with neurogenic amnesia for the traumatic event is recorded in 2 own patients and in 19 cases from the clinical literature. With a single exception, all patients were accident victims with closed head injuries. Only about three quarters of the patients completely fulfilled DSM-III-R criteria of PTSD. Nineteen patients displayed involuntary conscious memories of aspects of the traumatic event (presenting as recurrent intrusive thoughts, images or dreams) co-existent with a complete or partial lack of voluntary conscious memories of the trauma, suggesting that different memory systems and distinct brain mechanisms subserve these phenomena. The said clinical observations are discussed against the background of current neuropsychological models of multiple memory systems. The recorded cases demonstrate that declarative episodic memory is not necessary for symptoms of PTSD to emerge, whereas preserved functions of non-declarative memory systems represent a sufficient condition for the development of PTSD symptoms. PMID:11103682

  12. Neurogenic bladder: Highly selective rhizotomy of specific dorsal rootlets maybe a better choice.

    PubMed

    Zhu, Genying; Zhou, Mouwang; Wang, Wenting; Zeng, Fanshuo

    2016-02-01

    Spinal cord injury results not only in motor and sensory dysfunctions, but also in loss of normal urinary bladder functions. A number of clinical studies were focused on the strategies for improvement of functions of the bladder. Completely dorsal root rhizotomy or selective specific S2-4 dorsal root rhizotomy suppress autonomic hyper-reflexia but have the same defects: it could cause detrusor and sphincter over-relaxation and loss of reflexive erection in males. So precise operation needs to be considered. We designed an experimental trail to test the possibility on the basis of previous study. We found that different dorsal rootlets which conduct impulses from the detrusor or sphincter can be distinguished by electro-stimulation in SD rats. Highly selective rhizotomy of specific dorsal rootlets could change the intravesical pressure and urethral perfusion pressure respectively. We hypothese that for neurogenic bladder following spinal cord injury, highly selective rhizotomy of specific dorsal rootlets maybe improve the bladder capacity and the detrusor sphincter dyssynergia, and at the same time, the function of other pelvic organ could be maximize retainment. PMID:26643667

  13. Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats

    PubMed Central

    Glenn, Melissa J.; Gibson, Erin M.; Kirby, Elizabeth D.; Mellott, Tiffany J.; Blusztajn, Jan K.; Williams, Christina L.

    2008-01-01

    Increased dietary intake of choline early in life improves performance of adult rats on memory tasks and prevents their age-related memory decline. Because neurogenesis in the adult hippocampus also declines with age, we investigated whether prenatal choline availability affects hippocampal neurogenesis in adult Sprague–Dawley rats and modifies their neurogenic response to environmental stimulation. On embryonic days (ED) 12−17, pregnant rats ate a choline-supplemented (SUP-5 g/kg), choline sufficient (SFF-1.1 g/kg), or choline-free (DEF) semisynthetic diet. Adult offspring either remained in standard housing or were given 21 daily visits to explore a maze. On the last ten exploration days, all rats received daily injections of 5-bromo-2-deoxyuridine (BrdU, 100 mg/kg). The number of BrdU+ cells was significantly greater in the dentate gyrus in SUP rats compared to SFF or DEF rats. While maze experience increased the number of BrdU+ cells in SFF rats to the level seen in the SUP rats, this enriching experience did not alter cell proliferation in DEF rats. Similar patterns of cell proliferation were obtained with immunohistochemical staining for neuronal marker doublecortin, confirming that diet and exploration affected hippocampal neurogenesis. Moreover, hippocampal levels of the brain-derived neurotrophic factor (BDNF) were increased in SUP rats as compared to SFF and DEF animals. We conclude that prenatal choline intake has enduring effects on adult hippocampal neurogenesis, possibly via up-regulation of BDNF levels, and suggest that these alterations of neurogenesis may contribute to the mechanism of life-long changes in cognitive function governed by the availability of choline during gestation. PMID:17445242

