The Nuclear Receptor TLX Is Required for Gliomagenesis within the Adult Neurogenic Niche

PubMed Central

Zou, Yuhua; Niu, Wenze; Qin, Song; Downes, Michael; Burns, Dennis K.

2012-01-01

Neural stem cells (NSCs) continually generate functional neurons in the adult brain. Due to their ability to proliferate, deregulated NSCs or their progenitors have been proposed as the cells of origin for a number of primary central nervous system neoplasms, including infiltrating gliomas. The orphan nuclear receptor TLX is required for proliferation of adult NSCs, and its upregulation promotes brain tumor formation. However, it is unknown whether TLX is required for gliomagenesis. We examined the genetic interactions between TLX and several tumor suppressors, as well as the role of TLX-dependent NSCs during gliomagenesis, using mouse models. Here, we show that TLX is essential for the proliferation of adult NSCs with a single deletion of p21, p53, or Pten or combined deletion of Pten and p53. While brain tumors still form in Tlx mutant mice, these tumors are less infiltrative and rarely associate with the adult neurogenic niches, suggesting a non-stem-cell origin. Taken together, these results indicate a critical role for TLX in NSC-dependent gliomagenesis and implicate TLX as a therapeutic target to inhibit the development of NSC-derived brain tumors. PMID:23028043

The nuclear receptor TLX is required for gliomagenesis within the adult neurogenic niche.

PubMed

Zou, Yuhua; Niu, Wenze; Qin, Song; Downes, Michael; Burns, Dennis K; Zhang, Chun-Li

2012-12-01

Neural stem cells (NSCs) continually generate functional neurons in the adult brain. Due to their ability to proliferate, deregulated NSCs or their progenitors have been proposed as the cells of origin for a number of primary central nervous system neoplasms, including infiltrating gliomas. The orphan nuclear receptor TLX is required for proliferation of adult NSCs, and its upregulation promotes brain tumor formation. However, it is unknown whether TLX is required for gliomagenesis. We examined the genetic interactions between TLX and several tumor suppressors, as well as the role of TLX-dependent NSCs during gliomagenesis, using mouse models. Here, we show that TLX is essential for the proliferation of adult NSCs with a single deletion of p21, p53, or Pten or combined deletion of Pten and p53. While brain tumors still form in Tlx mutant mice, these tumors are less infiltrative and rarely associate with the adult neurogenic niches, suggesting a non-stem-cell origin. Taken together, these results indicate a critical role for TLX in NSC-dependent gliomagenesis and implicate TLX as a therapeutic target to inhibit the development of NSC-derived brain tumors.

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…

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. © 2016 Wiley Periodicals, Inc.

Management of Neurogenic Bladder.

PubMed

Sripathi, Venkataramani; Mitra, Aparajita

2017-07-01

This article provides a comprehensive summary of the clinical approach, investigative modalities and management of a child with neurogenic bladder disease due to myelodysplasia. It is aimed at pediatric physicians and surgeons working in developing nations. The methodologies suggested are simple and can be practised even in resource poor regions. The goal of management is avoidance of Chronic kidney disease and for this, meticulous bladder management is the key.

Cytoarchitecture and Ultrastructure of Neural Stem Cell Niches and Neurogenic Complexes Maintaining Adult Neurogenesis in the Olfactory Midbrain of Spiny Lobsters, Panulirus argus

PubMed Central

Schmidt, Manfred; Derby, Charles D.

2013-01-01

New interneurons are continuously generated in small proliferation zones within neuronal somata clusters in the olfactory deutocerebrum of adult decapod crustaceans. Each proliferation zone is connected to a clump of cells containing one neural stem cell (i.e., adult neuroblast), thus forming a “neurogenic complex.” Here we provide a detailed analysis of the cytoarchitecture of neurogenic complexes in adult spiny lobsters, Panulirus argus, based on transmission electron microscopy and labeling with cell-type-selective markers. The clump of cells is composed of unique bipolar clump-forming cells that collectively completely envelop the adult neuroblast and are themselves ensheathed by a layer of processes of multipolar cell body glia. An arteriole is attached to the clump of cells, but dye perfusion experiments show that hemolymph has no access to the interior of the clump of cells. Thus, the clump of cells fulfills morphological criteria of a protective stem cell niche, with clump-forming cells constituting the adult neuroblast’s microenvironment together with the cell body glia processes separating it from other tissue components. Bromodeoxyuridine pulse-chase experiments with short survival times suggest that adult neuroblasts are not quiescent but rather cycle actively during daytime. We propose a cell lineage model in which an asymmetrically dividing adult neuroblast repopulates the pool of neuronal progenitor cells in the associated proliferation zone. In conclusion, as in mammalian brains, adult neurogenesis in crustacean brains is fueled by neural stem cells that are maintained by stem cell niches that preserve elements of the embryonic microenvironment and contain glial and vascular elements. PMID:21523781

Cytoarchitecture and ultrastructure of neural stem cell niches and neurogenic complexes maintaining adult neurogenesis in the olfactory midbrain of spiny lobsters, Panulirus argus.

PubMed

Schmidt, Manfred; Derby, Charles D

2011-08-15

New interneurons are continuously generated in small proliferation zones within neuronal somata clusters in the olfactory deutocerebrum of adult decapod crustaceans. Each proliferation zone is connected to a clump of cells containing one neural stem cell (i.e., adult neuroblast), thus forming a "neurogenic complex." Here we provide a detailed analysis of the cytoarchitecture of neurogenic complexes in adult spiny lobsters, Panulirus argus, based on transmission electron microscopy and labeling with cell-type-selective markers. The clump of cells is composed of unique bipolar clump-forming cells that collectively completely envelop the adult neuroblast and are themselves ensheathed by a layer of processes of multipolar cell body glia. An arteriole is attached to the clump of cells, but dye perfusion experiments show that hemolymph has no access to the interior of the clump of cells. Thus, the clump of cells fulfills morphological criteria of a protective stem cell niche, with clump-forming cells constituting the adult neuroblast's microenvironment together with the cell body glia processes separating it from other tissue components. Bromodeoxyuridine pulse-chase experiments with short survival times suggest that adult neuroblasts are not quiescent but rather cycle actively during daytime. We propose a cell lineage model in which an asymmetrically dividing adult neuroblast repopulates the pool of neuronal progenitor cells in the associated proliferation zone. In conclusion, as in mammalian brains, adult neurogenesis in crustacean brains is fueled by neural stem cells that are maintained by stem cell niches that preserve elements of the embryonic microenvironment and contain glial and vascular elements. Copyright © 2011 Wiley-Liss, Inc.

Droxidopa: a review of its use in symptomatic neurogenic orthostatic hypotension.

PubMed

Keating, Gillian M

2015-02-01

The norepinephrine prodrug droxidopa (NORTHERA™) is approved in the US for the treatment of orthostatic dizziness, lightheadedness, or the 'feeling that you are about to black out' in adults with symptomatic neurogenic orthostatic hypotension associated with primary autonomic failure (e.g. Parkinson's disease, multiple system atrophy or pure autonomic failure), dopamine β-hydroxylase deficiency or nondiabetic autonomic neuropathy. This article reviews the clinical efficacy and tolerability of droxidopa in symptomatic neurogenic orthostatic hypotension, as well as summarizing its pharmacological properties. Oral droxidopa was effective in the shorter-term treatment of patients with symptomatic neurogenic orthostatic hypotension, with improvements seen in symptoms, the impact of symptoms on daily activities and standing systolic blood pressure. More data are needed to confirm the longer-term efficacy of droxidopa. Droxidopa was generally well tolerated, although patients should be monitored for supine hypertension.

Provider Adherence to Implementation of Clinical Practice Guidelines for Neurogenic Bowel in Adults With Spinal Cord Injury

PubMed Central

Goetz, Lance L; Nelson, Audrey L; Guihan, Marylou; Bosshart, Helen T; Harrow, Jeffrey J; Gerhart, Kevin D; Krasnicka, Barbara; Burns, Stephen P

2005-01-01

Background/Objectives: Clinical Practice Guidelines (CPGs) have been published on a number of topics in spinal cord injury (SCI) medicine. Research in the general medical literature shows that the distribution of CPGs has a minimal effect on physician practice without targeted implementation strategies. The purpose of this study was to determine (a) whether dissemination of an SCI CPG improved the likelihood that patients would receive CPG recommended care and (b) whether adherence to CPG recommendations could be improved through a targeted implementation strategy. Specifically, this study addressed the “Neurogenic Bowel Management in Adults with Spinal Cord Injury” Clinical Practice Guideline published in March 1998 by the Consortium for Spinal Cord Medicine Methods: CPG adherence was determined from medical record review at 6 Veterans Affairs SCI centers for 3 time periods: before guideline publication (T1), after guideline publication but before CPG implementation (T2), and after targeted CPG implementation (T3). Specific implementation strategies to enhance guideline adherence were chosen to address the barriers identified by SCI providers in focus groups before the intervention. Results: Overall adherence to recommendations related to neurogenic bowel did not change between T1 and T2 (P = not significant) but increased significantly between T2 and T3 (P < 0.001) for 3 of 6 guideline recommendations. For the other 3 guideline recommendations, adherence rates were noted to be high at T1. Conclusions: While publication of the CPG alone did not alter rates of provider adherence, the use of a targeted implementation plan resulted in increases in adherence rates with some (3 of 6) CPG recommendations for neurogenic bowel management. PMID:16869086

Neurogenic contributions made by dietary regulation to hippocampal neurogenesis.

PubMed

Park, Hee Ra; Lee, Jaewon

2011-07-01

Adult neural stem cells in the dentate gyrus of the hippocampus are negatively and positively regulated by a broad range of environmental stimuli that include aging, stress, social interaction, physical activity, and dietary modulation. Interestingly, dietary regulation has a distinct outcome, such that reduced dietary intake enhances neurogenesis, whereas excess calorie intake by a high-fat diet has a negative effect. As a type of metabolic stress, dietary restriction (DR) is also known to extend life span and increase resistance to age-related neurodegenerative diseases. However, the potential application of DR as a "neurogenic enhancer" in humans remains problematic because of the severity of restriction and the protracted duration of the treatment required. Therefore, the authors consider that an understanding of the neurogenic mechanisms of DR would provide a basis for the identification of the pharmacological and nutraceutical interventions that mimic the beneficial effects of DR without limiting caloric intake. The current review describes the regulatory effect of DR on hippocampal neurogenesis and presents a possible neurogenic mechanism. © 2011 New York Academy of Sciences.

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

Management of oropharyngeal neurogenic dysphagia in adults.

PubMed

Miles, Anna; Allen, Jacqui E

2015-12-01

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

Neurodevelopmental origin and adult neurogenesis of the neuroendocrine hypothalamus

PubMed Central

Maggi, Roberto; Zasso, Jacopo; Conti, Luciano

2015-01-01

The adult hypothalamus regulates many physiological functions and homeostatic loops, including growth, feeding and reproduction. In mammals, the hypothalamus derives from the ventral diencephalon where two distinct ventricular proliferative zones have been described. Although a set of transcription factors regulating the hypothalamic development has been identified, the exact molecular mechanisms that drive the differentiation of hypothalamic neural precursor cells (NPCs) toward specific neuroendocrine neuronal subtypes is yet not fully disclosed. Neurogenesis has been also reported in the adult hypothalamus at the level of specific niches located in the ventrolateral region of ventricle wall, where NPCs have been identified as radial glia-like tanycytes. Here we review the molecular and cellular systems proposed to support the neurogenic potential of developing and adult hypothalamic NPCs. We also report new insights on the mechanisms by which adult hypothalamic neurogenesis modulates key functions of this brain region. Finally, we discuss how environmental factors may modulate the adult hypothalamic neurogenic cascade. PMID:25610370

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline.

PubMed

Lupo, Giuseppe; Nisi, Paola S; Esteve, Pilar; Paul, Yu-Lee; Novo, Clara Lopes; Sidders, Ben; Khan, Muhammad A; Biagioni, Stefano; Liu, Hai-Kun; Bovolenta, Paola; Cacci, Emanuele; Rugg-Gunn, Peter J

2018-06-01

Adult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age-associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale. In this study, we compare the transcriptional, histone methylation and DNA methylation signatures of NSPCs derived from the subventricular zone (SVZ) of young adult (3 months old) and aged (18 months old) mice. Surprisingly, the transcriptional and epigenomic profiles of SVZ-derived NSPCs are largely unchanged in aged cells. Despite the global similarities, we detect robust age-dependent changes at several hundred genes and regulatory elements, thereby identifying putative regulators of neurogenic decline. Within this list, the homeobox gene Dbx2 is upregulated in vitro and in vivo, and its promoter region has altered histone and DNA methylation levels, in aged NSPCs. Using functional in vitro assays, we show that elevated Dbx2 expression in young adult NSPCs promotes age-related phenotypes, including the reduced proliferation of NSPC cultures and the altered transcript levels of age-associated regulators of NSPC proliferation and differentiation. Depleting Dbx2 in aged NSPCs caused the reverse gene expression changes. Taken together, these results provide new insights into the molecular programmes that are affected during mouse NSPC aging, and uncover a new functional role for Dbx2 in promoting age-related neurogenic decline. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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

PubMed

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

2012-07-01

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

Neurogenic Fever.

PubMed

Meier, Kevin; Lee, Kiwon

2017-02-01

Fever is a relatively common occurrence among patients in the intensive care setting. Although the most obvious and concerning etiology is sepsis, drug reactions, venous thromboembolism, and postsurgical fevers are all on the differential diagnosis. There is abundant evidence that fever is detrimental in acute neurologic injury. Worse outcomes are reported in acute stroke, subarachnoid hemorrhage, and traumatic brain injury. In addition to the various etiologies of fever in the intensive care setting, neurologic illness is a risk factor for neurogenic fevers. This primarily occurs in subarachnoid hemorrhage and traumatic brain injury, with hypothalamic injury being the proposed mechanism. Paroxysmal sympathetic hyperactivity is another source of hyperthermia commonly seen in the population with traumatic brain injury. This review focuses on the detrimental effects of fever on the neurologically injured as well as the risk factors and diagnosis of neurogenic fever.

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

PubMed Central

Downs, Jairon; Wolfe, Tracy; Walker, Heather

2014-01-01

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

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

PubMed Central

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

2016-01-01

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

Neurogenic Thoracic Outlet Syndrome Caused by Vascular Compression of the Brachial Plexus: A Report of Two Cases

PubMed Central

Hanna, Amgad; Bodden, Larry O'Neil; Siebiger, Gabriel R. L.

2018-01-01

Thoracic outlet syndrome (TOS) is caused by compression of the brachial plexus and/or subclavian vessels as they pass through the cervicothoracobrachial region, exiting the chest. There are three main types of TOS: neurogenic TOS, arterial TOS, and venous TOS. Neurogenic TOS accounts for approximately 95% of all cases, and it is usually caused by physical trauma (posttraumatic etiology), chronic repetitive motion (functional etiology), or bone or muscle anomalies (congenital etiology). We present two cases in which neurogenic TOS was elicited by vascular compression of the inferior portion of the brachial plexus. PMID:29497457

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

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.

Neurogenic Causes of Detrusor Underactivity

PubMed Central

Kadow, Brian T.; Tyagi, Pradeep; Chermansky, Christopher J.

2015-01-01

Detrusor underactivity (DU) is a poorly understood dysfunction of the lower urinary tract which arises from multiple etiologies. Symptoms of DU are non-specific, and a pressure-flow urodynamic study is necessary to differentiate DU from other conditions such as overactive bladder (OAB) or bladder outlet obstruction (BOO). The prevalence of DU ranges from 10–48%, and DU is most prevalent in elderly males. The pathophysiology underlying DU can be from both neurogenic and non-neurogenic causes. In this article, we review the neurogenic causes of detrusor underactivity, including diabetic bladder dysfunction, spinal cord injury, multiple sclerosis, Parkinson’s disease, cerebrovascular accident, traumatic brain injury, and Fowler’s syndrome. As knowledge about the underlying causes of DU advances, there have been several potential therapeutic approaches proposed to help those who suffer from this condition. PMID:26715948

Neurogenic stuttering: a review of the literature.

PubMed

Cruz, C; Amorim, H; Beca, G; Nunes, R

2018-01-16

Neurogenic stuttering is a disorder of neurologic origin in the rhythm of speech during which the patient knows exactly what he wants to say but is unable to because of an involuntary prolongation, cessation or repetition of a sound. To assemble new insights regarding the epidemiology, pathophysiology, diagnosis, evaluation and treatment of neurogenic stuttering. A review of all PubMed and Scopus published articles between January 2000 and September 2016 was performed. Thirty-three publications were analyzed. Neurogenic stuttering is a rare entity whose epidemiological incidence is yet not fully established. It is correlated with several neurological diseases and with several possible localizations within the nervous system. Notwithstanding the recent advances in the understanding of the underlying mechanism, it is not yet possible to establish a single pathophysiological mechanism of neurogenic stuttering. The differential diagnosis is complex and requires the detailed knowledge of other language disorders. The treatment is currently based on specific speech language therapy strategies. Neurogenic stuttering is a complex disorder which is not fully understood. Additional studies might help to better explain the underlying pathophysiological mechanism and to open doors to novel therapeutic methods.

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

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

PubMed

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

2017-01-01

Muscular hypertrophy secondary to denervation is very rare, but well-documented phenomena in adults. This is the first report of a child with neurogenic unilateral hypertrophy due to S1 radiculopathy. A 12-year-old girl presented with left calf hypertrophy and negative history of low back pain or trauma. The serum creatinine kinase level and inflammatory markers were normal. Magnetic resonance imaging showed muscle hypertrophy of the left gastrocnemius and revealed a protruded lumbar disc at the L5-S1 level. The protruded disc abuts the S1 root on the left side. Electromyography showed mild left S1 radiculopathy. Passive stretching and work load might clarify the origin of neurogenic hypertrophy but there is still a need for further evidence. Clinical, laboratory, magnetic resonance imaging and electromyography findings showed that S1 radiculopathy could be a cause of unilateral calf swelling in youth even in the absence of a history of back or leg pain. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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

Glucocorticoid inhibition of neuropathic limb edema and cutaneous neurogenic extravasation.

PubMed

Kingery, W S; Guo, T; Agashe, G S; Davies, M F; Clark, J D; Maze, M

2001-09-21

Sciatic nerve section in rats evokes chronic limb edema, pain behavior, and hindpaw hyperalgesia, a syndrome resembling the complex regional pain syndrome type II (CRPS II or causalgia) in man. Glucocorticoids such as methylprednisolone (MP) have been used as analgesic and anti-edematous agents in patients suffering from CRPS, and interestingly these therapeutic effects appear to persist in some patients after stopping the medication. Similar to the CRPS clinical response to glucocorticoids, we now demonstrate that chronic hindpaw edema in the sciatic transection CRPS model is reversed by a continuous infusion of MP (3 mg/kg/day over 21 days), and this anti-edematous effect persists for at least 1 week after discontinuing MP. Furthermore, there is a chronic increase in spontaneous protein extravasation in the hindpaw skin of rats after sciatic transection, similar to the increased protein extravasation observed in the edematous hands of CRPS patients. A 2-week infusion of MP (3 mg/kg/day) reduced spontaneous protein extravasation in the hindpaw skin by 80%. We postulated that increased spontaneous neurogenic extravasation resulted in development of limb edema in both the animal model and the CRPS patient, and that the anti-edematous effects of MP are due to an inhibition of spontaneous extravasation. Additional experiments examined the inhibitory effects of MP infusion on electrically-evoked neurogenic extravasation in the hindpaw skin of normal rats. MP inhibition was dose- and time-dependent, with an ED(50) of 1.2 mg/kg/day for a 14-day continuous infusion of MP, and a maximum inhibitory effect requiring 17 days of MP infusion (3 mg/kg/day). MP (3 mg/kg/day for 14 days) also blocked both capsaicin- and SP-evoked neurogenic extravasation, indicating a post-junctional inhibitory effect. Our interpretation is that increased spontaneous neurogenic extravasation in this CRPS model contributed to the development and maintenance of hindpaw edema, and that chronic MP

Increased pain and neurogenic inflammation in mice deficient of neutral endopeptidase.

PubMed

Krämer, Heidrun H; He, Lan; Lu, Bao; Birklein, Frank; Sommer, Claudia

2009-08-01

The complex regional pain syndrome (CRPS) is characterized by enhanced neurogenic inflammation, mediated by neuropeptides. Neutral endopeptidase (NEP) is a key enzyme in neuropeptide catabolism. We used NEP knock out (ko) mice to investigate whether NEP deficiency leads to increased pain behavior and signs of neurogenic inflammation after soft tissue trauma with and without nerve injury. After chronic constriction injury (CCI) of the right sciatic nerve, NEP ko mice were more sensitive to heat, to mechanical stimuli, and to cold than wild type mice. Tissue injury without nerve injury produced no differences between genotypes. After CCI, NEP ko mice showed increased hind paw edema but lower skin temperatures than wild type mice. Substance P (SP) and endothelin 1 (ET 1) determined by enzyme immuno assay (EIA) were increased in sciatic nerves from NEP ko mice after CCI. Tissue CGRP content did not differ between the genotypes. The results provide evidence that pain behavior and neurogenic inflammation are enhanced in NEP ko mice after nerve injury. These findings resemble human 'cold' CRPS and suggest that ET 1 plays an important role in the pathogenesis of CRPS with nerve injury.

Neurogenic vasodilatation and plasma leakage in the skin.

PubMed

Holzer, P

1998-01-01

1. Primary afferent nerve fibers control cutaneous blood flow and vascular permeability by releasing vasoactive peptides. These vascular reactions and the additional recruitment of leukocytes are commonly embodied in the term neurogenic inflammation. 2. Calcitonin gene-related peptide (CGRP) acting via CGRP1 receptors is the principal transmitter of neurogenic dilatation of arterioles whereas substance P (SP) and neurokinin A (NKA) acting via NK1 receptors mediate the increase in venular permeability. 3. Neurogenic vasodilatation and plasma protein leakage play a role in inflammation because many inflammatory and immune mediators including interleukin-1 beta, nitric oxide, prostanoids, protons, bradykinin, histamine, and 5-hydroxytryptamine can stimulate peptidergic afferent nerve fibers or enhance their excitability. 4. Neurogenic inflammatory reactions can be suppressed by alpha 2-adrenoceptor agonists, histamine acting via H1 receptors, 5-hydroxytryptamine acting via 5-HT1B receptors, opioid peptides, and somatostatin through prejunctional inhibition of peptide release from vasoactive afferent nerve fibers. CGRP, SP, and NKA receptor antagonists are powerful pharmacological tools to inhibit neurogenic inflammation at the postjunctional level. 5. Imbalance between the facilitatory and inhibitory influences on afferent nerve activity has a bearing on chronic inflammatory disease. Impaired nerve function represents a deficit in skin homeostasis while neuronal overactivity is a factor in allergic and hyperreactive disorders of the skin.

[Neurogenic inflammation and chronic rhinosinusitis].

PubMed

Lacroix, J S; Ricchetti Coignard, A

2005-10-19

The nasal mucosa is one of the anatomical region which have the highest density of sensory innervation. The function of this sensory innervation is probably linked to the protection of the lower airways against inhalation of airborne particles and potentially harmful substances. Chronic rhinosinusitis (CRS) is associated with nasal obstruction, rhinorrhea, loss of sense of smell and facial pain or headaches. When allergy or specific hyperreactivity, infection, systemic or genetic deseases have been excluded, the diagnosis of non specific hyperreactivity or neurogenic inflammation is proposed. Sensory neuropeptides released by sensory nerves endings have powerful proinflammatory effects. The best treatment yet available include nasal lavages and the local application of topical corticosteroid spray.

Surgical Management of Neurogenic Lower Urinary Tract Dysfunction.

PubMed

Gor, Ronak A; Elliott, Sean P

2017-08-01

Surgery for patients with neurogenic urinary tract dysfunction (nLUTD) is indicated when medical therapy fails, to correct conditions affecting patient safety, or when surgery can enhance the quality of life better than nonoperative management. Examples include failure of maximal medical therapy, inability to perform or aversion to clean intermittent catheterization, refractory incontinence, and complications from chronic, indwelling catheters. Adults with nLUTD have competing risk factors, including previous operations, obesity, poor nutritional status, complex living arrangements, impaired dexterity/paralysis, and impaired executive and cognitive function. Complications are common in this subgroup of patients requiring enduring commitments from surgeons, patients, and their caretakers. Copyright © 2017 Elsevier Inc. All rights reserved.

Electrical management of neurogenic lower urinary tract disorders.

PubMed

Joussain, C; Denys, P

2015-09-01

Management of lower urinary tract dysfunction (LUTD) in neurological diseases remains a priority because it leads to many complications such as incontinence, renal failure and decreased quality of life. A pharmacological approach remains the first-line treatment for patients with neurogenic LUTD, but electrical stimulation is a well-validated and recommended second-line treatment. However, clinicians must be aware of the indications, advantages and side effects of the therapy. This report provides an update on the 2 main electrical stimulation therapies for neurogenic LUTD - inducing direct bladder contraction with the Brindley procedure and modulating LUT physiology (sacral neuromodulation, tibial posterior nerve stimulation or pudendal nerve stimulation). We also describe the indications of these therapies for neurogenic LUTD, following international guidelines, as illustrated by their efficacy in patients with neurologic disorders. Electrical stimulation could be proposed for neurogenic LUTD as second-line treatment after failure of oral pharmacologic approaches. Nevertheless, further investigations are needed for a better understanding of the mechanisms of action of these techniques and to confirm their efficacy. Other electrical investigations, such as deep-brain stimulation and repetitive transcranial magnetic stimulation, or improved sacral anterior root stimulation, which could be associated with non-invasive and highly specific deafferentation of posterior roots, may open new fields in the management of neurogenic LUTD. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Uncoupling neurogenic gene networks in the Drosophila embryo.

PubMed

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

2017-04-01

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

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

PubMed

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

2012-08-15

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

Neurogenesis in the embryonic and adult brain: same regulators, different roles

PubMed Central

Urbán, Noelia; Guillemot, François

2014-01-01

Neurogenesis persists in adult mammals in specific brain areas, known as neurogenic niches. Adult neurogenesis is highly dynamic and is modulated by multiple physiological stimuli and pathological states. There is a strong interest in understanding how this process is regulated, particularly since active neuronal production has been demonstrated in both the hippocampus and the subventricular zone (SVZ) of adult humans. The molecular mechanisms that control neurogenesis have been extensively studied during embryonic development. Therefore, we have a broad knowledge of the intrinsic factors and extracellular signaling pathways driving proliferation and differentiation of embryonic neural precursors. Many of these factors also play important roles during adult neurogenesis, but essential differences exist in the biological responses of neural precursors in the embryonic and adult contexts. Because adult neural stem cells (NSCs) are normally found in a quiescent state, regulatory pathways can affect adult neurogenesis in ways that have no clear counterpart during embryogenesis. BMP signaling, for instance, regulates NSC behavior both during embryonic and adult neurogenesis. However, this pathway maintains stem cell proliferation in the embryo, while it promotes quiescence to prevent stem cell exhaustion in the adult brain. In this review, we will compare and contrast the functions of transcription factors (TFs) and other regulatory molecules in the embryonic brain and in adult neurogenic regions of the adult brain in the mouse, with a special focus on the hippocampal niche and on the regulation of the balance between quiescence and activation of adult NSCs in this region. PMID:25505873

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Richard R.; Brown, Craig E.; Brain Research Center, University of British Columbia, Vancouver, BC, V6T 1Z3

2007-12-21

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

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

PubMed

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

2016-04-01

Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation. HF offspring were exposed to maternal overnutrition (high fat diet; HF) during pregnancy and lactation. We determined the protein expression of energy sensors (mTOR, pAMPK), epigenetic factors (DNA methylase, DNMT1; histone deacetylase, SIRT1/HDAC1), neurogenic factors (Hes1, Mash1, Ngn3) and appetite/satiety neuropeptides (AgRP/POMC) in newborn hypothalamus and adult arcuate nucleus (ARC). Despite maternal obesity, male offspring born to obese dams had similar body weight at birth as Controls. However, when nursed by the same dams, male offspring of obese dams exhibited marked adiposity. At 1 day of age, HF newborn males had significantly decreased energy sensors, DNMT1 including Hes1 and Mash1, which may impact neuroprogenitor cell proliferation and differentiation. This is consistent with increased AgRP in HF newborns. At 6 months of age, HF adult males had significantly increased energy sensors and decreased histone deactylases. In addition, the persistent decreased Hes1, Mash1 as well as Ngn3 are consistent with increased AgRP and decreased POMC. Thus, altered energy sensors and epigenetic responses which modulate gene expression and adult neuronal differentiation may contribute to hyperphagia and obesity in HF male offspring. Copyright © 2016 Elsevier Ltd. All rights reserved.

Programmed Hyperphagia in Offspring of Obese Dams: Altered Expression of Hypothalamic Nutrient Sensors, Neurogenic Factors and Epigenetic Modulators

PubMed Central

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

2016-01-01

Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation. HF offspring were exposed to maternal overnutrition (high fat diet; HF) during pregnancy and lactation. We determined the protein expression of energy sensors (mTOR, pAMPK), epigenetic factors (DNA methylase, DNMT1; histone deacetylase, SIRT1/HDAC1), neurogenic factors (Hes1, Mash1, Ngn3) and appetite/satiety neuropeptides (AgRP/POMC) in newborn hypothalamus and adult arcuate nucleus (ARC). Despite maternal obesity, male offspring born to obese dams had similar body weight at birth as Controls. However, when nursed by the same dams, male offspring of obese dams exhibited marked adiposity. At 1 day of age, HF newborn males had significantly decreased energy sensors, DNMT1 including Hes1 and Mash1, which may impact neuroprogenitor cell proliferation and differentiation. This is consistent with increased AgRP in HF newborns. At 6 months of age, HF adult males had significantly increased energy sensors and decreased histone deactylases. In addition, the persistent decreased Hes1, Mash1 as well as Ngn3 are consistent with increased AgRP and decreased POMC. Thus, altered energy sensors and epigenetic responses which modulate gene expression and adult neuronal differentiation may contribute to hyperphagia and obesity in HF male offspring. PMID:26785315

An International Continence Society (ICS) report on the terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD).

PubMed

Gajewski, Jerzy B; Schurch, Brigitte; Hamid, Rizwan; Averbeck, Márcio; Sakakibara, Ryuji; Agrò, Enrico F; Dickinson, Tamara; Payne, Christopher K; Drake, Marcus J; Haylen, Bernie T

2018-03-01

The terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD) should be defined and organized in a clinically based consensus Report. This Report has been created by a Working Group under the auspices and guidelines of the International Continence Society (ICS) Standardization Steering Committee (SSC) assisted at intervals by external referees. All relevant definitions for ANLUTD were updated on the basis of research over the last 14 years. An extensive process of 18 rounds of internal and external review was involved to exhaustively examine each definition, with decision-making by collective opinion (consensus). A Terminology Report for ANLUTD, encompassing 97 definitions (42 NEW and 8 CHANGED, has been developed. It is clinically based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different groups involved not only in lower urinary tract dysfunction but additionally in many other medical specialties. A consensus-based Terminology Report for ANLUTD has been produced to aid clinical practice and research. © 2017 Wiley Periodicals, Inc.

Analysis of carbonated thin liquids in pediatric neurogenic dysphagia

PubMed Central

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

2015-01-01

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

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

PubMed Central

Stopa, Edward; Baird, Andrew; Sharma, Hari

2010-01-01

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

Inducible and Conditional Deletion of Extracellular Signal-regulated Kinase 5 Disrupts Adult Hippocampal Neurogenesis*

PubMed Central

Pan, Yung-Wei; Zou, Junhui; Wang, Wenbin; Sakagami, Hiroyuki; Garelick, Michael G.; Abel, Glen; Kuo, Chay T.; Storm, Daniel R.; Xia, Zhengui

2012-01-01

Recent studies have led to the exciting idea that adult-born neurons in the dentate gyrus of the hippocampus may play a role in hippocampus-dependent memory formation. However, signaling mechanisms that regulate adult hippocampal neurogenesis are not well defined. Here we report that extracellular signal-regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinase family, is selectively expressed in the neurogenic regions of the adult mouse brain. We present evidence that shRNA suppression of ERK5 in adult hippocampal neural stem/progenitor cells (aNPCs) reduces the number of neurons while increasing the number of cells expressing markers for stem/progenitor cells or proliferation. Furthermore, shERK5 attenuates both transcription and neuronal differentiation mediated by Neurogenin 2, a transcription factor expressed in adult hippocampal neural progenitor cells. By contrast, ectopic activation of endogenous ERK5 signaling via expression of constitutive active MEK5, an upstream activating kinase for ERK5, promotes neurogenesis in cultured aNPCs and in the dentate gyrus of the mouse brain. Moreover, neurotrophins including NT3 activate ERK5 and stimulate neuronal differentiation in aNPCs in an ERK5-dependent manner. Finally, inducible and conditional deletion of ERK5 specifically in the neurogenic regions of the adult mouse brain delays the normal progression of neuronal differentiation and attenuates adult neurogenesis in vivo. These data suggest ERK5 signaling as a critical regulator of adult hippocampal neurogenesis. PMID:22645146

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2008-03-01

This study presents survey data on 58 Dutch-speaking patients with neurogenic stuttering following various neurological injuries. Stroke was the most prevalent cause of stuttering in our patients, followed by traumatic brain injury, neurodegenerative diseases, and other causes. Speech and non-speech characteristics were analyzed separately for these four etiology groups. Results suggested possible group differences, including site of lesion and influence of speech conditions on stuttering. Other characteristics, such as within-word localization of disfluencies and presence of secondary behaviors were comparable across the etiology groups. The implications of our results for the diagnosis of neurogenic stuttering will be discussed. After reading this article, the reader will be able to: (1) provide a concise overview of the main literature on neurogenic stuttering; (2) discuss the speech and non-speech characteristics of neurogenic stuttering; (3) provide an overview of current clinical practices for intervention with neurogenic stuttering patients and their perceived outcome.

Management of vesicoureteral reflux in neurogenic bladder.

PubMed

Wu, Charlotte Q; Franco, Israel

2017-06-01

Vesicoureteral reflux (VUR) is a significant risk factor for pyelonephritis and renal scarring. VUR can occur through a defective ureterovesical junction (UVJ) or an overwhelmed normal UVJ mechanism such as in bladder dysfunction of congenital, acquired, or behavioral etiology. There are numerous causes for the development of a neurogenic bladder from spinal dysraphisms to spinal cord trauma and even centrally based abnormalities in children with apparently normal motor function (inappropriately termed nonneurogenic neurogenic bladder). The foundation of managing reflux in these neurogenic bladders is to maintain low bladder pressures which will commonly mean that compliance will be normal as well. There have been several publications that have shown that if bladder pressures are lowered simply with clean intermittent catheterization and medications that the reflux can resolve spontaneously. Alternatively, the patients that are in need of bladder augmentation can have spontaneous resolution of their reflux with the resulting increase in capacity. Surgical intervention is called for when bladder capacity is adequate and the reflux persists or if it is part of a larger operation to increase capacity and to manage outlet resistance. In some instances, reimplantation is necessary because the ureters interfere with the bladder neck procedure. Aside from open and robotic surgical intervention the use of endoscopic injectable agents is beginning to become more popular especially when combined with intravesical botulinum toxin A injections. Great strides are being made in the management of patients with neurogenic bladders and we are seeing more choices for the urologist to be able to manage these patients.

Treatment of Neurogenic Cough with Tramadol: A Pilot Study.

PubMed

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

2017-07-01

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

Epidemiology, Diagnosis, and Management of Neurogenic Orthostatic Hypotension

PubMed Central

Palma, Jose-Alberto; Kaufmann, Horacio

2017-01-01

Background Orthostatic hypotension (OH) is a sustained fall in blood pressure on standing which can cause symptoms of organ hypoperfusion. OH is associated with increased morbidity and mortality and leads to a significant number of hospital admissions particularly in the elderly (233 per 100,000 patients over 75 years of age in the US). OH can be due to volume depletion, blood loss, large varicose veins, medications, or due to defective activation of sympathetic nerves and reduced norepinephrine release upon standing (i.e., neurogenic OH). Methods and Findings Literature review. Neurogenic OH is a frequent and disabling problem in patients with synucleinopathies such as Parkinson disease, multiple system atrophy, and pure autonomic failure, and is commonly associated with supine hypertension. Several pharmacological and non-pharmacological therapeutic options are available. Conclusions Here we review the epidemiology, diagnosis, and management of neurogenic OH, and provide an algorithm for its treatment emphasizing the importance of removing aggravating factors, implementing non-pharmacologic measures, and selecting appropriate pharmacological treatments. PMID:28713844

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

PubMed

Przydacz, Mikolaj; Denys, Pierre; Corcos, Jacques

2017-09-01

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

Immunophenotypic and Molecular Analysis of Human Dental Pulp Stem Cells Potential for Neurogenic Differentiation

PubMed Central

Fatima, Nikhat; Khan, Aleem A.; Vishwakarma, Sandeep K.

2017-01-01

Background: Growing evidence shows that dental pulp (DP) tissues could be a potential source of adult stem cells for the treatment of devastating neurological diseases and several other conditions. Aims: Exploration of the expression profile of several key molecular markers to evaluate the molecular dynamics in undifferentiated and differentiated DP-derived stem cells (DPSCs) in vitro. Settings and Design: The characteristics and multilineage differentiation ability of DPSCs were determined by cellular and molecular kinetics. DPSCs were further induced to form adherent (ADH) and non-ADH (NADH) neurospheres under serum-free condition which was further induced into neurogenic lineage cells and characterized for their molecular and cellular diversity at each stage. Statistical Analysis Used: Statistical analysis used one-way analysis of variance, Student's t-test, Livak method for relative quantification, and R programming. Results: Immunophenotypic analysis of DPSCs revealed >80% cells positive for mesenchymal markers CD90 and CD105, >70% positive for transferring receptor (CD71), and >30% for chemotactic factor (CXCR3). These cells showed mesodermal differentiation also and confirmed by specific staining and molecular analysis. Activation of neuronal lineage markers and neurogenic growth factors was observed during lineage differentiation of cells derived from NADH and ADH spheroids. Greater than 80% of cells were found to express β-tubulin III in both differentiation conditions. Conclusions: The present study reported a cascade of immunophenotypic and molecular markers to characterize neurogenic differentiation of DPSCs under serum-free condition. These findings trigger the future analyses for clinical applicability of DP-derived cells in regenerative applications. PMID:28566856

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Mei-Fang

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 O{sub 2} 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,more » and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100 μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8 Hz) 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

Neurogenesis in the adult brain: implications for Alzheimer's disease.

PubMed

Galvan, Veronica; Bredesen, Dale E

2007-10-01

The function of neurogenesis in the adult brain is still unknown. Interventions such as environmental enrichment and exercise impinge on neurogenesis, suggesting that the process is regulated by experience. Conversely, a role for neurogenesis in learning has been proposed through 'cellular plasticity', a process akin to synaptic plasticity but operating at the network level. Although neurogenesis is stimulated by acute injury, and possibly by neurodegenerative processes such as Alzheimer's disease (AD), it does not suffice to restore function. While the role and direction of change in the neurogenic response at different stages of AD is still a matter of debate, it is possible that a deficit in neurogenesis may contribute to AD pathogenesis since at least one of the two regions ostensibly neurogenic in the adult human brain (the subgranular zone of the dentage gyrus and the ventriculo-olfactory neurogenic system) support high-level functions affected in early AD (associative memory and olfaction respectively). The age of onset and the rate of progression of sporadic forms of AD are highly variable. Sporadic AD may have a component of insufficient neurogenic replacement or insufficient neurogenic stimulation that is correlated with traits of personal history; the rate of neurogenesis and the survival of replicating progenitors is strongly modified by behavioral interventions known to impinge on the rate of neurogenesis and the probability of survival of newly born neurons--exercise, enriched experience, and learning. This view is consistent with epidemiological data suggesting that higher education and increased participation in intellectual, social and physical aspects of daily life are associated with slower cognitive decline in healthy elderly ("cognitive reserve") and may reduce the risk of AD. Although neurogenesis can be modulated exogenously by growth factors, stimulation of neurogenesis as a mean to treat neurodegeneration is still for the most part

Treatment of chronic neurogenic cough with in-office superior laryngeal nerve block.

PubMed

Simpson, C Blake; Tibbetts, Kathleen M; Loochtan, Michael J; Dominguez, Laura M

2018-04-18

Neurogenic cough is believed to result from a sensory neuropathy involving the internal branch of the superior laryngeal nerve (SLN). We present our outcomes for the treatment of neurogenic cough with localized blockade of the internal branch of the SLN. A retrospective chart review of patients who underwent in-office percutaneous SLN block for treatment of neurogenic cough between 2015 and 2017 was conducted. Patient demographics, indications for injection, and response to treatment were recorded and analyzed. Cough severity index (CSI) scores before and after treatment were compared. Twenty-three patients underwent percutaneous blockade of the internal branch of the SLN in the clinic setting, and five patients were excluded for incomplete records. The indication was neurogenic cough as a diagnosis of exclusion. The injectable substance used was a 1:1 mixture of a long-acting particulate corticosteroid and a local anesthetic. Unilateral injections were performed in 13 patients, and five patients underwent bilateral injections. Of the unilateral injections, 10 were left-sided. Patients underwent an average of 2.4 SLN block procedures (range 1-7). Mean follow-up time postinjection was 85.4 days (7-450 days). Cough severity index scores decreased significantly from an average of 26.8 pretreatment to 14.6 posttreatment (P < 0.0001). The SLN block is an effective treatment for neurogenic cough, with average CSI scores significantly improved following injection. Further study is necessary to determine the characteristics of patients' responses to treatment, long-term outcomes, and efficacy of the procedure when compared to placebo and other accepted treatments for neurogenic cough. 4. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

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

Adult hippocampal neurogenesis in the pathogenesis of addiction and dual diagnosis disorders.

PubMed

Chambers, R Andrew

2013-06-01

As knowledge deepens about how new neurons are born, differentiate, and wire into the adult mammalian brain, growing evidence depicts hippocampal neurogenesis as a special form of neuroplasticity that may be impaired across psychiatric disorders. This review provides an integrated-evidence based framework describing a neurogenic basis for addictions and addiction vulnerability in mental illness. Basic studies conducted over the last decade examining the effects of addictive drugs on adult neurogenesis and the impact of neurogenic activity on addictive behavior were compiled and integrated with relevant neurocomputational and human studies. While suppression of hippocampal neurogenic proliferation appears to be a universal property of addictive drugs, the pathophysiology of addictions involves neuroadaptative processes within frontal-cortical-striatal motivation circuits that the neurogenic hippocampus regulates via direct projections. States of suppressed neurogenic activity may simultaneously underlie psychiatric and cognitive symptoms, but also confer or signify hippocampal dysfunction that heightens addiction vulnerability in mental illness as a basis for dual diagnosis disorders. Research on pharmacological, behavioral and experiential strategies that enhance adaptive regulation of hippocampal neurogenesis holds potential in advancing preventative and integrative treatment strategies for addictions and dual diagnosis disorders. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Adult Hippocampal Neurogenesis in the Pathogenesis of Addiction and Dual Diagnosis Disorders

PubMed Central

Chambers, R. Andrew

2013-01-01

Background As knowledge deepens about how new neurons are born, differentiate, and wire into the adult mammalian brain, growing evidence depicts hippocampal neurogenesis as a special form of neuroplasticity that may be impaired across psychiatric disorders. This review provides an integrated-evidence based framework describing a neurogenic basis for addictions and addiction vulnerability in mental illness. Methods Basic studies conducted over the last decade examining the effects of addictive drugs on adult neurogenesis and the impact of neurogenic activity on addictive behavior were compiled and integrated with relevant neurocomputational and human studies. Results While suppression of hippocampal neurogenic proliferation appears to be a universal property of addictive drugs, the pathophysiology of addictions involves neuroadaptative processes within frontal-cortical-striatal motivation circuits that the neurogenic hippocampus regulates via direct projections. States of suppressed neurogenic activity may simultaneously underlie psychiatric and cognitive symptoms, but also confer or signify hippocampal dysfunction that heightens addiction vulnerability in mental illness as a basis for dual diagnosis disorders. Conclusions Research on pharmacological, behavioral and experiential strategies that enhance adaptive regulation of hippocampal neurogenesis holds potential in advancing preventative and integrative treatment strategies for addictions and dual diagnosis disorders. PMID:23279925

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.

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.

Neurogenic plasma leakage in mouse airways

PubMed Central

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

1999-01-01

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

NFIX Regulates Proliferation and Migration Within the Murine SVZ Neurogenic Niche

PubMed Central

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

2015-01-01

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

Memantine Inhibits α3β2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries

PubMed Central

Wu, Celeste Yin-Chieh; Chen, Po-Yi; Chen, Mei-Fang; Kuo, Jon-Son; Lee, Tony Jer-Fu

2012-01-01

Memantine, an NMDA receptor antagonist used for treatment of Alzheimer’s disease (AD), is known to block the nicotinic acetylcholine receptors (nAChRs) in the central nervous system (CNS). In the present study, we examined by wire myography if memantine inhibited α3β2-nAChRs located on cerebral perivascular sympathetic nerve terminals originating in the superior cervical ganglion (SCG), thus, leading to inhibition of nicotine-induced nitrergic neurogenic dilation of isolated porcine basilar arteries. Memantine concentration-dependently blocked nicotine-induced neurogenic dilation of endothelium-denuded basilar arteries without affecting that induced by transmural nerve stimulation, sodium nitroprusside, or isoproterenol. Furthermore, memantine significantly inhibited nicotine-elicited inward currents in Xenopous oocytes expressing α3β2-, α7- or α4β2-nAChR, and nicotine-induced calcium influx in cultured rat SCG neurons. These results suggest that memantine is a non-specific antagonist for nAChR. By directly inhibiting α3β2-nAChRs located on the sympathetic nerve terminals, memantine blocks nicotine-induced neurogenic vasodilation of the porcine basilar arteries. This effect of memantine is expected to reduce the blood supply to the brain stem and possibly other brain regions, thus, decreasing its clinical efficacy in the treatment of Alzheimer’s disease. PMID:22792283

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

PubMed

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

2011-09-14

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

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.

Two cases of neurogenic paralysis in medieval skeletal samples from Croatia.

PubMed

Novak, Mario; Čavka, Mislav; Šlaus, Mario

2014-12-01

Osteological changes consistent with neurogenic paralysis were observed in one male and one female skeleton recovered from two Croatian medieval sites - Virje and Zadar. Both skeletons display limb asymmetry typical of neurogenic paralysis that occurs during the childhood. The male skeleton displays atrophy and shortening of the right arm and the right femur, while the female skeleton exhibits identical changes on the right arm and both legs. Additionally, both skeletons exhibit scoliotic changes of the spine, and the female skeleton also displays bilateral hip dysplasia. Differential diagnosis included disorders such as cerebral palsy, poliomyelitis, cerebrovascular accident, and Rasmussen's encephalitis. These are the first cases of neurogenic paralysis (cerebral palsy and/or paralytic poliomyelitis) identified in Croatian archeological series. The Virje skeleton is only the third case of hemiplegia identified from archeological contexts (first with spinal scoliosis), while the Zadar skeleton represents the first case of triplegia reported in the paleopathological literature. Copyright © 2014 Elsevier Inc. All rights reserved.

The reliability of differentiating neurogenic claudication from vascular claudication based on symptomatic presentation.

PubMed

Nadeau, Mélissa; Rosas-Arellano, M Patricia; Gurr, Kevin R; Bailey, Stewart I; Taylor, David C; Grewal, Ruby; Lawlor, D Kirk; Bailey, Chris S

2013-12-01

Intermittent claudication can be neurogenic or vascular. Physicians use a profile based on symptom attributes to differentiate the 2 types of claudication, and this guides their investigations for diagnosis of the underlying pathology. We evaluated the validity of these symptom attributes in differentiating neurogenic from vascular claudication. Patients with a diagnosis of lumbar spinal stenosis (LSS) or peripheral vascular disease (PVD) who reported claudication answered 14 questions characterizing their symptoms. We determined the sensitivity, specificity and positive and negative likelihood ratios (PLR and NLR) for neurogenic and vascular claudication for each symptom attribute. We studied 53 patients. The most sensitive symptom attribute to rule out LSS was the absence of "triggering of pain with standing alone" (sensitivity 0.97, NLR 0.050). Pain alleviators and symptom location data showed a weak clinical significance for LSS and PVD. Constellation of symptoms yielded the strongest associations: patients with a positive shopping cart sign whose symptoms were located above the knees, triggered with standing alone and relieved with sitting had a strong likelihood of neurogenic claudication (PLR 13). Patients with symptoms in the calf that were relieved with standing alone had a strong likelihood of vascular claudication (PLR 20.0). The classic symptom attributes used to differentiate neurogenic from vascular claudication are at best weakly valid independently. However, certain constellation of symptoms are much more indicative of etiology. These results can guide general practitioners in their evaluation of and investigation for claudication.

How to Measure Quality-of-Life Concerns in Patients with Neurogenic Lower Urinary Tract Dysfunction.

PubMed

Patel, Darshan P; Myers, Jeremy B; Lenherr, Sara M

2017-08-01

There is an evolving role for quality-of-life measures and patient-reported outcomes in the evaluation of neurogenic lower urinary tract dysfunction. We review available health-related quality-of-life instruments and patient-reported outcomes measures used in the assessment of patients with neurogenic bladder. We also discuss considerations for incorporation of these measures into clinical and patient-reported research. Emphasizing patient-reported outcomes in neurogenic bladder research will guide clinicians and other stakeholders to improve quality of life in this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis

PubMed Central

Licht, Tamar; Rothe, Gadiel; Kreisel, Tirzah; Wolf, Brachi; Benny, Ofra; Rooney, Alasdair G.; ffrench-Constant, Charles; Enikolopov, Grigori; Keshet, Eli

2016-01-01

Several factors are known to enhance adult hippocampal neurogenesis but a factor capable of inducing a long-lasting neurogenic enhancement that attenuates age-related neurogenic decay has not been described. Here, we studied hippocampal neurogenesis following conditional VEGF induction in the adult brain and showed that a short episode of VEGF exposure withdrawn shortly after the generation of durable new vessels (but not under conditions where newly made vessels failed to persist) is sufficient for neurogenesis to proceed at a markedly elevated level for many months later. Continual neurogenic increase over several months was not accompanied by accelerated exhaustion of the neuronal stem cell (NSC) reserve, thereby allowing neurogenesis to proceed at a markedly elevated rate also in old mice. Neurogenic enhancement by VEGF preconditioning was, in part, attributed to rescue of age-related NSC quiescence. Remarkably, VEGF caused extensive NSC remodelling manifested in transition of the enigmatic NSC terminal arbor onto long cytoplasmic processes engaging with and spreading over even remote blood vessels, a configuration reminiscent of early postnatal “juvenile” NSCs. Together, these findings suggest that VEGF preconditioning might be harnessed for long-term neurogenic enhancement despite continued exposure to an “aged” systemic milieu. PMID:27849577

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

Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition.

PubMed

Costa Monteiro, Lucia Maria; Cruz, Glaura Nisya de Oliveira; Fontes, Juliana Marin; Saad Salles, Tania Regina Dias; Boechat, Marcia Cristina Bastos; Monteiro, Ana Carolina; Moreira, Maria Elizabeth Lopes

2018-01-01

Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we emphasize the importance of proactive

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

PubMed

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

2016-01-01

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

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...

[Symptom analysis of 537 patients with neurogenic intrapelvic syndrome].

PubMed

Masahiro, Takano; Shunji, Ogata; Ryoichi, Nozaki; Saburo, Hisano; Yasumitsu, Saiki; Mitsuko, Fukunaga; Shota, Takano; Masafumi, Tanaka; Shinichiro, Magata; Yasushi, Nakamura; Gentaro, Sakata; Kazutaka, Yamada

2010-12-01

To characterize the symptoms of neurogenic intrapelvic syndrome and the pathogenic mechanisms. A total of 537 patients with neurogenic intrapelvic syndrome were treated in the Takano Hospital between 2001 and 2005. Clinical data were analyzed retrospectively. The mean age was 58.5 years old. There were 205 males and 332 females. There were 80 patients(14.9%) who presented with only one symptom with anorectal pain being the most common one (43.8%, 35/80). One hundred and fifty-six(29.1%) patients had two symptoms with anorectal pain and difficult evacuation being the most common combination (26.3%, 41/156). There were 144 patients (26.8%) complained of 3 symptoms and the most common combination was anorectal pain, difficult evacuation, and abdominal discomfort (30.0%, 43/144). A combination of 4 symptoms was reported in 105 patients(19.6%) with the combination of anorectal pain, incontinence, abdominal discomfort, and lumbar discomfort being the most often(65.7%, 69/105). In addition, there were 52 patients(9.7%) who had above 5 symptoms simultaneously. The frequencies of the 5 symptoms were 73.6% for anorectal pain, 27.9% for incontinence, 69.6% for difficult evacuation, 55.3% for abdominal discomfort, and 53.6% for lumbar discomfort. Symptomatology of neurogenic intrapelvic syndrome is complicated. The pathogenic mechanism may be related to concurrent dysfunction of sacral nerve and pelvic splanchnic nerve.

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

PubMed

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

2015-03-01

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

Brain ACE2 shedding contributes to the development of neurogenic hypertension

PubMed Central

Chhabra, Kavaljit H.; Lazartigues, Eric

2015-01-01

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

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

PubMed

Alkhachroum, Ayham M; Saeed, Saba; Kaur, Jaspreet; Shams, Tanzila; DeGeorgia, Michael A

2016-03-11

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. 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. To the best of our knowledge, central neurogenic hyperventilation has not previously been described in a patient with Neuro-Behcet's disease.

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…

Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition

PubMed Central

Cruz, Glaura Nisya de Oliveira; Fontes, Juliana Marin; Saad Salles, Tania Regina Dias; Boechat, Marcia Cristina Bastos; Monteiro, Ana Carolina; Moreira, Maria Elizabeth Lopes

2018-01-01

Introduction Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. Methods Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). Results Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. Conclusion Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we

Chronic Pelvic Pain: Neurogenic or Non-Neurogenic? Warm Detection Threshold Testing Supports a Diagnosis of Pudendal Neuropathy.

PubMed

Antolak, Stanley J; Antolak, Christopher M

2018-03-01

Chronic pelvic pain (CPP) in men is rarely considered to have a neurogenic (neuropathic) basis. Separation of neurogenic from non-neurogenic pain is possible using clinical examination and neurophysiologic tests. A definite diagnosis of neuropathic pain can be made. We aim to demonstrate that definite pudendal neuropathic abnormalities can be supported by a quantitative sensory test (QST) called the warm temperature threshold detection (WDT) test in men with CPP. This is a retrospective review of 25 consecutive, unrecruited men evaluated in a private clinical practice beginning on January 1, 2010. The techniques of examination and neurophysiological testing have been standard since 2003. A private practice that is a referral center because of its focus on CPP of a neuropathic basis. Pinprick sensation was evaluated at 6 sites in the pudendal nerve territory (3 branches on each side). A WDT was performed at each nerve branch using a Physitemp NTE-2C Thermoprobe and Controller. This used a stepping algorithm from a neutral baseline of 31.5°C. Quantitative and subjective "qualitative responses" were recorded. Our preferred symptom score to evaluate pain level at consultation is the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). The results become the benchmark for comparison of responses following future treatments (not discussed). When possible, microscopy was used to evaluate prostate secretions for inflammatory prostatitis except in 2 men with CPP who had undergone previous radical prostatectomy for cancer. Observations were made of the skin in the pudendal territory. Our specific evaluation for neuropathy also sought evidence of multiple additional neuropathic pelvic pain generators. The WDT was abnormal in all men (88% quantitative), and pinprick sensation was abnormal in 92% of the men. The combination of tests provided a diagnosis of pudendal neuropathy in all patients, resulting in an accurate and timely explanation of the

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 ...

