van Dullemen Leon FA
Full Text Available Abstract Background Kidneys derived from brain dead donors have lower graft survival and higher graft-function loss compared to their living donor counterpart. Heat Shock Proteins (HSP are a large family of stress proteins involved in maintaining cell homeostasis. We studied the role of stress-inducible genes Heme Oxygenase-1 (HO-1, HSP27, HSP40, and HSP70 in the kidney following a 4 hour period of brain death. Methods Brain death was induced in rats (n=6 by inflating a balloon catheter in the epidural space. Kidneys were analysed for HSPs using RT-PCR, Western blotting, and immunohistochemistry. Results RT-PCR data showed a significant increase in gene expression for HO-1 and HSP70 in kidneys of brain dead rats. Western blotting revealed a massive increase in HO-1 protein in brain dead rat kidneys. Immunohistochemistry confirmed these findings, showing extensive HO-1 protein expression in the renal cortical tubules of brain dead rats. HSP70 protein was predominantly increased in renal distal tubules of brain dead rats treated for hypotension. Conclusion Renal stress caused by brain death induces expression of the cytoprotective genes HO-1 and HSP70, but not of HSP27 and HSP40. The upregulation of these cytoprotective genes indicate that renal damage occurs during brain death, and could be part of a protective or recuperative mechanism induced by brain death-associated stress.
Eric J. Neuberger
Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.
Vanessa de Oliveira-Carlos
Full Text Available The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 [Formula: see text] of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA [Formula: see text] cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA [Formula: see text] cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches.
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
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.
Li, Yifu; Xiong, Yunyi; Zhang, Huanxi; Li, Jun; Wang, Dong; Chen, Wenfang; Yuan, Xiaopeng; Su, Qiao; Li, Wenwen; Huang, Huiting; Bi, Zirong; Liu, Longshan; Wang, Changxi
This study aimed to investigate the protective effects of EGb761, a Ginkgo Biloba extract, against brain death-induced kidney injury. Sixty male Sprague Dawley rats were randomly divided into six groups: sham, brain-death (BD), BD + EGb b48h (48 hours before BD), BD + EGb 2 h (2 hours after BD), BD + EGb 1 h, and BD + EGb 0.5 h. Six hours after BD, serum sample and kidney tissues were collected for analyses. The levels of blood urea nitrogen (BUN) and serum creatinine significantly elevated in the BD group than in sham group. In all the EGb761-treated BD animals except for the BD + Gb 2 h group, the levels of BUN and serum creatinine significantly reduced (all P < 0.01). EGb761 attenuated tubular injury and lowered the histological score. In addition, the longer duration of drug treatment was, the better protective efficacy could be observed. EGb761 significantly reduced IL-1β, IL-6, TNF-α, MCP-1, IP-10 mRNA expression and macrophage infiltration in the kidney. EGb761 treatment at 48 hour before brain death significantly attenuate the levels of p-JNK-MAPK, p-p38-MAPK, and p-STAT3 proteins (all P < 0.05, compared to BD group). In summary, our data showed that EGb761 treatment protected donor kidney from BD-induced damages by blocking SAPK and JAK-STAT signalings. Early administration of EGb761 can provide better protective efficacy.
John, Cynthia A; Day, Michael W
Central neurogenic diabetes insipidus, syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome are secondary events that affect patients with traumatic brain injury. All 3 syndromes affect both sodium and water balance; however, they have differences in pathophysiology, diagnosis, and treatment. Differentiating between hypernatremia (central neurogenic diabetes insipidus) and the 2 hyponatremia syndromes (syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome) is critical for preventing worsening neurological outcomes in patients with head injuries.
Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka; Ishikawa, Hiroto; Yankee, Ernest; McGrogan, Michael; Case, Casey; Borlongan, Cesar V
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.
Tamura, Yasuhisa; Takahashi, Kayo; Takata, Kumi; Eguchi, Asami; Yamato, Masanori; Kume, Satoshi; Nakano, Masayuki; Watanabe, Yasuyoshi; Kataoka, Yosky
Neural stem cells in two neurogenic regions, the subventricular zone and the subgranular zone (SGZ) of the hippocampal dentate gyrus, can divide and produce new neurons throughout life. Hippocampal neurogenesis is related to emotions, including depression/anxiety, and the therapeutic effects of antidepressants, as well as learning and memory. The establishment of in vivo imaging for proliferative activity of neural stem cells in the SGZ might be used to diagnose depression and to monitor the therapeutic efficacy of antidepressants. Positron emission tomography (PET) imaging with 3'-deoxy-3'-[(18)F]fluoro-l-thymidine ([(18)F]FLT) has been studied to allow visualization of proliferative activity in two neurogenic regions of adult mammals; however, the PET imaging has not been widely used because of lower accumulation of [(18)F]FLT, which does not allow quantitative assessment of the decline in cellular proliferative activity in the SGZ under the condition of depression. We report the establishment of an enhanced PET imaging method with [(18)F]FLT combined with probenecid, an inhibitor of drug transporters at the blood-brain barrier, which can allow the quantitative visualization of neurogenic activity in rats. Enhanced PET imaging allowed us to evaluate reduced cell proliferation in the SGZ of rats with corticosterone-induced depression, and further the recovery of proliferative activity in rats under treatment with antidepressants. This enhanced [(18)F]FLT-PET imaging technique with probenecid can be used to assess the dynamic alteration of neurogenic activity in the adult mammalian brain and may also provide a means for objective diagnosis of depression and monitoring of the therapeutic effect of antidepressant treatment. Adult hippocampal neurogenesis may play a role in major depression and antidepressant therapy. Establishment of in vivo imaging for hippocampal neurogenic activity may be useful to diagnose depression and monitor the therapeutic efficacy of
Peter T. Dorsher
Full Text Available Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented.
... individuals speech Apraxia of speech—irregularities in the timing and inaccuracies in the movement of the muscles ... edited book with a chapter on neurogenic stuttering.) Market, K. E., Montague, J. C., Buffalo, J. C., & ...
... These include choral reading, singing, adaptation (repeated oral reading of the same passage) or speaking while under auditory ... in conjunction with the clients’ physicians. Some therapy techniques that help reduce the symptoms of developmental stuttering may also be effective with neurogenic ...
Since the first experimental reports showing the persistence of neurogenic activity in the adult mammalian brain, this field of neurosciences has expanded significantly. It is now widely accepted that neural stem and precursor cells survive during adulthood and are able to respond to various endogenous and exogenous cues by altering their proliferation and differentiation activity. Nevertheless, the pathway to therapeutic applications still seems to be long. This review attempts to summarize and revisit the available data regarding the plasticity potential of adult neural stem cells and of their normal microenvironment, the neurogenic niche. Recent data have demonstrated that adult neural stem cells retain a high level of pluripotency and that adult neurogenic systems can switch the balance between neurogenesis and gliogenesis and can generate a range of cell types with an efficiency that was not initially expected. Moreover, adult neural stem and precursor cells seem to be able to self-regulate their interaction with the microenvironment and even to contribute to its synthesis, altogether revealing a high level of plasticity potential. The next important step will be to elucidate the factors that limit this plasticity in vivo, and such a restrictive role for the microenvironment is discussed in more details.
Lei Joy X
Full Text Available Abstract Background Molecular changes in multiple biological processes contribute to the development of chronic neurodegeneration such as late onset Alzheimer's disease (LOAD. To discover how these changes are reflected at the level of gene expression, we used a subtractive transcription-based amplification of mRNA procedure to identify novel genes that have altered expression levels in the brains of Alzheimer's disease (AD patients. Among the genes altered in expression level in AD brains was a transcript encoding a novel protein, SDIM1, that contains 146 amino acids, including a typical signal peptide and two transmembrane domains. Here we examined its biochemical properties and putative roles in neuroprotection/neurodegeneration. Results QRT-PCR analysis of additional AD and control post-mortem human brains showed that the SDIM1 transcript was indeed significantly down regulated in all AD brains. SDIM1 is more abundant in NT2 neurons than astrocytes and present throughout the cytoplasm and neural processes, but not in the nuclei. In NT2 neurons, it is highly responsive to stress conditions mimicking insults that may cause neurodegeneration in AD brains. For example, SDIM1 was significantly down regulated 2 h after oxygen-glucose deprivation (OGD, though had recovered 16 h later, and also appeared significantly up regulated compared to untreated NT2 neurons. Overexpression of SDIM1 in neuro-progenitor cells improved cells' ability to survive after injurious insults and its downregulation accelerated cell death induced by OGD. Yeast two-hybrid screening and co-immunoprecipitation approaches revealed, both in vitro and in vivo, an interaction between SDIM1 and DNAJB4, a heat shock protein hsp40 homolog, recently known as an enhancer of apoptosis that also interacts with the mu opioid receptor in human brain. Overexpression of DNAJB4 alone significantly reduced cell viability and SDIM1 co-overexpression was capable of attenuating the cell death
Full Text Available Adult neurogenesis is a lifelong process that occurs in two main neurogenic niches of the brain, namely in the subventricular zone (SVZ of the lateral ventricles and in the subgranular zone (SGZ of the dentate gyrus (DG in the hippocampus. In the 1960s, studies on adult neurogenesis have been hampered by the lack of established phenotypic markers. The precise tracing of neural stem/progenitor cells (NPCs was therefore, not properly feasible. After the (partial identification of those markers, it was the lack of specific tools that hindered a proper experimental elimination and tracing of those cells to demonstrate their terminal fate and commitment. Nowadays, irradia-tion, cytotoxic drugs as well as genetic tracing/ablation procedures have moved the field forward and increased our understanding of neurogenesis processes in both physiological and pathological conditions. Newly formed NPC progeny from the SVZ can replace granule cells in the olfactory bulbs of rodents, thus contributing to orchestrate sophisticated odour behaviour. SGZ-derived new granule cells, instead, integrate within the DG where they play an essential role in memory functions. Furthermore, converging evidence claim that endogenous NPCs not only exert neurogenic functions, but might also have non-neurogenic homeostatic functions by the release of different types of neuroprotective molecules. Remarkably, these non-neurogenic homeostatic functions seem to be necessary, both in healthy and diseased conditions, for example for preventing or limiting tissue damage. In this review, we will discuss the neurogenic and the non-neurogenic functions of adult NPCs both in physiological and pathological conditions.
Frias, Bárbara; Santos, João; Morgado, Marlene; Sousa, Mónica Mendes; Gray, Susannah M Y; McCloskey, Karen D; Allen, Shelley; Cruz, Francisco; Cruz, Célia Duarte
Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients. Copyright © 2015 Frias et al.
Reznik, J E; Biros, E; Lamont, A C; Sacher, Y; Kibrik, O; Milanese, S; Gordon, S; Galea, M P
Neurogenic heterotopic ossification (NHO) is a complication of a neurological injury following traumatic brain injury (TBI) and may be present around major synovial joints. It is often accompanied by severe pain, which may lead to limitation in activities of daily living. Currently, a common intervention for NHO is surgery, which has been reported to carry many additional risks. This study was designed to assess the effect of extracorporeal shock wave therapy (ESWT) on pain in patients with TBI with chronic NHO. A series of single-case studies (n = 11) was undertaken with patients who had TBI and chronic NHO at the hip or knee. Each patient received four applications of high-energy EWST delivered to the affected joint over 8 weeks. Two-weekly follow-up assessments were carried out, and final assessments were made 3 and 6 months post-intervention. Pain was measured using the Faces Rating Scale, and X-rays were taken at baseline and 6-months post-intervention to physiologically measure the size of the NHO. The application of high-energy ESWT was associated with significant overall reduction of pain in patients with TBI and NHO (Tau-0.412, 95% confidence interval -0.672 to -0.159, p = 0.002). ESWT is a novel non-invasive intervention for reducing pain resulting from NHO in patients with TBI.
Reznik, J E; Biros, E; Sacher, Y; Kibrik, O; Milanese, S; Gordon, S; Galea, M P
Neurogenic heterotopic ossification (NHO) occurs as a complication of traumatic brain injury (TBI). Management of clinically significant NHO remains variable. Complications of mature NHO include limitation of mobility. The effect of the extracorporeal shock wave therapy (ESWT) on range of motion at hip and knee, and function in patients with TBI with chronic NHO was investigated. A series of single-case studies applying ESWT to chronic NHO at the hip or knee of 11 patients with TBI were undertaken at a rehabilitation hospital. Participants received four applications of high-energy EWST delivered to the affected hip or knee over a period of 8 weeks. Two-weekly follow- up assessments were carried out; final assessments were made 3 and 6 months post-intervention. Range of motion (ROM) and Functional Reach (FR) or Modified Functional Reach (MFR) were measured. Application of high-energy ESWT was associated with significant improvement in ROM (flexion) of the NHO-affected knee (Tau = 0.833, 95% CI 0.391-1.276, p = 0.002) and significant improvement of FR (Overall Tau 0.486, 95% CI 0.141-0.832, p = 0.006); no significant improvement in hip ROM or MFR. ESWT may improve mobility and balance of patients with TBI who have chronic NHO.
Sebastian, Swapna; Nair, Prem G; Thomas, Philip; Tyagi, Amit Kumar
To determine the type, severity and manifestation of dysphagia in patients with neurogenic etiology. Clinical documentation was done on the different etiologies, its manifestation, assessment findings and management strategies taken for patients with neurogenic oropharyngeal dysphagia who were referred for assessment and management of dysphagia over a period of three months in a tertiary care teaching hospital. Flexible endoscopic examination was done in all the patients. The severity of dysphagia in these patients were graded based on Gugging Swallowing Screen (GUSS). A total of 53 patients with neurogenic oropharyngeal dysphagia were evaluated by an otolaryngologist and a speech language pathologist over a period of three months. The grading of severity based on GUSS for these patients were done. There were 30 patients with recurrent laryngeal nerve injury due to various etiologies, one patient with Neurofibroma-vestibular schwanoma who underwent surgical excision, 16 patients with stroke, two patients with traumatic brain injury, two patients with Parkinsonism and two patients with myasthenia gravis. The manifestation of dysphagia was mainly in the form of prolonged masticatory time, oral transit time, and increased number of swallows required for each bolus, cricopharyngeal spasms and aspiration. Among the dysphagia patients with neurogenic etiology, dysphagia is manifested with a gradual onset and is found to have a progressive course in degenerative disorders. Morbidity and mortality may be reduced with early identification and management of neurogenic dysphagia.
Full Text Available 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 two 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.
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
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
Gholami, Shahram S; Rogers, Rodman; Chang, Johnny; Ho, Hoa-Chung; Grazziottin, Tulio; Lin, Ching-Schwun; Lue, Tom F
We examined neurogenic and vasculogenic erectile dysfunction associated with hypercholesterolemia and evaluated vascular endothelial growth factor (VEGF) and adeno-associated virus (AAV) mediated, brain derived neurotrophic factor (BDNF) for potential treatment. A total of 21, 2-month-old male rats were fed a 2% cholesterol diet and another seven were fed a normal diet. Two months later serum cholesterol levels were measured and test agents were given intracavernously. Those on normal diet (controls) received phosphate buffered saline (PBS). Those on cholesterol diet were randomly divided into 3 groups receiving PBS, VEGF (4 microg.) or AAV-BDNF (10 viral particles). Four months later erectile function was evaluated and cavernous tissues were collected for erectile dysfunction and immunohistochemical staining. Serum cholesterol levels were higher in rats fed the high fat diet than in controls. Intracavernous pressure was lower in cholesterol plus PBS treated rats than in rats of the other 3 groups. All hypercholesterolemic rats had less nerve content, fewer endothelial cells and higher smooth muscle content than rats with normal cholesterol levels. In cholesterol plus PBS treated rats electron microscopy showed hypermyelination and severe atrophy of axons, a remarkable decrease in the number and size of nonmyelinated axons, disarray of the smooth muscle cells with scant myofilaments and foamy cytoplasm, and denuded endothelial lining of the sinusoids covered by numerous platelets. VEGF and AAV-BDNF appeared to alleviate partially these changes. A high fat diet caused erectile dysfunction with accompanying neurological and vascular changes. VEGF and AAV-BDNF seemed to alleviate these problems.
Chanson, Philippe; Salenave, Sylvie
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.
Burhan M. Edrees
mities within the spinal cord, brain, or nervous supply. A number of nerves and muscles mostly work together for the attainment of specified function. A very common example regarding the blad- der is, urinary incontenince. In this condition, the brain is unable to control the functions of bladder, which results in neurogenic ...
Koyama, K; Moda, Y; Sone, A; Tanaka, H; Hino, Y
We encountered a rare patient with Hunter's syndrome who exhibited urinary retention as a result of a neurogenic bladder, uninhibited detrusor contractions, and detrusor-sphincter dyssynergia. Neurological findings were consistent with cervical myelopathy and cervical MR imaging showed very narrow segments at the cord level C2-4. We speculate that this Hunter's syndrome patient has cervical myelopathy and that this neurological dysfunction causes the neurogenic bladder. PMID:8014981
Full Text Available Sarcopenia is an aging-associated condition, which is currently characterized by the loss of muscle mass and muscle strength. However, there is no consensus regarding its characterization hitherto. As the world older adult population is on the rise, the impact of sarcopenia becomes greater. Due to the lack of effective treatments, sarcopenia is still a persisting problem among the global older adults and should not be overlooked. As a result, it is vital to investigate deeper into the mechanism underlying the pathogenesis of sarcopenia in order to develop more effective therapeutic interventions and to inscribe a more uniform characterization. The etiology of sarcopenia is currently found to be multifactorial, and most of the pharmacological researches are focused on the muscular factors in aging. Although the complete mechanism underlying the development of sarcopenia is still waiting to be elucidated, we propose in this article that the primary trigger of sarcopenia may be neurogenic in origin based on the intimate relationship between the nervous and muscular system, namely, the motor neuron and its underlying muscle fibers. Both of them are affected by the cellular environment and their physiological activity.
Schmelz, M; Petersen, Lars Jelstrup
The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge...... about neurogenic inflammation in human skin, including the involvement of mast cells....
Droxidopa is a first-in-class, orally available, synthetic amino acid precursor of norepinephrine that received accelerated Food and Drug Administration approval in February 2014 after Orphan Drug status for a debilitating condition known as symptomatic neurogenic orthostatic hypotension. Neurogenic disorders often lead to postural hypotension as a result of poor norepinephrine release from its storage sites. Clinical data suggest increases in standing systolic blood pressure and improvements in many other markers for subjective relief in patients with symptomatic neurogenic hypotension who received droxidopa therapy over 1-2 weeks. Studies evaluating the sustained effects of droxidopa are ongoing. With minimal drug interactions (even with carbidopa use) or adverse effects, droxidopa therapy can be used safely in patients with a variety of neurologic conditions; however, more data are needed to determine its appropriate pharmacotherapeutic role. In all, droxidopa is a safe and effective medication 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 secondary to primary autonomic failure (Parkinson's disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy.
Chen, Kuo-Chiang; Minor, Thomas X; Rahman, Nadeem U; Ho, Hao-Chung; Nunes, Lora; Lue, Tom F
To test the hypothesis that combined intracavernosal injection with vascular endothelial growth factor (VEGF) with adeno-associated virus-mediated brain-derived neurotrophic factor (AAV-BDNF) synergistically facilitates the neural regeneration and erectile function after cavernosal nerve injury. Forty Sprague-Dawley male rats were randomly divided into five equal groups: eight had a sham operation while 32 had bilateral cavernosal nerve freezing followed by an immediate intracavernosal injection with either phosphate-buffered saline (PBS), VEGF, AAV-BDNF, or AAV-BDNF + VEGF. Erectile function was assessed by cavernosal nerve electrostimulation at 3 months, and samples of the major pelvic ganglia and penile tissue were evaluated histologically. In this animal model of impotence from nerve injury, the recovery of erectile function was greatest in those receiving AAV-BDNF + VEGF; the mean (sd) maximal intracavernosal pressure in this group was 87.2 (20.78) cmH2O, compared with 37.3 (11.39) for VEGF alone and 49.8 (29.58) for AAV-BDNF alone. No erectile dysfunction was identified in the sham group, with a pressure of 100.7 (22.70) cmH2O, while all treatment groups significantly outperformed the PBS (control) group, at 29.3 (13.52) cmH2O. Furthermore, all animals receiving monotherapy or combined treatment had more NADPH-diaphorase-positive nerve fibres than controls but less than in the sham group. Bilateral cavernosal nerve freezing causes erectile dysfunction with accompanying neurological changes. Intracavernosal injection with either VEGF or AAV-BDNF alone enhances nerve regeneration, with combined therapy (VEGF and AAV-BDNF) promoting neural and erectile recovery additively.
Parolisi, Roberta; Cozzi, Bruno; Bonfanti, Luca
Adult neurogenesis has been implicated in brain plasticity and brain repair. In mammals, it is mostly restricted to specific brain regions and specific physiological functions. The function and evolutionary history of mammalian adult neurogenesis has been elusive so far. The largest neurogenic site in mammals (subventricular zone, SVZ) generates neurons destined to populate the olfactory bulb. The SVZ neurogenic activity appears to be related to the dependence of the species on olfaction since it occurs at high rates throughout life in animals strongly dependent on this function for their survival. Indeed, it dramatically decreases in humans, who do not depend so much on it. This study investigates whether the SVZ neurogenic site exists in mammals devoid of olfaction and olfactory brain structures, such as dolphins. Our results demonstate that a small SVZ-like region persists in these aquatic mammals. However, this region seems to have lost its neurogenic capabilities since neonatal stages. In addition, instead of the typical newly generated neuroblasts, some mature neurons were observed in the dolphin SVZ. Since cetaceans evolved from terrestrial ancestors, non-neurogenic SVZ may indicate extinction of adult neurogenesis in the absence of olfactory function, with the retention of an SVZ-like anatomical region either vestigial or of still unknown role.
Lee, Chan Ho; Shim, Su Jung; Kim, Hyun Jung; Yang, Hyuna; Kang, Youn Joo
Heterotopic ossification (HO) is frequently seen on rehabilitation units after spinal cord injuries, fractures, brain injuries, and limb amputations. Currently, there is no effective treatment for HO other than prophylaxis with anti-inflammatory medications, irradiation, and bisphosphonate administration. These prophylactic treatments are not effective for managing ectopic bone once it has formed. Here we describe three cases of established neurogenic HO treated with radiation therapy (RT). All patients had decreased serum alkaline phosphatase (ALP) and bone-specific ALP levels with decreased pain but increased range of motion immediately after RT. Post-treatment X-rays revealed no further growth of the HO. All patients maintained clinical and laboratory improvements 4 or 6 months after the RT. Our results suggest that RT is safe and effective in decreasing pain and activity of neurogenic HO.
Elena W. Adlaf
Full Text Available Throughout development, neural stem cells (NSCs give rise to differentiated neurons, astrocytes, and oligodendrocytes which together modulate perception, memory, and behavior in the adult nervous system. To understand how NSCs contribute to postnatal/adult brain remodeling and repair after injury, the lateral ventricular (LV neurogenic niche in the rodent postnatal brain serves as an excellent model system. It is a specialized area containing self-renewing GFAP+ astrocytes functioning as NSCs generating new neurons throughout life. In addition to this now well-studied regenerative process, the LV niche also generates astrocytes, playing an important role for glial scar formation after cortical injury. While LV NSCs can be clearly distinguished from their neuroblast and oligodendrocyte progeny via molecular markers, the astrocytic identity of NSCs has complicated their distinction from terminally-differentiated astrocytes in the niche. Our current models of postnatal/adult LV neurogenesis do not take into account local astrogenesis, or the possibility that cellular markers may be similar between non-dividing GFAP+ NSCs and their differentiated astrocyte daughters. Postnatal LV neurogenesis is regulated by NSC-intrinsic mechanisms interacting with extracellular/niche-driven cues. It is generally believed that these local effects are responsible for sustaining neurogenesis, though behavioral paradigms and disease states have suggested possibilities for neural circuit-level modulation. With recent experimental findings that neuronal stimulation can directly evoke responses in LV NSCs, it is possible that this exciting property will add a new dimension to identifying postnatal/adult NSCs. Here, we put forth a notion that neural circuit-level input can be a distinct characteristic defining postnatal/adult NSCs from non-neurogenic astroglia.
Full Text Available CD95 (Fas/APO-1, when bound by its cognate ligand CD95L, induces cells to die by apoptosis. We now show that elimination of CD95 or CD95L results in a form of cell death that is independent of caspase-8, RIPK1/MLKL, and p53, is not inhibited by Bcl-xL expression, and preferentially affects cancer cells. All tumors that formed in mouse models of low-grade serous ovarian cancer or chemically induced liver cancer with tissue-specific deletion of CD95 still expressed CD95, suggesting that cancer cannot form in the absence of CD95. Death induced by CD95R/L elimination (DICE is characterized by an increase in cell size, production of mitochondrial ROS, and DNA damage. It resembles a necrotic form of mitotic catastrophe. No single drug was found to completely block this form of cell death, and it could also not be blocked by the knockdown of a single gene, making it a promising way to kill cancer cells.
Ball, Martin J.
Acquired neurogenic communication disorders can affect language, speech, or both. Although neurogenic speech disorders have been researched for a considerable time, much of this work has been restricted to a few languages (mainly English, with German, French, Japanese and Chinese also represented). Further, the work has concentrated on monolingual speakers. In this account, I aim to outline the main acquired speech disorders, and give examples of research into multilingual aspects of this top...
Kesdangsakonwut, S; Sunden, Y; Yamada, K; Nishizono, A; Sawa, H; Umemura, T
Cardiomyopathies have been rarely described in rabbits. Here we report myocardial necrosis of the ventricular wall in rabbits with experimentally induced rabies. Myocardial lesions were found only in rabbits with brain lesions, and the severity of the cardiac lesions was proportional to that of the brain lesions. Neither the frequency nor the cumulative dose of anesthesia was related to the incidence or the severity of the myocardial lesions. The myocardial lesions were characterized by degeneration and/or necrosis of myocardial cells and were accompanied by contraction band necrosis, interstitial fibrosis, and infiltration of inflammatory cells. The brain lesions due to rabies virus infection were most prominent in the cerebral cortex, thalamus, hypothalamus, brainstem, and medulla. Rabies virus antigen was not found in the hearts of any rabbits. Based on these findings, the myocardial lesions were classified as neurogenic cardiomyopathy. © The Author(s) 2014.
Full Text Available Background. Loss of normal bowel function caused by nerve injury, neurological disease or congenital defects of the nervous system is termed neurogenic bowel dysfunction (NBD. It usually includes combinations of fecal incontinence, constipation, abdominal pain and bloating. When standard treatment of NBD fails surgical procedures are often needed. Neurostimulation has also been investigated, but no consensus exists about efficacy or clinical use. Methods. A systematic literature search of NBD treated by sacral anterior root stimulation (SARS, sacral nerve stimulation (SNS, peripheral nerve stimulation, magnetic stimulation, and nerve re-routing was made in Pubmed, Embase, Scopus, and the Cochrane Library. Results. SARS improves bowel function in some patients with complete spinal cord injury (SCI. Nerve re-routing is claimed to facilitate defecation through mechanical stimulation of dermatomes in patients with complete or incomplete SCI or myelomeningocele. SNS can reduce NBD in selected patients with a variety of incomplete neurological lesions. Peripheral stimulation using electrical stimulation or magnetic stimulation may represent non-invasive alternatives. Conclusion. Numerous methods of neurostimulation to treat NBD have been investigated in pilot studies or retrospective studies. Therefore, larger controlled trials with well-defined inclusion criteria and endpoints are recommended before widespread clinical use of neurostimulation against NBD.
Full Text Available Neurogenic pulmonary edema is a life threatening complication of severe central nervous system injury. The most common cause of neurogenic pulmonary edema is subarachnoid hemorrhage followed by head trauma and epilepsy. The rare causes are cervical spine trauma, multiplesclerosis, cerebellar hemorrhage and intracranial tumors. Neurogenic pulmonary edema is characterized by an increase in extravascular lung water in patients who have sustained a sudden change in neurologic condition. The exact pathophysiology is unclear but it probably involves an adrenergic response to the central nervous system injury which leads to increased catecholamine, pulmonary hydrostatic pressure and increased lung capillary permeability. The presenting symptoms are nonspecific and often include dyspnea, tachypnea, tachycardia, hypoxemia, pinkfroty secretion, bilateral pulmonary infiltrates and crackles. These symptoms start within minutes or hours and resolves 48-72 hours that typically for neurogenic pulmonary edema. Basic principles of treatment, surgical decompression, reduce intracranial pressure, controlled ventilation with suplemental oxygen, positive end expiratory pressure and diuresis. We report a case with neurogenic pulmonary edema that occured after head trauma. (Journal of the Turkish Society Intensive Care 2012; 10: 59-62
Li, Lai-Fung; Ka-Kit Leung, Gilberto; Lui, Wai-Man
Neurogenic bladder refers to dysfunction of the urinary bladder secondary to diseases of the nervous system that result in problems with urine storage, micturition, or both. The most common causes are multiple sclerosis and spinal cord injury. Patients commonly present with recurrent UTIs, obstructive uropathies, and urinary retention. Without proper treatment, neurogenic bladder may result in nephropathy and renal failure, both of which have a significant negative impact on the health and life expectancy of patients. Restoration of lost neural function using artificial stimulators is a feasible therapeutic strategy. This article reviews the pathophysiology of neurogenic bladder and the 2 most commonly employed sacral nerve stimulation methods-the Brindley procedure and sacral neuromodulation. Copyright © 2016 Elsevier Inc. All rights reserved.
Theys, Catherine; De Nil, Luc; Thijs, Vincent; van Wieringen, Astrid; Sunaert, Stefan
Neurogenic stuttering is an acquired speech disorder characterized by the occurrence of stuttering-like dysfluencies following brain damage. Because the onset of stuttering in these patients is associated with brain lesions, this condition provides a unique opportunity to study the neural processes underlying speech dysfluencies. Lesion localizations of 20 stroke subjects with neurogenic stuttering and 17 control subjects were compared using voxel-based lesion symptom mapping. The results showed nine left-hemisphere areas associated with the presence of neurogenic stuttering. These areas were largely overlapping with the cortico-basal ganglia-cortical network comprising the inferior frontal cortex, superior temporal cortex, intraparietal cortex, basal ganglia, and their white matter interconnections through the superior longitudinal fasciculus and internal capsule. These results indicated that stroke-induced neurogenic stuttering is not associated with neural dysfunction in one specific brain area but can occur following one or more lesion throughout the cortico-basal ganglia-cortical network. It is suggested that the onset of neurogenic stuttering in stroke subjects results from a disintegration of neural functions necessary for fluent speech. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.
Tarulli, Andrew W; Lim, Chun; Bui, Jonathan D; Saper, Clifford B; Alexander, Michael P
Central neurogenic hyperventilation is a rare condition with poorly understood pathophysiology. To describe a patient with central neurogenic hyperventilation caused by an infiltrative brainstem lymphoma. Based on analysis of this patient and other case reports, we propose that central neurogenic hyperventilation is uniquely the result of infiltrative tumors that stimulate pontine respiratory centers and central chemoreceptors.
J. D. Duffy
Full Text Available A case of neurogenic stuttering induced by the monoamine oxidase inhibitor tranylcypromine is described. The association of neurogenic stuttering with acquired lateralized motor deficits in the patient described is discussed with reference to current theories regarding the pathogenesis of neurogenic stuttering.
Josselyn, Sheena A; Frankland, Paul W
In the late 19th Century, Sigmund Freud described the phenomenon in which people are unable to recall events from early childhood as infantile amnesia. Although universally observed, infantile amnesia is a paradox; adults have surprisingly few memories of early childhood despite the seemingly exuberant learning capacity of young children. How can these findings be reconciled? The mechanisms underlying this form of amnesia are the subject of much debate. Psychological/cognitive theories assert that the ability to maintain detailed, declarative-like memories in the long term correlates with the development of language, theory of mind, and/or sense of "self." However, the finding that experimental animals also show infantile amnesia suggests that this phenomenon cannot be explained fully in purely human terms. Biological explanations of infantile amnesia suggest that protracted postnatal development of key brain regions important for memory interferes with stable long-term memory storage, yet they do not clearly specify which particular aspects of brain maturation are causally related to infantile amnesia. Here, we propose a hypothesis of infantile amnesia that focuses on one specific aspect of postnatal brain development--the continued addition of new neurons to the hippocampus. Infants (humans, nonhuman primates, and rodents) exhibit high levels of hippocampal neurogenesis and an inability to form lasting memories. Interestingly, the decline of postnatal neurogenesis levels corresponds to the emergence of the ability to form stable long-term memory. We propose that high neurogenesis levels negatively regulate the ability to form enduring memories, most likely by replacing synaptic connections in preexisting hippocampal memory circuits.
Gregory Paul Marshall
Full Text Available Microglia isolated from the neurogenic subependymal zone (SEZ and hippocampus (HC are capable of massive in vitro population expansion that is not possible with microglia isolated from non-neurogenic regions. We asked if this regional heterogeneity in microglial proliferative capacity is cell intrinsic, or is conferred by interaction with respective neurogenic or non-neurogenic niches. By combining SEZ and cerebral cortex (CTX primary tissue dissociates to generate heterospatial cultures, we find that exposure to the SEZ environment does not enhance CTX microglia expansion; however, the CTX environment exerts a suppressive effect on SEZ microglia expansion. Furthermore, addition of purified donor SEZ microglia to either CTX- or SEZ-derived cultures suppresses the expansion of host microglia, while the addition of donor CTX microglia enhances the over-all microglia yield. These data suggest that SEZ and CTX microglia possess intrinsic, spatially restricted characteristics that are independent of their in vitro environment, and that they represent unique and functionally distinct populations. Finally, we determined that the repeated supplementation of neurogenic SEZ cultures with expanded SEZ microglia allows for sustained levels of inducible neurogenesis, provided that the ratio of microglia to total cells remains within a fairly narrow range.
Full Text Available Abstract Background Interleukin-3 (IL-3 is an important glycoprotein involved in regulating biological responses such as cell proliferation, survival and differentiation. Its effects are mediated via interaction with cell surface receptors. Several studies have demonstrated the expression of IL-3 in neurons and astrocytes of the hippocampus and cortices in normal mouse brain, suggesting a physiological role of IL-3 in the central nervous system. Although there is evidence indicating that IL-3 is expressed in some neuronal populations, its physiological role in these cells is poorly known. Results In this study, we demonstrated the expression of IL-3 receptor in cortical neurons, and analyzed its influence on amyloid β (Aβ-treated cells. In these cells, IL-3 can activate at least three classical signalling pathways, Jak/STAT, Ras/MAP kinase and the PI 3-kinase. Viability assays indicated that IL-3 might play a neuroprotective role in cells treated with Aβ fibrils. It is of interest to note that our results suggest that cell survival induced by IL-3 required PI 3-kinase and Jak/STAT pathway activation, but not MAP kinase. In addition, IL-3 induced an increase of the anti-apoptotic protein Bcl-2. Conclusion Altogether these data strongly suggest that IL-3 neuroprotects neuronal cells against neurodegenerative agents like Aβ.
Al Taweel W; Seyam R
Waleed Al Taweel, Raouf SeyamDepartment of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaAbstract: 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...
Al Taweel W
Full Text Available Waleed Al Taweel, Raouf SeyamDepartment of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaAbstract: 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.Keywords: neurogenic bladder, spinal cord injury, urodynamics, intestine, intermittent catheterization
Myers, Jeremy B.; Mayer, Erik N.; Lenherr, Sara
Neurogenic bladder is a very broad disease definition that encompasses varied disease and injury states affecting the bladder. The majority of patients with neurogenic bladder dysfunction do not have concomitant intrinsic sphincteric deficiency (ISD), but when this occurs the challenges of management of urinary incontinence from neurogenic bladder are compounded. There are no guidelines for surgical correction of ISD in adults and most of the literature on treatment of the problem comes from ...
Palma-Zamora, Isaac D; Atiemo, Humphrey O
Neurogenic bladder is a chronic and disabling condition associated with multiple comorbidities and a widespread economic impact. Literature on cost of care and resource utilization is sparse and heterogeneous. Nonstandardized approaches, impact perspectives, and types of costs are used to describe the economic implications of neurogenic bladder. The financial toll is difficult to ascertain due to indirect and intangible costs exacerbated by the underlying disability. Health resource utilization based on clinical manifestations of neurogenic bladder may serve as an alternative measure. Understanding the multifold economic implications and health resource utilization patterns of neurogenic bladder may guide improvement of treatment strategies. Copyright © 2017 Elsevier Inc. All rights reserved.
de Carvalho, Mamede; Swash, Michael
Monomelic neurogenic syndromes are rare. Their classification and prognostic features have not been addressed in the European population. A prospective study of 17 patients with monomelic neurogenic amyotrophy, of upper or lower limb onset, with progression limited to one limb for three or more years. Clinical and neurophysiological studies were performed in the subsequent 3 or more years. Fifteen patients were of European origin and two were Asian. Those presenting with proximal monomelic weakness or with involvement of the posterior compartment of the lower leg showed no further progression after the initial period of development of the syndrome. Brisk reflexes in wasted muscles did not predict progression. Electromyographic signs of denervation in the opposite limb at presentation did not predict later progression. Transcranial magnetic stimulation (TMS) features of corticospinal dysfunction were a useful predictor of subsequent progression (p=0.01). One patient with lower limb onset developed conduction block with weakness in an upper limb nine years after presentation, and this upper limb weakness responded to IVIg therapy. This adult-onset European group of patients is different as compared with juvenile-onset Asian cases. The clinical syndromes appear heterogeneous, but neurophysiological investigations, in particular TMS, can be helpful in determining prognosis. Multifocal motor neuropathy should be considered when there is progression, even years after onset.
Taweel, Waleed Al; Seyam, Raouf
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
Full Text Available Proliferation of neural stem/progenitor cells (NSPCs in the adult brain is tightly controlled to prevent exhaustion and to ensure proper neurogenesis. Several extrinsic stimuli affect NSPC regulation. However, the lack of unique markers led to controversial results regarding the in vivo behavior of NSPCs to different stimuli. We recently identified SPOT14, which controls NSPC proliferation through regulation of de novo lipogenesis, selectively in low-proliferating NSPCs. Whether SPOT14-expressing (SPOT14+ NSPCs react in vivo to neurogenic regulators is not known. We show that aging is accompanied by a marked disappearance of SPOT14+ NSPCs, whereas running, a positive neurogenic stimulus, increases proliferation of SPOT14+ NSPCs. Furthermore, transient depletion of highly proliferative cells recruits SPOT14+ NSPCs into the proliferative pool. Additionally, we have established endogenous SPOT14 protein staining, reflecting transgenic SPOT14-GFP expression. Thus, our data identify SPOT14 as a potent marker for adult NSPCs that react dynamically to positive and negative neurogenic regulators.