  14. 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

  15. Neurogenic Bladder and Urodynamic Outcomes in Patients with Spinal Cord Myelopathy

    PubMed Central

    Dillon, Louise

    2015-01-01

    Background: Urodynamics (UDs) are routine in traumatic spinal cord injury (SCI), but there are few reports regarding nontraumatic spinal cord myelopathy (SCM) patients. Purpose: To describe the neurogenic bladder and UD outcomes in SCM patients and determine whether the UD recommendations result in clinically important changes to bladder management. Methods: This retrospective case study examined a series of SCM patients admitted to a spinal rehabilitation service who underwent UDs between January 1, 2000 and June 30, 2010. Results: Sixty-five UD tests were performed a median of 7 months post SCM. Most (n = 34; 57%) patients were male, and the median age was 60 years. Most patients (n = 46; 77%) were paraplegic and were continent of urine (n = 38; 58%). Thirty-five (46%) patients voided on sensation, 26 (40%) performed intermittent self-catheterization, and 9 (14%) had an indwelling catheter. The most common UD finding was overactive detrusor with no dysynergia (n = 31; 48%), followed by overactive detrusor with sphincter dysynergia (n = 16; 25%) and detrusor areflexia/underactive (n = 12; 18%). Key UD findings were median cystometric capacity 414 mL (interquartile range [IQR], 300–590), median maximum detrusor contraction 49.5 cmH2O (IQR, 25–85), and median residual volume post voiding 100 mL (IQR, 5–200). The recommendations for changes to bladder management following UDs resulted in clinically important changes to existing strategies in 57 studies (88%). Conclusions: Future studies should ascertain whether our screening protocol is appropriate, and a longer-term follow-up should examine the relationship between UD recommendations and prevention of complications. PMID:26363592

  16. Long-Term Cost-Effectiveness of Transanal Irrigation in Patients with Neurogenic Bowel Dysfunction

    PubMed Central

    Emmanuel, Anton; Kumar, Gayathri; Christensen, Peter; Mealing, Stuart; Størling, Zenia M.; Andersen, Frederikke; Kirshblum, Steven

    2016-01-01

    Background People suffering from neurogenic bowel dysfunction (NBD) and an ineffective bowel regimen often suffer from fecal incontinence (FI) and related symptoms, which have a huge impact on their quality of life. In these situations, transanal irrigation (TAI) has been shown to reduce these symptoms and improve quality of life. Aim To investigate the long-term cost-effectiveness of initiating TAI in patients with NBD who have failed standard bowel care (SBC). Methods A deterministic Markov decision model was developed to project the lifetime health economic outcomes, including quality-adjusted life years (QALYs), episodes of FI, urinary tract infections (UTIs), and stoma surgery when initiating TAI relative to continuing SBC. A data set consisting of 227 patients with NBD due to spinal cord injury (SCI), multiple sclerosis, spina bifida and cauda equina syndrome was used in the analysis. In the model a 30-year old individual with SCI was used as a base-case. A probabilistic sensitivity analysis was applied to evaluate the robustness of the model. Results The model predicts that a 30-year old SCI patient with a life expectancy of 37 years initiating TAI will experience a 36% reduction in FI episodes, a 29% reduction in UTIs, a 35% reduction in likelihood of stoma surgery and a 0.4 improvement in QALYs, compared with patients continuing SBC. A lifetime cost-saving of £21,768 per patient was estimated for TAI versus continuing SBC alone. Conclusion TAI is a cost-saving treatment strategy reducing risk of stoma surgery, UTIs, episodes of FI and improving QALYs for NBD patients who have failed SBC. PMID:27557052