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

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

PubMed Central

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

2014-01-01

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

The Role of Astrocytes in the Generation, Migration, and Integration of New Neurons in the Adult Olfactory Bulb

PubMed Central

Gengatharan, Archana; Bammann, Rodrigo R.; Saghatelyan, Armen

2016-01-01

In mammals, new neurons in the adult olfactory bulb originate from a pool of neural stem cells in the subventricular zone of the lateral ventricles. Adult-born cells play an important role in odor information processing by adjusting the neuronal network to changing environmental conditions. Olfactory bulb neurogenesis is supported by several non-neuronal cells. In this review, we focus on the role of astroglial cells in the generation, migration, integration, and survival of new neurons in the adult forebrain. In the subventricular zone, neural stem cells with astrocytic properties display regional and temporal specificity when generating different neuronal subtypes. Non-neurogenic astrocytes contribute to the establishment and maintenance of the neurogenic niche. Neuroblast chains migrate through the rostral migratory stream ensheathed by astrocytic processes. Astrocytes play an important regulatory role in neuroblast migration and also assist in the development of a vasculature scaffold in the migratory stream that is essential for neuroblast migration in the postnatal brain. In the olfactory bulb, astrocytes help to modulate the network through a complex release of cytokines, regulate blood flow, and provide metabolic support, which may promote the integration and survival of new neurons. Astrocytes thus play a pivotal role in various processes of adult olfactory bulb neurogenesis, and it is likely that many other functions of these glial cells will emerge in the near future. PMID:27092050

Neurogenic Orofacial Weakness and Speech in Adults With Dysarthria

PubMed Central

Makashay, Matthew J.; Helou, Leah B.; Clark, Heather M.

2017-01-01

Purpose This study compared orofacial strength between adults with dysarthria and neurologically normal (NN) matched controls. In addition, orofacial muscle weakness was examined for potential relationships to speech impairments in adults with dysarthria. Method Matched groups of 55 adults with dysarthria and 55 NN adults generated maximum pressure (Pmax) against an air-filled bulb during lingual elevation, protrusion and lateralization, and buccodental and labial compressions. These orofacial strength measures were compared with speech intelligibility, perceptual ratings of speech, articulation rate, and fast syllable-repetition rate. Results The dysarthria group demonstrated significantly lower orofacial strength than the NN group on all tasks. Lingual strength correlated moderately and buccal strength correlated weakly with most ratings of speech deficits. Speech intelligibility was not sensitive to dysarthria severity. Individuals with severely reduced anterior lingual elevation Pmax (< 18 kPa) had normal to profoundly impaired sentence intelligibility (99%–6%) and moderately to severely impaired speech (26%–94% articulatory imprecision; 33%–94% overall severity). Conclusions Results support the presence of orofacial muscle weakness in adults with dysarthrias of varying etiologies but reinforce tenuous links between orofacial strength and speech production disorders. By examining individual data, preliminary evidence emerges to suggest that speech, but not necessarily intelligibility, is likely to be impaired when lingual weakness is severe. PMID:28763804

Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response.

PubMed

Klempin, Friederike; Mosienko, Valentina; Matthes, Susann; Villela, Daniel C; Todiras, Mihail; Penninger, Josef M; Bader, Michael; Santos, Robson A S; Alenina, Natalia

2018-04-20

Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1-7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1-7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism.

Neurogenic bladder from occult herpes zoster.

PubMed

Rothrock, J F; Walicke, P A; Swenson, M R

1986-11-01

Active infection with herpes zoster may cause acute urinary retention, especially when it involves sacral dermatomes. Although frank retention usually develops days to weeks after eruption of the typical rash, bladder incompetence infrequently develops first, raising concern over other, more ominous etiologies. In the case presented, rash appearance was delayed until six weeks after the initial onset of urinary retention, a much longer interval than previously reported. Occult herpes zoster infection should be considered in patients presenting with an acute neurogenic bladder of obscure cause.

Transoral robotic surgery for neurogenic tumors of the prestyloid parapharyngeal space.

PubMed

Lee, Hyoung Shin; Kim, Jinna; Lee, Hyun Jin; Koh, Yoon Woo; Choi, Eun Chang

2012-08-01

The parapharyngeal space is a difficult area for a surgical approach due to anatomical complexity. We performed a minimally invasive and precise surgical technique to remove neurogenic tumors of the prestyloid parapharyngeal space using transoral robotic instrumentation. The mass was successfully removed in the two cases with three-dimensional visualization providing an excellent view of the resection margin and the dissection plane preserving the vital structures. An adequate resection margin was acquired, and no violation of the tumor capsule occurred. No significant complications were noted. Transoral robotic surgery was feasible for neurogenic tumors of the prestyloid parapharyngeal space, providing a sufficient resection margin and delicate dissection through excellent surgical views and instrumentation. Copyright © 2012. Published by Elsevier Ireland Ltd.

Neuroprostheses to treat neurogenic bladder dysfunction: current status and future perspectives.

PubMed

Rijkhoff, Nico J M

2004-02-01

Neural prostheses are a technology that uses electrical activation of the nervous system to restore function to individuals with neurological or sensory impairment. This article provides an introduction to neural prostheses and lists the most successful neural prostheses (in terms of implanted devices). The article then focuses on neurogenic bladder dysfunction and describes two clinically available implantable neural prostheses for treatment of neurogenic bladder dysfunction. Special attention is given to the usage of these neural prostheses in children. Finally, three new developments that may lead to a new generation of implantable neural prostheses for bladder control are described. They may improve the neural prostheses currently available and expand further the population of patients who can benefit from a neural prosthesis.

OnabotulinumtoxinA in the treatment of neurogenic bladder

PubMed Central

Gulamhusein, Aziz; Mangera, Altaf

2012-01-01

This review examines the evidence for use of onabotulinumtoxinA in the treatment of neurogenic lower urinary tract dysfunction. Since its first use in 1988 to treat detrusor sphincter dyssynergia, use of botulinum toxin has increased in this group of patients. We discuss the mechanism of action, patient selection, dosing, efficacy, and side effect profile of this now licensed treatment option. PMID:22977301

Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.

PubMed

Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

2015-01-01

Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.

Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

PubMed Central

Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

2015-01-01

Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

Postnatal exposure to N-ethyl-N-nitrosurea disrupts the subventricular zone in adult rodents.

PubMed

Capilla-Gonzalez, V; Gil-Perotin, S; Garcia-Verdugo, J M

2010-12-01

N-ethyl-N-nitrosurea (ENU), a type of N-nitrous compound (NOC), has been used as inductor for brain tumours due to its mutagenic effect on the rodent embryo. ENU also affected adult neurogenesis when administered during pregnancy. However, no studies have investigated the effect of ENU when exposured during adulthood. For this purpose, three experimental groups of adult mice were injected with ENU at different doses and killed shortly after exposure. When administered in adult mice, ENU did not form brain tumours but led to a disruption of the subventricular zone (SVZ), an adult neurogenic region. Analyses of the samples revealed a reduction in the numbers of neural progenitors compared with control animals, and morphological changes in ependymal cells. A significant decrease in proliferation was tested in vivo with 5-bromo-2-deoxyuridine administration and confirmed in vitro with a neurosphere assay. Cell death, assessed as active-caspase-3 reactivity, was more prominent in treated animals and cell death-related populations increased in parallel. Two additional groups were maintained for 45 and 120 days after five doses of ENU to study the potential regeneration of the SVZ, but only partial recovery was detected. In conclusion, exposure to ENU alters the organization of the SVZ and causes partial exhaustion of the neurogenic niche. The functional repercussion of these changes remains unknown, but exposure to NOCs implies a potential risk that needs further evaluation. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Notch Signaling Is Involved in Neurogenic Commitment of Human Periodontal Ligament-Derived Mesenchymal Stem Cells

PubMed Central

Osathanon, Thanaphum; Manokawinchoke, Jeeranan; Nowwarote, Nunthawan; Aguilar, Panuroot; Palaga, Tanapat

2013-01-01

Notch signaling plays critical roles in stem cells by regulating cell fate determination and differentiation. The aim of this study was to evaluate the participation of Notch signaling in neurogenic commitment of human periodontal ligament-derived mesenchymal stem cells (hPDLSCs) and to examine the ability to control differentiation of these cells using modified surfaces containing affinity immobilized Notch ligands. Neurogenic induction of hPDLSCs was performed via neurosphere formation. Cells were aggregated and form spheres as early 1 day in culture. In addition, the induced cells exhibited increased mRNA and protein expression of neuronal markers that is, β3-tubulin and neurofilament. During neuronal differentiation, a significant increase of Hes1 and Hey1 mRNA expression was noted. Using pharmacological inhibition (γ-secretase inhibitor) or genetic manipulation (overexpression of dominant negative mastermind-like transcription co-activators), neurosphere formation was attenuated and a marked decrease in neurogenic mRNA expression was observed. To confirm the role of Notch signaling in neuronal differentiation of hPDLSCs, the Notch ligand, Jagged-1, is bound to the surface using an affinity immobilization technique. The hPDLSC cultured on a Jagged-1-modified surface had increased expression of Notch signaling target genes, Hes-1 and Hey-1, confirming the activity and potency of surface-bound Jagged-1. Further, hPDLSC on surface-bound Jagged-1 under serum-free conditions showed multiple long and thin neurite-like extensions, and an increase in the expression of neurogenic mRNA markers was observed. Pretreatment of the cells with γ-secretase inhibitor, DAPT, before seeding on the Jagged-1-modified surface blocked development of the neurite-like morphology. Together, the results in this study suggest the involvement of Notch signaling in neurogenic commitment of hPDLSCs. PMID:23379739

L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience.

PubMed

Kaufmann, Horacio

2008-03-01

Neurogenic orthostatic hypotension results from failure to release norepinephrine, the neurotransmitter of sympathetic postganglionic neurons, appropriately upon standing. In double blind, cross over, placebo controlled trials, administration of droxidopa, a synthetic amino acid that is decarboxylated to norepinephrine by the enzyme L: -aromatic amino acid decarboxylase increases standing blood pressure, ameliorates symptoms of orthostatic hypotension and improves standing ability in patients with neurogenic orthostatic hypotension due to degenerative autonomic disorders. The pressor effect results from conversion of droxidopa to norepinephrine outside the central nervous system both in neural and non-neural tissue. This mechanism of action makes droxidopa effective in patients with central and peripheral autonomic disorders.

Pharmacotherapy in Pediatric Neurogenic Bladder Intravesical Botulinum Toxin Type A

PubMed Central

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

2012-01-01

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

Cardiovascular Safety of Droxidopa in Patients With Symptomatic Neurogenic Orthostatic Hypotension.

PubMed

White, William B; Hauser, Robert A; Rowse, Gerald J; Ziemann, Adam; Hewitt, L Arthur

2017-04-01

The norepinephrine prodrug droxidopa improves symptoms of neurogenic orthostatic hypotension, a condition that is associated with diseases of neurogenic autonomic failure (e.g., Parkinson disease, multiple system atrophy, pure autonomic failure). These conditions are more prevalent in older patients who also have cardiovascular co-morbidities. Hence, we evaluated the cardiovascular safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension who participated in randomized controlled studies (short-term studies of 1 to 2 weeks and an intermediate 8- to 10-week study) and long-term open-label studies. Rates of cardiovascular adverse events (AEs) for patients treated with droxidopa were 4.4% in the intermediate study and 10.8% in the long-term open-label studies. Adjusting for exposure time, cardiovascular AE rates were 0.30 events/patient-year in the short-term and intermediate studies and 0.15 events/patient-year in the long-term open-label studies. The incidence of treatment discontinuation due to blood pressure-related events was approximately 2.5%. Among patients with a history of cardiac disorders at baseline, the rates of cardiovascular-related and blood pressure-related AEs were nominally higher with droxidopa compared to placebo. Most of these events were minor atrial arrhythmias; none were major adverse cardiovascular events or deaths. In conclusion, small increases in cardiovascular AEs were observed with droxidopa compared to placebo; this was most evident in patients with preexisting cardiac disorders. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Development of upper tract stones in patients with congenital neurogenic bladder.

PubMed

Stephany, Heidi A; Clayton, Douglass B; Tanaka, Stacy T; Thomas, John C; Pope, John C; Brock, John W; Adams, Mark C

2014-02-01

Patients with neurogenic bladder are at increased risk of developing upper tract stones. We hypothesized that patients with lower urinary tract stone disease are at greater risk of developing upper tract stones. We performed a 10-year retrospective case-control study of patients with neurogenic bladder to determine the association between bladder and upper tract stones. Independent risk factors for upper tract stones were assessed. Cases and controls were matched 1:1. Univariable analysis was performed by Fisher's exact test and the Mann-Whitney U test. Multivariable logistic regression was performed. 52 cases and controls were identified. Cases were significantly more likely to be non-ambulatory, have bowel-urinary tract interposition, thoracic level dysraphism, and history of bladder stones. On multivariable analysis, independent predictors of stone formation were male sex (OR 2.82; p = 0.02), dysraphism involving the thoracic spine (OR 3.37; p = 0.014) bowel-urinary tract interposition (OR 2.611; p = 0.038), and a history of bladder stones (OR 3.57; p = 0.015). Patients with neurogenic bladder are at increased risk for upper tract stones. The presence of bladder stones may herald the development of upper tract stones. The predictors of stone disease identified should guide prospective studies to better understand the natural history of upper tract stone development in this population. Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-05-01

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

Is there a relationship between adult neurogenesis and neuron generation following injury across evolution?

PubMed

Ferretti, Patrizia

2011-09-01

All vertebrates can produce new neurons postnatally in discrete regions of their nervous system, but only some lower vertebrates (fish and amphibians) can significantly repair several neural structures, including brain, spinal cord, retina, olfactory and auditory-vestibular system, to compensate for neural tissue loss and recover significant functionality. Some regenerative ability, however, is found also in reptiles and birds, and even in mammals. The recognition that neurogenesis indeed occurs in the CNS of all adult vertebrates challenges the view that there is a simple relationship between maintenance of neurogenic regions in the adult CNS and regenerative capability. The aim of this review is to revisit this relationship in the light of recent literature focusing on selected examples of neurogenesis and regeneration, and discuss possible frameworks that may help to elucidate the relationship between adult neurogenesis and regeneration. This could provide useful paradigms for harnessing regeneration in the human CNS. © 2011 The Author. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

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

PubMed

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

2016-03-01

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

Selective ablation of nociceptive neurons for elimination of hyperalgesia and neurogenic inflammation.

PubMed

Tender, Gabriel C; Walbridge, Stuart; Olah, Zoltan; Karai, Laszlo; Iadarola, Michael; Oldfield, Edward H; Lonser, Russell R

2005-03-01

Neuropathic pain is mediated by nociceptive neurons that selectively express the vanilloid receptor 1 (VR1). Resiniferatoxin (RTX) is an excitotoxic VR1 agonist that causes destruction of VR1-positive neurons. To determine whether RTX can be used to ablate VR1-positive neurons selectively and to eliminate hyperalgesia and neurogenic inflammation without affecting tactile sensation and motor function, the authors infused it unilaterally into the trigeminal ganglia in Rhesus monkeys. Either RTX (three animals) or vehicle (one animal) was directly infused (20 microl) into the right trigeminal ganglion in Rhesus monkeys. Animals were tested postoperatively at 1, 4, and 7 weeks thereafter for touch and pain perception in the trigeminal distribution (application of saline and capsaicin to the cornea). The number of eye blinks, eye wipes, and duration of squinting were recorded. Neurogenic inflammation was tested using capsaicin cream. Animals were killed 4 (one monkey) and 12 (three monkeys) weeks postinfusion. Histological and immunohistochemical analyses were performed. Throughout the duration of the study, response to high-intensity pain stimulation (capsaicin) was selectively and significantly reduced (p < 0.001, RTX-treated compared with vehicle-treated eye [mean +/- standard deviation]): blinks, 25.7 +/- 4.4 compared with 106.6 +/- 20.8; eye wipes, 1.4 +/- 0.8 compared with 19.3 +/- 2.5; and squinting, 1.4 +/- 0.6 seconds compared with 11.4 +/- 1.6 seconds. Normal response to sensation was maintained. Animals showed no neurological deficit or sign of toxicity. Neurogenic inflammation was blocked on the RTX-treated side. Immunohistochemical analysis of the RTX-treated ganglia showed selective elimination of VR1-positive neurons. Nociceptive neurons can be selectively ablated by intraganglionic RTX infusion, resulting in the elimination of high-intensity pain perception and neurogenic inflammation while maintaining normal sensation and motor function. Analysis of

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

PubMed

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

2015-06-01

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

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

Urinary Tract Infection and Neurogenic Bladder.

PubMed

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

2015-11-01

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

Neurogenic transdifferentiation of human adipose-derived stem cells? A critical protocol reevaluation with special emphasis on cell proliferation and cell cycle alterations.

PubMed

Kompisch, Kai Michael; Lange, Claudia; Steinemann, Doris; Skawran, Britta; Schlegelberger, Brigitte; Müller, Reinhard; Schumacher, Udo

2010-11-01

Adipose-derived stem cells (ASCs) are reported to display multilineage differentiation potential, including neuroectodermal pathways. The aim of the present study was to critically re-evaluate the potential neurogenic (trans-)differentiation capacity of ASCs using a neurogenic induction protocol based on the combination of isobutylmethylxanthine (IBMX), indomethacin and insulin. ASCs isolated from lipo-aspirate samples of five healthy female donors were characterized and potential neurogenic (trans-)differentiation was assessed by means of immunohistochemistry and gene expression analyses. Cell proliferation and cell cycle alterations were studied, and the expression of CREB/ATF transcription factors was analyzed. ASCs expressed CD59, CD90 and CD105, and were tested negative for CD34 and CD45. Under neurogenic induction, ASCs adopted a characteristic morphology comparable to neur(on)al progenitors and expressed musashi1, β-III-tubulin and nestin. Gene expression analyses revealed an increased expression of β-III-tubulin, GFAP, vimentin and BDNF, as well as SOX4 in induced ASCs. Cell proliferation was significantly reduced under neurogenic induction; cell cycle analyses showed a G2-cell cycle arrest accompanied by differential expression of key regulators of cell cycle progression. Differential expression of CREB/ATF transcription factors could be observed on neurogenic induction, pointing to a decisive role of the cAMP-CREB/ATF system. Our findings may point to a potential neurogenic (trans-)differentiation of ASCs into early neur(on)al progenitors, but do not present definite evidence for it. Especially, the adoption of a neural progenitor cell-like morphology must not automatically be misinterpreted as a specific characteristic of a respective (trans-)differentiation process, as this may as well be caused by alterations of cell cycle progression.

Evidence against vasoactive intestinal polypeptide (VIP) as a dilator and in favour of substance P as a constrictor in airway neurogenic responses.

PubMed Central

Karlsson, J. A.; Persson, C. G.

1983-01-01

Propranolol-resistant neurogenic relaxation persisted in (carbachol-contracted) guinea-pig tracheae already relaxed by supramaximal concentrations of vasoactive intestinal polypeptide (VIP). Also, VIP relaxed preparations that were under neurogenic inhibition. In hilus bronchi, about 60% of a neurogenic contraction was atropine-resistant. (Arg5, D-Trp7.9) SP 5-11 specifically antagonized this contraction and those produced by exogenous substance P. Substance P, but not VIP, seems to be involved in nerve-mediated effects on guinea-pig airway tone. PMID:6197124

Evidence against vasoactive intestinal polypeptide (VIP) as a dilator and in favour of substance P as a constrictor in airway neurogenic responses.

PubMed

Karlsson, J A; Persson, C G

1983-07-01

Propranolol-resistant neurogenic relaxation persisted in (carbachol-contracted) guinea-pig tracheae already relaxed by supramaximal concentrations of vasoactive intestinal polypeptide (VIP). Also, VIP relaxed preparations that were under neurogenic inhibition. In hilus bronchi, about 60% of a neurogenic contraction was atropine-resistant. (Arg5, D-Trp7.9) SP 5-11 specifically antagonized this contraction and those produced by exogenous substance P. Substance P, but not VIP, seems to be involved in nerve-mediated effects on guinea-pig airway tone.

Diagnostic and prognostic contribution of laryngeal electromyography in unilateral vocal-fold immobility in adults.

PubMed

Focquet, A; Péréon, Y; Ségura, S; Ferron, C; Malard, O; Espitalier, F

2017-02-01

To study the diagnostic and prognostic contribution of laryngeal electromyography in unilateral vocal-fold immobility in adults. A retrospective study included patients with unilateral vocal-fold immobility undergoing laryngeal electromyography between 2007 and 2015. Neurogenic, normal or myogenic findings were compared to the clinical aspect. Prognosis for recovery was assessed from motor unit potentials on laryngeal electromyography, and compared to subsequent progress on laryngoscopy. Sixty-three patients (mean age, 59 years) were initially included; 2 were subsequently excluded from analysis. Mean time from onset of immobility to laryngeal electromyography was 7 months. 85% of the 61 patients showed neurogenic findings, indicating neural lesion; 13% showed normal electromyography, indicating cricoarytenoid joint ankylosis; and 1 patient showed a myogenic pattern. Neurogenic cases were usually secondary to cervical surgery. Thirty-eight patients were followed up. In total, 75% of patients showing reinnervation potentials recovered. The positive predictive value of laryngeal electromyography was 69.2%. Laryngeal electromyography is effective in specifying the origin of unilateral vocal-fold immobility in adults. It also has a prognostic role, lack of reinnervation potentials being a possible indication for early medialization surgery. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Impact of electromagnetic fields on stem cells: common mechanisms at the crossroad between adult neurogenesis and osteogenesis

PubMed Central

Leone, Lucia; Podda, Maria Vittoria; Grassi, Claudio

2015-01-01

In the recent years adult neural and mesenchymal stem cells have been intensively investigated as effective resources for repair therapies. In vivo and in vitro studies have provided insights on the molecular mechanisms underlying the neurogenic and osteogenic processes in adulthood. This knowledge appears fundamental for the development of targeted strategies to manipulate stem cells. Here we review recent literature dealing with the effects of electromagnetic fields on stem cell biology that lends support to their use as a promising tool to positively influence the different steps of neurogenic and osteogenic processes. We will focus on recent studies revealing that extremely-low frequency electromagnetic fields enhance adult hippocampal neurogenesis by inducing epigenetic modifications on the regulatory sequences of genes responsible for neural stem cell proliferation and neuronal differentiation. In light of the emerging critical role played by chromatin modifications in maintaining the stemness as well as in regulating stem cell differentiation, we will also attempt to exploit epigenetic changes that can represent common targets for electromagnetic field effects on neurogenic and osteogenic processes. PMID:26124705

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

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.

Neurogenic gene regulatory pathways in the sea urchin embryo.

PubMed

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

2016-01-15

During embryogenesis the sea urchin early pluteus larva differentiates 40-50 neurons marked by expression of the pan-neural marker synaptotagmin B (SynB) that are distributed along the ciliary band, in the apical plate and pharyngeal endoderm, and 4-6 serotonergic neurons that are confined to the apical plate. Development of all neurons has been shown to depend on the function of Six3. Using a combination of molecular screens and tests of gene function by morpholino-mediated knockdown, we identified SoxC and Brn1/2/4, which function sequentially in the neurogenic regulatory pathway and are also required for the differentiation of all neurons. Misexpression of Brn1/2/4 at low dose caused an increase in the number of serotonin-expressing cells and at higher dose converted most of the embryo to a neurogenic epithelial sphere expressing the Hnf6 ciliary band marker. A third factor, Z167, was shown to work downstream of the Six3 and SoxC core factors and to define a branch specific for the differentiation of serotonergic neurons. These results provide a framework for building a gene regulatory network for neurogenesis in the sea urchin embryo. © 2016. Published by The Company of Biologists Ltd.

Long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

PubMed

Isaacson, Stuart; Vernino, Steven; Ziemann, Adam; Rowse, Gerald J; Kalu, Uwa; White, William B

2016-10-01

The long-term safety of droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension in patients with Parkinson disease, pure autonomic failure, multiple system atrophy, or nondiabetic autonomic neuropathy was evaluated in a phase 3, multinational, open-label study in patients who previously participated in a double-blind, placebo-controlled clinical trial of droxidopa. A total of 350 patients received droxidopa 100 to 600 mg three times daily. Mean duration of droxidopa exposure was 363 days (range, 2-1133 days). Rates of serious adverse events (AEs), cardiac-related AEs, and supine hypertension were 24%, 5%, and 5%, respectively. Most AEs, including those of a cardiovascular nature, were not attributed by investigators to droxidopa. In this large cohort of patients with neurogenic orthostatic hypotension, droxidopa was well tolerated during long-term use. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

ERIC Educational Resources Information Center

Drew, Liam J.; Fusi, Stefano; Hen, René

2013-01-01

In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

Treatment of neurogenic diabetes insipidus.

PubMed

Chanson, Philippe; Salenave, Sylvie

2011-12-01

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

Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal Differentiation of Adult SVZ Progenitors.

PubMed

Kolb, Jasmine; Anders-Maurer, Marie; Müller, Tanja; Hau, Ann-Christin; Grebbin, Britta Moyo; Kallenborn-Gerhardt, Wiebke; Behrends, Christian; Schulte, Dorothea

2018-04-10

Adult neurogenesis is regulated by stem cell niche-derived extrinsic factors and cell-intrinsic regulators, yet the mechanisms by which niche signals impinge on the activity of intrinsic neurogenic transcription factors remain poorly defined. Here, we report that MEIS2, an essential regulator of adult SVZ neurogenesis, is subject to posttranslational regulation in the SVZ olfactory bulb neurogenic system. Nuclear accumulation of MEIS2 in adult SVZ-derived progenitor cells follows downregulation of EGFR signaling and is modulated by methylation of MEIS2 on a conserved arginine, which lies in close proximity to nested binding sites for the nuclear export receptor CRM1 and the MEIS dimerization partner PBX1. Methylation impairs interaction with CRM1 without affecting PBX1 dimerization and thereby allows MEIS2 nuclear accumulation, a prerequisite for neuronal differentiation. Our results describe a form of posttranscriptional modulation of adult SVZ neurogenesis whereby an extrinsic signal fine-tunes neurogenesis through posttranslational modification of a transcriptional regulator of cell fate. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Is nasogastric tube drainage required after reconstructive surgery for neurogenic bladder dysfunction?

PubMed

Erickson, Bradley A; Dorin, Ryan P; Clemens, J Quentin

2007-05-01

To determine whether the routine use of nasogastric tubes (NGTs) after bowel surgery for neurogenic bladder dysfunction improves outcomes. We retrospectively evaluated 54 consecutive patients (30 women, 24 men) with neurogenic bladder who underwent bladder reconstruction or replacement with bowel segments by one surgeon from December 2000 to August 2005. The first 32 [NGT(+)] had NGTs placed during the procedure, whereas the subsequent 22 [NGT(-)] did not. We compared short-term postoperative outcomes between groups. Patient age ranged from 17 to 74 years (mean, 42.6 years). Procedures included augmentation cystoplasty with or without creation of catheterizable stoma (31), ileovesicostomy (13), and ileal conduit (9). Mean age or mean operative time did not differ between the NGT(+) and NGT(-) groups. The NGT(-) patients experienced less time to oral intake (3.1 versus 4.4 days, P <0.01), fewer days to flatus (2.9 versus 4.0 days, P = 0.01), and fewer days to first bowel movement (4.4 versus 5.9 days, P = 0.01). We found no statistical differences in the incidence of postoperative complications. Overall hospital days were less in the NGT(-) patients, but this did not reach statistical significance (9.9 versus 11.0, P = 0.2). Routine use of NGTs in patients undergoing bladder reconstruction or replacement for neurogenic bladder dysfunction seems to confer no benefit. The omission of NGTs in this population is possible without increasing overall morbidity. These findings parallel those previously reported in neurologically intact patients undergoing urinary diversion.

Fetal Alcohol Exposure Reduces Adult Brain Plasticity. Science Briefs

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2007

2007-01-01

"Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This Brief summarizes the findings and implications of "Moderate Fetal Alcohol Exposure Impairs the Neurogenic Response to an Enriched Environment in Adult Mice" (I. Y. Choi; A. M. Allan; and L. A. Cunningham). Observations of mice…

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…

Alpha2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment.

PubMed

Yanpallewar, Sudhirkumar U; Fernandes, Kimberly; Marathe, Swananda V; Vadodaria, Krishna C; Jhaveri, Dhanisha; Rommelfanger, Karen; Ladiwala, Uma; Jha, Shanker; Muthig, Verena; Hein, Lutz; Bartlett, Perry; Weinshenker, David; Vaidya, Vidita A

2010-01-20

Slow-onset adaptive changes that arise from sustained antidepressant treatment, such as enhanced adult hippocampal neurogenesis and increased trophic factor expression, play a key role in the behavioral effects of antidepressants. alpha(2)-Adrenoceptors contribute to the modulation of mood and are potential targets for the development of faster acting antidepressants. We investigated the influence of alpha(2)-adrenoceptors on adult hippocampal neurogenesis. Our results indicate that alpha(2)-adrenoceptor agonists, clonidine and guanabenz, decrease adult hippocampal neurogenesis through a selective effect on the proliferation, but not the survival or differentiation, of progenitors. These effects persist in dopamine beta-hydroxylase knock-out (Dbh(-/-)) mice lacking norepinephrine, supporting a role for alpha(2)-heteroceptors on progenitor cells, rather than alpha(2)-autoreceptors on noradrenergic neurons that inhibit norepinephrine release. Adult hippocampal progenitors in vitro express all the alpha(2)-adrenoceptor subtypes, and decreased neurosphere frequency and BrdU incorporation indicate direct effects of alpha(2)-adrenoceptor stimulation on progenitors. Furthermore, coadministration of the alpha(2)-adrenoceptor antagonist yohimbine with the antidepressant imipramine significantly accelerates effects on hippocampal progenitor proliferation, the morphological maturation of newborn neurons, and the increase in expression of brain derived neurotrophic factor and vascular endothelial growth factor implicated in the neurogenic and behavioral effects of antidepressants. Finally, short-duration (7 d) yohimbine and imipramine treatment results in robust behavioral responses in the novelty suppressed feeding test, which normally requires 3 weeks of treatment with classical antidepressants. Our results demonstrate that alpha(2)-adrenoceptors, expressed by progenitor cells, decrease adult hippocampal neurogenesis, while their blockade speeds up antidepressant action

α2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment

PubMed Central

Yanpallewar, Sudhirkumar U.; Fernandes, Kimberly; Marathe, Swananda V.; Vadodaria, Krishna C.; Jhaveri, Dhanisha; Rommelfanger, Karen; Ladiwala, Uma; Jha, Shanker; Muthig, Verena; Hein, Lutz; Bartlett, Perry; Weinshenker, David; Vaidya, Vidita A.

2010-01-01

Slow-onset adaptive changes that arise from sustained antidepressant treatment, such as enhanced adult hippocampal neurogenesis and increased trophic factor expression, play a key role in the behavioral effects of antidepressants. α2-adrenoceptors contribute to the modulation of mood and are potential targets for the development of faster acting antidepressants. We investigated the influence of α2-adrenoceptors on adult hippocampal neurogenesis. Our results indicate that α2-adrenoceptor agonists, clonidine and guanabenz, decrease adult hippocampal neurogenesis through a selective effect on the proliferation, but not the survival or differentiation, of progenitors. These effects persist in dopamine β-hydroxylase knockout (Dbh −/−) mice lacking norepinephrine, supporting a role for α2-heteroceptors on progenitor cells, rather than α2-autoreceptors on noradrenergic neurons that inhibit norepinephrine release. Adult hippocampal progenitors in vitro express all the α2-adrenoceptor subtypes, and decreased neurosphere frequency and BrdU incorporation indicate direct effects of α2-adrenoceptor stimulation on progenitors. Further, co-administration of the α2-adrenoceptor antagonist yohimbine with the antidepressant imipramine significantly accelerates effects on hippocampal progenitor proliferation, the morphological maturation of newborn neurons, and the increase in expression of brain derived neurotrophic factor and vascular endothelial growth factor implicated in the neurogenic and behavioral effects of antidepressants. Finally, short duration (7 day) yohimbine and imipramine treatment results in robust behavioral responses in the novelty suppressed feeding test, which normally requires 3 weeks of treatment with classical antidepressants. Our results demonstrate that α2-adrenoceptors, expressed by progenitor cells, decrease adult hippocampal neurogenesis, while their blockade speeds up antidepressant action, highlighting their importance as targets for

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

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. © 2015 Wiley Publishing Asia Pty Ltd.

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

PubMed

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

To evaluate the association between early treatment and urodynamic improvement in pediatric and adolescent patients with neurogenic bladder. Retrospective longitudinal and observational study (between 1990 and 2013) including patients with neurogenic bladder and myelomeningocele treated based on urodynamic results. The authors evaluated the urodynamic follow-up (bladder compliance and maximum bladder capacity and pressure) considering the first urodynamic improvement in two years as the outcome variable and early referral as the exposure variable, using a descriptive and multivariate analysis with logistic regression model. Among 230 patients included, 52% had an early referral. The majority were diagnosed as overactive bladder with high bladder pressure (≥40cm H 2 O) and low bladder compliance (3mL/cmH 2 O) and were treated with oxybutynin and intermittent catheterization. Urodynamic follow-up results showed 68% of improvement at the second urodynamic examination decreasing bladder pressure and increasing bladder capacity and compliance. The percentage of incontinence and urinary tract infections decreased over treatment. Early referral (one-year old or less) increased by 3.5 the probability of urodynamic improvement in two years (95% CI: 1.81-6.77). Treatment onset within the first year of life improves urodynamic prognosis in patients with neurogenic bladder and triplicates the probability of urodynamic improvement in two years. The role of neonatologists and pediatricians in early referral is extremely important. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Neurogenic plasma exudation mediates grain dust-induced tissue injury in vivo.

PubMed

Gao, X P; Von Essen, S; Rubinstein, I

1997-02-01

The purpose of this study was to determine whether an aqueous extract of grain sorghum dust (GDE) elicits neurogenic plasma exudation in the oral mucosa in vivo. Using intravital microscopy, we found that GDE elicited significant, concentration-dependent leaky site formation and an increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass 70 kDa) from the hamster cheek pouch (P < 0.05). The selective, nonpeptide neurokinin(1) (substance P) receptor antagonists, CP-96,345 and RP-67580, but not the 2R,3R enantiomer CP-96,344, significantly attenuated GDE-induced leaky site formation and increase in clearance of FITC-dextran (P < 0.05). Indomethacin had no significant effects on GDE-induced responses. CP-96,345 had no significant effects of adenosine-induced leaky site formation and increase in clearance of FITC-dextran from the cheek pouch. We conclude that GDE elicits neurogenic plasma exudation from the oral mucosa in vivo. We suggest that this process is one mechanism whereby grain sorghum dust elicits immediate oral mucosa inflammation in vivo.

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…

Chronic Renal Failure Secondary to Unrecognized Neurogenic Bladder in A Child with Myelodysplasia.

PubMed

Ahmed, Shameem; Paul, Siba Prosad

2017-01-01

Myelodysplasia includes a group of developmental anomalies resulting from defects that occur during neural tube closure. Urological morbidity in patients with myelodysplasia is significant and if not treated appropriately in a timely manner can potentially lead to progressive renal failure, requiring dialysis or transplantation. We report the case of a 13-year old girl with neurogenic bladder who presented chronic renal failure secondary to lipomyelomeningocele with retethering of cord. She was managed with urinary indwelling catheterization until optimization of renal function and then underwent detethering of cord with excision and repair of residual lipomeningomyelocele. Her renal parameters improved gradually over weeks and then were managed on self clean intermittent catheterization. The case emphasizes the need for considering retethering of spinal cord in children with myelodysplasia where symptoms of neurogenic bladder and recurrent urinary tract infections occur.

Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

PubMed

Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka; Ishikawa, Hiroto; Yankee, Ernest; McGrogan, Michael; Case, Casey; Borlongan, Cesar V

2013-01-01

Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

Signaling mechanisms regulating adult neural stem cells and neurogenesis

PubMed Central

Faigle, Roland; Song, Hongjun

2012-01-01

Background Adult neurogenesis occurs throughout life in discrete regions of the mammalian brain and is tightly regulated via both extrinsic environmental influences and intrinsic genetic factors. In recent years, several crucial signaling pathways have been identified in regulating self-renewal, proliferation, and differentiation of neural stem cells, as well as migration and functional integration of developing neurons in the adult brain. Scope of review Here we review our current understanding of signaling mechanisms, including Wnt, notch, sonic hedgehog, growth and neurotrophic factors, bone morphogenetic proteins, neurotransmitters, transcription factors, and epigenetic modulators, and crosstalk between these signaling pathways in the regulation of adult neurogenesis. We also highlight emerging principles in the vastly growing field of adult neural stem cell biology and neural plasticity. Major conclusions Recent methodological advances have enabled the field to identify signaling mechanisms that fine-tune and coordinate neurogenesis in the adult brain, leading to a better characterization of both cell-intrinsic and environmental cues defining the neurogenic niche. Significant questions related to niche cell identity and underlying regulatory mechanisms remain to be fully addressed and will be the focus of future studies. General significance A full understanding of the role and function of individual signaling pathways in regulating neural stem cells and generation and integration of newborn neurons in the adult brain may lead to targeted new therapies for neurological diseases in humans. PMID:22982587

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

PubMed

Yaguchi, Shunsuke; Yaguchi, Junko; Inaba, Kazuo

2014-10-31

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

Tauroursodeoxycholic Acid Enhances Mitochondrial Biogenesis, Neural Stem Cell Pool, and Early Neurogenesis in Adult Rats.

PubMed

Soares, Rita; Ribeiro, Filipa F; Xapelli, Sara; Genebra, Tânia; Ribeiro, Maria F; Sebastião, Ana M; Rodrigues, Cecília M P; Solá, Susana

2018-05-01

Although neurogenesis occurs in restricted regions of the adult mammalian brain, neural stem cells (NSCs) produce very few neurons during ageing or after injury. We have recently discovered that the endogenous bile acid tauroursodeoxycholic acid (TUDCA), a strong inhibitor of mitochondrial apoptosis and a neuroprotective in animal models of neurodegenerative disorders, also enhances NSC proliferation, self-renewal, and neuronal conversion by improving mitochondrial integrity and function of NSCs. In the present study, we explore the effect of TUDCA on regulation of NSC fate in neurogenic niches, the subventricular zone (SVZ) of the lateral ventricles and the hippocampal dentate gyrus (DG), using rat postnatal neurospheres and adult rats exposed to the bile acid. TUDCA significantly induced NSC proliferation, self-renewal, and neural differentiation in the SVZ, without affecting DG-derived NSCs. More importantly, expression levels of mitochondrial biogenesis-related proteins and mitochondrial antioxidant responses were significantly increased by TUDCA in SVZ-derived NSCs. Finally, intracerebroventricular administration of TUDCA in adult rats markedly enhanced both NSC proliferation and early differentiation in SVZ regions, corroborating in vitro data. Collectively, our results highlight a potential novel role for TUDCA in neurologic disorders associated with SVZ niche deterioration and impaired neurogenesis.

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

Human dental pulp stem cells with highly angiogenic and neurogenic potential for possible use in pulp regeneration.

PubMed

Nakashima, Misako; Iohara, Koichiro; Sugiyama, Masahiko

2009-01-01

Dental caries is a common public health problem, causing early loss of dental pulp and resultant tooth loss. Dental pulp has important functions to sustain teeth providing nutrient and oxygen supply, innervation, reactionary/reparative dentin formation and immune response. Regeneration of pulp is an unmet need in endodontic therapy, and angiogenesis/vasculogenesis and neurogenesis are critical for pulp regeneration. Permanent and deciduous pulp tissue is easily available from teeth after extraction without ethical issues and has potential for clinical use. In this review, we introduce some stem cell subfractions, CD31(-)/CD146(-) SP cells and CD105(+) cells with high angiogenic and neurogenic potential, derived from human adult dental pulp tissue. Potential utility of these cells is addressed as a source of cells for treatment of cerebral and limb ischemia and pulp inflammation complete with angiogenesis and vasculogenesis.

Pyridostigmine treatment trial in neurogenic orthostatic hypotension.

PubMed

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

2006-04-01

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

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

PubMed

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

2013-02-01

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

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

PubMed Central

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

2011-01-01

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

Myopathy in CRPS-I: disuse or neurogenic?

PubMed

Hulsman, Natalie M; Geertzen, Jan H B; Dijkstra, Pieter U; van den Dungen, Jan J A M; den Dunnen, Wilfred F A

2009-08-01

The diagnosis Complex Regional Pain Syndrome type I (CRPS-I) is based on clinical symptoms, including motor symptoms. Histological changes in muscle tissue may be present in the chronic phase of CRPS-I. Aim of this study was to analyze skeletal muscle tissue from amputated limbs of patients with CRPS-I, in order to gain more insight in factors that may play a role in changes in muscles in CRPS-I. These changes may be helpful in clarifying the pathophysiology of CRPS-I. Fourteen patients with therapy resistant and longstanding CRPS-I, underwent an amputation of the affected limb. In all patients histological analysis showed extensive changes in muscle tissue, such as fatty degeneration, fibre atrophy and nuclear clumping, which was not related to duration of CRPS-I prior to amputation. In all muscles affected, both type 1 and type 2 fibre atrophy was found, without selective type 2 fibre atrophy. In four patients, type grouping was observed, indicating a sequence of denervation and reinnervation of muscle tissue. In two patients even large group atrophy was present, suggesting new denervation after reinnervation. Comparison between subgroups in arms and legs showed no difference in the number of changes in muscle tissue. Intrinsic and extrinsic muscles were affected equally. Our findings show that in the chronic phase of CRPS-I extensive changes can be seen in muscle tissue, not related to duration of CRPS-I symptoms. Signs of neurogenic myopathy were present in five patients.

Neurogenic fever after traumatic brain injury: an epidemiological study

PubMed Central

Thompson, H; Pinto-Martin, J; Bullock, M

2003-01-01

Objectives: To determine the incidence of neurogenic fever (NF) in a population of patients in the acute phase following severe traumatic brain injury (TBI); to identify factors associated with the development of NF following severe TBI in adults. Methods: Charts of patients admitted from 1996 to 1999 with severe TBI at a large, urban mid-Atlantic teaching hospital were retrospectively evaluated based on diagnostic criteria for each episode of hyperthermia to determine the diagnosis of NF. Data were collected regarding mechanism and area of injury, severity of injury, and demographic factors to determine potential predictors of NF. Results: Diffuse axonal injury (DAI) (OR 9.06, 95% CI 0.99 to 82.7) and frontal lobe injury of any type (OR 6.68, 95% CI 1.1 to 39.3) are independently predictive of an increased risk of development of NF following severe TBI. The presence of a skull fracture and lower initial Glasgow Coma Score (GCS) were individual predictors of development of NF, but did not contribute to the final model. Conclusions: These findings examine known and novel risk factors for this phenomenon in comparison to previously published literature on NF. A set of predictor variables was identified to help clinicians target patients at high risk for development of NF following severe TBI. It is hoped that earlier diagnosis and appropriate intervention for fever in the TBI patient will lead to improved outcomes. PMID:12700304

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

PubMed Central

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

2014-01-01

Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic–pituitary–adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism. PMID:24952232

Development, Regional Training Policy and Adult Education.

ERIC Educational Resources Information Center

Scheffknecht, J. J.

Interest in a regional and local approach to vocational training and adult education is increasing throughout the member nations of the Council of Europe. This is largely a result of the changing European economic order and the new internationalization of industrial strategies. Particularly needed is a targeted local and regional policy for the…

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

Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body.

PubMed

Ortega-Sáenz, Patricia; Villadiego, Javier; Pardal, Ricardo; Toledo-Aral, Juan José; López-Barneo, José

2015-01-01

The carotid body (CB) is a polymodal chemoreceptor that triggers the hyperventilatory response to hypoxia necessary for the maintenance of O(2) homeostasis essential for the survival of organs such as the brain or heart. Glomus cells, the sensory elements in the CB, are also sensitive to hypercapnia, acidosis and, although less generally accepted, hypoglycemia. Current knowledge on CB function is mainly based on studies performed on lower mammals, but the information on the human CB is scant. Here we describe the structure, neurotrophic properties, and cellular responses to hypoxia and hypoglycemia of CBs dissected from human cadavers. The adult CB parenchyma contains clusters of chemosensitive glomus (type I) and sustentacular (type II) cells as well as nestin-positive progenitor cells. This organ also expresses high levels of the dopaminotrophic glial cell line-derived neurotrophic factor (GDNF). GDNF production and the number of progenitor and glomus cells were preserved in the CBs of human subjects of advanced age. As reported for other mammalian species, glomus cells responded to hypoxia by external Ca(2+)-dependent increase of cytosolic [Ca(2+)] and quantal catecholamine release. Human glomus cells are also responsive to hypoglycemia and together the two stimuli, hypoxia and hypoglycemia, can potentiate each other's effects. The chemo-sensory responses of glomus cells are also preserved at an advanced age. Interestingly, a neurogenic niche similar to that recently described in rodents is also preserved in the adult human CB. These new data on the cellular and molecular physiology of the CB pave the way for future pathophysiological studies involving this organ in humans.

Adult Hippocampal Neurogenesis, Aging and Neurodegenerative Diseases: Possible Strategies to Prevent Cognitive Impairment.

PubMed

Vivar, Carmen

2015-01-01

The adult brain of humans and other mammals continuously generates new neurons throughout life. However, this neurogenic capacity is limited to two brain areas, the dentate gyrus (DG of the hippocampus and the subventricular zone (SVZ of the lateral ventricle. Although the DG generates new neurons, its neurogenic capacity declines with age and neurodegenerative diseases such as Alzheimer's disease (AD and Huntington's disease (HD. This review focuses on the role of newly-born neurons in cognitive processes, and discusses some of the strategies proposed in humans and animals to enhance neurogenesis and counteract age-related cognitive deficits, such as physical exercise and intake of natural products like omega-3 fatty acids, curcumin and flavanols.

Neuroinflammation and physical exercise as modulators of adult hippocampal neural precursor cell behavior.

PubMed

Pérez-Domínguez, Martha; Tovar-Y-Romo, Luis B; Zepeda, Angélica

2018-01-26

The dentate gyrus of the hippocampus is a plastic structure where adult neurogenesis constitutively occurs. Cell components of the neurogenic niche are source of paracrine as well as membrane-bound factors such as Notch, Bone Morphogenetic Proteins, Wnts, Sonic Hedgehog, cytokines, and growth factors that regulate adult hippocampal neurogenesis and cell fate decision. The integration and coordinated action of multiple extrinsic and intrinsic cues drive a continuous decision process: if adult neural stem cells remain quiescent or proliferate, if they take a neuronal or a glial lineage, and if new cells proliferate, undergo apoptotic death, or survive. The proper balance in the molecular milieu of this neurogenic niche leads to the production of neurons in a higher rate as that of astrocytes. But this rate changes in face of microenvironment modifications as those driven by physical exercise or with neuroinflammation. In this work, we first review the cellular and molecular components of the subgranular zone, focusing on the molecules, active signaling pathways and genetic programs that maintain quiescence, induce proliferation, or promote differentiation. We then summarize the evidence regarding the role of neuroinflammation and physical exercise in the modulation of adult hippocampal neurogenesis with emphasis on the activation of progression from adult neural stem cells to lineage-committed progenitors to their progeny mainly in murine models.

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

PubMed Central

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

2014-01-01

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

Does sacral pulsed electromagnetic field therapy have a better effect than transcutaneous electrical nerve stimulation in patients with neurogenic overactive bladder?

PubMed

Fergany, Lamyaa A; Shaker, Husain; Arafa, Magdy; Elbadry, Mohamed S

2017-06-01

To compare the effectiveness of pulsed electromagnetic field therapy (PEMFT) and transcutaneous electrical nerve stimulation (TENS) on neurogenic overactive bladder dysfunction (OAB) in patients with spinal cord injury (SCI). In all, 80 patients [50 men and 30 women, with a mean (SD) age of 40.15 (8.76) years] with neurogenic OAB secondary to suprasacral SCI were included. They underwent urodynamic studies (UDS) before and after treatment. Patients were divided into two equal groups: Group A, comprised 40 patients who received 20 min of TENS (10 Hz with a 700 s generated pulse), three times per week for 20 sessions; Group B, comprised 40 patients who received PEMFT (15 Hz with 50% intensity output for 5 s/min for 20 min), three times per week for 20 sessions. In Group B, there was a significant increase in the maximum cystometric capacity ( P  < 0.001), volume at first uninhibited detrusor contraction ( P  < 0.002), and maximum urinary flow rate ( P  < 0.02). The UDS showed that the effects of PEMFT in patients with neurogenic OAB secondary to suprasacral SCI was better than TENS for inducing an inhibitory effect on neurogenic detrusor overactivity.

Examination of validity in spoken language evaluations: Adult onset stuttering following mild traumatic brain injury.

PubMed

Roth, Carole R; Cornis-Pop, Micaela; Beach, Woodford A

2015-01-01

Reports of increased incidence of adult onset stuttering in veterans and service members with mild traumatic brain injury (mTBI) from combat operations in Iraq and Afghanistan lead to a reexamination of the neurogenic vs. psychogenic etiology of stuttering. This article proposes to examine the merit of the dichotomy between neurogenic and psychogenic bases of stuttering, including symptom exaggeration, for the evaluation and treatment of the disorder. Two case studies of adult onset stuttering in service members with mTBI from improvised explosive device blasts are presented in detail. Speech fluency was disrupted by abnormal pauses and speech hesitations, brief blocks, rapid repetitions, and occasional prolongations. There was also wide variability in the frequency of stuttering across topics and conversational situations. Treatment focused on reducing the frequency and severity of dysfluencies and included educational, psychological, environmental, and behavioral interventions. Stuttering characteristics as well as the absence of objective neurological findings ruled out neurogenic basis of stuttering in these two cases and pointed to psychogenic causes. However, the differential diagnosis had only limited value for developing the plan of care. The successful outcomes of the treatment serve to illustrate the complex interaction of neurological, psychological, emotional, and environmental factors of post-concussive symptoms and to underscore the notion that there are many facets to symptom presentation in post-combat health.

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

PubMed

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

2016-05-01

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

A historical perspective on the role of sensory nerves in neurogenic inflammation.

PubMed

Sousa-Valente, João; Brain, Susan D

2018-05-01

The term 'neurogenic inflammation' is commonly used, especially with respect to the role of sensory nerves within inflammatory disease. However, despite over a century of research, we remain unclear about the role of these nerves in the vascular biology of inflammation, as compared with their interacting role in pain processing and of their potential for therapeutic manipulation. This chapter attempts to discuss the progress in understanding, from the initial discovery of sensory nerves until the present day. This covers pioneering findings that these nerves exist, are involved in vascular events and act as important sensors of environmental changes, including injury and infection. This is followed by discovery of the contents they release such as the established vasoactive neuropeptides substance P and CGRP as well as anti-inflammatory peptides such as the opioids and somatostatin. The more recent emergence of the importance of the transient receptor potential (TRP) channels has revealed some of the mechanisms by which these nerves sense environmental stimuli. This knowledge enables a platform from which to learn of the potential role of neurogenic inflammation in disease and in turn of novel therapeutic targets.

Randomized Withdrawal Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension Responsive to Droxidopa

PubMed Central

Freeman, Roy; Mathias, Christopher J.; Low, Phillip; Hewitt, L. Arthur; Kaufmann, Horacio

2015-01-01

Abstract— We evaluated whether droxidopa, a prodrug converted to norepinephrine, is beneficial in the treatment of symptomatic neurogenic orthostatic hypotension, which results from failure to generate an appropriate norepinephrine response to postural challenge. Patients with symptomatic neurogenic orthostatic hypotension and Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa titration (100–600 mg, 3× daily). Responders then received an additional 7-day open-label treatment at their individualized dose. Patients were subsequently randomized to continue with droxidopa or withdraw to placebo for 14 days. We then assessed patient-reported scores on the Orthostatic Hypotension Questionnaire and blood pressure measurements. Mean worsening of Orthostatic Hypotension Questionnaire dizziness/lightheadedness score from randomization to end of study (the primary outcome; N=101) was 1.9±3.2 with placebo and 1.3±2.8 units with droxidopa (P=0.509). Four of the other 5 Orthostatic Hypotension Questionnaire symptom scores and all 4 symptom-impact scores favored droxidopa, with statistical significance for the patient’s self-reported ability to perform activities requiring standing a short time (P=0.033) and standing a long time (P=0.028). Furthermore, a post hoc analysis of a predefined composite score of all symptoms (Orthostatic Hypotension Questionnaire composite) demonstrated a significant benefit for droxidopa (P=0.013). There was no significant difference between groups for standing systolic blood pressure (P=0.680). Droxidopa was well tolerated. In summary, this randomized withdrawal droxidopa study failed to meet its primary efficacy end point. Additional clinical trials are needed to confirm that droxidopa is beneficial in symptomatic neurogenic orthostatic hypotension, as suggested by the positive secondary outcomes of this trial. Clinical Trial Registration— URL: http

Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa.

PubMed

Biaggioni, Italo; Freeman, Roy; Mathias, Christopher J; Low, Phillip; Hewitt, L Arthur; Kaufmann, Horacio

2015-01-01

We evaluated whether droxidopa, a prodrug converted to norepinephrine, is beneficial in the treatment of symptomatic neurogenic orthostatic hypotension, which results from failure to generate an appropriate norepinephrine response to postural challenge. Patients with symptomatic neurogenic orthostatic hypotension and Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa titration (100-600 mg, 3× daily). Responders then received an additional 7-day open-label treatment at their individualized dose. Patients were subsequently randomized to continue with droxidopa or withdraw to placebo for 14 days. We then assessed patient-reported scores on the Orthostatic Hypotension Questionnaire and blood pressure measurements. Mean worsening of Orthostatic Hypotension Questionnaire dizziness/lightheadedness score from randomization to end of study (the primary outcome; N=101) was 1.9±3.2 with placebo and 1.3±2.8 units with droxidopa (P=0.509). Four of the other 5 Orthostatic Hypotension Questionnaire symptom scores and all 4 symptom-impact scores favored droxidopa, with statistical significance for the patient's self-reported ability to perform activities requiring standing a short time (P=0.033) and standing a long time (P=0.028). Furthermore, a post hoc analysis of a predefined composite score of all symptoms (Orthostatic Hypotension Questionnaire composite) demonstrated a significant benefit for droxidopa (P=0.013). There was no significant difference between groups for standing systolic blood pressure (P=0.680). Droxidopa was well tolerated. In summary, this randomized withdrawal droxidopa study failed to meet its primary efficacy end point. Additional clinical trials are needed to confirm that droxidopa is beneficial in symptomatic neurogenic orthostatic hypotension, as suggested by the positive secondary outcomes of this trial. http://www.clinicaltrials.gov. Unique identifier: NCT00633880

Canine Adipose-Derived Stem Cells: Purinergic Characterization and Neurogenic Potential for Therapeutic Applications.

PubMed

Roszek, Katarzyna; Makowska, Noemi; Czarnecka, Joanna; Porowińska, Dorota; Dąbrowski, Marcin; Danielewska, Justyna; Nowak, Wiesław

2017-01-01

The presented results evidence that canine adipose-derived stem cells (ADSCs) represent the premature population of stem cells with great biological potential and properties. ADCS are easy to obtain and culture, able to differentiate into the neurogenic lineage as well as it is easy to control their proliferation rate with nucleotides and nucleosides or analogues. We report that in vitro cultured canine ADSCs response to adenosine- and ATP-mediated stimulation. Differences in canine ADSCs and human mesenchymal stem cells in ecto-nucleotidase activity have been observed. The ecto-nucleotidase activity changes during ADSCs in vitro transdifferentiation into neurogenic lineage are fast and simple to analyze. Therefore, the simple analysis of ecto-enzymes activity allows for verification of the stem cells quality: their stemness or initiation of the differentiation process. The biological potential of the cells isolated from canine fat, as well as the good quality control of this cell culture, make them a promising tool for both experimental and therapeutic usage. J. Cell. Biochem. 118: 58-65, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

PubMed

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

2015-01-01

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

[Clonazepam in therapy of neurogenic syncopal states].

PubMed

Musaeva, Z A

2001-01-01

27 patients with frequent neurogenic syncopes (NS) resistant to conventional therapy were treated with clonazepam. The average age of the patients was 29.8 +/- 11.6 years. There were 1-2 syncopes in a month. Both before and after the treatment an active orthostatic test was performed with ECG registration and following analysis of variability of the cardiac rhythm. Clonazepam was administered in a dose of 2-2.5 mg/day during 8-9 weeks. Clinical improvement in the form of a lack of syncopes was observed in 20 patients (74%); 3 patients (10%) had isolated lipothymic states; 2 patients discontinued the treatment because of side-effects (dizziness). The results of the examination of 23 patients 6 months after clonazepam therapy testified the stability of the therapeutic effect.

[Electromyographic differential diagnosis in cases of abducens nerve paresis with nuclear or distal neurogenic sive myogenic origine (author's transl)].

PubMed

Heuser, M

1979-09-01

Abducens nerve paresis may be of nuclear, of peripheral distal neurogenic origine, or is simulated by a myogenic weakness of abduction. Polygraphic emg analysis of the oculoauricularphenomenon (oap) permits a differentiation. In the emg, the oap proved to be a physiologic and constant automatic and always bilateral interaction between the hemolateral abducens nerve and both Nn. faciales with corresponding and obligatory coinnervation of the Mm. retroauricularis of the external ear. In case of medullary, nuclear or internuclear lesions, the oap is disturbed, instable, diminished or abolished, whereas in distal neurogenic or myogenic paresis, even in complete paralysis the oap is bilaterally well preserved.