Taylor, Matthew Pritam; Wrenn, Paul; O'Donnell, Andrew David
Injury to the spinal cord can result in loss of sympathetic innervation causing a drop in BP and HR, this condition is known as neurogenic shock. There is debate among the literature on how and when neurogenic shock presents and what values of HR and BP should be used to define it. Previous studies do not take into account multiple prehospital and emergency department recordings. To improve understanding of how neurogenic shock presents in humans, allowing better identification and treatment. The Trauma Audit and Research Network database for an adult major trauma centre was used to isolate patients with a spinal cord injury. Qualifying patients had all available BPs and HRs collated into a database. Patients with neurogenic shock were isolated, allowing data analysis. Out of 3069 trauma patients, 33 met the inclusion criteria, of which 15 experienced neurogenic shock. 87% of the patients who had neurogenic shock experienced it within 2 hours of injury. Neurogenic shock below the T6 level was less common (p=0.009); however, there were still four cases in the cohort. More patients with complete spinal cord injury had neurogenic shock (p=0.039). Neurogenic shock is variable and unpredictable. It can present in the prehospital environment and without warning in a patient with previously normal vital signs. The medical team should be aware of it in all patients with spinal cord injury regardless of injury level. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Vigil, Humberto R; Hickling, Duane R
There is a high incidence of urinary tract infection (UTI) in patients with neurogenic lower urinary tract function. This results in significant morbidity and health care utilization. Multiple well-established risk factors unique to a neurogenic bladder (NB) exist while others require ongoing investigation. It is important for care providers to have a good understanding of the different structural, physiological, immunological and catheter-related risk factors so that they may be modified when possible. Diagnosis remains complicated. Appropriate specimen collection is of paramount importance and a UTI cannot be diagnosed based on urinalysis or clinical presentation alone. A culture result with a bacterial concentration of ≥10(3) CFU/mL in combination with symptoms represents an acceptable definition for UTI diagnosis in NB patients. Cystoscopy, ultrasound and urodynamics should be utilized for the evaluation of recurrent infections in NB patients. An acute, symptomatic UTI should be treated with antibiotics for 5-14 days depending on the severity of the presentation. Antibiotic selection should be based on local and patient-based resistance patterns and the spectrum should be as narrow as possible if there are no concerns regarding urosepsis. Asymptomatic bacteriuria (AB) should not be treated because of rising resistance patterns and lack of clinical efficacy. The most important preventative measures include closed catheter drainage in patients with an indwelling catheter and the use of clean intermittent catheterization (CIC) over other methods of bladder management if possible. The use of hydrophilic or impregnated catheters is not recommended. Intravesical Botox, bacterial interference and sacral neuromodulation show significant promise for the prevention of UTIs in higher risk NB patients and future, multi-center, randomized controlled trials are required.
Pérez-Martín, Margarita; Rivera, Patricia; Blanco, Eduardo; Lorefice, Clara; Decara, Juan; Pavón, Francisco J.; Serrano, Antonia; Rodríguez de Fonseca, Fernando; Suárez, Juan
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
Full Text Available 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, 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.
Miyazato, Minoru; Kadekawa, Katsumi; Kitta, Takeya; Wada, Naoki; Shimizu, Nobutaka; de Groat, William C; Birder, Lori A; Kanai, Anthony J; Saito, Seiichi; Yoshimura, Naoki
The lower urinary tract's main functions are storage and elimination. The micturition reflex pathway is modulated by the spinobulbospinal reflex pathway as well as higher brain centers involved in the voluntary micturition control. Micturition is sensitive to numerous injuries, resulting in various types of dysfunction. Animal studies indicate that lower urinary tract dysfunction partly depends on plasticity of the neural pathways. Reflex plasticity is associated with changes in ion channels, receptors, and numerous mediators. Animal models may aid in understanding the mechanisms leading to pathologic conditions and the plasticity in reflex pathways to the lower urinary tract after neurogenic lesions. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available The capacity of the brain to generate new adult neurons is a recent discovery that challenges the old theory of an immutable adult brain. A new and fascinating field of research now focuses on this regenerative process. The two brain systems that constantly produce new adult neurons, known as the adult neurogenic systems, are the dentate gyrus (DG of the hippocampus and the lateral ventricules/olfactory bulb system. Both systems are involved in memory and learning processes. Different drugs of abuse, such as cocaine and MDMA, have been shown to produce cellular and molecular changes that affect adult neurogenesis. This review summarizes the effects that these drugs have on the adult neurogenic systems. The functional relevance of adult neurogenesis is obscured by the functions of the systems that integrate adult neurons. Therefore, we explore the effects that cocaine and MDMA produce not only on adult neurogenesis, but also on the DG and olfactory bulbs. Finally, we discuss the possible role of new adult neurons in cocaine- and MDMA-induced impairments. We conclude that, although harmful drug effects are produced at multiple physiological and anatomical levels, the specific consequences of reduced hippocampus neurogenesis are unclear and require further exploration.
Myers, Jeremy B; Mayer, Erik N; Lenherr, Sara
Neurogenic bladder is a very broad disease definition that encompasses varied disease and injury states affecting the bladder. The majority of patients with neurogenic bladder dysfunction do not have concomitant intrinsic sphincteric deficiency (ISD), but when this occurs the challenges of management of urinary incontinence from neurogenic bladder are compounded. There are no guidelines for surgical correction of ISD in adults and most of the literature on treatment of the problem comes from treatment of children with congenital diseases, such as myelomeningocele. Our goal, in this review, is to present some of the common surgical options for ISD [including artificial urinary sphincters, bladder slings, bladder neck reconstruction (BNR) and urethral bulking agents] and the evidence underlying these treatments in adults with neurogenic bladder.
Nagar, Shruti; Smith, Leslie E.; Morgan, William F.
The detrimental effects associated with exposure to ionizing radiation have long been thought to result from the direct targeting of the nucleus leading to DNA damage; however, the emergence of concepts such as radiation-induced genomic instability and bystander effects have challenged this dogma. After cellular exposure to ionizing radiation, we have isolated a number of clones of Chinese hamster-human hybrid GM10115 cells that demonstrate genomic instability as measured by chromosomal destabilization. These clones show dynamic and persistent generation of chromosomal rearrangements multiple generations after the original insult. We hypothesize that these unstable clones maintain this delayed instability phenotype by secreting factors into the culture medium. To test this hypothesis we transferred filtered medium from unstable cells to unirradiated GM10115 cells. No GM10115 cells were able to survive this medium. This phenomenon by which GM10115 cells die when cultured in medium from chromosomally unstable GM10115 clones is the death-inducing effect. Medium transfer experiments indicate that a factor or factors is/are secreted by unstable cells within 8 h of growth in fresh medium and result in cell killing within 24 h. These factors are stable at ambient temperature but do not survive heating or freezing, and are biologically active when diluted with fresh medium. We present the initial description and characterization of the death-inducing effect. This novel epigenetic effect of radiation has implications for radiation risk assessment and for health risks associated with radiation exposure.
Full Text Available Telomere dysfunction is known to induce growth arrest (senescence and cell death. However, the regulation of the senescence-death process is poorly understood. Here using a yeast dysfunctional telomere model cdc13-1, which carries a temperature sensitive-mutant telomere binding protein Cdc13p, we demonstrate that inhibition of TOR (Target of Rapamycin, a central regulator of nutrient pathways for cell growth, prevents cell death, but not growth arrest, induced by inactivation of Cdc13-1p. This function of TOR is novel and separable from its G1 inhibition function, and not associated with alterations in the telomere length, the amount of G-tails, and the telomere position effect (TPE in cdc13-1 cells. Furthermore, antioxidants were also shown to prevent cell death initiated by inactivation of cdc13-1. Moreover, inhibition of TOR was also shown to prevent cell death induced by inactivation of telomerase in an est1 mutant. Interestingly, rapamycin did not prevent cell death induced by DNA damaging agents such as etoposide and UV. In the aggregate, our results suggest that the TOR signaling pathway is specifically involved in the regulation of cell death initiated by telomere dysfunction.
Chen, Kevin; Henry, Rebecca A; Hughes, Stephanie M; Connor, Bronwen
Regional environmental cues present in the adult brain determine the fate of adult neural progenitor cells. To determine whether the growth factors BDNF or FGF2 can create a neurogenic environment outside the SVZ, we used AAV(1/2)-mediated gene transfer to produce ectopic BDNF or FGF2 expression in the normal adult rat striatum and transplanted SVZ-derived progenitor cells into this region. We observed that ectopic expression of BDNF in the striatum promoted neuronal differentiation of transplanted adult neural progenitor cells, while FGF2 expression supported the survival and proliferation of transplanted progenitor cells in the adult striatum. However, region-specific neuronal differentiation of transplanted progenitor cells was not observed in the adult striatum, suggesting ectopic BDNF or FGF2 expression was insufficient for the generation of mature neuronal phenotypes. This study provides direct in vivo evidence that ectopic striatal expression of either BDNF or FGF2 can induce neurogenesis in non-neurogenic regions of the adult brain.
Liubich L. D.
Full Text Available Aim. To evaluate the influence of the rat progenitor neurogenic cells supernatant (RPNS on the transplantable rat malignant brain glioma cells (strain 101.8 under conditions of cultivation. Methods. Primary cultures were obtained from glioma 101.8 fragments (n = 12 and intact brain of newborn rats (n = 9. RPNS was received from neurogenic cell suspensions of fetal rat brain on 8–11th (E8-11 and 12–16th (E12-16 days of gestation. Results: RPNS (E8-11 as well as RPNS (E12-16 showed a cytotoxic effect on the glioma 101.8 cells in short-term cultures, the level of which was dose-dependent and intensified with increasing duration of incubation. RPNS (E12-16 had a more pronounced cytotoxic action on the cells of glioma 101.8 compared with RPNS (E8-11. The cytotoxic index (CI of RPNS (E12-16 on the glioma 101.8 cells was significantly higher than CI determined in cell suspensions of normal rat brain (CI was (91.99 ± 2.37 % and (22.9 ± 4.97 % respectively over 48 h incubation with RPNS. After RPNS (E8-11 influence on the glioma 101.8 primary cultures the signs of dose-dependent cytotoxic effects were observed: the thinning of growth areas, appearance of dystrophic and necrobiotic changes in tumor cells and decreasing of a mitotic index. These features were strengthened under the RPNS (E12-16 influence. Conclusions. Fetal RPNS showed dose-dependent cytotoxic and antiproliferative effects on the cultivated glioma 101.8 cells, which were intensified with the increasing of rat brain gestational age and lengthening of the incubation duration. A prerequisite for such effects is likely the NPC ability to produce the substances with antitumor activity.
Pan, Yung-Wei; Chan, Guy C.K.; Kuo, Chay T.; Storm, Daniel R.; Xia, Zhengui
Although there is evidence suggesting that adult neurogenesis may contribute to hippocampus-dependent memory, signaling mechanisms responsible for adult hippocampal neurogenesis are not well characterized. Here we report that ERK5 MAP kinase is specifically expressed in the neurogenic regions of the adult mouse brain. The inducible and conditional knockout (icKO) of erk5 specifically in neural progenitors of the adult mouse brain attenuated adult hippocampal neurogenesis. It also caused defic...
Birklein, Frank; Schmelz, Martin
This review explains symptoms and nature of neuropeptide signaling and its importance for clinical symptoms of CRPS. Neurogenic inflammation regularly accompanies excitation of primary afferent nociceptors. It has two major components-plasma extravasation and vasodilatation. The most important mediators are the calcitonin gene-related peptide (CGRP) and substance P (SP). After peripheral trauma immune reaction (e.g. cytokines) and the attempts of the tissue to regenerate (e.g. growth factors) sensitize nociceptors and amplify neurogenic inflammation. This cascade of events has been demonstrated in rat models of CRPS. Clinical findings in these animals strongly resemble clinical findings in CRPS, and can be prevented by anti-cytokine and anti-neuropeptide treatment. In CRPS patients, there is meanwhile also plenty of evidence that neurogenic inflammation contributes to clinical presentation. Increased cytokine production was demonstrated, as well as facilitated neurogenic inflammation. Very recently even "non-inflammatory" signs of CRPS (hyperhidrosis, cold skin) have been linked to neuropeptide signaling. Surprisingly, there was even moderately increased neurogenic inflammation in unaffected body regions. This favors the possibility that CRPS patients share genetic similarities. The future search for genetic commonalities will help us to further unravel the "mystery" CRPS.
Goldfarb, Robert A; Pisansky, Andrew; Fleck, Joseph; Hoversten, Patrick; Cotter, Katherine J; Katorski, Jenna; Liberman, Daniel; Elliott, Sean P
Cerebral palsy is characterized by motor impairment following injury to the developing brain. Neurogenic lower urinary tract dysfunction is estimated to affect at least a third of children with cerebral palsy. However there are limited data as patients transition to adulthood. We sought to describe the symptoms, sequelae and management of neurogenic lower urinary tract dysfunction in adults with cerebral palsy. We retrospectively reviewed the charts of adult patients with cerebral palsy between 2011 and 2014. Patients with prior bladder reconstruction or catheterization based bladder drainage were excluded from study. Cerebral palsy severity was determined using GMFCS (Gross Motor Function Classification System). A conservative evaluation and treatment paradigm was used. Noninvasive treatments were encouraged. Specifically clean intermittent catheterization, which is often not feasible, is avoided unless urinary retention, hydronephrosis or refractory lower urinary tract symptoms develop. There were 121 patients included in final analysis. Median age was 25 and 61 patients (50%) had GMFCS level V. Noninvasive management failed in 28 of 121 patients (23%) as defined by hydronephrosis in 9, persistent urinary retention in 10 and refractory lower urinary tract symptoms/incontinence in 9. Urethral clean intermittent catheterization was poorly tolerated. Of all patients 25% showed evidence of urolithiasis during the study period. Surgical intervention was rare and associated with significant morbidity. Adults with cerebral palsy may present with variable signs and symptoms of neurogenic lower urinary tract dysfunction. Conservative treatment was successful in more than 75% of patients. Clean intermittent catheterization was poorly tolerated in patients in whom conservative treatment failed. Surgical intervention was rarely indicated and it should be reserved for select individuals. Copyright © 2016 American Urological Association Education and Research, Inc
Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger
Intradermal injection of capsaicin induces the axonal release of neuropeptides, vasodilatation and flare, e.g. neurogenic inflammation. The spatial profile of neurogenic inflammation in the skin has been studied in various experimental models. Polarization spectroscopy imaging introduced recently...
Rogers, William A; Goyal, Yogesh; Yamaya, Kei; Shvartsman, Stanislav Y; Levine, Michael S
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.
Full Text Available O edema pulmonar neurogênico é rara e grave complicação de pacientes com traumatismo craniencefálico (TCE. Pode ocorrer também em outras patologias do sistema nervoso central, tais como acidentes vasculares cerebrais (AVC, tumores ou após crises epilépticas, entre outras. Foram avaliados 36 casos com TCE grave e quatro pacientes com AVC, internados na UTI geral, no período de janeiro a setembro 1995. Nesse intervalo de tempo foram diagnosticados dois casos de edema pulmonar neurogênico, um ocorrendo em paciente com TCE grave e outro em paciente com AVC hemorrágico. O diagnóstico foi estabelecido pelo rápido desenvolvimento de edema pulmonar, com hipoxemia grave, queda da complacência pulmonar e infiltrados difusos bilaterais sem história prévia de aspiração traqueal ou outro fator de risco para o desenvolvimento de síndrome de angústia respiratória aguda. No primeiro paciente com trauma craniencefálico, o edema neurogênico foi diagnosticado na internação, uma hora após o trauma, com concomitante reação inflamatória grave e boa evolução em três dias. O outro caso, com AVC hemorrágico, desenvolveu edema neurogênico no quarto dia após drenagem de hematoma intraparenquimatoso, evoluindo para o óbito.Neurogenic pulmonary edema is a rare and serious complication in patients with head injury. It also may develop after a variety of cerebral insults such as subarachnoid hemorrhage, brain tumors and after epileptic seizures. Thirty six patients with severe head injury and four patients with cerebrovascular insults treated in Intensive Care Unit of HC-UNICAMP from January to September 1995 were evaluated. In this period there were two patients with neurogenic pulmonary edema, one with head injury and other with intracerebral hemorrhage. Diagnosis was made by rapid onset of pulmonary edema, severe hypoxemia, decrease of pulmonary complacence and diffuse pulmonary infiltrations, without previous history of tracheal
Full Text Available The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs niches might counteract the neuronal loss in Alzheimer’s disease (AD and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT and nuclear erythroid 2-related factor (Nrf2.
Sriramula, Srinivas; Lazartigues, Eric
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.
Burhan M. Edrees
Caudal Regression Syndrome/neurogenic bladder presented as recurrent urinary tract infection. Burhan M. Edrees. Department of Pediatrics, Medical College, Umm Al-Qura University, Saudi .... The pulse rate was 129 per minute, respiratory rate was 40 per ... strated abnormalities in the structures and functions of the renal.
Adriano Barreto Nogueira
Full Text Available The subgranular zone (SGZ of the dentate gyrus and the subventricular zone (SVZ are known neurogenic niches in adult mammals. Nonetheless, the existence of neurogenic niches in adult humans is controversial. We hypothesized that mapping neurogenic niches in the human temporal lobe could clarify this issue. Neurogenic niches and neurogenesis were investigated in 28 temporal lobes via immunostaining for nestin and doublecortin (DCX, respectively. Nestin was observed in a continuous layer formed by the SVZ, the subpial zone of the medial temporal lobe and the SGZ, terminating in the subiculum. In the subiculum, remarkable DCX expression was observed through the principal efferent pathway of the hippocampus to the fimbria. A possible explanation for the results is that the SVZ, the subpial zone of the medial temporal lobe and the SGZ form a unit containing neural stem cells that differentiate into neurons in the subiculum. Curiously, the area previously identified as the human rostral migratory stream may in truth be the fornix, which contains axons that originate in the subiculum. This study suggests that neurogenesis may occur in an orchestrated manner in a broad area of the human temporal lobe.
Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 7, No 2 (2009) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Neurogenic inflammation and ...
Rohrsted, Malene; Nordsten, Cecilie Bagi; Bagi, Per
on a systematic search of the PubMed database, a review of the current literature on the use of onabotulinum toxin A (Botox®) in the treatment of neurogenic detrusor overactivity is presented. Onabotulinum toxin A proved to be highly effective in the majority of studies, even though a wide range of injection...
El-Schich, Zahra; Mölder, Anna; Tassidis, Helena; Härkönen, Pirkko; Falck Miniotis, Maria; Gjörloff Wingren, Anette
We are using the label-free technique of holographic microscopy to analyze cellular parameters including cell number, confluence, cellular volume and area directly in the cell culture environment. We show that death-induced cells can be distinguished from untreated counterparts by the use of holographic microscopy, and we demonstrate its capability for cell death assessment. Morphological analysis of two representative cell lines (L929 and DU145) was performed in the culture flasks without any prior cell detachment. The two cell lines were treated with the anti-tumour agent etoposide for 1-3days. Measurements by holographic microscopy showed significant differences in average cell number, confluence, volume and area when comparing etoposide-treated with untreated cells. The cell volume of the treated cell lines was initially increased at early time-points. By time, cells decreased in volume, especially when treated with high doses of etoposide. In conclusion, we have shown that holographic microscopy allows label-free and completely non-invasive morphological measurements of cell growth, viability and death. Future applications could include real-time monitoring of these holographic microscopy parameters in cells in response to clinically relevant compounds. Copyright © 2015 Elsevier Inc. All rights reserved.
Full Text Available Abstract Background Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. Results Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10-10-10-6 M that display nM affinities for D2 and/or D4 receptors (clozapine, haloperidol, (±-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+-butaclamol and L-741,742. These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (--raclopride and remoxipride, two drugs that preferentially bind D2 over D4 receptors were ineffective, as well as the selective D3 receptor antagonist U 99194. Interestingly, (--raclopride (10-6 M was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10-6 M. Conclusion Taken together, these data suggest that D2-like receptors, particularly the D4 subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism.
Full Text Available Insulin resistance (IR is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER stress under IR condition using SH-SY5Y neuroblastoma cells. Apoptosis cell death signaling markers (cleaved Poly [ADP-ribose] polymerase 1 (PARP, p53, and Bax and ER stress markers (phosphorylated eIF2α (p-eIF2α, ATF4, CHOP, p-IRE1, and spliced XBP1 (sXBP1 were measured using reverse transcription-PCR, quantitative PCR, and western blottings. Immunofluorescence staining was also performed for p-ASK1 and p-IRE1. The mRNA or protein expressions of cell death signaling markers and ER stress markers were increased under IR condition, but significantly attenuated by melatonin treatment. Insulin-induced activation of ASK1 (p-ASK1 was also dose dependently attenuated by melatonin treatment. The regulatory effect of melatonin on neuronal cells under IR condition was associated with ASK1 signaling. In conclusion, the result suggested that melatonin may alleviate ER stress under IR condition, thereby regulating neuronal cell death signaling.
Schmitt, E; Paquet, C; Beauchemin, M; Dever-Bertrand, J; Bertrand, R
The Ced-9/Bcl-like family of genes codes for proteins that have antiapoptotic and proapoptotic activity. Several Bax isoproteins have been detected by 2-D gel electrophoresis, and a novel human member, designated as Bax-sigma, has been identified and cloned from human cancer promyelocytic cells. Bax-sigma contains BH-3, BH-1, and BH-2 domains, putative alpha-5 and alpha-6 helices, and the carboxy-terminal hydrophobic transmembrane domain but lacks amino acids 159 to 171 compared to Bax-alpha. mRNA expression analysis by reverse transcription-polymerase chain reaction and RNase protection assays have revealed that Bax-sigma is expressed in a variety of human cancer cell lines and normal tissues. To investigate the potential role of Bax-sigma in apoptosis, first its effects were compared to those of Bax-alpha by transient expression in human B lymphoma Namalwa cells. Both Bax-sigma and Bax-alpha promoted apoptosis, as detected by DNA fragmentation and morphological analysis by electron microscopy. The apoptosis induced by Bax-sigma and Bax-alpha was correlated with their expression, cytochrome c release, and caspase activation. In a yeast two-hybrid system, Bax-sigma interacted with several Ced-9/Bcl family members but had no affinity for the human Egl-1 homologs Bik and Bad and the Ced-4 homolog Apaf-1. In human cells, Bax-sigma function was counteracted by Bcl-xL overexpression, and co-immunoprecipitation experiments indicated that Bax-sigma was associated with Bcl-xL. Furthermore, Bax-sigma overexpression increased cell death induced by various concentrations of genotoxic agents with the most pronounced effect occurring at low camptothecin and vinblastine dose levels. Our results suggest that Bax-sigma, a novel variant of Bax, encodes a protein with a proapoptotic effect and mode of action similar to those of Bax-alpha. Copyright 2000 Academic Press.
Background Spirulina is a commercial alga well known to contain various antioxidants, especially phycocyanin. Apart from being sold as a nutraceutical, Spirulina is incorporated as a functional ingredient in food products and beverages. Most of the previous reports on antioxidant activity of Spirulina were based on chemical rather than cell-based assays. The primary objective of this study was to assess the antioxidant activity of aqueous extract from Spirulina based on its protective effect against cell death induced by free radicals. Methods The antioxidant activity of the cold water extract from food-grade Spirulina platensis was assessed using both chemical and cell-based assays. In the cell-based assay, mouse fibroblast cells (3T3) cells were incubated for 1 h in medium containing aqueous extract of Spirulina or vitamin C (positive control) at 25, 125 and 250 μg/mL before the addition of 50 μM 1,1-diphenyl-2-picrylhydrazyl (DPPH) or 3-ethylbenzothiazoline-6-sulfonic acid (ABTS). The cells were incubated for another 24 h before being assessed for cell death due to apoptosis using the Cell Death Detection ELISA Kit. Spectrophotometric assays based on DPPH and ABTS were also used to assess the antioxidant activity of the extract compared to vitamin C and vitamin E (positive controls). Results Spirulina extract did not cause cytotoxic effect on 3T3 cells within the range of concentrations tested (0 - 250 μg/mL). The extract reduced significantly (p Spirulina has a protective effect against apoptotic cell death due to free radicals. The potential application of incorporating Spirulina into food products and beverages to enhance their antioxidant capacity is worth exploring. PMID:20858231
Full Text Available Brucella species are Gram-negative, facultative intracellular bacteria that cause zoonotic brucellosis. Survival and replication inside macrophages is critical for establishment of chronic Brucella infection. Virulent smooth B. abortus strain 2308 inhibits programmed macrophage cell death and replicates inside macrophages. Cattle B. abortus vaccine strain RB51 is an attenuated rough, lipopolysaccharide O antigen-deficient mutant derived from smooth strain 2308. B. abortus rough mutant RA1 contains a single wboA gene mutation in strain 2308. Our studies demonstrated that live RB51 and RA1, but not strain 2308 or heat-killed Brucella, induced both apoptotic and necrotic cell death in murine RAW264.7 macrophages and bone marrow derived macrophages. The same phenomenon was also observed in primary mouse peritoneal macrophages from mice immunized intraperitoneally with vaccine strain RB51 using the same dose as regularly performed in protection studies. Programmed macrophage cell death induced by RB51 and RA1 was inhibited by a caspase-2 inhibitor (Z-VDVAD-FMK. Caspase-2 enzyme activation and cleavage were observed at the early infection stage in macrophages infected with RB51 and RA1 but not strain 2308. The inhibition of macrophage cell death promoted the survival of rough Brucella cells inside macrophages. The critical role of caspase-2 in mediating rough B. abortus induced macrophage cell death was confirmed using caspase-2 specific shRNA. The mitochondrial apoptosis pathway was activated in macrophages infected with rough B. abortus as demonstrated by increase in mitochondrial membrane permeability and the release of cytochrome c to cytoplasm in macrophages infected with rough Brucella. These results demonstrate that rough B. abortus strains RB51 and RA1 induce apoptotic and necrotic murine macrophage cell death that is mediated by caspase-2. The biological relevance of Brucella O antigen and caspase-2-mediated macrophage cell death in Brucella
Chen, Fang; He, Yongqun
Brucella species are Gram-negative, facultative intracellular bacteria that cause zoonotic brucellosis. Survival and replication inside macrophages is critical for establishment of chronic Brucella infection. Virulent smooth B. abortus strain 2308 inhibits programmed macrophage cell death and replicates inside macrophages. Cattle B. abortus vaccine strain RB51 is an attenuated rough, lipopolysaccharide O antigen-deficient mutant derived from smooth strain 2308. B. abortus rough mutant RA1 contains a single wboA gene mutation in strain 2308. Our studies demonstrated that live RB51 and RA1, but not strain 2308 or heat-killed Brucella, induced both apoptotic and necrotic cell death in murine RAW264.7 macrophages and bone marrow derived macrophages. The same phenomenon was also observed in primary mouse peritoneal macrophages from mice immunized intraperitoneally with vaccine strain RB51 using the same dose as regularly performed in protection studies. Programmed macrophage cell death induced by RB51 and RA1 was inhibited by a caspase-2 inhibitor (Z-VDVAD-FMK). Caspase-2 enzyme activation and cleavage were observed at the early infection stage in macrophages infected with RB51 and RA1 but not strain 2308. The inhibition of macrophage cell death promoted the survival of rough Brucella cells inside macrophages. The critical role of caspase-2 in mediating rough B. abortus induced macrophage cell death was confirmed using caspase-2 specific shRNA. The mitochondrial apoptosis pathway was activated in macrophages infected with rough B. abortus as demonstrated by increase in mitochondrial membrane permeability and the release of cytochrome c to cytoplasm in macrophages infected with rough Brucella. These results demonstrate that rough B. abortus strains RB51 and RA1 induce apoptotic and necrotic murine macrophage cell death that is mediated by caspase-2. The biological relevance of Brucella O antigen and caspase-2-mediated macrophage cell death in Brucella pathogenesis and
Full Text Available Abstract Background Spirulina is a commercial alga well known to contain various antioxidants, especially phycocyanin. Apart from being sold as a nutraceutical, Spirulina is incorporated as a functional ingredient in food products and beverages. Most of the previous reports on antioxidant activity of Spirulina were based on chemical rather than cell-based assays. The primary objective of this study was to assess the antioxidant activity of aqueous extract from Spirulina based on its protective effect against cell death induced by free radicals. Methods The antioxidant activity of the cold water extract from food-grade Spirulina platensis was assessed using both chemical and cell-based assays. In the cell-based assay, mouse fibroblast cells (3T3 cells were incubated for 1 h in medium containing aqueous extract of Spirulina or vitamin C (positive control at 25, 125 and 250 μg/mL before the addition of 50 μM 1,1-diphenyl-2-picrylhydrazyl (DPPH or 3-ethylbenzothiazoline-6-sulfonic acid (ABTS. The cells were incubated for another 24 h before being assessed for cell death due to apoptosis using the Cell Death Detection ELISA Kit. Spectrophotometric assays based on DPPH and ABTS were also used to assess the antioxidant activity of the extract compared to vitamin C and vitamin E (positive controls. Results Spirulina extract did not cause cytotoxic effect on 3T3 cells within the range of concentrations tested (0 - 250 μg/mL. The extract reduced significantly (p Conclusions The results showed that aqueous extract of Spirulina has a protective effect against apoptotic cell death due to free radicals. The potential application of incorporating Spirulina into food products and beverages to enhance their antioxidant capacity is worth exploring.
Chu, Wan-Loy; Lim, Yen-Wei; Radhakrishnan, Ammu Kutty; Lim, Phaik-Eem
Spirulina is a commercial alga well known to contain various antioxidants, especially phycocyanin. Apart from being sold as a nutraceutical, Spirulina is incorporated as a functional ingredient in food products and beverages. Most of the previous reports on antioxidant activity of Spirulina were based on chemical rather than cell-based assays. The primary objective of this study was to assess the antioxidant activity of aqueous extract from Spirulina based on its protective effect against cell death induced by free radicals. The antioxidant activity of the cold water extract from food-grade Spirulina platensis was assessed using both chemical and cell-based assays. In the cell-based assay, mouse fibroblast cells (3T3) cells were incubated for 1 h in medium containing aqueous extract of Spirulina or vitamin C (positive control) at 25, 125 and 250 μg/mL before the addition of 50 μM 1,1-diphenyl-2-picrylhydrazyl (DPPH) or 3-ethylbenzothiazoline-6-sulfonic acid (ABTS). The cells were incubated for another 24 h before being assessed for cell death due to apoptosis using the Cell Death Detection ELISA Kit. Spectrophotometric assays based on DPPH and ABTS were also used to assess the antioxidant activity of the extract compared to vitamin C and vitamin E (positive controls). Spirulina extract did not cause cytotoxic effect on 3T3 cells within the range of concentrations tested (0 - 250 μg/mL). The extract reduced significantly (p Spirulina has a protective effect against apoptotic cell death due to free radicals. The potential application of incorporating Spirulina into food products and beverages to enhance their antioxidant capacity is worth exploring.
Brant, William O.
Erectile dysfunction (ED) related to compromise of the nervous system is an increasingly common occurrence. This may be due to the multifactorial nature of ED, the myriad of disorders affecting the neurotransmission of erectogenic signals, and improved awareness and diagnosis of ED. Nevertheless, neurogenic ED remains poorly understood and characterized. Disease related factors such as depression, decreased physical and mental function, the burden of chronic illness, and loss of independence may preclude sexual intimacy and lead to ED as well. The amount of data regarding treatment options in subpopulations of differing neurologic disorders remains scarce except for men with spinal cord injury. The treatment options including phosphodiesterase inhibitors, intracavernosal or intraurethral vasoactive agents, vacuum erection devices (VED) and penile prosthetic implantation remain constant. This review discusses the options in specific neurologic conditions, and briefly provides insight into new and future developments that may reshape the management of neurogenic ED. PMID:26904415
Mingin Gerald C.
Full Text Available Spina bifida and myelodysplasia are associated with neurogenic abnormalities of the bladder and bowel function. All children with myelodysplasia require an evaluation of their urinary tract with ultrasound and urodynamics to confirm normal bladder and kidney function. Patients with anatomical and functional abnormalities require treatment, the mainstay being intermittent catheterization and anticholinergic medication. The treatment goals for patients with a neurogenic bladder are the preservation of the upper urinary tract, bladder and bowel continence, independence, autonomy, and facilitation of self-esteem. A minority of children will not respond to conservative therapy and will ultimately require surgical intervention. This review will discuss the surgical options for bladder augmentation, bladder neck reconstruction and closure, as well as the methods for the creation of continent catheterizable stomas. The timing, indications, and description for each procedure will be addressed. Finally, the antegrade continence enema procedure will be described for the management of refractory fecal incontinence.
Daniel Cabezalí Barbancho
Full Text Available Spontaneous bladder perforation is an uncommon event in childhood. It is usually associated with bladder augmentation. We are presenting a case of bladder rupture in an infant with neurogenic bladder without prior bladder surgery. Three days after lipomyelomeningocele excision the patient showed signs and symptoms of acute abdomen. The ultrasound exploration revealed significant amount of intraperitoneal free fluid and therefore a laparoscopic exploration was performed. A posterior bladder rupture was diagnosed and repaired laparoscopically. Currently, being 3 years old, she keeps successfully dry with clean intermittent catheterization. Neurogenic bladder voiding function can change at any time of its evolution and lead to complications. Early diagnosis of spontaneous bladder rupture is of paramount importance, so it is essential to think about it in the differential diagnosis of acute abdomen.
Segarra, Gloria; Medina, Pascual; Domenech, Cristina; Martínez León, Juan B; Vila, José M.; Aldasoro, Martin; Lluch, Salvador
The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin.Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant respon...
Sasaji, Tatsuro; Yamada, Noboru; Iwai, Kazuo
A 76-year-old man presented with a Denis Zone III sacral fracture after a traffic accident. He also developed urinary retention and perineal numbness. The patient was diagnosed with neurogenic bladder dysfunction caused by the sacral fracture. A computed tomogram (CT) revealed that third sacral lamina was fractured and displaced into the spinal canal, but vertebral body did not displace. The fracture lines began at the center of lamina and extended bilateraly. The fracture pattern was unique....
Bort, A A; Lar'kin, V I
To study the autonomic provision of orthostatic test in patients with neurogenic syncope. We examined 70 patients, aged from 18 to 56 years. Autonomic response was recorded by means of the autonomic index - minute volume of blood. The most informative indices were the minute volume of blood in the translation in orthostasis, minute the maximum volume of blood in the first half of orthostasis, the average minute volume of blood in the first half of the orthostasis.
Abreu, Evandro [Service de Radiologie et Imagerie Musculosquelettique, Centre de Consultation et Imagerie de l’Appareil Locomoteur, CHRU de Lille, 59037 Lille (France); Aubert, Sébastien, E-mail: email@example.com [Institut de Pathologie, Centre de Biologie-Pathologie, CHRU de Lille, 59037 Lille (France); Wavreille, Guillaume, E-mail: firstname.lastname@example.org [Service d’Orthopédie B, Hôpital R Salengro, CHRU de Lille, 59037 Lille (France); Gheno, Ramon; Canella, Clarissa [Service de Radiologie et Imagerie Musculosquelettique, Centre de Consultation et Imagerie de l’Appareil Locomoteur, CHRU de Lille, 59037 Lille (France); Cotten, Anne, E-mail: email@example.com [Service de Radiologie et Imagerie Musculosquelettique, Centre de Consultation et Imagerie de l’Appareil Locomoteur, CHRU de Lille, 59037 Lille (France)
Neoplasms of neurogenic origin account for about 12% of all benign and 8% of all malignant soft tissue neoplasms. Traumatic neuroma, Morton neuroma, lipomatosis of a nerve, nerve sheath ganglion, perineurioma, benign and malignant peripheral nerve sheath tumors (PNST) are included in this group of pathologies. Clinical and radiologic evaluation of patients with neurogenic tumors and pseudotumors often reveals distinctive features. In this context, advanced imaging techniques, especially ultrasound (US) and magnetic resonance (MR) play an important role in the characterization of these lesions. Imaging findings such as location of a soft tissue mass in the region of a major nerve, nerve entering or exiting the mass, fusiform shape, abnormalities of the muscle supplied by the nerve, split-fat sign, target sign and fascicular appearance should always evoke a peripheric nerve sheath neoplasm. Although no single imaging finding or combination of findings allows definitive differentiation between benign from malign peripheric neurogenic tumors, both US and MR imaging may show useful features that can lead us to a correct diagnosis and improve patient treatment. Traumatic neuromas and Morton neuromas are commonly associated to an amputation stump or are located in the intermetatarsal space. Lipomatosis of a nerve usually appears as a nerve enlargement, with thickened nerve fascicles, embedded in evenly distributed fat. Nerve sheath ganglion has a cystic appearance and commonly occurs at the level of the knee. Intraneural perineuroma usually affects young people and manifests as a focal and fusiform nerve enlargement. In this article, we review clinical characteristics and radiologic appearances of these neurogenic lesions, observing pathologic correlation, when possible.
Kim, Chanyang; Kim, Sehee; Park, Seungjoon
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.
Teper, Doron; Sunitha, Sukumaran; Martin, Gregory B; Sessa, Guido
Mitogen-activated protein kinase (MAPK) cascades play a fundamental role in signaling of plant immunity and mediate elicitation of cell death. Xanthomonas spp. manipulate plant signaling by using a type III secretion system to deliver effector proteins into host cells. We examined the ability of 33 Xanthomonas effectors to inhibit cell death induced by overexpression of components of MAPK cascades in Nicotiana benthamiana plants. Five effectors inhibited cell death induced by overexpression of MAPKKKα and MEK2, but not of MAP3Kε. In addition, expression of AvrBs1 in yeast suppressed activation of the high osmolarity glycerol MAPK pathway, suggesting that the target of this effector is conserved in eukaryotic organisms. These results indicate that Xanthomonas employs several type III effectors to suppress immunity-associated cell death mediated by MAPK cascades.
Bojić, Tijana; Perović, Vladimir R.; Glišić, Sanja
Neurocardiovascular diseases (NCVD) are the leading cause of death in the developed world and will remain so till 2020. In these diseases the pathologically changed nervous control of cardiovascular system has the central role. The actual NCV syndromes are neurogenic hypertension, representing the sympathetically mediated disorder, and vasovagal syncope, which is the vagally mediated disorders. Vasovagal syncope, the disease far from its etiological treatment, could benefit from recruiting and application of antimuscarinic drugs used in other parasympathetic disorders. The informational spectrum method (ISM), a method widely applied for the characterization of protein-protein interactions in the field of immunology, endocrinology and anti HIV drug discovery, was applied for the first time in the analysis of neurogenic hypertension and vasovagal syncope therapeutic targets. In silico analysis revealed the potential involvement of apelin in neurogenic hypertension. Applying the EIIP/ISM bioinformatics concept in investigation of drugs for treatment of vasovagal syncope suggests that 78% of tested antimuscarinic drugs could have anti vasovagal syncope effect. The presented results confirm that ISM is a promissing method for investigation of molecular mechanisms underlying pathophysiological proceses of NCV syndromes and discovery of therapeutics targets for their treatment. PMID:26834545
Full Text Available Neural stem/progenitor cells (NSC have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6% over other sources (range of 0%-27.5%, p<0.004. Whole genome expression analysis showed differential gene expression between these regionally-derived NSC, which involved the Notch, epidermal growth factor as well as interleukin pathways. We have shown the presence of phenotypically-distinct regionally-derived NSC from the mid-trimester CNS, which may reflect the ontological differences occurring within the CNS. Aside from informing on the role of such cells during fetal growth, they may be useful for different cellular therapy applications.
Full Text Available Introduction: Vision loss can be a consequence of numerous disorders of eye and neural pathway conveying visual input to brain. A variety of conditions can affect visual pathway producing neurogenic vision loss. The presentation and course of vision loss depends on the site of involvement and underlying etiology. We conducted this unprecedented study to evaluate the characteristics and outcome of various diseases of the visual pathway. Materials and Methods: In this prospective cohort study, we evaluated 64 patients with neurogenic visual impairment. Ophthalmological causes were excluded in all of them. Their presentation, ophthalmological characteristics and investigation findings were recorded. These patients were followed up till 6 months. Results: Out of 69 patients evaluated, 5 were excluded as they had ophthalmological abnormalities. The remaining 64 cases (113 eyes were enrolled. 54 cases were due to diseases of anterior visual pathway and rest 10 had cortical vision loss. The etiologic distribution is as follows: Isolated optic neuritis- 12 (19%, multiple sclerosis- 4 (6.3%, neuromyelitis optica- 5 (7.9%, tubercular meningitis- 15 (23.8%, non-arteritic ischemic optic neuropathy, ischemic optic neuropathy complicating cavernous sinus thrombosis, cryptococcal meningitis, malignant infiltration of optic nerve, Crouzon′s syndrome, calvarial thickening and traumatic occipital gliosis- 1 (1.6% case each, idiopathic intracranial hypertension, pituitary adenoma, acute disseminated encephalomyelitis, posterior reversible leukoencephalopathy- 3 (4.8% cases each, cortical venous thrombosis 5 (7.9%, subacute scleroing panencephalitis- 4 (6.3% cases. Conclusions: The diseases of anterior visual pathway were much more common than cortical vision loss. A majority of our patients had severe impairment of vision at presentation.