  17. Minocycline treatment ameliorates interferon-alpha- induced neurogenic defects and depression-like behaviors in mice

    PubMed Central

    Zheng, Lian-Shun; Kaneko, Naoko; Sawamoto, Kazunobu

    2015-01-01

    Interferon-alpha (IFN-α) is a proinflammatory cytokine that is widely used for the treatment of chronic viral hepatitis and malignancy, because of its immune-activating, antiviral, and antiproliferative properties. However, long-term IFN-α treatment frequently causes depression, which limits its clinical utility. The precise molecular and cellular mechanisms of IFN-α-induced depression are not currently understood. Neural stem cells (NSCs) in the hippocampus continuously generate new neurons, and some evidence suggests that decreased neurogenesis plays a role in the neuropathology of depression. We previously reported that IFN-α treatment suppressed hippocampal neurogenesis and induced depression-like behaviors via its receptors in the brain in adult mice. However, it is unclear how systemic IFN-α administration induces IFN-α signaling in the hippocampus. In this study, we analyzed the role of microglia, immune cells in the brain, in mediating the IFN-α-induced neurogenic defects and depressive behaviors. In vitro studies demonstrated that IFN-α treatment induced the secretion of endogenous IFN-α from microglia, which suppressed NSC proliferation. In vivo treatment of adult mice with IFN-α for 5 weeks increased the production of proinflammatory cytokines, including IFN-α, and reduced neurogenesis in the hippocampus. Both effects were prevented by simultaneous treatment with minocycline, an inhibitor of microglial activation. Furthermore, minocycline treatment significantly suppressed IFN-α-induced depressive behaviors in mice. These results suggest that microglial activation plays a critical role in the development of IFN-α-induced depression, and that minocycline is a promising drug for the treatment of IFN-α-induced depression in patients, especially those who are low responders to conventional antidepressant treatments. PMID:25674053

  18. Cholinergic Enhancement of Cell Proliferation in the Postnatal Neurogenic Niche of the Mammalian Spinal Cord

    PubMed Central

    Corns, Laura F.; Atkinson, Lucy; Daniel, Jill; Edwards, Ian J.; New, Lauryn

    2015-01-01

    Abstract The region surrounding the central canal (CC) of the spinal cord is a highly plastic area, defined as a postnatal neurogenic niche. Within this region are ependymal cells that can proliferate and differentiate to form new astrocytes and oligodendrocytes following injury and cerebrospinal fluid contacting cells (CSFcCs). The specific environmental conditions, including the modulation by neurotransmitters that influence these cells and their ability to proliferate, are unknown. Here, we show that acetylcholine promotes the proliferation of ependymal cells in mice under both in vitro and in vivo conditions. Using whole cell patch clamp in acute spinal cord slices, acetylcholine directly depolarized ependymal cells and CSFcCs. Antagonism by specific nicotinic acetylcholine receptor (nAChR) antagonists or potentiation by the α7 containing nAChR (α7*nAChR) modulator PNU 120596 revealed that both α7*nAChRs and non‐α7*nAChRs mediated the cholinergic responses. Using the nucleoside analogue EdU (5‐ethynyl‐2'‐deoxyuridine) as a marker of cell proliferation, application of α7*nAChR modulators in spinal cord cultures or in vivo induced proliferation in the CC region, producing Sox‐2 expressing ependymal cells. Proliferation also increased in the white and grey matter. PNU 120596 administration also increased the proportion of cells coexpressing oligodendrocyte markers. Thus, variation in the availability of acetylcholine can modulate the rate of proliferation of cells in the ependymal cell layer and white and grey matter through α7*nAChRs. This study highlights the need for further investigation into how neurotransmitters regulate the response of the spinal cord to injury or during aging. Stem Cells 2015;33:2864–2876 PMID:26038197