Position statement: a clinical approach to the management of adult non-neurogenic overactive bladder.

PubMed

Chung, Eric; Lee, Dominic; Gani, Johan; Gillman, Michael; Maher, Christopher; Brennan, Janelle; Johns Putra, Lydia; Ahmad, Laura; Chan, Lewis Lw

2018-01-15

Overactive bladder (OAB) is a highly prevalent medical condition that has an adverse impact on various health-related quality-of-life domains, including a significant psychosocial and financial burden. This position statement, formulated by members of the Urological Society of Australia and New Zealand and the UroGynaecological Society of Australasia, summarises the current recommendations for clinical diagnosis and treatment strategies in patients with non-neurogenic OAB, and guides clinicians in the decision-making process for managing the condition using evidence-based medicine. Main recommendations: Diagnosis and initial management should be based on thorough clinical history, examination and basic investigations to exclude underlying treatable causes such as urinary tract infection and urological malignancy. Initial treatment strategies for OAB involve conservative management with behavioural modification and bladder retraining. Second-line management involves medical therapy using anticholinergic or β3 agonist drugs provided there is adequate assessment of bladder emptying. If medical therapy is unsuccessful, further investigations with urodynamic studies and cystourethroscopy are recommended to guide further treatment. Intravesical botulinum toxin and sacral neuromodulation should be considered in medical refractory OAB. Changes in management as a result of this statement: OAB is a constellation of urinary symptoms and is a chronic condition with a low likelihood of cure; managing patient expectations is essential because OAB is challenging to treat. At present, the exact pathogenesis of OAB remains unclear and it is likely that there are multiple factors involved in this disease complex. Current medical treatment remains far from ideal, although minimally invasive surgery can be effective. Further research into the pathophysiology of this common condition will hopefully guide future developments in disease management.

Intra-regional and inter-regional abnormalities and cognitive control deficits in young adult smokers.

PubMed

Feng, Dan; Yuan, Kai; Li, Yangding; Cai, Chenxi; Yin, Junsen; Bi, Yanzhi; Cheng, Jiadong; Guan, Yanyan; Shi, Sha; Yu, Dahua; Jin, Chenwang; Lu, Xiaoqi; Qin, Wei; Tian, Jie

2016-06-01

Tobacco use during later adolescence and young adulthood may cause serious neurophysiological changes; rationally, it is extremely important to study the relationship between brain dysfunction and behavioral performances in young adult smokers. Previous resting state studies investigated the neural mechanisms in smokers. Unfortunately, few studies focused on spontaneous activity differences between young adult smokers and nonsmokers from both intra-regional and inter-regional levels, less is known about the association between resting state abnormalities and behavioral deficits. Therefore, we used fractional amplitude of low frequency fluctuation (fALFF) and resting state functional connectivity (RSFC) to investigate the resting state spontaneous activity differences between young adult smokers and nonsmokers. A correlation analysis was carried out to assess the relationship between neuroimaging findings and clinical information (pack-years, cigarette dependence, age of onset and craving score) as well as cognitive control deficits measured by the Stroop task. Consistent with previous addiction findings, our results revealed the resting state abnormalities within frontostriatal circuits, i.e., enhanced spontaneous activity of the caudate and reduced functional strength between the caudate and anterior cingulate cortex (ACC) in young adult smokers. Moreover, the fALFF values of the caudate were correlated with craving and RSFC strength between the caudate and ACC was associated with the cognitive control impairments in young adult smokers. Our findings could lead to a better understanding of intrinsic functional architecture of baseline brain activity in young smokers by providing regional and brain circuit spontaneous neuronal activity properties as well as their association with cognitive control impairments.

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

PubMed

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

2016-06-01

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

Implications of Recent Drug Approvals for Older Adults

PubMed Central

Eisenhower, Christine; Koronkowski, Michael; Marcum, Zachary

2016-01-01

More than 100 medications were approved by the US Food and Drug Administration as new drugs or for new indications in 2014 and 2015. Several of the new drugs may benefit older adults, but adverse events and pharmacokinetic changes due to aging must be considered. This article will focus on three recently approved drugs that are marketed for chronic conditions that can affect older adults: suvorexant, for treatment of insomnia; edoxaban, for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and for treatment of venous thromboembolism; and droxidopa, for treatment of symptomatic neurogenic orthostatic hypotension. Information about indications, mechanisms of action, dosing, efficacy, and safety are reviewed. The place of each agent in therapy for older adults is also discussed. PMID:27340374

Diagnosing and treating neurogenic orthostatic hypotension in primary care.

PubMed

Kuritzky, Louis; Espay, Alberto J; Gelblum, Jeffrey; Payne, Richard; Dietrich, Eric

2015-01-01

In response to a change in posture from supine or sitting to standing, autonomic reflexes normally maintain blood pressure (BP) by selective increases in arteriovenous resistance and by increased cardiac output, ensuring continued perfusion of the central nervous system. In neurogenic orthostatic hypotension (NOH), inadequate vasoconstriction and cardiac output cause BP to drop excessively, resulting in inadequate perfusion, with predictable symptoms such as dizziness, lightheadedness and falls. The condition may represent a central failure of baroreceptor signals to modulate cardiovascular function, a peripheral failure of norepinephrine release from cardiovascular sympathetic nerve endings, or both. Symptomatic patients may benefit from both non-pharmacologic and pharmacologic interventions. Among the latter, two pressor agents have been approved by the US Food and Drug Administration: the sympathomimetic prodrug midodrine, approved in 1996 for symptomatic orthostatic hypotension, and the norepinephrine prodrug droxidopa, approved in 2014, which is indicated for the treatment of symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson's disease, multiple system atrophy and pure autonomic failure). A wide variety of off-label options also have been described (e.g. the synthetic mineralocorticoid fludrocortisone). Because pressor agents may promote supine hypertension, NOH management requires monitoring of supine BP and also lifestyle measures to minimize supine BP increases (e.g. head-of-bed elevation). However, NOH has been associated with cognitive impairment and increases a patient's risk of syncope and falls, with the potential for serious consequences. Hence, concerns about supine hypertension - for which the long-term prognosis in patients with NOH is yet to be established - must sometimes be balanced by the need to address a patient's immediate risks.

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

PubMed

Cotta, Ana; Paim, Julia Filardi; da-Cunha-Junior, Antonio Lopes; Neto, Rafael Xavier; Nunes, Simone Vilela; Navarro, Monica Magalhaes; Valicek, Jaquelin; Carvalho, Elmano; Yamamoto, Lydia U; Almeida, Camila F; Braz, Shelida Vasconcelos; Takata, Reinaldo Issao; Vainzof, Mariz

2014-01-01

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. 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. 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.

Sacral neuromodulation for the treatment of neurogenic lower urinary tract dysfunction caused by multiple sclerosis: a single-centre prospective series.

PubMed

Engeler, Daniel S; Meyer, Daniel; Abt, Dominik; Müller, Stefanie; Schmid, Hans-Peter

2015-10-23

Sacral neuromodulation is well established in the treatment of refractory, non-neurogenic lower urinary tract dysfunction, but its efficacy and safety in patients with lower urinary tract dysfunction of neurological origin is unclear. Only few case series have been reported for multiple sclerosis. We prospectively evaluated the efficacy and safety of sacral neuromodulation in patients with multiple sclerosis. Seventeen patients (13 women, 4 men) treated with sacral neuromodulation for refractory neurogenic lower urinary tract dysfunction caused by multiple sclerosis were prospectively enrolled (2007-2011). Patients had to have stable disease and confirmed neurogenic lower urinary tract dysfunction. Voiding variables, adverse events, and subjective satisfaction were assessed. Sixteen (94 %) patients had a positive test phase with a >70 % improvement. After implantation of the pulse generator (InterStim II), the improvement in voiding variables persisted. At 3 years, the median voided volume had improved significantly from 125 (range 0 to 350) to 265 ml (range 200 to 350) (p < 0.001), the post void residual from 170 (range 0 to 730) to 25 ml (range 0 to 300) (p = 0.01), micturition frequency from 12 (range 6 to 20) to 7 (range 4 to 12) (p = 0.003), and number of incontinence episodes from 3 (range 0 to 10) to 0 (range 0 to 1) (p = 0.006). The median subjective degree of satisfaction was 80 %. Only two patients developed lack of benefit. No major complications occurred. Chronic sacral neuromodulation promises to be an effective and safe treatment of refractory neurogenic lower urinary tract dysfunction in selected patients with multiple sclerosis.

A critical review of recent clinical practice guidelines on the diagnosis and treatment of non-neurogenic male lower urinary tract symptoms

PubMed Central

Chua, Michael Erlano; Mendoza, Jonathan; See, Manuel; Esmena, Ednalyn; Aguila, Dean; Silangcruz, Jan Michael; Reyes, Buenaventura Jose; Luna, Saturnino; Morales, Marcelino

2015-01-01

Introduction: We provide an overview of the quality of recent clinical clinical practice guidelines (CPGs) for non-neurogenic male lower urinary tract symptoms (LUTS) and summarize the recommendations for their diagnosis, assessment, and treatment. Methods: We systematically searched recent (2008–2013) CPGs for non-neurogenic male LUTS. Eligible CPGs were assessed and appraised using Appraisal of Guidelines, Research and Evaluation II (AGREE II) tool by a CPG-appraisal group. The appraisal scores for each guideline were summarized according to each domain and in total. A recommendation summary was made across the guidelines for diagnostics, conservative management, medical, minimally invasive therapy, and surgical management. Results: A total of 8 guidelines were considered. According to AGREE II appraisal of guidelines, the National Institute for Health and Clinical Excellence (NICE), American Urological Association (AUA) and European Association of Urology (EAU) consistently scored high on the guideline domains assessed. Recommendations on diagnostics, conservative management, medical, and surgical management were consistent among the top 3 guidelines. However, we noted a discrepancy in recommending minimally invasive therapy as an alternative management of moderate to severe or bothersome non-neurogenic male LUTS secondary to benign prostatic enlargement (BPE); the NICE guideline, in particular, does not recommend using minimally invasive therapy. Conclusion: The quality of recent CPGs on non-neurogenic male LUTS was appraised and summarized. The guidelines from NICE, AUA and EAU were considered highly compliant to the AGREE II proposition for guideline formation and development. PMID:26279717

A critical review of recent clinical practice guidelines on the diagnosis and treatment of non-neurogenic male lower urinary tract symptoms.

PubMed

Chua, Michael Erlano; Mendoza, Jonathan; See, Manuel; Esmena, Ednalyn; Aguila, Dean; Silangcruz, Jan Michael; Reyes, Buenaventura Jose; Luna, Saturnino; Morales, Marcelino

2015-01-01

We provide an overview of the quality of recent clinical clinical practice guidelines (CPGs) for non-neurogenic male lower urinary tract symptoms (LUTS) and summarize the recommendations for their diagnosis, assessment, and treatment. We systematically searched recent (2008-2013) CPGs for non-neurogenic male LUTS. Eligible CPGs were assessed and appraised using Appraisal of Guidelines, Research and Evaluation II (AGREE II) tool by a CPG-appraisal group. The appraisal scores for each guideline were summarized according to each domain and in total. A recommendation summary was made across the guidelines for diagnostics, conservative management, medical, minimally invasive therapy, and surgical management. A total of 8 guidelines were considered. According to AGREE II appraisal of guidelines, the National Institute for Health and Clinical Excellence (NICE), American Urological Association (AUA) and European Association of Urology (EAU) consistently scored high on the guideline domains assessed. Recommendations on diagnostics, conservative management, medical, and surgical management were consistent among the top 3 guidelines. However, we noted a discrepancy in recommending minimally invasive therapy as an alternative management of moderate to severe or bothersome non-neurogenic male LUTS secondary to benign prostatic enlargement (BPE); the NICE guideline, in particular, does not recommend using minimally invasive therapy. The quality of recent CPGs on non-neurogenic male LUTS was appraised and summarized. The guidelines from NICE, AUA and EAU were considered highly compliant to the AGREE II proposition for guideline formation and development.

Ceftolozane/tazobactam for febrile UTI due to multidrug-resistant Pseudomonas aeruginosa in a patient with neurogenic bladder.

PubMed

Dinh, Aurélien; Davido, Benjamin; Calin, Ruxandra; Paquereau, Julie; Duran, Clara; Bouchand, Frédérique; Phé, Véronique; Chartier-Kastler, Emmanuel; Rottman, Martin; Salomon, Jérôme; Plésiat, Patrick; Potron, Anaïs

2017-01-01

Urinary tract infections (UTI) are a major public health problem among spinal cord injury (SCI) patients. They frequently involve multidrug-resistant (MDR) bacteria. Ceftolozane/tazobactam (C/T) is a novel antibiotic combination approved for complicated intra-abdominal and UTI caused by Gram-positive and Gram-negative organisms, including some MDR strains. Little is known about the use of this agent for complicated febrile UTI occurring among SCI patients with neurogenic bladder due to MDR Pseudomonas aeruginosa (PSA). We describe the case of a 35-year-old man with SCI due to multiple sclerosis, with a neurogenic bladder necessitating a bilateral nephrostomy and double J catheter, who developed a febrile UTI due to a MDR PSA, which was susceptible only to amikacin and colistin. Because of this MDR phenotype and the underlying kidney disease, a 1000 mg (1000 mg per 500 mg) dose of C/T was given as monotherapy every 8 h for 7 days, after 3 days of colistin and amikacin. Thanks to this treatment, the patient had a favorable outcome with no clinical signs of UTI or positive urine culture up to 1 month after diagnosis. C/T seems to be an effective and safe therapeutic option for febrile UTI due to MDR PSA in SCI patients with neurogenic bladder, even when administered in monotherapy for 10 days.

CGRP and nitric oxide of neuronal origin and their involvement in neurogenic vasodilatation in rat skin microvasculature

PubMed Central

Merhi, Merhi; Dusting, Greg J; Khalil, Zeinab

1998-01-01

Sensory nerves are important for the initiation of neurogenic inflammation and tissue repair. Both calcitonin gene-related peptide (CGRP) and nitric oxide (NO) have been implicated in neurogenic vasodilatation and inflammatory responses.A blister model in the rat hind footpad was used as a site to induce neurogenic vasodilatation in response to antidromic electrical stimulation of the sciatic nerve. Blood flux was monitored with a laser Doppler flow monitor.The quantitative contributions of CGRP and NO to vasodilatation were examined by use of the CGRP receptor antagonist CGRP8-37 and NO synthase inhibitors 7-nitroindazole (7-NI), 3-bromo 7-NI and NG-nitro L-arginine methyl ester (L-NAME). The potential modulatory role of endothelin was examined by use of the ETA receptor antagonist BQ-123.CGRP8-37 (10 μM) was perfused over the blister base before nerve stimulation and continuously throughout the post-stimulation period, resulting in a significant reduction (41%) in the blood flux vascular response.Pretreatment with the specific neuronal NO synthase inhibitors, 7-NI and 3-bromo 7-NI (10 mg kg−1, i.v.), and of the non-specific L-NAME (100 μM), resulted in significant inhibition of the blood flux response (36%, 72% and 57% decrease, respectively). In contrast, 7-NI treatment in young rats pretreated with capsaicin had no further effect on the vascular response, suggesting that the source of NO is the sensory nerves.BQ-123 (10 μM) significantly enhanced the stimulation-induced blood flux response (61% increase). When 7-NI was co-administered with either CGRP8-37 or BQ-123, the drug actions were additive, suggesting that there was no interaction between NO and CGRP or endothelin.These data suggest that both NO and CGRP participate in neurogenic vasodilatation in rat skin microvasculature and that this response is modulated by endogenous endothelin. PMID:9535014

Nitric oxide negatively regulates mammalian adult neurogenesis

NASA Astrophysics Data System (ADS)

Packer, Michael A.; Stasiv, Yuri; Benraiss, Abdellatif; Chmielnicki, Eva; Grinberg, Alexander; Westphal, Heiner; Goldman, Steven A.; Enikolopov, Grigori

2003-08-01

Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system.

Abdominal massage for neurogenic bowel dysfunction in people with multiple sclerosis (AMBER - Abdominal Massage for Bowel Dysfunction Effectiveness Research): study protocol for a randomised controlled trial.

PubMed

McClurg, Doreen; Goodman, Kirsteen; Hagen, Suzanne; Harris, Fional; Treweek, Sean; Emmanuel, Anton; Norton, Christine; Coggrave, Maureen; Doran, Selina; Norrie, John; Donnan, Peter; Mason, Helen; Manoukian, Sarkis

2017-03-29

Multiple sclerosis (MS) is a life-long condition primarily affecting younger adults. Neurogenic bowel dysfunction (NBD) occurs in 50-80% of these patients and is the term used to describe constipation and faecal incontinence, which often co-exist. Data from a pilot study suggested feasibility of using abdominal massage for the relief of constipation, but the effectiveness remains uncertain. This is a multi-centred patient randomised superiority trial comparing an experimental strategy of once daily abdominal massage for 6 weeks against a control strategy of no massage in people with MS who have stated that their constipation is bothersome. The primary outcome is the Neurogenic Bowel Dysfunction Score at 24 weeks. Both groups will receive optimised advice plus the MS Society booklet on bowel management in MS, and will continue to receive usual care. Participants and their clinicians will not be blinded to the allocated intervention. Outcome measures are primarily self-reported and submitted anonymously. Central trial staff who will manage and analyse the trial data will be unaware of participant allocations. Analysis will follow intention-to-treat principles. This pragmatic randomised controlled trial will demonstrate if abdominal massage is an effective, cost-effective and viable addition to the treatment of NBD in people with MS. ClinicalTrials.gov, ISRCTN85007023 . Registered on 10 June 2014.

Dorsal and ventral hippocampal adult-born neurons contribute to context fear memory.

PubMed

Huckleberry, Kylie A; Shue, Francis; Copeland, Taylor; Chitwood, Raymond A; Yin, Weiling; Drew, Michael R

2018-06-02

The hippocampus contains one of the few neurogenic niches within the adult brain-the subgranular zone of the dentate gyrus. The functional significance of adult-born neurons in this region has been characterized using context fear conditioning, a Pavlovian paradigm in which animals learn to associate a location with danger. Ablation or silencing of adult-born neurons impairs both acquisition and recall of contextual fear conditioning, suggesting that these neurons contribute importantly to hippocampal memory. Lesion studies indicate that CFC depends on neural activity in both the dorsal and ventral hippocampus, subregions with unique extrahippocampal connectivity and behavioral functions. Because most studies of adult neurogenesis have relied on methods that permanently ablate neurogenesis throughout the entire hippocampus, little is known about how the function of adult-born neurons varies along the dorsal-ventral axis. Using a Nestin-CreER T2 mouse line to target the optogenetic silencer Archaerhodopsin to adult-born neurons, we compared the contribution of dorsal and ventral adult-born neurons to acquisition, recall, and generalization of CFC. Acquisition of CFC was impaired when either dorsal or ventral adult-born neurons were silenced during training. Silencing dorsal or ventral adult-born neurons during test sessions decreased context-evoked freezing but did not impair freezing in a hippocampus-independent tone-shock freezing paradigm. Silencing adult-born neurons modestly reduced generalization of fear. Our data indicate that adult-born neurons in the dorsal and ventral hippocampus contribute to both memory acquisition and recall. The comparatively large behavioral effects of silencing a small number of adult-born neurons suggest that these neurons make a unique and powerful contribution to hippocampal function.

The Effect of Recombinant Tyrosine Hydroxylase Expression on the Neurogenic Differentiation Potency of Mesenchymal Stem Cells

PubMed Central

Duruksu, Gokhan; Karaoz, Erdal

2018-01-01

Objective Tyrosine hydroxylase (TH) is a rate-limiting enzyme in dopamine synthesis, making the enhancement of its activity a target for ensuring sufficient dopamine levels. Rat bone marrow mesenchymal stem cells (rBM-MSCs) are known to synthesize TH after differentiating into neuronal cells through chemical induction, but the effect of its ectopic expression on these cells has not yet been determined. This study investigated the effects of ectopic recombinant TH expression on the stemness characteristics of rBM-MSCs. Methods After cloning, a cell line with stable TH expression was maintained, and the proliferation, the gene expression profile, and differentiation potential of rBM-MSCs were analyzed. Analysis of the cells showed an increment in the proliferation rate that could be reversed by the neutralization of TH. Results The constitutive expression of TH in rBM-MSCs was successfully implemented, without significantly affecting their osteogenic and adipogenic differentiation potential. TH expression improved the expression of other neuronal markers, such as glial fibrillary acidic protein, β-tubulin, nestin, and c-Fos, confirming the neurogenic differentiation capacity of the stem cells. The expression of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) significantly increased after the chemical induction of neurogenic differentiation. Conclusion In this study, the expression of recombinant TH improved the neuroprotective effect of MSCs by upregulating the expression of BDNF and CNTF. Although the neuronal markers were upregulated, the expression of recombinant TH alone in rBM-MSCs was not sufficient for MSCs to differentiate into neurogenic cell lines. PMID:29656620

Etiology of Childhood Infectious Diarrhea in a Developed Region of China: Compared to Childhood Diarrhea in a Developing Region and Adult Diarrhea in a Developed Region.

PubMed

Wang, Xin; Wang, Jing; Sun, Hao; Xia, Shengli; Duan, Ran; Liang, Junrong; Xiao, Yuchun; Qiu, Haiyan; Shan, Guangliang; Jing, Huaiqi

2015-01-01

In China, great differences in economy, social characteristics and hygiene exist between developing and developed regions. A comparative study of infectious diarrhea between two regions was needed. Three groups of diarrheal patients were collected: children ≤5 year-olds from Beijing (developed region) and Henan Province (developing region), and adults over 18 year-olds from Beijing. A questionnaire was used to survey and feces samples were examined for 16 enteropathogens. We enrolled 1422 children and 1047 adults from developed region and 755 children from developing region. Virus positive rates were 32.98% for children and 23.67% for adults in developed region. The most prevalent pathogen for children was rotavirus whereas for adults was norovirus. Bacterial isolation rates were 13.92% for children from developed region, while 29.14% for children from the developing regions. For the greatest difference, Shigella accounted for 50.79% and was the dominant pathogen in the developing region, whereas in the developed region it was only 1.45%. There was no significant relationship between the local levels of development with diarrheogenic Escherichia coli (DEC) categories. But it was seen the notable differences between the population with different age: enteropathogenic E.coli (EPEC) and enteroaggregative E.coli (EAggEC) were the primary classes of DEC in children from both regions, whereas it was enterotoxigenic E.coli (ETEC) in adults. The symptoms of Shigella and Salmonella infection, such as bloody stools, white blood cells (WBC) and red blood cells (RBC) positivity and fever were similar in children, which may lead to the misidentification. Yersinia enterocolitica and shiga toxin-producing E.coli (STEC) infections were firstly reported in Beijing. There was a large difference in etiology of bacterial diarrhea between children in developing and developed regions of China.

Assessment of neurogenic bowel dysfunction impact after spinal cord injury using the International Classification of Functioning, Disability and Health.

PubMed

Pires, Jennifer M; Ferreira, Ana M; Rocha, Filipa; Andrade, Luis G; Campos, Inês; Margalho, Paulo; Laíns, Jorge

2018-05-09

Bowel function is frequently compromised after spinal cord injury (SCI). Regardless of this crucial importance in patients' lives, there is still scarce literature on the Neurogenic Bowel Dysfunction (NBD) deleterious impact on SCI patient's lives and only few studies correlating NBD severity with quality of life (QoL). To our knowledge there are no studies assessing the impact of NBD on the context of ICF domains. To assess NBD after SCI using ICF domains and to assess its impact in QoL. Retrospective data analysis and cross-sectional phone survey. Outpatient spinal cord injury setting. Portuguese adult spinal cord injury patients. Retrospective analysis of demographic data, lesion characteristics and bowel management methods at last inpatient discharge. Cross-sectional phone survey assessing current bowel management methods, the Neurogenic Bowel Dysfunction Score and a Likert scale questionnaire about the impact on ICF domains and QoL. 64 patients answered the questionnaire. The majority was male (65.6%), mean age 56.6±15.6 years, AIS A lesion (39.1%), with a traumatic cause (71.9%). The main bowel management methods were contact laxatives, suppositories and osmotic laxatives. 50.1% of patients scored moderate or severe NBD. Considering ICF domains, the greatest impact was in personal and environmental factors, with 39.1% reporting impact in financial costs, 45.3% in need of assistance, 45.3% in emotional health and 46.9% in loss of privacy. There was a significant association between severity of NBD and negative impact on QoL (p<0.05). The study confirms the major impact of NBD on personal and environmental factors of ICF and on the quality of life of SCI population. These findings confirm that it is relevant to identify the main ICF domains affected by NBD after SCI in order to address targeted interventions, working toward changes in health policies and psychosocial aspects.

Nuclear translocation of PKCα isoenzyme is involved in neurogenic commitment of human neural crest-derived periodontal ligament stem cells.

PubMed

Trubiani, Oriana; Guarnieri, Simone; Diomede, Francesca; Mariggiò, Maria A; Merciaro, Ilaria; Morabito, Caterina; Cavalcanti, Marcos F X B; Cocco, Lucio; Ramazzotti, Giulia

2016-11-01

Stem cells isolated from human adult tissue niche represent a promising source for neural differentiation. Human Periodontal Ligament Stem Cells (hPDLSCs) originating from the neural crest are particularly suitable for induction of neural commitment. In this study, under xeno-free culture conditions, in undifferentiated hPDLSCs and in hPDLSCs induced to neuronal differentiation by basic Fibroblast Growth Factor, the level of some neural markers have been analyzed. The hPDLSCs spontaneously express Nestin, a neural progenitor marker. In these cells, the neurogenic process induced to rearrange the cytoskeleton, form neurospheres and express higher levels of Nestin and Tyrosine Hydroxylase, indicating neural induction. Protein Kinase C (PKC) is highly expressed in neural tissue and has a key role in neuronal functions. In particular the Ca(2+) and diacylglycerol-dependent activation of PKCα isozyme is involved in the regulation of neuronal differentiation. Another main component of the pathways controlling neuronal differentiation is the Growth Associated Protein-43 (GAP-43), whose activity is strictly regulated by PKC. The aim of this study is to investigate the role of PKCα/GAP-43 nuclear signal transduction pathway during neuronal commitment of hPDLSCs. During hPDLSCs neurogenic commitment the levels of p-PKC and p-GAP-43 increased both in cytoplasmic and nuclear compartment. PKCα nuclear translocation induced GAP-43 movement to the cytoplasm, where it is known to regulate growth cone dynamics and neuronal differentiation. Moreover, the degree of cytosolic Ca(2+) mobilization appeared to be more pronounced in differentiated hPDLSCs than in undifferentiated cells. This study provides evidences of a new PKCα/GAP-43 nuclear signalling pathway that controls neuronal differentiation in hPDLSCs, leading the way to a potential use of these cells in cell-based therapy in neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Reliability of cystometrically obtained intravesical pressures in patients with neurogenic bladders.

PubMed

Hess, Marika J; Lim, Lance; Yalla, Subbarao V

2002-01-01

Urodynamic studies in patients with neurogenic bladder detect and categorize neurourodynamic states, identify the risk for urologic sequelae, and determine the necessity for interventions. Because urodynamic studies serves as a prognostic indicator and guides patient management, pressure measurements during the study must accurately represent bladder function under physiologic conditions. Because nonphysiologic bladder filling used during conventional urodynamic studies may alter the bladder's accommodative properties, we studied how closely the intravesical pressures obtained before filling cystometry resembled those obtained during the filling phase of the cystometrogram. Twenty-two patients (21 men, 1 woman) with neurogenic bladders underwent standard urodynamic studies. A 16F triple-lumen catheter was inserted into the bladder, and the intravesical pressures were recorded (physiologic volume-specific pressures, PVSP). After emptying the bladder, an equal volume of normal saline solution was reinfused, and the pressures were recorded again (cystometric volume-specific pressure, CVSP). All patients underwent routine fluoroscopically assisted urodynamic testing. The PVSP and the CVSP were compared using the Wilcoxon signed ranks test. P value of .05 was significant. The mean PVSP was 14.5 cmH2O (range, 4-42 cmH2O) and mean CVSP was 20.6 cmH2O (range, 6-70 cmH2O). The CVSP was significantly higher than the PVSP (P = .01). Filling pressures during cystometry (CVSP) were significantly higher than the pressures measured at rest (PVSP). This study also suggests a strong correlation between PVSP and CVSP.

Females have stronger neurogenic response than males after non-specific nasal challenge in patients with seasonal allergic rhinitis.

PubMed

Tomljenovic, Dejan; Baudoin, Tomislav; Megla, Zeljka Bukovec; Geber, Goran; Scadding, Glenis; Kalogjera, Livije

2018-07-01

Epidemiological studies show female predominance in the prevalence of non- allergic rhinitis (NAR) and local allergic rhinitis (LAR). Experimental studies show female patients with allergic rhinitis (AR) demonstrate higher levels of sensitivity to irritants and airway hyperresponsiveness than males. Bronchial asthma shows female predominance in post-puberty patients, and gender interaction with severe asthma endotypes. Fibromyalgia, chronic fatigue syndrome, migraine and chronic cough, syndromes, which are commonly related to neurokinin substance P (SP) in the literature, also show strong female predominance. Studies have demonstrated that sex hormones, primarily oestrogens, affect mast cell activation. Mast cell proteases can amplify neurogenic inflammatory responses including the release of SP. Based on human epidemiological data and animal experimental data we hypothesized that female patients have different interaction between mast cell activation and neurogenic inflammation, i.e. substance P release, resulting in a different nasal symptom profile. To test the hypothesis we performed allergen and non-specific nasal challenges in patients with seasonal allergic rhinitis (SAR) out of season and looked for gender differences in subjective and objective responses. The interaction between subjective and objective reactivity was evaluated through the comparison of subjective symptom scores, concentrations of neurokinin substance P (SP) and cellular markers in nasal lavages after low doses of nasal allergen challenges. Female allergic subjects tended to have higher substance P (SP) concentrations both before and after non-specific challenges. The difference between post-allergen and post - hypertonic saline (HTS) challenge was highly significant in female patients (p = 0.001), while insignificant in male subjects (p = 0.14). Female patients had significantly stronger burning sensation after HTS challenge than male. These data indicate difference in the

Adult Neurogenesis and Neurodegenerative Diseases: A Systems Biology Perspective

PubMed Central

Horgusluoglu, Emrin; Nudelman, Kelly; Nho, Kwangsik; Saykin, Andrew J.

2016-01-01

New neurons are generated throughout adulthood in two regions of the brain, the olfactory bulb and dentate gyrus of the hippocampus, and are incorporated into the hippocampal network circuitry; disruption of this process has been postulated to contribute to neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Known modulators of adult neurogenesis include signal transduction pathways, the vascular and immune systems, metabolic factors, and epigenetic regulation. Multiple intrinsic and extrinsic factors such as neurotrophic factors, transcription factors, and cell cycle regulators control neural stem cell proliferation, maintenance in the adult neurogenic niche, and differentiation into mature neurons; these factors act in networks of signaling molecules that influence each other during construction and maintenance of neural circuits, and in turn contribute to learning and memory. The immune system and vascular system are necessary for neuronal formation and neural stem cell fate determination. Inflammatory cytokines regulate adult neurogenesis in response to immune system activation, whereas the vasculature regulates the neural stem cell niche. Vasculature, immune/support cell populations (microglia/astrocytes), adhesion molecules, growth factors, and the extracellular matrix also provide a homing environment for neural stem cells. Epigenetic changes during hippocampal neurogenesis also impact memory and learning. Some genetic variations in neurogenesis related genes may play important roles in the alteration of neural stem cells differentiation into new born neurons during adult neurogenesis, with important therapeutic implications. In this review, we discuss mechanisms of and interactions between these modulators of adult neurogenesis, as well as implications for neurodegenerative disease and current therapeutic research. PMID:26879907

A novel intracerebral hemorrhage-induced rat model of neurogenic voiding dysfunction: Analysis of lower urinary tract function

PubMed Central

CHO, YOUNG-SAM; KO, IL-GYU; KIM, CHANG-JU; KIM, KHAE-HAWN

2015-01-01

Neurogenic lower urinary tract dysfunction (NLUTD) is a major problem in patients with various neurological disorders, and may result in debilitating symptoms and serious complications, including chronic renal failure and recurrent urinary tract infections. Clinically, stroke is associated with voiding dysfunction. However, lower urinary tract function evaluation in an intracerebral hemorrhage (ICH) model has not, to the best of our knowledge, been reported. Therefore, in the present study, lower urinary tract function in ICH-induced rats was investigated and the results were compared with those obtained in normal rats. The effects of ICH on peripheral bladder function and central micturition centers [medial preoptic area, ventrolateral gray, pontaine micturition center and spinal cord (lumbar 4 (L4)-L5)] were also examined. Adult female Sprague-Dawley rats were divided into two groups: Control ICH-induced. Induction of ICH in the hippocampal CA1 region was performed using a stereotaxic frame and type IV collagenase. The effects of ICH on the central micturition centers were investigated by simultaneously determining the extent of neuronal activation (c-Fos) and nerve growth factor (NGF) expression, and assessing voiding function (urodynamically using cystometry). The results revealed that induction of ICH significantly enhanced bladder contraction pressure and time, while simultaneously reducing voiding pressure and time. Furthermore, the c-Fos and NGF expression levels in the neuronal voiding centers were significantly increased in the rats with induced ICH as compared with the control rats. Therefore, this ICH-induced NLUTD rat model may be a more appropriate method to analyze NLUTD in stroke patients than a cerebral infarction model, as the former more accurately reflects the nature of the hemorrhage in the two types of stroke. PMID:25954993

G-Protein-Coupled Receptors in Adult Neurogenesis

PubMed Central

Doze, Van A.

2012-01-01

The importance of adult neurogenesis has only recently been accepted, resulting in a completely new field of investigation within stem cell biology. The regulation and functional significance of adult neurogenesis is currently an area of highly active research. G-protein-coupled receptors (GPCRs) have emerged as potential modulators of adult neurogenesis. GPCRs represent a class of proteins with significant clinical importance, because approximately 30% of all modern therapeutic treatments target these receptors. GPCRs bind to a large class of neurotransmitters and neuromodulators such as norepinephrine, dopamine, and serotonin. Besides their typical role in cellular communication, GPCRs are expressed on adult neural stem cells and their progenitors that relay specific signals to regulate the neurogenic process. This review summarizes the field of adult neurogenesis and its methods and specifies the roles of various GPCRs and their signal transduction pathways that are involved in the regulation of adult neural stem cells and their progenitors. Current evidence supporting adult neurogenesis as a model for self-repair in neuropathologic conditions, adult neural stem cell therapeutic strategies, and potential avenues for GPCR-based therapeutics are also discussed. PMID:22611178

Intermittent catheterization with hydrophilic catheters as a treatment of chronic neurogenic urinary retention.

PubMed

Chartier-Kastler, Emmanuel; Denys, Pierre

2011-01-01

Neurogenic bladder can be effectively managed with intermittent catheterization (IC) to improve or restore continence, but there is no consensus on which type of catheter is preferred. Hydrophilic catheters were developed to reduce urethral friction, thereby minimizing trauma and sticking, and making them more acceptable to the patient, and easier and safer to use. The objective of this article was to review the literature on the benefits of hydrophilic catheters in patients with neurogenic bladder. A large body of experimental and observational evidence, including randomized controlled trials, was identified using PubMed. Compared with plastic catheters that have been manually lubricated with gel, hydrophilic catheters reduce urinary tract infection and microhematuria. Hydrophilic catheters are also associated with high levels of patient satisfaction because they are comfortable to use. There is a wealth of evidence, including randomized controlled trials, to support the benefits of hydrophilic catheters in terms of safety and quality of life, especially in men with spinal cord injury. More data are required for spina bifida, multiple sclerosis, and in women. Further research is warranted, especially large-scale and long-term robust comparisons of different types of catheter, and in well-defined and stratified populations. Copyright © 2010 Wiley-Liss, Inc.

Adult Education, Social Inclusion and Cultural Diversity in Regional Communities

ERIC Educational Resources Information Center

Townsend, Rob

2008-01-01

This article presents the outcomes of recent research into adult education programs and experiences in the Shire of Campaspe, a region in northern Victoria. Research data of people from diverse cultural backgrounds reveal how individuals can utilize adult education as a space to explore their own social and cultural isolation in a regional…

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

PubMed

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

2017-02-01

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

Neurogenic detrusor overactivity in patients with spinal cord injury: evaluation and management.

PubMed

Sahai, Arun; Cortes, Eduardo; Seth, Jai; Khan, Muhammad Shamim; Panicker, Jalesh; Kelleher, Cornelius; Kessler, Thomas M; Fowler, Clare J; Dasgupta, Prokar

2011-12-01

Lower urinary tract dysfunction can have a significant impact on patients with spinal cord injury. Over the years, many treatment options have become available. This article reviews the assessment and management of neurogenic detrusor overactivity, with a particular focus on articles from the recent literature. Recent guidelines on the subject will be discussed. Management options include antimuscarinics and bladder emptying measures, botulinum toxin A, and neuromodulation in refractory cases and surgery for intractable cases. Recent and relevant publications in these areas will be summarized and discussed.

Adult Mammalian Neurogenesis and Motivated Behaviors.

PubMed

Jorgensen, Claudia

2018-05-31

Adult neurogenesis continues to captivate the curiosity of the scientific community; and researchers seem to have a particular interest in identifying the functional implications of such plasticity. While the majority of research focuses on the association between adult neurogenesis and learning and memory (including spatial learning associated with hippocampal neurogenesis and olfactory discrimination associated with neurogenesis in the olfactory system), the following review will explore the link to motivated behaviors. In particular, goal-directed behaviors such as sociosexual, parental, aggressive, as well as depression- and anxiety-like behaviors and their reciprocal association to adult neurogenesis will be evaluated. The review will detail research in humans and other mammalian species. Furthermore, the potential mechanisms underlying these neurogenic alterations will be highlighted. Lastly, the review will conclude with a discussion on the functional significance of these newly generated cells in mediating goal-directed behaviors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

[Laparoscopic cystectomy and transileal ureterostomy for neurogenic vesicosphincteric disorders. Evaluation of morbidity].

PubMed

Guillotreau, Julien; Gamé, Xavier; Castel-Lacanal, Evelyne; Mallet, Richard; De Boissezon, Xavier; Malavaud, Bernard; Marque, Philippe; Rischmann, Pascal

2007-04-01

To evaluate the morbidity and mortality of laparoscopic cystectomy combined with transileal ureterostomy to treat neurogenic vesicosphincteric disorders. Prospective study performed between february 2004 and april 2006 on 26 consecutive patients with a mean age of 55.0 +/- 12.7 years treated by laparoscopic cystectomy for neurogenic vesicosphincteric disorders. The underlying neurological disease was multiple sclerosis (MS) in 20 cases, spinal cord injury in 4 cases and transverse myelitis in 2 cases. The median preoperative ASA score was 3 (range: 2-3). No open conversion was necessary. One intraoperative complication was observed (vascular injury). No perioperative death was observed. The nasogastric tube was maintained postoperatively for an average of 8.69 +/- 5.9 hours. The mean time to resumption of oral fluids was 1.4 +/- 0.7 days and mean time to resumption of solids was 2.6 +/- 1.0 days. The mean time to resumption of bowel movements was 3.8 +/- 3.2 days. The mean intensive care stay was 3.9 +/- 1.1 days. Two postoperative complications were observed in the same patient (ileus and bronchial congestion). Postoperative narcotic analgesics were necessary in 60% of cases. The mean hospital stay was 10.3 +/- 4.1 days. Two late postoperative complications were observed in the same patient (two episodes of pyelonephritis). Laparoscopic cystectomy has a low morbidity in neurological patients, allowing early return of feeding and a moderate length of hospital stay.

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

PubMed

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

2006-09-01

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

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

PubMed

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

2014-08-01

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

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

Anxiety and the aging brain: stressed out over p53?

PubMed

Scrable, Heidi; Burns-Cusato, Melissa; Medrano, Silvia

2009-12-01

We propose a model in which cell loss in the aging brain is seen as a root cause of behavioral changes that compromise quality of life, including the onset of generalized anxiety disorder, in elderly individuals. According to this model, as stem cells in neurogenic regions of the adult brain lose regenerative capacity, worn-out, dead, or damaged neurons fail to be replaced, leaving gaps in function. As most replacement involves inhibitory interneurons, either directly or indirectly, the net result is the acquisition over time of a hyper-excitable state. The stress axis is subserved by all three neurogenic regions in the adult brain, making it particularly susceptible to these age-dependent changes. We outline a molecular mechanism by which hyper-excitation of the stress axis in turn activates the tumor suppressor p53. This reinforces the loss of stem cell proliferative capacity and interferes with the feedback mechanism by which the glucocorticoid receptor turns off neuroendocrine pathways and resets the axis.

Screening for depression and anxiety in childhood neurogenic bladder dysfunction.

PubMed

Kabra, Aashish T; Feustel, Paul J; Kogan, Barry A

2015-04-01

Patients with chronic illnesses are known to have anxiety disorders and are likely to be depressed. Anxiety and depression (A/D) has been studied in adults with spina bifida (SB), however, no study has directly screened for A/D in pediatric patients with neurogenic bladder (NB) and their caregivers. The aims of our study were to determine the prevalence of A/D in caregivers of all children with SB and other NB dysfunction and in adolescents with validated screening measures. This was a preliminary cross-sectional screening investigation for A/D in pediatric patients with NB and their caregivers and adolescents with NB. Pediatric patients were defined as ages birth to 19 years and adolescents as ages 10 years-19 years. A caregiver was self-defined as a primary parent/guardian who took care of the pediatric patient for a majority of their time on a daily basis. We contacted 75 families by mail, of which 15 returned the consent and completed the questionnaires. Subsequently, 25 consecutive families whose children were seen for routine office appointments by the pediatric urology service at the Albany Medical Center in New York participated in person. 22 adolescents completed the Hospital Anxiety and Depression Scale (HADS). 47 caregivers completed both the HADS and the Center for Epidemiologic Studies Depression Scale (CES-D). Depression among adolescents: Of the 22 adolescents who completed the HADS, the median HADS score was 5.5 (Inter-quartile range (IQR): 1.75-8.75) for anxiety and 1.5 (IQR: 0-4.25) for depression; both scores were within the normal range (<8/21). Individual abnormal HADS scores (≥8/21) were seen in 6/22 (27%) for anxiety and 1/22 (5%) for depression. Anxiety and depression among caregivers: Of the 47 caregivers who completed the HADS and CES-D, the median HADS score was 7 (IQR: 4-11) for anxiety and 4 (IQR: 1-7) for depression; both scores were within the normal range. Individual abnormal HADS scores were seen in 23/47 (49%) for anxiety and 10

Extragonadal germ cell tumour with the "burned out" phenomenon mimicking a retroperitioneal tumour of neurogenic origin.

PubMed

González, Rocío; Montoto Santomé, Paula; Iglesias Porto, Eva; Pérez Moreiras, M Isabel; Salem Ali, Mohammed; Mateo Cambón, Luis A; Bal Nieves, Fernando; Arija Val, J Felix

2012-12-01

To describe a case of retroperitoneal metastasis of a gonadal germ cell tumour with the "burned-out" phenomenon in a 35 year old patient with a suspected diagnosis of retroperitoneal tumour of neurogenic origin. With the clinical and radiological suspicion of retroperitoneal tumour of neurogenic origin the tumour was removed, via the retroperitoneal space. Pathology showed classic seminoma with foci of atypical or anaplastic seminoma, confined to the tissue sample. After a genital examination showing no alterations, a scrotal ultrasound was requested. This revealed a badly delimited hypoechogenic mass with microcalcifications in the left testis and a heterogeneous echostructure in the right testis, with hypoechogenic areas and some microcalcification. Bilateral orchiectomy was performed, with a pathological study compatible with residual scar tissue in the left testicle and focal findings of germ cell neoplasia, with no intratubular seminoma in the right testis. The suspicion of an extragonadal germ cell tumour with the "burned-out" phenomenon modifies the therapeutic attitude, which should begin with orchiectomy, followed by systemic chemotherapy and the surgery kept in reserve for those cases where residual malignant tissue persists.

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

PubMed

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

2017-03-02

Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2 + neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

Lack of genetic association of neutral endopeptidase (NEP) with complex regional pain syndrome (CRPS).

PubMed

Huehne, Kathrin; Schaal, Ute; Leis, Stefan; Uebe, Steffen; Gosso, M Florencia; van den Maagdenberg, Arn M J M; Maihöfner, Christian; Birklein, Frank; Rautenstrauss, Bernd; Winterpacht, Andreas

2010-03-12

Complex regional pain syndrome (CRPS) is a condition that is characterized by severe pain and exaggerated neurogenic inflammation, which may develop after injury or surgery. Neurogenic inflammation is mediated by neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P (SP) that are released from nociceptors. Genetic factors may play a role in CRPS as was suggested by the occurrence of familial cases and several genetic association studies investigating mainly the human leukocyte antigen (HLA) system. Here we investigated the role of neutral endopeptidase (NEP), a key enzyme in neuropeptide catabolism. NEP dysfunction resulting in reduced inactivation of neuropeptides may be a possible pathomechanism in CRPS. To this end, we tested a GT-repeat polymorphism in the NEP promoter region as well as 18 tag-SNPs in six linkage disequilibrium (LD) blocks in the NEP gene region in 320 CRPS patients and 376 controls. No significant genetic association was observed. Thus, we conclude that the NEP gene does not seem to be a major risk factor for CRPS. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Prospective study of the impact on quality of life of cystectomy with ileal conduit urinary diversion for neurogenic bladder dysfunction.

PubMed

Guillotreau, Julien; Castel-Lacanal, Evelyne; Roumiguié, Mathieu; Bordier, Benoit; Doumerc, Nicolas; De Boissezon, Xavier; Malavaud, Bernard; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

2011-11-01

Neurogenic bladder dysfunction has a negative impact on the patient's quality of life (QoL). Cystectomy with ileal conduit urinary diversion is a treatment option in patients in failure after conservative management. The objective of this study was to evaluate the impact of ileal conduit urinary diversion on the QoL of patients with neurogenic bladder dysfunction. From March 2004 to November 2010, 48 patients (36 women and 12 men with a mean age of 50.6  ±  11.8 years) treated by cystectomy with ileal conduit urinary diversion for neurogenic bladder dysfunction, prospectively completed, before and after surgery, two self-administered QoL questionnaires. Neurological diseases were multiple sclerosis in 38 cases, spinal cord injury in 7 cases, and other neurological disease in 3 cases. Cystectomy was performed by laparoscopy in all patients. QoL was measured by using two self-administered questionnaires, one questionnaire specific for urinary disorders validated in neurological patients, Qualiveen®, and the generic SF36-v2® questionnaire. Data were compared by Student's t test. Comparison of the Qualiveen® self-administered questionnaire scores and indices before and after surgery showed that, after surgery, patients presented a significant reduction of limitations (0.57 ± 0.64 vs. 1.55 ± 1.35, P < 0.001), constraints (2.12  ±  0.83 vs. 2.64  ±  1.12, P = 0.046) scores and the SIUP index (1.29 ± 0.65 vs. 1.79 ± 0.95, P = 0.015). No significant change in SF36-v2® scores was observed postoperatively. Ileal conduit urinary diversion improves the urinary QoL of patients with neurogenic bladder dysfunction by decreasing limitations and constraints induced by urinary disorders, but has no impact on general QoL. Copyright © 2011 Wiley Periodicals, Inc.

Adult education and the challenges of regional development: Policy and sustainability in North Denmark

NASA Astrophysics Data System (ADS)

Rasmussen, Palle; Staugaard, Hans Jørgen

2016-10-01

Adult education is governed at many levels - internationally, nationally and locally. The authors of this paper look at the challenges, structures and practices of adult education policy at the local level, more specifically in North Denmark (Northern Jutland), one of the five administrative regions of the Danish nation-state. In many ways, the current educational challenges in this remote region of Europe are similar to what can be observed worldwide and especially in countries which are generally considered welfare states. The authors see the growing social and educational divide between the region's peripheral areas and its largest city centre as a major challenge - for society as a whole and for adult education in particular. It is from this perspective that the authors describe the present structures of adult education in the region and the strategies employed by local authorities and educational institutions. This is followed by an evaluation of both structures and efforts in terms of their ability to cope with the challenges.

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

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

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

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

PubMed

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

2015-03-02

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

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.

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

PubMed

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

2013-12-01

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

Conserved and divergent functions of Pax6 underlie species-specific neurogenic patterns in the developing amniote brain.

PubMed

Yamashita, Wataru; Takahashi, Masanori; Kikkawa, Takako; Gotoh, Hitoshi; Osumi, Noriko; Ono, Katsuhiko; Nomura, Tadashi

2018-04-16

The evolution of unique organ structures is associated with changes in conserved developmental programs. However, characterizing the functional conservation and variation of homologous transcription factors (TFs) that dictate species-specific cellular dynamics has remained elusive. Here, we dissect shared and divergent functions of Pax6 during amniote brain development. Comparative functional analyses revealed that the neurogenic function of Pax6 is highly conserved in the developing mouse and chick pallium, whereas stage-specific binary functions of Pax6 in neurogenesis are unique to mouse neuronal progenitors, consistent with Pax6-dependent temporal regulation of Notch signaling. Furthermore, we identified that Pax6-dependent enhancer activity of Dbx1 is extensively conserved between mammals and chick, although Dbx1 expression in the developing pallium is highly divergent in these species. Our results suggest that spatiotemporal changes in Pax6-dependent regulatory programs contributed to species-specific neurogenic patterns in mammalian and avian lineages, which underlie the morphological divergence of the amniote pallial architectures. © 2018. Published by The Company of Biologists Ltd.

Effect of CB1 Ligands on Neurogenic and Myogenic Contractile Responses in the Guinea-Pig Ileum.

PubMed

Donnerer, Josef; Liebmann, Ingrid

2018-01-01

This study aimed at investigating whether the synthetic cannabinoid receptor agonist (+)-WIN 55212-2 has neurogenic and myogenic relaxant effects on the longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum. (+)-WIN 55212-2, 1-1,000 nmol/L, concentration-dependently inhibited both the electrical stimulation-induced cholinergic twitch responses as well as the myogenic smooth muscle contractions in the LMMP preparation. SR-141716A (rimonabant) 1-1,000 nmol/L, the cannabinoid CB1 receptor antagonist, being without effect on its own, antagonized the (+)-WIN 55212-2-induced effects. The allyl isothiocyanate (mustard oil, 100 µmol/L) induced a relaxant effect in the guinea-pig ileum, which can be regarded as neurogenic and myogenic, was augmented by (+)-WIN 55212-2, and inhibited by SR-141716A. (+)-WIN 55212-2 only moderately modified the 60 mmol/L KCl-evoked contractions. These results provide functional evidence that the CB1 agonist (+)-WIN 55212-2-induced inhibitory effects in the guinea-pig ileum are exerted both at the neuronal as well as at the intestinal smooth muscle cell level. © 2018 S. Karger AG, Basel.

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2013-01-01

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

Lifestyle Shapes the Dialogue between Environment, Microglia, and Adult Neurogenesis.

PubMed

Valero, Jorge; Paris, Iñaki; Sierra, Amanda

2016-04-20

Lifestyle modulates brain function. Diet, stress levels, and physical exercise among other factors influence the "brain cognitive reserve", that is, the capacity of the brain to maintain a normal function when confronting neurodegenerative diseases, injury, and/or aging. This cognitive reserve relays on several cellular and molecular elements that contribute to brain plasticity allowing adaptive responses to cognitive demands, and one of its key components is the hippocampal neurogenic reserve. Hippocampal neural stem cells give rise to new neurons that integrate into the local circuitry and contribute to hippocampal functions such as memory and learning. Importantly, adult hippocampal neurogenesis is well-known to be modulated by the demands of the environment and lifestyle factors. Diet, stress, and physical exercise directly act on neural stem cells and/or their progeny, but, in addition, they may also indirectly affect neurogenesis by acting on microglia. Microglia, the guardians of the brain, rapidly sense changes in the brain milieu, and it has been recently shown that their function is affected by lifestyle factors. However, few studies have analyzed the modulatory effect of microglia on adult neurogenesis in these conditions. Here, we review the current knowledge about the dialogue maintained between microglia and the hippocampal neurogenic cascade. Understanding how the communication between microglia and hippocampal neurogenesis is affected by lifestyle choices is crucial to maintain the brain cognitive reserve and prevent the maladaptive responses that emerge during disease or injury through adulthood and aging.

Neurogenic regulation of renal tubular sodium reabsorption.

PubMed

DiBona, G F

1977-08-01

The evidence supporting a role for direct neurogenic control of renal tubular sodium reabsorption is reviewed. Electron microscopic and fluorescence histochemical studies have demonstrated adrenergic nerve terminals in direct contact with basement membranes of mammalian (rat, dog, and monkey) renal tubular epithelial cells. Low-level direct or baroreceptor reflex stimulation of renal sympathetic nerves produces an increase in renal tubular sodium reabsorption without alterations in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow. Antinatriuresis was prevented by prior treatment of the kidney with guanethidine or phenoxybenzamine. Rat kidney micropuncture studies have localized a site of enhanced tubular sodium reabsorption to the proximal tubule. Possible indirect mediation of the antinatriuresis by other humoral agents known to be released from the kidney on renal nerve stimulation (angiotensin II, prostaglandin) was excluded by experiments with appropriate blocking agents. The possible effects of anesthesia and uncertainties about the completeness of surgical renal denervation and other tubular segmental sites of action are critically analyzed. The clinical implications of this mechanism in pathologic conditions of sodium and water retention are discussed and and a prospectus for future work is presented.

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.

Milrinone therapy for enterovirus 71-induced pulmonary edema and/or neurogenic shock in children: a randomized controlled trial.

PubMed

Chi, Chia-Yu; Khanh, Truong Huu; Thoa, Le Phan Kim; Tseng, Fan-Chen; Wang, Shih-Min; Thinh, Le Quoc; Lin, Chia-Chun; Wu, Han-Chieh; Wang, Jen-Ren; Hung, Nguyen Thanh; Thuong, Tang Chi; Chang, Chung-Ming; Su, Ih-Jen; Liu, Ching-Chuan

2013-07-01

Enterovirus 71-induced brainstem encephalitis with pulmonary edema and/or neurogenic shock (stage 3B) is associated with rapid mortality in children. In a small pilot study, we found that milrinone reduced early mortality compared with historical controls. This prospective, randomized control trial was designed to provide more definitive evidence of the ability of milrinone to reduce the 1-week mortality of stage 3B enterovirus 71 infections. Prospective, unicenter, open-label, randomized, controlled study. Inpatient ward of a large tertiary teaching hospital in Ho Chi Minh City, Vietnam. Children (≤ 18 yr old) admitted with proven enterovirus 71-induced pulmonary edema and/or neurogenic shock. Patients were randomly assigned to receive intravenous milrinone (0.5 μg/kg/min) (n = 22) or conventional management (n = 19). Both groups received dopamine or dobutamine and intravenous immunoglobulin. The primary endpoint was 1-week mortality. The secondary endpoints included length of ventilator dependence and hospital stay and adverse events. The median age was 2 years with a predominance of boys in both groups. The 1-week mortality was significantly lower, 18.2% (4/22) in the milrinone compared with 57.9% (11/19) in the conventional management group (relative risk = 0.314 [95% CI, 0.12-0.83], p = 0.01). The median duration of ventilator-free days was longer in the milrinone treatment group (p = 0.01). There was no apparent neurologic sequela in the survivors in either group, and no drug-related adverse events were documented. Milrinone significantly reduced the 1-week mortality of enterovirus 71-induced pulmonary edema and/or neurogenic shock without adverse effects. Further studies are needed to determine whether milrinone might be useful to prevent progression of earlier stages of brainstem encephalitis.