Shankaran, Mahalakshmi; King, Chelsea; Lee, Jean; Busch, Robert; Wolff, Mary; Hellerstein, Marc K
Neurogenesis occurs in discrete regions of adult mammalian brain, including the subgranular zone of the hippocampus. Hippocampal neurogenesis is enhanced by different classes of antidepressants, but screening for neurogenic actions of novel antidepressants has been inefficient because of limitations of 5-bromo-2'-deoxyuridine labeling techniques. We describe an efficient in vivo method for measuring hippocampal neurogenesis involving incorporation of the stable isotope, (2)H, into genomic DNA during labeling with (2)H(2)O (heavy water). Male rodents received 8 to 10% (2)H(2)O in drinking water; DNA was isolated from hippocampal progenitor cells or neurons. Label incorporation into progenitor cells of Swiss-Webster mice revealed subpopulation kinetics: 16% divided with t(1/2) of 2.7 weeks; the remainder did not divide over 1 year. Progenitor cell proliferation rates in mice were strain-dependent. Chronic antidepressant treatment for 3 weeks, with (2)H(2)O administered during the final week, increased progenitor cell proliferation across all the strains tested. Fluoxetine treatment increased (2)H incorporation into DNA of gradient-enriched neurons or flow-sorted neuronal nuclei 4 weeks after (2)H(2)O labeling, representing the survival and differentiation of newly divided cells into neurons. By screening 11 approved drugs for effects on progenitor cell proliferation, we detected previously unrecognized, dose-dependent enhancement of hippocampal progenitor cell proliferation by two statins and the anticonvulsant topiramate. We also confirmed stimulatory activity of other anticonvulsants and showed inhibition of progenitor cell proliferation by isotretinoin and prednisolone. In conclusion, stable isotope labeling is an efficient, high-throughput in vivo method for measuring hippocampal progenitor cell proliferation that can be used to screen for novel neurogenic drugs.
Zou, Benjing; Zhang, Yongli; Li, Yucheng; Wang, Zantao; Zhang, Ping; Zhang, Xiyin; Wang, Bingdong; Long, Zhixin; Wang, Feng; Song, Guo; Wang, Yan
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
Full Text Available AIM:To observe the curative effect of bandage contact lens in neurogenic keratitis.METHODS:Twenty cases of neurogenic keratitis were studied attheDepartment of Ophthalmology, the first Affiliated Hospital of China Medical University, between October 2012 and June 2013. These included 13 males and 7 females, aged from 35 to 88y. Patients were voluntarily divided into an experimental group (lens wearing group, n=10 and control group (drug therapy, n=10. In experimental group patients wore silicone hydrogel bandage soft contact lens. Both groups used the following eyedrops:0.5% levofloxacin TID; 0.5% Sodium carboxymethyl cellulose QID; fibroblast growth factor BID; ganciclovir BID [cases complicated with herpes simplex virus (HSV]; compound tropicamide BID (cases concurrent hypopyon. The healing time of corneal ulcer and complication rates were observed in the two groups.RESULTS: The healing time of corneal ulcer in the experimental group was 10.80±4.44d versus 46.70±13.88d in the control group (P＜0.05. No complications occurred in the experimental group, except for the lens falling off twice in one case, the patient recovered eight days after rewearing the lens. While in the control group, all cases vascularized, 2 cases were complicated with descemetocele that recovered with amniotic membrane transplantation and 1 case was complicated with corneal perforation that recovered by autologous conjunctival flap covering.CONCLUSION: Bandage contact lens is a safe and effective method of treating neurogenic keratitis and significantly shortened the healing time of corneal ulcer.
Wöllner, J; Krebs, J; Pannek, J
This is a retrospective chart analysis. The objective of this study was to evaluate the effect of sacral neuromodulation (SNM) in patients with neurogenic lower urinary tract dysfunction (NLUTD). This study was conducted in a spinal cord injury rehabilitation center in Switzerland. The charts of all patients who underwent SNM (testing and/or permanent implantation) because of NLUTD at our institution between 2007 and 2013 were evaluated. Treatment outcomes and complications were recorded. A total of 50 patients, 30 women and 20 men, with a mean age of 46 (±14) years, fulfilled the inclusion criteria. The most frequent cause for SNM was spinal cord injury in 35 patients (70%). Median duration of the underlying disease was 9.5 (±9.3) years. In all, 35 patients (70%) received a permanent implant. The complication rate was 16% (8/50). At the last follow-up, SNM was in use in 32 patients. In 26 patients with SNM because of detrusor overactivity, voiding frequency per 24 h was significantly reduced from 9 to 6, and daily pad use rate was significantly improved (2.6 versus 0.6 pads per 24h). On comparing urodynamic assessment of detrusor function before and under SNM, no significant suppression of neurogenic detrusor overactivity (NDO) was detected. In nine patients with chronic neurogenic urinary retention, median postvoid residual urine was significantly reduced from 370 to 59 ml. In all, 94% of the patients were either very satisfied or satisfied with SNM. SNM might be an additional therapy option in carefully selected patients with NLUTD. On the basis of our results, urodynamic evaluation before SNM is mandatory, as the procedure does not seem to be suited to significantly alleviate NDO.
Pınar Bingöl Kızıltunç
Full Text Available Purpose: To evaluate the clinical and treatment features of orbital neurogenic tumors. Material and Method: The records of 35 patients with orbital neurogenic tumors who were diagnosed and treated at Ankara University Faculty of Medicine, Department of Ophthalmology, between 1998 and 2011 were evaluated retrospectively. Results: Orbitotomy via a cutaneous approach was performed in 21 (60% cases and orbitotomy via a transconjunctival approach was performed in 7 (20% cases. Three (8% cases had been operated at different centers. Four (12% cases were diagnosed clinically. Total excisional biopsy was performed in 11 (31.4% cases, subtotal excisional biopsy was performed in 7 (20%, and incisional biopsy was performed in 10 (28.6% cases. 14 (40% 35 cases were diagnosed as meningioma, 12 (34% as peripheral nerve sheath tumor, and 9 (26% cases were diagnosed as optic nerve glioma. Six (43% meningioma cases were optic nerve sheath meningioma, 5 (36% were sphenoid wing meningioma, 2 (14% were ectopic meningioma, and 1 (7% was perisellar meningioma. Six (50% of peripheral nerve sheath tumors were schwannoma, 2 (16% were solitary neurofibroma, 4 (34% were plexiform neurofibroma. External beam radiotherapy was performed in 15 (42.8% cases, cyberknife radiosurgery in 1 (2.8% , chemotherapy in 1 (2.8%, and enucleation ( because of neovascular glaucoma and vitreous hemorrhage was performed in 1 (2.8% case. Discussion: The most common orbital neurogenic tumors are meningioma, peripheral nerve sheath tumor, and optic nerve glioma. For meningioma and glioma, external beam radiotherapy is required; for schwannoma and solitary neurofibroma, total excisional biopsy is the preferred treatment. The success of visual and anatomic results are high after treatment. (Turk J Ophthalmol 2013; 43: 335-9
Fei, G; Fang, X; Wang, G D; Liu, S; Wang, X Y; Xia, Y; Wood, J D
To test a hypothesis that: (i) duodenal pH and osmolarity are individually controlled at constant set points by negative feedback control centred in the enteric nervous system (ENS); (ii) the purinergic P2Y(1) receptor subtype is expressed by non-cholinergic secretomotor/vasodilator neurons, which represent the final common excitatory pathway from the ENS to the bicarbonate secretory glands. Ussing chamber and pH-stat methods investigated involvement of the P2Y(1) receptor in neurogenic stimulation of mucosal bicarbonate (HCO(3)(-)) secretion in guinea pig duodenum. ATP increased HCO(3)(-) secretion with an EC(50) of 160 nM. MRS2179, a selective P2Y(1) purinergic receptor antagonist, suppressed ATP-evoked HCO(3)(-) secretion by 47% and Cl(-) secretion by 63%. Enteric neuronal blockade by tetrodotoxin or exposure to a selective vasoactive intestinal peptide (VIP, VPAC(1)) receptor antagonist suppressed ATP-evoked HCO(3)(-) secretion by 61 and 41%, respectively, and Cl- by 97 and 70% respectively. Pretreatment with the muscarinic antagonist, scopolamine did not alter ATP-evoked HCO3(-) or Cl(-) secretion. Whereas acid directly stimulates the mucosa to release ATP and stimulate HCO(3)(-) secretion in a cytoprotective manner, neurogenically evoked HCO(3)(-) secretion accounts for feedback control of optimal luminal pH for digestion. ATP stimulates duodenal HCO(3)(-) secretion through an excitatory action at purinergic P2Y(1) receptors on neurons in the submucosal division of the ENS. Stimulation of the VIPergic non-cholinergic secretomotor/vasodilator neurons, which are one of three classes of secretomotor neurons, accounts for most, if not all, of the neurogenic secretory response evoked by ATP. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Martínez-Moreno, M; Batlle, M; Ortega, F J; Gimeno-Bayón, J; Andrade, C; Mahy, N; Rodríguez, M J
Diazoxide, a well-known mitochondrial KATP channel opener with neuroprotective effects, has been proposed for the effective and safe treatment of neuroinflammation. To test whether diazoxide affects the neurogenesis associated with excitotoxicity in brain injury, we induced lesions by injecting excitotoxic N-methyl-d-aspartate (NMDA) into the rat hippocampus and analyzed the effects of a daily oral administration of diazoxide on the induced lesion. Specific glial and neuronal staining showed that NMDA elicited a strong glial reaction associated with progressive neuronal loss in the whole hippocampal formation. Doublecortin immunohistochemistry and bromo-deoxyuridine (BrdU)-NeuN double immunohistochemistry revealed that NMDA also induced cell proliferation and neurogenesis in the lesioned non-neurogenic hippocampus. Furthermore, glial fibrillary acidic protein (GFAP)-positive cells in the injured hippocampus expressed transcription factor Sp8 indicating that the excitotoxic lesion elicited the migration of progenitors from the subventricular zone and/or the reprograming of reactive astrocytes. Diazoxide treatment attenuated the NMDA-induced hippocampal injury in rats, as demonstrated by decreases in the size of the lesion, neuronal loss and microglial reaction. Diazoxide also increased the number of BrdU/NeuN double-stained cells and elevated the number of Sp8-positive cells in the lesioned hippocampus. These results indicate a role for KATP channel activation in regulating excitotoxicity-induced neurogenesis in brain injury. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
Theys, C.; van Wieringen, A.; Sunaert, S.; Thijs, V.; De Nil, L. F.
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…
Okuda, S; Nishiyama, N.; Saito, H.; Katsuki, H
3-Hydroxykynurenine (3-HK) is a tryptophan metabolite whose level in the brain is markedly elevated under several pathological conditions, including Huntington disease and human immunodeficiency virus infection. Here we demonstrate that micromolar concentrations (1-100 microM) of 3-HK cause cell death in primary neuronal cultures prepared from rat striatum. The neurotoxicity of 3-HK was blocked by catalase and desferrioxamine but not by superoxide dismutase, indicating that the generation of ...
Zutelija Fattorini, Matija; Gagro, Alenka; Dapic, Tomislav; Krakar, Goran; Marjanovic, Josip
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.
Mendez, Mario F
Few publications deal with non-neurogenic language disorders (NNLDs), distinct from psychogenic speech disorders such as psychogenic dysphonia or stuttering. NNLDs are alterations in language owing to psychosomatic preoccupations, conversion disorder, psychiatric disorders, or other psychological reasons. To identify and classify the range of NNLDs and their characteristics. This review summarizes the literature on disturbances in language, broadly defined as the use of symbols for communication, which may have a psychogenic or psychiatric etiology. The literature suggests a classification for NNLDs that includes psychogenic aphasia with dysgrammatism; psychogenic "lalias" including oxylalia and agitolalia, palilalia and echolalia, xenolalia, glossolalia, and coprolalia; psychologically-mediated word usage; psychotic language; and psychogenic forms of the foreign accent syndrome. Clinicians and researchers have insufficiently emphasized the presence of NNLDs, their characteristics, and their identification. Yet, these disorders may be the first or predominant manifestation of a psychologically-mediated illness. There are 2 steps to recognition. The first is to know how to distinguish NNLDs from the manifestations of neurogenic language impairments after a neurological evaluation. The second step is awareness of specific associated and examination features that suggest the presence of a NNLD. Copyright © 2018 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Wei, Zheng; Angerer, Lynne M; Angerer, Robert C
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.
Kitchen, W J; Mohamed, Mohamed; Bhojak, Manesh; Wilby, Martin
This study examines the efficacy and long-term safety of a midline sparing decompression for patients with degenerative spondylolisthesis (DS). We specifically looked at the rate of re-operation with a lumbar fusion. Of the patients that did require a secondary fusion procedure, we examined retrospectively any risk factors (both clinical and radiological) that could have been identified pre-operatively to predict the necessity of a primary fusion procedure. Data was collected prospectively within a single surgeon practice at our institution. All patients had a diagnosis of neurogenic claudication secondary to DS. Radiological and clinical risk factors that could have predicted the requirement of a fusion procedure were retrospectively analysed. This is a study of 70 patients (46F:24M). The median age at surgery was 68 years. All patients had a diagnosis of neurogenic claudication and were treated with a mid-line sparing decompression. Following the primary procedure, patients' VAS and ODI scores for both leg and back pain improved significantly both at short-term follow-up (mean seven months) and sustained at long-term follow-up (range 16-57 months, mean 33 months; p < 0.0001 Wilcoxon matched pair ranks). Eight (11%) patients had symptom progression and required a further fusion procedure. We found that if on the pre-operative MRI, the patient had a facet joint angle of greater than 60°, and a preserved disc height (greater than 7 mm) this would increase the likelihood of the requirement for fusion. Of the patients that required a secondary fusion procedure, 6/8 patients (75%) had sagittal facets, hyperlordosis and a preserved disc height pre-operatively. A primary decompression using a midline sparing osteotomy is an effective procedure for the treatment of neurogenic claudication caused by DS. The second message is that on inspection of the pre-operative imaging, sagittally placed facet joints, a hyperlordosis and a preserved disc height then a fusion
Gao, Yuan; Qu, Bo; Shen, Yan; Su, Xiao-Jing; Dong, Xiao-Yan; Chen, Xue-Mei; Zhou, Yu-Hong; Pi, Hong-Ying
Neurogenic bladder is a dysfunction of the lower urinary tract caused by nervous system disorder. We investigated the trends in publication of articles under the topic "neurogenic bladder" using bibliometric analysis. Articles on neurogenic bladder, published between 1995 and 2014, were retrieved from the ISI Web of Science citation database. We analyzed the search results for authors, countries, institutions, journals, and top-cited papers. A total of 1,904 articles were retrieved. There was a small increase in the number of articles on neurogenic bladder from 1995 (n = 43) to 2014 (n = 117). The USA was the leading country in the total number of articles (n = 598). However, the number of publications from China has rapidly increased, and China was ranked second in 2014. Emmanuel Chartier-Kastler (n = 65) was the most productive author, and University of Paris VI (Paris 6) (n = 61) was the most productive institution. The Journal of Urology published the greatest number of articles on this topic (n = 285). Articles on neurogenic bladder were often published in a professional journal under the category Urology & Nephrology, Neurosciences & Neurology, or Rehabilitation. Visualization analysis based on co-citation networks was conducted using CiteSpace III. Visualization analysis revealed that the hot spots in neurogenic bladder were botulinum toxin-A, prazosin, bethanechol, and afferent pathways. These findings provide new insight into the publication trends and hot spots in neurogenic bladder.
Full Text Available Neurogenic bladder is a dysfunction of the lower urinary tract caused by nervous system disorder. We investigated the trends in publication of articles under the topic "neurogenic bladder" using bibliometric analysis. Articles on neurogenic bladder, published between 1995 and 2014, were retrieved from the ISI Web of Science citation database. We analyzed the search results for authors, countries, institutions, journals, and top-cited papers. A total of 1,904 articles were retrieved. There was a small increase in the number of articles on neurogenic bladder from 1995 (n = 43 to 2014 (n = 117. The USA was the leading country in the total number of articles (n = 598. However, the number of publications from China has rapidly increased, and China was ranked second in 2014. Emmanuel Chartier-Kastler (n = 65 was the most productive author, and University of Paris VI (Paris 6 (n = 61 was the most productive institution. The Journal of Urology published the greatest number of articles on this topic (n = 285. Articles on neurogenic bladder were often published in a professional journal under the category Urology & Nephrology, Neurosciences & Neurology, or Rehabilitation. Visualization analysis based on co-citation networks was conducted using CiteSpace III. Visualization analysis revealed that the hot spots in neurogenic bladder were botulinum toxin-A, prazosin, bethanechol, and afferent pathways. These findings provide new insight into the publication trends and hot spots in neurogenic bladder.
Full Text Available Traumatic neuromas are uncommon and benign lesions arising from a peripheral nerve injury during surgery. Here we describe a case with histopathologic features of both a traumatic neuroma and neurofibroma in a patient without integumentary physical exam findings nor prior surgical history. A 54 year old male was admitted for surgical debridement of a foot ulcer. During pre-operative evaluation and review of imaging multiple CT scans revealed a stable, 4 mm endobronchial lesion in the left lower lobe. Given history of nicotine abuse, bronchoscopy was performed. Bronchoscopy showed a pearly, polypoid lesion. Histopathological results showed strong positivity for S-100 protein and spindle cell proliferation. Repeat CT chest showed no new lesions in the bronchial tree. The rarity of this case is noted not only by the limited number of bronchial neurogenic tumors, but the combined features in this case of a traumatic neuroma and neurofibroma which has not been described.
Full Text Available A 76-year-old man presented with a Denis Zone III sacral fracture after a traffic accident. He also developed urinary retention and perineal numbness. The patient was diagnosed with neurogenic bladder dysfunction caused by the sacral fracture. A computed tomogram (CT revealed that third sacral lamina was fractured and displaced into the spinal canal, but vertebral body did not displace. The fracture lines began at the center of lamina and extended bilateraly. The fracture pattern was unique. The sacrum was osteoporosis, and this fracture may be based on osteoporosis. We performed laminectomy to decompress sacral nerve roots. One month after surgery, the patient was able to urinate. Three months after surgery, his bladder function recovered normally. One year after surgery, he returned to a normal daily life and had no complaints regarding urination. One-year postoperative CT showed the decompressed third sacrum without displacement.
K N Stamatiou
Full Text Available The urofacial syndrome is probably a subset of neurogenic bladder dysfunction syndromes characterized by detrusor-sphincter discoordination along with a characteristic inversion of facial expression with laughing. This characteristic facial expression can facilitate early detection of this disorder, which leads to poor bladder emptying with high residual urine, hydro-nephrosis with vesico-ureteral reflux and potentially renal failure if left untreated. The etiology of the urofacial syndrome is unknown. In our case, a 12-year-old boy of Middle-Eastern origin presented to the Outpatient Department of our hospital with left pyelonephritis, hydronephrosis and bladder dilatation. Voiding cystourethrography performed 15 days later revealed left vesicoureteral reflux. Cystoscopy revealed bladder trabeculation however an anatomic urethral obstruction was not noticed. Both, neurological examination and radiography of the lumbosacral spine were normal. Urodynamic evaluation revealed the typical findings of detrusor-sphincter discoordination.
Bolos, Marta; Spuch, Carlos; Ordoñez-Gutierrez, Lara; Wandosell, Francisco; Ferrer, Isidro; Carro, Eva
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.
Full Text Available Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer’s Disease, Parkinson’s Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been tested in vivo and in vitro as therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future.
Janicka, Martyna; Gubernator, Jerzy
Immunogenic cell death inducers (ICD inducers) are a diverse group of therapeutic molecules capable of eliciting an adaptive immune response against the antigens present on the surface of dying cancer cells. Most of these molecules suffer from low bioavailability, high toxicity and poor pharmacokinetics which limit their application. It is believed that nanotechnology, in particular nano-sized nanocarriers, can address most of the issues that limit the use of ICD inducers. Area covered: The mechanism of action of ICD inducers and their limitations is discussed. In addition, we cover the novel possibilities arising from the use of nanotechnology to improve delivery of ICD inducers to the target tissue as well as the restrictions of modern nanotechnology. Expert opinion: At present, nanocarrier formulations suffer from low bioavailability, poor pharmacokinetics and stability issues. Nonetheless, there is a tremendous future for combinatorial immune-pharmacological treatments of human tumors based on nanocarrier delivery of ICD inducers.
Vivian V. Costa
Full Text Available Zika virus (ZIKV infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N-methyl-d-aspartate receptor (NMDAR-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801, agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells. Moreover, in vivo experiments demonstrate that therapeutic memantine treatment prevents the increase of intraocular pressure (IOP induced by infection and massively reduces neurodegeneration and microgliosis in the brain of infected mice. Our results indicate that the blockade of NMDARs by memantine provides potent neuroprotective effects against ZIKV-induced neuronal damage, suggesting it could be a viable treatment for patients at risk for ZIKV infection-induced neurodegeneration.
Okuda, S; Nishiyama, N; Saito, H; Katsuki, H
3-Hydroxykynurenine (3-HK) is a tryptophan metabolite whose level in the brain is markedly elevated under several pathological conditions, including Huntington disease and human immunodeficiency virus infection. Here we demonstrate that micromolar concentrations (1-100 microM) of 3-HK cause cell death in primary neuronal cultures prepared from rat striatum. The neurotoxicity of 3-HK was blocked by catalase and desferrioxamine but not by superoxide dismutase, indicating that the generation of hydrogen peroxide and hydroxyl radical is involved in the toxicity. Measurement of peroxide levels revealed that 3-HK caused intracellular accumulation of peroxide, which was largely attenuated by application of catalase. The peroxide accumulation and cell death caused by 1-10 microM 3-HK were also blocked by pretreatment with allopurinol or oxypurinol, suggesting that endogenous xanthine oxidase activity is involved in exacerbation of 3-HK neurotoxicity. Furthermore, NADPH diaphorase-containing neurons were spared from toxicity of these concentrations of 3-HK, a finding reminiscent of the pathological characteristics of several neurodegenerative disorders such as Huntington disease. These results suggest that 3-HK at pathologically relevant concentrations renders neuronal cells subject to oxidative stress leading to cell death, and therefore that this endogenous compound should be regarded as an important factor in pathogenesis of neurodegenerative disorders.
Gopalakrishna, Rayudu; Gundimeda, Usha; Zhou, Sarah; Bui, Helena; Davis, Andrew; McNeill, Thomas; Mack, William
Although the function of laminin in the basement membrane is known, the function of soluble "neuronal" laminin is unknown. Since laminin is neuroprotective, we determined whether the soluble laminin-1 induces signaling for neuroprotection via its 67KDa laminin-1 receptor (67LR). Treatment of Neuroscreen-1 (NS-1) cells with laminin-1 or YIGSR peptide, which corresponds to a sequence in laminin-1 β1 chain that binds to 67LR, induced a decrease in the cell-surface expression of 67LR and caused its internalization. Furthermore, intracellular cAMP-elevating agents, dibutyryl-cAMP, forskolin, and rolipram, also induced this internalization. Both soluble laminin-1 and YIGSR induced a sustained elevation of intracellular cAMP under defined conditions, suggesting a causal role of cAMP in the endocytosis of 67LR. This endocytosis was not observed in cells deficient in protein kinase A (PKA) nor in cells treated with either SQ 22536, an inhibitor for adenylyl cyclase, or ESI-09, an inhibitor for the exchange protein directly activated by cAMP (Epac). In addition, when internalization occurred in NS-1 cells, 67LR and adenylyl cyclase were localized in early endosomes. Under conditions in which endocytosis had occurred, both laminin-1 and YIGSR protected NS-1 cells from cell death induced by serum withdrawal. However, under conditions in which endocytosis did not occur, neither laminin-1 nor YIGSR protected these cells. Conceivably, the binding of laminin-1 to 67LR causes initial signaling through PKA and Epac, which causes the internalization of 67LR, along with signaling enzymes, such as adenylyl cyclase, into early endosomes. This causes sustained signaling for protection against cell death induced by serum withdrawal. Copyright © 2017 Elsevier Inc. All rights reserved.
Lucia M. Costa Monteiro
Conclusion: 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.
Iartsev, V N; Karachentsev, O V; Dvoretskiĭ, D P
The effect of 0.03-1.0 μM noradrenaline on the neurogenic response to electrical field stimulation of the juvenile rat tail artery segment in control conditions, after cooling from 36 to 25 degrees C, and after solution pH decrease from 7.4 to 6.6 was studied. Noradrenaline was shown to potentiate neurogenic vasoconstriction diminished by low temperature or low pH. Decrease in neurogenic vasoconstriction being equal, low dose noradrenaline was most effective at low temperature and high dose noradrenaline was most effective at low pH. 1.0 μM noradrenaline was equally effective in both cases. Increase in the neurogenic tone of the rat tail artery evoked by noradrenaline at low temperature and acidosis may contribute to decrease in heat emission at low ambient temperature in vivo.
Farag, F.; Koens, M.J.; Sievert, K.D.; Ridder, D. de; Feitz, W.; Heesakkers, J.P.
BACKGROUND: There are many opinions but little firm knowledge about the optimal treatment of neurogenic stress urinary incontinence (NSUI). OBJECTIVE: To scrutinize the quality and surgical outcomes of the available treatment modalities in the published literature. EVIDENCE ACQUISITION: A systematic
Full Text Available Interferon-alpha (IFN-α is a proinflammatory cytokine that is widely used for the treatment of chronic viral hepatitis and malignancy, because of its immune-activating, antiviral, and antiproliferative properties. However, long-term IFN-α treatment frequently causes depression, which limits its clinical utility. The precise molecular and cellular mechanisms of IFN-α-induced depression are not currently understood. Neural stem cells (NSCs in the hippocampus continuously generate new neurons, and some evidence suggests that decreased neurogenesis plays a role in the neuropathology of depression. We previously reported that IFN-α treatment suppressed hippocampal neurogenesis and induced depression-like behaviors via its receptors in the brain in adult mice. However, it is unclear how systemic IFN-α administration induces IFN-α signaling in the hippocampus. In this study, we analyzed the role of microglia, immune cells in the brain, in mediating the IFN-α-induced neurogenic defects and depressive behaviors. In vitro studies demonstrated that IFN-α treatment induced the secretion of endogenous IFN-α from microglia, which suppressed NSC proliferation. In vivo treatment of adult mice with IFN-α for five weeks increased the production of proinflammatory cytokines, including IFN-α, and reduced neurogenesis in the hippocampus. Both effects were prevented by simultaneous treatment with minocycline, an inhibitor of microglial activation. Furthermore, minocycline treatment significantly suppressed IFN-α-induced depressive behaviors in mice. These results suggest that microglial activation plays a critical role in the development of IFN-α-induced depression, and that minocycline is a promising drug for the treatment of IFN-α-induced depression in patients, especially those who are low responders to conventional antidepressant treatments.
Full Text Available Introduction Neurogenic bladder can develop as a result of various degrees of neurogenic lesion in spina bifida. The degree of bladder dysfunction depends on the level and type of spina bifida. Due to results upon complete diagnostic protocols, treatment options are applied. Objective Comparison of therapy results of patients with occult spinal dysraphism with neurogenic bladder that under-went medicamentous therapy and medicamentous with electrotherapy treatment. Methods We had 49 patients with neurogenic bladder that were treated at the University Children's Hospital in Belgrade in the period 2003-2008. The first group of children received medicamentous therapy and the second group received medicamentous therapy with transcutaneous electric nerve stimulation. In both groups we evaluated 4 symptoms: daily enuresis, enuresis nocturna, urgency and frequency and 4 urodynamic parameters: lower bladder capacity, unstable contractions and residual urine and detrusor sphincter dyssynergia. Follow-up urodynamic evaluation was done after 3, 6 and 12 months respectively. Results Our findings pointed out a high statistical significance of improvement in all evaluated urodynamic parameters of neurogenic bladder (predominantly in bladder capacity in the group of children with combined therapy as well in resolution of symptoms (predominantly enuresis nocturna, urgency and frequency. Conclusion Combined therapy is more efficient in treatment of children with neurogenic bladder. Electrotherapy is non-invasive, easily applicable and has had a significant place in treatment of children with dysfunctional voiding.
Segarra, Gloria; Medina, Pascual; Domenech, Cristina; Martínez León, Juan B; Vila, José M; Aldasoro, Martin; Lluch, Salvador
The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin.Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant responses to electrical field stimulation and to vasoactive agents.Electrical field stimulation (0.5–2 Hz) and noradrenaline (3×10−10–3×10−5 M) caused frequency- and concentration-dependent contractions that were of greater magnitude in veins denuded of endothelium. The inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10−4 M) increased the adrenergic responses only in rings with endothelium.In preparations contracted with noradrenaline in the presence of guanethidine (10−6 M) and atropine (10−6 M), electrical stimulation induced frequency-dependent relaxations. This neurogenic relaxation was prevented by L-NAME, methylene blue (3×10−5 M) and tetrodotoxin (10−6 M), but was unaffected by removal of endothelium.Acetylcholine (10−8–3×10−5 M) and substance P (3×10−11–3×10−7 M) induced endothelium-dependent relaxations. In contrast, sodium nitroprusside (10−9–3×10−5 M) and papaverine (10−8–3×10−5 M) caused endothelium-independent relaxations.The results provide functional evidence that the human penile deep dorsal vein is an active component of the penile vascular resistance through the release of nitric oxide from both neural and endothelial origin. Dysfunction in any of these sources of nitric oxide should be considered in some forms of impotence. PMID:9690872
Full Text Available Neurogenic, heterotopic ossification is characterised by the formation of new, extraosseous (ectopic bone in soft tissue in patients with neurological disorders. A 33-year-old female, who was born with spina bifida, paraplegia, and diastasis of symphysis pubis, had indwelling urethral catheter drainage and was using oxybutynin bladder instillations. She was prescribed diuretic for swelling of feet, which aggravated bypassing of catheter. Hence, suprapubic cystostomy was performed. Despite anticholinergic therapy, there was chronic urine leak around the suprapubic catheter and per urethra. Therefore, the urethra was mobilised and closed. After closure of the urethra, there was no urine leak from the urethra, but urine leak persisted around the suprapubic catheter. Cystogram confirmed the presence of a Foley balloon inside the bladder; there was no urinary fistula. The Foley balloon ruptured frequently, leading to extrusion of the Foley catheter. X-ray of abdomen showed heterotopic bone formation bridging the gap across diastasis of symphysis pubis. CT of pelvis revealed heterotopic bone lying in close proximity to the balloon of the Foley catheter; the sharp edge of heterotopic bone probably acted like a saw and led to frequent rupture of the balloon of the Foley catheter. Unique features of this case are: (1 temporal relationship of heterotopic bone formation to suprapubic cystostomy and chronic urine leak; (2 occurrence of heterotopic ossification in pubic region; (3 complications of heterotopic bone formation viz. frequent rupture of the balloon of the Foley catheter by the irregular margin of heterotopic bone and difficulty in insertion of suprapubic catheter because the heterotopic bone encroached on the suprapubic track; (4 synostosis between pubic bones as a result of heterotopic ossification..Common aetiological factors for neurogenic, heterotopic ossification, such as forceful manipulation, trauma, or spasticity, were absent in this
Carnicero, E; Alonso, M I; Carretero, R; Lamus, F; Moro, J A; de la Mano, A; Fernández, J M F; Gato, A
There is a nondeveloped neurogenic potential in the adult mammalian brain, which could be the basis for neuroregenerative strategies. Many research efforts have been made to understand the control mechanisms which regulate the transition from a neural precursor to a neuron in the adult brain. Embryonic cerebrospinal fluid (CSF) is a complex fluid which has been shown to play a key role in neural precursor behavior during development, working as a powerful neurogenic inductor. We tested if the neurogenic properties of embryonic CSF are able to increase the neurogenic activity of neuronal precursors from the subventricular zone (SVZ) in the brains of adult mice. Our results show that mouse embryonic CSF significantly increases the neurogenic activity in precursor cells from adult brain SVZ. This intense neurogenic effect was specific for embryonic CSF and was not induced by adult CSF. Embryonic CSF is a powerful neurogenesis inductor in homologous neuronal precursors in the adult brain. This property of embryonic CSF could be a useful tool in neuroregeneration strategies.
Hulsman, Natalie M; Geertzen, Jan H B; Dijkstra, Pieter U; van den Dungen, Jan J A M; den Dunnen, Wilfred F A
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.
Merenkov, Vladimir V; Kovalev, Alexey N; Gorbunov, Vyacheslav V
Neurogenic pulmonary edema (NPE) is an acute life-threatening complication associated with many forms of central nervous system injury. NPE usually appears within minutes to hours after injury and has a high mortality rate if not recognized and treated appropriately. Lung ultrasound quickly provides at the bedside relevant information on the state of aeration and ventilation of the lung. We describe a case report of acute respiratory insufficiency after posterior cranial fossa surgery. The patient underwent a subtotal meningiomectomy. Postoperative course was complicated by respiratory failure with unstable hemodynamic parameters. The pulmonary edema was suspected, and sonography examination was performed. Lung ultrasound showed typical signs for non-cardiogenic pulmonary edema. Transthoracic echocardiography showed preserved left ventricle systolic function, but signs of the severe hypovolemia were found. We corrected for the preload and ventilator support settings. Within 24 h, her respiratory status improved with a resolution of the pulmonary edema. Lung ultrasound at the bedside can provide accurate information on lung status in neurocritically ill patients with acute respiratory failure. The addition of transthoracic echocardiography to lung sonography provides an additive insight on the eventual pulmonary involvement. Lung ultrasound has the potential to become a reference tool for bedside dynamic respiratory monitoring in the Neuro ICU.
Papathanasiou, E S; Zamba-Papanicolaou, E; Pantziaris, M; Kleopas, K; Kyriakides, T; Papacostas, S; Pattichis, C; Iliopoulos, I; Piperidou, C
To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using a tone pip auditory stimulus. Fourteen neurologically normal volunteers (Age range 26-45 years, 10 females and 4 males), and two patients with sensorineural hearing loss and possible multiple sclerosis respectively, were examined. Two channel recordings were obtained, the first channel being P3 referred to Fpz, and the second channel being P4 referred to Fpz. A 1 kHz tone pip stimulus with two cycles was delivered via headphones monoaurally with contralateral masking noise. A consistent negative wave with a mean absolute latency of 4.72 msec was obtained, which we have named N5. 25% of the ears tested had better responses at the ipsilateral parietal electrode. In the patient with bilateral sensorineural hearing loss, NVESTEPs was present, suggesting that the NVESTEP is not a cochlear response. In the patient with possible multiple sclerosis, an abnormal NVESTEP response and a normal BAEP response were found. Use of a tone-pip rather than a click auditory stimulus allows a lower click intensity to be used in the production of NVESTEP responses, leads to a shorter testing time, and is therefore more comfortable for the patient. This study adds to our impression that the NVESTEP may be a physiological response that can be used to assess the vestibular system and is different from the BAEP response. Further testing in patients with symptoms of dizziness and with disorders specific for the vestibular nerve is required.
Faezeh Javadi Larijani
Full Text Available The most common cause of neurogenic bladder dysfunction (NBD in newborn infants is myelomeningocele. The pathophysiology almost always involves the bladder detrusor sphincter dyssynergy (DSD, which if untreated can cause severe and irreversible damage to the upper and lower urinary tracts. Early diagnosis and adequate management of NBD is critical to prevent both renal damage and bladder dysfunction and to reduce chances for the future surgeries. Initial investigation of the affected newborn infant includes a renal and bladder ultrasound, measurement of urine residual, determination of serum creatinine level, and urodynamics study. Voiding cystogram is indicated when either hydronephrosis or DSD is present. The main goal of treatment is prevention of urinary tract deterioration and achievement of continuance at an appropriate age. Clean intermittent catheterization (CIC in combination with anticholinergic (oxybutynin and antibiotics are instituted in those with high filling and voiding pressures, DSD and/or high grade reflux immediately after the myelomeningocele is repaired. Botulium toxin-A injection into detrusor is a safe alternative in patients with insufficient response or significant side effects to anticholinergic (oral or intravesical instillation therapy. Surgery is an effective alternative in patients with persistent detrusor hyperactivity and/or dyssynergic detrusor sphincter despites of the CIC and maximum dosage of anticholinergic therapy. Children with NBD require care from a multidisciplinary team approach consisting of pediatricians, neurosurgeon, urologist, nephrologists, orthopedic surgeon, and other allied medical specialists.
Mahfouz, W; Corcos, J
Spinal cord injury (SCI) affects 11.5 to 53.4 individuals per million of the population in developed countries each year. SCI is caused by trauma, although it can also result from myelopathy, myelitis, vascular disease or arteriovenous malformations and multiple sclerosis. Patients with complete lesions of the spinal cord between spinal cord level T6 and S2, after they recover from spinal shock, generally exhibit involuntary bladder contractions without sensation, smooth sphincter synergy, but with detrusor striated sphincter dyssynergia (DESD). Those with lesions above spinal cord level T6 may experience, in addition, smooth sphincter dyssynergia and autonomic hyperreflexia. DESD is a debilitating problem in patients with SCI. It carries a high risk of complications, and even life expectancy can be affected. Nearly half of the patients with untreated DESD will develop deleterious urologic complications, due to high intravesical pressures, resulting in urolithiasis, urinary tract infection (UTI), vesicoureteral reflux (VUR), hydronephrosis, obstructive uropathy, and renal failure. The mainstay of treatment is the use of antimuscarinics and catheterization, but in those for whom this is not possible external sphincterotomy has been a last resort option. External sphincterotomy is associated with significant risks, including haemorrhage; erectile dysfunction and the possibility of redo procedures. Over the last decade alternatives have been investigated, such as urethral stents and intrasphincteric botulinum toxin injection. In this review, we will cover neurogenic DESD, with emphasis on definition, classifications, diagnosis and different therapeutic options available.
Full Text Available The piriform cortex receives input from the olfactory bulb and (via the entorhinal cortex sends efferents to the hippocampus, thereby connecting the two canonical neurogenic regions of the adult rodent brain. Doublecortin (DCX is a cytoskeleton-associated protein that is expressed transiently in the course of adult neurogenesis. Interestingly, the adult piriform cortex, which is usually considered non-neurogenic (even though some reports exist that state otherwise, also contains an abundant population of DCX-positive cells. We asked how similar these cells would be to DCX-positive cells in the course of adult hippocampal neurogenesis. Using BAC-generated transgenic mice that express GFP under the DCX promoter, we studied DCX-expression and electrophysiological properties of DCX-positive cells in the mouse piriform cortex in comparison with the dentate gyrus. While one class of cells in the piriform cortex indeed showed features similar to newly generated immature granule neurons, the majority of DCX cells in the piriform cortex was mature and revealed large Na+ currents and multiple action potentials. Furthermore, when proliferative activity was assessed, we found that all DCX-expressing cells in the piriform cortex were strictly postmitotic, suggesting that no DCX-positive "neuroblasts" exist here as they do in the dentate gyrus. We conclude that DCX in the piriform cortex marks a unique population of postmitotic neurons with a subpopulation that retains immature characteristics associated with synaptic plasticity. DCX is thus, per se, no marker of neurogenesis but might be associated more broadly with plasticity.