  19. Neurogenic mechanisms underlying the rapid onset of sympathetic responses to intermittent hypoxia.

    PubMed

    Mifflin, Steve; Cunningham, J Thomas; Toney, Glenn M

    2015-12-15

    Sleep apnea (SA) leads to metabolic abnormalities and cardiovascular dysfunction. Rodent models of nocturnal intermittent hypoxia (IH) are used to mimic arterial hypoxemias that occur during SA. This mini-review focuses on our work examining central nervous system (CNS) mechanisms whereby nocturnal IH results in increased sympathetic nerve discharge (SND) and hypertension (HTN) that persist throughout the 24-h diurnal period. Within the first 1-2 days of IH, arterial pressure (AP) increases even during non-IH periods of the day. Exposure to IH for 7 days biases nucleus tractus solitarius (NTS) neurons receiving arterial chemoreceptor inputs toward increased discharge, providing a substrate for persistent activation of sympathetic outflow. IH HTN is blunted by manipulations that reduce angiotensin II (ANG II) signaling within the forebrain lamina terminalis suggesting that central ANG II supports persistent IH HTN. Inhibition of the hypothalamic paraventricular nucleus (PVN) reduces ongoing SND and acutely lowers AP in IH-conditioned animals. These findings support a role for the PVN, which integrates information ascending from NTS and descending from the lamina terminalis, in sustaining IH HTN. In summary, our findings indicate that IH rapidly and persistently activates a central circuit that includes the NTS, forebrain lamina terminalis, and the PVN. Our working model holds that NTS neuromodulation increases transmission of arterial chemoreceptor inputs, increasing SND via connections with PVN and rostral ventrolateral medulla. Increased circulating ANG II sensed by the lamina terminalis generates yet another excitatory drive to PVN. Together with adaptations intrinsic to the PVN, these responses to IH support rapid onset neurogenic HTN. PMID:25997944

  20. 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.

  1. Sustained phosphorylation of MARCKS in differentiating neurogenic regions during chick embryo development.

    PubMed

    Zolessi, F R; Arruti, C

    2001-10-24

    MARCKS, a substrate for several kinases, has critical functions in morphogenetic processes involved in the development of the nervous system. We previously described the purification of MARCKS from chick embryo brain, using a monoclonal antibody (mAb 3C3), raised against embryonic neural retina. Here we show that mAb 3C3 is an antibody sensitive to phosphorylation state. We used it to explore the appearance and developmental progression of phospho-MARCKS (ph-MARCKS) during initial stages of neurogenesis in retina and spinal cord, and compared its distribution with total MARCKS. Before the onset of neural differentiation, MARCKS protein was already accumulated in neural and non-neural embryonic tissues, while ph-MARCKS immunoreactivity was weak, although ubiquitous too. A sudden increase of ph-MARCKS, paralleling a total MARCKS augmentation, was particularly noticeable in the earliest differentiating neurons in the neural retina. Ganglion cells displayed a high ph-MARCKS signal in the soma, as well as in the growing axon. A short time thereafter, a similar increase of ph-MARCKS was present across the entire width of the neural retina, where the differentiation of other neurons and photoreceptors occurs. The increase of ph-MARCKS in cells took place before the detection of the transcription factor Islet-1/2, an early neuronal differentiation molecular marker, in cells of the same region. Analogous phenomena were observed in cervical regions of the spinal cord, where motor neurons were differentiating. Neurogenic regions in the spinal cord contained higher amounts of ph-MARCKS than the floor plate. Taken together, these results strongly suggest that the appearance and relatively long-lasting presence of ph-MARCKS polypeptides are related to specific signaling pathways active during neurogenesis. PMID:11675128

  2. Stem Cells Expanded from the Human Embryonic Hindbrain Stably Retain Regional Specification and High Neurogenic Potency