Hydrogen Sulfide and Neurogenic Inflammation in Polymicrobial Sepsis: Involvement of Substance P and ERK-NF-κB Signaling

PubMed Central

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

2011-01-01

Hydrogen sulfide (H2S) has been shown to induce transient receptor potential vanilloid 1 (TRPV1)-mediated neurogenic inflammation in polymicrobial sepsis. However, endogenous neural factors that modulate this event and the molecular mechanism by which this occurs remain unclear. Therefore, this study tested the hypothesis that whether substance P (SP) is one important neural element that implicates in H2S-induced neurogenic inflammation in sepsis in a TRPV1-dependent manner, and if so, whether H2S regulates this response through activation of the extracellular signal-regulated kinase-nuclear factor-κB (ERK-NF-κB) pathway. Male Swiss mice were subjected to cecal ligation and puncture (CLP)-induced sepsis and treated with TRPV1 antagonist capsazepine 30 minutes before CLP. DL-propargylglycine (PAG), an inhibitor of H2S formation, was administrated 1 hour before or 1 hour after sepsis, whereas sodium hydrosulfide (NaHS), an H2S donor, was given at the same time as CLP. Capsazepine significantly attenuated H2S-induced SP production, inflammatory cytokines, chemokines, and adhesion molecules levels, and protected against lung and liver dysfunction in sepsis. In the absence of H2S, capsazepine caused no significant changes to the PAG-mediated attenuation of lung and plasma SP levels, sepsis-associated systemic inflammatory response and multiple organ dysfunction. In addition, capsazepine greatly inhibited phosphorylation of ERK1/2 and inhibitory κBα, concurrent with suppression of NF-κB activation even in the presence of NaHS. Furthermore, capsazepine had no effect on PAG-mediated abrogation of these levels in sepsis. Taken together, the present findings show that H2S regulates TRPV1-mediated neurogenic inflammation in polymicrobial sepsis through enhancement of SP production and activation of the ERK-NF-κB pathway. PMID:21931742

The effect of intravesical oxybutynin on the ice water test and on electrical perception thresholds in patients with neurogenic detrusor overactivity.

PubMed

Van Meel, Tom David; De Wachter, Stefan; Wyndaele, Jean Jacques

2010-03-01

The C-fiber-mediated bladder-cooling reflex and the determination of the current perception thresholds (CPTs) permit to investigate afferent LUT pathways. They have both been proposed to detect and differentiate neurologic bladder dysfunction. This study evaluates, prospectively, the effect of oxybutynin, an antimuscarinic with direct antispasmodic effect on smooth muscle, on repeated ice water test (IWT) and CPTs in patients with a known incomplete neurogenic bladder. Patients with a known incomplete lesion of the bladder innervation, detrusor overactivity during cystometric bladder filling and a continuous positive response to repeated IWT were included. After the initial tests, 30 mg intravesical oxybutynin (1 mg/ml) was instilled and left in the bladder for 15 min. Afterwards CPTs and IWT were re-assessed. After the drug application, the bladder-cooling reflex could not be initiated, even after three instillations, in 16/17 patients. The bladder CPT increased from 29.7 +/- 11.3 to 39.1 +/- 15.7 mA after oxybutynin (P = 0.001). No difference was found in CPT of the left forearm (P = 0.208). Intravesical oxybutynin blocks the bladder-cooling reflex and increases but does not block CPT sensation in the bladder in most patients with incomplete neurogenic lesion and detrusor overactivity. These results help explain the clinical effect of intravesical oxybutynin in neurogenic patients. They also indicate that a pharmacological local influence on C-fiber-related activity can give different clinical effects. (c) 2009 Wiley-Liss, Inc.

Potentiation of capsaicin-induced neurogenic inflammation by 5-HT7 receptors in the rat hind paw: Involvement of calcitonin gen-related peptide.

PubMed

Arreola-Peralta, Luis D; Altamirano-Reyna, Frida; Galindo-González, Deni M; Solis-Anguiano, Jessica G; Lacivita, Enza; Leopoldo, Marcello; Terrón, José A

2018-05-03

A decrease in the activation threshold of primary sensory neurons to transient receptor potential V1 (TRPV1) stimulation by serotonin 5-HT7 receptors has been reported but no confirmation if this might translate into facilitation of neurogenic inflammation has been provided. We analysed the modulation of capsaicin (CAP)-induced neurogenic inflammation in the rat hind paw by the selective 5-HT7 receptor agonist, LP-44, and the involvement of calcitonin gen-related peptide (CGRP) in this effect. Animals received intra-plantar injections (30 μL) of vehicle, CAP (0.05%, 0.1% and 0.2%), LP-44 (7.5 and 15 nmol) and the combination of LP-44 + CAP; then, the time course of the inflammatory responses was measured. The effect of the 5-HT7 receptor antagonist, SB-269970 (3 mg/kg, s.c.), on responses produced by LP-44 alone and combined with CAP was tested. As expected, CAP produced concentration- and time-dependent inflammatory responses in the hind paw. Interestingly, LP-44 by itself also produced inflammation in a concentration- and time-dependent manner, and magnified CAP-induced responses. Systemic pre-treatment with SB-269970 significantly blunted LP-44 (15 nmol)-induced inflammation as well as magnified inflammatory responses produced by the combination of LP-44 (7.5 and 15 nmol) + CAP (0.1%) thus confirming the involvement of 5-HT7 receptors. Finally, the non-peptide CGRP receptor antagonist, BIBN4096 (3 mg/kg, s.c.), strongly inhibited the potentiated inflammatory responses induced by LP-44 (7.5 and 15 nmol) + CAP (0.1%) thus substantiating their neurogenic nature. Thus, sensitization of CAP-sensitive primary sensory neurons by 5-HT7 receptors may result in facilitation of neurogenic inflammation involving CGRP in the rat hind paw. Copyright © 2018. Published by Elsevier Inc.

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer's disease.

PubMed

Ryan, Sinéad M; Kelly, Áine M

2016-05-01

It is now well established, at least in animal models, that exercise elicits potent pro-cognitive and pro-neurogenic effects. Alzheimer's disease (AD) is one of the leading causes of dementia and represents one of the greatest burdens on healthcare systems worldwide, with no effective treatment for the disease to date. Exercise presents a promising non-pharmacological option to potentially delay the onset of or slow down the progression of AD. Exercise interventions in mouse models of AD have been explored and have been found to reduce amyloid pathology and improve cognitive function. More recent studies have expanded the research question by investigating potential pro-neurogenic and anti-inflammatory effects of exercise. In this review we summarise studies that have examined exercise-mediated effects on AD pathology, cognitive function, hippocampal neurogenesis and neuroinflammation in transgenic mouse models of AD. Furthermore, we attempt to identify the optimum exercise conditions required to elicit the greatest benefits, taking into account age and pathology of the model, as well as type and duration of exercise. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-12-01

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

[Indices of 24-hour monitoring of arterial blood pressure in patients with neurogenic syncope and patients with chronic constitution- dependent hypotension].

PubMed

Musaeva, Z A; Khapaev, B A; Fedotova, A V; Oknin, V Iu

1999-01-01

Clinical-psychologic study, spectral analysis of heart rate variability, 24-h monitoring of arterial pressure (AP) were performed in 20 patients with chronic constitutional arterial hypotension and in 18 patients with neurogenic syncopal states. Both groups were characterised by considerable manifestations of the syndrome of autonomic dystonia, by emotional-personal disorders that correlated with elevated level of slow-waves of the second order in heart rhythms' spectrum. That testified activation of supersegmental sympathetic-adrenal systems. Disorders in sympathetic-parasympathetic correlations were specific in each group. In patients with arterial hypotension disorder of circadian rhythm was observed in the form of superfluous decrease of diastolic AP during sleep. Circadian rhythms in patients with neurogenic syncopes have parameters characteristic for normals showing a preverved chronobiologic AP regulation. A role of the alterations revealed in pathogenesis of arterial hypotensionis discussed.

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

PubMed Central

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

2008-01-01

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

Prospective evaluation of antibiotic treatment for urological procedure in patients presenting with neurogenic bladder.

PubMed

Weglinski, L; Rouzaud, C; Even, A; Bouchand, F; Davido, B; Duran, C; Salomon, J; Perronne, C; Denys, P; Chartier-Kastler, E; Dinh, A

2016-09-01

Patients presenting with neurogenic bladder often require urological procedures (urodynamic testing and botulinum toxin injections) and a preventive antibiotic therapy. We aimed to assess the efficacy of this little known strategy in a cohort of patients. All patients presenting with neurogenic bladder who underwent urological procedure were included in the study. They received an antibiotic therapy in accordance with the urine cytobacteriological examination results. The antibiotic therapy was initiated two days before the procedure and prolonged up until two days after the procedure if the culture was positive. Patients were treated with a single dose of fosfomycin-trometamol in case of a negative culture. The main study outcome was the occurrence of urinary tract infection (UTI), defined by a positive urine culture and symptoms, up until 14 days after the procedure. A total of 80 urological procedures were performed. Mean patient age was 47±13.1 years (sex ratio 1.22); 59 (73.8%) presented with asymptomatic bacteriuria before the procedure. Nine (11.1%) UTIs were recorded on Day 14, of which one (1.2%) was febrile. Two patients required an additional curative antibiotic therapy. No patient was hospitalized. Overall, 77.8% of UTIs were cured without antibiotic therapy. Screening and treating asymptomatic bacteriuria before urological procedures seems unnecessary and vainly exposes this population at high risk of infectious diseases to antibiotic therapies. This data should be confirmed by a randomized clinical trial. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Enrichment increases hippocampal neurogenesis independent of blood monocyte-derived microglia presence following high-dose total body irradiation.

PubMed

Ruitenberg, Marc J; Wells, Julia; Bartlett, Perry F; Harvey, Alan R; Vukovic, Jana

2017-06-01

Birth of new neurons in the hippocampus persists in the brain of adult mammals and critically underpins optimal learning and memory. The process of adult neurogenesis is significantly reduced following brain irradiation and this correlates with impaired cognitive function. In this study, we aimed to compare the long-term effects of two environmental paradigms (i.e. enriched environment and exercise) on adult neurogenesis following high-dose (10Gy) total body irradiation. When housed in standard (sedentary) conditions, irradiated mice revealed a long-lasting (up to 4 months) deficit in neurogenesis in the granule cell layer of the dentate gyrus, the region that harbors the neurogenic niche. This depressive effect of total body irradiation on adult neurogenesis was partially alleviated by exposure to enriched environment but not voluntary exercise, where mice were single-housed with unlimited access to a running wheel. Exposure to voluntary exercise, but not enriched environment, did lead to significant increases in microglia density in the granule cell layer of the hippocampus; our study shows that these changes result from local microglia proliferation rather than recruitment and infiltration of circulating Cx 3 cr1 +/gfp blood monocytes that subsequently differentiate into microglia-like cells. In summary, latent neural precursor cells remain present in the neurogenic niche of the adult hippocampus up to 8 weeks following high-dose total body irradiation. Environmental enrichment can partially restore the adult neurogenic process in this part of the brain following high-dose irradiation, and this was found to be independent of blood monocyte-derived microglia presence. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Infants and adults have similar regional functional brain organization for the perception of emotions.

PubMed

Rotem-Kohavi, N; Oberlander, T F; Virji-Babul, N

2017-05-22

An infant's ability to perceive emotional facial expressions is critical for developing social skills. Infants are tuned to faces from early in life, however the functional organization of the brain that supports the processing of emotional faces in infants is still not well understood. We recorded electroencephalography (EEG) brain responses in 8-10 month old infants and adults and applied graph theory analysis on the functional connections to compare the network organization at the global and the regional levels underlying the perception of negative and positive dynamic facial expressions (happiness and sadness). We first show that processing of dynamic emotional faces occurs across multiple brain regions in both infants and adults. Across all brain regions, at the global level, network density was higher in the infant group in comparison with adults suggesting that the overall brain organization in relation to emotion perception is still immature in infancy. In contrast, at the regional levels, the functional characteristics of the frontal and parietal nodes were similar between infants and adults, suggesting that functional regional specialization for emotion perception is already established at this age. In addition, in both groups the occipital, parietal and temporal nodes appear to have the strongest influence on information flow within the network. These results suggest that while the global organization for the emotion perception of sad and happy emotions is still under development, the basic functional network organization at the regional level is already in place early in infancy. Copyright © 2017 Elsevier B.V. All rights reserved.

Keewatin Region Educational Authority Pilot Adult Education Project: Computer-Assisted Learning. Final Report.

ERIC Educational Resources Information Center

Fahy, Patrick J.

This 2-year project attempted to improve local employment prospects of young adult Inuit in seven communities in the Keewatin Region in the Canadian Northwest Territories by providing them computer-assisted instruction (CAI) in adult basic education and high school equivalency upgrading programs; business, financial, and telecommunications…

Neurogenic regulation of cochlear blood flow occurs along the basilar artery, the anterior inferior cerebellar artery and at branch points of the spiral modiolar artery.

PubMed

Wangemann, Philine; Wonneberger, Kai

2005-11-01

The cochlea receives its main blood supply from the basilar artery via the anterior inferior cerebellar artery and the spiral modiolar artery. Morphologic studies have shown sympathetic innervation along the spiral modiolar artery of the gerbil and the guinea pig and functional studies in the isolated in vitro superfused spiral modiolar artery of the gerbil have demonstrated norepinephrine-induced vasoconstrictions via alpha(1A)-adrenergic receptors. It is current unclear whether the sympathetic innervation is physiologically relevant. Stimulation of sympathetic ganglia in guinea pigs has been shown to alter cochlear blood flow in situ. Whether these changes originated from local or more systemic changes in the vascular diameter remained uncertain. The goal of the present study was to demonstrate the presence or absence of neurogenic changes in the diameter of the isolated in vitro superfused spiral modiolar artery, anterior inferior cerebellar artery and basilar artery from the gerbil and the guinea pig. Vascular diameter was monitored by videomicroscopy. Electric field stimulation was used to elicit neurotransmitter release. A reversible inhibitory effect of 10(-6) M tetrodotoxin was taken as criterion to discriminate between neurogenic and myogenic changes in vascular diameter. Mesentery arteries of comparable diameter, which are known to respond with a neurogenic vasoconstriction to electric field stimulation, served as controls. Basilar artery, anterior inferior cerebellar artery, spiral modiolar artery and mesentery arteries constricted in response to electric field stimulation. No dilations were observed. Myogenic and neurogenic vasoconstrictions were observed in all vessels. These observations suggest that the sympathetic innervation of the basilar artery, the anterior inferior cerebellar artery and branch points of the spiral modiolar artery is involved in a physiologically relevant control of the vascular diameter in the gerbil and the guinea pig.

Polyvalent Adult Education Centres. Final Report of the Asian Regional Seminar on Polyvalent Adult Education Centres.

ERIC Educational Resources Information Center

Ministry of Education and Social Welfare, New Delhi (India).

The Asian Regional Seminar on Polyvalent Adult Education Centers, held during September, 1971 in Bombay, was attended by individuals representing United Nations agencies, Afghanistan, Cambodia, India, Indonesia, Iran, Japan, Republic of Korea, Laos, Malaysia, Nepal, Phillippines, Singapore, South Vietnam, and Thailand. Seminar objectives included…

Adolescence transitional care in neurogenic detrusor overactivity and the use of OnabotulinumtoxinA: A clinical algorithm from an Italian consensus statement.

PubMed

Palleschi, Giovanni; Mosiello, Giovanni; Iacovelli, Valerio; Musco, Stefania; Del Popolo, Giulio; Giannantoni, Antonella; Carbone, Antonio; Carone, Roberto; Tubaro, Andrea; De Gennaro, Mario; Marte, Antonio; Finazzi Agrò, Enrico

2018-03-01

OnabotulinumtoxinA (onaBNTa) for treating neurogenic detrusor overactivity (NDO) is widely used after its regulatory approval in adults. Although the administration of onaBNTa is still considered off-label in children, data have already been reported on its efficacy and safety. Nowadays, there is a lack of standardized protocols for treatment of NDO with onaBNTa in adolescent patients in their transition from the childhood to the adult age. With the aim to address this issue a consensus panel was obtained. A panel of leading urologists and urogynaecologists skilled in functional urology, neuro-urology, urogynaecology, and pediatric urology participated in a consensus-forming project using a Delphi method to reach national consensus on NDO-onaBNTa treatment in adolescence transitional care. In total, 11 experts participated. All panelists participated in the four phases of the consensus process. Consensus was reached if ≥70% of the experts agreed on recommendations. To facilitate a common understanding among all experts, a face-to-face consensus meeting was held in Rome in march 2015 and then with a follow-up teleconference in march 2017. By the end of the Delphi process, formal consensus was achieved for 100% of the items and an algorithm was then developed. This manuscript represents the first report on the onaBNTa in adolescents. Young adults should be treated as a distinct sub-population in policy, planning, programming, and research, as strongly sustained by national public health care. This consensus and the algorithm could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making. © 2017 Wiley Periodicals, Inc.

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

PubMed Central

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

2016-01-01

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

Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

PubMed

Kizil, Caghan; Iltzsche, Anne; Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

2015-01-01

Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

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

Randomized Trial of Clitoral Vacuum Suction Versus Vibratory Stimulation in Neurogenic Female Orgasmic Dysfunction.

PubMed

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

2018-02-01

To examine the safety and efficacy of using a clitoral vacuum suction device (CVSD) versus vibratory stimulation (V) to treat orgasmic dysfunction in women with multiple sclerosis (MS) or spinal cord injury (SCI). Randomized clinical trial. Two academic medical centers. Women (N=31) including 20 with MS and 11 with SCI. A 12-week trial of the use of a CVSD versus V. Female Sexual Function Inventory (FSFI) and Female Sexual Distress Scale (FSDS). Twenty-three women (18 MS, 5 SCI) completed the study including 13 of 16 randomized to CVSD and 10 of 15 randomized to V. There was a statistically significant increase in total FSFI score (P=.011), desire (P=.009), arousal (P=.009), lubrication (P=.008), orgasm (P=.012), and satisfaction (P=.049), and a significant decrease in distress as measured by FSDS (P=.020) in subjects using the CVSD. In subjects who used V, there was a statistically significant increase in the orgasm subscale of the FSFI (P=.028). Subjects using the CVSD maintained improvements 4 weeks after treatment. CVSD is safe and overall efficacious to treat female neurogenic sexual dysfunction related to MS and SCI. V is also safe and efficacious for female neurogenic orgasmic dysfunction; however, results were limited to the active treatment period. Because of ease of access and cost, clinicians can consider use of V for women with MS or SCI with orgasmic dysfunction. CVSD is recommended for women with multiple sexual dysfunctions or for whom V is ineffective. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Epidermal Growth Factor Treatment of the Adult Brain Subventricular Zone Leads to Focal Microglia/Macrophage Accumulation and Angiogenesis

PubMed Central

Lindberg, Olle R.; Brederlau, Anke; Kuhn, H. Georg

2014-01-01

Summary One of the major components of the subventricular zone (SVZ) neurogenic niche is the specialized vasculature. The SVZ vasculature is thought to be important in regulating progenitor cell proliferation and migration. Epidermal growth factor (EGF) is a mitogen with a wide range of effects. When stem and progenitor cells in the rat SVZ are treated with EGF, using intracerebroventricular infusion, dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited into the polyps. In the current study we demonstrate how polyps develop through distinct stages leading up to angiogenesis. As polyps progress, microglia/macrophages accumulate in the polyp core concurrent with increasing cell death. Both microglia/macrophage accumulation and cell death peak during angiogenesis and subsequently decline following polyp vascularization. This model of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of microglia/macrophages in acquired angiogenesis and can be used in detail to study angiogenesis in the adult brain. PMID:24749069

Neuroprotective, Neurogenic, and Amyloid Beta Reducing Effect of a Novel Alpha 2-Adrenoblocker, Mesedin, on Astroglia and Neuronal Progenitors upon Hypoxia and Glutamate Exposure

PubMed Central

Melkonyan, Magda M.; Hunanyan, Lilit; Lourhmati, Ali; Layer, Nikolas; Beer-Hammer, Sandra; Yenkoyan, Konstantin; Schwab, Matthias; Danielyan, Lusine

2017-01-01

Locus coeruleus-noradrenergic system dysfunction is known to contribute to the progression of Alzheimer’s disease (AD). Besides a variety of reports showing the involvement of norepinephrine and its receptor systems in cognition, amyloid β (Aβ) metabolism, neuroinflammation, and neurogenesis, little is known about the contribution of the specific receptors to these actions. Here, we investigated the neurogenic and neuroprotective properties of a new α2 adrenoblocker, mesedin, in astroglial primary cultures (APC) from C57BL/6 and 3×Tg-AD mice. Our results demonstrate that mesedin rescues neuronal precursors and young neurons, and reduces the lactate dehydrogenase (LDH) release from astroglia under hypoxic and normoxic conditions. Mesedin also increased choline acetyltransferase, postsynaptic density marker 95 (PSD95), and Aβ-degrading enzyme neprilysin in the wild type APC, while in the 3×Tg-AD APC exposed to glutamate, it decreased the intracellular content of Aβ and enhanced the survival of synaptophysin-positive astroglia and neurons. These effects in APC can at least partially be attributed to the mesedin’s ability of increasing the expression of Interleukine(IL)-10, which is a potent anti-inflammatory, neuroprotective neurogenic, and Aβ metabolism enhancing factor. In summary, our data identify the neurogenic, neuroprotective, and anti-amyloidogenic action of mesedin in APC. Further in vivo studies are needed to estimate the therapeutic value of mesedin for AD. PMID:29267189

In vivo transcriptional profile analysis reveals RNA splicing and chromatin remodeling as prominent processes for adult neurogenesis.

PubMed

Lim, Daniel A; Suárez-Fariñas, Mayte; Naef, Felix; Hacker, Coleen R; Menn, Benedicte; Takebayashi, Hirohide; Magnasco, Marcelo; Patil, Nila; Alvarez-Buylla, Arturo

2006-01-01

Neural stem cells and neurogenesis persist in the adult mammalian brain subventricular zone (SVZ). Cells born in the rodent SVZ migrate to the olfactory bulb (Ob) where they differentiate into interneurons. To determine the gene expression and functional profile of SVZ neurogenesis, we performed three complementary sets of transcriptional analysis experiments using Affymetrix GeneChips: (1) comparison of adult mouse SVZ and Ob gene expression profiles with those of the striatum, cerebral cortex, and hippocampus; (2) profiling of SVZ stem cells and ependyma isolated by fluorescent-activated cell sorting (FACS); and (3) analysis of gene expression changes during in vivo SVZ regeneration after anti-mitotic treatment. Gene Ontology (GO) analysis of data from these three separate approaches showed that in adult SVZ neurogenesis, RNA splicing and chromatin remodeling are biological processes as statistically significant as cell proliferation, transcription, and neurogenesis. In non-neurogenic brain regions, RNA splicing and chromatin remodeling were not prominent processes. Fourteen mRNA splicing factors including Sf3b1, Sfrs2, Lsm4, and Khdrbs1/Sam68 were detected along with 9 chromatin remodeling genes including Mll, Bmi1, Smarcad1, Baf53a, and Hat1. We validated the transcriptional profile data with Northern blot analysis and in situ hybridization. The data greatly expand the catalogue of cell cycle components, transcription factors, and migration genes for adult SVZ neurogenesis and reveal RNA splicing and chromatin remodeling as prominent biological processes for these germinal cells.

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

PubMed Central

2016-01-01

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

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

PubMed

Wenger, Y; Buzgariu, W; Galliot, B

2016-01-05

Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory-motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra, we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors (Dlx, Dlx1, DMBX1/Manacle, Ets1, Gli3, KLF11, LMX1A, ZNF436, Shox1), epitheliopeptides (Arminins, PW peptide), neurosignalling components (CAMK1D, DDCl2, Inx1), ligand-ion channel receptors (CHRNA1, NaC7), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution. © 2015 The Authors.

Predicting geographically distributed adult dental decay in the greater Auckland region of New Zealand.

PubMed

Rocha, C M; Kruger, E; Whyman, R; Tennant, M

2014-06-01

To model the geographic distribution of current (and treated) dental decay on a high-resolution geographic basis for the Auckland region of New Zealand. The application of matrix-based mathematics to modelling adult dental disease-based on known population risk profiles to provide a detailed map of the dental caries distribution for the greater Auckland region. Of the 29 million teeth in adults in the region some 1.2 million (4%) are suffering decay whilst 7.2 million (25%) have previously suffered decay and are now restored. The model provides a high-resolution picture of where the disease burden lies geographically and presents to health planners a method for developing future service plans.

Meta-analysis of the safety and efficacy of droxidopa for neurogenic orthostatic hypotension.

PubMed

Elgebaly, Ahmed; Abdelazeim, Bassant; Mattar, Omar; Gadelkarim, Mohamed; Salah, Rehab; Negida, Ahmed

2016-06-01

Droxidopa has been approved for the treatment of neurogenic orthostatic hypotension (NOH) under the US Food and Drug Administration accelerated approval program, which warrants confirmatory evidence on long-term efficacy of droxidopa. Hereby, we synthesize evidence from published randomized controlled trials (RCTs) about the safety and efficacy of droxidopa for patients with neurogenic orthostatic hypotension. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager version 5.3 for Windows. Subgroup analysis and sensitivity analysis were conducted to investigate long-term durability of droxidopa against placebo. Four RCTs with a total of 485 patients (droxidopa, n = 246; placebo, n = 239) were eligible for the final analysis. The mean difference (MD) of change in the main outcomes from baseline to endpoint favored droxidopa than placebo [Orthostatic Hypotension Questionnaire (OHQ) MD -0.61, P = 0.004; dizziness/lightheadedness score MD -0.83, P = 0.008; and standing systolic blood pressure (SBP) MD 4.09, P = 0.03]. The efficacy of droxidopa decreased gradually after 2 weeks, and its statistical significance was lost after 8 weeks (OHQ score MD -0.18, P = 0.61; dizziness/lightheadedness score MD -0.71, P = 0.11; and standing SBP MD 2.96, P = 0.29). None of the adverse events were significantly higher in the case of droxidopa compared to placebo. Droxidopa is a safe and effective drug for the short-term management of NOH symptoms. However, current evidence is insufficient to confirm the efficacy of droxidopa for long-term use. Therefore, further studies with increased sample size are needed.

Kinin B1 Receptor Promotes Neurogenic Hypertension Through Activation of Centrally Mediated Mechanisms.

PubMed

Sriramula, Srinivas; Lazartigues, Eric

2017-12-01

Hypertension is associated with increased activity of the kallikrein-kinin system. Kinin B1 receptor (B1R) activation leads to vasoconstriction and inflammation. Despite evidence supporting a role for the B1R in blood pressure regulation, the mechanisms by which B1R could alter autonomic function and participate in the pathogenesis of hypertension remain unidentified. We sought to explore whether B1R-mediated inflammation contributes to hypertension and investigate the molecular mechanisms involved. In this study, we tested the hypothesis that activation of B1R in the brain is involved in the pathogenesis of hypertension, using the deoxycorticosterone acetate-salt model of neurogenic hypertension in wild-type and B1R knockout mice. Deoxycorticosterone acetate-salt treatment in wild-type mice led to significant increases in B1R mRNA and protein levels and bradykinin levels, enhanced gene expression of carboxypeptidase N supporting an increase in the B1R ligand, associated with enhanced blood pressure, inflammation, sympathoexcitation, autonomic dysfunction, and impaired baroreflex sensitivity, whereas these changes were blunted or prevented in B1R knockout mice. B1R stimulation was further shown to involve activation of the ASK1-JNK-ERK1/2 and NF-κB pathways in the brain. To dismiss potential developmental alterations in knockout mice, we further used B1R blockade selectively in the brain of wild-type mice. Supporting the central origin of this mechanism, intracerebroventricular infusion of a specific B1R antagonist, attenuated the deoxycorticosterone acetate-salt-induced increase in blood pressure in wild-type mice. Our data provide the first evidence of a central role for B1R-mediated inflammatory pathways in the pathogenesis of deoxycorticosterone acetate-salt hypertension and offer novel insights into possible B1R-targeted therapies for the treatment of neurogenic hypertension. © 2017 American Heart Association, Inc.

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

PubMed

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

2012-01-01

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

Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult Mammalian Carotid Body.

PubMed

Annese, Valentina; Navarro-Guerrero, Elena; Rodríguez-Prieto, Ismael; Pardal, Ricardo

2017-04-18

Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs) display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs) are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is hypoxia inducible factor (HIF) dependent and sensitive to hypoxia-released vascular cytokines such as erythropoietin. Our data highlight a remarkable physiological plasticity in an adult population of tissue-specific stem cells and could have impact on the use of these cells for cell therapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Adult Education Regional Planning

ERIC Educational Resources Information Center

California Community Colleges, Chancellor's Office, 2015

2015-01-01

For more than one hundred and fifty years, until 2008, California was an undisputed national leader in its commitment to adult education. The state's investment in adult learners topped $750 million, a sum greater than the combined total of every other state in the nation. However, for the past several years recession and fiscal crisis have left…

Expression and function of orphan nuclear receptor TLX in adult neural stem cells.

PubMed

Shi, Yanhong; Chichung Lie, D; Taupin, Philippe; Nakashima, Kinichi; Ray, Jasodhara; Yu, Ruth T; Gage, Fred H; Evans, Ronald M

2004-01-01

The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

Heparan sulfate niche for cell proliferation in the adult brain.

PubMed

Mercier, Frederic; Arikawa-Hirasawa, Eri

2012-02-29

In adulthood, new neurons and glial cells are generated from stem cells in restricted zones of the brain, namely the olfactory bulb (OB), rostral migratory stream (RMS), subventricular zone (SVZ) of the lateral ventricle, sub-callosum zone (SCZ) and sub-granular layer (SGL) of the dentate gyrus. What makes these zones germinal? We previously reported that N-sulfated heparan sulfates (N-sulfated HS) present in specialized extracellular matrix structures (fractones) and vascular basement membranes bind the neurogenic factor FGF-2 (fibroblast growth factor-2) next to stem cells in the anterior SVZ of the lateral ventricle, the most neurogenic zone in adulthood. To determine to which extent cell proliferation is associated with N-sulfated HS, we mapped N-sulfated HS and proliferating cells by immunohistochemistry throughout the adult mouse brain. We found that cell proliferation is associated with N-sulfated HS in the OB, RMS, the whole germinal SVZ, and the SCZ. Cell proliferation was weakly associated with N-sulfated HS in the SGL, but the SGL was directly connected to a sub-cortical N-sulfated HS+ extension of the meninges. The NS-sulfated HS+ structures were blood vessels in the OB, RMS and SCZ, and primarily fractones in the SVZ. N-sulfated HS+ fractones, blood vessels and meninges formed a continuum that coursed along the OB, SVZ, RMS, SCZ and SGL, challenging the view that these structures are independent germinal entities. These results support the possibility that a single anatomical system might be globally responsible for mitogenesis and ultimately the production of new neurons and glial cells in the adult brain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chronic low back pain in older adults: prevalence, reliability, and validity of physical examination findings.

PubMed

Weiner, Debra K; Sakamoto, Sara; Perera, Subashan; Breuer, Paula

2006-01-01

To develop a structured physical examination protocol that identifies common biomechanical and soft-tissue abnormalities for older adults with chronic low back pain (CLBP) that can be used as a triage tool for healthcare providers and to test the interobserver reliability and discriminant validity of this protocol. Cross-sectional survey and examination. Older adult pain clinic. One hundred eleven community-dwelling adults aged 60 and older with CLBP and 20 who were pain-free. Clinical history for demographics, pain duration, previous lumbar surgery or advanced imaging, neurogenic claudication, and imaging clinically serious symptoms. Physical examination for scoliosis, functional leg length discrepancy, pain with lumbar movement, myofascial pain (paralumbar, piriformis, tensor fasciae latae (TFL)), regional bone pain (sacroiliac joint (SIJ), hip, vertebral body), and fibromyalgia. Scoliosis was prevalent in those with (77.5%) and without pain (60.0%), but prevalence of SIJ pain (84% vs 5%), fibromyalgia tender points (19% vs 0%), myofascial pain (96% vs 10%), and hip pain (48% vs 0%) was significantly different between groups (P < .001). Interrater reliability was excellent for SIJ pain (0.81), number of fibromyalgia tender points (0.84), and TFL pain (0.81); good for scoliosis (0.43), kyphosis (0.66), lumbar movement pain (0.75), piriformis pain (0.71), and hip disease by internal rotation (0.56); and marginal for leg length (0.00) and paravertebral pain (0.39). Biomechanical and soft tissue pathologies are common in older adults with CLBP, and many can be assessed reliably using a brief physical examination. Their recognition may save unnecessary healthcare expenditure and patient suffering.

Progenitor cell dynamics in the Newt Telencephalon during homeostasis and neuronal regeneration.

PubMed

Kirkham, Matthew; Hameed, L Shahul; Berg, Daniel A; Wang, Heng; Simon, András

2014-04-08

The adult newt brain has a marked neurogenic potential and is highly regenerative. Ventricular, radial glia-like ependymoglia cells give rise to neurons both during normal homeostasis and after injury, but subpopulations among ependymoglia cells have not been defined. We show here that a substantial portion of GFAP(+) ependymoglia cells in the proliferative hot spots of the telencephalon has transit-amplifying characteristics. In contrast, proliferating ependymoglia cells, which are scattered along the ventricular wall, have stem cell features in terms of label retention and insensitivity to AraC treatment. Ablation of neurons remodels the proliferation dynamics and leads to de novo formation of regions displaying features of neurogenic niches, such as the appearance of cells with transit-amplifying features and proliferating neuroblasts. The results have implication both for our understanding of the evolutionary diversification of radial glia cells as well as the processes regulating neurogenesis and regeneration in the adult vertebrate brain.

Ileal loop ureteroileostomy in patients with neurogenic bladder. Personal experience with 54 patients.

PubMed

Kambouris, A A; Allaben, R D; Carpenter, W S; Shumaker, E J

1976-02-01

(1) In a six year experience with ileal loops in patients with neurogenic bladder, 49% of the patients were paralyzed, 30% had multiple sclerosis, and 91% had recurrent or persistent urinary tract infection. Reflux, incontinence, retention, and bladder calculi were additional indications for supravesical urinary diversions. (2) All loops were performed in a similar manner, most of them placed retroperitoneally, and a vigorous program of postoperative care was followed. There were no postoperative deaths, and a moderate number of complications occurred in 51.8% of the patients. (3) The participation of the enterostomal therapist is the preparation of the patient and in the immediate and long-term stomal care has been invaluable and is strongly recommended.

Postural sway and regional cerebellar volume in adults with attention-deficit/hyperactivity disorder

PubMed Central

Hove, Michael J.; Zeffiro, Thomas A.; Biederman, Joseph; Li, Zhi; Schmahmann, Jeremy; Valera, Eve M.

2015-01-01

Objective Motor abnormalities, including impaired balance and increased postural sway, are commonly reported in children with ADHD, but have yet to be investigated in adults with ADHD. Furthermore, although these abnormalities are thought to stem from cerebellar deficits, evidence for an association between the cerebellum and these motor deficits has yet to be provided for either adults or children with ADHD. Method In this study, we measured postural sway in adults with ADHD and controls, examining the relationship between sway and regional cerebellar gray matter volume. Thirty-two ADHD and 28 control participants completed various standing-posture tasks on a Wii balance board. Results Postural sway was significantly higher for the ADHD group compared to the healthy controls. Higher sway was positively associated with regional gray matter volume in the right posterior cerebellum (lobule VIII/IX). Conclusion These findings show that sway abnormalities commonly reported in children with ADHD are also present in adults, and for the first time show a relationship between postural control atypicalities and the cerebellum in this group. Our findings extend the literature on motor abnormalities in ADHD and contribute to our knowledge of their neural substrate. PMID:26106567

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

PubMed

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

2017-06-23

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

Fractone-heparan sulphates mediate FGF-2 stimulation of cell proliferation in the adult subventricular zone.

PubMed

Douet, V; Kerever, A; Arikawa-Hirasawa, E; Mercier, F

2013-04-01

Fractones are extracellular matrix structures that form a niche for neural stem cells and their immediate progeny in the subventricular zone of the lateral ventricle (SVZa), the primary neurogenic zone in the adult brain. We have previously shown that heparan sulphates (HS) associated with fractones bind fibroblast growth factor-2 (FGF-2), a powerful mitotic growth factor in the SVZa. Here, our objective was to determine whether the binding of FGF-2 to fractone-HS is implicated in the mechanism leading to cell proliferation in the SVZa. Heparitinase-1 was intracerebroventricularly injected with FGF-2 to N-desulfate HS proteoglycans and determine whether the loss of HS and of FGF-2 binding to fractones modifies FGF-2 effect on cell proliferation. We also examined in vivo the binding of Alexa-Fluor-FGF-2 in relationship with the location of HS immunoreactivity in the SVZa. Heparatinase-1 drastically reduced the stimulatory effect of FGF-2 on cell proliferation in the SVZa. Alexa-Fluor-FGF-2 binding was strictly co-localized with HS immunoreactivity in fractones and adjacent vascular basement membranes in the SVZa. Our results demonstrate that FGF-2 requires HS to stimulate cell proliferation in the SVZa and suggest that HS associated with fractones and vascular basement membranes are responsible for activating FGF-2. Therefore, fractones and vascular basement membranes may function as a HS niche to drive cell proliferation in the adult neurogenic zone. © 2013 Blackwell Publishing Ltd.

Transcutaneous stimulation of the posterior tibial nerve for treating refractory urge incontinence of idiopathic and neurogenic origin.

PubMed

Valles-Antuña, C; Pérez-Haro, M L; González-Ruiz de L, C; Quintás-Blanco, A; Tamargo-Diaz, E M; García-Rodríguez, J; San Martín-Blanco, A; Fernandez-Gomez, J M

2017-09-01

To assess the efficacy of treatment with transcutaneous posterior tibial nerve stimulation (TPTNS) in patients with urge urinary incontinence, of neurogenic or nonneurogenic origin, refractory to first-line therapeutic options. We included 65 patients with urge urinary incontinence refractory to medical treatment. A case history review, a urodynamic study and a somatosensory evoked potentials (SEP) study were conducted before the TPTNS, studying the functional urological condition by means of a voiding diary. The treatment consisted of 10 weekly sessions of TPTNS lasting 30minutes. Some 57.7% of the patients showed abnormal tibial SEPs, and 42% showed abnormal pudendal SEPs. A statistically significant symptomatic improvement was observed in all clinical parameters after treatment with TPTNS, and 66% of the patients showed an overall improvement, regardless of sex, the presence of underlying neurological disorders, detrusor hyperactivity in the urodynamic study or SEP disorders. There were no adverse effects during the treatment. TPTNS is an effective and well tolerated treatment in patients with urge incontinence refractory to first-line therapies and should be offered early in the treatment strategy. New studies are needed to identify the optimal parameters of stimulation, the most effective treatment protocols and long-term efficacy, as well as its applicability to patients with a neurogenic substrate. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Adult Education and the Challenges of Regional Development: Policy and Sustainability in North Denmark

ERIC Educational Resources Information Center

Rasmussen, Palle; Staugaard, Hans Jørgen

2016-01-01

Adult education is governed at many levels--internationally, nationally and locally. The authors of this paper look at the challenges, structures and practices of adult education policy at the local level, more specifically in North Denmark (Northern Jutland), one of the five administrative regions of the Danish nation-state. In many ways, the…

IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

PubMed Central

Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

2016-01-01

The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

PubMed Central

Piedimonte, G; McDonald, D M; Nadel, J A

1991-01-01

Glucocorticoids inhibit plasma extravasation induced in the rat tracheal mucosa by substance P and other tachykinins released from sensory nerves. This study was performed to determine whether this antiinflammatory effect of glucocorticoids is mediated by the tachykinin-degrading enzymes neutral endopeptidase (NEP) and kininase II (angiotensin converting enzyme, ACE). In addition, we studied the effect of dexamethasone on a nonpeptide inflammatory mediator, platelet-activating factor (PAF), which is not degraded by NEP or ACE. Adult male pathogen-free F344 rats were treated for 2 d with dexamethasone (0.5 mg/kg per d i.p.), or with the vehicle used to dissolve the steroid. The magnitude of plasma extravasation produced by an intravenous injection of substance P (5 micrograms/kg) or PAF (10 micrograms/kg) was then assessed by using Monastral blue pigment as an intravascular tracer. The role of NEP and ACE activities in the changes produced by dexamethasone was investigated by examining the effect of the selective inhibitors of these enzymes, phosphoramidon and captopril. Dexamethasone reduced the substance P-induced extravasation by 57% but did not affect the PAF-induced extravasation. The suppressive effect of dexamethasone on substance P-induced extravasation was completely reversed by simultaneously inhibiting NEP and ACE activities, but the inhibition of these enzymes had no effect on PAF-induced extravasation, regardless of whether the rats were pretreated with dexamethasone or not. These results suggest that NEP and ACE mediate a selective inhibitory effect of glucocorticoids on neurogenic plasma extravasation. PMID:1711545

Relationships between regional cerebellar volume and sensorimotor and cognitive function in young and older adults

PubMed Central

Bernard, Jessica A.; Seidler, Rachael D.

2013-01-01

The cerebellum has been implicated in both sensorimotor and cognitive function, but is known to undergo volumetric declines with advanced age. Individual differences in regional cerebellar volume may therefore provide insight into performance variability across the lifespan, as has been shown with other brain structures and behaviors. Here, we investigated whether there are regional age differences in cerebellar volume in young and older adults, and whether these volumes explain, in part, individual differences in sensorimotor and cognitive task performance. We found that older adults had smaller cerebellar volume than young adults; specifically, lobules in the anterior cerebellum were more impacted by age. Multiple regression analyses for both age groups revealed associations between sensorimotor task performance in several domains (balance, choice reaction time, and timing) and regional cerebellar volume. There were also relationships with working memory, but none with measures of general cognitive or executive function. Follow-up analyses revealed several differential relationships with age between regional volume and sensorimotor performance. These relationships were predominantly selective to cerebellar regions that have been implicated in cognitive functions. Therefore, it may be the cognitive aspects of sensorimotor task performance that are best explained by individual differences in regional cerebellar volumes. In sum, our results demonstrate the importance of regional cerebellar volume with respect to both sensorimotor and cognitive performance, and we provide additional insight into the role of the cerebellum in age-related performance declines. PMID:23625382

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

PubMed

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

2017-03-01

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

Norepinephrine precursor therapy in neurogenic orthostatic hypotension.

PubMed

Kaufmann, Horacio; Saadia, Daniela; Voustianiouk, Andrei; Goldstein, David S; Holmes, Courtney; Yahr, Melvin D; Nardin, Rachel; Freeman, Roy

2003-08-12

In patients with neurogenic orthostatic hypotension (NOH), the availability of the sympathetic neurotransmitter norepinephrine (NE) in the synaptic cleft is insufficient to maintain blood pressure while in the standing posture. We determined the effect of oral administration of the synthetic amino acid L-threo-3,4-dihydroxyphenylserine (L-DOPS), which is decarboxylated to NE by the enzyme L-aromatic amino acid decarboxylase (L-AADC) in neural and nonneural tissue, on blood pressure and orthostatic tolerance in 19 patients with severe NOH (8 with pure autonomic failure and 11 with multiple-system atrophy). A single-blind dose-titration study determined the most appropriate dose for each patient. Patients were then enrolled in a double-blind, placebo-controlled, crossover trial. L-DOPS significantly raised mean blood pressure both supine (from 101+/-4 to 141+/-5 mm Hg) and standing (from 60+/-4 to 100+/-6 mm Hg) for several hours and improved orthostatic tolerance in all patients. After L-DOPS, blood pressure increases were closely associated with increases in plasma NE levels. Oral administration of carbidopa, which inhibits L-AADC outside the blood-brain barrier, blunted both the increase in plasma NE and the pressor response to L-DOPS in all patients Acute administration of L-DOPS increases blood pressure and improves orthostatic tolerance in patients with NOH. The pressor effect results from conversion of L-DOPS to NE outside the central nervous system.

Regional nonuniformity of normal adult human left ventricle.

PubMed

Bogaert, J; Rademakers, F E

2001-02-01

Regional nonuniformity is a feature of both diseased and normal left ventricles (LV). With the use of magnetic resonance (MR) myocardial tagging, we performed three-dimensional strain analysis on 87 healthy adults in local cardiac and fiber coordinate systems (radial, circumferential, longitudinal, and fiber strains) to characterize normal nonuniformities and to test the validity of wall thickening as a parameter of regional function. Regional morphology included wall thickness and radii of curvature measurements. With respect to transmural nonuniformity, subendocardial strains exceeded subepicardial strains. Going from base to apex, wall thickness and circumferential radii of curvature decreased, whereas longitudinal radii of curvature increased. All of the strains increased from LV base to apex, resulting in a higher ejection fraction (EF) at the apex than at the base (70.9 +/- 0.4 vs. 62.4 +/- 0.4%; means +/- SE, P < 0.0001). When we looked around the circumference of the ventricle, the anterior part of the LV was the flattest and thinnest and showed the largest wall thickening (46.6 +/- 1.2%) but the lowest EF (64.7 +/- 0.5%). The posterior LV wall was thicker, more curved, and showed a lower wall thickening (32.8 +/- 1.0%) but a higher EF (71.3 +/- 0.5%). The regional contribution of the LV wall to the ejection of blood is thus highly variable and is not fully characterized by wall thickening alone. Differences in regional LV architecture and probably local stress are possible explanations for this marked functional nonuniformity.

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

PubMed

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

2016-04-01

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

Acute and Chronic Electroconvulsive Seizures (ECS) Differentially Regulate the Expression of Epigenetic Machinery in the Adult Rat Hippocampus.

PubMed

Pusalkar, Madhavi; Ghosh, Shreya; Jaggar, Minal; Husain, Basma Fatima Anwar; Galande, Sanjeev; Vaidya, Vidita A

2016-09-01

Electroconvulsive seizure treatment is a fast-acting antidepressant therapy that evokes rapid transcriptional, neurogenic, and behavioral changes. Epigenetic mechanisms contribute to altered gene regulation, which underlies the neurogenic and behavioral effects of electroconvulsive seizure. We hypothesized that electroconvulsive seizure may modulate the expression of epigenetic machinery, thus establishing potential alterations in the epigenetic landscape. We examined the influence of acute and chronic electroconvulsive seizure on the gene expression of histone modifiers, namely histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone (lysine) demethylases as well as DNA modifying enzymes, including DNA methyltransferases, DNA demethylases, and methyl-CpG-binding proteins in the hippocampi of adult male Wistar rats using quantitative real time-PCR analysis. Further, we examined the influence of acute and chronic electroconvulsive seizure on global and residue-specific histone acetylation and methylation levels within the hippocampus, a brain region implicated in the cellular and behavioral effects of electroconvulsive seizure. Acute and chronic electroconvulsive seizure induced a primarily unique, and in certain cases bidirectional, regulation of histone and DNA modifiers, and methyl-CpG-binding proteins, with an overlapping pattern of gene regulation restricted to Sirt4, Mll3, Jmjd3, Gadd45b, Tet2, and Tet3. Global histone acetylation and methylation levels were predominantly unchanged, with the exception of a significant decline in H3K9 acetylation in the hippocampus following chronic electroconvulsive seizure. Electroconvulsive seizure treatment evokes the transcriptional regulation of several histone and DNA modifiers, and methyl-CpG-binding proteins within the hippocampus, with a predominantly distinct pattern of regulation induced by acute and chronic electroconvulsive seizure. © The Author 2016. Published by Oxford

Acute and Chronic Electroconvulsive Seizures (ECS) Differentially Regulate the Expression of Epigenetic Machinery in the Adult Rat Hippocampus

PubMed Central

Pusalkar, Madhavi; Ghosh, Shreya; Jaggar, Minal; Husain, Basma Fatima Anwar; Galande, Sanjeev

2016-01-01

Background: Electroconvulsive seizure treatment is a fast-acting antidepressant therapy that evokes rapid transcriptional, neurogenic, and behavioral changes. Epigenetic mechanisms contribute to altered gene regulation, which underlies the neurogenic and behavioral effects of electroconvulsive seizure. We hypothesized that electroconvulsive seizure may modulate the expression of epigenetic machinery, thus establishing potential alterations in the epigenetic landscape. Methods: We examined the influence of acute and chronic electroconvulsive seizure on the gene expression of histone modifiers, namely histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone (lysine) demethylases as well as DNA modifying enzymes, including DNA methyltransferases, DNA demethylases, and methyl-CpG-binding proteins in the hippocampi of adult male Wistar rats using quantitative real time-PCR analysis. Further, we examined the influence of acute and chronic electroconvulsive seizure on global and residue-specific histone acetylation and methylation levels within the hippocampus, a brain region implicated in the cellular and behavioral effects of electroconvulsive seizure. Results: Acute and chronic electroconvulsive seizure induced a primarily unique, and in certain cases bidirectional, regulation of histone and DNA modifiers, and methyl-CpG-binding proteins, with an overlapping pattern of gene regulation restricted to Sirt4, Mll3, Jmjd3, Gadd45b, Tet2, and Tet3. Global histone acetylation and methylation levels were predominantly unchanged, with the exception of a significant decline in H3K9 acetylation in the hippocampus following chronic electroconvulsive seizure. Conclusions: Electroconvulsive seizure treatment evokes the transcriptional regulation of several histone and DNA modifiers, and methyl-CpG-binding proteins within the hippocampus, with a predominantly distinct pattern of regulation induced by acute and chronic electroconvulsive seizure. PMID

Monoamine uptake inhibitors block alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation.

PubMed

Long, Cheng; Chen, Mei-Fang; Sarwinski, Susan J; Chen, Po-Yi; Si, Minliang; Hoffer, Barry J; Evans, M Steven; Lee, Tony J F

2006-07-01

We have proposed that activation of cerebral perivascular sympathetic alpha7-nicotinic acetylcholine receptors (alpha7-nAChRs) by nicotinic agonists releases norepinephrine, which then acts on parasympathetic nitrergic nerves, resulting in release of nitric oxide and vasodilation. Using patch-clamp electrophysiology, immunohistochemistry, and in vitro tissue bath myography, we tested this axo-axonal interaction hypothesis further by examining whether blocking norepinephrine reuptake enhanced alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation. The results indicated that choline- and nicotine-induced alpha7-nAChR-mediated nitrergic neurogenic relaxation in endothelium-denuded isolated porcine basilar artery rings was enhanced by desipramine and imipramine at lower concentrations (0.03-0.1 microM) but inhibited at higher concentrations (0.3-10 microM). In cultured superior cervical ganglion (SCG) neurons of the pig and rat, choline (0.1-30 mM)-evoked inward currents were reversibly blocked by 1-30 microM mecamylamine, 1-30 microM methyllycaconitine, 10-300 nM alpha-bungarotoxin, and 0.1-10 microM desipramine and imipramine, providing electrophysiological evidence for the presence of similar functional alpha7-nAChRs in cerebral perivascular sympathetic neurons of pigs and rats. In alpha7-nAChR-expressing Xenopus oocytes, choline-elicited inward currents were attenuated by alpha-bungarotoxin, imipramine, and desipramine. These monoamine uptake inhibitors appeared to directly block the alpha7-nAChR, resulting in diminished nicotinic agonist-induced cerebral nitrergic vasodilation. The enhanced nitrergic vasodilation by lower concentrations of monoamine uptake inhibitors is likely due to a greater effect on monoamine uptake than on alpha7-nAChR blockade. These results further support the hypothesis of axo-axonal interaction in nitrergic regulation of cerebral vascular tone.

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

Global, Regional and Local Influences on Adult Literacy Policy in England

ERIC Educational Resources Information Center

Hamilton, Mary

2014-01-01

This paper explores the relationship between global, regional and local influences on adult literacy policy and practice in the UK through a discourse analysis of policy-related texts. The analysis is framed by theoretical perspectives from literacy studies and socio-material theory. The paper identifies a number of specific features in the UK…

Stem cells distribution, cellular proliferation and migration in the adult Austrolebias charrua brain.

PubMed

Torres-Pérez, Maximiliano; Rosillo, Juan Carlos; Berrosteguieta, Ines; Olivera-Bravo, Silvia; Casanova, Gabriela; García-Verdugo, José Manuel; Fernández, Anabel Sonia

2017-10-15

Our previous studies demonstrated that Austrolebias charrua annual fish is an excellent model to study adult brain cell proliferation and neurogenesis due to the presence of active and fast neurogenesis in several regions during its short lifespan. Our main goal was to identify and localize the cells that compose the neurogenic areas throughout the Austrolebias brain. To do this, we used two thymidine halogenated analogs to detect cell proliferation at different survival times: 5-chloro-2'-deoxyuridine (CldU) at 1day and 5-iodo-2'-deoxyuridine (IdU) at 30days. Three types of proliferating cells were identified: I - transient amplifying or fast cycling cells that uptake CldU; II - stem cells or slow cycling cells, that were labeled with both CldU and IdU and did not migrate; and III - migrant cells that uptake IdU. Mapping and 3D-reconstruction of labeled nuclei showed that type I and type II cells were preferentially found close to ventricle walls. Type III cells appeared widespread and migrating in tangential and radial routes. Use of proliferation markers together with Vimentin or Nestin evidenced that type II cells are the putative stem cells that are located at the ventricular lumen. Double label cells with IdU+ and NeuN or HuC/D allowed us identify migrant neurons. Quantitation of labeled nuclei indicates that the proportion of putative stem cells is around 10% in all regions of the brain. This percentage of stem cells suggests the existence of a constant brain cell population in Austrolebias charrua that seems functional to the maintainance of adult neurogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Tree Changes or Wholesale Changes: The Role of Adult Education in Transitions in Regional Life

ERIC Educational Resources Information Center

Townsend, Robert; Delves, Melinda

2009-01-01

Regional adult education and training providers have been required in recent decades to adapt to funding structures rather than engage with their local communities. This has meant providing education programs that are funded based on national or State and Territory based policy frameworks, often linked to human capital development. Adult education…

Altered neurogenic and mechanical responses to acetylcholine, ATP and substance P in detrusor from rat with outlet obstruction.

PubMed

Pinna, C; Sanvito, P; Puglisi, L

2006-08-22

The well-known side effects of anticholinergic compounds used to treat urinary incontinence caused by detrusor overactivity have addressed the interest on other pharmacological intervention. The purpose of the present work was to investigate the possible changes in purinergic and cholinergic components of parasympathetic neurotransmission in obstructed rat bladders with detrusor overactivity, and to examine the effect of the association of suramin, atropine and indomethacin on nerve-mediated responses to electrical field stimulation (EFS). Mechanical responses to exogenous acetylcholine, ATP and substance P were also evaluated. Altered sensitivities to acetylcholine and to the sensory neurotransmitter substance P, but unchanged sensitivity to the stable ATP analogue alpha,beta-methyleneATP were observed in bladders from obstructed rats. Suramin and atropine inhibited purinergic and cholinergic components of the neurogenic responses evoked by EFS in detrusor strips from control and obstructed rats. Interestingly, suramin enhanced the antagonistic effect of atropine on neurogenic responses of detrusor strips at all frequencies of stimulation tested. Our results suggest that the association between an antimuscarinic drug and an antagonist of P2X purinoceptors such as suramin might be helpful to reduce the therapeutic dosage of the antimuscarinic drug, along with its side effects. This approach may be of interest in the therapy of patients with bladder incontinence caused by detrusor overactivity, which do not even respond to a maximal dosage of antimuscarinic drug.

Effects of the novel norepinephrine prodrug, droxidopa, on ambulatory blood pressure in patients with neurogenic orthostatic hypotension.

PubMed

Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Hewitt, L Arthur; Rowse, Gerald J; White, William B

2016-10-01

The prodrug droxidopa increases blood pressure (BP) in patients with neurogenic orthostatic hypotension. The BP profile of droxidopa in neurogenic orthostatic hypotension patients (n = 18) was investigated using ambulatory BP monitoring. Following dose optimization and a washout period, 24-hour "off-drug" data were collected. "On-drug" assessment was conducted after 4-5 weeks of droxidopa treatment (mean dose, 444 mg, three times daily). Ambulatory monitoring off drug revealed that 90% of patients already had abnormalities in the circadian BP profile and did not meet criteria for normal nocturnal BP dipping. On treatment, both overall mean 24-hour systolic and diastolic BPs were higher compared to off drug (137/81 mm Hg vs. 129/76 mm Hg; P = .017/.002). Mean daytime systolic BP was significantly higher with droxidopa (8.4 ± 3.1 mm Hg; P = .014). Although nocturnal BP was not significantly higher on droxidopa versus off treatment (P = .122), increases in nocturnal (supine) BP ≥10 mm Hg were observed in four cases (22%). Severe supine systolic hypertensive readings at night (>200 mm Hg) were captured in one case and only while on treatment. These data demonstrate that ambulatory BP monitoring is useful to evaluate the circadian BP profile after initiating treatment with a pressor agent. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Nootropic agents stimulate neurogenesis. Brain Cells, Inc.: WO2007104035.