Belmadani, Abdelhak; Ren, Dongjun; Bhattacharyya, Bula J; Rothwangl, Katharina B; Hope, Thomas J; Perlman, Harris; Miller, Richard J
We identified a previously unknown neurogenic region at the dorsal surface of the hippocampus; (the "subhippocampal zone," SHZ) in the adult brain. Using a reporter mouse in which SHZ cells and their progeny could be traced through the expression of EGFP under the control of the CXCR4 chemokine receptor promoter we observed the presence of a pool of EGFP expressing cells migrating in direction of the dentate gyrus (DG), which is maintained throughout adulthood. This population appeared to originate from the SHZ where cells entered a caudal migratory stream (aCMS) that included the fimbria, the meninges and the DG. Deletion of CXCR4 from neural stem cells (NSCs) or neuroinflammation resulted in the appearance of neurons in the DG, which were the result of migration of NSCs from the SHZ. Some of these neurons were ectopically placed. Our observations indicate that the SHZ is a neurogenic zone in the adult brain through migration of NSCs in the aCMS. Regulation of CXCR4 signaling in these cells may be involved in repair of the DG and may also give rise to ectopic granule cells in the DG in the context of neuropathology. © 2015 Wiley Periodicals, Inc.
.... In this review clinical practice, dissimilarities with adult patients and clinical experience about neurogenic bladder and bowel in paediatric spinal cord injury patients are presented. Anahtar Kelimeler...
Conclusion: Simultaneous ureteral reimplantation reduces postop HVUR significantly. We recommend augmentation and simultaneous ureteral reimplantation in children with HVUR and neurogenic bladder if technically feasible.
Kevin L. O’Hara
Full Text Available Tanoak (Notholithocarpus densiflorus syn. Lithocarpus densiflorus is one of the most widespread and abundant associates of coast redwood (Sequoia sempervirens, but little is known about the structural relationships between these two species. Knowledge of such relationships is essential for a thorough understanding of the impacts of sudden oak death (caused by the exotic pathogen Phytophthora ramorum, which is currently decimating tanoak populations throughout the redwood range. In this study, we utilized a stratified plot design and a stand reconstruction technique to assess structural impacts, at present and in the future, of this emerging disease. We found that residual trees in diseased plots were more aggregated than trees in unaffected plots, and we predicted that the loss of tanoak will lead to the following short-term changes: greater average diameter, height, height-to-live-crown, and crown length, as well as an increase in average nearest neighbor differences for diameter, height, and crown length. In addition, plots lacking tanoak (living or dead—as compared to plots with tanoak—exhibited greater average diameter and increased nearest neighbor differences with regard to diameter, height, and crown length. We also conducted a preliminary exploration of how sudden oak death-induced structural changes compare with typical old-growth characteristics, and how this disease may affect the structure of old-growth forests.
Full Text Available Resveratrol (trans-3,4,5'-trihydroxystilbene is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3 was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.
Full Text Available Non-thermal plasmas are gaseous mixtures of molecules, radicals, and excited species with a small proportion of ions and energetic electrons. Non-thermal plasmas can be generated with any high electro-magnetic field. We studied here the pathological effects, and in particular cell death, induced by nanosecond-pulsed high voltage generated plasmas homogeneously applied on cell cultures and nude mouse skin. In vitro, Jurkat cells and HMEC exhibited apoptosis and necrosis, in dose-dependent manner. In vivo, on nude mouse skin, cell death occurred for doses above 113 J/cm(2 for the epidermis, 281 J/cm(2 for the dermis, and 394 J/cm(2 for the hypodermis. Using electron microscopy, we characterized apoptosis for low doses and necrosis for high doses. We demonstrated that these effects were not related to thermal, photonic or pH variations, and were due to the production of free radicals. The ability of cold plasmas to generate apoptosis on cells in suspension and, without any sensitizer, on precise skin areas, opens new fields of application in dermatology for extracorporeal blood cell treatment and the eradication of superficial skin lesions.
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
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
Kabra, Aashish T; Feustel, Paul J; Kogan, Barry A
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 (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 10/47 (21%) for depression. Abnormal CES-D scores (>15) were seen in 15/47 (32
Yeun Goo Chung
Full Text Available Neurogenic detrusor overactivity and the associated loss of bladder control are among the most challenging complications of spinal cord injury (SCI. Anticholinergic agents are the mainstay for medical treatment of detrusor overactivity. However, their use is limited by significant side effects such that a search for new treatments is warranted. Inosine is a naturally occurring purine nucleoside with neuroprotective, neurotrophic and antioxidant effects that is known to improve motor function in preclinical models of SCI. However, its effect on lower urinary tract function has not been determined. The objectives of this study were to determine the effect of systemic administration of inosine on voiding function following SCI and to delineate potential mechanisms of action. Sprague-Dawley rats underwent complete spinal cord transection, or cord compression by application of an aneurysm clip at T8 for 30 sec. Inosine (225 mg/kg or vehicle was administered daily via intraperitoneal injection either immediately after injury or after a delay of 8 wk. At the end of treatment, voiding behavior was assessed by cystometry. Levels of synaptophysin (SYP, neurofilament 200 (NF200 and TRPV1 in bladder tissues were measured by immunofluorescence imaging. Inosine administration decreased overactivity in both SCI models, with a significant decrease in the frequency of spontaneous non-voiding contractions during filling, compared to vehicle-treated SCI rats (p<0.05, including under conditions of delayed treatment. Immunofluorescence staining demonstrated increased levels of the pan-neuronal marker SYP and the Adelta fiber marker NF200, but decreased staining for the C-fiber marker, TRPV1 in bladder tissues from inosine-treated rats compared to those from vehicle-treated animals, including after delayed treatment. These findings demonstrate that inosine prevents the development of detrusor overactivity and attenuates existing overactivity following SCI, and may
Moraes, Davi J A; Machado, Benedito H; Paton, Julian F R
Why sympathetic activity rises in neurogenic hypertension remains unknown. It has been postulated that changes in the electrical excitability of medullary pre-sympathetic neurones are the main causal mechanism for the development of sympathetic overactivity in experimental hypertension. Here we review recent data suggesting that enhanced sympathetic activity in neurogenic hypertension is, at least in part, dependent on alterations in the electrical excitability of medullary respiratory neurones and their central modulation of sympatho-excitatory networks. We also present results showing a critical role for carotid body tonicity in the aetiology of enhanced central respiratory modulation of sympathetic activity in neurogenic hypertension. We propose a novel hypothesis of respiratory neurone channelopathy induced by carotid body overactivity in neurogenic hypertension that may contribute to sympathetic excess. Moreover, our data support the notion of targeting the carotid body as a potential novel therapeutic approach for reducing sympathetic vasomotor tone in neurogenic hypertension. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.
Summers, Richard L.; Baker, Stephen D.; Sterling, Sarah A.; Porter, John M; Jones, Alan E.
Objective Neurogenic shock considered a distributive type of shock secondary to loss of sympathetic outflow to the peripheral vasculature. In this study, we examine the hemodynamic profiles of a series of trauma patients with a diagnosis of neurogenic shock. Methods Hemodynamic data were collected on a series of trauma patients determined to have spinal cord injuries with neurogenic shock. A well-established integrated computer model of human physiology was used to analyze and categorize the hemodynamic profiles from a system analysis perspective. A differentiation between these categories was presented as the percent of total patients. Results Of the 9 patients with traumatic neurogenic shock, the etiology of shock was decrease in peripheral vascular resistance (PVR) in 3 (33%; 95% confidence interval, 12%–65%), loss of vascular capacitance in 2 (22%; 6%–55%) and mixed peripheral resistance and capacitance responsible in 3 (33%; 12%–65%), and purely cardiac in 1 (11%; 3%–48%). The markers of sympathetic outflow had no correlation to any of the elements in the patients' hemodynamic profiles. Conclusions Results from this study suggest that hypotension of neurogenic shock can have multiple mechanistic etiologies and represents a spectrum of hemodynamic profiles. This understanding is important for the treatment decisions in managing these patients. PMID:23566731
Summers, Richard L; Baker, Stephen D; Sterling, Sarah A; Porter, John M; Jones, Alan E
Neurogenic shock considered a distributive type of shock secondary to loss of sympathetic outflow to the peripheral vasculature. In this study, we examine the hemodynamic profiles of a series of trauma patients with a diagnosis of neurogenic shock. Hemodynamic data were collected on a series of trauma patients determined to have spinal cord injuries with neurogenic shock. A well-established integrated computer model of human physiology was used to analyze and categorize the hemodynamic profiles from a system analysis perspective. A differentiation between these categories was presented as the percent of total patients. Of the 9 patients with traumatic neurogenic shock, the etiology of shock was decrease in peripheral vascular resistance (PVR) in 3 (33%; 95% confidence interval, 12%-65%), loss of vascular capacitance in 2 (22%; 6%-55%) and mixed peripheral resistance and capacitance responsible in 3 (33%; 12%-65%), and purely cardiac in 1 (11%; 3%-48%). The markers of sympathetic outflow had no correlation to any of the elements in the patients' hemodynamic profiles. Results from this study suggest that hypotension of neurogenic shock can have multiple mechanistic etiologies and represents a spectrum of hemodynamic profiles. This understanding is important for the treatment decisions in managing these patients. Copyright © 2013 Elsevier Inc. All rights reserved.
Traumatic brain injuries sustained in the Afghanistan and Iraq wars. Am. J. Nurs. 108, 40–47. Martin, M., et al., 2002. Involvement of CB1 cannabinoid ...S.B., et al., 2009. Population variation in glial fibrillary acidic protein levels in brain ageing: relationship to Alzheimer -type pathology and
Yasumoto, Jun; Kasai, Hirotake; Yoshimura, Kentaro; Otoguro, Teruhime; Watashi, Koichi; Wakita, Takaji; Yamashita, Atsuya; Tanaka, Tomohisa; Takeda, Sen; Moriishi, Kohji
The relationship between hepatitis B virus (HBV) infection and lipid accumulation remains largely unknown. In this study, we investigated the effect of HBV propagation on lipid droplet growth in HBV-infected cells and HBV-producing cell lines, HepG2.2.15 and HBV-inducible Hep38.7-Tet. The amount of intracellular triglycerides was significantly reduced in HBV-infected and HBV-producing cells compared with HBV-lacking control cells. Electron and immunofluorescent microscopic analyses showed that the average size of a single lipid droplet (LD) was significantly less in the HBV-infected and HBV-producing cells than in the HBV-lacking control cells. Cell death-inducing DFF45-like effectors (CIDEs) B and C (CIDEB and CIDEC), which are involved in LD expansion for the improvement of lipid storage, were expressed at a significantly lower level in HBV-infected or HBV-producing cells than in HBV-lacking control cells, while CIDEA was not detected in those cells regardless of HBV production. The activity of the CIDEB and CIDEC gene promoters was impaired in HBV-infected or HBV-producing cells compared to HBV-lacking control cells, while CIDEs potentiated HBV core promoter activity. The amount of HNF4α, that can promote the transcription of CIDEB was significantly lower in HBV-producing cells than in HBV-lacking control cells. Knockout of CIDEB or CIDEC significantly reduced the amount of supernatant HBV DNA, intracellular viral RNA and nucleocapsid-associated viral DNA, while the expression of CIDEB or CIDEC recovered HBV production in CIDEB- or CIDEC-knockout cells. These results suggest that HBV regulates its own viral replication via CIDEB and CIDEC.
M. A. A. Omran
Full Text Available We investigated the in vitro process of cell death caused by Egyptian cobra venom on primary human embryonic kidney (293T and mouse myoblast (C2C12 cell lines. The aim of these studies was to provide further information about triggering cell death, and suggest methods for eliminating unwanted cells, such as tumour cells. Both cell lines were treated with 10, 20, and 50 m g/ml of Egyptian cobra (Naja haje venom in serum free media (SFM and incubated for 8 hours. Total activities of the lactate dehydrogenase (LDH and creatine kinase (CK released in the culture during venom incubation were used as an indicator of the venom in vitro cytotoxicity. Cell injury was morphologically recognized and apoptosis determined by a Fluorescing Apoptosis Detection System and confirmed by staining nuclear DNA with DAPI. Our data clearly demonstrated marked cytotoxic effects and acute cell injury for both cell lines. Release of LDH and CK into the culture media induced by the venom correlates well with the morphological changes and extent of cell death. Mostly, these consequences were time and dose-dependent in both cell lines. The results obtained from this study indicated that cobra venom cause cell death by two different mechanisms: necrosis and induction of apoptosis. The apoptotic mechanism, accompanied by cell necrosis, mediated cell destruction of both tested cell lines; however, necrosis was predominant in the C2C12 cell line while apoptosis, in 293T cells. This unusual form of cell death induced by cobra venom may represent a combination of apoptosis and necrosis within the same cell. This is a first-hand investigation showing the apoptotic effects of N. haje venom at the cellular level. However, the contribution of the apoptotic pathway may be dependent on concentration and/or time of exposure to snake venom.
Fung, Shin Yee; Lee, Mui Li; Tan, Nget Hong
Snake venom LAAOs have been reported to exhibit a wide range of pharmacological activities, including cytotoxic, edema-inducing, platelet aggregation-inducing/platelet aggregation-inhibiting, bactericidal and antiviral activities. A heat-stable form of l-amino acid oxidase isolated from king cobra (Ophiophagus hannah) venom (OH-LAAO) has been shown to exhibit very potent cytotoxicity against human tumorigenic cells but not in their non-tumorigenic counterparts, and the cytotoxicity was due to the apoptosis-inducing effect of the enzyme. In this work, the molecular mechanism of cell death induced by OH-LAAO was investigated. The enzyme exerts its apoptosis-inducing effect presumably via both intrinsic and extrinsic pathways as suggested by the increase in caspase-8 and -9 activities. Oligonucleotide microarray analysis showed that the expression of a total of 178 genes was significantly altered as a result of oxidative stress induced by the hydrogen peroxide generated by the enzyme. Of the 178 genes, at least 27 genes are involved in apoptosis and cell death. These alterations of gene expression was presumably caused by the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidative modifications of signaling molecules that eventually lead to apoptosis and cell death. The very substantial up-regulation of cytochrome P450 genes may also contribute to the potent cytotoxic action of OH-LAAO by producing excessive reactive oxygen species (ROS). In conclusion, the potent apoptosis inducing activity of OH-LAAO was likely due to the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidation of signalling molecules. Copyright © 2015 Elsevier Ltd. All rights reserved.
Iartsev, V N; Karachentseva, O V; Dvoretskiĭ, D P
The effect of 0.03--1.0 μM noradrenaline on the response to electrical field stimulation of the juvenile rat tail artery segment at 36 degrees C and after cooling to 25 degrees C was studied. At 25 degrees C, the neurogenic vasoconstriction was inhibited, but low dose noradrenaline potentiate the constriction. This potentiation was greater at 25 degrees C than at 36 degrees C, following spontaneous decline in the constriction counteracted by noradrenaline. At low temperature, the potentiative effects of noradrenaline were greater at high frequency of electrical field stimulation. The phenomenon of increase in the noradrenaline-evoked potentiation of neurogenic vasoconstriction inhibited by cold may be of importance for thermoregulation. It could provide restoration of diminished effectiveness of the neurogenic contractile signal thus leading to low heat emission at low temperature.
Full Text Available The HTLV-1 virus is a known agent involved in the development of HAM/TSP. Past studies have typically observed patients with autonomic dysfunction consisting of detrusor overactivity and detrusor-sphincter dyssynergia, with the occasional observation of underactive detrusor or detrusor arreflexia. However, studies have not yet evaluated the progression of neurogenic bladder over time. In this paper, we describe a HAM/TSP patient with the initial development of overactive detrusor, and subsequent development of detrusor arreflexia. Given a paucity of studies characterizing the effects of HTLV-1 on the autonomic nervous system, particularly aspects controlling continence, this patient's clinical course may represent one type of end point for patients with HAM/TSP and neurogenic bladder. Further cohort or case-series studies, with particular emphasis on the progression of neurogenic bladder, are needed to evaluate the significance of this described case in relation to typical disease progression patterns.
Biering-Sørensen, F; Læssøe, Line; Sønksen, J
Present the possibility for treatment of male infertility, spasticity, and neurogenic detrusor overactivity in spinal cord lesioned (SCL) individuals with penile vibratory stimulation (PVS).......Present the possibility for treatment of male infertility, spasticity, and neurogenic detrusor overactivity in spinal cord lesioned (SCL) individuals with penile vibratory stimulation (PVS)....
Conclusion: In elderly male patients with non-neurogenic OAB, more severe storage symptoms are associated with a lower maximum flow rate and a more prominent IPP, indicating that a significant cause of male non-neurogenic OAB is prostate associated.
Zhao, Yong; Jiang, Hui; Liu, Xin-wei; Chen, Jian-Ting; Xiang, Liang-Bi; Zhou, Da-Peng
Mesenchymal stem cells derived from adipose tissue have the capacity to differentiate into endodermal, mesoderm and ectodermal cell lineages in vitro, which are an ideal engraft in tissue-engineered repair. In this study, mouse adipose-derived stem cells (ADSCs) were isolated from subcutaneous fat. The markers of ADSCs, CD13, CD29, CD44, CD71, CD73, CD90, CD105, CD166, Nestin, GFAP and MAP-2 were detected by immunofluorescence assays. The ADSCs were cultured in cocktail factors (including ATRA, GGF-2, bFGF, PDGF and forskolin) for neurogenic differentiation. The neurogenic cells markers, Nestin, GFAP and MAP-2 were analyzed using immunofluorescence and real-time PCR after dramatic changes in morphology. Neurogenic cells from ADSCs were autologous transplanted into the mouse of spinal cord injury for observation neurogenic cells colonization in spinal cord. The result demonstrated that the mouse ADSCs were positive for the CD13, CD29, CD44, CD71, CD73, CD90, CD105 and CD166 but negative for neurogenic cell markers, MAP-2, GFAP and Nestin. After neurogenic differentiation, the neurogenic cells were positive for neurogenic cell special markers, gene expression level showed a time-lapse increase, and the cells were successful colonized into spinal cord. In conclusion, our research shows that a population of neuronal cells can be specifically generated from ADSCs and that induced cells may allow for participation in tissue-repair.
Keenan, G F; Ashcroft, G P; Roditi, G H; Hutchison, J D; Evans, N T; Mikecz, P; Chaloner, F; Dodd, M; Leonard, C; Porter, R W
Ten subjects (seven with neurogenic claudication and three control subjects) underwent examination of lower limb muscle blood flow before and after exercise using positron emission tomography. To investigate the hypothesis that lower limb muscle ischemia was the origin of symptoms in neurogenic claudication. Patients with neurogenic claudication secondary to spinal stenosis experience lower limb discomfort after exercise similar to that of ischemic claudication. However, they do not have clinical evidence of peripheral vascular disease. The authors postulated that the lower limb discomfort in patients with neurogenic claudication may arise from muscle ischemia due to inadequate dilatation of arterioles in response to exercise, this itself arising secondary to sympathetic dysfunction due to spinal stenosis. Using O15-labeled water and positron emission tomography measured thigh and leg muscle blood flow response to exercise bilaterally in seven patients with unilateral neurogenic claudication and three control subjects were measured. The average values obtained for mid-thigh and mid-calf muscle perfusion at rest were 2.57 ml/min/100 g tissue (2.23-3.90) and 2.39 ml/min/100 g tissue (2.03-3.46), respectively. The average values obtained from mid-thigh and mid-calf perfusion after exercise were 4.41 ml/min/100 g tissue (2.8-6.0) and 4.87 ml/min/100 g (2.2-11.7). We found no difference in muscle perfusion between symptomatic and asymptomatic limbs in this group of patients. These studies suggest that muscle ischemia is not the origin of symptoms in most patients with neurogenic claudication.
Full Text Available Blayne Welk,1 Sarah A Morrow,2 Wendy Madarasz,3 Patrick Potter,4 Keith Sequeira41Department of Surgery, Division of Urology, 2Department of Clinical Neurosciences, Western University, London, ON, Canada; 3St Joseph's Health Care, London Ontario, Canada; 4Department of Physical Medicine and Rehabilitation, Western University, London, ON, CanadaBackground: There is no single patient-reported instrument that was developed specifically to assess symptoms and bladder-related consequences for neurogenic bladder dysfunction. The purpose of this study was to identify and consolidate items for a novel measurement tool for this population.Methods: Item generation was based on a literature review of existing instruments, open-ended semistructured interviews with patients, and expert opinion. Judgment-based item reduction was performed by a multidisciplinary expert group. The proposed questionnaire was sent to external experts for review.Results: Eight neurogenic quality of life measures and 29 urinary symptom-specific instruments were identified. From these, 266 relevant items were extracted and used in the creation of the new neurogenic symptom score. Qualitative interviews with 16 adult patients with neurogenic bladder dysfunction as a result of spinal cord injury, multiple sclerosis, or spina bifida were completed. Dominant themes included urinary incontinence, urinary tract infections, urgency, and bladder spasms. Using the literature review and interview data, 25 proposed items were reviewed by 12 external experts, and the questions evaluated based on importance on a scale of 1 (not important to 5 (very important. Retained question domains had high mean importance ratings of 3.1 to 4.3 and good agreement with answer hierarchy.Conclusion: The proposed neurogenic bladder symptom score is a novel patient-reported outcome measure. Further work is underway to perform a data-based item reduction and to assess the validity and reliability of this instrument
Alkhachroum, Ayham M; Saeed, Saba; Kaur, Jaspreet; Shams, Tanzila; DeGeorgia, Michael A
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.
Heyrani, Nasser; Picinic Norheim, Elizabeth; Elaine Ku, Yeelan; Nick Shamie, Arya
Lumbar spinal stenosis (LSS) is a disabling medical condition in which narrowing of the spinal canal compresses the spinal cord and nerves causing a condition called neurogenic intermittent claudication (NIC). Decompressive spine surgery is the standard of care for patients who fail to improve with conservative management. However, oftentimes, patients who suffer from LSS are elderly individuals with multiple co-morbidities who cannot withstand the risks of decompressive surgery. X-Stop, a novel and minimally invasive FDA approved interspinous process implant, has come into the scene as an alternative to decompressive surgery, and can be inserted under local anesthetic with minimal blood loss. Despite its growing support in medical literature as an effective and conservative treatment of NIC, X-Stop remains a fairly new form of treatment. The aim of this study is to assess the clinical efficacy of its use. Fifty consecutive patients with at least two-year follow-up had a confirmed diagnosis of NIC secondary to LSS by computed tomography or magnetic resonance imaging (MRI) and subsequently received an X-Stop implant. Subjects' ages ranged from 64 to 95 with a mean age of 79, while the gender distribution comprised of 23 males and 27 females. Zurich Claudication Questionnaire (ZCQ) was used to assess patient outcome measures in three domains: physical function (PF), patient satisfaction (PS), and symptom severity (SS). The visual analog scale (VAS) was used to assess trends in pain with a scale from 0-10, with 0 defined as "pain-free" and 10 designated as "the worst pain imaginable". Compared to pre-op scores, PF, SS, and VAS scores for back, buttock and leg pain had a significant mean decrease at 6, 12, 24 months post-op (P 38) and 74% (17.23) were achieved at six months, 12 months, and 24 months respectively. X-Stop is a safe and effective treatment for NIC that provides marked relief of symptoms with sustained beneficial outcomes at up to two years of follow
Bartolome, G; Prosiegel, M; Yassouridis, A
The purpose of this prospective cohort study was: (1) to document and investigate long-term post-treatment outcome focusing on swallowing disability; and (2) to reveal variables predicting successful functional follow-up results in 63 patients with neurogenic dysphagia. All patients were admitted to an inpatient neurologic rehabilitation unit. Information was gathered through chart review and questionnaires. Functional outcome was categorized according to the degree of feeding status: (1) total tube feeding; (2) oral and tube feeding combined; (3) oral feeding with compensation; and (4) total oral feeding. 'Improvement' was determined as a positive shift in the type of feeding, 'deterioration' as a negative shift and 'no change' was defined as remaining at the same nutritional level. The safety of feeding was assessed by tracking the occurrence of pneumonia. Seventy percent of the patients achieved an improved immediate outcome after therapy. During long-term follow-up examinations, 43% of all patients showed further improvement, 57% did not show any change in their feeding ability and no deterioration was reported for any patient. Comparisons of the relative frequencies of the feeding modalities before and after therapy revealed a significant reduction in tube feeders and a significant increase in oral feeders with compensation during inpatient-treatment. The outpatient-interval showed a significant shift in total oral feeders without compensations but no significant improvement within the tube feeders and within the partial oral feeders. The improvement in nutritional status was not associated with an increased risk of pneumonia. Additional comparisons of the relative frequencies of the compensatory strategies indicated a significant reduction in all treatment techniques at final follow-up. Using logistic regression, predictors of successful post-discharge outcome involved a decreasing pre-treatment interval and unexpectedly low Barthel-ADL mobility scores. As a
Huang, Yan; Wu, Sun; Zhang, Yuan; Zi, Youmei; Yang, Man; Guo, Yan; Zhang, Lingxiu; Wang, Lihua
To explore the exact mechanisms of programmed cell death (PCD) induced by Type II anti-CD20 mAb in CD20+ non-Hodgkin lymphoma (NHL) cells, and to provide theoretical basis for anti-tumor ability of new CD20 mAb. After incubation with Rituximab (a Type I anti-CD20 mAb) and Tositumomab (a Type II anti-CD20 mAb), Raji cells were stained by annexin V & propidium iodide (PI). The ratio of programmed death cells were measured by two channel flow cytometry (FCM). Before the treatment of anti-CD20 mAbs, Raji cells was incubated with a caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (Z-VAD-FMK) and a dihydroceramide synthase inhibitor fumonisin B1 (FB1) for 30 minutes to assess their inhibitory effect on PCD. High performance liquid chromatography (HPLC) was utilized to compare the ratio of programmed death cells between the pretreatment group (treated by Rituximab and Tositumomab) and the non-pretreatment group. The anti-CD20 mAbs-treated Raji cells were collected, and the ceramide levels in the Raji cells in the different pretreatment groups were also examined by HPLC, and the inhibitory effect of FB1 on the changes of ceramide levels in the Raji cells was measured. The Raji cells were incubated with different concentration C2-ceramide, C2-Ceramide-induced PCD was also evaluated by annexin V & PI staining after 16 hours. Tositumomab (10 µg/mL) but not Rituximab (10 µg/mL) can induce significant PCD (28.6±4.2)% in Raji cells, with significant difference (t=26.48, P0.05). The cellular ceramide levels in Raji cells were significantly elevated after the treatment of Tositumomab (t=28.48, P0.05). The dihydroceramide synthase inhibitor FB1 can significantly inhibit the elevated cellular ceramide levels (F=20.18, P<0.01) and cell programmed death induced by Tositumomab (F=17.02, P<0.01). Type II but not Type I anti-CD20 mAbs can induce caspase independent PCD in CD20+ NHL cells through the elevation of cellular ceramide levels
Fjorback, M.V.; Rey, F. van; Rijkhoff, N.J.M.; Nohr, M.; Petersen, T.; Heesakkers, J.P.
AIMS: Transcutaneous electrical stimulation of the dorsal penile/clitoral nerve (DPN) has been shown to suppress detrusor contractions in patients with neurogenic detrusor overactivity (NDO). However, the long-term use of surface electrodes in the genital region may not be well tolerated and may
Warrenburg, B.P.C. van de; Zwarts, M.J.; Engelen, B.G.M. van
Neurogenic muscle (pseudo) hypertrophy of the calf was diagnosed in a 60-year-old man, who presented with chronic, painless and unilateral calf enlargement caused by a chronic S1 radiculopathy due to a lumbar disc hernia in the L5-S1 interspace. The differential diagnosis of a swelling of the calf
Wu, Wei; Jin, Yu-Qing; Gao, Zhen
The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types represents a great potential technology for regenerative medicine. In the present study, the potential of key developmental adipogenic, neurogenic and hepatogenic regulators to reprogram human fibroblasts into adipocytes, neurocytes and hepatocytes was investigated. The results demonstrated that direct reprogramming of octamer-binding transcription factor 4 (Oct4) and CCAAT-enhancer-binding protein (C/EBP)β activated C/EBPα and peroxisome proliferator-activated receptor-γ expression, inducing the conversion of fibroblasts into adipocytes. Similarly, direct reprogramming of the transcription factors sex determining region-box 2, trans-acting T-cell specific transcription factor (GATA-3) and neurogenic differentiation 1 in fibroblasts may induce neurogenic differentiation through hemagglutinating virus of Japan envelope (HVJ-E) transfection. Moreover, hepatogenic differentiation was induced by combining the direct reprogramming of Oct4, GATA-3, hepatocyte nuclear factor 1 homeobox α and forkhead box protein A2 in fibroblasts. These results demonstrate that specific transcription factors and reprogramming factors are able to directly reprogram fibroblasts into adipogenic, neurogenic and hepatogenic differentiation lineages by HVJ-E transfection. PMID:28587331
Cruz, Ana Sofia; Menezes, Sónia; Silva, Maria
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.
E. Kurt (Erkan); S.H. Bakker-Niezen (S.)
textabstractEpidural lipomatosis is most frequently seen in patients on chronic steroid treatment. Only twelve cases of idiopathic spinal epidural lipomatosis have been described. In this report we present an additional case of this condition in a middle-aged male presenting with neurogenic
Fode, Mikkel; Ohl, Dana A; Sønksen, Jens
Normal fertility is dependent on intravaginal delivery of semen through ejaculation. This process is highly dependent on an intact ejaculatory reflex arc, which can be disrupted through any type of trauma or disease causing damage to the CNS and/or peripheral nerves. Neurogenic anejaculation...
Fabbro, Franco, Ed.
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…
Michael R Foret
Full Text Available Histone 3 Lysine 9 (H3K9 methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3 is enriched in an adult neural stem cell niche- the subventricular zone (SVZ on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche.
Full Text Available La neurogenética es una disciplina emergente en el Perú que vincula la investigación básica con la práctica clínica. El Centro de Investigación Básica en Neurogenética, es el único centro en el Perú dedicado a la atención especializada de enfermedades neurogenéticas. La investigación en esta área está estrechamente ligada a la enfermedad de Huntington, desde la genotipificación del gen HTT por PCR, hasta los actuales estudios de haplogrupos en esta enfermedad. La investigación en otras enfermedades monogénicas permitió la implementación de metodologías alternativas para la genotipificación del síndrome X frágil y distrofia miotónica tipo 1. Esfuerzos colaborativos nacionales e internacionales han permitido conocer nuevas variantes genéticas en enfermedades complejas, como la enfermedad de Parkinson y Alzheimer. El entrenamiento multidisciplinario y la mentoría fomentan la formación de nuevos especialistas en neurogenética, permitiendo el crecimiento sostenido de esta disciplina en el país. El impulso de la investigación en el Perú ha impulsado el crecimiento de la investigación en neurogenética; sin embargo, las limitaciones en infraestructura, tecnología y capacitación aún son un reto para el crecimiento de investigación en esta disciplina
Aydinoglu, Fatma; Yilmaz, Sakir N; Coskun, Banu; Daglioglu, Nebile; Ogulener, Nuran
.... The neurogenic- and endothelium-dependent relaxation of corpus cavernosum smooth muscle and the degenerative effect of subacute ethanol treatment on the endothelial cells of corpus cavernosum was investigated in mice...
de Vocht, T. F.; Chrzan, R.; Dik, P.; Klijn, A. J.; de Jong, T. P. V. M.
PURPOSE: We evaluated the effectiveness of bladder neck injection as a supplementary treatment for persistent low pressure incontinence after unsatisfactory fascial sling procedures in patients with neurogenic lower urinary tract dysfunction. MATERIALS AND METHODS: A total of 89 patients with
Waleed Al Taweel
Conclusion: Intradetrusor onabotulinumtoxinA injections are an effective and well-tolerated treatment for neurogenic overactive bladder that will increase patient satisfaction and improve QOL with persisted clinical efficacy for more than 8 months.
Lee, Young-Hee; Kim, Jung Moon; Im, Hyung Tae; Lee, Kye-Wook; Kim, Sung Hoon; Hur, Dong Min
Objective To evaluate the effect of semiconditional electrical stimulation of the pudendal nerve afferents for the neurogenic detrusor overactivity in patients with spinal cord injury. Forty patients (36 males, 4 males) with spinal cord injury who had urinary incontinence and frequency, as well as felt bladder contraction with bladder filling sense or autonomic dysreflexic symptom participated in this study. Method Patients with neurogenic detrusor overactivity were subdivided into complete i...
Yartsev, V N; Karachentseva, O V
The effect of 0.03-1.0 μM noradrenaline on the neurogenic contractile response to electrical field stimulation of the juvenile rat tail artery segment in control conditions and after the solution pH decrease from 7.4 to 6.6 was studied. Acidosis were shown to inhibit this response significantly at all frequencies of stimulation used (3, 5, 10, and 40 Hz). Noradrenaline potentiated neurogenic vasoconstriction diminished spontaneously or by low pH. The potentiative effect of noradrenaline in acidic solution was more pronounced at higher frequencies of stimulation and noradrenaline concentrations. This phenomenon can, at least in part, account for blood flow redistribution from less important organs to vital ones during exercise which is characterized by acidosis, augmented sympathetic nerve activity and increased levels of noradrenaline.
Full Text Available 148 patients with anorectal malformations (ARM were examined. Using clinical, X-ray, ultrasound and urodynamical methods of detections, factors which can cause bladder dysfunction in anorectal malformations are revealed. It was noted that patients with high and low forms of this defect have significant percentage of neurogenec disorders of urination. Absence of anomalies of spinal column development does not exclude these children from the group of scheduled profound urologic investigation. We propose ultrasound measurement of bladder wall thickness and 4-hour monitoring of voiding, urodynamic examination as early diagnostic methods of neurogenic bladder dysfunctions. For timely revealing and treatment of neurogenic disorders of urination we recommend urologic inves¬tigation to all ARM patients. Improvement of diagnostic methods and development of algorithm of revealing mentioned pathologies against ARM with the aim to prevent com¬plications in the urinary system, being perspective in decreasing lethality and disability.
Alkhachroum, Ayham M.; Saeed, Saba; Kaur, Jaspreet; Shams, Tanzila; De Georgia, Michael A.
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
Yong Guan; Sun Wendong; Shengtian Zhao; Tongyan Liu; Yuqiang Liu; Xiulin Zhang; Mingzhen Yuan
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 ...
Smego, Allison R; Backeljauw, Philippe; Gutmark-Little, Iris
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.
末盛, 毅; 高橋, 省二; 夏目, 修; 山本, 雅司; 山田, 薫; 百瀬, 均; 塩見, 努
Three patients with contracted bladder caused by neurogenic bladder underwent ileocystoplasty. The primary diagnosis was meningomyelocele for all of them. The operative procedure adopted was Goodwin's Cup-patch method. All cases have obtained increased bladder capacity with improvement of bladder compliance and have been free from urinary incontinence. They were followed up by using clean intermittent self catheterization. Ileocystoplasty combined with clean intermittent self catheterization ...
Lucia M. Costa Monteiro
Full Text Available Abstract Objective: To evaluate the association between early treatment and urodynamic improvement in pediatric and adolescent patients with neurogenic bladder. Methodology: 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. Results: Among 230 patients included, 52% had an early referral. The majority were diagnosed as overactive bladder with high bladder pressure (≥40 cm H2O and low bladder compliance (3 mL/cmH2O and were treated with oxybutynin and intermittent catheterization. Urodynamic follow-up results showed 68% of improvement at the second urodynamic examination decreasing bladder pressure and increasing bladder capacity and compliance. The percentage of incontinence and urinary tract infections decreased over treatment. Early referral (one-year old or less increased by 3.5 the probability of urodynamic improvement in two years (95% CI: 1.81-6.77. Conclusion: 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.
Seipel, R.; Langner, S.; Lippa, M.; Kuehn, J.P.; Hosten, N. [Ernst Moritz Arndt Universitaet Greifswald, Institut fuer Diagnostische Radiologie und Neuroradiologie, Greifswald (Germany); Platz, T. [An-Institut der Ernst-Moritz-Arndt-Universitaet, BDH-Klinik Greifswald GmbH, Neurologisches Rehabilitationszentrum und Querschnittgelaehmtenzentrum, Greifswald (Germany)
To retrospectively evaluate neurogenic heterotopic ossification in an early neurological rehabilitation population (phases B and C) with respect to epidemiology and morphology on conventional radiographs. Over a 4-year period, 1,463 patients treated at a clinic for early neurological rehabilitation were evaluated for clinical symptoms of neurogenic heterotopic ossification. In case of clinical suspicion, plain radiographs of the expected sites were obtained. If heterotopic ossification was detected, the initial and subsequent radiographs were retrospectively analyzed for sites, size, and morphology. Immature lesions were categorized as small (<10 mm) or large (10-100 mm). The prevalence rate of neurogenic heterotopic ossification was 2.05%. The condition was most common in young male adults. The hip was the most common site accounting for more than half of the cases. Two or more ossifications were seen in 56.7% of the affected patients with approximately two-thirds showing bilateral symmetric involvement of corresponding joint regions. The size of ossifications strongly varied interindividually. Small immature lesions demonstrated less progression in size than large lesions during maturation (P < 0.05). Standard radiographs, as a fast and inexpensive technique, allow the expected size progression of heterotopic ossifications during maturation to be estimated, which is relevant in terms of therapeutic decisions, patient mobilization, and neurological rehabilitation. (orig.)
Wei, Zheng; Yaguchi, Junko; Yaguchi, Shunsuke; Angerer, Robert C; Angerer, Lynne M
Two major signaling centers have been shown to control patterning of sea urchin embryos. Canonical Wnt signaling in vegetal blastomeres and Nodal signaling in presumptive oral ectoderm are necessary and sufficient to initiate patterning along the primary and secondary axes, respectively. Here we define and characterize a third patterning center, the animal pole domain (APD), which contains neurogenic ectoderm, and can oppose Wnt and Nodal signaling. The regulatory influence of the APD is normally restricted to the animal pole region, but can operate in most cells of the embryo because, in the absence of Wnt and Nodal, the APD expands throughout the embryo. We have identified many constituent APD regulatory genes expressed in the early blastula and have shown that expression of most of them requires Six3 function. Furthermore, Six3 is necessary for the differentiation of diverse cell types in the APD, including the neurogenic animal plate and immediately flanking ectoderm, indicating that it functions at or near the top of several APD gene regulatory networks. Remarkably, it is also sufficient to respecify the fates of cells in the rest of the embryo, generating an embryo consisting of a greatly expanded, but correctly patterned, APD. A fraction of the large group of Six3-dependent regulatory proteins are orthologous to those expressed in the vertebrate forebrain, suggesting that they controlled formation of the early neurogenic domain in the common deuterostome ancestor of echinoderms and vertebrates.