    PubMed Central

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

    2013-01-01

    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. PMID:23884946

  3. Dural neurogenic inflammation induced by neuropathic pain is specific to cranial region.

    PubMed

    Filipović, B; Matak, I; Lacković, Z

    2014-05-01

    Up to now, dural neurogenic inflammation (DNI) has been studied primarily as a part of migraine pain pathophysiology. A recent study from our laboratory demonstrated the occurrence of DNI in response to peripheral trigeminal nerve injury. In this report, we characterize the occurrence of DNI after different peripheral nerve injuries in and outside of the trigeminal region. We have used the infraorbital nerve constriction injury model (IoNC) as a model of trigeminal neuropathic pain. Greater occipital nerve constriction injury (GoNC), partial transection of the sciatic nerve (ScNT) and sciatic nerve constriction injury (SCI) were employed to characterize the occurrence of DNI in response to nerve injury outside of the trigeminal region. DNI was measured as colorimetric absorbance of Evans blue plasma protein complexes. In addition, cellular inflammatory response in dural tissue was histologically examined in IoNC and SCI models. In comparison to the strong DNI evoked by IoNC, a smaller but significant DNI has been observed following the GoNC. However, DNI has not been observed either in cranial or in lumbar dura following ScNT and SCI. Histological evidence has demonstrated a dural proinflammatory cell infiltration in the IoNC model, which is in contrast to the SCI model. Inflammatory cell types (lymphocytes, plasma cells, and monocytes) have indicated the presence of sterile cellular inflammatory response in the IoNC model. To our knowledge, this is the first observation that the DNI evoked by peripheral neuropathic pain is specific to the trigeminal area and the adjacent occipital area. DNI after peripheral nerve injury consists of both plasma protein extravasation and proinflammatory cell infiltration. PMID:24366531

  4. 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. PMID:26184852

  5. 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

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

    PubMed

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

    2016-05-21

    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. PMID:27124547

  7. Protein Kinase Cδ Mediates Neurogenic but Not Mitogenic Activation of Mitogen-Activated Protein Kinase in Neuronal Cells

    PubMed Central

    Corbit, Kevin C.; Foster, David A.; Rosner, Marsha Rich

    1999-01-01

    In several neuronal cell systems, fibroblast-derived growth factor (FGF) and nerve growth factor (NGF) act as neurogenic agents, whereas epidermal growth factor (EGF) acts as a mitogen. The mechanisms responsible for these different cellular fates are unclear. We report here that although FGF, NGF, and EGF all activate mitogen-activated protein (MAP) kinase (extracellular signal-related kinase [ERK]) in rat hippocampal (H19-7) and pheochromocytoma (PC12) cells, the activation of ERK by the neurogenic agents FGF and NGF is dependent upon protein kinase Cδ (PKCδ), whereas ERK activation in response to the mitogenic EGF is independent of PKCδ. Antisense PKCδ oligonucleotides or the PKCδ-specific inhibitor rottlerin inhibited FGF- and NGF-induced, but not EGF-induced, ERK activation. In contrast, EGF-induced ERK activation was inhibited by the phosphatidylinositol-3-kinase inhibitor wortmannin, which had no effect upon FGF-induced ERK activation. Rottlerin also inhibited the activation of MAP kinase kinase (MEK) in response to activated Raf, but had no effect upon c-Raf activity or ERK activation by activated MEK. These results indicate that PKCδ functions either downstream from or in parallel with c-Raf, but upstream of MEK. Inhibition of PKCδ also blocked neurite outgrowth induced by FGF and NGF in PC12 cells and by activated Raf in H19-7 cells, indicating a role for PKCδ in the neurogenic effects of FGF, NGF, and Raf. Interestingly, the PKCδ requirement is apparently cell type specific, since FGF-induced ERK activation was independent of PKCδ in NIH 3T3 murine fibroblasts, in which FGF is a mitogen. These data demonstrate that PKCδ contributes to growth factor specificity and response in neuronal cells and may also promote cell-type-specific differences in growth factor signaling. PMID:10330161

  8. 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

  9. [Spinal lipoma with a dural closure defect as a cause of neurogenic bladder and chronic renal failure].

    PubMed

    Eichler, I; Ungersböck, K; Waldhauser, F; Balzar, E; Nürnberger, N; Pflüger, H; Frisch, H

    1986-04-01

    It is reported on a 6-year-old boy, in whom 3 years after the appearance of a neurogenic disturbance of the urinary bladder a lipoma in the spinal canal of the inferior thoracic region was diagnosed myelographically. The operative removal of the growing and displacing fatty tissue which by a (congenital?) dural gap continued in epidural direction indeed resulted in a far-reaching regression of the paresis of the lower extremities, not, however, in an improvement of the urological picture of the disease. The renal insufficiency caused by the hydronephrosis was no more reversible, which emphasizes the importance of the early diagnosis of this relatively infrequent malformation. PMID:3727820

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

    PubMed Central

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

    2015-01-01

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