PubMed

Taupin, Philippe

2009-05-01

The application is in the field of adult neurogenesis, neural stem cells and cellular therapy. It aims to characterize the activity of nootropic agents on adult neurogenesis in vitro. Nootropic agents are substances improving cognitive and mental abilities. AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) and nootropic agents were assessed for the potential to differentiate human neural progenitor and stem cells into neuronal cells in vitro. They were also tested for their behavioural activity on the novel object recognition task. AMPA, piracetam, FK-960 and SGS-111 induce and stimulate neuronal differentiation of human-derived neural progenitor and stem cells. SGS-111 increases the number of visits to the novel object. The neurogenic activity of piracetam and SGS-111 is mediated through AMPA receptor. The neurogenic activity of SGS-111 may contribute and play a role in its nootropic activity. These results suggest that nootropic agents may elicit some of their effects through their neurogenic activity. The application claims the use of nootropic agents for their neurogenic activity and for the treatment of neurological diseases, disorders and injuries, by stimulating or increasing the generation of neuronal cells in the adult brain.

What is CAR doing in the middle of the adult neurogenic road?

PubMed Central

Junyent, Felix; Coré, Nathalie; Cremer, Harold

2017-01-01

ABSTRACT The molecular and cellular basis of adult neurogenesis has attracted considerable attention for fundamental and clinical applications because neural stem cells and newborn neurons may, one day, be harnessed to replace neurons and allow cognitive improvement in the diseased brain. In rodents, neural progenitors are located in the dentate gyrus and the sub/periventricular zone. In the dentate gyrus the generation of newborn neurons is associated with plasticity, including regulation of memory. The role of subventricular zone neural precursors that migrate to the olfactory bulb is less characterized. Identifying factors that impact neural stem cell proliferation, migration and differentiation is therefore sine qua non before we can harness their potential. Here, we expand upon our recent results showing that CAR, the coxsackievirus and adenovirus receptor, is among the developing list of key players when it comes to the complex process of integrating newborn neurons into existing circuits in the mature brain. PMID:28516108

Negative regulation of TLX by IL-1β correlates with an inhibition of adult hippocampal neural precursor cell proliferation.

PubMed

Ryan, Sinead M; O'Keeffe, Gerard W; O'Connor, Caitriona; Keeshan, Karen; Nolan, Yvonne M

2013-10-01

Adult hippocampal neurogenesis is modulated by a number of intrinsic and extrinsic factors including local signalling molecules, exercise, aging and inflammation. Inflammation is also a major contributor to several hippocampal-associated disorders. Interleukin-1beta (IL-1β) is the most predominant pro-inflammatory cytokine in the brain, and an increase in its concentration is known to decrease the proliferation of both embryonic and adult hippocampal neural precursor cells (NPCs). Recent research has focused on the role of nuclear receptors as intrinsic regulators of neurogenesis, and it is now established that the orphan nuclear receptor TLX is crucial in maintaining the NPC pool in neurogenic brain regions. To better understand the involvement of TLX in IL-1β-mediated effects on hippocampal NPC proliferation, we examined hippocampal NPC proliferation and TLX expression in response to IL-1β treatment in an adult rat hippocampal neurosphere culture system. We demonstrate that IL-1β reduced the proliferation of hippocampal NPCs and TLX expression in a dose and time-dependent manner and that co-treatment with IL-1β receptor antagonist or IL-1 receptor siRNA prevented these effects. We also report a dose-dependent effect of IL-1β on the composition of cell phenotypes in the culture and on expression of TLX in these cells. This study thus provides evidence of an involvement of TLX in IL-1β-induced changes in adult hippocampal neurogenesis, and offers mechanistic insight into disorders in which neuroinflammation and alterations in neurogenesis are characteristic features. Copyright © 2013 Elsevier Inc. All rights reserved.

GABA-CREB signalling regulates maturation and survival of newly generated neurons in the adult hippocampus

PubMed Central

Jagasia, Ravi; Steib, Kathrin; Englberger, Elisabeth; Herold, Sabine; Faus-Kessler, Theresa; Saxe, Michael; Gage, Fred H.; Song, Hongjun; Lie, D. Chichung

2009-01-01

Survival and integration of new neurons in the hippocampal circuit are rate-limiting steps in adult hippocampal neurogenesis. Neuronal network activity is a major regulator of these processes, yet little is known about the respective downstream signalling pathways. Here, we investigate the role of CREB signalling in adult hippocampal neurogenesis. CREB is activated in new granule neurons during a distinct developmental period. Loss of CREB function in a cell-autonomous fashion impairs dendritic development, decreases the expression of the neurogenic transcription factor NeuroD and of the neuronal microtubule associated protein, DCX, and compromises the survival of newborn neurons. In addition, GABA-mediated excitation regulates CREB activation at early developmental stages. Importantly, developmental defects following loss of GABA-mediated excitation can be compensated by enhanced CREB signalling. These results indicate that CREB signalling is a central pathway in adult hippocampal neurogenesis, regulating the development and survival of new hippocampal neurons downstream of GABA-mediated excitation. PMID:19553437

Neurogenic bowel management after spinal cord injury: Malaysian experience.

PubMed

Engkasan, Julia Patrick; Sudin, Siti Suhaida

2013-02-01

To describe the bowel programmes utilized by individuals with spinal cord injury; and to determine the association between the outcome of the bowel programmes and various interventions to facilitate defecation. A cross-sectional study. Individuals with spinal cord injury who have neurogenic bowel dysfunction. Face-to-face interviews were conducted using a self-constructed questionnaire that consisted of: (i) demographic and clinical characteristics of the participants; (ii) interventions to facilitate defecation; (iii) bowel care practices; (iv) outcome of the bowel programme (incidence of incontinence and duration of the evacuation procedure); and (v) participant satisfaction with their bowel programme. The majority (79.2%) of subjects used multiple interventions for bowel care. Duration of the evacuation procedure was more than 60 min in 28.0% of participants. Water intake of more than 2 l/day was associated with longer duration of bowel care. Only 8.0% of participants had at least one episode of incontinence per month. The majority of participants (84.8%) were satisfied with their bowel programme. Patients used multiple interventions to manage their bowels and spent a substantial amount of time performing bowel care. Nevertheless, the incidence of incontinence was low and satisfaction with their bowel programme was high.

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

PubMed Central

Linsenmeyer, Todd A.

2013-01-01

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

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�

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

PubMed

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

2015-01-01

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

Neurogenic bowel dysfunction: Clinical management recommendations of the Neurologic Incontinence Committee of the Fifth International Consultation on Incontinence 2013.

PubMed

Cotterill, Nikki; Madersbacher, Helmut; Wyndaele, Jean J; Apostolidis, Apostolos; Drake, Marcus J; Gajewski, Jerzy; Heesakkers, John; Panicker, Jalesh; Radziszewski, Piotr; Sakakibara, Ryuji; Sievert, Karl-Dietrich; Hamid, Rizwan; Kessler, Thomas M; Emmanuel, Anton

2018-01-01

Evidence-based guidelines for the management of neurological disease and lower bowel dysfunction have been produced by the International Consultations on Incontinence (ICI). These are comprehensive guidelines, and were developed to have world-wide relevance. To update clinical management of neurogenic bowel dysfunction from the recommendations of the 4th ICI, 2009. A series of evidence reviews and updates were performed by members of the working group. The resulting guidelines were presented at the 2012 meeting of the European Association of Urology for consultation, and modifications applied to deliver evidence based conclusions and recommendations for the scientific report of the 5th edition of the ICI in 2013. The current review is a synthesis of the conclusions and recommendations, including the algorithms for initial and specialized management of neurogenic bowel dysfunction. The pathophysiology is described in terms of spinal cord injury, multiple sclerosis, and Parkinson's disease. Assessment requires detailed history and clinical assessment, general investigations, and specialized testing, if required. Treatment primarily focuses on optimizing stool consistency and regulating bowel evacuation to improve quality of life. Symptom management covers conservative and interventional measures to promote good habits and assist stool evacuation, along with prevention of incontinence. Education is essential to achieving optimal bowel management. The review offers a pragmatic approach to management in the context of complex pathophysiology and varied evidence base. © 2017 Wiley Periodicals, Inc.

Dorsal Vagal Complex Modulates Neurogenic Airway Inflammation in a Guinea Pig Model With Esophageal Perfusion of HCl.

PubMed

Chen, Zhe; Sun, Lejia; Chen, Hui; Gu, Dachuan; Zhang, Weitao; Yang, Zifeng; Peng, Tao; Dong, Rong; Lai, Kefang

2018-01-01

Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER) is involved in the esophageal-bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC) on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl) following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD) and substance P (SP) expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha) retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The microinjection of glutamic acid (Glu) or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA), lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER.

Dorsal Vagal Complex Modulates Neurogenic Airway Inflammation in a Guinea Pig Model With Esophageal Perfusion of HCl

PubMed Central

Chen, Zhe; Sun, Lejia; Chen, Hui; Gu, Dachuan; Zhang, Weitao; Yang, Zifeng; Peng, Tao; Dong, Rong; Lai, Kefang

2018-01-01

Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER) is involved in the esophageal–bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC) on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl) following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD) and substance P (SP) expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha) retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The microinjection of glutamic acid (Glu) or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA), lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER. PMID:29867575

Pain, sensory function, and neurogenic inflammatory response in young women with low mood.

PubMed

Lehoux, Cory P; Abbott, Frances V

2011-03-01

To determine the relationship of mood status to pain complaints, sensory function, neurogenic inflammatory response, and general health in young women. Ninety-three women aged 18-29 participated in the study and were categorized by SCL-90-R depression score into low-mood (n=21) and normal-mood (n=72) groups. All subjects were below the threshold for possible clinical depression. Low mood was associated with decreased tactile sensitivity, reduced response to topical capsaicin, and increased complaints of back, joint, muscle, and visceral pain, but not headache, when compared to normal mood controls. Low mood was also associated with reported poorer health and physical functioning, increased psychopathology, and family history of mood problems. These data show that even subclinical low mood is associated with marked alterations in health and psychophysiological function. Copyright © 2011 Elsevier Inc. All rights reserved.

Supplement to the Final Report of the Adult Education Association of the U.S.A. to the U.S. Office of Education; the Regional Conferences Project on Adult Basic Education.

ERIC Educational Resources Information Center

Adult Education Association of U.S.A., Washington, DC.

Based on a project on adult basic education conducted in 1966 by the Adult Education Association of the U.S.A., this document provides a detailed description of regional and national conference activities, together with the roster, programs, speeches, papers, and working materials developed during the project. In general, the regional conferences…

Regional Differences in Correlates of Daily Walking among Middle Age and Older Australian Rural Adults: Implications for Health Promotion

PubMed Central

Dollman, James; Hull, Melissa; Lewis, Nicole; Carroll, Suzanne; Zarnowiecki, Dorota

2016-01-01

Rural Australians are less physically active than their metropolitan counterparts, and yet very little is known of the candidate intervention targets for promoting physical activity in rural populations. As rural regions are economically, socially and environmentally diverse, drivers of regular physical activity are likely to vary between regions. This study explored the region-specific correlates of daily walking among middle age and older adults in rural regions with contrasting dominant primary industries. Participants were recruited through print and electronic media, primary care settings and community organisations. Pedometers were worn by 153 adults for at least four days, including a weekend day. A questionnaire identified potential intra-personal, social and environmental correlates of physical activity, according to a social ecological framework. Regression modelling identified independent correlates of daily walking separately in the two study regions. In one region, there were independent correlates of walking from all levels of the social ecological framework. In the other region, significant correlates of daily walking were almost all demographic (age, education and marital status). Participants living alone were less likely to be physically active regardless of region. This study highlights the importance of considering region-specific factors when designing strategies for promoting regular walking among rural adults. PMID:26761020

Flexible endoscopic evaluation of swallowing (FEES) for neurogenic dysphagia: training curriculum of the German Society of Neurology and the German stroke society.

PubMed

Dziewas, Rainer; Glahn, Jörg; Helfer, Christine; Ickenstein, Guntram; Keller, Jochen; Ledl, Christian; Lindner-Pfleghar, Beate; G Nabavi, Darius; Prosiegel, Mario; Riecker, Axel; Lapa, Sriramya; Stanschus, Sönke; Warnecke, Tobias; Busse, Otto

2016-02-25

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

When should video be added to conventional urodynamics in adults and is it justified by the evidence? ICI-RS 2014.

PubMed

Anding, Ralf; Rosier, Peter; Smith, Phillip; Gammie, Andrew; Giarenis, Ilias; Rantell, Angela; Thiruchelvam, Nikesh; Arlandis, Salvador; Cardozo, Linda

2016-02-01

To debate and evaluate the evidence base regarding the added value of video to urodynamics in adults and to define research questions. In the ICI-RS Meeting 2014 a Think Tank analyzed the current guidelines recommending video urodynamics (VUD) and performed a literature search to determine the level of evidence for the additional value of the imaging with urodynamic assessment of both neurogenic and non-neurogenic lower urinary tract dysfunction. Current guidelines do not specify the added value of imaging to urodynamics. Recommendations are based on single center series and expert opinion. Standard imaging protocols are not available and evidence regarding the balance between number and timing of pictures, patient positioning, and exposure time on the one hand and diagnosis on the other hand is lacking. On the basis of expert consensus VUD is relevant in the follow-up of patients with spinal dysraphism. Evidence for the value of VUD in non-neurogenic lower urinary tract dysfunction is sparse. There is some evidence that VUD is not necessary in uncomplicated female SUI, but expert opinion suggests it might improve the evaluation of patients with recurrent SUI. There is only low level evidence for the addition of video to urodynamics. The ICI-RS Think Tank encourages better reporting of results of imaging and systematic reporting of X-ray doses. Specific research hypotheses regarding the added value of imaging are recommended. The panel suggests the development of standards for technically optimal VUD that is practically achievable with machines that are on the market. © 2016 Wiley Periodicals, Inc.

Neurogenic regulation of proximal bicarbonate and chloride reabsorption.

PubMed

Cogan, M G

1986-01-01

Although a change in renal nerve activity is known to alter proximal reabsorption, it is unclear whether reabsorption of NaHCO3 or NaCl or both are affected. Sprague-Dawley rats (n = 10) were studied using free-flow micropuncture techniques during euvolemia and following acute ipsilateral denervation. Glomerular filtration rate and single nephron glomerular filtration rate were stable. Absolute proximal bicarbonate reabsorption fell following denervation (933 +/- 40 to 817 +/- 30 pmol/min) with a parallel reduction in chloride reabsorption (1,643 +/- 116 to 1,341 +/- 129 peq/min). Urinary sodium, potassium, bicarbonate, and chloride excretion all increased significantly. To further assess the physiological significance of neurogenic modulation of proximal transport, other rats (n = 6) were subjected to acute unilateral nephrectomy (AUN). There is evidence that AUN induces a contralateral natriuresis (renorenal reflex) at least partially by causing inhibition of efferent renal nerve traffic. AUN caused significant changes in proximal NaHCO3 and NaCl reabsorption as well as in whole kidney electrolyte excretion in the same pattern as had denervation. Prior denervation of the remaining kidney prevented the proximal and whole kidney response to AUN (n = 6). In conclusion, depression of renal nerve activity inhibits both NaHCO3 and NaCl reabsorption in the rat superficial proximal convoluted tubule. The data are consistent with the hypothesis that changes in renal nerve activity modify whole kidney electrolyte excretion under physiological conditions at least partially by regulating proximal transport.

[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.

Persistent α-Fetoprotein Elevation in Healthy Adults and Mutational Analysis of α-Fetoprotein Promoter, Enhancer, and Silencer Regions.

PubMed

Jeon, Yejoo; Choi, Yun Suk; Jang, Eun Sun; Kim, Jin Wook; Jeong, Sook-Hyang

2017-01-15

α-Fetoprotein (AFP) is normally <10 ng/mL in adults without malignancy or liver regeneration. However, hereditary or nonhereditary persistence of AFP in healthy adults may be encountered in clinical practice. This study describes four cases of persistent AFP elevation in healthy adults and investigates mutations in key transcription regulatory regions of the AFP gene as potential drivers of AFP overexpression. Four healthy adults with persistently elevated AFP levels (12.1 to 186.1 ng/mL) for >1 year, and 20 controls with low AFP levels (<0.61 to 2.9 ng/mL) were included in the study. AFP levels were collected from the families of two of the patients. We sequenced five regions that are critical for AFP expression: a promoter, two enhancers, and two silencers. One of the two cases in which family information was represented is the first case of hereditary persistence of AFP in South Korea. Mutations related to AFP overexpression were not found in the transcription regulatory regions among the four patients. Persistent AFP elevation is a heterogeneous condition with or without a hereditary pattern and may be caused by factors outside of transcription regulatory region changes. Further research on the mechanism of AFP elevation is needed.

Persistent α-Fetoprotein Elevation in Healthy Adults and Mutational Analysis of α-Fetoprotein Promoter, Enhancer, and Silencer Regions

PubMed Central

Jeon, Yejoo; Choi, Yun Suk; Jang, Eun Sun; Kim, Jin Wook; Jeong, Sook-Hyang

2017-01-01

Background/Aims α-Fetoprotein (AFP) is normally <10 ng/mL in adults without malignancy or liver regeneration. However, hereditary or nonhereditary persistence of AFP in healthy adults may be encountered in clinical practice. This study describes four cases of persistent AFP elevation in healthy adults and investigates mutations in key transcription regulatory regions of the AFP gene as potential drivers of AFP overexpression. Methods Four healthy adults with persistently elevated AFP levels (12.1 to 186.1 ng/mL) for >1 year, and 20 controls with low AFP levels (<0.61 to 2.9 ng/mL) were included in the study. AFP levels were collected from the families of two of the patients. We sequenced five regions that are critical for AFP expression: a promoter, two enhancers, and two silencers. Results One of the two cases in which family information was represented is the first case of hereditary persistence of AFP in South Korea. Mutations related to AFP overexpression were not found in the transcription regulatory regions among the four patients. Conclusions Persistent AFP elevation is a heterogeneous condition with or without a hereditary pattern and may be caused by factors outside of transcription regulatory region changes. Further research on the mechanism of AFP elevation is needed. PMID:27609486

Activity-dependent signaling mechanisms regulating adult hippocampal neural stem cells and their progeny.

PubMed

Crowther, Andrew J; Song, Juan

2014-08-01

Adult neural stem cells (NSCs) reside in a restricted microenvironment, where their development is controlled by subtle and presently underexplored cues. This raises a significant question: what instructions must be provided by this supporting niche to regulate NSC development and functions? Signaling from the niche is proposed to control many aspects of NSC behavior, including balancing the quiescence and proliferation of NSCs, determining the cell division mode (symmetric versus asymmetric), and preventing premature depletion of stem cells to maintain neurogenesis throughout life. Interactions between neurogenic niches and NSCs also govern the homeostatic regulation of adult neurogenesis under diverse physiological, environmental, and pathological conditions. An important implication from revisiting many previously-identifi ed regulatory factors is that most of them (e.g., the antidepressant fluoxetine and exercise) affect gross neurogenesis by acting downstream of NSCs at the level of intermediate progenitors and neuroblasts, while leaving the NSC pool unaffected. Therefore, it is critically important to address how various niche components, signaling pathways, and environmental stimuli differentially regulate distinct stages of adult neurogenesis.

Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

PubMed Central

Cardin, Velia

2016-01-01

Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

MILD® Is an Effective Treatment for Lumbar Spinal Stenosis with Neurogenic Claudication: MiDAS ENCORE Randomized Controlled Trial.

PubMed

Benyamin, Ramsin M; Staats, Peter S; MiDAS Encore, Investigators

2016-05-01

Lumbar spinal stenosis (LSS) is a common degenerative condition of the spine, which is a major cause of pain and functional disability for the elderly. Neurogenic claudication symptoms are a hallmark of LSS, where patients develop low back or leg pain when walking or standing that is relieved by sitting or lumbar flexion. The treatment of LSS generally begins with conservative management such as physical therapy, home exercise programs, and oral analgesics. Once these therapies fail, patients commonly move forward with interventional pain treatment options such as epidural steroid injections (ESIs) or MILD® as the next step. To assess improvement of function and reduction in pain for Medicare beneficiaries following treatment with MILD (treatment group) in LSS patients with neurogenic claudication and verified ligamentum flavum hypertrophy and to compare to a control group receiving ESIs. Prospective, multi-center, randomized controlled clinical trial. Twenty-six US interventional pain management centers. Patients in this trial were randomized one to one into 2 study arms. A total of 302 patients were enrolled, with 149 randomized to MILD and 153 to the active control. Outcomes are assessed using the Oswestry Disability Index (ODI), Numeric Pain Rating Scale (NPRS) and Zurich Claudication Questionnaire (ZCQ). Primary efficacy is the proportion of ODI responders, tested for statistical superiority of the MILD group versus the ESI group. ODI responders are defined as patients achieving the validated Minimal Important Change (MIC) of = 10 point improvement in ODI from baseline to follow-up. Similarly, secondary efficacy is the proportion of NPRS and ZCQ responders using validated MIC thresholds. Primary safety is the incidence of device- or procedure-related adverse events in each group. This report presents safety and efficacy results at 1-year follow-up. Outcomes at 2 years will be collected and reported for patients in the MILD group only. At 1-year follow-up, ODI

Stable region for maxillary dental cast superimposition in adults, studied with the aid of stable miniscrews.

PubMed

Chen, G; Chen, S; Zhang, X Y; Jiang, R P; Liu, Y; Shi, F H; Xu, T M

2011-05-01

To identify a stable and reproducible reference region to superimpose serial maxillary dental models in adult extraction cases. Fifteen adult volunteers were enrolled. To reduce protrusion, bilateral maxillary first premolars were extracted in all volunteers. Each volunteer received six miniscrews, including two loaded miniscrews used to retract anterior teeth and four unloaded miniscrews. Impressions for maxillary models were taken at T1 (1 week after miniscrew placement) and T2 (17 months later). Dental models were created and then scanned using a laser scanner. Stability of the miniscrews was evaluated, and dental models were registered using stationary miniscrews. The palatal region, where deviation was within 0.5 mm in all subjects, was determined to be the stable region. Reproducibility of the new palatal region for 3D digital model superimposition was evaluated. Deviation of the medial 2/3 of the palatal region between the third rugae and the line in contact with the distal surface of the bilateral maxillary first molars was within 0.5 mm. Tooth movement of 15 subjects was measured to evaluate the validity of the new 3D superimposition method. Displacements were 8.18 ± 2.94 mm (central incisor) and 2.25 ± 0.73 mm (first molar) measured by miniscrew superimposition, while values of 7.81 ± 2.53 mm (central incisor) and 2.29 ± 1.03 mm (first molar) were measured using the 3D palatal vault regional superimposition method; no significant difference was observed. The medial 2/3 of the third rugae and the regional palatal vault dorsal to it is a stable region to register 3D digital models for evaluation of orthodontic tooth movement in adult patients. © 2011 John Wiley & Sons A/S.

[Original strategy for prevention of recurrent symptomatic urinary tract infections in patients with neurogenic bladder: Bacterial interference, state of the art].

PubMed

Falcou, L; Davido, B; Even, A; Bouchand, F; Salomon, J; Sotto, A; Denys, P; Dinh, A

2018-05-01

Urinary tract infection (UTI) is the most common complication in patients with neurogenic bladder. The long-term use of antibiotic drugs induces an increase in antimicrobial resistance and adverse drug reactions. Bacterial interference is a new concept to prevent recurrent UTI which consists in a bladder colonization with low virulence bacteria. We performed a literature review on this emerging therapy. Literature review of bacterial interference to prevent symptomatic urinary tract infection in neurological population. Seven prospectives study including 3 randomized, double-blind and placebo controlled trial were analyzed. The neurological population was spinal cord injured in most cases. The bladder colonization was performed with 2 non-pathogen strains of Escherichia coli: HU 2117 and 83972. At 1 month, 38 to 83% of patients were colonized. Mean duration of colonization was 48.5 days to 12.3 months. All studies showed that colonization might reduce the number of urinary tract infections and is safe with absence of serious side effects. Bacterial interference is a promising alternative therapy for the prevention of recurrent symptomatic urinary tract infections in neurogenic patients. This therapy should have developments for a daily use practice and for a long-term efficacy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Development and aging of a brain neural stem cell niche.

PubMed

Conover, Joanne C; Todd, Krysti L

2017-08-01

In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the ventricular-subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new neurons to the olfactory bulb throughout adulthood; however, with increasing age stem cell numbers are reduced and neurogenic capacity is significantly diminished, but new olfactory bulb neurons continue to be produced even in old age. Humans, in contrast, show little to no new neurogenesis after two years of age and whether V-SVZ neural stem cells persist in the adult human brain remains unclear. Here, we review functional and organizational differences in the V-SVZ stem cell niche of mice and humans, and examine how aging affects the V-SVZ niche and its associated functions. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of number needed to treat for droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

PubMed

François, Clément; Rowse, Gerald J; Hewitt, L Arthur; Vo, Pamela; Hauser, Robert A

2016-08-18

Droxidopa is an orally active prodrug that significantly improved dizziness/lightheadedness measured using the Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 in patients with neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson disease, multiple system atrophy, and pure autonomic failure), dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. The efficacy and safety of droxidopa were assessed by determining the number needed to treat (NNT) and the number needed to harm (NNH). Data collected in randomized, placebo-controlled clinical studies in adults with a clinical diagnosis of symptomatic nOH were pooled for efficacy and safety analyses. NNT and NNH were calculated as reciprocals of the risk difference (difference in event rates) for droxidopa versus placebo. The NNT for droxidopa for improvement in OHSA Item 1 was <10. The NNH for adverse events (AEs) leading to discontinuation in the pooled studies was 81. The likelihood of being helped or harmed (LHH) calculated from pooled analysis of the NNT for ≥2 units of improvement in OHSA Item 1 score and the NNH for discontinuations due to AEs were 7.8, 8.8, 3.1, and 3.5 for weeks 1, 2, 4, and 8 after randomization, respectively. Droxidopa is efficacious for treatment of nOH, with an NNT below 10 and an acceptable tolerability profile with NNH ranging from 23 to 302 in the pooled analysis of frequently occurring AEs. Based on the LHH for the pooled analysis at week 1, droxidopa is 7.8 times more likely than placebo to show a clinical benefit than result in discontinuation because of an AE. ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.

Recurrent spontaneous hypoglycaemia causes loss of neurogenic and neuroglycopaenic signs in infants with congenital hyperinsulinism.

PubMed

Christesen, Henrik T; Brusgaard, Klaus; Hussain, Khalid

2012-04-01

Hypoglycaemia-associated autonomic failure (HAAF) with impaired neurogenic and neuroglycopaenic responses occurs in adults following recent, repeated hypoglycaemia. We aimed to evaluate whether HAAF also occurs in patients with infant-onset congenital hyperinsulinism (CHI). A controlled fast was performed in (i) seven CHI infants with initial symptomatic hypoglycaemia and three recent episodes of spontaneous recurrent hypoglycaemia each lasting <5 min and in (ii) seven infants with idiopathic ketotic hypoglycaemia for control. At the time of hypoglycaemia (blood glucose <3 mmol/l or clinical signs), blood was drawn for serum insulin, cortisol, glucagon, adrenalin and nor-adrenalin. Signs of hypoglycaemia were documented. In CHI patients, the ABCC8 and KCNJ11 genes were analysed by denaturing high performance liquid chromatography (DHPLC) and/or direct bidirectional sequencing. Two CHI patients had a paternal ABCC8 mutation, five had no mutations. When repeated hypoglycaemia was provoked, all CHI patients exhibited a complete loss of clinical signs of hypoglycaemia, along with a global blunting of the counter-regulatory hormones cortisol, glucagon, growth hormone, adrenalin and nor-adrenalin responses (median values 256 nmol/l, 23 pmol/l, 5·6 mU/l, 390 pmol/l and 2·9 nmol/l, respectively), irrespective of mutational status. In the controls, hypoglycaemia was always clinically overt with normal counter-regulatory cortisol, glucagon, adrenalin and nor-adrenalin responses (530 nmol/l, 60, 920 pmol/l and 4·0 nmol/l, respectively). Recurrent hyperinsulinaemic hypoglycaemia even of short duration blunts the autonomic, neuroglycopaenic and glucose counter-regulatory hormonal responses in patients with infant-onset CHI resulting in clinically silent hypoglycaemia. Tight, or continuous, glucose monitoring is therefore recommended, especially in conservatively treated patients. © 2012 Blackwell Publishing Ltd.

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.

Structural and cognitive social capital and depression among older adults in two Nordic regions.

PubMed

Forsman, A K; Nyqvist, F; Schierenbeck, I; Gustafson, Y; Wahlbeck, K

2012-01-01

To study the association between structural and cognitive aspects of social capital and depression among older adults in two Nordic regions. Data were retrieved from a postal survey targeting older adults aged 65, 70, 75 and 80 years (N=6 838, response rate=64%) residing in the Västerbotten region (Sweden), and the Österbotten region (Finland) in 2010. The associations between structural (measured by frequency of social contact with friends and neighbours) and cognitive (measured by experienced trust in friends and neighbours) aspects of social capital and depression (measured by Geriatric Depression Scale, GDS-4) were tested by logistic regression analyses. Both low structural and cognitive social capital as defined in the study showed statistically significant associations with depression in older adults. Only experienced trust in neighbours failed to show significant association with depression. In addition, being single and being 80 years of age indicated a higher risk of depression as defined by GDS-4. The findings underline the connection between adequate levels of both structural and cognitive individual social capital and mental health in later life. They also suggest that the connection differs depending on various network types; the cognitive aspect of relationships between friends was connected to depression, while the connection was not found for neighbours. Further, the oldest age group in the sample (80 years of age) is pointed out as a population especially vulnerable for depression that should not be overlooked in mental health promotion and depression prevention.

α1A-Adrenergic Receptor Antagonism Improves Erectile and Cavernosal Responses in Rats With Cavernous Nerve Injury and Enhances Neurogenic Responses in Human Corpus Cavernosum From Patients With Erectile Dysfunction Secondary to Radical Prostatectomy.

PubMed

Martínez-Salamanca, Juan I; La Fuente, José M; Martínez-Salamanca, Eduardo; Fernández, Argentina; Pepe-Cardoso, Augusto J; Louro, Nuno; Carballido, Joaquín; Angulo, Javier

2016-12-01

Cavernous nerve injury (CNI) in rats and radical prostatectomy (RP) in men result in loss of nitrergic function and increased adrenergic-neurogenic contractions of cavernosal tissue. To evaluate the modulation of the α-adrenergic system as a strategy to relieve erectile dysfunction (ED) and functional cavernosal alterations induced by CNI. A non-selective α-blocker (phentolamine 1 mg/kg daily), a selective α 1A -blocker (silodosin [SILOD] 0.1 mg/kg daily), or vehicle was orally administered for 4 weeks after bilateral crush CNI (BCNI). Erectile and neurogenic responses of the corpus cavernosum (CC) were evaluated. The acute effects of SILOD also were evaluated in vivo (0.03 mg/kg intravenously) and ex vivo (10 nmol/L). The effects of SILOD and tadalafil (TAD) on nitrergic relaxations were determined in human CC from patients with ED with a vascular etiology or ED secondary to RP. Erectile responses in vivo in rats and neurogenic contractions and relaxations of rat and human CC. Long-term treatment with SILOD significantly improved erectile responses and allowed for the potentiation of erectile responses by acute treatment with TAD (0.3 mg/kg intravenously) in rats with BCNI. SILOD partly recovered nitrergic relaxations and normalized neurogenic contractions in CC from rats with BCNI. Long-term treatment with SILOD partly prevented BCNI-induced decreases in neuronal nitric oxide synthase expression. Acute administration of SILOD (0.03 mg/kg intravenously) improved erectile responses in vivo and potentiated nitrergic relaxation and decreased neurogenic contractions ex vivo in CC from rats with BCNI. In human CC from patients with ED with a vascular etiology, TAD (30 nmol/L), SILOD (10 nmol/L), or their combination increased nitrergic relaxations. Potentiation by TAD was lost in human CC from patients with ED after RP but was recovered after co-treatment with SILOD. α-Adrenergic modulation, especially selective α 1A -blockade, improves erectile and

Area-Specific Regulation of Quiescent Neural Stem Cells by Notch3 in the Adult Mouse Subependymal Zone.

PubMed

Kawai, Hiroki; Kawaguchi, Daichi; Kuebrich, Benjamin D; Kitamoto, Takeo; Yamaguchi, Masahiro; Gotoh, Yukiko; Furutachi, Shohei

2017-12-06

In the adult mammalian brain, neural stem cells (NSCs) generate new neurons throughout the mammal's lifetime. The balance between quiescence and active cell division among NSCs is crucial in producing appropriate numbers of neurons while maintaining the stem cell pool for a long period. The Notch signaling pathway plays a central role in both maintaining quiescent NSCs (qNSCs) and promoting cell division of active NSCs (aNSCs), although no one knows how this pathway regulates these apparently opposite functions. Notch1 has been shown to promote proliferation of aNSCs without affecting qNSCs in the adult mouse subependymal zone (SEZ). In this study, we found that Notch3 is expressed to a higher extent in qNSCs than in aNSCs while Notch1 is preferentially expressed in aNSCs and transit-amplifying progenitors in the adult mouse SEZ. Furthermore, Notch3 is selectively expressed in the lateral and ventral walls of the SEZ. Knockdown of Notch3 in the lateral wall of the adult SEZ increased the division of NSCs. Moreover, deletion of the Notch3 gene resulted in significant reduction of qNSCs specifically in the lateral and ventral walls, compared with the medial and dorsal walls, of the lateral ventricles. Notch3 deletion also reduced the number of qNSCs activated after antimitotic cytosine β-D-arabinofuranoside (Ara-C) treatment. Importantly, Notch3 deletion preferentially reduced specific subtypes of newborn neurons in the olfactory bulb derived from the lateral walls of the SEZ. These results indicate that Notch isoforms differentially control the quiescent and proliferative steps of adult SEZ NSCs in a domain-specific manner. SIGNIFICANCE STATEMENT In the adult mammalian brain, the subependymal zone (SEZ) of the lateral ventricles is the largest neurogenic niche, where neural stem cells (NSCs) generate neurons. In this study, we found that Notch3 plays an important role in the maintenance of quiescent NSCs (qNSCs), while Notch1 has been reported to act as a regulator

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

PubMed Central

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

2017-01-01

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

Educational inequalities in young-adult mortality between the 1990s and the 2000s: regional differences in Belgium.

PubMed

De Grande, Hannelore; Vandenheede, Hadewijch; Deboosere, Patrick

2015-01-01

This study addresses educational inequalities in young-adult mortality between the 1990s and the 2000s by comparing trends in the three different regions in Belgium stratified by sex. Social inequalities in mortality are of major concern to public health but are rarely studied at young ages. Substantial health differences have been found between the Flemish (FR) and Walloon region (WR) concerning (healthy) life expectancy and avoidable mortality, but little is known about regional differentials in young-adult mortality, and comparisons with the Brussels-Capital Region (BCR) have thus far never been made. Data are derived from record linkage between the Belgian censuses of 1991 and 2001 and register data on death and emigration for the periods 01/03/1991-01/03/1999 and 01/10/2001-01/10/2009. Analyses are restricted to young adults aged 25 to 34 years at the moment of each of the censuses. Absolute (directly standardized mortality rates (ASMRs)) and relative (mortality rate ratio using Poisson regression) measures were calculated. There is a significant drop in young-adult mortality between the 1990s and the 2000s in all regions and both sexes, with the strongest decline in the BCR (e.g. ASMR of men declined from 165.6 [151.1-180.1] per 100,000 person years to 73.8 [88.3-98.3]). The mortality rates remain highest in the WR in the 2000s Between the 1990s and the 2000s, a remarkable change in the educational distribution occurred as well, with much lower proportions of primary educated in all regions in the 2000s in favour of higher proportions in all other educational levels, especially in higher education. All educational groups show lower mortality over time, except for lower educated men in the FR. There is a positive evolution towards lower mortality among the young-adult Belgian population. The WR trails behind in this evolution, which calls for tailored preventive actions. Educational inequalities are marked in all regions and time periods. A more general

Are Global and Regional Improvements in Life Expectancy and in Child, Adult and Senior Survival Slowing?

PubMed Central

Hum, Ryan J.; Verguet, Stéphane; Cheng, Yu-Ling; McGahan, Anita M.; Jha, Prabhat

2015-01-01

Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year2; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year2; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year2. Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year2. Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health–primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest. PMID:25992949

Differences in maximal strength and endurance of the tongue according to region in healthy adults

PubMed Central

Oh, Dong-Hwan; Park, Ji-Su; Kim, Won-Jin

2017-01-01

[Purpose] The purpose of this study was to identify differences in maximal strength and endurance of the tongue among healthy adults. [Subjects and Methods] A total of 60 healthy volunteers (30 men; 30 women; age range, 20–26 years) were recruited and evaluated for maximal strength and endurance of the anterior and posterior regions of the tongue using the Iowa Oral Performance Instrument. [Results] Tongue strength in the anterior region was greater than that in the posterior region. In contrast, tongue endurance in the posterior region was greater than that in the anterior region. [Conclusion] In conclusion, these results confirm that the anterior region of the tongue exhibits greater strength, whereas the posterior region exhibits greater endurance. PMID:29184299

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

PubMed Central

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

2015-01-01

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

Cognitive deficits in adult rats by lead intoxication are related with regional specific inhibition of cNOS.

PubMed

García-Arenas, Guadalupe; Ramírez-Amaya, Victor; Balderas, Israela; Sandoval, Jimena; Escobar, Martha L; Ríos, Camilo; Bermúdez-Rattoni, Federico

2004-02-04

It is well known that lead can affect several cognitive abilities in developing animals. In this work, we investigate the effects of different sub-chronic lead doses (0, 65, 125, 250 and 500 ppm of lead acetate in their drinking water for 14 days) in the performance of male adult rats in a water maze, cue maze and inhibitory avoidance tasks. We found that the acquisition of these tasks was not affected by lead, however, the highest dosage of lead (500 ppm) impaired memory consolidation in spatial and inhibitory avoidance tasks, but not in cue maze task while the 250 ppm dose only affected retrieval of spatial memory. Additionally, hippocampal long-term potentiation (LTP) induction in the perforant path after exposing adult rats to different doses of lead was studied. LTP induction was affected in a dose-dependent manner, and treatments of 250 and 500 ppm completely blocked LTP. We investigated the effects of lead intoxication on the activity of constitutive nitric oxide synthase (cNOS) in different brain regions of adult animals. The activity of cNOS was significantly inhibited in the hippocampus and cerebellum but not in the frontal cortex and brain stem, although lead had accumulated in all brain regions. These results suggest that lead intoxication can impair memory in adult animals and this impairment might be related with region-specific effects on cNOS activity.

Neurogenic bowel dysfunction (NBD) translation and linguistic validation to classical Arabic.

PubMed

Mallek, A; Elleuch, M H; Ghroubi, S

2016-09-01

To translate and linguistically validate in classical Arabic; the French version of the neurogenic bowel dysfunction (NBD). Arabic translation of the NBD score was obtained by the "forward translation/backword translation" method. Patients with multiple sclerosis (MS) and spinal cord injury were included. Evaluation of intestinal and anorectal disorders was conducted by the self-administered questionnaire NBD, which was filled twice two weeks apart. An item-by-item analysis was made. The feasibility, acceptability, internal consistency using Cronbach's alpha, and test-retest repeatability by non-parametric Spearman correlation were studied. Twenty-three patients with colorectal disorders secondary to neurological disease were included, the average age was 40.79±9.16years and the sex-ratio was 1.85. The questionnaire was feasible and acceptable, no items were excluded. The spearman correlation was of 0.842. Internal consistency was judged good through the Cronbach's alpha was of 0.896. The Arabic version of NBD was reproducible and construct validity was satisfactory. The study of its responsiveness to change with a larger number of patients will be the subject of further work. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Preoperative Duplex Scanning is a Helpful Diagnostic Tool in Neurogenic Thoracic Outlet Syndrome.

PubMed

Orlando, Megan S; Likes, Kendall C; Mirza, Serene; Cao, Yue; Cohen, Anne; Lum, Ying Wei; Freischlag, Julie A

2016-01-01

To evaluate the diagnostic role of venous and arterial duplex scanning in neurogenic thoracic outlet syndrome (NTOS). Retrospective review of patients who underwent duplex ultrasonography prior to first rib resection and scalenectomy (FRRS) for NTOS from 2005 to 2013. Abnormal scans included ipsilateral compression (IC) with abduction of the symptomatic extremity (>50% change in subclavian vessel flow), contralateral (asymptomatic side) compression (CC) or bilateral compression (BC). A total of 143 patients (76% female, average age 34, range 13-59) underwent bilateral preoperative duplex scanning. Ipsilateral compression was seen in 44 (31%), CC in 12 (8%), and BC in 14 (10%). Seventy-three (51%) patients demonstrated no compression. Patients with IC more often experienced intraoperative pneumothoraces (49% vs. 25%, P < .05) and had positive Adson tests (86% vs. 61%, P < .02). Compression of the subclavian vein or artery on duplex ultrasonography can assist in NTOS diagnosis. Ipsilateral compression on abduction often correlates with Adson testing. © The Author(s) 2016.

Neurogenic lower urinary tract dysfunction: Clinical management recommendations of the Neurologic Incontinence committee of the fifth International Consultation on Incontinence 2013.

PubMed

Drake, Marcus John; Apostolidis, Apostolos; Cocci, Andrea; Emmanuel, Anton; Gajewski, Jerzy B; Harrison, Simon C W; Heesakkers, John P F A; Lemack, Gary E; Madersbacher, Helmut; Panicker, Jalesh N; Radziszewski, Piotr; Sakakibara, Ryuji; Wyndaele, Jean Jacques

2016-08-01

Evidence-based guidelines for the management of neurological disease and lower urinary tract dysfunction have been produced by the International Consultations on Incontinence (ICI). These are comprehensive guidelines, and were developed to have world-wide relevance. To update clinical management of neurogenic bladder dysfunction from the recommendations of the fourth ICI, 2009. A series of evidence reviews and updates were performed by members of the working group. The resulting guidelines were presented at the 2012 meeting of the European Association of Urology for consultation, and consequently amended to deliver evidence-based conclusions and recommendations in 2013. The current review is a synthesis of the conclusions and recommendations, including the algorithms for initial and specialized management of neurogenic lower urinary tract dysfunction. The pathophysiology is categorized according to the nature of onset of neurological disease and the part(s) of the nervous system affected. Assessment requires clinical evaluation, general investigations, and specialized testing. Treatment primarily focuses on ensuring safety of the patient and optimizing quality of life. Symptom management covers conservative and interventional measures to aid urine storage and bladder emptying, along with containment of incontinence. A multidisciplinary approach to management is essential. The review offers a pragmatic review of management in the context of complex pathophysiology and varied evidence base. Neurourol. Urodynam. 35:657-665, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Landscape of Research on Older Adults' Health in the Arab Region: Is It Demography-Driven or Development-Dependent?

PubMed

Sibai, Abla Mehio; Rizk, Anthony; Costanian, Christy; Beard, John Roland

2017-07-01

To describe the quantity, methods, themes, and collaboration profiles of research on older adults' health in the Arab world, and map research productivity against demographic, economic, and development indicators. A scoping review of research on older adults' health drawing from 7 databases and covering the period 1994-2013. Aging research output has increased 6-fold over the study period, with middle-income countries showing the sharpest rise. The majority of the reviewed publications are descriptive in nature, oriented toward examining the extent of disease or factors associated with various morbidity and mortality outcomes (88.5%). Despite the increasing regional instability, there is a dearth of studies on "seniors in emergencies." Collaboration with international coauthors (16.0%) has been more frequent than with regional coauthors (4.2%). Correlation analysis suggests that research production has been more strongly influenced by literacy rates than by population aging indicators, Gross Domestic Product, or government investment in research and development. This study lays the basis for a "roadmap" for research on older adults' health in the Arab region. It calls for cooperation among various stakeholders to produce a targeted and well-informed research agenda that is more responsive to emerging and context-specific needs of older adults in the region. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pharyngeal electrical stimulation device for the treatment of neurogenic dysphagia: technology update.

PubMed

Restivo, Domenico A; Hamdy, Shaheen

2018-01-01

Neurogenic dysphagia (ND) can occur in patients with nervous system diseases of varying etiologies. Moreover, recovery from ND is not guaranteed. The therapeutic approaches for oropharyngeal ND have drastically changed over the last decade, mainly due to a better knowledge of the neurophysiology of swallowing along with the progress of neuroimaging and neurophysiological studies. For this reason, it is a priority to develop a treatment that is repeatable, safe, and can be carried out at the bedside as well as for outpatients. Pharyngeal electrical stimulation (PES) is a novel rehabilitation treatment for ND. PES is carried out via location-specific intraluminal catheters that are introduced transnasally and enable clinicians to stimulate the pharynx directly. This technique has demonstrated increasingly promising evidence in improving swallowing performance in patients with ND associated with stroke and multiple sclerosis, probably by increasing the corticobulbar excitability and inducing cortical reorganization of swallowing motor cortex. In this article, we update the reader as to both the physiologic background and past and current studies of PES in an effort to highlight the clinical progress of this important technique.

Indomethacin promotes survival of new neurons in the adult murine hippocampus accompanied by anti-inflammatory effects following MPTP-induced dopamine depletion.

PubMed

Hain, Elisabeth G; Sparenberg, Maria; Rasińska, Justyna; Klein, Charlotte; Akyüz, Levent; Steiner, Barbara

2018-05-26

Parkinson's disease (PD) is characterized by dopaminergic cell loss and inflammation in the substantia nigra (SN) leading to motor deficits but also to hippocampus-associated non-motor symptoms such as spatial learning and memory deficits. The cognitive decline is correlated with impaired adult hippocampal neurogenesis resulting from dopamine deficit and inflammation, represented in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) mouse model of PD. In the inflammatory tissue, cyclooxygenase (COX) is upregulated leading to an ongoing inflammatory process such as prostaglandin-mediated increased cytokine levels. Therefore, inhibition of COX by indomethacin may prevent the inflammatory response and the impairment of adult hippocampal neurogenesis. Wildtype C57Bl/6 and transgenic Nestin-GFP mice were treated with MPTP followed by short-term or long-term indomethacin treatment. Then, aspects of inflammation and neurogenesis were evaluated by cell counts using immunofluorescence and immunohistochemical stainings in the SN and dentate gyrus (DG). Furthermore, hippocampal mRNA expression of neurogenesis-related genes of the Notch, Wnt, and sonic hedgehog signaling pathways and neurogenic factors were assessed, and protein levels of serum cytokines were measured. Indomethacin restored the reduction of the survival rate of new mature neurons and reduced the amount of amoeboid CD68+ cells in the DG after MPTP treatment. Indomethacin downregulated genes of the Wnt and Notch signaling pathways and increased neuroD6 expression. In the SN, indomethacin reduced the pro-inflammatory cellular response without reversing dopaminergic cell loss. Indomethacin has a pro-neurogenic and thereby restorative effect and an anti-inflammatory effect on the cellular level in the DG following MPTP treatment. Therefore, COX inhibitors such as indomethacin may represent a therapeutic option to restore adult neurogenesis in PD.

Effectiveness of pseudoephedrine as adjunctive therapy for neurogenic shock after acute spinal cord injury: a case series.

PubMed

Wood, G Christopher; Boucher, Andrew B; Johnson, Jessica L; Wisniewski, Jennifer N; Magnotti, Louis J; Croce, Martin A; Swanson, Joseph M; Boucher, Bradley A; Fabian, Timothy C

2014-01-01

To evaluate the effectiveness of pseudoephedrine as adjunctive therapy for neurogenic shock in patients with acute spinal cord injury (SCI). Case series. Academic medical center. Thirty-eight patients admitted to the trauma intensive care unit between September 2005 and October 2012 with an acute SCI and who received more than 1 day of pseudoephedrine for one or more of the following: treatment of bradycardia (heart rate ≤ 50 beats/min), treatment of hypotension (systolic blood pressure < 90 mm Hg), or were receiving intravenous vasopressor support. The effect of adjunctive pseudoephedrine (PSE) was categorized as a success if vasopressors were discontinued after the initiation of PSE or improvement in the number of episodes of bradycardia was noted after the initiation of PSE as evidenced by decreased use of atropine. The effect of pseudoephedrine was categorized as a failure if it did not meet one of the criteria for success. The effect of pseudoephedrine was categorized as inconclusive if there were confounding factors such as vasopressors being restarted for another indication after initial discontinuation. Pseudoephedrine was successful in 31/38 (82%) patients, failed in 2/38 (5%) patients, and had inconclusive results in 5/38 (13%) patients. The mean ± SD time to successful weaning of intravenous vasopressors was 7 ± 7 days. Daily maximum pseudoephedrine doses ranged from 60-720 mg. Mean ± SD duration of pseudoephedrine therapy was 32 ± 23 days (range 2-135 days), with 64.5% of surviving patients discharged while receiving pseudoephedrine. These data suggest that pseudoephedrine is an effective adjunctive therapy in facilitating the discontinuation of intravenous vasopressors and/or atropine in patients with acute SCI with neurogenic shock, although patients will typically require long durations of therapy. © 2013 Pharmacotherapy Publications, Inc.

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

PubMed

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

2016-11-01

Food-derived peptides, such as β-casomorphin BCM7, have potential to cross the gastrointestinal tract and blood-brain barrier and are associated with neurological disorders and neurodevelopmental disorders. We previously established a novel mechanism through which BCM7 affects the antioxidant levels in neuronal cells leading to inflammatory consequences. In the current study, we elucidated the effects of casein-derived peptides on neuronal development by using the neurogenesis of neural stem cells (NSCs) as an experimental model. First, the transient changes in intracellular thiol metabolites during NSC differentiation (neurogenesis) were investigated. Next, the neurogenic effects of food-derived opioid peptides were measured, along with changes in intracellular thiol metabolites, redox status and global DNA methylation levels. We observed that the neurogenesis of NSCs was promoted by human BCM7 to a greater extent, followed by A2-derived BCM9 in contrast to bovine BCM7, which induced increased astrocyte formation. The effect was most apparent when human BCM7 was administered for 1day starting on 3days postplating, consistent with immunocytochemistry. Furthermore, neurogenic changes regulated by bovine BCM7 and morphine were associated with an increase in the glutathione/glutathione disulfide ratio and a decrease in the S-adenosylmethionine/S-adenosylhomocysteine ratio, indicative of changes in the redox and the methylation states. Finally, bovine BCM7 and morphine decreased DNA methylation in differentiating NSCs. In conclusion, these results suggest that food-derived opioid peptides and morphine regulated neurogenesis and differentiation of NSCs through changes in the redox state and epigenetic regulation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of ethanol on immune response in the brain: region-specific changes in adolescent versus adult mice.

PubMed

Kane, Cynthia J M; Phelan, Kevin D; Douglas, James C; Wagoner, Gail; Johnson, Jennifer W; Xu, Jihong; Phelan, Patrick S; Drew, Paul D

2014-02-01

Alcohol use occurs across the life span beginning in adolescence and continuing through adulthood. Ethanol (EtOH)-induced pathology varies with age and includes changes in neurogenesis, neurodegeneration, and glial cell activation. EtOH-induced changes in glial activation and immune activity are believed to contribute to EtOH-induced neuropathology. Recent studies indicate an emerging role of glial-derived neuroimmune molecules in alcohol abuse and addiction. Adolescent and adult C57BL/6 mice were treated via gavage with 6 g/kg EtOH for 10 days, and tissue was harvested 1 day post treatment. We compared the effects of EtOH on chemokine and cytokine expression and astrocyte glial fibrillary acidic protein (GFAP) immunostaining and morphology in the hippocampus, cerebellum, and cerebral cortex. EtOH increased mRNA levels of the chemokine CCL2/MCP-1 in all 3 regions of adult mice relative to controls. The cytokine interleukin-6 (IL-6) was selectively increased only in the adult cerebellum. EtOH did not affect mRNA levels of the cytokine tumor necrosis factor-alpha (TNF-α) in any of these brain regions in adult animals. Interestingly, CCL2, IL-6, and TNF-α mRNA levels were not increased in the hippocampus, cerebellum, or cortex of adolescent mice. EtOH treatment of adult and adolescent mice resulted in increased GFAP immunostaining. Collectively, these data indicate an age- and region-specific susceptibility to EtOH regulation of neuroinflammatory and addiction-related molecules as well as astrocyte phenotype. These studies may have important implications concerning differential alcohol-induced neuropathology and alcohol addiction across the life span. Copyright © 2013 by the Research Society on Alcoholism.

Blood-brain barrier-supported neurogenesis in healthy and diseased brain.

PubMed

Pozhilenkova, Elena A; Lopatina, Olga L; Komleva, Yulia K; Salmin, Vladimir V; Salmina, Alla B

2017-05-24

Adult neurogenesis is one of the most important mechanisms contributing to brain development, learning, and memory. Alterations in neurogenesis underlie a wide spectrum of brain diseases. Neurogenesis takes place in highly specialized neurogenic niches. The concept of neurogenic niches is becoming widely accepted due to growing evidence of the important role of the microenvironment established in the close vicinity to stem cells in order to provide adequate control of cell proliferation, differentiation, and apoptosis. Neurogenic niches represent the platform for tight integration of neurogenesis and angiogenesis supported by specific properties of cerebral microvessel endothelial cells contributing to establishment of partially compromised blood-brain barrier (BBB) for the adjustment of local conditions to the current metabolic needs of stem and progenitor cells. Here, we review up-to-date data on microvascular dynamics in activity-dependent neurogenesis, specific properties of BBB in neurogenic niches, endothelial-driven mechanisms of clonogenic activity, and future perspectives for reconstructing the neurogenic niches in vitro.

cis-Regulatory control of the initial neurogenic pattern of onecut gene expression in the sea urchin embryo.

PubMed

Barsi, Julius C; Davidson, Eric H

2016-01-01

Specification of the ciliated band (CB) of echinoid embryos executes three spatial functions essential for postgastrular organization. These are establishment of a band about 5 cells wide which delimits and bounds other embryonic territories; definition of a neurogenic domain within this band; and generation within it of arrays of ciliary cells that bear the special long cilia from which the structure derives its name. In Strongylocentrotus purpuratus the spatial coordinates of the future ciliated band are initially and exactly determined by the disposition of a ring of cells that transcriptionally activate the onecut homeodomain regulatory gene, beginning in blastula stage, long before the appearance of the CB per se. Thus the cis-regulatory apparatus that governs onecut expression in the blastula directly reveals the genomic sequence code by which these aspects of the spatial organization of the embryo are initially determined. We screened the entire onecut locus and its flanking region for transcriptionally active cis-regulatory elements, and by means of BAC recombineered deletions identified three separated and required cis-regulatory modules that execute different functions. The operating logic of the crucial spatial control module accounting for the spectacularly precise and beautiful early onecut expression domain depends on spatial repression. Previously predicted oral ectoderm and aboral ectoderm repressors were identified by cis-regulatory mutation as the products of goosecoid and irxa genes respectively, while the pan-ectodermal activator SoxB1 supplies a transcriptional driver function. Copyright © 2015. Published by Elsevier Inc.

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

PubMed

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

1995-11-01

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

Regional Resource Initiative. A Blueprint for Sharing Resources and Expertise in Adult Education and Literacy across State Lines.

ERIC Educational Resources Information Center

Tennessee Univ., Knoxville. Center for Literacy Studies.

The Arizona Adult Literacy and Technology Resource Center and the University of Tennessee's Center for Literacy Studies undertook a collaborative project to explore the feasibility and effectiveness of regional sharing of resources and expertise in field of adult education and literacy education. The project's goals were as follows: involve a…

Experiencing Unmet Medical Needs or Delayed Care Because of Cost: Foreign-Born Adults in the U.S. by Region of Birth.

PubMed

Choi, Sunha

2016-10-01

Healthy People 2020 in the United States highlights timely access to necessary health care as a major factor that can reduce health-related disparities. This study examined the prevalence of delaying/missing necessary health care because of cost among foreign-born adults (26+ years old) in the United States by their region of origin, after controlling for geographic clustering at the county and state levels. Using the pooled 2007-2011 National Health Interview Survey and linked state/county-level data, this study analyzed data on 61,732 foreign-born adults from nine regions of birth. Three-level multilevel modeling (state > county > individual) was conducted. The age-adjusted percentages of foreign-born adults who delayed/missed necessary health care because of cost varied by region of birth, ranging from 7.0% (Southeast Asia) and 11.9% (Europe) to 15.5% (Mexico/Central America/Caribbean) and 16.7% (the Middle East). However, after controlling for geographic clustering and other individual-level covariates (e.g., insurance), adults from Mexico/Central America/Caribbean were less likely to delay or not receive necessary care compared to their counterparts from all other parts of the world except for those from Asian regions. This study implies that disparities can be reduced if some known risk factors (e.g., insurance) are improved among foreign-born adults. © The Author(s) 2016.