Castro-Gago, Manuel; Dacruz-Alvarez, David; Pintos-Martínez, Elena; Beiras-Iglesias, Andrés; Arenas, Joaquín; Martín, Miguel Ángel; Martínez-Azorín, Francisco
Choline kinase beta gene (CHKB) mutations have been identified in Megaconial Congenital Muscular Dystrophy (MDCMC) patients, a very rare inborn error of metabolism with 21 cases reported worldwide. We report the case of a Spanish boy of Caucasian origin who presented a generalized congenital muscular hypotonia, more intense at lower limb muscles, mildly elevated creatine kinase (CK), serum aspartate transaminase (AST) and lactate. Electromyography (EMG) showed neurogenic potentials in the proximal muscles. Histological studies of a muscle biopsy showed neurogenic atrophy with enlarged mitochondria in the periphery of the fibers, and complex I deficiency. Finally, genetic analysis showed the presence of a homozygous mutation in the gene for choline kinase beta (CHKB: NM_005198.4:c.810T>A, p.Tyr270(∗)). We describe here the second Spanish patient whit mutation in CHKB gene, who despite having the same mutation, presented an atypical aspect: congenital neurogenic muscular atrophy progressing to a combined neuropathic and myopathic phenotype (mixed pattern). Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Chu, David I; Balsara, Zarine R; Routh, Jonathan C; Ross, Sherry S; Wiener, John S
Malone antegrade continence enemas are used in the management of neurogenic bowel to attain fecal continence. Several different irrigation solutions have been described but glycerin, an osmotic laxative that promotes peristalsis, has rarely been mentioned or studied. We assessed clinical outcomes in our patients with a Malone antegrade continence enema using glycerin based irrigation. We retrospectively reviewed patients with neurogenic bowel who underwent a Malone antegrade continence enema procedure between 1997 and 2011. Glycerin diluted with tap water followed by a tap water flush is our preferred irrigation protocol. Bowel regimen outcomes examined included fecal continence, emptying time, leakage from stoma, enema volume, frequency and independence. Of the 23 patients with followup greater than 6 months 19 used glycerin based irrigation. Average age at surgery was 8.8 years. Patients using glycerin instilled a median of 30 ml (mean 29) glycerin and 50 ml (131) tap water. Fecal continence rate was 95% and stoma leakage rate was 16%, and only 16% of patients required daily irrigation. Glycerin is a viable and effective alternative irrigant for antegrade enemas of neurogenic bowel, with an excellent fecal continence rate. The volume of irrigant needed is typically less than 90 ml, which is much less than in published reports using tap water alone. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Sadiq, Saima; Faiq, Syed Muhammmad; Idrees, Muhammad Khalid
To find the frequency and types of spinal dysraphism in patients presenting with neurogenic bladder dysfunction. The cross-sectional study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, from February to September 2011, and comprised patients of either gender 5-15 years of age with neurogenic bladder suspected to be due to lumbosacral dysraphism. They all had magnetic resonance imaging of lumbosacral spine. All images were reviewed by an experienced radiologist and patients were diagnosed as having spinal dysraphism and were categorised according to the radiological features. Data was analysed using SPSS 10. Of the 175 patients in the study, 96(55%) were males and 79(45%) were females with an overall mean age of 7.3±2.15 years (range: 5-15 years). Spinal bony defects were found in 110(62.8%) patients, and of these, 96(87%) had spinal dysraphism. Myelomeningocele, meningocele and sacral agenesis was found in 58(60.4%) of the 96 patient with spinal dysraphism. Spinal dysraphism is the most common cause of neurogenic bladder in children up to 15 years of age and myelomeningocele, meningocele and sacral agenesis comprised more than 60% of such cases.
Vainshtein, A.; Veenman, L; Shterenberg, A; Singh, S; Masarwa, A; Dutta, B.; Island, B; Tsoglin, E; Levin, E.; Leschiner, S; Maniv, I; Pe?er, L; Otradnov, I; Zubedat, S; Aga-Mizrachi, S
Expanding on a quinazoline scaffold, we developed tricyclic compounds with biological activity. These compounds bind to the 18?kDa translocator protein (TSPO) and protect U118MG (glioblastoma cell line of glial origin) cells from glutamate-induced cell death. Fascinating, they can induce neuronal differentiation of PC12 cells (cell line of pheochromocytoma origin with neuronal characteristics) known to display neuronal characteristics, including outgrowth of neurites, tubulin expression, and ...
Traiffort, Elisabeth; Angot, Elodie; Ruat, Martial
The discovery of a Sonic Hedgehog (Shh) signaling pathway in the mature vertebrate CNS has paved the way to the characterization of the functional roles of Shh signals in normal and diseased brain. Shh is proposed to participate in the establishment and maintenance of adult neurogenic niches and to regulate the proliferation of neuronal or glial precursors in several brain areas. Consistent with its role during brain development, misregulation of Shh signaling is associated with tumorigenesis while its recruitement in damaged neural tissue might be part of the regenerating process. This review focuses on the most recent data of the Hedgehog pathway in the adult brain and its relevance as a novel therapeutic approach for brain diseases including brain tumors.
Stocker, Sean D.; Monahan, Kevin D.; Browning, Kirsteen N.
Excess dietary salt intake is a major contributing factor to the pathogenesis of salt-sensitive hypertension. Strong evidence suggests that salt-sensitive hypertension is attributed to renal dysfunction, vascular abnormalities, and activation of the sympathetic nervous system. Indeed, sympathetic nerve transections or interruption of neurotransmission in various brain centers lowers arterial blood pressure (ABP) in many salt-sensitive models. The purpose of this article is to discuss recent evidence that supports a role of plasma or cerebrospinal fluid hypernatremia as a key mediator of sympathoexcitation and elevated ABP. Both experimental and clinical studies using time-controlled sampling have documented that a diet high in salt increases plasma and cerebrospinal fluid sodium concentration. To the extent it has been tested, acute and chronic elevations in sodium concentration activates the sympathetic nervous system in animals and humans. A further understanding of how the central nervous system detects changes in plasma or cerebrospinal fluid sodium concentration may lead to new therapeutic treatment strategies in salt-sensitive hypertension. PMID:24052211
Brand, A; Gil, S; Yavin, E
A major reason for brain tissue vulnerability to oxidative damage is the high content of polyunsaturated fatty acids (PUFAs). Oligodendroglia-like OLN 93 cells lack PUFAs and are relatively insensitive to oxidative stress. When grown in serum-free defined medium in the presence of 0.1 mM docosahexaenoic acid (DHA; 22:6 n-3) for 3 days, OLN 93 cells release in the medium 2.6-fold more thiobarbituric acid-reactive substances (TBARS) after a 30-min exposure to 0.1 mM H2O2 and 50 microM Fe2+. Release of TBARS was substantially decreased by approximately 20 and 30% on coincubation with either 1 mM N-monomethylethanolamine or N,N'-dimethylethanolamine (dEa), respectively. The protective effect of dEa was concentration- and time-dependent and was still visible after dEa removal, suggesting a long-lasting mechanism of protection. After 24 h following H2O2-induced stress, cell death monitored by cell sorting showed 16% of the cells in the sub-G1 area, indicative of apoptotic cell death. DHA-supplemented cultures showed 35% cell death, whereas cosupplements with dEa reduced cell death to 12%, indicating cell rescue. Although the exact mechanism for this protection is not known, the nature of the polar head group and the degree of unsaturation may determine the ultimate resistance of nerve cells to oxidative stress.
Yamada, Taihei; Kerever, Aurelien; Yoshimura, Yusuke; Suzuki, Yuji; Nonaka, Risa; Higashi, Kyohei; Toida, Toshihiko; Mercier, Frederic; Arikawa-Hirasawa, Eri
Adult neurogenesis in the subventricular zone of the lateral ventricle decreases with age. In the subventricular zone, the specialized extracellular matrix structures, known as fractones, contact neural stem cells and regulate neurogenesis. Fractones are composed of extracellular matrix components, such as heparan sulfate proteoglycans. We previously found that fractones capture and store fibroblast growth factor 2 (FGF-2) via heparan sulfate binding, and may deliver FGF-2 to neural stem cells in a timely manner. The heparan sulfate (HS) chains in the fractones of the aged subventricular zone are modified based on immunohistochemistry. However, how aging affects fractone composition and subsequent FGF-2 signaling and neurogenesis remains unknown. The formation of the FGF-fibroblast growth factor receptor-HS complex is necessary to activate FGF-2 signaling and induce the phosphorylation of extracellular signal-regulated kinase (Erk1/2). In this study, we observed a reduction in HS 6-O-sulfation, which is critical for FGF-2 signal transduction, and failure of the FGF-2-induced phosphorylation of Erk1/2 in the aged subventricular zone. In addition, we observed increased HS 6-O-endo-sulfatase, an enzyme that may be responsible for the HS modifications in aged fractones. In conclusion, the data revealed that heparan sulfate 6-O-sulfation is reduced and FGF-2-dependent Erk1/2 signaling is impaired in the aged subventricular zone. HS modifications in fractones might play a role in the reduced neurogenic activity in aging brains. © 2017 International Society for Neurochemistry.
Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy
Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas
Markman, John D; Frazer, Maria E; Rast, Shirley A; McDermott, Michael P; Gewandter, Jennifer S; Chowdhry, Amit K; Czerniecka, Kate; Pilcher, Webster H; Simon, Lee S; Dworkin, Robert H
To test the effects of pregabalin on the induction of neurogenic claudication. This study was a randomized, double-blind, active placebo-controlled, 2-period, crossover trial. Twenty-nine subjects were randomized to receive pregabalin followed by active placebo (i.e., diphenhydramine) or active placebo followed by pregabalin. Each treatment period lasted 10 days, including a 2-step titration. Periods were separated by a 10-day washout period, including a 3-day taper phase after the first period. The primary outcome variable was the time to first moderate pain symptom (Numeric Rating Scale score ≥4) during a 15-minute treadmill test (Tfirst). Secondary outcome measures included pain intensity at rest, pain intensity at the end of the treadmill test, distance walked, and validated self-report measures of pain and functional limitation including the Roland-Morris Disability Questionnaire, modified Brief Pain Inventory-Short Form, Oswestry Disability Index, and Swiss Spinal Stenosis Questionnaire. No significant difference was found between pregabalin and active placebo for the time to first moderate pain symptom (difference in median Tfirst = -1.08 [95% confidence interval -2.25 to 0.08], p = 0.61). In addition, none of the secondary outcome measures of pain or functional limitation were significantly improved by pregabalin compared with active placebo. Pregabalin was not more effective than active placebo in reducing painful symptoms or functional limitations in patients with neurogenic claudication associated with lumbar spinal stenosis. This study provides Class I evidence that for patients with neurogenic claudication, compared with diphenhydramine, pregabalin does not increase the time to moderate pain during a treadmill test. © 2014 American Academy of Neurology.
Zaragoza Torres, Raúl Ignacio; Galarza-Flores, Mario Eduardo; Gómez-Castellanos, Julio Cesar; Barrera-de León, Juan Carlos
Augmentation cystoplasty is a successful surgical procedure for the management of neurogenic bladder in children in order to improve urodynamic parameters. The aim of this article is to describe urodynamic changes after augmentation cystoplasty in children with myelomeningocele. A descriptive cross-sectional study including children aged 8-16 years with a myelomeningocele operated on for augmentation cystoplasty surgery with sigmoid colon segments due to a neurogenic bladder from the years 2003-2013. A urodynamic study was conducted before and after the surgical procedure. Non-probabilistic sample of consecutive cases. Descriptive statistics with frequencies and percentages, medians, and ranges. Inferential intra-group comparison with the Wilcoxon test and inter-group with Mann-Whitney U. SPSS 20.0 statistical package. The study included 50 patients, of whom 25 were male and 25 were female, with a median age of 12 years (range, 6-15 years). Bladder capacity improved from 52.8% to 95.9% (p<0.001), uninhibited contractions 1.4-1.8, contraction intensity 47-8.5 (p<0.001), mean pre-surgical and post-surgical filling pressure 40.8cm H2O and 11.0cm H2O, respectively (p<0.001), mean emptying pressure 48.5 vs. 3.6cm H2O (p<0.001), and bladder accommodation 4.6 vs. 41.3cm H2O (p<0.001). Augmentation cystoplasty with sigmoid colon significantly improved urodynamic parameters, such as bladder accommodation and filling pressure in children with myelomeningocele-associated neurogenic bladder. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.
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
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
Denard, Patrick J.; Holton, Kathleen F.; Miller, Jessica; Fink, Howard A.; Kado, Deborah M.; Marshall, Lynn M.; Yoo, Jung U.
Background Context Degenerative spondylolisthesis is a presumed cause of back pain. Previous studies of spondylolisthesis and back pain included only women or combined results for men and women. Comparisons of the frequency of back pain, neurogenic symptoms, and functional limitations specifically among elderly men with and without spondylolisthesis are needed. Purpose To determine associations of prevalent spondylolisthesis with back pain symptoms, neurogenic symptoms, and functional limitations among elderly men. Study Design/ Setting: Cross-sectional epidemiologic study conducted within the Osteoporotic Fractures in Men (MrOS) cohort. The MrOS cohort is comprised of 5,995 community dwelling men ages ≥65 years who were recruited at 6 US academic medical centers. Extensive self-reported data and lumbar spine radiographs were obtained for all MrOS participants at baseline. Patient Sample For this study, 300 men were selected at random specifically for the evaluation of spondylolisthesis on the baseline spine radiographs. Outcome Measures Standardized questionnaires were used to assess self-reported back pain, leg pain (radiculopathy), lower extremity numbness (paresthesias) and lower extremity weakness occurring in the past 12 months, and to ascertain current difficulty with activities of daily living. Methods In the present study, radiographic spondylolisthesis was classified as forward slip of ≥5%. Prevalence of back pain, neurogenic symptoms and difficulty with activities of daily living were compared between men with and without spondylolisthesis using chisquare or Fisher’s exact tests. Results Spondylolisthesis was present among 92 (31%) men. Among men with and without spondylolisthesis, back pain (63% vs. 67%, p=0.46) and moderate/severe back pain (41% vs. 38%, p=0.76) were reported with similar frequency. Men with spondylolisthesis more often reported radiculopathy (33% vs. 22%, p=0.06), paresthesias (18% vs. 11%, p= 0.10) and weakness (18% vs. 9%, p=0
Maus, Timothy P
Spinal stenosis in either the cervical or lumbar spinal segments is one of the most common indications for spine imaging and intervention, particularly among the elderly. This article examines the pathophysiology and imaging of the corresponding clinical syndromes, cervical spondylotic myelopathy or neurogenic intermittent claudication. The specificity fault of spine imaging is readily evident in evaluation of spinal stenosis, as many patients with anatomic cervical or lumbar central canal narrowing are asymptomatic. Imaging also may be insensitive to dynamic lesions. Those imaging features that identify symptomatic patients, or predict response to interventions, are emphasized. Copyright © 2012 Elsevier Inc. All rights reserved.
Palla, Alessandro; Rossi, Stefano; Fanucci, Luca
Patients with impaired bladder volume sensation have the necessity to monitor bladder level in order to avoid urinary tract infections and urinary reflux that can lead to renal failure. In this paper the the effectiveness of an embedded and wearable solution for bladder volume monitoring using the bioimpedance measurement is tested. Data are streamed real-time using Bluetooth wireless technology. The bioimpedance measurements on a healthy subject prove the effectiveness of the proposed solution. In the future the system will be evaluated in real world scenarios with patients affected by spinal paralysis and bladder neurogenic dysfunction.
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.
Hechtman, Jaclyn F; Harpaz, Noam
Primary neurogenic gastrointestinal polyps are encountered relatively frequently in routine pathology practice. They encompass a variety of neoplastic entities with clinical, morphologic, and molecular features that reflect the diversity of neural elements within the gastrointestinal system. Although most are benign and encountered incidentally, accurate diagnosis may have important clinical implications because of the associations of certain neurogenic polyps with familial syndromes or other conditions. We review the pathology of these polyps with an emphasis on the diagnostic challenges that they pose and on newly described subtypes.
Nassini, Romina; Pedretti, Pamela; Moretto, Nadia
The transient receptor potential ankyrin 1 (TRPA1) channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS) in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic...... inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express...
Ji Hee Kim
Full Text Available Objective. To investigate the effects and safety of the aqueous extract of the dried, immature fruit of Poncirus trifoliata (L. Raf., known as Poncirus fructus (PF, in spinal cord injury (SCI patients with neurogenic bowel. Methods. Thirty-one SCI patients with neurogenic bowel were recruited. Patients were evaluated based on clinical information, constipation score, Bristol Stool Form Scale, stool retention score using plain abdominal radiograph, and colon transit time. PF was administered in dosages of 800 mg each prior to breakfast and lunch for 14 days. Results. The morphological feature of the stool before and after administration indicated a statistically significant difference from 3.52 ± 1.33 to 4.32 ± 1.44 points (p<0.05. Stool retention score before and after administration of PF was represented with low significance (7.25 ± 1.60 to 6.46 ± 1.53 points in the whole colon (p<0.05, and the colon transit time was significantly shortened (57.41 ± 20.7 to 41.2 ± 25.5 hours in terms of the whole transit time (p<0.05. Side effects were observed in 7 people (28.0% consisting of 2 people with soft stools and 5 people with diarrhea. Conclusion. For SCI patients, PF administration significantly improved defecation patterns, defecation retention, and colon transit time. PF could be an effective aid to improve colonic motility and constipation.
Guan, Yong; Wendong, Sun; Zhao, Shengtian; Liu, Tongyan; Liu, Yuqiang; Zhang, Xiulin; Yuan, Mingzhen
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
Pereira, Ulysse; Garcia-Le Gal, Caridad; Le Gal, Grégoire; Boulais, Nicholas; Lebonvallet, Nicolas; Dorange, Germaine; Lefeuvre, Luc; Gougerot, Agnés; Misery, Laurent
Sangre de drago (SD) is a viscous bright red resin collected from Croton lechleri trees that grow in the South American jungle. This sap is used extensively in the native pharmacopoeia to treat skin disorders. Its effectiveness as an inhibitor of neurogenic inflammation has been recently demonstrated. To understand the underlying mechanisms of these effects, we examined the ability of SD to reduce substance P (SP) release in an in vitro model of cutaneous neurogenic inflammation (CNI). This model is based on an enzyme immunoassay of SP (an inducer of CNI) in a porcine co-culture of dorsal root ganglion neurons and keratinocytes. After incubation with different concentrations of SD, we noted an immediate and significant dose-dependent decrease in basal SP release, with average values of 32% at 1% SD (v/v) and 26% at 0.1% (v/v). On the other hand, pretreatment (72 or 1 h) of the co-culture with 1% SD (v/v) was sufficient to induce a 111% (72 h) or 65% (1 h) inhibition of capsaicin-induced SP release, while 0.1% SD (v/v) triggered a 109% (72 h) or 30% (1 h) inhibition. We conclude that sangre de drago is a potent inhibitor of CNI through direct inhibition of neuropeptide release by sensory afferent nerves.
Hagan, Robert R; Ricci, Joseph A; Eberlin, Kyle R
Thoracic outlet syndrome (TOS) is a cause of upper extremity and shoulder dysfunction. TOS can present with a wide range of symptoms due to compression of the brachial plexus or its branches during their passage through the cervicothoracobrachial region or scalene triangle. There are three types of TOS: arterial, venous, and neurogenic. Neurogenic TOS (nTOS) is by far the most frequent type and represents more than 95% of all cases. Historically, surgical intervention for all types of TOS has evolved based on the treatment for a vascular etiology and has typically included a first rib resection. Despite nTOS being by far the more common type, most previous interventions have not considered treatment via peripheral nerve decompression.We describe surgical treatment of nTOS, performed on an outpatient basis, which focuses on the surgical decompression of the structures associated with the scalene triangle in conjunction with release of the pectoralis minor insertion through limited incisions. The procedure avoids the morbidity associated with first rib resection and is successful in ameliorating nTOS symptoms. Further, we propose a nomenclature shift to scalene triangle syndrome (STS) to reflect the nerve and arterial compressions needing to be addressed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Full Text Available 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 (CXCL12-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-to-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.
Full Text Available While neurogenic stem cells have been identified in rodent and human skin, their manipulation and further characterization are hampered by a lack of specific markers. Here, we perform genetic tracing of the progeny of boundary cap (BC cells, a neural-crest-derived cell population localized at peripheral nerve entry/exit points. We show that BC derivatives migrate along peripheral nerves to reach the skin, where they give rise to terminal glia associated with dermal nerve endings. Dermal BC derivatives also include cells that self-renew in sphere culture and have broad in vitro differentiation potential. Upon transplantation into adult mouse dorsal root ganglia, skin BC derivatives efficiently differentiate into various types of mature sensory neurons. Together, this work establishes the embryonic origin, pathway of migration, and in vivo neurogenic potential of a major component of skin stem-like cells. It provides genetic tools to study and manipulate this population of high interest for medical applications.
Full Text Available 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.
Jane M. Lewis
Full Text Available Patients with spina bifida and a neurogenic bladder have traditionally been managed with clean intermittent catheterization and pharmacotherapy in order to treat abnormal bladder wall dynamics, protect the upper urinary tract from damage, and achieve urinary continence. However, some patients will fail this therapy and require surgical reconstruction in the form of bladder augmentation surgery using reconfigured intestine or stomach to increase the bladder capacity while reducing the internal storage pressure. Despite functional success of bladder augmentation in achieving a low pressure reservoir, there are several associated complications of this operation and patients do not have the ability to volitionally void. For these reasons, alternative treatments have been sought. Two exciting alternative approaches that are currently being investigated are tissue engineering and neuromodulation. Tissue engineering aims to create new bladder tissue for replacement purposes with both “seeded” and “unseeded” technology. Advances in the fields of nanotechnology and stem cell biology have further enhanced these tissue engineering technologies. Neuromodulation therapies directly address the root of the problem in patients with spina bifida and a neurogenic bladder, namely the abnormal relationship between the nerves and the bladder wall. These therapies include transurethral bladder electrostimulation, sacral neuromodulation, and neurosurgical techniques such as selective sacral rhizotomy and artificial somatic-autonomic reflex pathway construction. This review will discuss both tissue engineering techniques and neuromodulation therapies in more detail including rationale, experimental data, current status of clinical application, and future direction.
Cho, Young-Sam; Ko, Il-Gyu; Kim, Sung-Eun; Lee, Sung-Min; Shin, Mal-Soon; Kim, Chang-Ju; Kim, Sang-Hoon; Jin, Jun-Jang; Kim, Khae-Hawn
Spinal cord injury (SCI) deteriorates various physical functions, in particular, bladder problems occur as a result of damage to the spinal cord. Stem cell therapy for SCI has been focused as the new strategy to treat the injuries and to restore the lost functions. The oral mucosa cells are considered as the stem cells-like progenitor cells. In the present study, we investigated the effects of oral mucosa stem cells on the SCI-induced neurogenic bladder in relation with apoptotic neuronal cell death and cell proliferation. The contraction pressure and the contraction time in the urinary bladder were increased after induction of SCI, in contrast, transplantation of the oral mucosa stem cells decreased the contraction pressure and the contraction time in the SCI-induced rats. Induction of SCI initiated apoptosis in the spinal cord tissues, whereas treatment with the oral mucosa stem cells suppressed the SCI-induced apoptosis. Disrupted spinal cord by SCI was improved by transplantation of the oral mucosa stem cells, and new tissues were increased around the damaged tissues. In addition, transplantation of the oral mucosa stem cells suppressed SCI-induced neuronal activation in the voiding centers. Transplantation of oral mucosa stem cells ameliorates the SCI-induced neurogenic bladder symptoms by inhibiting apoptosis and by enhancing cell proliferation. As the results, SCI-induced neuronal activation in the neuronal voiding centers was suppressed, showing the normalization of voiding function.
Opisso, E; Borau, A; Rodríguez, A; Hansen, J; Rijkhoff, N J M
We investigated whether patients with neurogenic detrusor overactivity can sense the onset of bladder contraction and in turn suppress the contraction by electrical stimulation of the dorsal penile-clitoral nerve. A total of 67 patients with different neurological disorders were recruited to undergo 3 filling cystometries. The first cystometry was done without stimulation. The second cystometry was performed with automatic controlled stimulation based on detrusor pressure. The third cystometry was done with patient controlled stimulation using a push button. Four females and 13 males underwent all 3 fillings. Compared to cystometry 1 average bladder capacity for cystometries 2 and 3 was 60% higher. Compared to peak pressure for cystometry 1 average peak pressure during suppressed contractions for cystometries 2 and 3 was 49% and 26% lower, respectively. The average delay of the onset of stimulation during cystometry 3 with respect to cystometry 2 was 5.7 seconds. The study shows that patient controlled genital nerve stimulation is as effective as automatic controlled stimulation to treat neurogenic detrusor overactivity. Thus, patient controlled stimulation is feasible in select patients, although patients must be trained in the technique.
... on the cause. They often include symptoms of urinary incontinence . Symptoms of overactive bladder may include: Having to ... urinary diversion) Support Groups If you are having urinary incontinence, organizations are available for further information and support. ...
Young, Megan M.; Takahashi, Yoshinori; Khan, Osman; Park, Sungman; Hori, Tsukasa; Yun, Jong; Sharma, Arun K.; Amin, Shantu; Hu, Chang-Deng; Zhang, Jianke; Kester, Mark; Wang, Hong-Gang
Autophagy and apoptosis are two evolutionarily conserved processes that regulate cell fate in response to cytotoxic stress. However, the functional relationship between these two processes remains far from clear. Here, we demonstrate an autophagy-dependent mechanism of caspase-8 activation and initiation of the apoptotic cascade in response to SKI-I, a pan-sphingosine kinase inhibitor, and bortezomib, a proteasome inhibitor. Autophagy is induced concomitantly with caspase-8 activation, which is responsible for initiation of the caspase cascade and the mitochondrial amplification loop that is required for full execution of apoptosis. Inhibition of autophagosome formation by depletion of Atg5 or Atg3 results in a marked suppression of caspase-8 activation and apoptosis. Although caspase-8 self-association depends on p62/SQSTM1, its self-processing requires the autophagosomal membrane. Caspase-8 forms a complex with Atg5 and colocalizes with LC3 and p62. Moreover, FADD, an adaptor protein for caspase-8 activation, associates with Atg5 on Atg16L- and LC3-positive autophagosomal membranes and loss of FADD suppresses cell death. Taken together, these results indicate that the autophagosomal membrane serves as a platform for an intracellular death-inducing signaling complex (iDISC) that recruits self-associated caspase-8 to initiate the caspase-8/-3 cascade. PMID:22362782
Yamada, T; Marubashi, W; Niwa, M
Hybrid lethality expressed in the interspecific hybrid of Nicotiana suaveolens Lehm. x N. tabacum L. cv. Hicks-2 is one of the mechanisms for reproductive isolation and it is temperature-sensitive. Apoptotic changes were detected in the cells of hybrid seedlings and calli expressing lethality at 28 degrees C but not under high-temperature conditions (36 degrees C), when the lethality is suppressed. Condensation of chromatin, fragmentation of nuclei and cytoplasmic reduction are the cytological changes associated with apoptosis leading to hybrid lethality. Fragmentation of nuclei was correlated with the lethal symptoms in both hybrid seedlings and calli, as confirmed by fluorimetry of the nuclear DNA using laser scanning cytometry. Agarose gel analysis of DNA extracted from hybrid seedlings and calli showing lethal symptoms revealed a specific ladder pattern suggesting nucleosomal fragmentation which is one of the biochemical changes of apoptosis. In-situ detection using terminal deoxyribonucleotidyl transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) showed that this process occurred in distinct stages on each organ of hybrid seedlings and centripetally in hybrid calli. From these results, we confirmed that cell death inducing hybrid lethality was indeed apoptosis.
Dong, Yachen; Hu, Jingjin; Fan, Linlin; Chen, Qihe
As a typical harmful inhibitor in cellulosic hydrolyzates, acetic acid not only hinders bioethanol production, but also induces cell death in Saccharomyces cerevisiae. Herein, we conducted both transcriptomic and metabolomic analyses to investigate the global responses under acetic acid stress at different stages. There were 295 up-regulated and 427 down-regulated genes identified at more than two time points during acetic acid treatment (150 mM, pH 3.0). These differentially expressed genes (DEGs) were mainly involved in intracellular homeostasis, central metabolic pathway, transcription regulation, protein folding and stabilization, ubiquitin-dependent protein catabolic process, vesicle-mediated transport, protein synthesis, MAPK signaling pathways, cell cycle, programmed cell death, etc. The interaction network of all identified DEGs was constructed to speculate the potential regulatory genes and dominant pathways in response to acetic acid. The transcriptional changes were confirmed by metabolic profiles and phenotypic analysis. Acetic acid resulted in severe acidification in both cytosol and mitochondria, which was different from the effect of extracellular pH. Additionally, the imbalance of intracellular acetylation was shown to aggravate cell death under this stress. Overall, this work provides a novel and comprehensive understanding of stress responses and programmed cell death induced by acetic acid in yeast. PMID:28209995
Elsamanoudy, Ayman Z; Abdalla, Hussein Abdelaziz; Hassanien, Mohammed; Gaballah, Mohammad A
This is the first study to investigate spermatozoal cell death-inducing DNA fragmentation factor-α-like effector A (CIDEA) gene expression and DNA fragmentations in the spermatozoa of men diagnosed with metabolic syndrome (MS) who have normal seminograms with unexplained infertility, and to correlate these parameters with seminal glucose concentration. This study included 120 participants: 75 male subjects with MS (38 fertile and 37 infertile), and a control group of 45 fertile males without MS. HOMA-IR, semen analysis, and biochemical measurement of seminal plasma insulin and glucose levels were carried out. Spermatozoal insulin gene and CIDEA gene expressions were performed by the RT-PCR method. The percentage of spermatozoal DNA fragmentation was also estimated. The spermatozoal insulin and CIDEA gene expression, as well as the DNA fragmentation, were significantly higher in the infertile MS group than in the fertile MS group, and significantly higher in both the MS groups than in the control group. Seminal glucose concentration showed significant positive correlations with seminal insulin level, spermatozoa insulin, CIDEA gene expression, and DNA fragmentation. Moreover, there was a positive correlation between spermatozoa CIDEA gene expression and DNA fragmentation. It can be concluded that MS may affect male fertility at the molecular level, through its possible inducing effect of spermatozoa CIDEA and insulin gene expression, DNA fragmentation, and increased seminal glucose.
Moojen, Wouter A.; Arts, Mark P.; Bartels, Ronald H. M. A.; Jacobs, Wilco C. H.; Peul, Wilco C.
Despite an increasing implantation rate of interspinous process distraction (IPD) devices in the treatment of intermittent neurogenic claudication (INC), definitive evidence on the clinical effectiveness of implants is lacking. The main objective of this review was to perform a meta-analysis of all
Li, Xiao-Shi; Quan, Chang-Yi; Li, Gang; Cai, Qi-Liang; Hu, Bin; Wang, Jiu-Wei; Niu, Yuan-Jie
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.
Full Text Available Abstract Background The paired homeobox protein Pax6 is essential for proliferation and pluripotency of retinal progenitors. However, temporal changes in Pax6 protein expression associated with the generation of various retinal neurons have not been characterized with regard to the cell cycle. Here, we examine the dynamic changes of Pax6 expression among chicken retinal progenitors as they progress through the neurogenic cell cycle, and determine the effects of altered Pax6 levels on retinogenesis. Results We provide evidence that during the preneurogenic to neurogenic transition, Pax6 protein levels in proliferating progenitor cells are down-regulated. Neurogenic retinal progenitors retain a relatively low level of Pax6 protein, whereas postmitotic neurons either elevate or extinguish Pax6 expression in a cell type-specific manner. Cell imaging and cell cycle analyses show that neurogenic progenitors in the S phase of the cell cycle contain low levels of Pax6 protein, whereas a subset of progenitors exhibits divergent levels of Pax6 protein upon entering the G2 phase of the cell cycle. We also show that M phase cells contain varied levels of Pax6, and some correlate with the onset of early neuronal marker expression, forecasting cell cycle exit and cell fate commitment. Furthermore, either elevating or knocking down Pax6 attenuates cell proliferation and results in increased cell death. Reducing Pax6 decreases retinal ganglion cell genesis and enhances cone photoreceptor and amacrine interneuron production, whereas elevating Pax6 suppresses cone photoreceptor and amacrine cell fates. Conclusion These studies demonstrate for the first time quantitative changes in Pax6 protein expression during the preneurogenic to neurogenic transition and during the neurogenic cell cycle. The results indicate that Pax6 protein levels are stringently controlled in proliferating progenitors. Maintaining a relatively low Pax6 protein level is necessary for S phase
Schneider, Marc P; Gross, Tobias; Bachmann, Lucas M; Blok, Bertil F M; Castro-Diaz, David; Del Popolo, Giulio; Groen, Jan; Hamid, Rizwan; Karsenty, Gilles; Pannek, Jürgen; Hoen, Lisette 't; Kessler, Thomas M
Tibial nerve stimulation (TNS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option for patients with an underlying neurological disorder. We systematically reviewed all available evidence on the efficacy and safety of TNS for treating neurogenic lower urinary tract dysfunction (NLUTD). The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. After screening 1943 articles, 16 studies (4 randomized controlled trials [RCTs], 9 prospective cohort studies, 2 retrospective case series, and 1 case report) enrolling 469 patients (283 women and 186 men) were included. Five studies reported on acute TNS and 11 on chronic TNS. In acute and chronic TNS, the mean increase of maximum cystometric capacity ranged from 56 to 132mL and from 49 to 150mL, and the mean increase of bladder volume at first detrusor overactivity ranged from 44 to 92mL and from 93 to 121mL, respectively. In acute and chronic TNS, the mean decrease of maximum detrusor pressure during the storage phase ranged from 5 to 15cm H2O and from 4 to 21cm H2O, respectively. In chronic TNS, the mean decrease in number of voids per 24h, in number of leakages per 24h, and in postvoid residual ranged from 3 to 7, from 1 to 4, and from 15 to 55mL, respectively. No TNS-related adverse events have been reported. Risk of bias and confounding was high in most studies. Although preliminary data of RCTs and non-RCTs suggest TNS might be effective and safe for treating NLUTD, the evidence base is poor, derived from small, mostly noncomparative studies with a high risk of bias and confounding. More reliable data from well-designed RCTs are needed to reach definitive conclusions. Early data suggest tibial nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required. Copyright © 2015 European Association of Urology. Published by
Lee, Young-Hee; Kim, Jung Moon; Im, Hyung Tae; Lee, Kye-Wook; Kim, Sung Hoon; Hur, Dong Min
To evaluate the effect of semiconditional electrical stimulation of the pudendal nerve afferents for the neurogenic detrusor overactivity in patients with spinal cord injury. Forty patients (36 males, 4 males) with spinal cord injury who had urinary incontinence and frequency, as well as felt bladder contraction with bladder filling sense or autonomic dysreflexic symptom participated in this study. Patients with neurogenic detrusor overactivity were subdivided into complete injury and incomplete injury groups by ASIA classification and subdivided into tetraplegia and paraplegia groups by neurologic level of injury. Bladder function, such as bladder volumes infused to the bladder until the first occurrence of neurogenic detrusor overactivity (V(ini)) and the last contraction suppressed by electrical stimulation (V(max)) was measured by water cystometry (CMG) and compared with the results of each subgroup. Among the 40 subjects, 35 patients showed neurogenic detrusor overactivity in the CMG study. Among these 35 patients, detrusor overactivity was suppressed effectively by pudendal nerve afferent electrical stimulation in 32 patients. The infusion volume until the occurrence of the first reflex contraction (V(ini)) was 99.4±80.3 ml. The volume of saline infused to the bladder until the last contraction suppressed by semiconditional pudendal nerve stimulation (V(max)) was 274.3±93.2 ml, which was significantly greater than V(ini). In patients with good response to the pudendal nerve afferent stimulation, the bladder volume significantly increased by stimulation in all the patients. In this study, semiconditional electrical stimulation on the dorsal penile afferent nerve could effectively inhibit neurogenic detrusor overactivity and increase bladder volume in patients with spinal cord injury.
Migaud, Martine; Butrille, Lucile; Batailler, Martine
To cope with variations in the environment, most mammalian species exhibit seasonal cycles in physiology and behaviour. Seasonal plasticity during the lifetime contributes to seasonal physiology. Over the years, our ideas regarding adult brain plasticity and, more specifically, hypothalamic plasticity have greatly evolved. Along with the two main neurogenic regions, namely the hippocampal subgranular and lateral ventricle subventricular zones, the hypothalamus, which is the central homeostatic regulator of numerous physiological functions that comprise sexual behaviours, feeding and metabolism, also hosts neurogenic niches. Both endogenous and exogenous factors, including the photoperiod, modulate the hypothalamic neurogenic capacities. The present review describes the effects of season on adult morphological plasticity and neurogenesis in seasonal species, for which the photoperiod is a master environmental cue for the successful programming of seasonal functions. In addition, the potential functional significance of adult neurogenesis in the mediation of the seasonal control of reproduction and feeding is discussed. Copyright © 2014 Elsevier Inc. All rights reserved.
Šedý, Jiří; Zicha, Josef; Kuneš, Jaroslav; Jendelová, Pavla; Syková, Eva
Roč. 58, č. 2 (2009), s. 269-277 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LC554; GA ČR GA309/06/1246 Grant - others:EC FP6 projekt RESCUE(FR) LSHB-CT-2005-518233; GA MZd(CZ) 1A8697; GA MZd(CZ) NR8339; GA MŠk(CZ) 1M0538; GA MŠk(CZ) 1M0510 Program:1M; 1M Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50110509 Keywords : neurogenic pulmonary edema * rat * spinal cord injury Subject RIV: FH - Neurology Impact factor: 1.430, year: 2009
Bekci, Tumay; Yucel, Serap; Turgut, Eser; Soylu, Aysegul Idil
Pelvic arteriovenous malformations (AVMs) are uncommon lesions and only a rare number of male cases have been reported. Their clinical presentations are variable and imaging modalities have an important place in diagnosis and treatment planning. We present the imaging findings of a giant congenital pelvic AVM that was diagnosed in a 30-year-old male patient eight years ago and which progressed despite follow-up and treatment, causing cardiac failure, diplegia, and neurogenic bladder. Pelvic AVMs are uncommon lesions and they can present with various symptoms based on their locations and sizes. Delays in the diagnosis and treatment can cause local and systemic complications. Imaging is very important in the diagnosis of pelvic AVM.
Starita, A; Majidi, D; Giordano, A; Battaglia, M; Cioni, R
Specialist tutors have to transfer two types of knowledge to doctors who are specialising in a particular clinic: public declarative knowledge, including facts, notions, principles in that particular field; and their own private procedural knowledge acquired in years of direct experience. Embodying this knowledge into an expert system means that this information can be shared more rapidly, and tutoring is easier. This paper presents a tutorial expert system for neurological clinics which can emulate the diagnostic process of an expert neurologist for neurogenic diseases of the lower limbs, assist users in planning the optimal sequence of NG and EMG tests, interpret the results of these tests, and help users to achieve the most suitable diagnosis.
Meseguer, Victor; Alpizar, Yeranddy A.; Luis, Enoch; Tajada, Sendoa; Denlinger, Bristol; Fajardo, Otto; Manenschijn, Jan-Albert; Fernández-Peña, Carlos; Talavera, Arturo; Kichko, Tatiana; Navia, Belén; Sánchez, Alicia; Señarís, Rosa; Reeh, Peter; Pérez-García, María Teresa; López-López, José Ramón; Voets, Thomas; Belmonte, Carlos; Talavera, Karel; Viana, Félix
Gram-negative bacterial infections are accompanied by inflammation and somatic or visceral pain. These symptoms are generally attributed to sensitization of nociceptors by inflammatory mediators released by immune cells. Nociceptor sensitization during inflammation occurs through activation of the Toll-like receptor 4 (TLR4) signalling pathway by lipopolysaccharide (LPS), a toxic by-product of bacterial lysis. Here we show that LPS exerts fast, membrane delimited, excitatory actions via TRPA1, a transient receptor potential cation channel that is critical for transducing environmental irritant stimuli into nociceptor activity. Moreover, we find that pain and acute vascular reactions, including neurogenic inflammation (CGRP release) caused by LPS are primarily dependent on TRPA1 channel activation in nociceptive sensory neurons, and develop independently of TLR4 activation. The identification of TRPA1 as a molecular determinant of direct LPS effects on nociceptors offers new insights into the pathogenesis of pain and neurovascular responses during bacterial infections and opens novel avenues for their treatment.