Evaluation of neurogenic dysphagia in Iraqi patients with acute stroke.

PubMed

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

2010-04-01

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

Trends in the educational gradient of mortality among US adults aged 45 to 84 years: bringing regional context into the explanation.

PubMed

Montez, Jennifer Karas; Berkman, Lisa F

2014-01-01

We investigated trends in the educational gradient of US adult mortality, which has increased at the national level since the mid-1980s, within US regions. We used data from the 1986-2006 National Health Interview Survey Linked Mortality File on non-Hispanic White and Black adults aged 45 to 84 years (n = 498,517). We examined trends in the gradient within 4 US regions by race-gender subgroup by using age-standardized death rates. Trends in the gradient exhibited a few subtle regional differences. Among women, the gradient was often narrowest in the Northeast. The region's distinction grew over time mainly because low-educated women in the Northeast did not experience a significant increase in mortality like their counterparts in other regions (particularly for White women). Among White men, the gradient narrowed to a small degree in the West. The subtle regional differences indicate that geographic context can accentuate or suppress trends in the gradient. Studies of smaller areas may provide insights into the specific contextual characteristics (e.g., state tax policies) that have shaped the trends, and thus help explain and reverse the widening mortality disparities among US adults.

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

PubMed

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

2011-08-01

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

[Efficacy of Botulinum-A toxin injection into bladder to treat neurogenic incontinence in patients with spinal cord injury: comparison of two doses].

PubMed

Fu, Guang; Wu, Juan; Cong, Huiling; Zha, Lihua; Li, Dong; Ju, Yanhe; Chen, Guoqing; Xiong, Zhongsheng; Liao, Limin

2015-12-19

To evaluate the efficacy of Botulinum-A toxin injection into bladder to treat neurogenic incontinence in patients with spinal cord injury and compare effectiveness of two different doses (200 U and 300 U). Between January 2009 and October 2014, A total of 60 adult patients with spinal cord injury above the sacral (mean age, 32 years; male 56, female 4) were selected in Beijing Bo'ai Hospital of China Rehabilitation Research Center. All the patients kept voiding diary and underwent urodynamic examination before operation. All the patients were allocated with a random number table into 200 U Botulinum-A toxin injection group or 300 U group (both n=30). In the 200 U group, 200 U of Botulinum-A toxin were dissolved in 10 ml of normal saline, which was injected into 20 different sites (0.5 ml for each site) of bladder wall, including 10 outside the bladder trigone and the remaining 10 inside trigone. In the 300 U group, 300 U of Botulinum-A toxin were dissolved in 15 ml of normal saline, which was injected into 30 different sites (0.5 ml for each site) in bladder outside of the bladder trigone using a flexible cystoscopic needle. The evaluation of the effects and follow-up included voiding diary, urodynamic testing and observation of adverse and toxic effects. At baseline, mean urinary incontinence frequencies were (15.2±3.2) episodes/day and (16.2±2.9) episodes/day in 200 U and 300 U group, which reduced to (2.9±1.2) episodes/day and (2.5±1.4) episodes/day, respectively in week 4 (P<0.05). However, continence rate was not significantly different between the two dose groups [63% (19/30) vs 70% (21/30), P>0.05]. The effect of botulinum-A toxin started to be observed from the 1(st) posttreatment week on average. Obvious improvements in maximum cystometric capacity, end-filling maximum detrusor pressure, and bladder compliance were observed at week 4 as shown by urodynamics (all P<0.05), but with no significant difference between the 200 U and 300 U groups. In the

Botulinum toxin in spinal cord injury patients with neurogenic detrusor overactivity

PubMed Central

Cho, Young Sam; Kim, Khae Hawn

2016-01-01

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

Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

PubMed Central

López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

2016-01-01

Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice

Intradetrusor Injections of Onabotulinum Toxin-A in Children With Urinary Incontinence due to Neurogenic Detrusor Overactivity Refractory to Antimuscarinic Treatment.

PubMed

Tarcan, Tufan; Akbal, Cem; Sekerci, Cağri A; Top, Tuncay; Simşek, Ferruh

2014-04-01

This was a prospective single-arm study to assess the efficacy and safety of intradetrusor injections of onabotulinum toxin-A in children with urinary incontinence associated with neurogenic detrusor overactivity due to myelomeningocele. All patients had failed the first-line treatment of a combination of oral antimuscarinics and intermittent catheterization. The study group consisted of 31 children with myelomeningocele with a mean age of 7.95 years (range, 5-3 years) who were followed up for a mean of 29 weeks. The amount of onabotulinum toxin A injected was 10 U/kg with a maximal dose of 300 U. There were 20 to 30 injection sites with rigid cystoscopic guidance under general anesthesia. Thirty of 31 patients reported dryness between intermittent catheterization intervals. The mean reduction in maximum detrusor pressure and the mean increase in maximum cystometric capacity from baseline were 53% and 51.5%, respectively, 6 weeks after injection. We found a 324% increase in mean bladder compliance and a 57% increase in mean intermittent catheterization volumes. The mean duration of efficacy was 28 weeks with a single injection and 36 weeks for repeated injections (minimum, 16 weeks; maximum, 52 weeks). The mean time interval between repeated onabotulinum toxin-A injections was 7 months (maximum, 13 months). Intradetrusor injections of onabotulinum toxin-A were well tolerated. Onabotulinum toxin-A injections into the bladder wall provide a significant symptomatic and urodynamic improvement in children with neurogenic detrusor overactivity due to myelomeningocele who are on intermittent catheterization. The treatment seems to be safe and very well tolerated.

Regional fat distribution in adolescent and adult females with anorexia nervosa: A longitudinal study.

PubMed

El Ghoch, Marwan; Milanese, Chiara; Calugi, Simona; Müller, Manfred J; Pourhassan, Maryam; Ruocco, Antonella; Dalle Grave, Riccardo

2015-12-01

No study has yet compared body fat distribution before and after weight restoration in adolescent and adult patients with anorexia nervosa (AN) treated according to the same protocol. The study was set up to measure body fat distribution before and after short-term weight restoration in adolescent and adult patients with AN treated according to the same protocol in a specialist inpatient unit. We recruited 33 consecutive adolescent female patients with AN, and 33 controls matched by age and post-treatment BMI centile, as well as 33 adult female patients with AN, and 33 controls matched by age and post-treatment BMI. Dual-energy X-ray absorptiometry (DXA) was used to assess body composition before and after short-term weight restoration (BMI ≥ 18.5 kg/m²). Compared with controls, both adolescents and adults with AN showed that a greater amount of fat was lost from the extremities than the trunk before weight restoration, and that there was a central adiposity phenotype after short-term weight restoration. There were no significant differences in body fat distribution between adolescents and adults with AN before or after short-term weight restoration. Adolescent and adult females with AN have similar body fat distribution both before and after short-term weight restoration, and show a central adiposity phenotype after short-term weight restoration. The clinical implications of this finding are as yet unknown. Clinical Trials Registry- Regional Fat Distribution in Adolescent Girls and Adults with Anorexia Nervosa (ISRCTN73572502). Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Use of Anthropometry for the Prediction of Regional Body Tissue Distribution in Adults: Benefits and Limitations in Clinical Practice

PubMed Central

Scafoglieri, Aldo; Clarys, Jan Pieter; Cattrysse, Erik; Bautmans, Ivan

2014-01-01

Regional body composition changes with aging. Some of the changes in composition are considered major risk factors for developing obesity related chronic diseases which in turn may lead to increased mortality in adults. The role of anthropometry is well recognized in the screening, diagnosis and follow-up of adults for risk classification, regardless of age. Regional body composition is influenced by a number of intrinsic and extrinsic factors. Therapeutic measures recommended to lower cardiovascular disease risk include lifestyle changes. The aim of this review is to systematically summarize studies that assessed the relationships between anthropometry and regional body composition. The potential benefits and limitations of anthropometry for use in clinical practice are presented and suggestions for future research given. PMID:25489489

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

PubMed

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

2014-12-01

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

Network modeling of adult neurogenesis: shifting rates of neuronal turnover optimally gears network learning according to novelty gradient.

PubMed

Chambers, R Andrew; Conroy, Susan K

2007-01-01

Apoptotic and neurogenic events in the adult hippocampus are hypothesized to play a role in cognitive responses to new contexts. Corticosteroid-mediated stress responses and other neural processes invoked by substantially novel contextual changes may regulate these processes. Using elementary three-layer neural networks that learn by incremental synaptic plasticity, we explored whether the cognitive effects of differential regimens of neuronal turnover depend on the environmental context in terms of the degree of novelty in the new information to be learned. In "adult" networks that had achieved mature synaptic connectivity upon prior learning of the Roman alphabet, imposition of apoptosis/neurogenesis before learning increasingly novel information (alternate Roman < Russian < Hebrew) reveals optimality of informatic cost benefits when rates of turnover are geared in proportion to the degree of novelty. These findings predict that flexible control of rates of apoptosis-neurogenesis within plastic, mature neural systems optimizes learning attributes under varying degrees of contextual change, and that failures in this regulation may define a role for adult hippocampal neurogenesis in novelty- and stress-responsive psychiatric disorders.

Synaptic Regulator α-Synuclein in Dopaminergic Fibers Is Essentially Required for the Maintenance of Subependymal Neural Stem Cells.

PubMed

Perez-Villalba, Ana; Sirerol-Piquer, M Salomé; Belenguer, Germán; Soriano-Cantón, Raúl; Muñoz-Manchado, Ana Belén; Villadiego, Javier; Alarcón-Arís, Diana; Soria, Federico N; Dehay, Benjamin; Bezard, Erwan; Vila, Miquel; Bortolozzi, Analía; Toledo-Aral, Juan José; Pérez-Sánchez, Francisco; Fariñas, Isabel

2018-01-24

Synaptic protein α-synuclein (α-SYN) modulates neurotransmission in a complex and poorly understood manner and aggregates in the cytoplasm of degenerating neurons in Parkinson's disease. Here, we report that α-SYN present in dopaminergic nigral afferents is essential for the normal cycling and maintenance of neural stem cells (NSCs) in the brain subependymal zone of adult male and female mice. We also show that premature senescence of adult NSCs into non-neurogenic astrocytes in mice lacking α-SYN resembles the effects of dopaminergic fiber degeneration resulting from chronic exposure to 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine or intranigral inoculation of aggregated toxic α-SYN. Interestingly, NSC loss in α-SYN-deficient mice can be prevented by viral delivery of human α-SYN into their sustantia nigra or by treatment with l-DOPA, suggesting that α-SYN regulates dopamine availability to NSCs. Our data indicate that α-SYN, present in dopaminergic nerve terminals supplying the subependymal zone, acts as a niche component to sustain the neurogenic potential of adult NSCs and identify α-SYN and DA as potential targets to ameliorate neurogenic defects in the aging and diseased brain. SIGNIFICANCE STATEMENT We report an essential role for the protein α-synuclein present in dopaminergic nigral afferents in the regulation of adult neural stem cell maintenance, identifying the first synaptic regulator with an implication in stem cell niche biology. Although the exact role of α-synuclein in neural transmission is not completely clear, our results indicate that it is required for stemness and the preservation of neurogenic potential in concert with dopamine. Copyright © 2018 the authors 0270-6474/18/380815-12$15.00/0.

In-vivo RGB marking and multicolour single-cell tracking in the adult brain

PubMed Central

Gomez-Nicola, Diego; Riecken, Kristoffer; Fehse, Boris; Perry, V. Hugh

2014-01-01

In neuroscience it is a technical challenge to identify and follow the temporal and spatial distribution of cells as they differentiate. We hypothesised that RGB marking, the tagging of individual cells with unique hues resulting from simultaneous expression of the three basic colours red, green and blue, provides a convenient toolbox for the study of the CNS anatomy at the single-cell level. Using γ-retroviral and lentiviral vector sets we describe for the first time the in-vivo multicolour RGB marking of neurons in the adult brain. RGB marking also enabled us to track the spatial and temporal fate of neural stem cells in the adult brain. The application of different viral envelopes and promoters provided a useful approach to track the generation of neurons vs. glial cells at the neurogenic niche, allowing the identification of the prominent generation of new astrocytes to the striatum. Multicolour RGB marking could serve as a universal and reproducible method to study and manipulate the CNS at the single-cell level, in both health and disease. PMID:25531807

Enriched expression of the ciliopathy gene Ick in cell proliferating regions of adult mice.

PubMed

Tsutsumi, Ryotaro; Chaya, Taro; Furukawa, Takahisa

2018-04-07

Cilia are essential for sensory and motile functions across species. In humans, ciliary dysfunction causes "ciliopathies", which show severe developmental abnormalities in various tissues. Several missense mutations in intestinal cell kinase (ICK) gene lead to endocrine-cerebro-osteodysplasia syndrome or short rib-polydactyly syndrome, lethal recessive developmental ciliopathies. We and others previously reported that Ick-deficient mice exhibit neonatal lethality with developmental defects. Mechanistically, Ick regulates intraflagellar transport and cilia length at ciliary tips. Although Ick plays important roles during mammalian development, roles of Ick at the adult stage are poorly understood. In the current study, we investigated the Ick gene expression in adult mouse tissues. RT-PCR analysis showed that Ick is ubiquitously expressed, with enrichment in the retina, brain, lung, intestine, and reproductive system. In the adult brain, we found that Ick expression is enriched in the walls of the lateral ventricle, in the rostral migratory stream of the olfactory bulb, and in the subgranular zone of the hippocampal dentate gyrus by in situ hybridization analysis. We also observed that Ick staining pattern is similar to pachytene spermatocyte to spermatid markers in the mature testis and to an intestinal stem cell marker in the adult small intestine. These results suggest that Ick is expressed in proliferating regions in the adult mouse brain, testis, and intestine. Copyright © 2018 Elsevier B.V. All rights reserved.

Occlusion of Tracheostomy Tubes Does Not Alter Pharyngeal Phase Kinematics But Reduces Penetration by Enhancing Pharyngeal Clearance: A Prospective Study in Patients With Neurogenic Dysphagia.

PubMed

Ledl, Christian; Ullrich, Ylva Yasmin

2017-04-01

Tracheostomy tubes (TT) are often needed in patients with severe neurologic injuries to protect the respiratory system from aspiration. However, TTs alter physiological oral-nasal airflow and are suspected to influence the pattern of pharyngeal swallowing. The aim of this work was to evaluate the effect of TT occlusion on pharyngeal swallowing physiology and to determine penetration-aspiration (PA) values of open versus closed TTs in neurogenic dysphagia. Prospective controlled clinical study with 20 tracheotomized patients after unilateral hemispheric stroke. Pharyngeal manometry and flexible endoscopic evaluation of swallowing were performed simultaneously to determine pharyngoesophageal pressure and timing, as well as PA scores with open and occluded TTs. In each condition, patients had to swallow 5 mL of puree 5 times. Pharyngoesophageal pressure amplitudes, duration, and timing of the swallows did not change as a result of the tracheostomy tube status. Penetration-aspiration values were significantly lower in the occluded tube condition (P = 0.024). Airflow and tracheostomy tube status did not influence the physiology of pharyngoesophageal swallowing in patients with neurogenic dysphagia. However, occluded TTs permitted the voluntary clearance of laryngeal residue and resulted in improved PA scores. We recommend performing dysphagia therapy in tracheotomized patients as soon as possible with uncuffed and occluded tubes.

Soft tissue fibrosarcoma of pre maxillary region in an adult: report of a unique pathological entity

PubMed Central

Naik, Smitha K.; Astekar, Madhusudhan; Rao, Dinesh

2012-01-01

Fibrosarcoma of the oral and maxillofacial region is a rare entity with poor prognosis. Most common sites are the extremities, with only one percent of fibrosarcoma arising in the head and neck area. Oral fibrosarcoma are locally infiltrative and destructive, spreads by haematogenous dissemination. The positive immunostaining for vimentin, together with negativity for muscular immunomarkers help to diagnosis the fibrosarcoma. Surgical management of fibrosarcoma in maxillofacial region is far from satisfactory, because of lack of inadequate clearance. This paper describes an unusual case of soft tissue fibrosarcoma of premaxillary region in an adult aged 71 years. PMID:24765457

Body art practices and health risks: young adults' knowledge in two regions of southern Italy.

PubMed

Gallè, F; Quaranta, A; Napoli, C; Di Onofrio, V; Alfano, V; Montagna, M T; Liguori, G

2012-01-01

In the past several decades the number of individuals, particularly young adults, acquiring body art has increased very seriously in occidental society. In order to verify young adults' practices and knowledge of the risks related to body art, an investigation was conducted among university freshmen in Bari (Apulia Region) and Naples (Campania Region), both in Southern Italy. The study was carried out during the period 2008-2010 through an anonymous questionnaire distributed to 3,868 people selected among 26 Degree Courses of the University of Bari and Naples Parthenope. The two regional samples were matched for age and sex. On the whole, 84.4% declare to know the infectious risks associated with body art practices, but only 4.1% of them correctly identified the infectious diseases which can be transmitted through these procedures; while 59.2% of the sample declared that non-infectious diseases can occur after a tattoo or a piercing, but only 5.4% of them correctly identified allergies, cysts, bleeding and scars. The possible occurrence of infectious and non-infectious diseases has been acknowledged by most students in Apulia region (89.7 versus 79.1% and 64.8 versus 53.6% respectively). In this Region, of the 1,001 (32.4%) pierced and 597 (19.8%) tattooed youths 23.4% reported complications. Campania region youths reported a greater number of complications than Apulia did (30.3 versus 13.1%) and they also purchased more frequently their tattoos or piercings in unauthorized facilities (35.3% versus 15.9%). With regard to the knowledge of health risks associated to body art, it has been registered a higher awareness of infectious than non-infectious diseases. Information about freshmen's knowledge and practices could help in effective planning of health promotion strategies.

Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory.

PubMed

Pristerà, Andrea; Saraulli, Daniele; Farioli-Vecchioli, Stefano; Strimpakos, Georgios; Costanzi, Marco; di Certo, Maria Grazia; Cannas, Sara; Ciotti, Maria Teresa; Tirone, Felice; Mattei, Elisabetta; Cestari, Vincenzo; Canu, Nadia

2013-11-01

Different pathological tau species are involved in memory loss in Alzheimer's disease, the most common cause of dementia among older people. However, little is known about how tau pathology directly affects adult hippocampal neurogenesis, a unique form of structural plasticity implicated in hippocampus-dependent spatial learning and mood-related behavior. To this aim, we generated a transgenic mouse model conditionally expressing a pathological tau fragment (26-230 aa of the longest human tau isoform, or N-tau) in nestin-positive stem/progenitor cells. We found that N-tau reduced the proliferation of progenitor cells in the adult dentate gyrus, reduced cell survival and increased cell death by a caspase-3-independent mechanism, and recruited microglia. Although the number of terminally differentiated neurons was reduced, these showed an increased dendritic arborization and spine density. This resulted in an increase of anxiety-related behavior and an impairment of episodic-like memory, whereas less complex forms of spatial learning remained unaltered. Understanding how pathological tau species directly affect neurogenesis is important for developing potential therapeutic strategies to direct neurogenic instructive cues for hippocampal function repair. Copyright © 2013 Elsevier Inc. All rights reserved.

Cerebroventricular Microinjection (CVMI) into Adult Zebrafish Brain Is an Efficient Misexpression Method for Forebrain Ventricular Cells

PubMed Central

Kizil, Caghan; Brand, Michael

2011-01-01

The teleost fish Danio rerio (zebrafish) has a remarkable ability to generate newborn neurons in its brain at adult stages of its lifespan-a process called adult neurogenesis. This ability relies on proliferating ventricular progenitors and is in striking contrast to mammalian brains that have rather restricted capacity for adult neurogenesis. Therefore, investigating the zebrafish brain can help not only to elucidate the molecular mechanisms of widespread adult neurogenesis in a vertebrate species, but also to design therapies in humans with what we learn from this teleost. Yet, understanding the cellular behavior and molecular programs underlying different biological processes in the adult zebrafish brain requires techniques that allow manipulation of gene function. As a complementary method to the currently used misexpression techniques in zebrafish, such as transgenic approaches or electroporation-based delivery of DNA, we devised a cerebroventricular microinjection (CVMI)-assisted knockdown protocol that relies on vivo morpholino oligonucleotides, which do not require electroporation for cellular uptake. This rapid method allows uniform and efficient knockdown of genes in the ventricular cells of the zebrafish brain, which contain the neurogenic progenitors. We also provide data on the use of CVMI for growth factor administration to the brain – in our case FGF8, which modulates the proliferation rate of the ventricular cells. In this paper, we describe the CVMI method and discuss its potential uses in zebrafish. PMID:22076157

Dose-response study of topical allyl isothiocyanate (mustard oil) as a human surrogate model of pain, hyperalgesia, and neurogenic inflammation.

PubMed

Andersen, Hjalte H; Lo Vecchio, Silvia; Gazerani, Parisa; Arendt-Nielsen, Lars

2017-09-01

Despite being a ubiquitous animal pain model, the natural TRPA1-agonist allyl isothiocyanate (AITC, also known as "mustard oil") has only been sparsely investigated as a potential human surrogate model of pain, sensitization, and neurogenic inflammation. Its dose-response as an algogenic, sensitizing irritant remains to be elucidated in human skin. Three concentrations of AITC (10%, 50%, and 90%) and vehicle (paraffin) were applied for 5 minutes to 3 × 3 cm areas on the volar forearms in 14 healthy volunteers, and evoked pain intensity (visual analog scale 0-100 mm) and pain quality were assessed. In addition, a comprehensive battery of quantitative sensory tests was conducted, including assessment of mechanical and thermal sensitivity. Neurogenic inflammation was quantified using full-field laser perfusion imaging. Erythema and hyperpigmentation were assessed before, immediately after, and ≈64 hours after AITC exposure. AITC induced significant dose-dependent, moderate-to-severe spontaneous burning pain, mechanical and heat hyperalgesia, and dynamic mechanical allodynia (P < 0.05). No significant differences in induced pain hypersensitivity were observed between the 50% and 90% AITC concentrations. Acute and prolonged inflammation was evoked by all concentrations, and assessments by full-field laser perfusion imaging demonstrated a significant dose-dependent increase with a ceiling effect from 50% to 90%. Topical AITC application produces pain and somatosensory sensitization in a dose-dependent manner with optimal concentrations recommended to be >10% and ≤50%. The model is translatable to humans and could be useful in pharmacological proof-of-concept studies of TRPA1-antagonists, analgesics, and anti-inflammatory compounds or for exploratory clinical purposes, eg, loss- or gain-of-function in peripheral neuropathies.

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

PubMed

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

2016-01-01

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

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

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

PubMed

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

2016-02-29

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

Heterogeneity and Fgf dependence of adult neural progenitors in the zebrafish telencephalon.

PubMed

Ganz, Julia; Kaslin, Jan; Hochmann, Sarah; Freudenreich, Dorian; Brand, Michael

2010-08-15

Adult telencephalic neurogenesis is a conserved trait of all vertebrates studied. It has been investigated in detail in rodents, but very little is known about the composition of neurogenic niches and the cellular nature of progenitors in nonmammalian vertebrates. To understand the components of the progenitor zones in the adult zebrafish telencephalon and the link between glial characteristics and progenitor state, we examined whether canonical glial markers are colocalized with proliferation markers. In the adult zebrafish telencephalon, we identify heterogeneous progenitors that reside in two distinct glial domains. We find that the glial composition of the progenitor zone is linked to its proliferative behavior. Analyzing both fast-cycling proliferating cells as well as slowly cycling progenitors, we find four distinct progenitor types characterized by differential expression of glial markers. Importantly, a significant proportion of progenitors do not display typical radial glia characteristics. By blocking or activating Fgf signaling by misexpression of a dominant negative Fgf-receptor 1 or Fgf8a, respectively, we find that ventral and dorsal progenitors in the telencephalon also differ in their requirement for Fgf signaling. Together with data on the expression of Fgf signaling components in the ventricular zone of the telencephalon, this suggests that Fgf signaling directly regulates proliferation of specific subsets of adult telencephalic progenitors in vivo. Taken together our results show that adult neural progenitor cells are heterogeneous with their respect to distribution into two distinct glial domains and their dependence upon Fgf signaling as a proliferative cue in the zebrafish telencephalon.

A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.

PubMed

Guenther, Catherine A; Wang, Zhen; Li, Emma; Tran, Misha C; Logan, Catriona Y; Nusse, Roel; Pantalena-Filho, Luiz; Yang, George P; Kingsley, David M

2015-08-01

Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an "injury response" control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications

PubMed Central

Torossian, Frédéric; Guerton, Bernadette; Anginot, Adrienne; Alexander, Kylie A.; Desterke, Christophe; Soave, Sabrina; Tseng, Hsu-Wen; Arouche, Nassim; Boutin, Laetitia; Kulina, Irina; Salga, Marjorie; Jose, Beulah; Pettit, Allison R.; Clay, Denis; Vlachos, Erica; Genet, Guillaume; Debaud, Charlotte; Denormandie, Philippe; Genet, François; Sims, Natalie A.; Banzet, Sébastien; Levesque, Jean-Pierre; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

2017-01-01

Neurogenic heterotopic ossification (NHO) is the formation of ectopic bone generally in muscles surrounding joints following spinal cord or brain injury. We investigated the mechanisms of NHO formation in 64 patients and a mouse model of spinal cord injury–induced NHO. We show that marrow from human NHOs contains hematopoietic stem cell (HSC) niches, in which mesenchymal stromal cells (MSCs) and endothelial cells provide an environment supporting HSC maintenance, proliferation, and differentiation. The transcriptomic signature of MSCs from NHOs shows a neuronal imprinting associated with a molecular network required for HSC support. We demonstrate that oncostatin M (OSM) produced by activated macrophages promotes osteoblastic differentiation and mineralization of human muscle-derived stromal cells surrounding NHOs. The key role of OSM was confirmed using an experimental model of NHO in mice defective for the OSM receptor (OSMR). Our results provide strong evidence that macrophages contribute to NHO formation through the osteogenic action of OSM on muscle cells within an inflammatory context and suggest that OSM/OSMR could be a suitable therapeutic target. Altogether, the evidence of HSCs in ectopic bones growing at the expense of soft tissue in spinal cord/brain-injured patients indicates that inflammation and muscle contribute to HSC regulation by the brain-bone-blood triad. PMID:29093266

Do patients with neurogenic bladder treated with clean intermittentcatheterization need antibacterial prophylaxis?

PubMed

Akil, İpek; Özen, Çınar; Cengiz, Beyhan

2016-06-23

In this study, we investigated the effectiveness of antibiotic prophylaxis (ABP) with respect to the incidence of symptomatic urinary tract infections (UTIs) and evaluated the development of renal scarring in patients treated with clean intermittent catheterization (CIC). A total of 22 patients were included in the study. The patients were administered ABP in the first year (the ABP-received period) but not in the second year (the ABP-discontinued period). Twenty-eight of all cultures taken in the ABP-received period (18.2%) and 25 (16.2%) of the ABP-discontinued cultures were considered to be indicative of symptomatic UTIs (P = 0.65). The multiple antibiotic resistance rate of microorganisms in cultures taken during the ABP-discontinued period (47; 30.5%) was lower than that in those taken in the ABP-received period (62; 40.3%), (P = 0.07). There was no difference between the ABP-received and ABP-discontinued periods with respect to the development of new lesions according to dimercaptosuccinic acid results (P = 0.14). Routine ABP usage is not protective against the development of symptomatic UTIs and new lesions in neurogenic bladder patients receiving CIC. Furthermore, the growth of resistant microorganisms increased in the ABP-received period.

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

PubMed

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

2017-02-01

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

Rapid transport of CCL11 across the blood-brain barrier: regional variation and importance of blood cells.

PubMed

Erickson, Michelle A; Morofuji, Yoichi; Owen, Joshua B; Banks, William A

2014-06-01

Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine.

Rapid Transport of CCL11 across the Blood-Brain Barrier: Regional Variation and Importance of Blood Cells

PubMed Central

Erickson, Michelle A.; Morofuji, Yoichi; Owen, Joshua B.

2014-01-01

Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine. PMID:24706984

Memory-enhancing effects of Cuscuta japonica Choisy via enhancement of adult hippocampal neurogenesis in mice.

PubMed

Moon, Minho; Jeong, Hyun Uk; Choi, Jin Gyu; Jeon, Seong Gak; Song, Eun Ji; Hong, Seon-Pyo; Oh, Myung Sook

2016-09-15

It is generally accepted that functional and structural changes within the hippocampus are involved in learning and memory and that adult neurogenesis in this region may modulate cognition. The extract of Cuscuta japonica Choisy (CJ) is a well-known traditional Chinese herbal medicine that has been used since ancient times as a rejuvenation remedy. The systemic effects of this herb are widely known and can be applied for the treatment of a number of physiological diseases, but there is a lack of evidence describing its effects on brain function. Thus, the present study investigated whether CJ would enhance memory function and/or increase hippocampal neurogenesis using mice orally administered with CJ water extract or vehicle for 21days. Performance on the novel object recognition and passive avoidance tests revealed that treatment with CJ dose-dependently improved the cognitive function of mice. Additionally, CJ increased the Ki-67-positive proliferating cells and the number of doublecortin-stained neuroblasts in the dentate gyrus (DG) of the hippocampus, and double labeling with 5-bromo-2-deoxyuridine and neuronal specific nuclear protein showed that CJ increased the number of mature neurons in the DG. Finally, CJ resulted in the upregulated expression of neurogenic differentiation factor, which is essential for the maturation and differentiation of granule cells in the hippocampus. Taken together, the present findings indicate that CJ stimulated neuronal cell proliferation, differentiation, and maturation, which are all processes associated with neurogenesis. Additionally, these findings suggest that CJ may improve learning and memory via the enhancement of adult hippocampal neurogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional recovery of the dentate gyrus after a focal lesion is accompanied by structural reorganization in the adult rat.

PubMed

Zepeda, Angélica; Aguilar-Arredondo, Andrea; Michel, Gabriela; Ramos-Languren, Laura Elisa; Escobar, Martha L; Arias, Clorinda

2013-03-01

The adult brain is highly plastic and tends to undergo substantial reorganization after injury to compensate for the lesion effects. It has been shown that such reorganization mainly relies on anatomical and biochemical modifications of the remaining cells which give rise to a network rewiring without reinstating the original morphology of the damaged region. However, few studies have analyzed the neurorepair potential of a neurogenic structure. Thus, the aim of this work was to analyze if the DG could restore its original morphology after a lesion and to establish if the structural reorganization is accompanied by behavioral and electrophysiological recovery. Using a subepileptogenic injection of kainic acid (KA), we induced a focal lesion in the DG and assessed in time (1) the loss and recovery of dependent and non dependent DG cognitive functions, (2) the anatomical reorganization of the DG using a stereological probe and immunohistochemical markers for different neuronal maturation stages and, (3) synaptic plasticity as assessed through the induction of in vivo long-term potentiation (LTP) in the mossy fiber pathway (CA3-DG). Our results show that a DG focal lesion with KA leads to a well delimited region of neuronal loss, disorganization of the structure, the loss of associated mnemonic functions and the impairment to elicit LTP. However, behavioral and synaptic plasticity expression occurs in a time dependent fashion and occurs along the morphological restoration of the DG. These results provide novel information on neural plasticity events associated to functional reorganization after damage.

Body mass index of adults with intellectual disability participating in Special Olympics by world region.

PubMed

Temple, V A; Foley, J T; Lloyd, M

2014-03-01

People with intellectual disability (ID) experience poorer health and have more unmet health needs compared with people without ID, and they are often absent from population health surveillance. The aim of this study was to describe the body mass index (BMI) status of adult Special Olympics participants by world region and gender. Additionally, the general influence of age and gender on overweight/obesity of all participants was explored. A total of 11 643 (7150 male and 4493 female) Special Olympics BMI records were available from the Special Olympics International Health Promotion database. BMI was compared by gender and world region. Logistic regression was used to examine whether age and gender were associated with the likelihood of being overweight/obese (BMI ≥ 25.0). Overall, 5.5% of the sample was underweight, 36.1% in the normal range, 24.7% overweight and 32.1% obese, and levels of overweight/obesity were very high in North America. Both age and gender were significant predictors of overweight/obesity (odds ratios 1.06 and 0.59, respectively). Our findings demonstrate that adult Special Olympics participants have high levels of overweight and obesity; particularly among women and those from North America. It is crucial that those who work with, care for, coach and live with adults with ID who participate in Special Olympics increase efforts to promote healthy weight status. © 2013 The Authors. Journal of Intellectual Disability Research © 2013 John Wiley & Sons Ltd, MENCAP & IASSIDD.

[Providing adults and children with vitamin A and carotenoids in different regions of the CIS].

PubMed

Spirichev, V B; Blazheevich, N V; Isaeva, V A

1995-01-01

Population based studies of vitamin nutritional status in Russia, Ukranian, Belarus and Baltic States in 1983-1991 give evidence about satisfied vitamin A nutritional status and insufficient carotenoids nutrition of population. The retinol level below 30 MK2/dl (lower reference level) was revealed in 6% of the adults, 19% of the children and 6% of the pregnant women. The level of carotene below 80 MK2/dl took place in 39% of the adults, 28% of the children and 18% of the pregnant women. Worst vitamin A and carotene nutritional status was detected in adults and children living in Mogilevskaya and Gomelskaya regions suffering from accident on Chernobyl station as well as inhabitants of large industrial centres (Ekaterinburg, Orenburg, Kemerovo, Norilsk, Zaporoz'e) with bad ecological situation It was pointed on probable connection between insufficient consumption of carotene and increased risk of cancer and cardiovascular diseases. It is recommended the realization of large-scale actions upon cardinal improvement of vitamin A and carotene supplying of population.

Mandibular fractures: a comparative analysis between young and adult patients in the southeast region of Turkey

PubMed Central

ATILGAN, Serhat; EROL, Behçet; YAMAN, Ferhan; YILMAZ, Nezih; UCAN, Musa Can

2010-01-01

Objective The purpose of this study was to review and compare the differences between mandibular fractures in young and adult patients. Material and Methods Patients treated at the Oral and Maxillofacial Department of Dicle University during a five-year period between 2000 and 2005 were retrospectively evaluated with respect to age groups, gender, etiology, localization and type of fractures, treatment methods and complications. Result 532 patients were included in the study, 370 (70%) males and 162 (30%) females, with a total of 744 mandibular fractures. The mean age of young patients was 10, with a male-female ratio of 2:1. The mean age of adult patients was 28, with a male-female ratio of 3:1. The most common causes of injury were falls (65%) in young patients and traffic accidents (38%) in adults. The most common fracture sites were the symphysis (35%) and condyle (36%) in young patients, and the symphysis in adults (36%). Mandibular fractures were generally treated by arch bar and maxillomandibular fixation in both young (67%) and adult (39%) patients, and 43% of the adult patients were treated by open reduction and internal fixation. Conclusion There was a similar gender, monthly and type of treatment distribution in both young and adult patients in the southeast region of Turkey. However, there were differences regarding age, etiology and fracture site. These findings between young and adult patients are broadly similar to those from other studies. Analysis of small differences may be an important factor in assessing educational and socioeconomic environments. PMID:20379677

Preservation of normal lung regions in the adult respiratory distress syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maunder, R.J.; Shuman, W.P.; McHugh, J.W.

1986-05-09

In this report, the authors challenge the commonly held assumption that the adult respiratory distress syndrome (ARDS) is a homogeneous process associated with generalized and relatively uniform damage to the alveolar capillary membrane. They studied 13 patients with ARDS, comparing the pulmonary parenchymal changes seen by standard bedside chest roentgenograms with those seen by computed tomography of the chest. Three patients demonstrated generalized lung involvement by both radiologic techniques. In another eight patients, despite the appearance of generalized involvement on the standard chest x-ray film, the computed tomographic scans showed patchy infiltrates interspersed with areas of normal-appearing lung. Two patientsmore » showed patchy involvement by both techniques. The fact that ARDS spares some regions of lung parenchyma is useful knowledge in understanding the gas-exchange abnormalities of ARDS, the variable responsiveness to positive end-expiratory pressure, and the occurrence of oxygen toxicity. The problem of regional inhomogeneity should also be kept in mind when interpreting lung biopsy specimens or bronchoalveolar lavage fluid in patients with ARDS.« less

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.

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

PubMed

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

2017-03-01

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

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

PubMed

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

2015-04-03

Repeated forced swimming test (rFST) may detect gradual effects of antidepressants in adult rats. Antidepressants, as enrichment, affected behavior and neurogenesis in rats. However, the influence of enrichment on behavioral and neurogenic effects of antidepressants is unknown. Here, effects of antidepressants on rFST and hippocampal neurogenesis were investigated in rats under enriched conditions. Behaviors of male Wistar rats, housed from weaning in standard (SE) or enriched environment (EE), were registered during rFST. The rFST consisted of 15min of swimming (pretest) followed by 5min of swimming in the first (test), seventh (retest 1) and fourteenth (retest 2) days after pretest. One hour before the test, rats received an intraperitoneal injection of saline (1ml/kg), fluoxetine (2.5mg/kg) or imipramine (2.5 or 5mg/kg). These treatments were performed daily until the day of the retest 2. After retest 2, rats were euthanized for the identification of markers for neurogenesis in the hippocampus. Fluoxetine or imipramine decreased immobility in retests 1 and 2, as compared to saline. EE abolished these differences. In EE, fluoxetine or imipramine (5mg/kg) reduced immobility time in retest 2, as compared to the test. Independent of the housing conditions, fluoxetine and imipramine (5mg/kg) increased the ratio of immature neurons per progenitor cell in the hippocampus. In summary, antidepressants or enrichment counteracted the high immobility in rFST. Enrichment changed the effects of antidepressants in rFST depending on the type, and the dose of a substance but failed to change neurogenesis in control or antidepressant treated-rats. Effects of antidepressants and enrichment on rFST seemed neurogenesis-independent. Copyright © 2014 Elsevier Inc. All rights reserved.

Immunological aspects of the complex regional pain syndrome (CRPS).

PubMed

Krämer, Heidrun H

2012-01-01

Limb trauma can lead to the development of a complex regional pain syndrome (CRPS). CRPS is a descriptive term of a variety of different symptoms. According to the current IASP-approved criteria, human CRPS can be diagnosed if a combination of signs is present: continuing pain and hyperalgesia, disproportionate to the initial trauma, skin temperature and colour asymmetry, sweating asymmetry, edema, decreased range of motion, and trophic changes. The diagnosis and treatment of human CRPS can be demanding and the pathophysiology underlying the disease is still under investigation. Immunological aspects are considered to play an important role in the development of CRPS. The impact of elevated pro-inflammatory cytokines systemically as well as locally, increased neurogenic inflammation and auto-antibodies in the pathophysiological development of CRPS are discussed in this review.

Adult polyglucosan body disease presenting as a unilateral progressive plexopathy.

PubMed

Naddaf, Elie; Kassardjian, Charles D; Kurt, Yasemin Gulcan; Akman, Hasan Orhan; Windebank, Anthony J

2016-06-01

Adult polyglucosan body disease (APBD) usually presents with progressive spastic paraparesis, neurogenic bladder, and distal lower limb sensory abnormalities. It is caused by mutations in the glycogen branching enzyme gene (GBE1). We describe a woman with an unusual phenotype manifesting as progressive left brachial more than lumbosacral plexopathies, with central sensory and corticospinal tract involvement. Magnetic resonance imaging of the brain and cervical spine showed abnormal T2 signal within the ventral pons and medulla bilaterally, involving the pyramidal tracts and the medial leminisci. There was also medullary and cervical spine atrophy. On nerve biopsy, large polyglucosan bodies were noted in the endoneurium. The patient was found to be compound heterozygous for 2 novel mutations in GBE1. Peripheral blood leukocyte GBE activity was markedly reduced to 7% of normal, confirming the diagnosis of APBD. In this report we describe a new phenotype of APBD associated with 2 novel mutations. Muscle Nerve 53: 976-981, 2016. © 2016 Wiley Periodicals, Inc.

Time of correlation of low-frequency fluctuations in the regional laser Doppler flow signal from human skin

NASA Astrophysics Data System (ADS)

Folgosi-Correa, M. S.; Nogueira, G. E. C.

2012-06-01

The laser Doppler flowmetry allows the non-invasive assessment of the skin perfusion in real-time, being an attractive technique to study the human microcirculation in clinical settings. Low-frequency oscillations in the laser Doppler blood flow signal from the skin have been related to the endothelial, endothelial-metabolic, neurogenic and myogenic mechanisms of microvascular flow control, in the range 0.005-0.0095 Hz, 0.0095-0.021 Hz, 0.021-0.052 Hz and 0.052- 0.145 Hz respectively. The mean Amplitude (A) of the periodic fluctuations in the laser Doppler blood flow signal, in each frequency range, derived from the respective wavelet-transformed coefficients, has been used to assess the function and dysfunctions of each mechanism of flow control. Known sources of flow signal variances include spatial and temporal variability, diminishing the discriminatory capability of the technique. Here a new time domain method of analysis is proposed, based on the Time of Correlation (TC) of flow fluctuations between two adjacent sites. Registers of blood flow from two adjacent regions, for skin temperature at 32 0C (basal) and thermally stimulated (42 0C) of volar forearms from 20 healthy volunteers were collected and analyzed. The results obtained revealed high time of correlation between two adjacent regions when thermally stimulated, for signals in the endothelial, endothelial-metabolic, neurogenic and myogenic frequency ranges. Experimental data also indicate lower variability for TC when compared to A, when thermally stimulated, suggesting a new promising parameter for assessment of the microvascular flow control.

Geographic Region Matters in the Relation Between Perceived Racial Discrimination and Psychiatric Disorders Among Black Older Adults.

PubMed

Kim, Giyeon; Parmelee, Patricia; Bryant, Ami N; Crowther, Martha R; Park, Soohyun; Parton, Jason M; Chae, David H

2017-11-10

This study examined whether the relation between perceived racial discrimination and psychiatric disorders varied by large geographic region among Black older adults in the United States. Black adults aged 55 or older who had experienced racial/ethnic-specific discrimination were drawn from the National Survey of American Life (NSAL). Logistic regression analysis was used to examine main and interaction effects. Results show that there was a significant main effect of perceived racial discrimination, indicating that greater perceived discrimination was significantly associated with increased odds of having any past-year psychiatric disorder. The interaction of region by perceived racial discrimination was significant: The effect of perceived racial discrimination on any past-year psychiatric disorder was stronger among Blacks in the West than those in the South. Findings suggest that whereas, in general, perceived racial discrimination is a risk factor for poor mental health among older Blacks, this association may differ by geographic region. Additional research examining reasons for this variation is needed. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Steadiness of Spinal Regions during Single-Leg Standing in Older Adults with and without Chronic Low Back Pain

PubMed Central

Kuo, Yi-Liang; Huang, Kuo-Yuan; Chiang, Pei-Tzu; Lee, Pei-Yun; Tsai, Yi-Ju

2015-01-01

The aims of this study were to compare the steadiness index of spinal regions during single-leg standing in older adults with and without chronic low back pain (LBP) and to correlate measurements of steadiness index with the performance of clinical balance tests. Thirteen community-dwelling older adults (aged 55 years or above) with chronic LBP and 13 age- and gender-matched asymptomatic volunteers participated in this study. Data collection was conducted in a university research laboratory. Measurements were steadiness index of spinal regions (trunk, thoracic spine, lumbar spine, and pelvis) during single-leg standing including relative holding time (RHT) and relative standstill time (RST), and clinical balance tests (timed up and go test and 5-repetition sit to stand test). The LBP group had a statistically significantly smaller RHT than the control group, regardless of one leg stance on the painful or non-painful sides. The RSTs on the painful side leg in the LBP group were not statistically significantly different from the average RSTs of both legs in the control group; however, the RSTs on the non-painful side leg in the LBP group were statistically significantly smaller than those in the control group for the trunk, thoracic spine, and lumbar spine. No statistically significant intra-group differences were found in the RHTs and RSTs between the painful and non-painful side legs in the LBP group. Measurements of clinical balance tests also showed insignificant weak to moderate correlations with steadiness index. In conclusion, older adults with chronic LBP demonstrated decreased spinal steadiness not only in the symptomatic lumbar spine but also in the other spinal regions within the kinetic chain of the spine. When treating older adults with chronic LBP, clinicians may also need to examine their balance performance and spinal steadiness during balance challenging tests. PMID:26024534

Safety and Durability of Effect with Long-Term, Open-Label Droxidopa Treatment in Patients with Symptomatic Neurogenic Orthostatic Hypotension (NOH303).

PubMed

Isaacson, Stuart; Shill, Holly A; Vernino, Steven; Ziemann, Adam; Rowse, Gerald J

2016-10-19

Neurogenic orthostatic hypotension (nOH) is associated with insufficient norepinephrine release in response to postural change. The objective of this study was to evaluate the long-term safety and durability of efficacy of the norepinephrine precursor droxidopa in patients with symptomatic nOH. This multinational study consisted of 3 sequential phases: a 3-month open-label droxidopa treatment phase followed by a 2-week double-blind, placebo-controlled withdrawal phase, and a 9-month open-label extension phase in which all patients received droxidopa. Patients were adults diagnosed with symptomatic nOH associated with Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. Efficacy was evaluated using patient- and investigator-reported questionnaire responses and the orthostatic standing test. Safety was assessed through adverse event (AE) reports and vital signs. A total of 102 patients received treatment with droxidopa. Initial improvements from baseline in patient-reported nOH symptom severity and impact on daily activities, evaluated using the Orthostatic Hypotension Questionnaire, exceeded 50% and were maintained throughout the 12-month study. Decreased nOH severity was also reflected in clinician and patient ratings on the Clinical Global Impression questionnaire. Standing systolic and diastolic blood pressures were increased from baseline throughout the study with droxidopa treatment. The most frequently reported AEs were falls, urinary tract infection, and headache. There was a low incidence (≤2%) of cardiac AEs (eg, first-degree atrioventricular block, supraventricular extrasystoles). Long-term, open-label treatment with droxidopa for up to 12 months was generally well tolerated and provided durable improvements in nOH signs and symptoms.

Gray matter regions statistically mediating the cross-sectional association of eotaxin and set-shifting among older adults with major depressive disorder.

PubMed

Smagula, Stephen F; Karim, Helmet T; Lenze, Eric J; Butters, Meryl A; Wu, Gregory F; Mulsant, Benoit H; Reynolds, Charles F; Aizenstein, Howard J

2017-12-01

Eotaxin is a chemokine that exerts negative effects on neurogenesis. We recently showed that peripheral eotaxin levels correlate with both lower gray matter volume and poorer executive performance in older adults with major depressive disorder. These findings suggest that the relationship between eotaxin and set-shifting may be accounted for by lower gray matter volume in specific regions. Prior studies have identified specific gray matter regions that correlate with set-shifting performance, but have not examined whether these specific gray matter regions mediate the cross-sectional association between eotaxin and set-shifting. In 27 older adults (mean age: 68 ± 5.2 years) with major depressive disorder, we performed a whole brain (voxel-wise) analysis testing whether/where gray matter density statistically mediates the cross-sectional association of eotaxin and set-shifting performance. We found the association between eotaxin and set-shifting performance was fully statistically mediated by lower gray matter density in left middle cingulate, right pre-/post-central, lingual, inferior/superior frontal, cuneus, and middle temporal regions. The regions identified above may be both susceptible to a potential neurodegenerative effect of eotaxin, and critical to preserving set-shifting function. Longitudinal and intervention studies are needed to further evaluate whether targeting eotaxin levels will prevent neurodegeneration and executive impairment in older adults with depression. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation

PubMed Central

Geribaldi-Doldán, Noelia; Flores-Giubi, Eugenia; Murillo-Carretero, Maribel; García-Bernal, Francisco; Carrasco, Manuel; Macías-Sánchez, Antonio J.; Domínguez-Riscart, Jesús; Verástegui, Cristina; Hernández-Galán, Rosario

2016-01-01

Background: Neuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system. Methodology: We have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain. Results: We have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo. Conclusions: This work suggests that protein kinase C activation is a promising strategy to expand the endogenous neural progenitor cell population to promote neurogenesis and highlights the potential of 12-deoxyphorbols as pharmaceutical

12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation.

PubMed

Geribaldi-Doldán, Noelia; Flores-Giubi, Eugenia; Murillo-Carretero, Maribel; García-Bernal, Francisco; Carrasco, Manuel; Macías-Sánchez, Antonio J; Domínguez-Riscart, Jesús; Verástegui, Cristina; Hernández-Galán, Rosario; Castro, Carmen

2015-07-29

Neuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system. We have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain. We have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo. This work suggests that protein kinase C activation is a promising strategy to expand the endogenous neural progenitor cell population to promote neurogenesis and highlights the potential of 12-deoxyphorbols as pharmaceutical agents to facilitate neuronal renewal. © The

Phenotypic and Gene Expression Modification with Normal Brain Aging in GFAP-Positive Astrocytes and Neural Stem Cells

PubMed Central

Bernal, Giovanna M.; Peterson, Daniel A.

2011-01-01

Summary Astrocytes secrete growth factors that are both neuroprotective and supportive for the local environment. Identified by glial fibrillary acidic protein (GFAP) expression, astrocytes exhibit heterogeneity in morphology and in expression of phenotypic markers and growth factors throughout different adult brain regions. In adult neurogenic niches, astrocytes secrete vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) within the neurogenic niche, and are also a source of special GFAP-positive multipotent neural stem cells (NSCs). Normal aging is accompanied by a decline in CNS function and reduced neurogenesis. We asked if a decreased availability of astrocyte-derived factors may contribute to the age-related decline in neurogenesis. Determining alterations of astrocytic activity in the aging brain is crucial for understanding CNS homeostasis in aging and for assessing appropriate therapeutic targets for an aging population. We found region-specific alterations in gene expression of GFAP, VEGF and FGF-2 and their receptors in the aged brain corresponding to changes in astrocytic reactivity, supporting astrocytic heterogeneity and demonstrating a differential aging effect. We found that GFAP-positive NSCs uniquely coexpress both VEGF and its key mitotic receptor Flk-1 in both young and aged hippocampus, indicating a possible autocrine/paracrine signaling mechanism. VEGF expression is lost once NSCs commit to a neuronal fate, but Flk-1-mediated sensitivity to VEGF signaling is maintained. We propose that age-related astrocytic changes result in reduced VEGF and FGF-2 signaling, which in turn limits neural stem cell and progenitor cell maintenance and contributes to decreased neurogenesis. PMID:21385309

Intrinsic brain abnormalities in young healthy adults with childhood trauma: A resting-state functional magnetic resonance imaging study of regional homogeneity and functional connectivity.

PubMed

Lu, Shaojia; Gao, Weijia; Wei, Zhaoguo; Wang, Dandan; Hu, Shaohua; Huang, Manli; Xu, Yi; Li, Lingjiang

2017-06-01

Childhood trauma confers great risk for the development of multiple psychiatric disorders; however, the neural basis for this association is still unknown. The present resting-state functional magnetic resonance imaging study aimed to detect the effects of childhood trauma on brain function in a group of young healthy adults. In total, 24 healthy individuals with childhood trauma and 24 age- and sex-matched adults without childhood trauma were recruited. Each participant underwent resting-state functional magnetic resonance imaging scanning. Intra-regional brain activity was evaluated by regional homogeneity method and compared between groups. Areas with altered regional homogeneity were further selected as seeds in subsequent functional connectivity analysis. Statistical analyses were performed by setting current depression and anxiety as covariates. Adults with childhood trauma showed decreased regional homogeneity in bilateral superior temporal gyrus and insula, and the right inferior parietal lobule, as well as increased regional homogeneity in the right cerebellum and left middle temporal gyrus. Regional homogeneity values in the left middle temporal gyrus, right insula and right cerebellum were correlated with childhood trauma severity. In addition, individuals with childhood trauma also exhibited altered default mode network, cerebellum-default mode network and insula-default mode network connectivity when the left middle temporal gyrus, right cerebellum and right insula were selected as seed area, respectively. The present outcomes suggest that childhood trauma is associated with disturbed intrinsic brain function, especially the default mode network, in adults even without psychiatric diagnoses, which may mediate the relationship between childhood trauma and psychiatric disorders in later life.

Some regional variations in dietary patterns in a random sample of British adults.

PubMed

Whichelow, M J; Erzinclioglu, S W; Cox, B D

1991-05-01

Comparison was made of the reported frequency of consumption or choice of 30 food items by 8860 adults in the 11 standard regions of Great Britain, with the use of log-linear analysis to allow for the age, sex, social class and smoking habit variations between the regions. The South-East was taken as the base region against which the others were compared. The number of food items for which there were significant differences from the South-East were Scotland 23, North 25, North-West and Yorkshire/Humberside 20, Wales 19, West Midlands 15, East Midlands 10, East Anglia 8, South-West 7 and Greater London 9. Overall the findings confirm a North/South trend in relation to eating habits, even when demographic and smoking-habit variations are taken into account, with the frequent consumption of many fruit and vegetable products being much less common and of several high-fat foods (chips, processed meats and fried food) more common in Scotland, Wales and the northern part of England. In most regions there was a significantly lower frequency of consumption of fresh fruit, fruit juice, 'brown' bread, pasta/rice, poultry, skimmed/semi-skimmed milk, light desserts and nuts, and a higher consumption of red meat, fish and fried food than in the South-East.

Factors Released from Endothelial Cells Exposed to Flow Impact Adhesion, Proliferation, and Fate Choice in the Adult Neural Stem Cell Lineage.

PubMed

Dumont, Courtney M; Piselli, Jennifer M; Kazi, Nadeem; Bowman, Evan; Li, Guoyun; Linhardt, Robert J; Temple, Sally; Dai, Guohao; Thompson, Deanna M

2017-08-15

The microvasculature within the neural stem cell (NSC) niche promotes self-renewal and regulates lineage progression. Previous work identified endothelial-produced soluble factors as key regulators of neural progenitor cell (NPC) fate and proliferation; however, endothelial cells (ECs) are sensitive to local hemodynamics, and the effect of this key physiological process has not been defined. In this study, we evaluated adult mouse NPC response to soluble factors isolated from static or dynamic (flow) EC cultures. Endothelial factors generated under dynamic conditions significantly increased neuronal differentiation, while those released under static conditions stimulated oligodendrocyte differentiation. Flow increases EC release of neurogenic factors and of heparin sulfate glycosaminoglycans that increase their bioactivity, likely underlying the enhanced neuronal differentiation. Additionally, endothelial factors, especially from static conditions, promoted adherent growth. Together, our data suggest that blood flow may impact proliferation, adhesion, and the neuron-glial fate choice of adult NPCs, with implications for diseases and aging that reduce flow.

Hippocampal Adult Neurogenesis is Enhanced by Chronic Eszopiclone Treatment in Rats

PubMed Central

Methippara, Melvi; Bashir, Tariq; Suntsova, Natalia; Szymusiak, Ron; McGinty, Dennis

2010-01-01

Summary The adult hippocampal dentate gyrus (DG) exhibits cell proliferation and neurogenesis throughout life. We examined the effects of daily administration of eszopiclone (Esz), a commonly used hypnotic drug and GABA agonist, compared to vehicle, on DG cell proliferation and neurogenesis, and on sleep-wake patterns. Esz was administered during the usual sleep period of rats, to mimic typical use in humans. Esz treatment for 7 days did not affect the rate of cell proliferation, as measured by 5-bromo-2’-deoxyuridine (BrdU) immunostaining. However, twice daily Esz administration for two weeks increased survival of newborn cells, by 46%. Most surviving cells exhibited a neuronal phenotype, identified BrdU-NeuN double-labeling. NeuN (Neuronal nuclei) is a marker of neurons. NREM sleep was increased on day one, but not on days 7 or 14 of Esz administration. Delta EEG activity was increased on days 1 and 7 of treatment, but not on day 14. There is evidence that enhancement of DG neurogenesis is a critical component of the effects of antidepressant treatments of major depressive disorder (MDD). Adult born DG cells are responsive to GABAergic stimulation which promotes cell maturation. The present study suggests that Esz, presumably acting as a GABA agonist, has pro-neurogenic effects in the adult DG. This result is consistent with evidence that Esz enhances antidepressant treatment response of MDD patients with insomnia. PMID:20408925

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

PubMed

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

2012-01-01

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

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain

PubMed Central

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain. PMID:23440889

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

PubMed

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

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

PubMed Central

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

2015-01-01

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

Localized CT-Guided Irradiation Inhibits Neurogenesis in Specific Regions of the Adult Mouse Brain

PubMed Central

Ford, E. C.; Achanta, P.; Purger, D.; Armour, M.; Reyes, J.; Fong, J.; Kleinberg, L.; Redmond, K.; Wong, J.; Jang, M. H.; Jun, H.; Song, H-J.; Quinones-Hinojosa, A.

2011-01-01

Radiation is used in the study of neurogenesis in the adult mouse both as a model for patients undergoing radiation therapy for CNS malignancies and as a tool to interrupt neurogenesis. We describe the use of a dedicated CT-guided precision device to irradiate specific sub-regions of the adult mouse brain. Improved CT visualization was accomplished with intrathecal injection of iodinated contrast agent, which enhances the lateral ventricles. T2-weighted MRI images were also used for target localization. Visualization of delivered beams (10 Gy) in tissue was accomplished with immunohistochemical staining for the protein γ-H2AX, a marker of DNA double-strand breaks. γ-H2AX stains showed that the lateral ventricle wall could be targeted with an accuracy of 0.19 mm (n = 10). In the hippocampus, γ-H2AX staining showed that the dentate gyrus can be irradiated unilaterally with a localized arc treatment. This resulted in a significant decrease of proliferative neural progenitor cells as measured by Ki-67 staining (P < 0.001) while leaving the contralateral side intact. Two months after localized irradiation, neurogenesis was significantly inhibited in the irradiated region as seen with EdU/NeuN double labeling (P < 0.001). Localized radiation in the rodent brain is a promising new tool for the study of neurogenesis. PMID:21449714

Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change.

PubMed

Storsve, Andreas B; Fjell, Anders M; Tamnes, Christian K; Westlye, Lars T; Overbye, Knut; Aasland, Hilde W; Walhovd, Kristine B

2014-06-18

Human cortical thickness and surface area are genetically independent, emerge through different neurobiological events during development, and are sensitive to different clinical conditions. However, the relationship between changes in the two over time is unknown. Additionally, longitudinal studies have almost invariably been restricted to older adults, precluding the delineation of adult life span trajectories of change in cortical structure. In this longitudinal study, we investigated changes in cortical thickness, surface area, and volume after an average interval of 3.6 years in 207 well screened healthy adults aged 23-87 years. We hypothesized that the relationships among metrics are dynamic across the life span, that the primary contributor to cortical volume reductions in aging is cortical thinning, and that magnitude of change varies with age and region. Changes over time were seen in cortical area (mean annual percentage change [APC], -0.19), thickness (APC, -0.35), and volume (APC, -0.51) in most regions. Volume changes were primarily explained by changes in thickness rather than area. A negative relationship between change in thickness and surface area was found across several regions, where more thinning was associated with less decrease in area, and vice versa. Accelerating changes with increasing age was seen in temporal and occipital cortices. In contrast, decelerating changes were seen in prefrontal and anterior cingulate cortices. In conclusion, a dynamic relationship between cortical thickness and surface area changes exists throughout the adult life span. The mixture of accelerating and decelerating changes further demonstrates the importance of studying these metrics across the entire adult life span. Copyright © 2014 the authors 0270-6474/14/348488-11$15.00/0.

GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boku, Shuken, E-mail: shuboku@med.hokudai.ac.jp; Nakagawa, Shin; Takamura, Naoki

2013-05-17

Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression andmore » secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.« less

Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women.

PubMed

Li, Bingbing; Cheng, Gang; Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

2016-01-01

Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects' Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and

Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women

PubMed Central

Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

2016-01-01

Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects’ Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and

The Effect of an Experimental Missile Wound to the Brain on Brain Electrolytes, Regional Cerebral Blood Flow and Blood Brain Barrier Permeability.

DTIC Science & Technology

1987-02-10

lung: 2 of 76 missile-wounded cats died from fulminant lung failure - C and probable neurogenic pulmonary edema. Phenomena affecting lung function w...have observed at least 3 mild cases of pulmonary decompensation plus 2 fulminating , fatal instances of neurogenic pulmonary edema. These findings suggest...can be artificially elevated owing to their rapid synthesis following decapitation and before freezing. This process itself subjects brain cells to

Feline dry eye syndrome of presumed neurogenic origin: a case report

PubMed Central

Sebbag, Lionel; Pesavento, Patricia A; Carrasco, Sebastian E; Reilly, Christopher M; Maggs, David J

2018-01-01

Case summary A 14-year-old female spayed Abyssinian cat, which about 1 year previously underwent thoracic limb amputation, radiotherapy and chemotherapy for an incompletely excised vaccine-related fibrosarcoma, was presented for evaluation of corneal opacity in the left eye (OS). The ocular surface of both eyes (OU) had a lackluster appearance and there was a stromal corneal ulcer OS. Results of corneal aesthesiometry, Schirmer tear test-1 (STT-1) and tear film breakup time revealed corneal hypoesthesia, and quantitative and qualitative tear film deficiency OU. Noxious olfactory stimulation caused increased lacrimation relative to standard STT-1 values suggesting an intact nasolacrimal reflex. Various lacrimostimulants were administered in succession; namely, 1% pilocarpine administered topically (15 days) or orally (19 days), and topically applied 0.03% tacrolimus (47 days). Pilocarpine, especially when given orally, was associated with notable increases in STT-1 values, but corneal ulceration remained/recurred regardless of administration route, and oral pilocarpine resulted in gastrointestinal upset. Tacrolimus was not effective. After 93 days, the cat became weak and lame and a low thyroxine concentration was detected in serum. The cat was euthanized and a necropsy performed. Both lacrimal glands were histologically normal, but chronic neutrophilic keratitis and reduced conjunctival goblet cell density were noted OU. Relevance and novel information The final diagnosis was dry eye syndrome (DES) of presumed neurogenic origin, associated with corneal hypoesthesia. This report reinforces the importance of conducting tearfilm testing in cats with ocular surface disease, as clinical signs of DES were different from those described in dogs. PMID:29318025

Feline dry eye syndrome of presumed neurogenic origin: a case report.

PubMed

Sebbag, Lionel; Pesavento, Patricia A; Carrasco, Sebastian E; Reilly, Christopher M; Maggs, David J

2018-01-01

A 14-year-old female spayed Abyssinian cat, which about 1 year previously underwent thoracic limb amputation, radiotherapy and chemotherapy for an incompletely excised vaccine-related fibrosarcoma, was presented for evaluation of corneal opacity in the left eye (OS). The ocular surface of both eyes (OU) had a lackluster appearance and there was a stromal corneal ulcer OS. Results of corneal aesthesiometry, Schirmer tear test-1 (STT-1) and tear film breakup time revealed corneal hypoesthesia, and quantitative and qualitative tear film deficiency OU. Noxious olfactory stimulation caused increased lacrimation relative to standard STT-1 values suggesting an intact nasolacrimal reflex. Various lacrimostimulants were administered in succession; namely, 1% pilocarpine administered topically (15 days) or orally (19 days), and topically applied 0.03% tacrolimus (47 days). Pilocarpine, especially when given orally, was associated with notable increases in STT-1 values, but corneal ulceration remained/recurred regardless of administration route, and oral pilocarpine resulted in gastrointestinal upset. Tacrolimus was not effective. After 93 days, the cat became weak and lame and a low thyroxine concentration was detected in serum. The cat was euthanized and a necropsy performed. Both lacrimal glands were histologically normal, but chronic neutrophilic keratitis and reduced conjunctival goblet cell density were noted OU. The final diagnosis was dry eye syndrome (DES) of presumed neurogenic origin, associated with corneal hypoesthesia. This report reinforces the importance of conducting tearfilm testing in cats with ocular surface disease, as clinical signs of DES were different from those described in dogs.

Characterization of kinin receptors modulating neurogenic contractions of the mouse isolated vas deferens.

PubMed

Maas, J; Rae, G A; Huidobro-Toro, J P; Calixto, J B

1995-04-01

1. This study analyses the receptors mediating the effects of bradykinin (BK) and analogues on neurogenic twitch contractions of the mouse isolated vas deferens evoked, in the presence of captopril (3 microM), by electrical field stimulation with trains of 4 rectangular 0.5 ms pulses of supramaximal strength, delivered at a frequency of 10 Hz every 20 s. 2. BK (0.1-300 nM) induced a graded potentiation of twitches, with an EC50 (geometric mean and 95% confidence limits) of 4.5 nM (1.7-11.6) and an Emax of 315 +/- 19 mg per 10 mg of wet tissue (n = 6). Similar results were obtained in tissues challenged with Lys-BK, [Hyp3]-BK, Met,Lys-BK and the selective B2 receptor agonist [Tyr(Me)8]-BK (0.1-300 nM). 3. The selective B2 receptor antagonists, Hoe 140 (1-10 nM) and NPC 17731 (3-30 nM), caused graded rightward shifts of the curve to BK-induced twitch potentiation, yielding apparent pA2 values of 9.65 +/- 0.09 and 9.08 +/- 0.13, respectively, and Schild plot slopes not different from 1. Both antagonists (100 nM) failed to modify similar twitch potentiations induced by substance P (3 nM) or endothelin-1 (1 nM). Preincubation with the selective B1 receptor antagonist, [Leu8,des-Arg9]-BK (1 microM), increased the potentiating effect of BK on twitches at 30-300 nM. 4. In contrast to BK, the selective B1 receptor agonist, [des-Arg9]-BK (0.3-1000 nM) reduced the amplitude of twitches in a graded fashion, with an IC50 of 13.7 nM (10.4-16.1) and an Imax of 175 +/- 11 mg (n = 4). The twitch depression induced by [des-Arg9]-BK (300 nM) was not affected by Hoe140 (30nM) or NPC 17731 (100nM), but was abolished by the selective B1 receptor antagonist,[Leu8,des-Arg9]-BK (1 microM), which did not modify the twitch inhibitory effect of clonidine (1 nM) or morphine (300 nM).5. In non-stimulated preparations, BK (100 nM) also potentiated, in a Hoe 140-sensitive (10 nM)manner, the contractions induced by ATP (100 microM), but not by noradrenaline (10 microM), whereas[des-Arg9]-BK (300 n

Risk of urinary tract infection after detrusor botulinum toxin A injections for refractory neurogenic detrusor overactivity in patients with no antibiotic treatment.

PubMed

Mouttalib, Sofia; Khan, Shahid; Castel-Lacanal, Evelyne; Guillotreau, Julien; De Boissezon, Xavier; Malavaud, Bernard; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

2010-12-01

To determine if antibiotic prophylaxis is required for intradetrusor botulinum toxin A (BoNT-A) injections. This was a prospective non-randomized study. Inclusion criteria were adult patients with neurogenic detrusor overactivity who failed anticholinergic-based first-line treatment and had sterile urine culture 7 days before injections, a negative dipstick test on the day of the injections, and were performing clean intermittent self-catheterization. Injections were performed using a rigid cystoscope, under local anaesthetic. Patients received BoNT-A as either Botox® (Allergan Inc., Irvine, CA, USA) 300 U in 30 sites or Dysport® (Ipsen Ltd, Ipsen, Paris, France) 750 U in 20 sites. Urine culture was done 6 days and 6 weeks after the injections. If urinary tract infection (UTI) was suspected, a physician performed a complete physical examination. The primary outcome criterion was the occurrence of UTI during the first week after injections. In all, 42 patients (22 women, 20 men) with a mean (sd) age 45.3 (16.4) years were included. A symptomatic UTI occurred during the first week after the injections in three patients (7.1%). The urinary colonization rate was 31% and 26% at 6 days and 6 weeks after injection, respectively. The most common bacterium was Escherichia coli (62.5%). There were no differences between 20 and 30 injection sites or between the sexes. The rate of UTI after intradetrusor injections of BoNT-A was 7.1%. The most frequent bacterium involved was Escherichia coli. These results indicate that antibiotic prophylaxis for intradetrusor BoNT-A injections seems necessary. © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

Network Modeling of Adult Neurogenesis: Shifting Rates of Neuronal Turnover Optimally Gears Network Learning according to Novelty Gradient

PubMed Central

Chambers, R. Andrew; Conroy, Susan K.

2010-01-01

Apoptotic and neurogenic events in the adult hippocampus are hypothesized to play a role in cognitive responses to new contexts. Corticosteroid-mediated stress responses and other neural processes invoked by substantially novel contextual changes may regulate these processes. Using elementary three-layer neural networks that learn by incremental synaptic plasticity, we explored whether the cognitive effects of differential regimens of neuronal turnover depend on the environmental context in terms of the degree of novelty in the new information to be learned. In “adult” networks that had achieved mature synaptic connectivity upon prior learning of the Roman alphabet, imposition of apoptosis/neurogenesis before learning increasingly novel information (alternate Roman < Russian < Hebrew) reveals optimality of informatic cost benefits when rates of turnover are geared in proportion to the degree of novelty. These findings predict that flexible control of rates of apoptosis–neurogenesis within plastic, mature neural systems optimizes learning attributes under varying degrees of contextual change, and that failures in this regulation may define a role for adult hippocampal neurogenesis in novelty- and stress-responsive psychiatric disorders. PMID:17214558

Unilateral repetitive tibial nerve stimulation improves neurogenic claudication and bilateral F-wave conduction in central lumbar spinal stenosis.

PubMed

Nakajima, Noritsuna; Tani, Toshikazu; Kiyasu, Katsuhito; Kumon, Masashi; Taniguchi, Shinichirou; Takemasa, Ryuichi; Tadokoro, Nobuaki; Nishida, Kazuya; Ikeuchi, Masahiko

2018-03-01

Repetitive electrical nerve stimulation of the lower limb may improve neurogenic claudication in patients with lumbar spinal stenosis (LSS) as originally described by Tamaki et al. We tested if this neuromodulation technique affects the F-wave conduction on both sides to explore the underlying physiologic mechanisms. We studied a total of 26 LSS patients, assigning 16 to a study group receiving repetitive tibial nerve stimulation at the ankle (RTNS) on one leg, and 10 to a group without RTNS. RTNS conditioning consisted of a 0.3-ms duration square-wave pulse with an intensity 20% above the motor threshold, delivered at a rate of 5 Hz for 5 min. All patients underwent the walking test and the F-wave and M-wave studies for the tibial nerve on both sides twice; once as the baseline, and once after either the 5-min RTNS or 5-min rest. Compared to the baselines, a 5-min RTNS increased claudication distance (176 ± 96 m vs 329 ± 133 m; p = 0.0004) and slightly but significantly shortened F-wave minimal onset latency (i.e., increased F-wave conduction velocity) not only on the side receiving RTNS (50.7 ± 4.0 ms vs 49.2 ± 4.2 ms; p = 0.00081) but also on the contralateral side (50.1 ± 4.6 ms vs 47.9 ± 4.2 ms; p = 0.011). A 5-min rest in the group not receiving RTNS neither had a significant change on claudication distance nor on any F-wave measurements. The M response remained unchanged in both groups. The present study verified a beneficial effect of unilaterally applied RTNS of a mild intensity on neurogenic claudication and bilateral F-wave conduction. Our F-wave data suggest that this type of neuromodulation could be best explained by an RTNS-induced widespread sympathetic tone reduction with vasodilation, which partially counters a walking-induced further decline in nerve blood flow in LSS patients who already have ischemic cauda equina. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights

Practical and adequate approach to modeling light propagation in an adult head with low-scattering regions by use of diffusion theory.

PubMed

Koyama, Tatsuya; Iwasaki, Atsushi; Ogoshi, Yosuke; Okada, Eiji

2005-04-10

A practical and adequate approach to modeling light propagation in an adult head with a low-scattering cerebrospinal fluid (CSF) region by use of diffusion theory was investigated. The diffusion approximation does not hold in a nonscattering or low-scattering regions. The hybrid radiosity-diffusion method was adopted to model the light propagation in the head with a nonscattering region. In the hybrid method the geometry of the nonscattering region is acquired as a priori information. In reality, low-level scattering occurs in the CSF region and may reduce the error caused by the diffusion approximation. The partial optical path length and the spatial sensitivity profile calculated by the finite-element method agree well with those calculated by the Monte Carlo method in the case in which the transport scattering coefficient of the CSF layer is greater than 0.3 mm(-1). Because it is feasible to assume that the transport scattering coefficient of a CSF layer is 0.3 mm(-1), it is practical to adopt diffusion theory to the modeling of light propagation in an adult head as an alternative to the hybrid method.

Practical and adequate approach to modeling light propagation in an adult head with low-scattering regions by use of diffusion theory

NASA Astrophysics Data System (ADS)

Koyama, Tatsuya; Iwasaki, Atsushi; Ogoshi, Yosuke; Okada, Eiji

2005-04-01

A practical and adequate approach to modeling light propagation in an adult head with a low-scattering cerebrospinal fluid (CSF) region by use of diffusion theory was investigated. The diffusion approximation does not hold in a nonscattering or low-scattering regions. The hybrid radiosity-diffusion method was adopted to model the light propagation in the head with a nonscattering region. In the hybrid method the geometry of the nonscattering region is acquired as a priori information. In reality, low-level scattering occurs in the CSF region and may reduce the error caused by the diffusion approximation. The partial optical path length and the spatial sensitivity profile calculated by the finite-element method agree well with those calculated by the Monte Carlo method in the case in which the transport scattering coefficient of the CSF layer is greater than 0.3 mm^-1. Because it is feasible to assume that the transport scattering coefficient of a CSF layer is 0.3 mm^-1, it is practical to adopt diffusion theory to the modeling of light propagation in an adult head as an alternative to the hybrid method.

Integrated analysis of droxidopa trials for neurogenic orthostatic hypotension.

PubMed

Biaggioni, Italo; Arthur Hewitt, L; Rowse, Gerald J; Kaufmann, Horacio

2017-05-12

Droxidopa, a prodrug of norepinephrine, was approved for treatment of neurogenic orthostatic hypotension (nOH) due to primary autonomic disorders based on 3 randomized double-blind studies. We performed safety and efficacy analyses of this pooled dataset (n = 460). Efficacy was assessed using Orthostatic Hypotension Questionnaire (OHQ) scores (composite and individual items). Safety and tolerability were also examined. Droxidopa improved virtually all nOH symptom scores compared with placebo, significantly reducing OHQ composite score (-2.68 ± 2.20 vs -1.82 ± 2.34 units; P < 0.001), dizziness/lightheadedness score (-3.0 ± 2.9 vs -1.8 ± 3.1 units; P < 0.001), and 3 of 5 other symptom assessments (visual disturbances, weakness, and fatigue [P ≤ 0.010]). Droxidopa significantly improved 3 of 4 measures of activities of daily living (standing a long time, walking a short time, and walking a long time [P ≤ 0.003]) and significantly increased upright systolic blood pressure (11.5 ± 20.5 vs 4.8 ± 21.0 mmHg for placebo; P < 0.001). Droxidopa was effective in patients using inhibitors of dopa decarboxylase (DDCI; the enzyme that converts droxidopa to norepinephrine), but its efficacy was numerically greater in non-DDCI users. Droxidopa was well-tolerated. Rates of most adverse events were similar between groups. Supine hypertension rates were low, but slightly higher in patients receiving droxidopa (≤7.9% vs ≤4.6% for placebo); patients with severe hypertension at screening were excluded from these studies. Droxidopa is effective for the treatment of nOH in patients with primary autonomic disorders and is generally well-tolerated. A longer trial is underway to confirm efficacy beyond the ≤2 to 10 - week period assessed in the current trials. ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.

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

Identify changes of brain regional homogeneity in early and later adult onset patients with first-episode depression using resting-state fMRI.

PubMed

Shen, Zonglin; Jiang, Linling; Yang, Shuran; Ye, Jing; Dai, Nan; Liu, Xiaoyan; Li, Na; Lu, Jin; Liu, Fang; Lu, Yi; Sun, Xuejin; Cheng, Yuqi; Xu, Xiufeng

2017-01-01

Previous work exhibited different brain grey matter volume (GMV) changes between patients with early adult onset depression (EOD, age 18-29) and later adult onset depression (LOD, age 30-44) by using 30-year-old as the cut-off age. To identify whether regional homogeneity (ReHo) changes are also different between EOD and LOD by using same cut-off age, we used resting-state functional magnetic resonance imaging (fMRI) to detect the abnormal ReHo between patients with EOD and LOD in the present study. Resting-state fMRI scans of 58 patients with EOD, 62 patients with LOD, 60 young healthy controls (HC), and 52 old HC were obtained. The ReHo approach was used to analyze the images. The ANOVA analysis revealed that the ReHo values in the frontoparietal, occipital, and cerebellar regions were significantly different among the four groups. Relative to patients with LOD, patients with EOD displayed significantly increased ReHo in the left precuneus, and decreased ReHo in the right fusiform. The ReHo values in the left precuneus and the right fusiform had no significant correlation with the score of the depression rating scale or illness duration in both patient subgroups. Compared to young HC, patients with EOD showed significantly increased ReHo in the right frontoparietal regions and the right calcarine. Furthermore, the increased ReHo in the right frontoparietal regions, right insula and left hippocampus, and decreased ReHo in the left inferior occipital gyrus, right middle occipital gyrus, left calcarine, and left supplementary motor area were observed in patients with LOD when compared to old HC. The ReHo of brain areas that were related to mood regulation was changed in the first-episode, drug-naive adult patients with MDD. Adult patients with EOD and LOD exhibited different ReHo abnormalities relative to each age-matched comparison group, suggesting that depressed adult patients with different age-onset might have different pathological mechanism.

Radial glia in the proliferative ventricular zone of the embryonic and adult turtle, Trachemys scripta elegans.

PubMed

Clinton, Brian K; Cunningham, Christopher L; Kriegstein, Arnold R; Noctor, Stephen C; Martínez-Cerdeño, Verónica

2014-01-01

To better understand the role of radial glial (RG) cells in the evolution of the mammalian cerebral cortex, we investigated the role of RG cells in the dorsal cortex and dorsal ventricular ridge of the turtle, Trachemys scripta elegans. Unlike mammals, the glial architecture of adult reptile consists mainly of ependymoradial glia, which share features with mammalian RG cells, and which may contribute to neurogenesis that continues throughout the lifespan of the turtle. To evaluate the morphology and proliferative capacity of ependymoradial glia (here referred to as RG cells) in the dorsal cortex of embryonic and adult turtle, we adapted the cortical electroporation technique, commonly used in rodents, to the turtle telencephalon. Here, we demonstrate the morphological and functional characteristics of RG cells in the developing turtle dorsal cortex. We show that cell division occurs both at the ventricle and away from the ventricle, that RG cells undergo division at the ventricle during neurogenic stages of development, and that mitotic Tbr2+ precursor cells, a hallmark of the mammalian SVZ, are present in the turtle cortex. In the adult turtle, we show that RG cells encompass a morphologically heterogeneous population, particularly in the subpallium where proliferation is most prevalent. One RG subtype is similar to RG cells in the developing mammalian cortex, while 2 other RG subtypes appear to be distinct from those seen in mammal. We propose that the different subtypes of RG cells in the adult turtle perform distinct functions.

Radial glia in the proliferative ventricular zone of the embryonic and adult turtle, Trachemys scripta elegans

PubMed Central

Clinton, Brian K; Cunningham, Christopher L; Kriegstein, Arnold R; Noctor, Stephen C; Martínez-Cerdeño, Verónica

2014-01-01

To better understand the role of radial glial (RG) cells in the evolution of the mammalian cerebral cortex, we investigated the role of RG cells in the dorsal cortex and dorsal ventricular ridge of the turtle, Trachemys scripta elegans. Unlike mammals, the glial architecture of adult reptile consists mainly of ependymoradial glia, which share features with mammalian RG cells, and which may contribute to neurogenesis that continues throughout the lifespan of the turtle. To evaluate the morphology and proliferative capacity of ependymoradial glia (here referred to as RG cells) in the dorsal cortex of embryonic and adult turtle, we adapted the cortical electroporation technique, commonly used in rodents, to the turtle telencephalon. Here, we demonstrate the morphological and functional characteristics of RG cells in the developing turtle dorsal cortex. We show that cell division occurs both at the ventricle and away from the ventricle, that RG cells undergo division at the ventricle during neurogenic stages of development, and that mitotic Tbr2+ precursor cells, a hallmark of the mammalian SVZ, are present in the turtle cortex. In the adult turtle, we show that RG cells encompass a morphologically heterogeneous population, particularly in the subpallium where proliferation is most prevalent. One RG subtype is similar to RG cells in the developing mammalian cortex, while 2 other RG subtypes appear to be distinct from those seen in mammal. We propose that the different subtypes of RG cells in the adult turtle perform distinct functions. PMID:27504470

Thyroid hormone accelerates the differentiation of adult hippocampal progenitors.

PubMed

Kapoor, R; Desouza, L A; Nanavaty, I N; Kernie, S G; Vaidya, V A

2012-09-01

Disrupted thyroid hormone function evokes severe physiological consequences in the immature brain. In adulthood, although clinical reports document an effect of thyroid hormone status on mood and cognition, the molecular and cellular changes underlying these behavioural effects are poorly understood. More recently, the subtle effects of thyroid hormone on structural plasticity in the mature brain, in particular on adult hippocampal neurogenesis, have come to be appreciated. However, the specific stages of adult hippocampal progenitor development that are sensitive to thyroid hormone are not defined. Using nestin-green fluorescent protein reporter mice, we demonstrate that thyroid hormone mediates its effects on hippocampal neurogenesis by influencing Type 2b and Type 3 progenitors, although it does not alter proliferation of either the Type 1 quiescent progenitor or the Type 2a amplifying neural progenitor. Thyroid hormone increases the number of doublecortin (DCX)-positive Type 3 progenitors, and accelerates neuronal differentiation into both DCX-positive immature neurones and neuronal nuclei-positive granule cell neurones. Furthermore, we show that this increase in neuronal differentiation is accompanied by a significant induction of specific transcription factors involved in hippocampal progenitor differentiation. In vitro studies using the neurosphere assay support a direct effect of thyroid hormone on progenitor development because neurospheres treated with thyroid hormone are shifted to a more differentiated state. Taken together, our results indicate that thyroid hormone mediates its neurogenic effects via targeting Type 2b and Type 3 hippocampal progenitors, and suggests a role for proneural transcription factors in contributing to the effects of thyroid hormone on neuronal differentiation of adult hippocampal progenitors. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

Regional body volumes, BMI, waist circumference, and percentage fat in severely obese adults.

PubMed

Wang, Jack; Gallagher, Dympna; Thornton, John C; Yu, Wen; Weil, Rich; Kovac, Betty; Pi-Sunyer, F Xavier

2007-11-01

This study presents total body volume (TBV) and regional body volume, and their relationships with widely used body composition indices [BMI, waist circumference (WC), and percentage body fat (% fat)] in severely obese adults (BMI >or=35 kg/m(2)). We measured TBV, trunk volume (TV), arm volume (AV), leg volume (LV), and WC and estimated % fat in 32 severely obese persons with BMI 36 to 62 kg/m(2) (23 women; age, 19 to 65 years; weight, 91 to 182 kg) and in 58 persons with BMI <35 kg/m(2) (28 women; age, 18 to 83 years; weight, 48 to 102 kg) using a newly validated 3-day photonic image scanner (3DPS, Model C9036-02, Hamamatsu Co., Japan) and calculated TV/TBV, AV/TBV, and LV/TBV. Men had significantly larger TBV and higher TV/TBV and AV/TBV, but significantly lower LV/TBV than women, independently of BMI. TV/TBV increased while AV/TBV and LV/TBV decreased with increasing BMI, WC, and % fat, and the rate of increase in TV/TBV per % fat was significantly greater in severely obese individuals than in individuals with BMI <35 kg/m(2). The relationships for TBV with % fat were much lower than with BMI or WC. Body volume gains were mainly in the trunk region in adults, irrespective of sex or BMI. For a given BMI, WC, or % fat, men had a significantly larger TV than women. The implication is that men could have higher health risks due to having higher trunk body weight as a proportion of total body weight compared with severely obese or less severely obese women.

Relationships between years of education, regional grey matter volumes, and working memory-related brain activity in healthy older adults.

PubMed

Boller, Benjamin; Mellah, Samira; Ducharme-Laliberté, Gabriel; Belleville, Sylvie

2017-04-01

The aim of this study was to examine the relationships between educational attainment, regional grey matter volume, and functional working memory-related brain activation in older adults. The final sample included 32 healthy older adults with 8 to 22 years of education. Structural magnetic resonance imaging (MRI) was used to measure regional volume and functional MRI was used to measure activation associated with performing an n-back task. A positive correlation was found between years of education and cortical grey matter volume in the right medial and middle frontal gyri, in the middle and posterior cingulate gyri, and in the right inferior parietal lobule. The education by age interaction was significant for cortical grey matter volume in the left middle frontal gyrus and in the right medial cingulate gyrus. In this region, the volume loss related to age was larger in the low than high-education group. The education by age interaction was also significant for task-related activity in the left superior, middle and medial frontal gyri due to the fact that activation increased with age in those with higher education. No correlation was found between regions that are structurally related with education and those that are functionally related with education and age. The data suggest a protective effect of education on cortical volume. Furthermore, the brain regions involved in the working memory network are getting more activated with age in those with higher educational attainment.

[Spinal cord injury with neurogenic lower urinary tract dysfunction as a potential risk factor for bladder carcinoma].

PubMed

Böthig, Ralf; Fiebag, Kai; Kowald, Birgitt; Hirschfeld, Sven; Thietje, Roland; Kurze, Ines; Schöps, Wolfgang; Böhme, Holger; Kaufmann, Albert; Zellner, Michael; Kadhum, Thura; Golka, Klaus

2018-05-29

 Life expectancy for people with spinal cord injury/disease (SCI/D) is increasing, due to modern advances in treatment methods and in neuro-urology. However, with the increased life expectancy the risk of developing urinary bladder cancer is gaining importance. How is this patient group different from the general population?  Single-centre retrospective evaluation of consecutive patient data with spinal cord injury and proven urinary bladder cancer.  Between January 1st 1998 and March 31st 2017, 32 (3 female, 29 male) out of a total of 6432 patients with SCI/D were diagnosed with bladder cancer.The average age at bladder cancer diagnosis was 54.5 years, which is well below the average for bladder cancer cases in the general population (male: 74, female: 75).Twenty-seven patients suffered from urodynamically confirmed neurogenic detrusor overactivity, while five patients (all male) had detrusor acontractility.The median latency period between the onset of SCI/D and tumor diagnosis was 29.5 years. Temporary indwelling catheterisation was found in four patients for only 1.61 % of the overall latency period of all patients.The majority of the patients (n = 27) had transitional cell carcinoma, while five had squamous cell carcinoma. Of the 32 patients, 25 (78 %) had muscle invasive bladder cancer at ≥ T2 at the time of diagnosis. Regarding tumour grading, 23 out of 32 patients showed a histologically poorly differentiated G3 carcinoma; two patients each had G2 and G1 tumours repectively (no information on tumour grading was available in five patients).The median survival for all patients was 11.5 months. The prognosis of patients with squamous cell carcinoma was even worse; 4 out of 5 died within 7 months (median 4 months).  The significantly younger age at onset and the frequency of invasive, poorly differentiated tumour at diagnosis indicate that SCI/D influences both bladder cancer risk and prognosis significantly. The latency period between

Neurogenic effects of β-amyloid in the choroid plexus epithelial cells in Alzheimer's disease.

PubMed

Bolos, Marta; Spuch, Carlos; Ordoñez-Gutierrez, Lara; Wandosell, Francisco; Ferrer, Isidro; Carro, Eva

2013-08-01

β-amyloid (Aβ) can promote neurogenesis, both in vitro and in vivo, by inducing neural progenitor cells to differentiate into neurons. The choroid plexus in Alzheimer's disease (AD) is burdened with amyloid deposits and hosts neuronal progenitor cells. However, neurogenesis in this brain tissue is not firmly established. To investigate this issue further, we examined the effect of Aβ on the neuronal differentiation of choroid plexus epithelial cells in several experimental models of AD. Here we show that Aβ regulates neurogenesis in vitro in cultured choroid plexus epithelial cells as well as in vivo in the choroid plexus of APP/Ps1 mice. Treatment with oligomeric Aβ increased proliferation and differentiation of neuronal progenitor cells in cultured choroid plexus epithelial cells, but decreased survival of newly born neurons. These Aβ-induced neurogenic effects were also observed in choroid plexus of APP/PS1 mice, and detected also in autopsy tissue from AD patients. Analysis of signaling pathways revealed that pre-treating the choroid plexus epithelial cells with specific inhibitors of TyrK or MAPK diminished Aβ-induced neuronal proliferation. Taken together, our results support a role of Aβ in proliferation and differentiation in the choroid plexus epithelial cells in Alzheimer's disease.

[Scoliosis: the bent spine].

PubMed

Radl, R; Maafe, M; Ziegler, S

2011-05-01

Scoliosis, a permanent abnormal curvature of the spine to the side, is divided into four forms: idiopathic (infantile, juvenile and adolescent, accounting for 80% of cases), neurogenic, congenital and adult scoliosis. Most patients with adolescent idiopathic scoliosis initially have mainly cosmetic problems. However, neurogenic, congenital and adult scoliosis can lead to severe clinical symptoms. The leading symptom is back pain caused by secondary changes. In recent years the Lenke classification has been proven to be a reliable tool for disease classification. Non-progressive scoliosis is usually treated conservatively. In the case of Cobb angles of greater than 50°, surgical therapy is recommended in patients presenting before adulthood. Technical improvements in implants and the optimisation of surgical methods have set a trend in the direction of surgical therapy.

From Politicized Adult Education to Market Oriented Adult Higher Education: How Adult Education Practice in One Region is Different from Another

ERIC Educational Resources Information Center

Wang, Victor C. X.; Mott, Vivian W.

2010-01-01

This study investigated the general instructional modes of adult educators in Southeast China and Northeast China. The study utilized Conti's (1983, 2004) Principles of Adult Learning Scale (PALS) to measure instructional modes of adult educators. Data were collected from 112 randomly selected participants engaged in teaching Chinese adult…

Memory retrieval-induced activation of adult-born neurons generated in response to damage to the dentate gyrus.

PubMed

Aguilar-Arredondo, Andrea; Zepeda, Angélica

2018-07-01

The dentate gyrus (DG) is a neurogenic structure that exhibits functional and structural reorganization after injury. Neurogenesis and functional recovery occur after brain damage, and the possible relation between both processes is a matter of study. We explored whether neurogenesis and the activation of new neurons correlated with DG recovery over time. We induced a DG lesion in young adult rats through the intrahippocampal injection of kainic acid and analyzed functional recovery and the activation of new neurons after animals performed a contextual fear memory task (CFM) or a control spatial exploratory task. We analyzed the number of BrdU+ cells that co-localized with doublecortin (DCX) or with NeuN within the damaged DG and evaluated the number of cells in each population that were labelled with the activity marker c-fos after either task. At 10 days post-lesion (dpl), a region of the granular cell layer was devoid of cells, evidencing the damaged area, whereas at 30 dpl this region was significantly smaller. At 10 dpl, the number of BrdU+/DCX+/c-fos positive cells was increased compared to the sham-lesion group, but CFM was impaired. At 30 dpl, a significantly greater number of BrdU+/NeuN+/c-fos positive cells was observed than at 10 dpl, and activation correlated with CFM recovery. Performance in the spatial exploratory task induced marginal c-fos immunoreactivity in the BrdU+/NeuN+ population. We demonstrate that neurons born after the DG was damaged survive and are activated in a time- and task-dependent manner and that activation of new neurons occurs along functional recovery.

Awareness, perceptions and use of snus among young adults from the upper Midwest region of the USA.

PubMed

Choi, Kelvin; Forster, Jean

2013-11-01

Since its introduction in 2006, snus has been aggressively marketed by tobacco companies. However, little is known about the awareness, perceptions and use of snus among young adults after Camel and Marlboro snus were sold nationwide in 2010. Data were collected from 2607 young adults (ages 20-28) who participated in the Minnesota Adolescent Community Cohort Study in 2010-2011. Data include awareness of snus, ever and past 30-day use, perceived potential of snus as a quit aid, and perceived harmfulness and addictiveness of snus relative to cigarettes. The authors assessed the associations between these outcome variables and socio-demographic characteristics. Overall, 64.8% of participants were aware of snus, 14.5% ever used snus and 3.2% used snus in the past 30 days. Men and participants who smoked >100 cigarettes in their lifetime were associated with these three outcomes (p<0.05). Among those who were aware of snus, 16.3% agreed snus can help people quit smoking, 17.3% agreed snus is less harmful than cigarettes and 11.3% agreed snus is less addictive than cigarettes. These perceptions were associated with ever use and the past 30-day use of snus (p<0.05). In this regional sample of US young adults, the majority of young adults were aware of snus, and over one in 10 had used snus. More young adults in the sample than the overall US adult population believed that snus is less harmful than cigarettes. Perceptions of snus are associated with snus use. Strategic health communication interventions targeting young adults to confront the positive perceptions associated with snus may be needed to curb the interest in snus.

Endogenous cannabinoid receptor agonists inhibit neurogenic inflammations in guinea pig airways.

PubMed

Yoshihara, Shigemi; Morimoto, Hiroshi; Ohori, Makoto; Yamada, Yumi; Abe, Toshio; Arisaka, Osamu

2005-09-01

Although neurogenic inflammation via the activation of C fibers in the airway must have an important role in the pathogenesis of asthma, their regulatory mechanism remains uncertain. The pharmacological profiles of endogenous cannabinoid receptor agonists on the activation of C fibers in airway tissues were investigated and the mechanisms how cannabinoids regulate airway inflammatory reactions were clarified. The effects of endogenous cannabinoid receptor agonists on electrical field stimulation-induced bronchial smooth muscle contraction, capsaicin-induced bronchoconstriction and capsaicin-induced substance P release in guinea pig airway tissues were investigated. The influences of cannabinoid receptor antagonists and K+ channel blockers to the effects of cannabinoid receptor agonists on these respiratory reactions were examined. Both endogenous cannabinoid receptor agonists, anandamide and palmitoylethanolamide, inhibited electrical field stimulation-induced guinea pig bronchial smooth muscle contraction, but not neurokinin A-induced contraction. A cannabinoid CB2 antagonist, SR 144528, reduced the inhibitory effect of endogenous agonists, but not a cannabinoid CB1 antagonist, SR 141716A. Inhibitory effects of agonists were also reduced by the pretreatment of large conductance Ca2+ -activated K+ channel (maxi-K+ channel) blockers, iberiotoxin and charybdotoxin, but not by other K+ channel blockers, dendrotoxin or glibenclamide. Anandamide and palmitoylethanolamide blocked the capsaicin-induced release of substance P-like immunoreactivity from guinea pig airway tissues. Additionally, intravenous injection of palmitoylethanolamide dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, but not neurokinin A-induced reaction. However, anandamide did not reduce capsaicin-induced guinea pig bronchoconstriction. These findings suggest that endogenous cannabinoid receptor agonists inhibit the activation of C fibers via cannabinoid CB2 receptors and

Effect of adult onset hypothyroidism on behavioral parameters and acetylcholinesterase isoforms activity in specific brain regions of male mice.

PubMed

Vasilopoulou, Catherine G; Constantinou, Caterina; Giannakopoulou, Dimitra; Giompres, Panagiotis; Margarity, Marigoula

2016-10-01

Thyroid hormones (TH) are essential for normal development and function of mammalian central nervous system (CNS); TH dysregulation has been implicated in several cognitive and behavioral deficits related to dysfunctions of neurotransmitter systems. In the present study, we investigated the effects of adult onset hypothyroidism on the activity of acetylcholinesterase (AChE) and on related behavioral parameters. For this purpose we used adult male Balb/cJ mice that were divided randomly into euthyroid and hypothyroid animal groups. Animals were rendered hypothyroid through administration of 1% w/v KClO4 in their drinking water for 8weeks. At the end of the treatment, learning/memory procedures were examined through step-through passive avoidance task while fear/anxiety was assessed using elevated plus-maze (EPM) and open-field (OF) tests. AChE activity was determined colorimetrically in two different fractions, salt-soluble fraction (SS) (containing mainly the G1 isoform) and detergent-soluble fraction (DS) (containing mainly the G4 isoform) in cerebral cortex, cerebellum, midbrain, hippocampus and striatum. Our results indicate that adult onset hypothyroidism caused significant memory impairment and increased fear/anxiety. Moreover, the activity of both isoforms of AChE was reduced in all brain regions examined in a brain region- and isoform-specific manner. Copyright © 2016. Published by Elsevier Inc.

Autistic Traits, ADHD Symptoms, Neurological Soft Signs and Regional Cerebral Blood Flow in Adults with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Manouilenko, Irina; Pagani, Marco; Stone-Elander, Sharon; Odh, Richard; Brolin, Fredrik; Hatherly, Robert; Jacobsson, Hans; Larsson, Stig A.; Bejerot, Susanne

2013-01-01

The resting regional cerebral blood flow (rCBF) patterns related to co-occurring symptoms such as inattention, hyperactivity, neurological soft signs and motor problems have not yet been disclosed in autism spectrum disorders (ASD). In this study thirteen adults with ASD and ten matched neurotypical controls underwent PET. The scores of rating…

Phenotypic and gene expression modification with normal brain aging in GFAP-positive astrocytes and neural stem cells.

PubMed

Bernal, Giovanna M; Peterson, Daniel A

2011-06-01

Astrocytes secrete growth factors that are both neuroprotective and supportive for the local environment. Identified by glial fibrillary acidic protein (GFAP) expression, astrocytes exhibit heterogeneity in morphology and in the expression of phenotypic markers and growth factors throughout different adult brain regions. In adult neurogenic niches, astrocytes secrete vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) within the neurogenic niche and are also a source of special GFAP-positive multipotent neural stem cells (NSCs). Normal aging is accompanied by a decline in CNS function and reduced neurogenesis. We asked whether a decreased availability of astrocyte-derived factors may contribute to the age-related decline in neurogenesis. Determining alterations of astrocytic activity in the aging brain is crucial for understanding CNS homeostasis in aging and for assessing appropriate therapeutic targets for an aging population. We found region-specific alterations in the gene expression of GFAP, VEGF, and FGF-2 and their receptors in the aged brain corresponding to changes in astrocytic reactivity, supporting astrocytic heterogeneity and demonstrating a differential aging effect. We found that GFAP-positive NSCs uniquely coexpress both VEGF and its key mitotic receptor Flk-1 in both young and aged hippocampus, indicating a possible autocrine/paracrine signaling mechanism. VEGF expression is lost once NSCs commit to a neuronal fate, but Flk-1-mediated sensitivity to VEGF signaling is maintained. We propose that age-related astrocytic changes result in reduced VEGF and FGF-2 signaling, which in turn limits NSC and progenitor cell maintenance and contributes to decreased neurogenesis. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Using Telerehabilitation to Assess Apraxia of Speech in Adults

ERIC Educational Resources Information Center

Hill, Anne Jane; Theodoros, Deborah; Russell, Trevor; Ward, Elizabeth

2009-01-01

Background: Telerehabilitation is the remote delivery of rehabilitation services via information technology and telecommunication systems. There have been a number of studies that have used videoconferencing to assess speech and language skills in people with acquired neurogenic communication disorders. However, few studies have focused on cases…

Adolescent binge drinking alters adult brain neurotransmitter gene expression, behavior, brain regional volumes, and neurochemistry in mice

PubMed Central

Coleman, Leon G.; He, Jun; Lee, Joohwi; Styner, Martin; Crews, Fulton T.

2013-01-01

Background Binge-drinking is common in human adolescents. The adolescent brain is undergoing structural maturation and has a unique sensitivity to alcohol neurotoxicity. Therefore, adolescent binge ethanol may have long-term effects on the adult brain that alter brain structure and behaviors that are relevant to alcohol use disorders. Methods In order to determine if adolescent ethanol binge drinking alters the adult brain, male C57BL/6 mice were treated with either water or ethanol during adolescence (5g/kg/day i.g., post-natal days P28-37) and assessed during adulthood (P60-P88). An array of neurotransmitter-specific genes, behavioral tests (i.e. reversal learning, prepulse inhibition, and open field), and post-mortem brain structure using MRI and immunohistochemistry, were employed to assess persistent alterations in adult brain. Results At P38, 24 hours after adolescent ethanol (AE) binge, many neurotransmitter genes, particularly cholinergic and dopaminergic, were reduced by ethanol treatment. Interestingly, dopamine receptor type 4 mRNA was reduced and confirmed using immunohistochemistry. Normal control maturation (P38-P88) resulted in decreased neurotransmitter mRNA, e.g. an average decrease of 56%. Following adolescent ethanol treatment, adults showed greater gene expression reductions than controls, averaging 73%. Adult spatial learning assessed in the Morris water maze was not changed by adolescent ethanol treatment, but reversal learning experiments revealed deficits. Assessment of adult brain region volumes using MRI indicated that the olfactory bulb and basal forebrain were smaller in adults following adolescent ethanol. Immunohistochemical analyses found reduced basal forebrain area and fewer basal forebrain cholinergic neurons. Conclusions Adolescent binge ethanol treatment reduces adult neurotransmitter gene expression, particularly cholinergic genes, reduces basal forebrain and olfactory bulb volumes, and causes a reduction in the density of basal

Regional deposition of nasal sprays in adults: A wide ranging computational study.

PubMed

Kiaee, Milad; Wachtel, Herbert; Noga, Michelle L; Martin, Andrew R; Finlay, Warren H

2018-05-01

The present work examines regional deposition within the nose for nasal sprays over a large and wide ranging parameter space by using numerical simulation. A set of 7 realistic adult nasal airway geometries was defined based on computed tomography images. Deposition in 6 regions of each nasal airway geometry (the vestibule, valve, anterior turbinate, posterior turbinate, olfactory, and nasopharynx) was determined for varying particle diameter, spray cone angle, spray release direction, particle injection speed, and particle injection location. Penetration of nasal spray particles through the airway geometries represented unintended lung exposure. Penetration was found to be relatively insensitive to injection velocity, but highly sensitive to particle size. Penetration remained at or above 30% for particles exceeding 10 μm in diameter for several airway geometries studied. Deposition in the turbinates, viewed as desirable for both local and systemic nasal drug delivery, was on average maximized for particles ranging from ~20 to 30 μm in diameter, and for low to zero injection velocity. Similar values of particle diameter and injection velocity were found to maximize deposition in the olfactory region, a potential target for nose-to-brain drug delivery. However, olfactory deposition was highly variable between airway geometries, with maximum olfactory deposition ranging over 2 orders of magnitude between geometries. This variability is an obstacle to overcome if consistent dosing between subjects is to be achieved for nose-to-brain drug delivery. Copyright © 2018 John Wiley & Sons, Ltd.

Overexpression of tissue-nonspecific alkaline phosphatase increases the expression of neurogenic differentiation markers in the human SH-SY5Y neuroblastoma cell line.

PubMed

Graser, Stephanie; Mentrup, Birgit; Schneider, Doris; Klein-Hitpass, Ludger; Jakob, Franz; Hofmann, Christine

2015-10-01

Patients suffering from the rare hereditary disease hypophosphatasia (HPP), which is based on mutations in the ALPL gene, tend to develop central nervous system (CNS) related issues like epileptic seizures and neuropsychiatric illnesses such as anxiety and depression, in addition to well-known problems with the mineralization of bones and teeth. Analyses of the molecular role of tissue-nonspecific alkaline phosphatase (TNAP) in transgenic SH-SY5Y(TNAPhigh) neuroblastoma cells compared to SH-SY5Y(TNAPlow) cells indicate that the enzyme influences the expression levels of neuronal marker genes like RNA-binding protein, fox-1 homolog 3 (NEUN) and enolase 2, gamma neuronal (NSE) as well as microtubule-binding proteins like microtubule-associated protein 2 (MAP2) and microtubule-associated protein tau (TAU) during neurogenic differentiation. Fluorescence staining of SH-SY5Y(TNAPhigh) cells reveals TNAP localization throughout the whole length of the developed projection network and even synapsin Ι co-localization with strong TNAP signals at some spots at least at the early time points of differentiation. Additional immunocytochemical staining shows higher MAP2 expression in SH-SY5Y(TNAPhigh) cells and further a distinct up-regulation of tau and MAP2 in the course of neurogenic differentiation. Interestingly, transgenic SH-SY5Y(TNAPhigh) cells are able to develop longer cellular processes compared to control cells after stimulation with all-trans retinoic acid (RA). Current therapies for HPP prioritize improvement of the bone phenotype. Unraveling the molecular role of TNAP in extraosseous tissues, like in the CNS, will help to improve treatment strategies for HPP patients. Taking this rare disease as a model may also help to dissect TNAP's role in neurodegenerative diseases and even improve future treatment of common pathologies. Copyright © 2015 Elsevier Inc. All rights reserved.

Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

PubMed

Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

2012-01-01

Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

Adult immunization with 13-valent pneumococcal vaccine in Campania region, South Italy: an economic evaluation.

PubMed

Liguori, Giorgio; Parlato, Antonino; Zamparelli, Alessandro Sanduzzi; Belfiore, Patrizia; Gallé, Francesca; Di Onofrio, Valeria; Riganti, Carla; Zamparelli, Bruno

2014-01-01

Pneumococcal pneumonia has a high clinical burden in terms of morbidity, mortality and hospitalization rate, with heavy implications for worldwide health systems. In particular, higher incidence and mortality rates of community-acquired pneumonia (CAP) cases, with related costs, are registered among elderly. This study aimed to an economic evaluation about the immunization with PCV13 in the adult population in Campania region, South Italy. For this purpose we performed, considering a period of 5 y, a budget impact analysis (BIA) and a cost-effectiveness analysis which considered 2 scenarios of immunization compared with lack of immunization for 2 targeted cohorts: first, the high risk subjects aged 50-79 y, and second the high risk individuals aged 50-64 y, together with all those aged 65 y. Regarding the first group, the decrease of pneumonia could give savings equal to €29,005,660, while the immunization of the second cohort could allow savings equal to €10,006,017. The economic evaluation of pneumococcal vaccine for adult groups represents an essential instrument to support health policies. This study showed that both hypothesized immunization strategies could produce savings. Obtained results support the use of pneumococcal conjugate vaccine for adults. This strategy could represent a sustainable and savings-producer health policy.

Adult hearing-aid users with cochlear dead regions restricted to high frequencies: Implications for amplification.

PubMed

Pepler, Anna; Lewis, Kathryn; Munro, Kevin J

2016-01-01

Cochlear dead regions (DR) are common in adult hearing-aid users, but are usually restricted to high frequencies. The aim was to determine the benefit of high-frequency amplification for ears with and without high-frequency DRs. Participants were fitted with the study hearing aid and tested under four conditions: unfiltered (NAL-NL2 prescription), and low-pass filtered at 1.5, 2, and 3 kHz. VCV stimuli were presented at 65 dB (A) in quiet and in 20-talker babble at a signal-to-babble ratio of 0 dB. Experienced adult hearing-aid users: one group of 18 with a DR edge frequency above 1.5 kHz, and a group of 18 matched controls. Overall performance was best in the unfiltered condition. There was no significant difference in mean performance between the two groups when tested in quiet. However, the DR group obtained less benefit from high-frequency amplification when tested in babble: the mean difference between the unfiltered and 3-kHz filtered condition was 6% and 13% for the DR group and controls, respectively. In adults with a moderate hearing loss and a restricted DR, speech recognition was always best in the unfiltered condition, although mean performance in babble was lower for the DR group.

Neurogenic Effects of Ghrelin on the Hippocampus.

PubMed

Kim, Chanyang; Kim, Sehee; Park, Seungjoon

2017-03-08

Mammalian neurogenesis continues throughout adulthood in the subventricular zone of the lateral ventricle and in the subgranular zone of the dentate gyrus in the hippocampus. It is well known that hippocampal neurogenesis is essential in mediating hippocampus-dependent learning and memory. Ghrelin, a peptide hormone mainly synthesized in the stomach, has been shown to play a major role in the regulation of energy metabolism. A plethora of evidence indicates that ghrelin can also exert important effects on neurogenesis in the hippocampus of the adult brain. The aim of this review is to discuss the current role of ghrelin on the in vivo and in vitro regulation of neurogenesis in the adult hippocampus. We will also discuss the possible role of ghrelin in dietary restriction-induced hippocampal neurogenesis and the link between ghrelin-induced hippocampal neurogenesis and cognitive functions.

Assessment of effects of atomoxetine in adult patients with ADHD: consistency among three geographic regions in a response maintenance study.

PubMed

Tanaka, Yoko; Escobar, Rodrigo; Upadhyaya, Himanshu P

2017-06-01

A previous study (Upadhyaya et al. in Eur J Psychiatry 2013b; 27:185-205) reported that adults with attention-deficit/hyperactivity disorder (ADHD) demonstrated maintenance of response for up to 25 weeks after initially responding to atomoxetine treatment. In the present report, the consistency of treatment effect across three geographic regions (Europe, United States/Canada [US/Can], and Latin America [Latin Am]) was explored. Data were analyzed from a phase 3, multicenter, randomized, double-blind, maintenance-of-response (randomized withdrawal) trial of atomoxetine versus placebo in adults with ADHD. Patients were randomized to atomoxetine (N = 266) or placebo (N = 258) for 25 weeks. Consistency assessments included the interaction test, pairwise t tests, noninferiority, and the criteria from Basic Principles on Global Clinical Trials (Ministry of Health, Labour and Welfare of Japan 2007). Atomoxetine-treated patients maintained the improved ADHD symptoms relative to placebo-treated patients on the Conners' Adult ADHD Rating Scale Investigator-Rated: Screening Version 18-Item (CAARS-Inv:SV) total score in all three regions (atomoxetine-placebo mean difference = -4.55, -3.18, and -0.07 for Europe, US/Can, and Latin Am, respectively). For the Latin Am region, the mean change in total score (0.41) was notably smaller for the placebo group than for Europe (5.87) and US/Can (4.39). Similar results were observed for the CAARS-Inv:SV hyperactivity/impulsivity and inattention subscale scores. Overall, patients maintained the response with atomoxetine treatment compared to placebo; however, the magnitude of treatment effect differed among the regions studied, being numerically higher in the EU and US/Can than Latin Am. Trial registration http://www.clinicaltrials.gov/(NCT00700427 ).

Comparison of radio frequency energy absorption in ear and eye region of children and adults at 900, 1800 and 2450 MHz.

PubMed

Keshvari, J; Lang, S

2005-09-21

The increasing use of mobile communication devices, especially mobile phones by children, has triggered discussions on whether there is a larger radio frequency (RF) energy absorption in the heads of children compared to that of adults. The objective of this study was to clarify possible differences in RF energy absorption in the head region of children and adults using computational techniques. Using the finite-difference time-domain (FDTD) computational method, a set of specific absorption rate (SAR) calculations were performed for anatomically correct adult and child head models. A half-wave dipole was used as an exposure source at 900, 1800 and 2450 MHz frequencies. The ear and eye regions were studied representing realistic exposure scenarios to current and upcoming mobile wireless communication devices. The differences in absorption were compared with the maximum energy absorption of the head model. Four magnetic resonance imaging (MRI) based head models, one female, one adult, two child head models, aged 3 and 7 years, were used. The head models greatly differ from each other in terms of size, external shape and the internal anatomy. The same tissue dielectric parameters were applied for all models. The analyses suggest that the SAR difference between adults and children is more likely caused by the general differences in the head anatomy and geometry of the individuals rather than age. It seems that the external shape of the head and the distribution of different tissues within the head play a significant role in the RF energy absorption.

Adult Neurogenesis in Sheep: Characterization and Contribution to Reproduction and Behavior

PubMed Central

Lévy, Frederic; Batailler, Martine; Meurisse, Maryse; Migaud, Martine

2017-01-01

Sheep have many advantages to study neurogenesis in comparison to the well-known rodent models. Their development and life expectancy are relatively long and they possess a gyrencephalic brain. Sheep are also seasonal breeders, a characteristic that allows studying the involvement of hypothalamic neurogenesis in the control of seasonal reproduction. Sheep are also able to individually recognize their conspecifics and develop selective and lasting bonds. Adult olfactory neurogenesis could be adapted to social behavior by supporting recognition of conspecifics. The present review reveals the distinctive features of the hippocampal, olfactory, and hypothalamic neurogenesis in sheep. In particular, the organization of the subventricular zone and the dynamic of neuronal maturation differs from that of rodents. In addition, we show that various physiological conditions, such as seasonal reproduction, gestation, and lactation differently modulate these three neurogenic niches. Last, we discuss recent evidence indicating that hypothalamic neurogenesis acts as an important regulator of the seasonal control of reproduction and that olfactory neurogenesis could be involved in odor processing in the context of maternal behavior. PMID:29109674

[Characteristics of lip-mouth region in smiling position from 80 adults with acceptable faces and individual normal occlusions].

PubMed

Zhang, J; Chen, Y; Zhou, X

1997-07-01

The Characteristics of Lip-mouth region including the soft and hard tissues in smiling position with frontal fixed position photographic computered analysis was studied. The examples were 80 adults (40 males and 40 females) with acceptable faces and individual normal occlusions. The age was between 17-25 years of age. The method adopting maximum smiling position to study the lip-mouth region is scientific, and the maximum smile line could be divided into three categories: low smile line-a-counted for 16.25% of the total samples; average smile line--68.75%; high smile line--15%.