Furlan, Giacomo; Cuccioli, Valentina; Vuillemin, Nelly; Dirian, Lara; Muntasell, Anna Janue; Coolen, Marion; Dray, Nicolas; Bedu, Sébastien; Houart, Corinne; Beaurepaire, Emmanuel; Foucher, Isabelle; Bally-Cuif, Laure
Spatiotemporal variations of neurogenesis are thought to account for the evolution of brain shape. In the dorsal telencephalon (pallium) of vertebrates, it remains unresolved which ancestral neurogenesis mode prefigures the highly divergent cytoarchitectures that are seen in extant species. To gain insight into this question, we developed genetic tools to generate here the first 4-dimensional (3D + birthdating time) map of pallium construction in the adult teleost zebrafish. Using a Tet-On-based genetic birthdating strategy, we identify a "sequential stacking" construction mode where neurons derived from the zebrafish pallial germinal zone arrange in outside-in, age-related layers from a central core generated during embryogenesis. We obtained no evidence for overt radial or tangential neuronal migrations. Cre-lox-mediated tracing, which included following Brainbow clones, further demonstrates that this process is sustained by the persistent neurogenic activity of individual pallial neural stem cells (NSCs) from embryo to adult. Together, these data demonstrate that the spatiotemporal control of NSC activity is an important driver of the macroarchitecture of the zebrafish adult pallium. This simple mode of pallium construction shares distinct traits with pallial genesis in mammals and non-mammalian amniotes such as birds or reptiles, suggesting that it may exemplify the basal layout from which vertebrate pallial architectures were elaborated. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Opisso, E.; Borau, A.; Rijkhoff, N. J. M.
The goal of this study was to investigate whether real-time external urethral sphincter (EUS) EMG-controlled dorsal genital nerve (DGN) stimulation can suppress undesired detrusor bladder contractions in patients with both neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia (DSD). Detrusor pressure (Pdet) and EUS EMG were recorded in 12 neurogenic patients who underwent two filling cystometries. The first one was without stimulation and was intended to confirm the NDO and DSD and to set the EMG detection threshold. The second one was with real-time EMG-controlled stimulation of DGNs. Two detection methods were analyzed to detect bladder contractions. The first method was a Kurtosis-scaled root mean square (RMS) detector and was used on-line. The second was a simple RMS detector and was used off-line. Of 12 patients included, 10 patients showed both NDO and DSD. In nine of these ten patients relevant EMG concomitant to detrusor activity was detected and stimulation could suppress at least one detrusor contraction. The second filling compared to the first one showed an increase of 84% in bladder capacity (p = 0.002) and a decrease of 106% in Pdet (p = 0.002). Nine false-positive detections occurred during the ten fillings with electrical stimulation. The mean increases of both time and Pdet between stimulation and bladder contraction onsets for method 1 were 1.8 s and 4 cmH2O and for method 2 were 0.9 s and 2 cmH2O, respectively. This study shows that EUS EMG can be used in real time to detect the onset of a bladder contraction. In combination with DGN stimulation has been shown to be feasible to suppress undesired bladder contractions and in turn to increase bladder capacity in subjects with both NDO and DSD.
Manach, Q; Dommergues, M; Denys, P; Loiseau, K; Idiard-Chamois, B; Chartier-Kastler, E; Phé, V
Data are scarce regarding pregnancy and delivery among women with a neurogenic bladder due to congenital spinal cord defects. To report the obstetrical and urological outcomes of women with congenital spinal cord defects and vesico-sphincteric disorders. A retrospective multicentric study included all consecutive women with a neurogenic bladder due to congenital spinal defects, who delivered between January 2005 and December 2014. The following data were collected: demographics, neuro-urological disease characteristics, urological and obstetrical history, complications during pregnancy, neonatal outcomes, and changes in urological symptoms. Overall, sixteen women, median age 29,4 years old (IQR 22-36), had a total of 20 pregnancies and 21 births (15 caesareans, 5 vaginal deliveries). Prior to the beginning of their first pregnancy, 12 patients were under intermittent self-catheterization. Symptomatic urinary tract infections during pregnancy occurred in 11 pregnancies, including 4 pyelonephritis. In 4 women, stress urinary incontinence had worsened but recovered post-partum. In 3 women, de novo clean intermittent catheterization became necessary and had to be continued post-partum. During 3 pregnancies, anticholinergic treatment had been started or increased because of urge urinary incontinence worsened. These changes were maintained after delivery. The median gestational age at birth was 39.0 weeks (IQR 37.8-39.5). There were 15 caesarean sections, of which 9 were indicated to prevent a potential aggravation of vesico-sphincteric disorders. Among the 5 pregnancies with vaginal delivery, there was no post-partum alteration of the sphincter function. Successful pregnancy outcome is possible in women with congenital spinal cord defects and vesico-sphincteric disorders but it requires managing an increased risk of urinary tract infections, caesarean section, and occasionally worsened urinary incontinence. 5. Copyright © 2017 Elsevier Masson SAS. All
Alexander, Marcalee; Bashir, Khurram; Alexander, Craig; Marson, Lesley; Rosen, Raymond
To examine safety and efficacy of use of a clitoral vacuum suction device (CVSD) versus vibratory stimulation (V) to treat orgasmic dysfunction in women with MS or SCI. Randomized clinical trial. Two academic medical centers. Thirty-one women including 20 with MS and 11 with SCI. A 12-week trial of the use of a CVSD versus V MAIN OUTCOME MEASURES: Female Sexual Function Inventory (FSFI) and Female Sexual Distress Scale (FSDS). 23 women (18 MS; 5 SCI) completed the study including 13/16 randomized to CVSD and 10/15 randomized to V. There was a statistically significant increase in total FSFI score (p=.011), desire (p=. 009), arousal (p=.009), lubrication (p=.008), orgasm (p=.012), and satisfaction (p=.049) and a significant decrease in distress as measured by FSDS (p=.020) in subjects using the CVSD. In subjects who used V, there was a statistically significant increase in the orgasm subscale of the FSFI (p=.028). Subjects using the CVSD maintained improvements 4 weeks after treatment. CVSD is safe and overall efficacious to treat female neurogenic sexual dysfunction related to MS and SCI. V is also safe and efficacious to female neurogenic orgasmic dysfunction; however, results were limited to the active treatment period. Due to ease of access and cost, clinicians can consider use of V for women with MS or SCI with orgasmic dysfunction. CVSD is recommended for women with multiple sexual dysfunctions or for whom V is ineffective. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Nitta, Masahiro; Tamaki, Tetsuro; Tono, Kayoko; Okada, Yoshinori; Masuda, Maki; Akatsuka, Akira; Hoshi, Akio; Usui, Yukio; Terachi, Toshiro
BACKGROUND.: Postoperative neurogenic bladder dysfunction is a major complication of radical hysterectomy for cervical cancer and is mainly caused by unavoidable damage to the bladder branch of the pelvic plexus (BBPP) associated with colateral blood vessels. Thus, we attempted to reconstitute disrupted BBPP and blood vessels using skeletal muscle-derived multipotent stem cells that show synchronized reconstitution capacity of vascular, muscular, and peripheral nervous systems. METHODS.: Under pentobarbital anesthesia, intravesical pressure by electrical stimulation of BBPP was measured as bladder function. The distal portion of BBPP with blood vessels was then cut unilaterally (experimental neurogenic bladder model). Measurements were performed before, immediately after, and at 4 weeks after transplantation as functional recovery. Stem cells were obtained from the right soleus and gastrocnemius muscles after enzymatic digestion and cell sorting as CD34/45 (Sk-34) and CD34/45 (Sk-DN). Suspended cells were autografted around the damaged region, whereas medium alone and CD45 cells were transplanted as control groups. To determine the morphological contribution of the transplanted cells, stem cells obtained from green fluorescent protein transgenic mouse muscles were transplanted into a nude rat model and were examined by immunohistochemistry and immunoelectron microscopy. RESULTS.: At 4 weeks after surgery, the transplantation group showed significantly higher functional recovery ( approximately 80%) than the two controls ( approximately 28% and 24%). The transplanted cells showed an incorporation into the damaged peripheral nerves and blood vessels after differentiation into Schwann cells, perineurial cells, vascular smooth muscle cells, pericytes, and fibroblasts around the bladder. CONCLUSION.: Transplantation of multipotent Sk-34 and Sk-DN cells is potentially useful for the reconstitution of damaged BBPP.
Full Text Available Jürgen Pannek, Jens Wöllner Neuro-Urology, Swiss Paraplegic Center, Nottwil, Switzerland Introduction: 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. Diagnostics: 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. Treatment: 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. Prevention: 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. Conclusion: 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. Keywords: neurogenic lower urinary tract dysfunction, spinal cord injury, prophylaxis
Full Text Available The objective of this study was to assess the clinical outcome of vesicoureteral reflux (VUR after augmentation cystoplasty alone in patients with a hypocompliant neurogenic bladder. Between January 2009 and December 2014, 29 patients with a hypocompliant bladder associated with VUR confirmed by videourodynamics (VUD preoperatively were recruited in this study. All patients had undergone bladder augmentation with a generous detubularized segment of bowel at our institution. No effort had been made to correct the existing reflux. Preoperative assessment included urinalysis, kidney function tests, ultrasonography, and videourodynamic evaluation. All patients had various degrees of VUR. The status of VUR and bladder function were studied by VUD. The mean follow-up period was 2.2 years (range 0.5–5.5 years. The VUD manifested a significant improvement of bladder capacity, diminution of intravesical pressure, and resolution of reflux after bladder augmentation. After the surgery, 24/29 (83% no longer had reflux, 3/29 (10% showed improvement in reflux, and 2/29 (7% demonstrated no change in reflux. In addition, 16/21 (76% patients had reflux Grades I-III; 100% patients with reflux Grades IV and V had complete cessation of reflux. Only one patient had symptomatic urinary infection after the surgery. Augmentation enterocystoplasty without ureteral reimplantation is thus effective and adequate for patients with high-pressure and hypocompliant neurogenic bladder. Therefore, ureteral reimplantation is not necessary when augmentation enterocystoplasty is recommended for patients with high-pressure, low-compliant bladder and VUR.
Manintveld, Olivier C; te Lintel Hekkert, Maaike; Keijzer, Elisabeth; Verdouw, Pieter D; Duncker, Dirk J
Endogenous adenosine is a trigger for ischemic myocardial preconditioning (IPC). Although intravascular administration of adenosine has been used to further unravel the mechanism of protection by IPC, it is questionable whether adenosine and IPC employ the same signaling pathways to exert cardioprotection. We therefore investigated whether the active metabolic barrier of the endothelium prevents an increase in myocardial interstitial adenosine concentrations by intravenous adenosine, using microdialysis, and also the role of NO and activation of a neurogenic pathway in the cardioprotection by adenosine. In pentobarbital-anesthetized rats, area at risk and infarct size (IS) were determined 120 min after a 60-min coronary artery occlusion (CAO), using trypan blue and nitro-blue-tetrazolium staining, respectively. IPC with a single 15-min CAO and a 15-min adenosine infusion (ADO, 200 μg min−1 i.v.) limited IS to the same extent (IS=41±6% and IS=40±4%, respectively) compared to control rats (IS=63±3%, both P<0.05). However, IPC increased myocardial interstitial adenosine levels seven-fold from 4.3±0.7 to 27.1±10.0 μM (P<0.05), while ADO had no effect on interstitial adenosine (4.1±1.2 μM), or any of the other purines. The NO synthase inhibitor Nω-nitro-L-arginine (LNNA), which did not affect IS (IS=62±3%), attenuated the protection by ADO (IS=56±3%; P<0.05 vs ADO, P=NS vs LNNA). The ganglion blocker hexamethonium, which had also no effect on IS (IS=66±3%), blunted the protection by ADO (IS=55±4%; P<0.05 vs ADO and vs hexamethonium). These observations demonstrate that cardioprotection by ADO is dependent on NO, and is primarily mediated by activation of a neurogenic pathway. PMID:15895104
Abe, Takashige; Sazawa, Ataru; Harabayashi, Toru; Oishi, Yuichiro; Miyajima, Naoto; Tsuchiya, Kunihiko; Maruyama, Satoru; Okada, Hiromi; Shinohara, Nobuo
Due to variations in location and size, laparoscopic surgery for paraaortic or paracaval neurogenic tumors is challenging. We evaluated the surgical outcomes, as well as surgical tips and tricks. Between 2000 and 2015, 25 procedures were performed in 24 patients. One patient underwent second surgery due to the recurrence of paraganglioma. Data were collected on the tumor diameter, tumor location, perioperative outcomes, pathology, and last-known disease status. Regarding the operative procedures, we reviewed the operative charts or videos to identify surgical tips and tricks. The median tumor diameter was 5.0 cm (range 1.5-10). The tumor location was suprahilar in 10, hilar in 6, and infrahilar in 9 cases. Regarding the approach, a transperitoneal approach was selected in 24 cases and retroperitoneal approach in 1. The median operative time and blood loss were 208 min (range 73-513) and 10 mL (range 0-1020), respectively. No patient required blood transfusion or conversion to open surgery. Pathological examination revealed paraganglioma in 12, ganglioneuroma in 7, and schwannoma in 6 cases. At the last follow-up, 23 patients were free of disease, while one patient developed metastatic multiple recurrence of paraganglioma 54 months after the second laparoscopic surgery. A review of the surgical records revealed several tips and tricks, including taping the vena cava/renal vein (n = 2) being helpful for detaching a retrocaval tumor from these great vessels, or rotating the kidney to provide a favorable operative view of tumors behind the renal hilum (n = 2). In recent cases, 3D-CT was helpful for preoperative planning. Laparoscopic resection of paraaortic or paracaval neurogenic tumors is feasible in experienced hands. Surgeons should be familiar with detaching maneuvers around great vessels and the mobilization of adjacent organs. Careful preoperative planning is mandatory.
Linsenmeyer, Todd A.
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
Anandhan, Annadurai; Rodriguez-Rocha, Humberto; Bohovych, Iryna; Griggs, Amy M; Zavala-Flores, Laura; Reyes-Reyes, Elsa M; Seravalli, Javier; Stanciu, Lia A; Lee, Jaekwon; Rochet, Jean-Christophe; Khalimonchuk, Oleh; Franco, Rodrigo
Gene multiplications or point mutations in alpha (α)-synuclein are associated with familial and sporadic Parkinson's disease (PD). An increase in copper (Cu) levels has been reported in the cerebrospinal fluid and blood of PD patients, while occupational exposure to Cu has been suggested to augment the risk to develop PD. We aimed to elucidate the mechanisms by which α-synuclein and Cu regulate dopaminergic cell death. Short-term overexpression of wild type (WT) or mutant A53T α-synuclein had no toxic effect in human dopaminergic cells and primary midbrain cultures, but it exerted a synergistic effect on Cu-induced cell death. Cell death induced by Cu was potentiated by overexpression of the Cu transporter protein 1 (Ctr1) and depletion of intracellular glutathione (GSH) indicating that the toxic effects of Cu are linked to alterations in its intracellular homeostasis. Using the redox sensor roGFP, we demonstrated that Cu-induced oxidative stress was primarily localized in the cytosol and not in the mitochondria. However, α-synuclein overexpression had no effect on Cu-induced oxidative stress. WT or A53T α-synuclein overexpression exacerbated Cu toxicity in dopaminergic and yeast cells in the absence of α-synuclein aggregation. Cu increased autophagic flux and protein ubiquitination. Impairment of autophagy by overexpression of a dominant negative Atg5 form or inhibition of the ubiquitin/proteasome system (UPS) with MG132 enhanced Cu-induced cell death. However, only inhibition of the UPS stimulated the synergistic toxic effects of Cu and α-synuclein overexpression. Our results demonstrate that α-synuclein stimulates Cu toxicity in dopaminergic cells independent from its aggregation via modulation of protein degradation pathways. Copyright © 2014 Elsevier Inc. All rights reserved.
Kozaki, Ikko; Shimizu, Kazunori; Honda, Hiroyuki
Intracellular functional peptides that play a significant role inside cells have been receiving a lot of attention as regulators of cellular activity. Previously, we proposed a novel screening system for intracellular functional peptides; it combined a photo-cleavable peptide array system with cell-penetrating peptides (CPPs). Various peptides can be delivered into cells and intracellular functions of the peptides can be assayed by means of our system. The aim of the present study was to demonstrate that the proposed screening system can be used for assessing the intracellular activity of peptides. The cell death-inducing peptide (LNLISKLF) identified in a mitochondria-targeting domain (MTD) of the Noxa protein served as an original peptide sequence for screening of peptides with higher activity via modification of the peptide sequence. We obtained 4 peptides with higher activity, in which we substituted serine (S) at the fifth position with phenylalanine (F), valine (V), tryptophan (W), or tyrosine (Y). During analysis of the mechanism of action, the modified peptides induced an increase in intracellular calcium concentration, which was caused by the treatment with the original peptide. Higher capacity for cell death induction by the modified peptides may be caused by increased hydrophobicity or an increased number of aromatic residues. Thus, the present work suggests that the intracellular activity of peptides can be assessed using the proposed screening system. It could be used for identifying intracellular functional peptides with higher activity through comprehensive screening. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
Full Text Available BACKGROUND: Clear therapeutic guidelines for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP are missing due to the lack of randomized double-blind controlled clinical trials. Moderate yet similar clinical benefit has been demonstrated for IFN-α and high-dose ascorbic acid (AA monotherapy in a large open clinical trial. However, there is a lack of in vivo and in vitro studies exploring and comparing the effects of high-dose AA and IFN-α treatment in the context of HAM/TSP. Therefore, we performed the first comparative analysis of the ex vivo and in vitro molecular and cellular mechanisms of action of IFN-α and high-dose AA in HAM/TSP. PRINCIPAL FINDINGS: Through thymidine incorporation and quantification of Th1/Th2/Th17 cytokines, we demonstrate that high-dose AA displays differential and superior antiproliferative and immunomodulatory effects over IFN-α in HAM/TSP PBMCs ex vivo. In addition, high-dose AA, but not IFN-α, induced cell death in both HAM/TSP PBMCs and HTLV-1-infected T-cell lines MT-2 and MT-4. Microarray data combined with pathway analysis of MT-2 cells revealed AA-induced regulation of genes associated with cell death, including miR-155. Since miR-155 has recently been demonstrated to up-regulate IFN-γ, this microRNA might represent a novel therapeutic target in HAM/TSP, as recently demonstrated in multiple sclerosis, another neuroinflammatory disease. On the other hand, IFN-α selectively up-regulated antiviral and immune-related genes. CONCLUSIONS: In comparison to IFN-α, high-dose AA treatment has superior ex vivo and in vitro cell death-inducing, antiproliferative and immunomodulatory anti-HTLV-1 effects. Differential pathway activation by both drugs opens up avenues for targeted treatment in specific patient subsets.
Larsen, Annette Burkhart; Thomsen, Louiza Bohn; Moos, Torben
cells (BCECs) and their intermingling tight junctions. Polypeptides like brain derived neurotropic factor (BDNF), erythropoietin (EPO), and FGL peptide (part of Neuronal adhesion molecule (NCAM)) are acknowledged for their neuroprotective and neurogenerative effects. Generally, however...... has been to investigate the usage of BCEC as factories for recombinant protein production. A non-viral gene carrier was prepared from pullulan-spermine conjugated with plasmid DNA (Thomsen et al., 2011). In vitro transfection of Rat Brain Endothelial Cells (RBE4) and Human Brain Microvascular......, Moos T. Gene delivery by pullulan derivatives in brain capillary endothelial cells for protein secretion. J Control Release. 2011 Jan 18....
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...
Adami, Raffaella; Bottai, Daniele
The saying "mens sana in corpore sano" has a particular resonance these days because, for the majority who have a very sedentary occupation, the everyday rhythms of life do not compel us to do much physical exercise. Recently published data indicate that exercise can counteract the effects of neurological diseases such as Alzheimer's disease and have prompted research on the beneficial effects of movement on the brain and brain neurogenesis. This might lead us to hypothesize that the absence or reduction of movements, especially those with antigravity effects, could induce a deterioration of the brain. This Review discusses current knowledge of the relationship between neurogenic capacity and the lack of motor activity in human and animal models. © 2016 Wiley Periodicals, Inc.
W.A. Moojen (Wouter); M.P. Arts (Mark); R. Brand (René); B.W. Koes (Bart); W.C. Peul (Wilco)
textabstractAbstract. Background. Decompressive laminotomy is the standard surgical procedure in the treatment of patients with canal stenosis related intermittent neurogenic claudication. New techniques, such as interspinous process implants, claim a shorter hospital stay, less post-operative pain
Yang, Yang; Lin, Ye; Duan, Xiaoyu; Lv, He; Xing, Weinan; Li, Qingzhang; Gao, Xuejun; Hou, Xiaoming
Adequate lipid synthesis by the mammary gland during lactation is essential for the survival of mammalian offspring. Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) is a lipid droplet-associated protein and functions to promote lipid accumulation and inhibit lipolysis in mice and human adipocytes. However, the function of CIDEC in regulation of milk lipid synthesis in dairy cow mammary gland remains largely unknown. In this study, 6 multiparous Holstein cows (parity = 3) in early lactation were allocated to high-fat milk (milk yield 33.9 ± 2.1 kg/d, milk fat >3.5%, n = 3) and low-fat milk (milk yield 33.7 ± 0.5 kg/d, milk fat milk fat content. Lactating cows were slaughtered at 90 d in milk and mammary tissues were collected to detect CIDEC localization. Immunofluorescence staining of sections of lactating mammary glands with high- and low-fat milk showed that CIDEC was expressed in the cytoplasm of epithelial cells and localized to lipid droplets. Lipid droplets and CIDEC protein were also detected in isolated lactating mammary epithelial cells of dairy cows. Immunostaining of CIDEC in isolated mammary epithelial cells also confirmed its presence in the nucleus. The knockdown of CIDEC in cultured bovine mammary epithelial cells decreased milk lipid content and reduced expression of genes associated with mammary de novo fatty acid synthesis, short- and long-chain intracellular fatty acid activation, triacylglycerol synthesis, and transcription regulation. These genes included those for acetyl-CoA carboxylase (ACC, -60%), fatty acid synthase (FASN, -65%), acyl-CoA synthetase short-chain family member 2 (ACSS2, -50%), acyl-CoA synthetase long-chain family member 1 (ACSL1, -30%), diacylglycerol acyltransferase 1 (DGAT1, -60%), sterol regulatory element-binding protein 1 (SREBP1, -45%), and SREBP cleavage activating protein (SCAP, -66%). Conversely, in cells overexpressing CIDEC, triacylglycerol content was increased, and transcription of
Miyagawa, Hideo [Nagoya City Univ. (Japan). Medical School
The correlation in the title was evaluated since vagus nerve in the thoracic cavity had not been assessed by CT hitherto. For the purpose to examine the nerve imaging, subjects were a patient of neurofibromatosis and a normal volunteer. CT was done with Siemens Somato Plus 4 and General Electric-Yokokawa HiSpeed Advantage SG. For the same purpose, 100 cases of thoracic image by the latter apparatus were retrospectively assessed. Finally, the correlation in the title was examined retrospectively with combination of MR imaging in 9 cases who had undergone a surgery treatment of vagal neurogenic tumors (4 malignant and 4 benign cases of schwannoma and 1 neurofibromatosis). The nerve was found to be imaged by the ordinary CT and thus, which was thought to be useful for surgery, prognosis assessment and diagnosis of neurogenic tumors together with MRI. (K.H.)
Waleed Al Taweel
Full Text Available Aim: The aim of this study is to determine the current trends in the management and surveillance of the NB population secondary to spinal cord injury (SCI or myelomeningocele by certified urologist working in Saudi Arabia and to compare it to the current guidelines. Materials and Methods: A cross-sectional study was conducted using a 12-points questionnaire distributed to urologists working in Saudi Arabia and registered at the Saudi medical association. The assessment and follow-up of upper and lower urinary tract function in neurogenic bladder patients, their optimal frequency and management of related infections were the topics of inquiry. Results: Of the 272 urologists surveyed, 105 responded, yielding a response rate of 38%. Eighty-nine percent of respondents said that ultrasound was their diagnostic tool of choice for upper tract evaluation. Sixty-one percent of respondents said that they would follow their patients with a multichannel urodynamic study. Forty percent of urologists stated that they would treat asymptomatic bacteriuria. Clean intermittent catheterization (CIC was the most common modality chosen for the management of neurogenic bladder in patients with emptying difficulties. Conclusion: This study confirms that most urologists in Saudi Arabia involved with neurogenic bladder management. However, more than one third of the urologists do not have urodynamic machine and only two of the reporting practitioners has a videourodynamic machine. The results emphasize the need for clear guidelines in this field of urology in Saudi Arabia. Highly specialized rehabilitation centers for neurogenic bladder secondary to SCI are required for optimal care and urologist teaching.
Full Text Available Einleitung: Pharmakotherapie, der saubere Einmalkatheterismus (clean intermittent catheterization = CIC und die Infektionsprophylaxe sind die drei Säulen der konservativen Therapie bei Patienten mit neurogener Blasenfunktionsstörung. Während der Pubertät werden die Patienten zunehmend unabhängiger vom Elternhaus. Gleichzeitig nimmt jedoch die Compliance der Medikamenteneinnahme und der Durchführung des regelmäßigen CIC ab. Der orthopädische und/oder neurologische Status kann sich ebenfalls verändern. Dies kann letztlich zum Fehlschlagen der konservativen Therapie (Inkontinenz, Restharn, Verschlechterung der Funktion des oberen Harntraktes führen. In einem multidisziplinären Team wird diese Problematik der Kinder und Jugendlichen unter Berücksichtigung der Wünsche des Patienten als auch der medizinischen Ziele (z. B. Schutz der Nierenfunktion in unserer Klinik diskutiert. Die Harnableitung wurde hierbei in einigen Fällen als notwendige Kompromißlösung angesehen. In der vorliegenden retrospektiven Studie untersuchten wir, ob die Harnableitung auch langfristig ein sicheres Verfahren darstellt. Material und Methode: Zwischen 1967 und 1997 erfolgte bei 149 Kindern und Heranwachsenden die Anlage einer Harnableitung. 129 Patienten konnten durchschnittlich 11,8 Jahre (0,8-28,5 nachbeobachtet werden. Das durchschnittliche Alter bei der Operation betrug 12,1 Jahre (0,8-20. Ein Colon-Conduit wurde bei 59 Patienten (in der Mehrzahl der Fälle vor der Ära des CIC und der kontinenten Harnableitung angelegt, eine orthotope Blasensubstitution erfolgte bei 12, eine kontinente kutane Harnableitung bei 58 Patienten (50 % Rollstuhlfahrer. Ergebnisse: Der obere Harntrakt blieb bei 95-97 % der renoureteralen Einheiten (RUE stabil, bzw. verbesserte sich. Alle Patienten mit einer orthotopen Blasensubstitution sind tagsüber kontinent; eine Patientin benötigt zur Sicherheit zeitweise eine Vorlage während der Nacht. 7 der 12 Patienten führen einen
Full Text Available Jürgen Pannek, Franziska Rademacher, Jens Wöllner Neuro-Urology, Swiss Paraplegic Center, Nottwil, Switzerland Introduction: Screening for bladder cancer in patients with neurogenic lower urinary tract dysfunction is a challenge. Cystoscopy alone is not sufficient to detect bladder tumors in this patient group. We investigated the usefulness of combined cystoscopy and urine cytology.Materials and methods: By a systematic chart review, we identified all patients with neurogenic lower urinary tract dysfunction who underwent combined cystoscopy and urine cytology testing. In patients with suspicious findings either in cytology or cystoscopy, transurethral resection was performed.Results: Seventy-nine patients (age 54.8±14.3 years, 38 female, 41 male were identified; 44 of these used indwelling catheters. Cystoscopy was suspicious in 25 patients and cytology was suspicious in 17 patients. Histologically, no tumor was found in 15 patients and bladder cancer was found in 6 patients. Sensitivity for both cytology and cystoscopy was 83.3%; specificity was 43.7% for cytology and 31.2% for cystoscopy. One bladder tumor was missed by cytology and three tumors were missed by cystoscopy. If a biopsy was taken only if both findings were suspicious, four patients would have been spared the procedure, and one tumor would not have been diagnosed.Conclusion: A combination of cystoscopy and urine cytology can improve bladder tumor detection rates and lower the number of unnecessary biopsies. Keywords: bladder cancer, neurogenic lower urinary tract dysfunction, urine cytology, cystoscopy
Pannek, Jürgen; Göcking, Konrad; Bersch, Ulf
In a small subset of patients with neurogenic lower urinary tract dysfunction, insertion of suprapubic catheters (SPC) cannot be avoided. If SPC has to be utilized, catheter clamping and anticholinergic medication are often recommended, but evidence supporting this view is scarce. We determined the influence of anticholinergic medication and catheter clamping on urodynamic parameters and the status of the urinary tract in patients with chronic suprapubic catheterization. In a retrospective study, the results of urodynamic testing, sonographic evaluations, and urinalyses of 85 patients with chronic (>1 year) suprapubic catheterization due to neurogenic bladder dysfunction were analyzed. The 51 male and 34 female patients (mean age 55 years) were managed with an SPC for 65.3 ± 48.0 months. Forty patients had an SPC for more than 60 months. Comparing the results before SPC insertion with the last follow-up examination, no significant differences in detrusor compliance and maximum detrusor pressure were detected, whereas bladder capacity significantly decreased. In three patients, alterations of the upper urinary tract were found. The results were not significantly different between the patients using anticholinergic medication and/or catheter clamping and those who did not. According to our study, routine use of anticholinergic medication and clamping of catheter does not seem to be necessary to preserve detrusor compliance and renal function in patients with SPC and neurogenic bladder dysfunction.
Yaguchi, Shunsuke; Yaguchi, Junko; Inaba, Kazuo
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.
Full Text Available ... About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain Brain ... called the hypothalamic-pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life— ...
Ali, Amira A H; Schwarz-Herzke, Beryl; Stahr, Anna; Prozorovski, Timour; Aktas, Orhan; von Gall, Charlotte
Hippocampal neurogenesis undergoes dramatic age-related changes. Mice with targeted deletion of the clock geneBmal1 (Bmal1(-/-)) show disrupted regulation of reactive oxygen species homeostasis, accelerated aging, neurodegeneration and cognitive deficits. As proliferation of neuronal progenitor/precursor cells (NPCs) is enhanced in young Bmal1(-/-) mice, we tested the hypothesis that this results in premature aging of hippocampal neurogenic niche in adult Bmal1(-/-) mice as compared to wildtype littermates. We found significantly reduced pool of hippocampal NPCs, scattered distribution, enhanced survival of NPCs and an increased differentiation of NPCs into the astroglial lineage at the expense of the neuronal lineage. Immunoreaction of the redox sensitive histone deacetylase Sirtuine 1, peroxisomal membrane protein at 70 kDa and expression of the cell cycle inhibitor p21(Waf1/CIP1) were increased in adult Bmal1(-/-) mice. In conclusion, genetic disruption of the molecular clockwork leads to accelerated age-dependent decline in adult neurogenesis presumably as a consequence of oxidative stress.
Gutiérrez-Martín, P; Vírseda-Chamorro, M; Salinas Casado, J; Gómez-Rodríguez, A; Esteban-Fuertes, M
To determine the urodynamic efficacy and factors that influence the urodynamic results of treatment of neurogenic detrusor hyperactivity with intradetrusor injection of botulinum toxin type A (BTX-A) in patients with spinal cord injury (SCI). A retrospective study was conducted with a cohort of 70 patients composed of 40 men and 30 women with stable SCI (mean age, 39 ± 13.3 years) who underwent an intradetrusor injection of 300 IUs of BTX-A. A urodynamic study was conducted prior to the injection and 6 ± 4.3 months after the treatment. New urodynamic studies were subsequently performed up to an interval of 16 ± 12.2 months. The BTX-A significantly increased (p treatment and lesion age showed no influence in terms of the increase in bladder capacity. The indwelling urinary catheter (IUC) was the only statistically significant negative factor. The urodynamic effect of BTX-A is maintained for a considerable time interval. The IUC negatively influences the result of the treatment. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.
Miller, M J; Vergnolle, N; McKnight, W; Musah, R A; Davison, C A; Trentacosti, A M; Thompson, J H; Sandoval, M; Wallace, J L
This study was designed to determine if the Amazonian medicinal sangre de grado, confers benefit by suppressing the activation of sensory afferent nerves. (i) vasorelaxation of rat mesenteric arteries in response to calcitonin gene-related peptide; (ii) rat paw edema in response to protease- activating peptide receptor 2-activating peptide; (iii) rat paw hyperalgesia in response to low-dose protease-activating peptide receptor 2-activating peptide or prostaglandin E2; (iv) gastric hyperemia in response luminal capsaicin; (v) a clinical trial of a sangre de grado balm in pest control workers. The parent botanical was fractionated for evaluation of potential active components. In preconstricted rat mesenteric arteries, highly diluted sangre de grado (1:10,000) caused a shift to the right of the calcitonin gene-related peptide dose-response curve (p sangre de grado balm (1% concentration, p sangre de grado balm. A fraction possessing analgesic and capsaicin antagonistic properties was isolated and high-performance liquid chromatography and gas chromatography-mass spectrometry analysis indicated that it was a proanthocyandin oligomer. In pest control workers, sangre de grado balm (Zangrado) was preferred over placebo, for the relief of itching, pain, discomfort, edema, and redness in response to wasps, fire ants, mosquitoes, bees, cuts, abrasions, and plant reactions. Subjects reported relief within minutes. We conclude that sangre de grado is a potent inhibitor of sensory afferent nerve mechanisms and supports its ethnomedical use for disorders characterized by neurogenic inflammation.
Claeys, Kristl G; Abicht, Angela; Häusler, Martin; Kleinle, Stephanie; Wiesmann, Martin; Schulz, Jörg B; Horvath, Rita; Weis, Joachim
Neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) is caused by m.8993T>G/C mutations in the mitochondrial adenosine triphosphate synthase subunit 6 gene (MT-ATP6). Traditionally, heteroplasmy levels between 70% and 90% lead to NARP, and >90% result in Leigh syndrome. In this study we report a 30-year-old man with NARP and m.8993T>G in MT-ATP6. Although the patient carried the mutation in homoplasmic state in blood with similarly high levels in urine (94%) and buccal swab (92%), he presented with NARP and not the expected, more severe Leigh phenotype. The mutation could not be detected in any of the 3 analyzed tissues of the mother, indicating a large genetic shift between mother and offspring. Nerve biopsy revealed peculiar endoneurial Schwann cell nuclear accumulations, clusters of concentrically arranged Schwann cells devoid of myelinated axons, and degenerated mitochondria. We emphasize the phenotypic variability of the m.8993T>G MT-ATP6 mutation and the need for caution in predictive counseling in such patients. Muscle Nerve 54: 328-333, 2016. © 2016 Wiley Periodicals, Inc.
Sebbag, Lionel; Pesavento, Patricia A; Carrasco, Sebastian E; Reilly, Christopher M; Maggs, David J
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.
Tyler, Christina R.; Solomon, Benjamin R.; Ulibarri, Adam L.; Allan, Andrea M.
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
Malandraki, Georgia A; Rajappa, Akila; Kantarcigil, Cagla; Wagner, Elise; Ivey, Chandra; Youse, Kathleen
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 (PDysphagia Rehabilitation approach was safe and improved physiological and some functional swallowing outcomes in our sample; however, further investigation is needed before it can be widely applied. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Full Text Available 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.
Full Text Available Background: Neurogenic stuttering (NS is the most frequently occurring acquired form of stuttering in children and adults. This form of stuttering is primarily caused by neurological incidents. Owing to controversies with regard to similarities between developmental stuttering (DS and NS symptomatology, differential diagnosis is problematic. Differential diagnosis will guide the appropriate management of persons who stutter (PWS.Objectives: The aim of this study was to describe and highlight the characteristics of NS in order to compile a preliminary checklist for accurate diagnosis and intervention.Method: An explorative, applied mixed method, multiple case study research design was followed. Purposive sampling was used to select four participants. A comprehensive assessment battery was compiled for data collection.Results: The results revealed a distinct pattern of core stuttering behaviours in NS, although discrepancies existed regarding stuttering severity and frequency. It was also found that DS and NS can co-occur. The case history and the core stuttering pattern are important considerations during differential diagnosis, as these are the only consistent characteristics in people with NS.Conclusion: It is unlikely that all the symptoms of NS are present in an individual. The researchers scrutinised the findings of this study and the findings of previous literature to compile a potentially workable checklist.
Pannek, Jürgen; Wöllner, Jens
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.
Lundie, Mariska; Erasmus, Zandria; Zsilavecz, Ursula; Van der Linde, Jeannie
Neurogenic stuttering (NS) is the most frequently occurring acquired form of stuttering in children and adults. This form of stuttering is primarily caused by neurological incidents. Owing to controversies with regard to similarities between developmental stuttering (DS) and NS symptomatology, differential diagnosis is problematic. Differential diagnosis will guide the appropriate management of persons who stutter (PWS). The aim of this study was to describe and highlight the characteristics of NS in order to compile a preliminary checklist for accurate diagnosis and intervention. An explorative, applied mixed method, multiple case study research design was followed. Purposive sampling was used to select four participants. A comprehensive assessment battery was compiled for data collection. The results revealed a distinct pattern of core stuttering behaviours in NS, although discrepancies existed regarding stuttering severity and frequency. It was also found that DS and NS can co-occur. The case history and the core stuttering pattern are important considerations during differential diagnosis, as these are the only consistent characteristics in people with NS. It is unlikely that all the symptoms of NS are present in an individual. The researchers scrutinised the findings of this study and the findings of previous literature to compile a potentially workable checklist.
Opisso, Eloy; Borau, Albert; Rijkhoff, Nico J M
To investigate the effects of subject controlled dorsal genital nerve (DGN) electrical stimulation on neurogenic detrusor overactivity (NDO) in subjects at home. Subjects underwent a 5-day study at home with DGN stimulation. Stimulation was provided with surface electrodes placed either on the dorsal penile shaft in males and on or close to the clitoris in females. The days 1 and 5 were with no stimulation whereas days 2-4 were with stimulation. Two urodynamic studies were performed at the beginning and at the end of the study. A bladder diary was obtained. Eleven subjects with NDO and with urge incontinence were included. One subject stopped the protocol before the end of the 5-day trial and two did not undergo the second urodynamic study. The subjects showed a statistically significant increase in bladder capacities compared to baseline (P = 0.047). Mean volume per day voided significantly increased over the study within the subjects. Differences between day 1 and day 5 were statistically significant (P = 0.028). The feasibility and the globally positive outcomes of the study indicate that the stimulation of the dorsal genital nerve can be an option for the treatment of the NDO. Copyright © 2012 Wiley Periodicals, Inc.
Fjorback, M V; Van Rey, F S; Rijkhoff, N J M; Nøhr, M; Petersen, T; Heesakkers, J P
Transcutaneous electrical stimulation of the dorsal penile/clitoral nerve (DPN) has been shown to suppress detrusor contractions in patients with neurogenic detrusor overactivity (NDO). However, the long-term use of surface electrodes in the genital region may not be well tolerated and may introduce hygienic challenges. The aim of this study was to assess whether electrical stimulation of the sacral dermatomes could suppress detrusor contractions in multiple sclerosis (MS) patients with NDO, hereby providing an alternative to DPN stimulation. A total of 14 MS patients (8 M, 6 F) with low bladder capacity (stimulation was applied. In the second and third filling electrical stimulation of either the DPN or sacral dermatomes was applied automatically whenever the detrusor pressure exceeded 10 cmH2O. The control filling showed detrusor overactivity in 12 of the 14 patients. In 10 of the 12 patients one or more detrusor contractions could be suppressed with DPN stimulation. Electrical stimulation of the sacral dermatomes failed to suppress detrusor contractions in all patients. Although therapeutic effects may be present from stimulation of the sacral dermatomes, we were unable to demonstrate any acute effects during urodynamics. For this reason stimulation of the sacral dermatomes is not an option in a system that relies on the acute suppression of a detrusor contraction. Copyright (c) 2007 Wiley-Liss, Inc.
Hansen, J; Media, S; Nøhr, M; Biering-Sørensen, F; Sinkjaer, T; Rijkhoff, N J M
The feasibility of automatic event driven electrical stimulation of the dorsal penile/clitoral nerve in the treatment of neurogenic detrusor overactivity (NDO) was evaluated in individuals with spinal cord injury. The study included 2 women and 14 men older than 18 years with NDO, bladder capacity below 500 ml and complete or incomplete suprasacral spinal cord injury. Detrusor pressure (Pdet) was recorded during ordinary, natural bladder filling. In a similar subsequent recording Pdet was used to trigger electrical stimulation when pressure exceeded 10 cm H2O. Of the 16 patients enrolled in this study 13 had increased bladder capacity together with a storage pressure decrease as a result of automatic, event driven electrical stimulation. In 2 patients stimulation could not inhibit the first undesired contraction, leakage occurred and finally 1 could not tolerate stimulation. During stimulated filling Pdet never exceeded 55 cm H2O. Thus, storage pressure was sufficiently low to prevent kidney damage. An average bladder capacity increase of 53% was achieved. This study demonstrates the feasibility of automatic, event driven electrical stimulation in the treatment of NDO. Although the setup in this experiment is not suitable in a clinical setting, the treatment modality is promising and it warrants further investigation.
Castilla-Ortega, Estela; Ladrón de Guevara-Miranda, David; Blanco, Eduardo; Serrano, Antonia; Pedraz, María; Estivill-Torrús, Guillermo; Pavón, Francisco; Rodriguez de Fonseca, Fernando; Santín, Luis Javier
Recently, adult hippocampal neurogenesis has been proposed as a putative neuroplastic mechanism involved in those behavioural processes. In this work, we studied the effect of the inhibition of adult hippocampal neurogenesis using the DNA alkylating agent temozolomide (TMZ), in cocaine-induced conditioned place preference (CPP) behaviour. In a first experiment, we investigated both CPP acquisition/expression and the functional brain circuits underlying CPP expression in control and neurogenes...
Sun, Wei; Cornwell, Adam; Li, Jiashu
is also expressed by neural progenitor cells. Transcriptome comparisons of SOX9 cells with GLT1 cells showed that the two populations of cells exhibit largely overlapping gene expression. Expression of SOX9 did not decrease during aging and was instead upregulated by reactive astrocytes in a number...
Simons, Andre; Hamdy, Shaheen
Dysphagia is common sequela of brain injury with as many as 50% of patients suffering from dysphagia following stroke. Currently, the majority of guidelines for clinical practice in the management of dysphagia focus on the prevention of complications while any natural recovery takes place. Recently, however, non-invasive brain stimulation (NIBS) techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have started to attract attention and are applied to investigate both the physiology of swallowing and influences on dysphagia. TMS allows for painless stimulation of the brain through an intact skull-an effect which would normally be impossible with electrical currents due to the high resistance of the skull. By comparison, tDCS involves passing a small electric current (usually under 2 mA) produced by a current generator over the scalp and cranium external to the brain. Initial studies used these techniques to better understand the physiological mechanisms of swallowing in healthy subjects. More recently, a number of studies have investigated the efficacy of these techniques in the management of neurogenic dysphagia with mixed results. Controversy still exists as to which site, strength and duration of stimulation yields the greatest improvement in dysphagia. And while multiple studies have suggested promising effects of NIBS, more randomised control trials with larger sample sizes are needed to investigate the short- and long-term effects of NIBS in neurogenic dysphagia.
Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics provides information on how the brain works, how mental illnesses ...
... Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...
Full Text Available ... Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...
Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... learning more about how the brain grows and works in healthy people, and how normal brain development ...
Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin
numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether......Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation...
Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin
Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation...
Salga, Marjorie [Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Physical Medicine and Rehabilitation, Garches (France); Jourdan, Claire [Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Physical Medicine and Rehabilitation, Garches (France); Universite de Versailles Saint Quentin en Yvelines, Handi-Resp, (EA4047), Versailles (France); Durand, Marie-Christine [Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Neurophysiology, Garches (France); Universite de Versailles Saint Quentin en Yvelines, Groupement de Recherche Clinique et Technologique sur le Handicap (GRCTH, EA 4497), Versailles (France); Hangard, Chloe; Carlier, Robert-Yves [Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Medical Imaging, Garches (France); Denormandie, Philippe [Universite de Versailles Saint Quentin en Yvelines, Groupement de Recherche Clinique et Technologique sur le Handicap (GRCTH, EA 4497), Versailles (France); Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Orthopaedic Surgery, Garches (France); Genet, Francois [Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Physical Medicine and Rehabilitation, Garches (France); Universite de Versailles Saint Quentin en Yvelines, Groupement de Recherche Clinique et Technologique sur le Handicap (GRCTH, EA 4497), Versailles (France); Military Medical Service, Hopital d' Instruction des Armees Percy, Department of Physical Medicine and Rehabilitation, Clamart (France)
To describe the characteristics of neurogenic heterotopic ossification (NHO) based on clinical tests, electroneuromyography (ENMG) and CT in a database of patients with lesions of the central nervous system who required sciatic nerve neurolysis along with posterior hip NHO resection, and to determine the respective roles of ENMG and CT in the management of posterior hip NHOs in patients who are unable to communicate or express pain. The consistency of the ENMG results with clinical findings, CT results and macroscopic signs of lesions was retrospectively assessed after sciatic nerve neurolysis and ablation of 55 posterior hip NHOs. Sciatic nerve neurolysis was necessary in 55 cases (47.4 %; 55 out of 116). CT showed contact of the NHO with the nerve in all cases: 5 in contact with no deflection, 3 in contact with deflection, 21 moulded into a gutter and 26 entrapped in the NHO. There were clinical signs of sciatic nerve lesion in 21.8 % of cases (12 out of 55). ENMG showed signs of sciatic nerve lesions in only 55.6 % (10 out of 18), only 4 of whom presented with clinical signs of a nerve lesion. No significant relationship was found between clinical symptoms and ENMG findings of sciatic nerve compression (n = 13, p = 0.77). Nerve compression by NHO is likely an underdiagnosed condition, particularly in patients who are unable to communicate. Diagnosis of sciatic compression by NHO should be based on regular clinical examinations and CT. ENMG is not sufficiently sensitive to be used alone for surgical decision-making. (orig.)
Sanders, C; Bray, L; Driver, C; Harris, V
Neurogenic bowel dysfunction in children is a lifelong condition often resulting in the need for active bowel management programmes, such as transanal irrigation. Parents are central in the decision-making process to initiate and carry out treatments until such a time their child becomes independent. Minimal research has focussed on examining parents' experiences of undertaking transanal irrigation with their child. This study aimed to explore parents' experiences of learning about and using irrigation with their child and how parents motivated their children to become independent. Semi-structured telephone interviews were conducted with parents with experience of using transanal irrigation with their child. Interviews were undertaken by a parent researcher. Data were analysed using qualitative content analysis. Eighteen telephone interviews (16 mothers, 1 father and 1 carer) were conducted. Parents shared how they had negotiated getting started and using transanal irrigation with their child. They discussed a sense of success derived from their confidence in using and mastering irrigation, the process of making decisions to continue or stop using irrigation and how they motivated themselves and their child to continue with the irrigation regime. Challenges included minimizing their child's distress during the irrigation procedure and how they negotiated and moved towards their child becoming independent. Despite the emotional difficulty parents experienced as a result of the invasive nature of transanal irrigation most parents reported an improvement in their child's faecal continence which positively impacted on the child and family's lives. The child's physical ability and emotional readiness to develop independent irrigation skills in the future concerned some parents. The experiences shared by parents in this study has the capacity to inform transanal irrigation nursing and medical care. © 2013 John Wiley & Sons Ltd.
Full Text Available 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.
Aydogdu, Ibrahim; Kiylioglu, Nefati; Tarlaci, Sultan; Tanriverdi, Zeynep; Alpaydin, Sezin; Acarer, Ahmet; Baysal, Leyla; Arpaci, Esra; Yuceyar, Nur; Secil, Yaprak; Ozdemirkiran, Tolga; Ertekin, Cumhur
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, pdysphagia 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.
Herbst, C; Tippler, B; Shams, H; Simmet, T
1. The possible contribution of endogenous endothelin (ET) to the pathogenesis of seizure-associated pulmonary oedema was examined in mechanically ventilated rats after intravenous bolus injection of the gamma-aminobutyric acid (GABA) antagonist, bicuculline (1.2 mg kg-1). 2. Recurrent seizure activity elicited by bicuculline injection led to rapidly developing pulmonary oedema. Within 4 min after bicuculline application (1.2 mg kg-1), arterial O2 partial pressure (PaO2) significantly dropped from 17.49 +/- 1.20 kPa to 7.51 +/- 2.21 kPa (P 0.05) after phosphoramidon pretreatment. In contrast, vehicle-treated animals that received bicuculline showed both significant hypercapnia as well as profound hypoxia. Phosphoramidon significantly diminished the maximum increase in Paw by 76.7 +/- 12.4% (P 0.05) in BQ-123-treated animals. In contrast, vehicle-treated animals that received bicuculline exhibited significant hypercapnia as well as profound hypoxia. BQ-123 significantly reduced the increase in Paw by 51.3 +/- 12.8% (P < 0.01). It affected MABP only slightly and had no effect on the acidosis.6. These results suggest that ET peptides play a significant role in this model of neurogenic pulmonary oedema and may act as mediators of respiratory distress. The deleterious effects of endogenous ET in this model are primarily mediated via the ETA receptor, for they were inhibited by the ETA receptor antagonist, BQ-123. ETA receptor antagonists may therefore be of potential therapeutic value in respiratory distress.
Full Text Available Stuart H Isaacson, Julia Skettini Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA Abstract: 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. Keywords: (presyncope, norepinephrine, autonomic, lightheadedness, treatment, falls
Zhang, Wei; Jiao, Lin; Xiong, Jun
To observe the effect of suspending-moxibustion stimulation of "Dazhui" (GV 14) with different quantities on the levels of nerve growth factor(NGF) , substance P(SP) , calcitonin gene-related peptide (CGRP), neurokinin A (NKA) , neurokinin B (NKB) and phosphorylated extracellular signal-regulated kinases (pERK) in the bronchoalveolar lavage fluid (BALF) of asthma rats, so as to analyze its mechanisms underlying improving asthma. Sixty male SD rats were randomly divided into six groups: blank control, model, 15 min-moxibustion (15 min-moxi), 30 min-moxi, 60 min-moxi and 90 min-moxi (n = 10 rats in each group). The asthma model was established by intraperitoneal injection of suspension of egg protein, magaldrate, and inactivated Bacillus pertussis (on day 1 and 8), and inhaling the atomized ovalbumin saline (from day 15 on for 14 days). Mild moxibustion was conducted at "Dazhui" (GV 14) for 15 min, 30 min, 60 min and 90 min, respectively, once daily for 7 days. The levels of NGF, SP, CGRP, NKA, NKB, and pERK in the BALF were detected by ELISA (enzyme-linked immuno sorbent assay). The contents of NGF, SP, CGRP, NKA, NKB and pERK in the BALF in the model group were obviously higher than those in the blank control group (P 0.05). Suspending-moxibustion stimulation of GV 14 can down-regulate the contents of NGF, SP, CGRP, NKA, NKB, and pERK levels in the BALF in asthma rats, suggesting a relief of neurogenic inflammation reaction after moxibustion. The effect of moxibustion presents a time-dependant manner and peaks at 60 min.
Cristiano M. Gomes
Full Text Available PURPOSE: To report our experience with the use of the botulinum toxin-A (BoNT/A formulations Botox® and Prosigne® in the treatment of neurogenic detrusor overactivity (NDO. MATERIALS AND METHODS: At a single institution, 45 consecutive patients with refractory urinary incontinence due to NDO received a single intradetrusor (excluding the trigone treatment with botulinum toxin type A 200 or 300 units. Botox was used for the first 22 patients, and Prosigne for the subsequent 23 patients. Evaluations at baseline and week 12 included assessment of continence and urodynamics. Safety evaluations included monitoring of vital signs, hematuria during the procedure, hospital stay, and spontaneous adverse event reports. RESULTS: A total of 42 patients were evaluated (74% male; mean age, 34.8 years. Significant improvements from baseline in maximum cystometric capacity (MCC, maximum detrusor pressure during bladder contraction, and compliance were observed in both groups (P < 0.05. Improvement in MCC was significantly greater with Botox versus Prosigne (+103.3% vs. +42.2%; P = 0.019. Continence was achieved by week 12 in 16 Botox recipients (76.2% and 10 Prosigne recipients (47.6%; P = 0.057. No severe adverse events were observed. Mild adverse events included 2 cases of transient hematuria on the first postoperative day (no specific treatment required, and 3 cases of afebrile urinary tract infection. CONCLUSIONS: Botox and Prosigne produce distinct effects in patients with NDO, with a greater increase in MCC with Botox. Further evaluation will be required to assess differences between these formulations.
Krebs, J; Wöllner, J; Pannek, J
Retrospective investigation. To investigate the association of patient and injury characteristics, as well as bladder management, with the occurrence of patient-reported, symptomatic urinary tract infection(s) UTI(s) in patients with chronic neurogenic lower urinary tract dysfunction (NLUTD). Tertiary urologic referral center. The patient database was screened for patients with chronic (>12 months) NLUTD who had presented between 2008 and 2012. Patient characteristics, bladder evacuation management, the annual number of patient-reported, symptomatic UTIs and the type of prophylactic treatment to prevent UTIs were collected. Binary logistic regression analysis was used to investigate the effects of the investigated risk factors on the occurrence of symptomatic UTI(s) and recurrent symptomatic UTIs (⩾3 annual UTIs). The data of 1104 patients with a mean NLTUD duration of 20.3±11.6 years were investigated. The evacuation method was a significant (P⩽0.004) predictor for the occurrence of symptomatic UTI and recurrent symptomatic UTIs. The greatest annual number of symptomatic UTIs was observed in patients using transurethral indwelling catheters, and the odds of experiencing a UTI and recurrent UTIs were increased more than 10- and 4-fold, respectively. The odds of a UTI or recurrent UTIs were also increased significantly (P⩽0.014) in patients using intermittent catheterization (IC). Botulinum toxin injections into the detrusor increased the odds of a UTI ~10-fold (P=0.03). The bladder evacuation method is the main predictor for symptomatic UTIs in individuals with NLUTD. Transurethral catheters showed the highest odds of symptomatic UTI and should be avoided whenever possible.
Krebs, J; Wöllner, J; Pannek, J
Retrospective investigation. To investigate the association of patient and injury characteristics with bladder evacuation by indwelling catheterization in patients with chronic neurogenic lower urinary tract dysfunction (NLUTD). Tertiary urologic referral center. The patient database was screened for patients with chronic (>12 months) NLUTD. Patient characteristics and bladder management details were collected. Binary logistic regression analysis was used to investigate the effects of the investigated factors on bladder evacuation by indwelling catheterization. The data of 1263 patients with a median age of 47 years (range 11-89 years) and a median NLTUD duration of 15.2 years (range 1.0-63.4 years) were investigated. The most common bladder evacuation method was intermittent catheterization (IC; 41.3%) followed by triggered reflex voiding (25.7%), suprapubic catheterization (11.8%), sacral anterior root stimulation (7.3%), spontaneous voiding (7.0%), abdominal straining (5.7%) and transurethral catheterization (1.3%). Female gender, tetraplegia, an age older than 45 years and injury duration were significant (<0.001) predictors of indwelling catheterization. The odds of bladder evacuation by indwelling catheterization were increased ~2.5, 3 and 4 times in women, patients older than 45 years and tetraplegics, respectively. IC is the most common bladder evacuation method. However, the majority of individuals with NLUTD are using other evacuation methods, because factors such as functional deficiencies, mental impairment or the social situation are relevant for choosing a bladder evacuation method. Individuals at risk of indwelling catheterization can be identified based on female gender, age, injury severity and injury duration.
Full Text Available PURPOSE: Neurogenic detrusor overactivity (NDO is common in patients who suffer from multiple sclerosis (MS. When the usual pharmacological treatment fails, botulinum toxin type A (BTX-A injections can be proposed. The safety and efficacy of this treatment are already well known, but only a few studies focus on its use in patients with MS. MATERIALS AND METHODS: Seventy-one patients with MS underwent their first BTX-A injection for refractory NDO. They had clinical and urodynamic cystometry assessment before and three months after injection. The patients were divided in three groups according to treatment efficacy: full success (total urinary continence, no overactive detrusor, improvement, or total failure (urge incontinence and overactive detrusor. RESULTS: 77% of the patients had clinical improvement or full success of the treatment with a reduction of their urgency and incontinence. Significant urodynamic improvement after treatment was shown on different parameters: volume at first involuntary bladder contraction (p = 0.0000001, maximum cystometric capacity (p = 0.0035, maximum detrusor pressure (p = 0.0000001. 46% of the patients were in the "full success" group. 31% of the patients had a partial improvement. 23% of the patients had no efficacy of the treatment. Duration of MS was a predictive factor of treatment failure (p = 0.015. CONCLUSIONS: Despite that a full success was obtained in 46% of the cases, BTX-A injection therapy failed to treat refractory NDO in 23% of patients suffering from MS. Duration of the disease was a predictive factor for an inefficient treatment. The injection therapy should be considered as soon as oral anticholinergic drugs fail to reduce NDO.
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.
Yun, M. J.; Go, D. H.; Yoo, Y. H.; Shin, K. H.; Lee, J. D [College of Medicine, Yonsei University, Seoul (Korea, Republic of)
The differentiation between benign and malignant nerve sheath tumors is difficult based on conventional radiological imaging. This study was undertaken to investigate the value of FDG PET in distinguishing benign from malignant neurogenic tumors of nerve sheath origin. We performed a retrospective review of the medical record to select patients with nerve sheath tumors who had underdone FDG PET imaging. Fifteen patients (7F: 8M) with benign or malignant nerve sheath tumors were included in this study. Of the 15 patients, 9 were diagnosed with the known neurofibromatosis type I. A total of 19 nerve sheath tumors were included from the 15 patients. All patients had undergone FDG PET to evaluate for malignant potential of the known lesions. Images of FDG PET were semi-quantitatively analyzed and a region of interest (ROI) was placed over the area of the maximum FDG uptake and an average standardized uptake value was taken for final analysis. There were 5 malignant peripheral nerve sheath tumors, 5 schwannomas, and 9 neurofibromas. The mean SUV was 2 (ranged from 1.6 to 3.3) for schwannomas, 1.3 (0.7 to 2.5) for neurofibromas, and 8.4 (4.6 to 12.2) for malignant peripheral nerve sheath tumors. Of 14 benign tumors, all except one schwannoma showed a SUV less than 3. When a cutoff SUV of 4 was used to differentiate the nerve sheath tumors, all tumors were correctly classified as benign or malignant, respectively. Among the 9 patients diagnosed with neurofibromatosis type I. 4 had malignant peripheral nerve sheath tumors and FDG PET accurately detected all the 4 lesions with malignant transformation. According to our results, FDG PET seems to have a great potential for accurately characterizing benign versus malignant nerve sheath tumors. It appears to be extremely useful for patients with neurofibromatosis to localize the lesion with malignant transformation.
Full Text Available 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.
Utomo, Elaine; Groen, Jan; Blok, Bertil F M
The most common type of functional bladder outlet obstruction in patients with neurogenic bladder is detrusor-sphincter dyssynergia (DSD). The lack of co-ordination between the bladder and the external urethral sphincter muscle (EUS) in DSD can result in poor bladder emptying and high bladder pressures, which may eventually lead to progressive renal damage. To assess the effectiveness of different surgical therapies for the treatment of functional bladder outlet obstruction (i.e. DSD) in adults with neurogenic bladder dysfunction. We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, and handsearching of journals and conference proceedings (searched 20 February 2014), and the reference lists of relevant articles. Randomised controlled trials (RCTs) or quasi-RCTs comparing a surgical treatment of DSD in adults suffering from neurogenic bladder dysfunction, with no treatment, placebo, non-surgical treatment, or other surgical treatment, alone or in combination. Two review authors independently assessed trial quality and extracted data. We included five trials (total of 199 participants, average age of 40 years). The neurological diseases causing DSD were traumatic spinal cord injury (SCI), multiple sclerosis (MS), or congenital malformations.One trial compared placement of sphincteric stent prosthesis with sphincterotomy. For urodynamic measurements, results for postvoid residual urine volume (PVR) and cystometric bladder capacity were inconclusive and consistent with benefit of either sphincteric stent prosthesis or sphincterotomy at three, six, 12, and 24 months. Results for maximum detrusor pressure (Pdet.max) were also inconclusive at three, six, and 12 months; however, after two years, the Pdet.max after sphincterotomy was lower than after stent placement (mean difference (MD) -30 cmH2O, 95% confidence interval (CI) 8.99 to
Desai, Mina; Han, Guang; Ross, Michael G
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.
Pannek, Jürgen; Göcking, Konrad; Bersch, Ulf
To evaluate the influence of repeated botulinum neurotoxin A (BoNT-A) treatments on detrusor function in patients with neurogenic detrusor overactivity (DOA) due to spinal cord lesions. In a retrospective study, urodynamic evaluations of 27 consecutive patients with neurogenic DOA due to spinal cord lesions who received at least five BoNT-A treatments were analysed. After the first BoNT-A treatment, bladder capacity, reflex volume, continence status and detrusor compliance were significantly improved and maximum detrusor pressure (P(detmax)) was significantly reduced. The mean number of BoNT-A treatments was 7.1. Compared with the results of the first treatment, the incontinence rate (seven patients) and the number of patients with an elevated P(detmax) (five patients) were slightly increased after the final BoNT-A treatment. The long-term success rate was 74%. Every fourth patient needed a major surgical intervention. There was a significant decrease in P(detmax) before BoNT-A treatments, indicating that detrusor contraction strength did not completely recover after treatment. Our study confirmed the long-term efficacy of repeated BoNT-A treatments in patients with neurogenic DOA. However, in long-term follow-up, every fourth patient required surgical interventions. Moreover, our data give the first hint that BoNT-A may lead to impaired detrusor contraction strength, which could influence future treatment options. Prospective studies are necessary to elucidate the impact of repeated BoNT-A treatments on detrusor function and the interactions with future treatment options.
Barbara S. Beltz
Full Text Available New neurons continue to be born and integrated into the brains of adult decapod crustaceans. Evidence in crayfish indicates that the 1st-generation neural precursors that generate these adult-born neurons originate in the immune system and travel to the neurogenic niche via the circulatory system. These precursors are attracted to the niche, become integrated amongst niche cells, and undergo mitosis within a few days; both daughters of this division migrate away from the niche toward the brain clusters where they will divide again and differentiate into neurons. In the crustacean brain, the rate of neuronal production is highly sensitive to serotonin (5-hydroxytryptamine, 5-HT levels. These effects are lineage-dependent, as serotonin's influence is limited to late 2nd-generation neural precursors and their progeny. Experiments indicate that serotonin regulates adult neurogenesis in the crustacean brain by multiple mechanisms: via direct effects of serotonin released from brain neurons into the hemolymph or by local release onto target cells, or by indirect influences via a serotonin-mediated release of agents from other regions, such as hormones from the sinus gland and cytokines from hematopoietic tissues. Evidence in crayfish also indicates that serotonin mediates the attraction of neural precursors generated by the immune system to the neurogenic niche. Thus, studies in the crustacean brain have revealed multiple roles for this monoamine in adult neurogenesis, and identified several pathways by which serotonin influences the generation of new neurons.
Mar, Philip L; Shibao, Cyndya A; Garland, Emily M; Black, Bonnie K; Biaggioni, Italo; Diedrich, André; Paranjape, Sachin Y; Robertson, David; Raj, Satish R
Patients with neurogenic orthostatic hypotension (OH) typically have impaired sympathetic nervous system tone and therefore low levels of upright plasma norepinephrine (NE) (noradrenaline). We report a subset of patients who clinically have typical neurogenic OH but who paradoxically have elevated upright levels of plasma NE. We retrospectively studied 83 OH patients evaluated at the Vanderbilt Autonomic Dysfunction Center between August 2007 and May 2013. Based on standing NE, patients were dichotomized into a hyperadrenergic OH group [hyperOH: upright NE ≥ 3.55 nmol/l (600 pg/ml), n=19] or a non-hyperadrenergic OH group [nOH: upright NE < 3.55 nmol/l (600 pg/ml), n=64]. Medical history and data from autonomic testing, including the Valsalva manoeuvre (VM), were analysed. HyperOH patients had profound orthostatic falls in blood pressure (BP), but less severe than in nOH [change in SBP (systolic blood pressure): -53 ± 31 mmHg compared with -68 ± 33 mmHg, P=0.050; change in DBP (diastolic blood pressure): -18 ± 23 mmHg compared with -30 ± 17 mmHg, P=0.01]. The expected compensatory increase in standing heart rate (HR) was similarly blunted in both hyperOH and nOH groups [84 ± 15 beats per minute (bpm) compared with 82 ± 14 bpm; P=0.6]. HyperOH patients had less severe sympathetic failure as evidenced by smaller falls in DBP during phase 2 of VM and a shorter VM phase 4 BP recovery time (16.5 ± 8.9 s compared with 31.6 ± 16.6 s; P<0.001) than nOH patients. Neurogenic hyperOH patients have severe neurogenic OH, but have less severe adrenergic dysfunction than nOH patients. Further work is required to understand whether hyperOH patients will progress to nOH or whether this represents a different disorder.
Bernard, J M; Péréon, Y; Fayet, G; Guihéneuc, P
Most techniques used to monitor spinal cord tracts are sensitive to the effects of anesthesia, particularly to volatile anesthetic agents. The aim of this prospective study was to show that evoked potentials recorded from the peripheral nerves after spinal cord stimulation, so-called neurogenic motor evoked potentials, are resistant to clinical concentrations of isoflurane or desflurane, compared with somatosensory-evoked potentials. Twenty-three patients were studied during surgery to correct scoliosis. The background anesthetic consisted of a continuous infusion of propofol. Isoflurane (n = 12) or desflurane (n = 11) were then introduced to achieve 0.5 and 1.0 end-tidal minimum alveolar concentrations (MAC), both in 50% oxygen-nitrous oxide and in 100% oxygen. Somatosensory-evoked potentials were elicited and recorded using a standard method, defining cortical P40 and subcortical P29. Neurogenic motor-evoked potentials were elicited by electric stimulation of the spinal cord via needle electrodes placed by the surgeon in the rostral part of the surgical field. Responses were recorded from needle electrodes inserted in the right and left popliteal spaces close to the sciatic nerve. Stimulus intensity was adjusted to produce a supramaximal response; that is, an unchanged response in amplitude with subsequent increases in stimulus intensity. Measurements were obtained before introducing volatile agents and 20 min after obtaining a stable level of each concentration. Isoflurane and desflurane in both 50% oxygen-nitrous oxide and 100% oxygen were associated with a significant decrease in the amplitude and an increase in the latency of the cortical P40, whereas subcortical P29 latency did not vary significantly. Typical neurogenic motor-evoked potentials were obtained in all patients without volatile anesthetic agents, consisting of a biphasic wave, occurring 15 to 18 ms after stimulation, with an amplitude ranging from 1.3 to 4.1 microV. Latency or peak
Full Text Available Thoracic outlet syndrome [TOS] caused by a tumor of the rib is rare and has been reported only 12 times in the literature over the past one and one-half centuries, with the majority of cases due to osteochondroma. We report a case of chondrosarcoma of right 1st rib causing neurogenic TOS that was resected via posterolateral thoracotomy and biopsy confirmed a grade I chondrosarcoma. In the treatment of chondrosarcoma, chemotherapy and radiotherapy are less effective, and appropriate surgery is needed.
Buzzi, M. G.; Moskowitz, M. A.
1. We describe the actions of GR43175, a 5-hydroxytryptamine1 (5-HT1)-like receptor agonist, on neurogenically-mediated plasma protein extravasation within an important pain-sensitive intracranial tissue, the dura mater. 2. GR43175 markedly attenuated extravasation of 125I-albumin from blood vessels within ipsilateral dura mater when administered to rats (100 micrograms kg-1) fifteen minutes before unilateral electrical trigeminal stimulation (1.2 mA, 5 Hz, 5 ms, 5 min); the ratio (stimulated...
Carolina Castelli Silvério
Full Text Available OBJETIVO: verificar a evolução na ingesta oral e a ocorrência de broncopneumonias (BCP em pacientes hospitalizados com disfagia orofaríngea neurogênica, após atuação fonoaudiológica. MÉTODOS: 50 pacientes adultos, divididos em grupos: I: 31 pacientes pós-acidente vascular encefálico; II: sete pacientes pós-traumatismo crânio-encefálico; III: 12 pacientes com demência. Foram levantadas as informações antes e após a atuação fonoaudiológica: nível da Functional Oral Intake Scale (FOIS, ocorrência de BCP; número de atendimentos fonoaudiológicos e motivo de interrupção destes. RESULTADOS: houve aumento significativo dos níveis da escala FOIS e redução do percentual de ocorrência de BCP nos três grupos estudados. Nos grupos pós-AVE e demência a interrupção da fonoterapia ocorreu devido à alta hospitalar, enquanto que no grupo pós-TCE devido à alta fonoaudiológica. CONCLUSÃO: os pacientes deste estudo demonstraram avançar das consistências alimentares na ingesta oral, e redução da ocorrência de BCP, após a intervenção fonoaudiológica com relação à disfagia.PURPOSE: to investigate the development in oral intake and the incidence of bronchopneumonia (BCP in hospitalized patients with neurogenic oropharyngeal dysphagia, after speech and language therapy intervention. METHODS: 50 adult patients, divided in three groups: I: 31 post stroke patients; II: seven brain injury patients ; III: 12 dementia patients. Data collected before and after the speech and language therapy intervention were: staff classification in Functional Oral Intake Scale (FOIS, incidence of BCP, number of therapies and reason for their interruption. RESULTS: significant increase in the levels of FOIS scale and reduction in incidence of pneumonia in the three studied groups. In the post stroke and dementia groups the reason for therapy interruption was hospital discharge, and in the group of brain injury the reason was speech and
... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...
Behr-Roussel, Delphine; Oger, Stéphanie; Pignol, Bernadette; Pham, Emmanuel; Le Maux, Amélie; Chabrier, Pierre-Etienne; Caisey, Stéphanie; Compagnie, Sandrine; Picaut, Philippe; Bernabé, Jacques; Alexandre, Laurent; Giuliano, François; Denys, Pierre
Two botulinum toxins A have been evaluated for the treatment of refractory neurogenic detrusor overactivity (NDO) in humans: Dysport (abobotulinumtoxinA) and Botox (onabotulinumtoxinA). However, these two distinct commercialized products have different potency units and are not interchangeable. Assessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord-injured (SCI) rats with NDO. Female, adult, Sprague-Dawley rats (n=98) underwent T8-T9 spinal cord transection. Nineteen days after spinal cord injury, rats received intradetrusor injections (25μl injected, eight sites) of vehicle (V); Dysport 2, 5, 7.5, 10, and 12.5 U; and Botox 0.8, 2, 5, 7.5, and 10 U. Two days after injection, continuous cystometry was performed in conscious rats. Voiding contractions (VC) were assessed by duration of VC, intercontraction interval, voided volume, maximal pressure, pressure threshold change, and intravesical baseline pressure (BP), while nonvoiding contractions (NVC) were evaluated by amplitude, frequency, and volume threshold to elicit NVC. MEDs for Dysport and Botox were determined by analysis of variance step-down trend test. MEDs for Dysport and Botox were 10 U and 7.5 U, respectively. Regarding VC, only BP significantly decreased after 10 U Dysport and 7.5 U Botox compared to V (from 3.7±0.6 to 1.5±0.1 and 1.4±0.3mm Hg, respectively; pBotox (7.5 U) significantly inhibited NVC by decreasing their amplitude (from 7.4±1.1 to 5.8±0.5 and 5.4±0.6mm Hg, respectively; pBotox under standardized conditions showing similar inhibiting effects on NDO, albeit at different MEDs. It highlights the importance of distinguishing each preparation for predicted outcomes and doses to be used. Further studies in patients with NDO are warranted to confirm these experimental results. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Nambiar, Arjun; Lucas, Malcolm
This chapter focuses on the position of botulinum toxin type A in the treatment pathway for overactive bladder (OAB) and neurogenic lower urinary tract dysfunction associated with neurogenic detrusor overactivity (NDO), and the recommendations of the major international guideline groups. Recommendations of different guideline groups may vary, especially when evidence is weak, often because of differences in methodology and panel composition. Relevant guidelines from the European Association of Urology, American Urological Association, and the UK National Institute for Care and Clinical Excellence were reviewed, and the recommendations that form the basis of the treatment algorithms have been discussed. Any differences between guidelines have been highlighted and special emphasis made on the position of botulinum toxin type A in these pathways. In all the reviewed guidelines, botulinum toxin type A is recommended, alongside sacral nerve neuromodulation, to treat OAB and NDO in patients who have failed oral therapy. The evidence base is consistent, but further evidence is required regarding optimal dosing regimens and injection technique. © 2014 Wiley Periodicals, Inc.
Mitsui, T; Moriya, K; Kitta, T; Kon, M; Nonomura, K
We investigated relation of preoperative renal scar to incidence of postoperative metabolic acidosis following ileocystoplasty in patients with neurogenic bladder. Thirty patients with neurogenic bladder, who underwent ileocystoplasty, were enrolled in the present study. Median age at ileocystoplasty was 13.9 years and median follow-up period after ileocystoplasty was 8.2 years. Metabolic acidosis was defined based on the outlined criteria: base excess (BE) is less than 0 mmol l(-1). Preoperative examination revealed that no apparent renal insufficiency was identified in blood analysis, although preoperative (99m)Tc-DMSA scintigraphy indicated abnormalities such as renal scar in 14 patients (47%). Incidence of postoperative metabolic acidosis was compared between patients with and without preoperative renal scar, which may reflect some extent of renal tubular damage. Postoperative metabolic acidosis was identified in 13 patients (43%). Incidence of postoperative metabolic acidosis was significantly higher in patients with renal scar (11/14, 79%) compared with patients without renal scar (2/16, 13%; Pmetabolic acidosis postoperatively. Compared with patients without preoperative renal scar, pH (Pmetabolic acidosis was significantly implicated in preoperative renal scar. If renal abnormalities are preoperatively identified in imaging tests, we need to care patients carefully regarding metabolic acidosis and subsequent comorbidities following ileocystoplasty.
Full Text Available In response to pain, neurokinin 1 (NK1 receptor availability is altered in the central nervous system. The NK1 receptor and its primary agonist, substance P, also play a crucial role in peripheral tissue in response to pain, as part of neurogenic inflammation. However, little is known about alterations in NK1 receptor availability in peripheral tissue in chronic pain conditions and very few studies have been performed on human beings. Ten subjects with chronic tennis elbow were therefore examined by positron emission tomography (PET with the NK1 specific radioligand [(11C]GR205171 before and after treatment with graded exercise. The radioligand signal intensity was higher in the affected arm as compared with the unaffected arm, measured as differences between the arms in volume of voxels and signal intensity of this volume above a reference threshold set as 2.5 SD above mean signal intensity of the unaffected arm before treatment. In the eight subjects examined after treatment, pain ratings decreased in all subjects but signal intensity decreased in five and increased in three. In conclusion, NK1 receptors may be activated, or up-regulated in the peripheral, painful tissue of a chronic pain condition. This up-regulation does, however, have moderate correlation to pain ratings. The increased NK1 receptor availability is interpreted as part of ongoing neurogenic inflammation and may have correlation to the pathogenesis of chronic tennis elbow.ClinicalTrials.gov NCT00888225 http://clinicaltrials.gov/
Prévinaire, J G; Soler, J M; Bordji, H; Fiolet, M C; Navaux, M A; Mortier, P E
Bowel symptoms (constipation and incontinence) are frequent in patients with a neurologic disease, but rarely assessed in rehabilitation centres. To study the prevalence of neurogenic bowel dysfunction (NBD) in those patients, and to assess its severity with the Patient Global Impression of Severity (PGI-S). Prospective study by questionnaires, with the Neurogenic Bowel Dysfunction Score (0-47) and the PGI-S, a 1-item questionnaire (absent, mild, moderate, severe) for the severity of the bowel symptoms, and the Bristol Stool Chart for stool consistency. All patients presenting a chronic (>2months) neurological disease were included. Inclusion of 169 patients, 97 with spinal cord injury, 42 with multiple sclerosis and 30 with hemiplegia. In each population, prevalence of constipation was 67 %, 45 % and 17 %, of pelvic floor dyssynergia 82 %, 45 % and 27 %, and leakages (gas or stools) de 74 %, 48 % and 43 %, respectively. Moderate to severe bowel symptoms were seen in 61 % of spinal cord injury, 43 % of multiple sclerosis and 23 % of hemiplegic patients, with NBD scores of 11.9±6.5, 5.7±4.9 and 3.7±4.2, respectively (Ptools to assess the presence of bowel symptoms in clinical practice. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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
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.
Bettler, D.; Pearson, S.; Yedvobnick, B. [Emory Univ., Atlanta, GA (United States)
The Drosophila neurogenic loci encode a diverse group of proteins that comprise an inhibitory signal transduction pathway. The pathway is used throughout development in numerous contexts. We have examined the distribution of the neurogenic locus mastermind protein (Mam). Mam is expressed through all germlayers during early embryogenesis, including ectodermal precursors to both neuroblasts and epidermoblasts. Mam is subsequently down-regulated within the nervous system and then reexpressed. It persists in the nervous system through late embryogenesis and postembryonically. Mam is ubiquitously expressed in wing and leg imaginal discs and is not down-regulated in sensory organ precursor cells of the wing margin or notum. In the eye disc, Mam shows most prominent expression posterior to the morphogenetic furrow. Expression of the protein during oogenesis appears limited to follicle cells. Immunohistochemical detection of Mam on polytene chromosomes revealed binding at >100 sites. Chromosome colocalization studies with RNA polymerase and the groucho corepressor protein implicate Mam in transcriptional regulation. 94 refs., 8 figs., 1 tab.
Full Text Available Context: In patients with neurogenic lower urinary tract dysfunction due to Spinal Cord Injury (SCI, recurrent Urinary Tract Infections (UTI, is a frequently encountered clinical problem. Often, conventional preventive measures are not successful. Aims: To treat the patients of SCI suffering from recurrent UTI with classical homoeopathy as add-on to standard urologic care. Materials and Methods: After exclusion of morphological abnormalities and initiation of a standard regime for prophylaxis, all patients with a neurogenic lower urinary tract dysfunction due to SCI, with more than three symptomatic UTI/year, were offered additional homoeopathic care. Symptoms were fever, incontinence, increased spasticity, decreased bladder capacity or pain/decreased general health combined with significant bacteriuria. Descriptive statistics was used for analysis. Results: Eight patients were followed up for a median period of 15 months. Five patients remained free of UTI, whereas UTI frequency was reduced in three patients. Conclusion: Our initial experience with homoeopathic prevention of UTI as add on to standard urologic prophylactic measures is encouraging. For an evidence-based evaluation of this concept, prospective studies are required. Keys for the positive outcome of this case series are co-operation of well-qualified partners, mutual respect and the motivation to co-operate closely.