Striking a Balance: Academic Advising and the Advisory Working Alliance with Adult Master's-Level Credential Candidates at Regional Campuses

ERIC Educational Resources Information Center

Saunders, Cindy Franklin

2012-01-01

Purpose: The purpose of this study was to describe the advising approaches and the training received by academic advisors to form an advisory working alliance with adult master's-level credential candidates in educator preparation programs at regional campuses in Southern and Central California. This advisory working alliance concept includes: (a)…

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.

Management of urinary tract infections in patients with neurogenic bladder: challenges and solutions.

PubMed

Pannek, Jürgen; Wöllner, Jens

2017-01-01

Urinary tract infections (UTIs) are one of the most common morbidities in persons with neurogenic lower urinary tract dysfunction (NLUTD). They are associated with a significant morbidity and mortality, and they affect the quality of life of the affected patients. Diagnosis and treatment of UTI in this group of patients are challenging. In this review, the current strategies regarding diagnosis, treatment, and prevention are summarized. it is important to correctly diagnose a UTI, as treatment of bacteriuria should strictly be avoided. A UTI is defined as a combination of laboratory findings (leukocyturia and bacteriuria) and symptoms. Laboratory findings without symptoms are classified as asymptomatic bacteriuria. Routine urine screening is not advised. Only UTI should be treated; treatment of asymptomatic bacteriuria is not indicated. Prior to treatment, urine for a urine culture should be obtained. Antibiotic treatment for ~7 days is advised. In recurrent UTI, bladder management should be optimized and morphologic causes for UTI should be excluded. If UTIs persist, medical prophylaxis should be considered. Currently, no prophylactic measure with evidence-based efficacy exists. Long-term antibiotic prophylaxis should be used merely as an ultimate measure. Among the various mentioned innovative approaches for UTI prevention, bacteriophages, intravesical instillations, complementary and alternative medicine techniques, and probiotics seem to be most promising. Recently, several promising innovative options for UTI prophylaxis have been developed which may help overcome the current therapeutic dilemma. However, further well designed studies are necessary to evaluate the safety and efficacy of these approaches.

Review of the efficacy and safety of transanal irrigation for neurogenic bowel dysfunction.

PubMed

Emmanuel, A

2010-09-01

Neurogenic bowel dysfunction (NBD) is a common occurrence after spinal cord injury (SCI) and in patients with spina bifida or multiple sclerosis. The impact of NBD on well-being is considerable, affecting both physical and psychological aspects of quality of life. Transanal irrigation (TAI) of the colon promotes the evacuation of faeces by introducing water into the colon and rectum through a catheter inserted into the anus. Regular and controlled evacuation in this manner aims at preventing both constipation and faecal soiling. The aim of this study was to review current evidence for the efficacy and safety of TAI in patients with NBD. A literature search was conducted in PubMed. All identified papers were assessed for relevance based on the title and abstract; this yielded 23 studies that were considered to be of direct relevance to the topic of the review. A multicentre, randomized, controlled trial has supported observational reports in demonstrating that TAI offers significant benefits over conservative bowel management in patients with SCI, in terms of managing constipation and faecal incontinence, reducing NBD symptoms and improving quality of life. Among other populations with NBD, TAI shows the greatest promise in children with spina bifida; however, further investigation is required. The overall safety profile of TAI is good, with few, and rare, adverse effects. Building on the positive data reported for patients with SCI, continued evaluation in the clinical trial setting is required to further define the utility of TAI in other populations with NBD.

Microglial brain region-dependent diversity and selective regional sensitivities to ageing

PubMed Central

Grabert, Kathleen; Michoel, Tom; Karavolos, Michail H; Clohisey, Sara; Baillie, J Kenneth; Stevens, Mark P; Freeman, Tom C; Summers, Kim M; McColl, Barry W

2015-01-01

Microglia play critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific spatially-restricted patterns, the origins of which are unknown. We performed the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse and reveal that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during ageing. Microglial diversity may enable regionally localised homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration. PMID:26780511

Onabotulinumtoxin A for treating overactive/poor compliant bladders in children and adolescents with neurogenic bladder secondary to myelomeningocele.

PubMed

Marte, Antonio

2012-12-28

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

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

PubMed Central

Marte, Antonio

2012-01-01

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

Differences in regional adiposity, bone mineral density, and physical exercise participation based on exercise self-efficacy among senior adults.

PubMed

Glenn, J M; Gray, M; Vincenzo, J L

2015-10-01

The impact of exercise self-efficacy levels (ESE) on exercise participation, levels of body fat (BF), and bone mineral density (BMD) are unclear in senior-aged adults. The purpose of this study was to investigate effects of ESE on exercise participation, regional distribution of BF, and BMD among seniors. Senior adults (N.=76; 36 males, 40 females) were separated into tertiles (T1, age=60.4±1.4; T2, age=61.3±1.4; T3, age=60.4±1.5) based on self-reported levels of ESE. BMD and regional BF were measured using dual-energy x-ray absorptiometry and exercise participation levels were measured using the Rapid Physical-Activity Questionnaire. MANOVA revealed a significant Wilks Lambda (p < 0.001) and univariate analysis was completed for exercise participation levels, android BF, gynoid BF, and spinal BMD. ANOVA revealed T3 was significantly lower for android BF (p=0.002) than T1 and T2 (30% and 26%, respectively) while gynoid BF was significantly lower (p=0.012) for T3 (24%) compared to T1. When evaluating exercise participation levels, T3 was significantly higher (p < 0.001) than T1 or T2. Spinal BMD was significantly higher (p=0.030) between T2 (10%) and T1. ESE is an important factor in senior adults ability to maintain longitudinal health.

Report: Joint Conference: Second Annual Region IV Conference on Adult Education and Second Regional Institute Southeastern Region Adult Basic Education Staff Development Project. (Daytona Beach, Florida, February 14-18, 1970).

ERIC Educational Resources Information Center

Southern Regional Education Board, Atlanta, GA.

Two simultaneous conferences on Adult Education and Adult Basic Education were held because it was considered that interaction between the two conference groups would be mutually beneficial. The defined goal of this joint institute was: the identification of problems, strategies, and priorities as they relate to an on-going plan for staff…

Renal preservation in children with neurogenic bladder-sphincter dysfunction followed in a national program.

PubMed

Wide, Peter; Glad Mattsson, Gunilla; Mattsson, Sven

2012-04-01

Neurogenic bladder-sphincter dysfunction (NBSD) constitutes the major reason for morbidity in children with spina bifida. The aim of this study was to identify risk factors for renal damage in children with NBSD followed according to the Swedish national guidelines. Records and cystometries from 6 to 16 years (median 11) follow up of 41 consecutive children born 1993-2003 with NBSD were evaluated. The children were divided into a high pressure group (baseline pressure above 30 cmH(2)O at maximal clean intermittent catheterization volume in at least two cystometries) and a low pressure group. Most children (34/41) were followed from birth. Although renal scarring on DMSA-scintigraphy was found in 5/41 children, all but one had normal renal function. Two already had renal scars on entering the follow-up program at age 2.5 and 3 years. Renal scarring was more frequent in the high pressure group (P < 0.01). Most children with renal scars (4/5) had a combination of low compliant bladder and insufficient compliance with treatment and follow up. High baseline pressure is confirmed as a risk factor that, in combination with complex social issues, creates a demanding situation for families and professionals. A structured early follow up with treatment compliance effectively prevents renal damage. Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Impact of experimental hypothyroidism on monoamines level in discrete brain regions and other peripheral tissues of young and adult male rats.

PubMed

Hassan, Wafaa A; Aly, Mona S; Rahman, Taghride Abdel; Shahat, Asmaa S

2013-06-01

The levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats were measured following experimentally induced hypothyroidism. Hypothyroidism induced by daily oral administration of propylthiouracil (PTU, 5mg/kg body wt) caused a significant reduction in DA levels in most of the tissues examined of both young and adult rats after 21 and 28 days, in NE levels after all the time intervals studied in young rats, and after 21 and 28 days in adult rats. 5-HT exhibited a significant reduction in the selected brain regions and blood plasma after 21 and 28 days and in cardiac muscle after all the time intervals in the two age groups of animals. It may be suggested that the changes in monoamine levels induced by hypothyroidism may be due to disturbance in the synthesis and release of these amines through the neurons impairment or may be due to an alteration pattern of their synthesizing and/or degradative enzymes. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Adults Experiencing Homelessness in the US–Mexico Border Region: A Photovoice Project

PubMed Central

Moya, Eva Margarita; Chavez-Baray, Silvia M.; Loweree, Jacqueline; Mattera, Brian; Martinez, Nahomi

2017-01-01

Homelessness is a social, economic, and political crisis in the United States. In particular, the US–Mexico Border region has seen a surge of homelessness, specifically among veterans, women victims of intimate partner violence, and immigrants. In 2014, 12 persons in El Paso, TX, with experience of being homeless used the photovoice methodology to participate in a project titled, “The Voices and Images of the Residents of the Opportunity Center for the Homeless: A Visual Project on the Identity and Challenges Homeless Adults Face on the Border Region.” The project was led by faculty from the Department of Social Work and facilitated by graduate students from the Departments of Social Work, Sociology, and Anthropology at the University of Texas at El Paso. In partnership with the Opportunity Center for the Homeless, a community-based organization, a gallery of photographs with respective narratives was produced along with a video documentary. The participants identified four themes: broken systems, invisibility, opportunities and what works, and growth and determination. These themes represent participants’ life experiences with homelessness and their aspirations. In addition to the photo gallery, participants supported the development of a Call to Action asking the community, policy, and decision makers to commit to changing the current social, economic, and political conditions affecting individuals experiencing homelessness. The gallery, Call to Action, and overall participant experiences with photovoice were shared during local, regional, and national conferences and events, including three State of the Homeless Conferences led by the Opportunity Center for the Homeless in partnership with the university. PMID:28580355

Prevalence and trends of metabolic syndrome among adults in the asia-pacific region: a systematic review.

PubMed

Ranasinghe, P; Mathangasinghe, Y; Jayawardena, R; Hills, A P; Misra, A

2017-01-21

The Asia-Pacific region is home to nearly half of the world's population. The region has seen a recent rapid increase in the prevalence of obesity, type-2 diabetes and cardiovascular disease. The present systematic review summarizes the recent prevalence and trends of Metabolic Syndrome (MetS) among adults in countries of the Asia-Pacific Region. Data on MetS in Asia-Pacific countries were obtained using a stepwise process by searching the online Medline database using MeSH terms 'Metabolic Syndrome X' and 'Epidemiology/EP'. For the purpose of describing prevalence data for the individual countries, studies that were most recent, nationally representative or with the largest sample size were included. When evaluating secular trends in prevalence in a country we only considered studies that evaluated the temporal change in prevalence between similar populations, prospective studies based on the same population or National surveys conducted during different time periods. This literature search yielded a total of 757 articles, and five additional article were identified by screening of reference lists. From this total, 18 studies were eligible to be included in the final analysis. Of the 51 Asia-Pacific countries (WHO) we only located data for 15. There was wide between country variation in prevalence of MetS. A national survey from Philippines conducted in 2003 revealed the lowest reported prevalence of 11.9% according to NCEP ATP III criteria. In contrast, the highest recorded prevalence in the region (49.0%) came from a study conducted in urban Pakistan (Karachchi, 2004). Most studies reported a higher prevalence of MetS in females and urban residents. Data on secular trends were available for China, South Korea and Taiwan. An increase in the prevalence of MetS was observed in all three countries. Despite differences in methodology, diagnostic criteria and age of subjects studied, the Asia-Pacific region is facing a significant epidemic of MetS. In most countries

Sensitization to allergens of house-dust mite in adults with atopic dermatitis in a cold temperature region.

PubMed

Holm, L; van Hage-Hamsten, M; Ohman, S; Scheynius, A

1999-07-01

An IgE-mediated contact reaction to airborne allergens has been suggested as one important pathogenetic mechanism in atopic dermatitis (AD). The house-dust mite (HDM) might be a common allergen involved. In Scandinavia, sensitization to HDM has been rare, probably because of the cold, dry climate. However, recent studies indicate high levels of domestic mites and HDM allergen in 15-20% of homes in central and northern Sweden. To evaluate the importance of the HDM in patients with AD in the Stockholm region, we screened 81 adult Stockholm residents with AD, for the prevalence and degree of sensitization to the HDM, according to specific IgE (RAST), skin prick test (SPT), and atopy patch test (APT). We also assessed the HDM exposure in their homes and correlated the results with clinical history, severity of the dermatitis, and type of residence during childhood and today. The sensitization rate to HDM was high (56% according to RAST, 24% according to SPT, and 47% according to APT), and 20% of the patients were exposed to HDM allergens in their beds. Mite exposure seemed to aggravate the dermatitis in highly sensitized patients. The results indicate that we have to take the HDM into account when discussing aggravating factors in adult patients with AD in the Stockholm region.

Detailed histological structure of human hair follicle bulge region at different ages: a visible niche for nesting adult stem cells.

PubMed

Wang, Xiong; Shi, Ying; Zhou, Qiong; Liu, Xiaoming; Xu, Shizheng; Lei, Tiechi

2012-10-01

In the bulge region of the hair follicle, a densely and concentrically packed cell mass is encircled by the arrector pili muscle (APM), which offers a specilized microenvironment (niche) for housing heterogeneous adult stem cells. However, the detailed histological architecture and the cellular composition of the bulge region warrants intensive study and may have implications for the regulation of hair follicle growth regulation. This study was designed to define the gene-expression profiles of putative stem cells and lineage-specific precursors in the mid-portions of plucked hair follicles prepared according to the presence of detectable autofluorescence. The structure was also characterized by using a consecutive sectioning technique. The bulge region of the hair follicle with autofluorescence was precisely excised by employing a micro-dissection procedure. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to identify the gene expression profiles specific for epithelial, melanocyte and stromal stem cells in the bulge region of the hair follicle visualized by autofluorescence. The morphology and its age-dependent changes of bulge region of the hair follicles with autofluorescence segment were also examined in 9 scalp skin specimens collected from patients aged 30 weeks to 75 years, by serial sectioning and immuno-staining. Gene expression profile analysis revealed that there were cells with mRNA transcripts of Dct(Hi)Tyrase(Lo)-Tyrp1(Lo)MC1R(Lo)MITF(Lo)/K15(Hi)/NPNT(Hi) in the bulge region of the hair follicle with autofluorescence segments, which differed from the patterns in hair bulbs. Small cell-protrusions that sprouted from the outer root sheath (ORS) were clearly observed at the APM inserting level in serial sections of hair follicles by immunohistological staining, which were characteristically replete with K15+/K19+expressing cells. Likewise, the muscle bundles of APM positive for smooth muscle actin intimately

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

PubMed

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

2016-12-01

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

Suprapubic cystostomy for neurogenic bladder using Lowsley retractor method: a procedure revisited.

PubMed

Edokpolo, Leonard U; Foster, Harris E

2011-11-01

To report our experience with the Lowsley retractor method for suprapubic cystostomy (SPC) in patients with neurogenic bladder (NGB). A retrospective study was performed of 44 patients with NGB who underwent SPC with the Lowsley retractor method. The subjects were selected from 90 patients undergoing SPC by 1 surgeon from 1995 to 2010. The age, sex, indication, anesthesia type, catheter type, blood loss, fluids administered, and duration and complications were recorded. A total of 49 primary catheter placements were performed in 44 patients. A total of 23 men and 21 women were included. The etiology of NGB was spinal cord injury and multiple sclerosis in 38 subjects (86%). The mean age was 44 years (range 18-86). The cases were performed under general anesthesia, except for 8 (16%) that were successfully performed with local and monitored anesthesia. The operation time documented in 19 cases (39%) was 20.2 ± 5.5 minutes (range 11-31). The Foley catheter size ranged from 16F to 22F. The blood loss was minimal, and there were no intraoperative complications or incorrect catheter placements. One patient returned with significant hematuria 1 day after the procedure. No other minor or major complications were noted. Patients with NGB have been shown to have a greater risk of complication during percutaneous suprapubic catheter placement. SPC using the Lowsley retractor was described by Zeidman et al in 1988. Their report did not detail the patient characteristics or operative experience. To our knowledge, no other institutional experience with the technique has been reported. The present report describes the Lowsley retractor method as a quick and safe ambulatory procedure for patients with NGB. Published by Elsevier Inc.

Protein expression differs between neural progenitor cells from the adult rat brain subventricular zone and olfactory bulb.

PubMed

Maurer, Martin H; Feldmann, Robert E; Bürgers, Heinrich F; Kuschinsky, Wolfgang

2008-01-16

Neural progenitor cells can be isolated from various regions of the adult mammalian brain, including the forebrain structures of the subventricular zone and the olfactory bulb. Currently it is unknown whether functional differences in these progenitor cell populations can already be found on the molecular level. Therefore, we compared protein expression profiles between progenitor cells isolated from the subventricular zone and the olfactory bulb using a proteomic approach based on two-dimensional gel electrophoresis and mass spectrometry. The subventricular zone and the olfactory bulb are connected by the Rostral Migratory Stream (RMS), in which glial fibrillary acidic protein (GFAP)-positive cells guide neuroblasts. Recent literature suggested that these GFAP-positive cells possess neurogenic potential themselves. In the current study, we therefore compared the cultured neurospheres for the fraction of GFAP-positive cells and their morphology of over a prolonged period of time. We found significant differences in the protein expression patterns between subventricular zone and olfactory bulb neural progenitor cells. Of the differentially expressed protein spots, 105 were exclusively expressed in the subventricular zone, 23 showed a lower expression and 51 a higher expression in the olfactory bulb. The proteomic data showed that more proteins are differentially expressed in olfactory bulb progenitors with regard to proteins involved in differentiation and microenvironmental integration, as compared to the subventricular zone progenitors. Compared to 94% of all progenitors of the subventricular zone expressed GFAP, nearly none in the olfactory bulb cultures expressed GFAP. Both GFAP-positive subpopulations differed also in morphology, with the olfactory bulb cells showing more branching. No differences in growth characteristics such as doubling time, and passage lengths could be found over 26 consecutive passages in the two cultures. In this study, we describe

The regional association of rising type 2 diabetes incidence with magnesium in drinking water among young adults.

PubMed

Kousa, Anne; Puustinen, Niina; Karvonen, Marjatta; Moltchanova, Elena

2012-01-01

The incidence of type 2 diabetes is increasing among Finnish young adults. A slightly increased risk in men was found in the north-east and western part of the country. The higher risk areas in women were found in the western coastal area and in eastern Finland. The present register-based study aimed to evaluate the regional association of the incidence of type 2 diabetes among young adults with the concentration of magnesium in local ground water. The association was evaluated using Bayesian modeling of geo-referenced data aggregated into a regular 10 km × 10 km grid cells. No marked association was found, although suggestive findings were detected for magnesium in well water and diabetes in young adult women. The results of this register-based study did not completely rule out the association of well water magnesium with the geographical variation of type 2 diabetes. The incidence of type 2 diabetes was much higher among individuals aged 40 or over. These suggestive findings indicate that the association between magnesium and type 2 diabetes would also be worth examining among individuals over 40 years of age. Copyright © 2011 Elsevier Inc. All rights reserved.

Antipsychotics promote GABAergic interneuron genesis in the adult rat brain: Role of heat-shock protein production.

PubMed

Kaneta, Hiroo; Ukai, Wataru; Tsujino, Hanako; Furuse, Kengo; Kigawa, Yoshiyasu; Tayama, Masaya; Ishii, Takao; Hashimoto, Eri; Kawanishi, Chiaki

2017-09-01

Current antipsychotics reduce positive symptoms and reverse negative symptoms in conjunction with cognitive behavioral issues with the goal of restoring impaired occupational and social functioning. However, limited information is available on their influence on gliogenesis or their neurogenic properties in adult schizophrenia brains, particularly on GABAergic interneuron production. In the present study, we used young adult subventricular zone (SVZ)-derived progenitor cells expressing proteoglycan NG2 cultures to examine the oligodendrocyte and GABAergic interneuron genesis effects of several kinds of antipsychotics on changes in differentiation function induced by exposure to the NMDA receptor antagonist MK-801. We herein demonstrated that antipsychotics promoted or restored changes in the oligodendrocyte/GABAergic interneuron differentiation functions of NG2(+) cells induced by the exposure to MK-801, which was considered to be one of the drug-induced schizophrenia model. We also demonstrated that antipsychotics restored heat-shock protein (HSP) production in NG2(+) cells with differentiation impairment. The antipsychotics olanzapine, aripiprazole, and blonanserin, but not haloperidol increased HSP90 levels, which were reduced by the exposure to MK-801. Our results showed that antipsychotics, particularly those recently synthesized, exerted similar GABAergic interneuron genesis effects on NG2(+) neuronal/glial progenitor cells in the adult rat brain by increasing cellular HSP production, and also suggest that HSP90 may play a crucial role in the pathophysiology of schizophrenia and is a key target for next drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Scaling of adult regional body mass and body composition as a whole to height: Relevance to body shape and body mass index.

PubMed

Schuna, John M; Peterson, Courtney M; Thomas, Diana M; Heo, Moonseong; Hong, Sangmo; Choi, Woong; Heymsfield, Steven B

2015-01-01

Adult body mass (MB) empirically scales as height (Ht) squared (MB ∝ Ht(2) ), but does regional body mass and body composition as a whole also scale as Ht(2) ? This question is relevant to a wide range of biological topics, including interpretation of body mass index (BMI). Dual-energy X-ray absorptiometry (DXA) was used to quantify regional body mass [head (MH), trunk, arms, and legs] and whole-body composition [fat, lean soft tissue (LST), and bone mineral content (BMC)] in non-Hispanic (NH) white, NH black, Mexican American, and Korean adults participating in the National Health and Nutrition Examination Survey (NHANES; n = 17,126) and Korean NHANES (n = 8,942). Regression models were developed to establish Ht scaling powers for each measured component with adjustments for age and adiposity. Exploratory analyses revealed a consistent scaling pattern across men and women of the four population groups: regional mass powers, head (∼0.8-1) < arms and trunk (∼1.8-2.3) < legs (∼2.3-2.6); and body composition, LST (∼2.0-2.3) < BMC (∼2.1-2.4). Small sex and population differences in scaling powers were also observed. As body mass scaled uniformly across the eight sex and population groups as Ht(∼2) , tall and short subjects differed in body shape (e.g., MH/MB ∝ Ht(-∼1) ) and composition. Adult human body shape and relative composition are a function of body size as represented by stature, a finding that reveals a previously unrecognized phenotypic heterogeneity as defined by BMI. These observations provide new pathways for exploring mechanisms governing the interrelations between adult stature, body morphology, biomechanics, and metabolism. © 2014 Wiley Periodicals, Inc.

Region-specific reduction in brain volume in young adults with perinatal hypoxic-ischaemic encephalopathy.

PubMed

Bregant, Tina; Rados, Milan; Vasung, Lana; Derganc, Metka; Evans, Alan C; Neubauer, David; Kostovic, Ivica

2013-11-01

A severe form of perinatal hypoxic-ischaemic encephalopathy (HIE) carries a high risk of perinatal death and severe neurological sequelae while in mild HIE only discrete cognitive disorders may occur. To compare total brain volumes and region-specific cortical measurements between young adults with mild-moderate perinatal HIE and a healthy control group of the same age. MR imaging was performed in a cohort of 14 young adults (9 males, 5 females) with a history of mild or moderate perinatal HIE. The control group consisted of healthy participants, matched with HIE group by age and gender. Volumetric analysis was done after the processing of MR images using a fully automated CIVET pipeline. We measured gyrification indexes, total brain volume, volume of grey and white matter, and of cerebrospinal fluid. We also measured volume, thickness and area of the cerebral cortex in the parietal, occipital, frontal, and temporal lobe, and of the isthmus cinguli, parahippocampal and cingulated gyrus, and insula. The HIE patient group showed smaller absolute volumetric data. Statistically significant (p < 0.05) reductions of gyrification index in the right hemisphere, of cortical areas in the right temporal lobe and parahippocampal gyrus, of cortical volumes in the right temporal lobe and of cortical thickness in the right isthmus of the cingulate gyrus were found. Comparison between the healthy group and the HIE group of the same gender showed statistically significant changes in the male HIE patients, where a significant reduction was found in whole brain volume; left parietal, bilateral temporal, and right parahippocampal gyrus cortical areas; and bilateral temporal lobe cortical volume. Our analysis of total brain volumes and region-specific corticometric parameters suggests that mild-moderate forms of perinatal HIE lead to reductions in whole brain volumes. In the study reductions were most pronounced in temporal lobe and parahippocampal gyrus. Copyright © 2013 European

Potamotrygon motoro stingray venom induces both neurogenic and inflammatory pain behavior in rodents.

PubMed

Kimura, L F; Santos-Neto, M; Barbaro, K C; Picolo, G

2018-05-25

Freshwater stingray accidents cause an immediate, intense, and unrelieved pain which is followed by edema, erythema and necrosis formation. Treatment for stingray envenomation is based on administration of analgesic, antipyretic and anti-inflammatory drugs. Concerning pain control, it is prescribed to immerse punctured limb on hot water to alleviate pain. There are no studies demonstrating specific targets on which stingray venom acts to promote pain. Therefore, the aim of this work was to investigate some mechanisms of Potamotrygon motoro venom (PmV) that contribute to nociception induction. Evaluating spontaneous pain behavior in mice injected i.pl. with PmV, it was seen that PmV induced both neurogenic and inflammatory pain. PmV also induced hyperalgesia in both mice and rats, evaluated through electronic von Frey and rat paw pressure test, respectively. Partial inhibition of hyperalgesia was observed in mice treated with cromolyn or promethazine, which indicated that mast cell and histamine via H1 receptor participate in the inflammatory pain. To search for some targets involved in PmVinduced hyperalgesia, the participation of TRPV1, calcium channels, neurokinins, CGRP, and norepinephrine, was evaluated in rats. It was seen that PmV-induced hyperalgesia occurs with the participation of neurokinins, mainly via NK1 receptor, CGRP, and calcium influx, through both P/Q and L-type voltage-dependent calcium channels, besides TRPV1 activation. The data presented herein indicate that PmV causes hyperalgesia in rodents which is dependent on the participation of several neuroinflammatory mediators. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-01-01

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. To investigate the long-term cost-effectiveness of initiating TAI in patients with NBD who have failed standard bowel care (SBC). 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. 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. 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.

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

PubMed

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

2016-01-01

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. 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. 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 insuficiente 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. 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. Copyright© by the International Brazilian Journal of Urology.

Thinking about Seeing: perceptual sources of knowledge are encoded in the theory of mind brain regions of sighted and blind adults

PubMed Central

Koster-Hale, Jorie; Bedny, Marina; Saxe, Rebecca

2014-01-01

Blind people's inferences about how other people see provide a window into fundamental questions about the human capacity to think about one another's thoughts. By working with blind individuals, we can ask both what kinds of representations people form about others’ minds, and how much these representations depend on the observer having had similar mental states themselves. Thinking about others’ mental states depends on a specific group of brain regions, including the right temporo-parietal junction (RTPJ). We investigated the representations of others’ mental states in these brain regions, using multivoxel pattern analyses (MVPA). We found that, first, in the RTPJ of sighted adults, the pattern of neural response distinguished the source of the mental state (did the protagonist see or hear something?) but not the valence (did the protagonist feel good or bad?). Second, these neural representations were preserved in congenitally blind adults. These results suggest that the temporo-parietal junction contains explicit, abstract representations of features of others’ mental states, including the perceptual source. The persistence of these representations in congenitally blind adults, who have no first-person experience with sight, provides evidence that these representations emerge even in the absence of first-person perceptual experiences. PMID:24960530

Thinking about seeing: perceptual sources of knowledge are encoded in the theory of mind brain regions of sighted and blind adults.

PubMed

Koster-Hale, Jorie; Bedny, Marina; Saxe, Rebecca

2014-10-01

Blind people's inferences about how other people see provide a window into fundamental questions about the human capacity to think about one another's thoughts. By working with blind individuals, we can ask both what kinds of representations people form about others' minds, and how much these representations depend on the observer having had similar mental states themselves. Thinking about others' mental states depends on a specific group of brain regions, including the right temporo-parietal junction (RTPJ). We investigated the representations of others' mental states in these brain regions, using multivoxel pattern analyses (MVPA). We found that, first, in the RTPJ of sighted adults, the pattern of neural response distinguished the source of the mental state (did the protagonist see or hear something?) but not the valence (did the protagonist feel good or bad?). Second, these neural representations were preserved in congenitally blind adults. These results suggest that the temporo-parietal junction contains explicit, abstract representations of features of others' mental states, including the perceptual source. The persistence of these representations in congenitally blind adults, who have no first-person experience with sight, provides evidence that these representations emerge even in the absence of relevant first-person perceptual experiences. Copyright © 2014 Elsevier B.V. All rights reserved.

Increased autophagy contributes to impaired smooth muscle function in neurogenic lower urinary tract dysfunction.

PubMed

Eberli, Daniel; Horst, Maya; Mortezavi, Ashkan; Andersson, Karl-Erik; Gobet, Rita; Sulser, Tullio; Simon, Hans-Uwe; Salemi, Souzan

2018-05-24

To explore whether autophagy plays a role in the remodeling of bladder smooth muscle cells (SMCs) in children with neurogenic lower urinary tract dysfunction (NLUTD), we investigated the effect of autophagy in NLUTD in the paediatric population. Bladder biopsies were taken from children with NLUTD and healthy donors as controls. Samples were labeled with the SMC markers calponin, smoothelin, and the autophagy proteins LC3, ATG5, and Beclin1. The contractile ability of bladder derived SMCs was investigated. ATG5 gene and protein was upregulated in NLUTD muscle tissue compared to normal bladder. NLUTD muscle exhibited a punctated immunostaining pattern for LC3 in a subset of the SMCs, confirming the accumulation of autophagosomes. Pronounced elevation of ATG5 in the SMC in NLUTD tissue was associated with a downregulation of the key contractile proteins smoothelin and calponin. Pharmacological blocking of autophagy completely stopped the cells growth in normal bladder SMCs. Inhibition of autophagy in the NLUTD SMCs, with already elevated levels of ATG5, resulted in a reduction of ATG5 protein expression to the basal level found in normal controls. Our study suggests that autophagy is an important factor affecting the remodeling of SMCs and the alteration of functionality in bladder smooth muscle tissue in the NLUTD. Since autophagy can be influenced by oral medication, this finding might lead to novel strategies preventing the deterioration of NLUTD muscle. © 2018 Wiley Periodicals, Inc.

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

Metabolic Syndrome and Associated Factors in Adults of the Amazon Region

PubMed Central

2016-01-01

Metabolic syndrome (MS) plays a key role in the origin of cardiovascular diseases. Studies on the MS in Brazil are recent, and its epidemiology in more isolated regions such as the Amazon is still unknown. The study aimed to estimate the prevalence of MS and associated factors in adults of the Brazilian Amazon. This study was conducted in 2012–2013. It is a cross-sectional population-based study, involving 787 adults randomly selected from the urban area of four cities in the state of Pará, in the Brazilian Eastern Amazon. The participants underwent anthropometric measurements, laboratory examination, and were questioned about their lifestyle. MS was defined by the Joint Interim Statement criteria, using the multiple logistic regression to investigate the potential association of risk factors with the presence of MS. The overall prevalence of MS was 34.1% (95% CI = 30.8–37.4), increasing linearly with the increasing body mass index and age. From 40–49 years of age, MS was observed in about half of the women (46.0%), while men only experienced a high prevalence in the fifth decade of life (43.3%). The low HDL-c (64.4%) and abdominal obesity (58.9%) were higher in women (p < 0.001), while for men, high blood pressure was significantly higher (p < 0.001). Individuals aged 40–59 years old (odds ratio [OR] = 3.35 [95% CI = 2.30–4.90]), ≥ 60 years old (OR = 5.80 [3.63–9.27]), overweight (OR = 4.17 [2.77–6.29]), and obese (OR = 8.82 [5.56–13.98]) were more likely to have MS. The study population experienced high cardiometabolic risk, requiring government efforts to control MS and related risk factors, especially obesity. PMID:27936021

Prevalence of nocturnal frontal lobe epilepsy in the adult population of Bologna and Modena, Emilia-Romagna region, Italy.

PubMed

Vignatelli, Luca; Bisulli, Francesca; Giovannini, Giada; Licchetta, Laura; Naldi, Ilaria; Mostacci, Barbara; Rubboli, Guido; Provini, Federica; Tinuper, Paolo; Meletti, Stefano

2015-03-01

To estimate the prevalence of nocturnal frontal lobe epilepsy (NFLE) in the adults of two areas of the Emilia-Romagna region (northeast Italy) and to describe the clinical features from a population-based perspective. Population-based retrospective cohort study including adults with NFLE. Two areas of the Emilia-Romagna region: the city of Bologna (330,901 adult residents) and five districts of the province of Modena (424,007). Prevalence day: December 31, 2010. Patients with NFLE collected from multiple databases of neurologic hub centers of the districts involved. Diagnostic criteria: clinical history of sleep related bizarre motor attacks and videopolysomnographic recording confirming the typical features of NFLE. Inclusion criteria for prevalence calculation: residence in one of the two geographic areas on the prevalence day and an "active" or "in remission with treatment" form of NFLE. Six subjects from Bologna and eight from Modena were included. Crude prevalence (per 100,000 residents) was 1.8 (95% confidence interval 0.7-4.0) in Bologna and 1.9 (0.8-3.7) in Modena. Similarly, the main clinical features were consistent: onset during adolescence (median age 11-13 y), mainly hyperkinetic seizures, nonlesional form in more than two-thirds of cases, an active form of epilepsy in more than two-thirds of cases. A family history of epilepsy was reported only for two patients. This epidemiologic study establishes that NFLE is a rare epileptic condition, fulfilling the definition for rare disease. Because of methodological limitations of our case ascertainment, the estimates we disclose must be considered the minimum prevalence. © 2015 Associated Professional Sleep Societies, LLC.

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

2016-06-30

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.

Role of brain-derived neurotrophic factor during the regenerative response after traumatic brain injury in adult zebrafish.

PubMed

Cacialli, Pietro; Palladino, Antonio; Lucini, Carla

2018-06-01

Several mammalian animal models of traumatic brain injury have been used, mostly rodents. However, reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time. The brain of adult zebrafish, a teleost fish widely used as vertebrate model, possesses high regenerative properties after injury due to the presence of numerous stem cells niches. The ventricular lining of the zebrafish dorsal telencephalon is the most studied neuronal stem cell niche because its dorso-lateral zone is considered the equivalent to the hippocampus of mammals which contains one of the two constitutive neurogenic niches of mammals. To mimic TBI, stab wound in the dorso-lateral telencephalon of zebrafish was used in studies devoted to fish regenerative properties. Brain-derived neurotrophic factor, which is known to play key roles in the repair process after traumatic brain lesions, persists around the lesioned area of injured telencephalon of adult zebrafish. These results are extensively compared to reparative processes in rodent brain. Considering the complete repair of the damaged area in fish, it could be tempting to consider brain-derived neurotrophic factor as a factor contributing to create a permissive environment that enables the establishment of new neuronal population in damaged brain.

Quiescence and activation of stem and precursor cell populations in the subependymal zone of the mammalian brain are associated with distinct cellular and extracellular matrix signals

USDA-ARS?s Scientific Manuscript database

The subependymal zone (SEZ) of the lateral ventricles is one of the areas of the adult brain where new neurons are continuously generated from neural stem cells (NSCs), via rapidly dividing precursors. This neurogenic niche is a complex cellular and extracellular microenvironment, highly vascularize...

Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial.

PubMed

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

2014-07-22

To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH). 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. 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. 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. 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. © 2014 American Academy of Neurology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greene, Carol Ann, E-mail: carol.greene@auckland.ac.nz; Chang, Chuan-Yuan; Fraser, Cameron J.

Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. Themore » switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors.« less

Expression of Idh1R132H in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis.

PubMed

Bardella, Chiara; Al-Dalahmah, Osama; Krell, Daniel; Brazauskas, Pijus; Al-Qahtani, Khalid; Tomkova, Marketa; Adam, Julie; Serres, Sébastien; Lockstone, Helen; Freeman-Mills, Luke; Pfeffer, Inga; Sibson, Nicola; Goldin, Robert; Schuster-Böeckler, Benjamin; Pollard, Patrick J; Soga, Tomoyoshi; McCullagh, James S; Schofield, Christopher J; Mulholland, Paul; Ansorge, Olaf; Kriaucionis, Skirmantas; Ratcliffe, Peter J; Szele, Francis G; Tomlinson, Ian

2016-10-10

Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1 R132H in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced α-ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1 R132H mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[Assessment of individual iodine intake by the adult population in the Potsdam region on the basis of sea fish and iodized salt consumption].

PubMed

Pfaff, G; Georg, T

1995-06-01

Iodized salt has a high acceptance in the Potsdam region: 82% of the interviewed people use iodized salt, 13% do not use it, and only 5% of the probands were not able to make any statements. The current average iodine intake for adults is 76 micrograms/day. Only 5% of the adult population has an iodine intake of more than 100 micrograms/day. An efficient elimination of iodine deficiency in Germany requires a broad usage of iodized salt in the food industry.

Adult Seborrheic Dermatitis

PubMed Central

2011-01-01

Seborrheic dermatitis is a common chronic-recurrent inflammatory disorder that most commonly affects adults; however, a more transient infantile form also occurs. The definitive cause of seborrheic dermatitis is unknown. However, proliferation of Malassezia species has been described as a contributing factor. The adult form of seborrheic dermatitis affects up to approximately five percent of the general population. The disorder commonly affects the scalp, face, and periauricular region, with the central chest, axillae, and genital region also involved in some cases. Pruritus is not always present and is relatively common, especially with scalp disease. A variety of treatments are available including topical corticosteroids, topical antifungal agents, topical calcineurin inhibitors, and more recently, a nonsteroidal “device ”cream. This article reviews the practical topical management of seborrheic dermatitis in the United States, focusing on the adult population. PMID:21607192

Economic burden of underweight and overweight among adults in the Asia-Pacific region: a systematic review.

PubMed

Hoque, Mohammad Enamul; Mannan, Munim; Long, Kurt Z; Al Mamun, Abdullah

2016-04-01

To assess the economic burden of underweight and overweight among adults in the Asia-Pacific region. Systematic review of articles published until March 2015. Seventeen suitable articles were found, of which 13 assess the economic burden of overweight/obesity and estimate that it accounts for 1.5-9.9% of a country's total healthcare expenditure. Four articles on the economic burden of underweight estimate it at 2.5-3.8% of the country's total GDP. Using hospital data, and compared to normal weight individuals, four articles estimated extra healthcare costs for overweight individuals of 7-9.8% and more, and extra healthcare costs for obese individuals of 17-22.3% and higher. Despite methodological diversity across the studies, there is a consensus that both underweight and overweight impose a substantial financial burden on healthcare systems in the Asia-Pacific region. © 2016 John Wiley & Sons Ltd.

Hypothalamic neurogenesis persists in the aging brain and is controlled by energy-sensing IGF-I pathway.

PubMed

Chaker, Zayna; George, Caroline; Petrovska, Marija; Caron, Jean-Baptiste; Lacube, Philippe; Caillé, Isabelle; Holzenberger, Martin

2016-05-01

Hypothalamic tanycytes are specialized glial cells lining the third ventricle. They are recently identified as adult stem and/or progenitor cells, able to self-renew and give rise to new neurons postnatally. However, the long-term neurogenic potential of tanycytes and the pathways regulating lifelong cell replacement in the adult hypothalamus are largely unexplored. Using inducible nestin-CreER(T2) for conditional mutagenesis, we performed lineage tracing of adult hypothalamic stem and/or progenitor cells (HySC) and demonstrated that new neurons continue to be born throughout adult life. This neurogenesis was targeted to numerous hypothalamic nuclei and produced different types of neurons in the dorsal periventricular regions. Some adult-born neurons integrated the median eminence and arcuate nucleus during aging and produced growth hormone releasing hormone. We showed that adult hypothalamic neurogenesis was tightly controlled by insulin-like growth factors (IGF). Knockout of IGF-1 receptor from hypothalamic stem and/or progenitor cells increased neuronal production and enhanced α-tanycyte self-renewal, preserving this stem cell-like population from age-related attrition. Our data indicate that adult hypothalamus retains the capacity of cell renewal, and thus, a substantial degree of structural plasticity throughout lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

Scaling of Adult Regional Body Mass and Body Composition as a Whole to Height: Relevance to Body Shape and Body Mass Index

PubMed Central

Schuna, John M.; Peterson, Courtney M.; Thomas, Diana M.; Heo, Moonseong; Hong, Sangmo; Choi, Woong; Heymsfield, Steven B.

2015-01-01

Objectives Adult body mass (MB) empirically scales as height (Ht) squared (MB ∝ Ht2), but does regional body mass and body composition as a whole also scale as Ht2? This question is relevant to a wide range of biological topics, including interpretation of body mass index. Methods Dual-energy x-ray absorptiometry (DXA) was used to quantify regional body mass (head [MH], trunk, arms, legs) and whole-body composition (fat, lean soft tissue [LST], and bone mineral content [BMC]) in non-Hispanic (NH) white, NH black, Mexican American, and Korean adults participating in the National Health and Nutrition Examination Survey (NHANES; n=17,126) and Korean NHANES (n=8,942). Regression models were developed to establish Ht scaling powers for each measured component with adjustments for age and adiposity. Results Exploratory analyses revealed a consistent scaling pattern across men and women of the four race/ethnic groups: regional mass powers, head (~0.8-1) < arms and trunk (~1.8-2.3) < legs (~2.3-2.6); and body composition, LST (~2.0-2.3) < BMC (~2.1-2.4). Small sex and race/ethnic differences in scaling powers were also observed. As body mass scaled uniformly across the eight sex and race/ethnic groups as Ht~2, tall and short subjects differed in body shape (e.g., Mh/Mb ∝ Ht−~1) and composition. Conclusions Adult human body shape and relative composition are a function of body size as defined by stature, a finding that has important implications in multiple areas of biological research. PMID:25381999

Harnessing neurogenesis for the possible treatment of Parkinson's disease.

PubMed

Lamm, Omri; Ganz, Javier; Melamed, Eldad; Offen, Daniel

2014-08-15

The discovery of neurogenesis in the adult brain has created new possibilities for therapeutics in neurodegenerative diseases. Neural precursor cells, which have been found in various parts of the brain, e.g., the subventricular zone (SVZ) and substantia nigra (SN), have promising potential to replace the extensive loss of neurons occurring in neurodegenerative disorders. In Parkinson's disease (PD) the degeneration of nigral dopaminergic neurons and consequently the nigrostriatal pathway, which has been found to innervate proximally to the SVZ, causes motor and cognitive impairments. There is strong evidence that neurogenesis is impaired in PD, which has been related to the nonmotor symptoms of the disease. Recent evidence supports that this impairment in neurogenesis is partially caused by the lack of dopamine in one of the adult neurogenic niches, the SVZ. Thus, restoring the dopaminergic pathway in PD patients may have implications not only for motor function improvement, but for other cognitive and autonomic symptoms. Currently, there are no effective treatments that can stop or reverse the neurodegeneration process in the brain. Here we review the neurogenic process and observed alterations found in PD animal models and postmortem brains of PD patients. Finally, we review several attempts to stimulate the neurogenic process for nigral and/or striatal dopaminergic restoration by transgenic expression, exercise, or cell therapy. © 2014 Wiley Periodicals, Inc.

Prevalence and determinants of common mental illness among adult residents of Harari Regional State, Eastern Ethiopia

PubMed Central

Hunduma, Gari; Girma, Mulugeta; Digaffe, Tesfaye; Weldegebreal, Fitsum; Tola, Assefa

2017-01-01

Introduction Common mental disorders include depression, anxiety and somatoform disorders are a public health problem in developed as well as developing countries. It represents a psychiatric morbidity with significant prevalence, affecting all stages of life and cause suffering to the individuals, their family and communities. Despite this fact, little information about the prevalence of common mental illness is available from low and middle-income countries including Ethiopia. The aim of this study was to determine the magnitude of common mental disorders and its associated factors among adult residents of Harari Region. Methods Comparative cross-sectional, quantitative community-based survey was conducted From February 1, 2016 to March 30, 2016 in Harari Regional State using multi-stage sampling technique. A total of 968 residents was selected using two stage sampling technique. Of this 901 were participated in the study. Validated and Pretested Self reported questionnaire (SQR_20) was used to determine the maginitude of common mental disorders. Data was entered and analyzed using Epi-info version 3.5.1 and SPSS-17 for windows statistical packages. Univirate, Bi-variate and multivariate logistic regression analysis with 95% CI was employed in order to infer associations. Results The prevalence of common mental illnesses among adults in our study area was 14.9%. The most common neurotic symptoms in this study were often head ache (23.2%), sleep badly (16%) and poor appetite (13.8%). Substance use like Khat chewing (48.2%), tobacco use (38.2%) and alcohol use (10.5%) was highly prevalent health problem among study participant. In multivariate logistic regression analysis, respondents age between 25-34 years, 35-44 years, 45-54 years and above 55years were 6.4 times (AOR 6.377; 95% CI: 2.280-17.835), 5.9 times (AOR 5.900; 95% CI: 2.243-14.859), 5.6 times (AOR 5.648; 95% CI: 2.200-14.50) and 4.1 times (AOR 4.110; 95% CI: 1.363-12.393) more likely having common

Implementation of Information Communication Technology in the Teaching/Learning Process for Sustainable Development of Adults in West Africa Sub Sahara Region

ERIC Educational Resources Information Center

Nwobi, Anthonia; Ngozi, Ugwuoke; Rufina, Nwachukwu; Ogbonnaya, Kingsley A.

2016-01-01

This study examines the implementation of information technology in the teaching/learning process for sustainable development of adults in West Africa Sub Sahara Region (WASSR). Three research questions and two hypotheses guided the study. The population for the study was 3071 participants and instructors drawn from 10 education centres that were…

Alterations in monoamines level in discrete brain regions and other peripheral tissues in young and adult male rats during experimental hyperthyroidism.

PubMed

Hassan, Wafaa A; Rahman, Taghride Abdel; Aly, Mona S; Shahat, Asmaa S

2013-08-01

The present study was conducted to investigate the effect of experimentally-induced hyperthyroidism on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats (60 rats of each age). Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 500 μg/kg body wt.) for 21 consecutive days. Induction of hyperthyroidism caused a significant elevation in DA and 5-HT levels in most of the tissues studied of both young and adult animals after 7, 14, and 21 days. NE content significantly decreased after 21 days in most of the brain regions examined and after 14 and 21 days in blood plasma of young rats following hyperthyroidism. In adult rats, NE content decreased after 14 and 21 days in cardiac muscle and after 21 days only in adrenal gland. It may be suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanism.

PubMed

de Garavilla, L; Vergnolle, N; Young, S H; Ennes, H; Steinhoff, M; Ossovskaya, V S; D'Andrea, M R; Mayer, E A; Wallace, J L; Hollenberg, M D; Andrade-Gordon, P; Bunnett, N W

2001-08-01

Thrombin, generated in the circulation during injury, cleaves proteinase-activated receptor 1 (PAR1) to stimulate plasma extravasation and granulocyte infiltration. However, the mechanism of thrombin-induced inflammation in intact tissues is unknown. We hypothesized that thrombin cleaves PAR1 on sensory nerves to release substance P (SP), which interacts with the neurokinin 1 receptor (NK1R) on endothelial cells to cause plasma extravasation. PAR1 was detected in small diameter neurons known to contain SP in rat dorsal root ganglia by immunohistochemistry and in situ hybridization. Thrombin and the PAR1 agonist TFLLR-NH(2) (TF-NH(2)) increased [Ca(2+)](i) >50% of cultured neurons (EC(50)s 24 mu ml(-1) and 1.9 microM, respectively), assessed using Fura-2 AM. The PAR1 agonist completely desensitized responses to thrombin, indicating that thrombin stimulates neurons through PAR1. Injection of TF-NH(2) into the rat paw stimulated a marked and sustained oedema. An NK1R antagonist and ablation of sensory nerves with capsaicin inhibited oedema by 44% at 1 h and completely by 5 h. In wild-type but not PAR1(-/-) mice, TF-NH(2) stimulated Evans blue extravasation in the bladder, oesophagus, stomach, intestine and pancreas by 2 - 8 fold. Extravasation in the bladder, oesophagus and stomach was abolished by an NK1R antagonist. Thus, thrombin cleaves PAR1 on primary spinal afferent neurons to release SP, which activates the NK1R on endothelial cells to stimulate gap formation, extravasation of plasma proteins, and oedema. In intact tissues, neurogenic mechanisms are predominantly responsible for PAR1-induced oedema.

Perceived barriers to the regionalization of adult critical care in the United States: a qualitative preliminary study

PubMed Central

Kahn, Jeremy M; Asch, Rebecca J; Iwashyna, Theodore J; Rubenfeld, Gordon D; Angus, Derek C; Asch, David A

2008-01-01

Background Regionalization of adult critical care services may improve outcomes for critically ill patients. We sought to develop a framework for understanding clinician attitudes toward regionalization and potential barriers to developing a tiered, regionalized system of care in the United States. Methods We performed a qualitative study using semi-structured interviews of critical care stakeholders in the United States, including physicians, nurses and hospital administrators. Stakeholders were identified from a stratified-random sample of United States general medical and surgical hospitals. Key barriers and potential solutions were identified by performing content analysis of the interview transcriptions. Results We interviewed 30 stakeholders from 24 different hospitals, representing a broad range of hospital locations and sizes. Key barriers to regionalization included personal and economic strain on families, loss of autonomy on the part of referring physicians and hospitals, loss of revenue on the part of referring physicians and hospitals, the potential to worsen outcomes at small hospitals by limiting services, and the potential to overwhelm large hospitals. Improving communication between destination and source hospitals, provider education, instituting voluntary objective criteria to become a designated referral center, and mechanisms to feed back patients and revenue to source hospitals were identified as potential solutions to some of these barriers. Conclusion Regionalization efforts will be met with significant conceptual and structural barriers. These data provide a foundation for future research and can be used to inform policy decisions regarding the design and implementation of a regionalized system of critical care. PMID:19014704

Morphological and cellular characterization of the fetal canine (Canis lupus familiaris) subventricular zone, rostral migratory stream and olfactory bulb.

PubMed

Orechio, Dailiany; Aguiar, Bruna Andrade; Diniz, Giovanne Baroni; Bittencourt, Jackson Cioni; Haemmerle, Carlos A; Watanabe, Ii-Sei; Miglino, Maria Angelica; Castelucci, Patricia

2018-05-12

The existence of neurogenesis in the adult brain is a widely recognized phenomenon, occurring in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyrus in several vertebrate species. Neural precursors originated in the SVZ migrate to the main olfactory bulb (MOB), originating the rostral migratory stream (RMS) in the process. To better understand the formation of the adult neurogenic niches in dogs, we investigated the cellular composition and morphological organization of these areas in 57 days-old dog fetuses. Using multiple immunohistochemical markers, we demonstrated that the SVZ in the canine fetus is remarkably similar to the adult SVZ, with glial GFAP-immunoreactive (-ir) cells, DCX-ir neuroblasts and SOX2-ir neuronal progenitors tangentially organized along the dorsal lateral ventricle. The fetal RMS has all the features of its adult counterpart and closely resembles the RMS of other mammalian species. The late-development canine MOB has most of the neurochemical features of the adult MOB, including an early-developed TH-ir population and maturing CALR-ir interneurons, but CALB-ir neurons in the granule cell layer will only appear in the post-partum period. Taken together, our results suggest that the canine fetal development of adult neurogenic niches closely resembles those of primates, and dogs may be suitable models of human adult neurogenesis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Application of data mining techniques to explore predictors of upper urinary tract damage in patients with neurogenic bladder.

PubMed

Fang, H; Lu, B; Wang, X; Zheng, L; Sun, K; Cai, W

2017-08-17

This study proposed a decision tree model to screen upper urinary tract damage (UUTD) for patients with neurogenic bladder (NGB). Thirty-four NGB patients with UUTD were recruited in the case group, while 78 without UUTD were included in the control group. A decision tree method, classification and regression tree (CART), was then applied to develop the model in which UUTD was used as a dependent variable and history of urinary tract infections, bladder management, conservative treatment, and urodynamic findings were used as independent variables. The urethra function factor was found to be the primary screening information of patients and treated as the root node of the tree; Pabd max (maximum abdominal pressure, >14 cmH2O), Pves max (maximum intravesical pressure, ≤89 cmH2O), and gender (female) were also variables associated with UUTD. The accuracy of the proposed model was 84.8%, and the area under curve was 0.901 (95%CI=0.844-0.958), suggesting that the decision tree model might provide a new and convenient way to screen UUTD for NGB patients in both undeveloped and developing areas.

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

PubMed

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

2010-01-01

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

[Features of daily rhythm of arterial pressure in patients with primary arterial hypertension and neurogenic syncope conditions].

PubMed

Musaeva, Z A; Oknin, V Iu; Khapaev, B A; Fedotova, A V; Veĭn, A M

2002-01-01

A comparative analysis of parameters of systemic BP in patients with primary arterial hypotension (PAH) and in patients with neurogenic syncopes (NS) in the cycle sleep-awake. Blood pressure was investigated in 20 patients with PAH aged 16-44 years and 18 patients with NS aged 16-49 years. 24-h ambulatory monitoring of BP was made on the monitor ABPM-02/M (Meditech, Hungary). Rhythm indices of BP in NS patients corresponded to age normal criteria. 24-h arrhythmia of BP in PAH patients manifests with excessive drop of diastolic BP in sleep (55% patients were overdippers). PAH and NS patients differ maximally by hypotonic load in sleep: 1.0 +/- 0.7% in NS vs 15.4 +/- 3.2% in PAH. Hypotonia episodes in awake PAH patients were registered at each 4th-5th measurement of BP, in NS patients--at each 11th-13th. Heart rate in awake PAH patients is higher than in healthy subjects. Hypotonic load in sleep carries the highest differentially-diagnostic importance. This makes more perspective examinations of such patients in the cycle sleep-awake. The changes observed in PAH patients evidence for activation of cerebral sympathico-adrenal systems participating in baroreflex regulation.

Adult Education Information and Referral Hot-Line. Adult Education Special Project. Final Report, July 1980-June 1981.

ERIC Educational Resources Information Center

Morgan, Jim

A toll-free adult education information and referral hotline provided information and referral services to approximately 1500 adults in Region IX in Texas from September 1980 to June 1981. Adult education co-ops and testing centers forwarded pertinent program information (class schedules, General Educational Development testing information) to the…

Atypical white-matter microstructure in congenitally deaf adults: A region of interest and tractography study using diffusion-tensor imaging.

PubMed

Karns, Christina M; Stevens, Courtney; Dow, Mark W; Schorr, Emily M; Neville, Helen J

2017-01-01

Considerable research documents the cross-modal reorganization of auditory cortices as a consequence of congenital deafness, with remapped functions that include visual and somatosensory processing of both linguistic and nonlinguistic information. Structural changes accompany this cross-modal neuroplasticity, but precisely which specific structural changes accompany congenital and early deafness and whether there are group differences in hemispheric asymmetries remain to be established. Here, we used diffusion tensor imaging (DTI) to examine microstructural white matter changes accompanying cross-modal reorganization in 23 deaf adults who were genetically, profoundly, and congenitally deaf, having learned sign language from infancy with 26 hearing controls who participated in our previous fMRI studies of cross-modal neuroplasticity. In contrast to prior literature using a whole-brain approach, we introduce a semiautomatic method for demarcating auditory regions in which regions of interest (ROIs) are defined on the normalized white matter skeleton for all participants, projected into each participants native space, and manually constrained to anatomical boundaries. White-matter ROIs were left and right Heschl's gyrus (HG), left and right anterior superior temporal gyrus (aSTG), left and right posterior superior temporal gyrus (pSTG), as well as one tractography-defined region in the splenium of the corpus callosum connecting homologous left and right superior temporal regions (pCC). Within these regions, we measured fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and white-matter volume. Congenitally deaf adults had reduced FA and volume in white matter structures underlying bilateral HG, aSTG, pSTG, and reduced FA in pCC. In HG and pCC, this reduction in FA corresponded with increased RD, but differences in aSTG and pSTG could not be localized to alterations in RD or AD. Direct statistical tests of hemispheric asymmetries in these

Urban vs. rural differences in prescription opioid misuse among adults in the United States: informing region specific drug policies and interventions.

PubMed

Rigg, Khary K; Monnat, Shannon M

2015-05-01