Kneist, W; Heintz, A; Wolf, H K; Junginger, T
The objective of the present prospective study was to determine the frequency of pelvic autonomic nerve preservation (PANP) during total mesorectal excision (TME) for rectal carcinoma, and to identify a possible link between PANP and postoperative micturition disturbances. Between March 1997 and February 2003, 229 patients with adenocarcinoma of the rectum were operated on with sphincter preservation in 178 (78%) cases. In 101 (48%) patients, the tumor did not invade the muscularis propria. To determine influence parameters on the achievement of complete PANP, a multivariate analysis was performed. The number of complete-partial-or nonidentification of the nerves (superior hypogastric plexus up to the neurovascular bundles) was documented and correlated with micturition disturbances. The pelvic autonomic nerves were identified completely in 169 (74%), partially in 25 (11%), and could not be demonstrated in 35 (15%) patients. Multivariate analysis showed multivisceral resection ( p, p<0.001), and tumor site (middle/upper third vs lower third of rectum, p= 0.011) to exert an independent influence on the achievement of complete PANP. Twenty (8.8%) patients needed a long-term urinary catheter. Preservation of the parasympathetic nerves was associated with low bladder dysfunction rates (4.1 vs 22.4%, p<0.001). To minimize the risk of postoperative micturition disturbances due to neurogenic bladder, pelvic autonomic nerves should be identified during TME. Neurogenic bladder after TME is a useful parameter to assess the quality of surgical treatment for rectal carcinoma.
Fjorback, Morten Voss; Rijkhoff, Nico; Petersen, Thor; Nohr, Mads; Sinkjaer, Thomas
The aim of this study was to evaluate the effect of automatic event driven electrical stimulation on the dorsal penile/clitoral nerve for management of neurogenic detrusor overactivity in patients suffering from Multiple Sclerosis. A total of 10 patients participated in the study. Detrusor pressure was recorded during physiological filling of the bladder and electrical stimulation was applied with surface electrodes whenever the detrusor pressure exceeded 10 cm H(2)O. In seven of the eight patients, where neurogenic detrusor overactivity was observed an average of 12 detrusor contractions could be inhibited by stimulation. In one patient, however, stimulation failed to inhibit the detrusor contractions. The average increase in bladder volume from first suppressed detrusor contraction until leakage was 94% (range: 22-366%). On average, the time from first suppressed contraction until leakage was 15 min and 50 sec (range: 4 min 58 sec-32 min 5 sec) with an average physiological filling rate of 8 ml/min. Urgency was effectively suppressed at the onset of stimulation. The results indicate that involuntary detrusor contractions in patients with multiple sclerosis can effectively be inhibited with event driven stimulation, hereby improving bladder capacity and reducing the number of incontinence episodes. However, the used method for detecting detrusor contractions is not suitable in a chronic setting and alternative techniques needs to be investigated if stimulation should be applied automatically.
Full Text Available ... PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, and ongoing research that helps ...
Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics ... depression experience when starting treatment. Gene Studies ... medication. This information may someday make it possible to predict who ...
Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics ... fear hub," which activates our natural "fight-or-flight" response to confront or escape from a dangerous ...
Symptoms Brain lesions By Mayo Clinic Staff A brain lesion is an abnormality seen on a brain-imaging test, such as ... tomography (CT). On CT or MRI scans, brain lesions appear as dark or light spots that don' ...
Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle- ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...
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Chua, Michael Erlano; Mendoza, Jonathan; See, Manuel; Esmena, Ednalyn; Aguila, Dean; Silangcruz, Jan Michael; Reyes, Buenaventura Jose; Luna, Saturnino; Morales, Marcelino
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
Andersen, Hjalte Holm; Imai, Yosuke; Petersen, Kristian Kjær
forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive...
P.J. Jongen (Peter); B.F.M. Blok (Bertil); J.P. Heesakkers (John P.); M. Heerings (Marco); W.A. Lemmens (Wim A.); R. Donders (Rogier)
textabstractBackground: The Actionable questionnaire is an 8-item tool to screen patients with multiple sclerosis (MS) for neurogenic bladder problems, identifying those patients who might benefit from urological referral and bladder-specific treatment. The original scoring yields a total score of 0
Jongen, Peter Joseph; Blok, Bertil F.; Heesakkers, John P.; Heerings, Marco; Lemmens, Wim A.; Donders, Rogier
Background: The Actionable questionnaire is an 8-item tool to screen patients with multiple sclerosis (MS) for neurogenic bladder problems, identifying those patients who might benefit from urological referral and bladder-specific treatment. The original scoring yields a total score of 0 to 24 with
Jongen, P.J.; Blok, B.F.; Heesakkers, J.P.F.A.; Heerings, M.; Lemmens, W.A.J.G.; Donders, R.
BACKGROUND: The Actionable questionnaire is an 8-item tool to screen patients with multiple sclerosis (MS) for neurogenic bladder problems, identifying those patients who might benefit from urological referral and bladder-specific treatment. The original scoring yields a total score of 0 to 24 with
Chen, Zhili; Venkat, Poornima; Seyfried, Don; Chopp, Michael; Yan, Tao; Chen, Jieli
Neurocardiology is an emerging specialty that addresses the interaction between the brain and the heart, that is, the effects of cardiac injury on the brain and the effects of brain injury on the heart. This review article focuses on cardiac dysfunction in the setting of stroke such as ischemic stroke, brain hemorrhage, and subarachnoid hemorrhage. The majority of post-stroke deaths are attributed to neurological damage, and cardiovascular complications are the second leading cause of post-stroke mortality. Accumulating clinical and experimental evidence suggests a causal relationship between brain damage and heart dysfunction. Thus, it is important to determine whether cardiac dysfunction is triggered by stroke, is an unrelated complication, or is the underlying cause of stroke. Stroke-induced cardiac damage may lead to fatality or potentially lifelong cardiac problems (such as heart failure), or to mild and recoverable damage such as neurogenic stress cardiomyopathy and Takotsubo cardiomyopathy. The role of location and lateralization of brain lesions after stroke in brain-heart interaction; clinical biomarkers and manifestations of cardiac complications; and underlying mechanisms of brain-heart interaction after stroke, such as the hypothalamic-pituitary-adrenal axis; catecholamine surge; sympathetic and parasympathetic regulation; microvesicles; microRNAs; gut microbiome, immunoresponse, and systemic inflammation, are discussed. © 2017 American Heart Association, Inc.
membrane permeability, mitochondrial, peroxisomal and lysosomal dysfunction, and the induction of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY. Altogether, our data obtained in 158N oligodendrocytes provide evidence that argan oil is able to counteract the toxic effects of 7KC on nerve cells, thus suggesting that some of its compounds could prevent or mitigate neurodegenerative diseases to the extent that they are able to cross the blood‐brain barrier.
Kim, N; Azadzoi, K M; Goldstein, I; Saenz de Tejada, I
This study was initiated to characterize nonadrenergic-noncholinergic (NANC) inhibitory neurotransmission in penile corpus cavernosum. Using organ baths, isometric tension measurements were made in strips of human and rabbit corpus cavernosum. In examining endothelium-mediated responses, cumulative additions of exogenous acetylcholine elicited dose-dependent relaxations which were significantly reduced or completely inhibited in tissues treated with NG-monomethyl L-arginine (L-NMMA; an inhibitor of nitric oxide synthesis), oxyhemoglobin (a nitric oxide scavenger), or methylene blue (a guanylate cyclase blocker). Tissues exposed to hypoxic conditions (PO2 = 5-10 mmHg) also did not respond to exogenous acetylcholine. Mechanical removal of the endothelium in human corporal strips or in situ treatment of rabbit corpora with detergent blocked the relaxation to acetylcholine. Transmural electrical stimulation of corporal tissue strips denuded of functional endothelium, in the presence of adrenergic blockade with bretylium and muscarinic receptor blockade with atropine, caused frequency-dependent relaxation. This neurogenic relaxation was reduced or prevented by L-NMMA, oxyhemoglobin, methylene blue, and hypoxia. The effects of L-NMMA were reversed by L-arginine and the effects of hypoxia were readily reversed by normoxic conditions. Authentic, exogenous nitric oxide relaxed corporal strips which were contracted with adrenergic agonists and this effect was significantly inhibited by oxyhemoglobin. It is concluded that (a) endothelium-mediated responses of corpus cavernosum smooth muscle are mediated by a diffusible nitric oxide-like substance; (b) NANC neurogenic inhibitory responses do not require functional endothelium, and (c) nitric oxide, or a closely related substance, may act as an inhibitory neurotransmitter in penile corpus cavernosum smooth muscle. Images PMID:1647413
Kneist, Werner; Kauff, Daniel W; Naumann, Gert; Lang, Hauke
Nerve sparing in functional pelvic floor surgery is strongly recommended as intraoperative damage to the autonomic nerves may predispose to persistent or worsened anorectal and urogenital function. The aim of this study was to investigate the intraoperative neural topography above the pelvic floor in patients undergoing laparoscopic resection rectopexy in combination with electrophysiologic neuromapping. Ten consecutive female patients underwent laparoscopic resection rectopexy for rectal prolapse. Intraoperative identification of pelvic autonomic nerves was carried out with a novel intraoperative neuromonitoring system based on electric stimulation under simultaneous electromyography of the internal anal sphincter and manometry of the bladder. Neuromonitoring results were compared to patients' preoperative anorectal and urogenital function and their functional results at the 3-month follow-up. Laparoscopy in combination with electrophysiologic neuromapping revealed neurogenic pathways to the lower segment of the rectum during surgical mobilization. In all procedures, intraoperative neuromonitoring finally confirmed functional nerve integrity to the internal anal sphincter and the bladder. Patients with preoperatively diagnosed fecal incontinence were continent at the 3-month follow-up. The Wexner score improved in median from preoperative 4 (range 1-18) to 1 (range 0-3) at follow-up (p = 0.012). Cleveland Clinical Constipation Score improved in median from 10 (range 5-17) to 3 (range 1-7; p = 0.005). In none of the investigated patients a new onset of urinary dysfunction did occur. No change in sexual function was observed. Laparoscopy in combination with electrophysiologic neuromapping during nerve-sparing resection rectopexy identified and preserved neurogenic pathways heading to the lower segment of the rectum above the level of the pelvic floor.
A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...
Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics ... basic, working unit of the brain and nervous system, which processes and transmits information. neurotransmitter —A chemical produced by neurons that carries ...
Full Text Available ... learning more about how the brain grows and works in healthy people, and how normal brain development and function can go awry, leading to mental illnesses. Brain Basics will introduce you to some of this science, such as: ... of the brain communicate and work with each other How changes in the brain ...
Lewis, Kate M; Harford-Wright, Elizabeth; Vink, Robert; Nimmo, Alan J; Ghabriel, Mounir N
It is not yet known how tumour cells traverse the blood-brain barrier (BBB) to form brain metastases. Substance P (SP) release is a key component of neurogenic inflammation which has been recently shown to increase the permeability of the BBB following CNS insults, making it a possible candidate as a mediator of tumour cell extravasation into the brain. This study investigated the properties of the BBB in the early stages of tumour cell invasion into the brain, and the possible involvement of SP. Male Wistar rats were injected with Walker 256 breast carcinoma cells via the internal carotid artery and euthanised at 1, 3, 6 and 9 days post tumour inoculation. Culture medium-injected animals served as controls at 1 and 9 days. Evidence of tumour cell extravasation across the BBB was first observed at 3 days post-inoculation, which corresponded with significantly increased albumin (p tumoral area (p cerebral metastases may be a SP-mediated process.
Young, John K; Heinbockel, Thomas; Gondré-Lewis, Marjorie C
Recent research has determined that newborn neurons in the dentate gyrus of the hippocampus of the macaque are frequently adjacent to astrocytes immunoreactive for fatty acid binding protein-7 (FABP7). To investigate if a similar relationship between FABP7-positive (FABP7+) astrocytes and proliferating cells exists in the rodent brain, sections of brains from juvenile rats were stained by immunohistochemistry to demonstrate newborn cells (antibody to Ki67 protein) and FABP7+ astrocytes. In rat brains, FABP7+ astrocytes were particularly abundant in the dentate gyrus of the hippocampus and were frequently close to dividing cells immunoreactive for Ki67 protein. FABP7+ astrocytes were also present in the olfactory bulbs, arcuate nucleus of the hypothalamus, and in the dorsal medulla subjacent to the area postrema, sites where more modest numbers of newborn neurons can also be found. These data suggest that regional accumulations of FABP7+ astrocytes may represent reservoirs of cells having the potential for neurogenesis. Because FABP7+ astrocytes are particularly abundant in the hippocampus, and since the gene for FABP7 has been linked to Alzheimer's disease, age-related changes in FABP7+ astrocytes (mitochondrial degeneration) may be relevant to age-associated disorders of the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.
Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...
Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...
Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... brain. DNA —The "recipe of life," containing inherited genetic information that helps to define physical and some ...
Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ... grow there are differences in brain development in children who develop bipolar disorder than children who do ...
Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as they grow there are differences in brain development in children who develop bipolar disorder than children ...
Full Text Available ... imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain ... imaging technique that uses magnetic fields to take pictures of the brain's structure. mutation —A change in ...
Full Text Available ... as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the brain ... specialized for the function of conducting messages. A neuron has three basic parts: Cell body which includes ...
Full Text Available ... of the brain's structure, studies show that brain growth in children with autism appears to peak early. And as they grow there are differences in brain development in children who develop bipolar disorder than children ...
Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...
Full Text Available ... the Brain Meet Sarah Sarah is a middle-aged woman who seemed to have it all. She ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...
Full Text Available ... about how the brain grows and works in healthy people, and how normal brain development and function ... chart how the brain develops over time in healthy people and are working to compare that with ...
Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle- ... unit of the brain and nervous system, which processes and transmits information. neurotransmitter —A chemical produced by ...
Full Text Available ... Mental Illnesses Clinical Trials Outreach Outreach Home Stakeholder Engagement Outreach Partnership Program Alliance for Research Progress Coalition ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ...
Full Text Available ... in Real Life Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video ... and epigenetic changes can be passed on to future generations. Further understanding of genes and epigenetics may ...
Full Text Available ... can lead to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits ... tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything we do relies on ...
Roth, Carole R; Cornis-Pop, Micaela; Beach, Woodford A
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.
Full Text Available ... pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah ... axis —A brain-body circuit which plays a critical role in the body's response to stress. impulse — ...
Full Text Available ... time in healthy people and are working to compare that with brain development in people mental disorders. Genes and environmental ... the brain than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures ...
Full Text Available ... of cells in the body, the results can affect many aspects of life. Scientists are continually learning more about how the brain grows and works in healthy people, and how normal brain development and function can go awry, leading ... the environment affect the brain The basic structure of the brain ...
Full Text Available ... basic working unit of the brain and nervous system. These cells are highly specialized for the function of conducting messages. ... specialized brain systems. We have many specialized brain systems that work ... research are listed below. Amygdala —The brain's "fear hub," which ...
Yamada, Makiko; Clark, Jessica; McClelland, Christine; Capaldo, Emily; Ray, Ayush; Iulianella, Angelo
The hippocampus arises from the medial region of the subventricular (SVZ) within the telencephalon. It is one of two regions in the postnatal brain that harbors neural progenitors (NPs) capable of giving rise to new neurons. Neurogenesis in the hippocampus is restricted to the subgranular zone (SGZ) of the dentate gyrus (DG) where it contributes to the generation of granule cell layer (gcl) neurons. It is thought that SGZ progenitors are heterogeneous, differing in their morphology, expression profiles, and developmental potential, however it is currently unknown whether they display differences in their developmental origins and cell fate-restriction in the DG. Here we demonstrate that Cux2 is a marker for SGZ progenitors and nascent granule cell neurons in the perinatal brain. Cux2 was expressed in the presumptive hippocampal forming region of the embryonic forebrain from E14.5 onwards. At fetal stages, Cux2 was expressed in early-forming Prox1(+) granule cell neurons as well as the SVZ of the DG germinal matrix. In the postnatal brain, Cux2 was expressed in several types of progenitors in the SGZ of the DG, including Nestin/Sox2 double-positive radial glia, Sox2(+) cells that lacked a radial glial process, DCX(+) neuroblasts, and Calretinin-expressing nascent neurons. Another domain characterized by a low level of Cux2 expression emerged in Calbindin(+) neurons of the developing DG blades. We used Cux2-Cre mice in genetic fate-mapping studies and showed almost exclusive labeling of Calbindin-positive gcl neurons, but not in any progenitor cell types or astroglia. This suggests that Cux2(+) progenitors directly differentiate into gcl neurons and do not self-renew. Interestingly, developmental profiling of cell fate revealed an outside-in formation of gcl neurons in the DG, likely reflecting the activity of Cux2 in the germinative matrices during DG formation and maturation. However, DG morphogenesis proceeded largely normally in hypomorphic Cux2 mutants lacking
Full Text Available Chronic peritoneal dialysis (PD therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis.
Simon, Felipe; Tapia, Pablo; Armisen, Ricardo; Echeverria, Cesar; Gatica, Sebastian; Vallejos, Alejandro; Pacheco, Alejandro; Sanhueza, Maria E.; Alvo, Miriam; Segovia, Erico
Chronic peritoneal dialysis (PD) therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH) solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC) death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis. PMID:28659813
Rodríguez-Franco, María Isabel; Fuente Revenga, Mario de la; Pérez Martín, María Concepción; Pérez Castillo, Ana; Morales-García, José A.; Alonso-Gil, Sandra
[EN] The invention, which is intended for use in the pharmaceutics and research field, relates to novel chemical entities derived from melatonin and having neurogenic properties, melatonin and/or serotonin receptor-modulating properties, and antioxidant and/or cholinergic properties. Experiments on mice have shown that they can be used for the in vivo regeneration of damaged neuronal populations, without leading to tumours. The invention also relates to methods for producing these novel compo...
Full Text Available 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
Wang, Lin; Wang, Kaile; Chu, Xiao; Li, Tieshan; Shen, Nana; Fan, Chenglei; Niu, Zhenyuan; Zhang, Xiaochen; Hu, Luoman
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
Full Text Available Die etablierte Therapie der neurogenen Detrusorhyperaktivität bei Kindern besteht in der Gabe von Anticholinergika und begleitendem intermittierendem Einmalkatheterismus. Eine hohe Nebenwirkungsrate der Anticholinergika oder eine nicht ausreichende Dämpfung der Detrusoraktivität limitiert jedoch die Anwendung und zwingt nicht selten zu einem operativen Vorgehen. Wir untersuchten deshalb die Wirksamkeit von Botulinumtoxin-A (BTX-A auf die neurogene Detrusorhyperaktivität bei Kindern mit neurogener Blasenfunktionsstörung. Hierzu wurden 24 Kinder (11 Mädchen, 13 Jungen; 2,520 (Ø 11,9 Jahre mit maximalem Detrusordruck 40 cm H2O trotz anticholinerger Medikation in die Studie eingeschlossen. Nach urodynamischer Evaluierung wurden gewichtsadaptiert 85300 U BTX-A (Botox(R zystoskopisch an 3040 Stellen in den M. detrusor injiziert. Urodynamische Kontrollen erfolgten nach 1, 3 und 6 Monaten. Urodynamisch fand sich ein erhöhtes Reflexvolumen nach 1 Monat um +84 %, nach 3 Monaten um +68 % und nach 6 Monaten um +23 %. Entsprechend verhielten sich die Maximalkapazitäten: +35 % (nach 1 Monat, +23 % (nach 3 Monaten und +36 % (nach 6 Monaten. Die Maximaldrücke veränderten sich im o.g. Zeitraum um 41 %, 22 % bzw. +4 %. Die korrespondierenden Veränderungen der Inkontinenzrate betrug 46 %, 15 % bzw. 13 %. Bei 5 Kindern konnte jedoch auch mit dieser Therapie keine zufriedenstellende Drucksituation sichergestellt werden; nach der daraufhin durchgeführten Blasenaugmentation fanden sich in den Blasenresektaten histomorphologisch typische BTX-A bedingte Veränderungen, die jedoch in ihrer Ausprägung keinen signifikanten Gradienten aufwiesen. Zusammenfassend läßt sich festhalten, daß es nach Botulinumtoxin-A-Injektion in den Detrusormuskel bei der Mehrzahl der Patienten zu einer ausgeprägten und therapeutisch relevanten Verbesserung sämtlicher urodynamischer Parameter bei sehr guter Verträglichkeit des Medikamentes kommt
Viers, B R; Elliott, D S; Kramer, S A
We review our experience with artificial urinary sphincter and augmentation cystoplasty in patients with neurogenic bladder. This is the largest known series to specifically evaluate cuff only artificial urinary sphincter at augmentation cystoplasty. A total of 18 males underwent simultaneous artificial urinary sphincter and augmentation cystoplasty at our institution between 1982 and 2012, of whom 13 (72%) underwent cuff only artificial urinary sphincter. Outcomes included urinary continence, emptying modality, artificial urinary sphincter status, complications and additional procedures. Of the patients undergoing augmentation cystoplasty and cuff only artificial urinary sphincter 10 (77%) were initially continent. Average time of continence was 52.9 months. Four patients (31%) required no additional procedures and remained continent. Urinary incontinence developed in 3 patients (23%) immediately postoperatively and in 6 (46%) subsequently. Ultimately 9 patients (69%) required conversion to complete artificial urinary sphincter at a mean of 36.9 months postoperatively. Overall 12 patients (92%) were continent at followup. There were no artificial sphincter specific complications in patients undergoing the cuff only procedure with conversion to complete artificial urinary sphincter. After conversion to complete artificial urinary sphincter 3 patients (23%) experienced artificial sphincter specific complications. Reoperation was performed in 10 patients (77%), for 13 total procedures (1.3 per patient). There were no complications with cuff only artificial urinary sphincter and 6 complications with complete artificial urinary sphincter (p = 0.025). Finally, patients undergoing cuff only artificial urinary sphincter requiring revision were younger than those not requiring revision (15.6 vs 30.8 years, p = 0.026). Simultaneous cuff only artificial urinary sphincter and augmentation cystoplasty appears safe and efficacious in patients with neurogenic bladder, with fewer
Luo, Yu-long; Li, Pei-bo; Zhang, Chen-chen; Zheng, Yan-fang; Wang, Sheng; Nie, Yi-chu; Zhang, Ke-jian; Su, Wei-wei
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.
Kelly, Maryellen S; Dorgalli, Crystal; McLorie, Gordon; Khoury, Antoine E
To determine the ability of Peristeen® transanal irrigation system to reduce symptoms of neurogenic bowel dysfunction (NBD) in patients using the validated neurogenic bowel dysfunction scoring system for the pediatric population. Patients 3-21 years with NBD whose current bowel program was unsuccessful were given the Neurogenic Bowel Dysfunction (NBoDS) score sheet before initiating Peristeen®, and at 2 weeks, 2 months, and 6 months after. All patients were started on Peristeen® with tap water (20 ml/kg) per daily irrigation. Mean and paired t-tests were completed. 24 patients were enrolled and had follow-up. Mean age was 10.5 years (range 3-21 years), 25%, 50%, 25% had thoracic, lumbar and sacral level lesions respectively. Mean NBoDS score at initiation of Peristeen® was 20.21 (±5.56), n = 24. The mean score after two weeks of use was 12.75 (±4.40), n = 24. There was a statistically significant decrease of 7.46 (95%CI, 5.07-9.84) points, t(23) = 6.47, P irrigation system provides a significant reduction in NBoDS scores in pediatric patients with NBD. Peristeen® should be considered when other conservative bowel management options have been unsuccessful. Neurourol. Urodynam. 36:632-635, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Vincent, Lucile; Vang, Derek; Nguyen, Julia; Benson, Barbara; Lei, Jianxun; Gupta, Kalpna
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.
Iurlaro, Raffaella; Muñoz‐Pinedo, Cristina
.... Many conditions that impose stress on cells, including hypoxia, starvation, infections and changes in secretory needs, challenge the folding capacity of the cell and promote endoplasmic reticulum stress...
Iurlaro, Raffaella; Muñoz-Pinedo, Cristina
The endoplasmic reticulum is an organelle with multiple functions. The synthesis of transmembrane proteins and proteins that are to be secreted occurs in this organelle. Many conditions that impose stress on cells, including hypoxia, starvation, infections and changes in secretory needs, challenge the folding capacity of the cell and promote endoplasmic reticulum stress. The cellular response involves the activation of sensors that transduce signaling cascades with the aim of restoring homeostasis. This is known as the unfolded protein response, which also intersects with the integrated stress response that reduces protein synthesis through inactivation of the initiation factor eIF2α. Central to the unfolded protein response are the sensors PERK, IRE1 and ATF6, as well as other signaling nodes such as c-Jun N-terminal kinase 1 (JNK) and the downstream transcription factors XBP1, ATF4 and CHOP. These proteins aim to restore homeostasis, but they can also induce cell death, which has been shown to occur by necroptosis and, more commonly, through the regulation of Bcl-2 family proteins (Bim, Noxa and Puma) that leads to mitochondrial apoptosis. In addition, endoplasmic reticulum stress and proteotoxic stress have been shown to induce TRAIL receptors and activation of caspase-8. Endoplasmic reticulum stress is a common feature in the pathology of numerous diseases because it plays a role in neurodegeneration, stroke, cancer, metabolic diseases and inflammation. Understanding how cells react to endoplasmic reticulum stress can accelerate discovery of drugs against these diseases. © 2015 FEBS.
Mulay, Shrikant R; Kumar, Santhosh V; Lech, Maciej; Desai, Jyaysi; Anders, Hans-Joachim
The nephrons of the kidney are independent functional units harboring cells of a low turnover during homeostasis. As such, physiological renal cell death is a rather rare event and dead cells are flushed away rapidly with the urinary flow. Renal cell necrosis occurs in acute kidney injuries such as thrombotic microangiopathies, necrotizing glomerulonephritis, or tubular necrosis. All of these are associated with intense intrarenal inflammation, which contributes to further renal cell loss, an autoamplifying process referred to as necroinflammation. But how does renal cell necrosis trigger inflammation? Here, we discuss the role of danger-associated molecular patterns (DAMPs), mitochondrial (mito)-DAMPs, and alarmins, as well as their respective pattern recognition receptors. The capacity of DAMPs and alarmins to trigger cytokine and chemokine release initiates the recruitment of leukocytes into the kidney that further amplify necroinflammation. Infiltrating neutrophils often undergo neutrophil extracellular trap formation associated with neutrophil death or necroptosis, which implies a release of histones, which act not only as DAMPs but also elicit direct cytotoxic effects on renal cells, namely endothelial cells. Proinflammatory macrophages and eventually cytotoxic T cells further drive kidney cell death and inflammation. Dissecting the molecular mechanisms of necroinflammation may help to identify the best therapeutic targets to limit nephron loss in kidney injury. Copyright © 2016 Elsevier Inc. All rights reserved.
Spicker, Jeppe; Pedersen, Henrik Toft; Nielsen, Henrik Bjørn
, three toxins (ANIT, DMN and NMF) and three non-toxins (Caeruelein, Dinitrophenol and Rosiglitazone). We identified three gene transcripts with exceptional predictive performance towards liver toxicity and/or changes in histopathology. The three genes were: glucokinase regulatory protein (GCKR...
The intricate mechanism of swallowing can be divided into three phases: oral, pharyngeal, and esophageal. Dysphagia is a disruption in the swallowing process, which include difficulty in transporting (or a lack of transporting) a food or liquid bolus from the mouth through the pharynx and esophagus into the stomach. Causes of disruptions in the swallowing process can be divided into superior (oropharyngeal) and inferior (esophageal) according to Paradowski et al. Neurlologic dysphagia may be caused by a disruption in different parts of the central nervous system (supranuclear level, level of motor and sensory nuclei taking part in swallowing process, peripherial nerves level and a pathology of muscle cells and spindles) or neuromuscular and muscular disorders. Neuromuscular disorders causes according to Waśko-Czopnik et al. are: stroke, brain tumors, brain injury, bulbar and pseudobulbar paralysis, neurodegenerative diseases (amyotrophic lateral sclerosis, multiple sclerosis), tabes dorsalis, multisystem degenerations, Parkinson's disease, delayed dyskineses, Huntington's disease, myasthenia and myasthenic syndromes, myopathies and peripherial neuropathies. The correct diagnosis evaluation include history taking, physical examination with palpation and consultations (laryngological, gastrological and neurological). According to Halama radiological esophagogram, videofluoroscopy, flexible endoscopic examination, ultrasound examination, manometry, electromyography, scintigraphy and 24 hour pH monitoring are main diagnostic procedures of dysphagia. Some of the reasons for the neurologic dysphagia may be treated by surgical and pharmacological methods. Neurologic dysphagia rehabilitation is difficult, long-lasting and often falling far short of expected results. Primary it should include neurologic cause treatment if it is possible. According to WHO International Classification of Functioning and Health in 2001 non-invasive methods of dysphagia treatment may be
Tomasković, Igor; Tomić, Miroslav; Nikles, Sven; Neretljak, Ivan; Milicić, Valerija
The aim of this study was to assess the Croatian urologists' management of non-neurogenic male lower urinary tract symptoms (LUTS) and their compliance with the European Association of Urology (EAU) guidelines. A cross-sectional survey included 51/179 Croatian urologists. We developed a questionnaire with questions addressing compliance with EAU guidelines. The rate of performing recommended evaluations on the initial assessment of patients with benign prostate hyperplasia (BPH)/LUTS varied from 8.0% (serum creatinine and voiding diary) to 100.0% (physical examination, prostate specific antigen and ultrasound). The international prostate symptom score was performed by 31%, analysis of urine sediment by 83%, urine culture by 53%, and serum creatinine by 8% of surveyed urologists. Only 8% of urologists regularly used bladder diary in patients with symptoms of nocturia. Our results indicated that 97% of urologists preferred alpha blockers as the first choice of treatment; 5-alpha reductase inhibitors (5ARI) were mostly prescribed (84%) in combination with an alpha-blocker, preferably as a continuous treatment, whilst 29% of urologists used to discontinue 5ARI after 1-2 years. Half of the Croatian urologists used antimuscarinics in the treatment of BPH/LUTS and recommended phytotherapeutic drugs in their practice. In conclusion, Croatian urologists do not completely comply with the guidelines available.
Full Text Available Abstract Background Neurogenic Para-Osteo-Arthropathy (NPOA occurs as a consequence of central nervous system injuries or some systemic conditions. They are characterized by bone formation around the main joints. Methods In order to define some biological features of NPOAs, histological and immunohistological studies of the soft tissue surrounding osteoma and Ultrasound examination (US of NPOA before the appearance of abnormal ossification on plain radiographs were performed. Results We have observed a great number of ossifying areas scattered in soft tissues. US examination have also shown scattered ossifying areas at the early stage of ossification. A high osteogenic activity was detected in these tissues and all the stages of the endochondral process were observed. Mesenchymal cells undergo chondrocytic differentiation to further terminal maturation with hypertrophy, which sustains mineralization followed by endochondral ossification process. Conclusion We suggest that periosteoma soft tissue reflect early stage of osteoma formation and could be a model to study the mechanism of osteoma formation and we propose a mechanism of the NPOA formation in which sympathetic dystony and altered mechanical loading induce changes which could be responsible for the cascade of cellular events leading to cartilage and bone formation.
Ghasemi, M; Sadeghipour, H; Shafaroodi, H; Nezami, B G; Gholipour, T; Hajrasouliha, A R; Tavakoli, S; Nobakht, M; Moore, K P; Mani, A R; Dehpour, A R
Background and purpose: Relaxation of corpus cavernosum, which is mediated by nitric oxide (NO) released from non-adrenergic non-cholinergic (NANC) neurotransmission, is critical for inducing penile erection and can be affected by many pathophysiological conditions. However, the peripheral effect of liver cirrhosis on erectile function is as yet unknown. The aim of the present study was to investigate the effect of biliary cirrhosis on NANC-mediated relaxation of rat corpus cavernosum and the possible roles of endocannabinoid and nitric oxide systems in this model. Experimental approach: Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, strips of corpus cavernosum were mounted in a standard organ bath and NANC-mediated relaxations were obtained by applying electrical field stimulation. Key results: The NANC-mediated relaxation was enhanced in corporal strips from cirrhotic animals. Anandamide potentiated the relaxations in both groups. Either AM251 (CB1 antagonist) or capsazepine (vanilloid VR1 antagonist), but not AM630 (CB2 antagonist), prevented the enhanced relaxations of cirrhotic strips. Either the non-selective NOS inhibitor L-NAME or the selective neuronal NOS inhibitor L-NPA inhibited relaxations in both groups, but cirrhotic groups were more resistant to the inhibitory effects of these agents. Relaxations to sodium nitroprusside (NO donor) were similar in tissues from the two groups. Conclusions and implications: Cirrhosis potentiates the neurogenic relaxation of rat corpus cavernosum probably via the NO pathway and involving cannabinoid CB1 and vanilloid VR1 receptors. PMID:17486141
Li, Huaqiong; Wen, Feng; Chen, Huizhi; Pal, Mintu; Lai, Yuekun; Zhao, Allan Zijian; Tan, Lay Poh
In this study, hybrid micropatterned grafts constructed via a combination of microcontact printing and electrospinning techniques process were utilized to investigate the influencing of patterning directions on human mesenchymal stem cells (hMSCs) differentiation to desired phenotypes. We found that the stem cells could align and elongate along the direction of the micropattern, where they randomly distributed on nonmicropatterned surfaces. Concomitant with patterning effect of component on stem cell alignment, a commensurate increase on the expression of neural lineage commitment markers, such as microtubule associated protein 2 (MAP2), Nestin, NeuroD1, and Class III β-Tubulin, were revealed from mRNA expression by quantitative Real Time PCR (qRT-PCR) and MAP2 expression by immunostaining. In addition, the effect of electrospun fiber orientation on cell behaviors was further examined. An angle of 45° between the direction of micropatterning and orientation of aligned fibers was verified to greatly prompt the outgrowth of filopodia and neurogenesis of hMSCs. This study demonstrates that the significance of hybrid components and electrospun fiber alignment in modulating cellular behavior and neurogenic lineage commitment of hMSCs, suggesting promising application of porous scaffolds with smart component and topography engineering in clinical regenerative medicine.
Ana Claudia Paradella
Full Text Available ABSTRACT Intravesical botulinum toxin A (BoNTA injection has been widely used for the treatment of detrusor overactivity in patients with neurogenic bladder due to spinal cord injury who do not respond to conventional treatment. There is no consensus about antibiotic prophylaxis for this procedure. We conducted a retrospective analysis of medical records of adult patients with spinal cord injury who underwent detrusor BoNTA injection between January of 2007 and December of 2013 in a rehabilitation hospital. Occurrence of symptomatic urinary tract infection (UTI was assessed in 3 groups in accordance with their use of antibiotics (prophylactic dosage, 3 days, more than 3 days for the treatment of asymptomatic bacteriuria. All patients were performing self or assisted clean intermittent bladder catheterization and underwent a rigid cystoscopy, under general or regional anesthesia with sedation, and the drug used was Botox®. A total of 616 procedures were performed during the study period. There were 11 identified cases of UTI (1.8% with a trend to a higher rate in the group that used antibiotics for longer time. This report shows that a single dose of antibiotics before the detrusor BoNTA injection is enough to prevent UTI. Randomized clinical trial should be conducted for definitive conclusions.
Comer, Christine M; White, Derrick; Conaghan, Philip G; Bird, Howard A; Redmond, Anthony C
To explore possible mechanisms underpinning symptom relief and improved walking tolerance in patients with neurogenic claudication (NC) when pushing a shopping trolley by evaluating the effects of a shopping trolley on spinal posture and loading patterns. An exploratory study of kinematic and kinetic changes in walking with and without pushing a shopping trolley in persons with NC symptoms and a comparison with asymptomatic control subjects. A primary care-based musculoskeletal service. Participants (n=8) with NC symptoms who have anecdotally reported symptomatic improvement when walking with a shopping trolley and a control group of asymptomatic persons (n=8). Shopping trolley. Changes in lumbar spinal sagittal posture and ground reaction force. Subjects with NC and asymptomatic controls walked with significantly more flexed spinal posture (increase in flexion, 3.40°; z=3.516; Pshopping trolley. However, at the midstance point of the gait cycle, controls showed minimal reliance on the trolley, whereas, people with NC showed continued offloading. Both posture and loading are affected by pushing a shopping trolley; however, patients with NC were found to offload the spine throughout the stance phase of gait, whereas asymptomatic controls did not. Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Wenger, Y; Buzgariu, W; Galliot, B
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.
Przydacz, Mikolaj; Denys, Pierre; Corcos, Jacques
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.
Ana Claudia Paradella
Full Text Available Intravesical botulinum toxin A (BoNTA injection has been widely used for the treatment of detrusor overactivity in patients with neurogenic bladder due to spinal cord injury who do not respond to conventional treatment. There is no consensus about antibiotic prophylaxis for this procedure. We conducted a retrospective analysis of medical records of adult patients with spinal cord injury who underwent detrusor BoNTA injection between January of 2007 and December of 2013 in a rehabilitation hospital. Occurrence of symptomatic urinary tract infection (UTI was assessed in 3 groups in accordance with their use of antibiotics (prophylactic dosage, 3 days, more than 3 days for the treatment of asymptomatic bacteriuria. All patients were performing self or assisted clean intermittent bladder catheterization and underwent a rigid cystoscopy, under general or regional anesthesia with sedation, and the drug used was Botox®. A total of 616 procedures were performed during the study period. There were 11 identified cases of UTI (1.8% with a trend to a higher rate in the group that used antibiotics for longer time. This report shows that a single dose of antibiotics before the detrusor BoNTA injection is enough to prevent UTI. Randomized clinical trial should be conducted for definitive conclusions.
Krebs, Jörg; Pavlicek, David; Stoyanov, Jivko; Pannek, Jürgen; Wöllner, Jens
To prospectively investigate the association of bladder function with the nerve growth factor (NGF) concentration in the urine of individuals with neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI). Individuals with chronic SCI and NLUTD presenting for a routine urologic examination at a tertiary urologic referral center were recruited for the study. Patient characteristics, the current bladder evacuation method and urodynamic parameters were collected. As controls, individuals with normal bladder function were recruited from the staff of a SCI rehabilitation center. The urinary NGF concentration was measured in triplicates by enzyme linked immunosorbent assay with a minimal sensitivity of 10 pg/ml. The data of 10 and 37 individuals with normal bladder function and NLUTD, respectively, were analyzed. The urinary NGF concentration was below 10 pg/ml in all investigated samples. The urinary NGF concentration did not differentiate between individuals with normal bladder function and those with NLUTD. At least in patients with SCI, the urinary NGF concentration does not seem to be a clinically relevant biomarker for NLUTD. Neurourol. Urodynam. 36:659-662, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Wefer, Björn; Ehlken, Birgit; Bremer, Jörn; Burgdörfer, Harald; Domurath, Burkhard; Hampel, Christian; Kutzenberger, Johannes; Seif, Christoph; Sievert, Karl D; Berger, Karin; Pannek, Jürgen
To evaluate treatment outcomes and resource consumption of patients with neurogenic detrusor overactivity (NDO) before and after botulinum toxin A (Botox) therapy in Germany. In a multi-center, cross-sectional, retrospective cohort study, data of patients with NDO 12 months before and after the first Botox therapy were analyzed. 214 patients (mean age 38 +/- 14.8 years, 145 male, 69 female) with NDO due to spinal cord injury (81%); myelomeningocele (14%), or Multiple Sclerosis (5%) from seven hospitals were included. Mean interval between treatments was 8 months. Following treatment, mean maximum detrusor pressure, maximum cystometric capacity and detrusor compliance improved significantly. Prior to Botox therapy, 68% reported urinary tract infections (UTI), 63% had incontinence episodes, and 58% used incontinence aids. These numbers decreased significantly (p < 0.05) after treatment to 28, 33, and 28%, respectively. In patients using incontinence aids, mean costs per patient decreased from 2euro to 1euro per day, whereas the mean cost of drugs to treat UTIs per patient decreased from 163euro to 80euro per year, respectively. This is the first study demonstrating the clinical usefulness of Botox therapy in clinical practice. Successful treatment resulted in lower costs for NDO associated morbidity due to less need for incontinence aids and UTI medication.
Kneist, Werner; Kauff, Daniel W; Gockel, Ines; Huppert, Sabine; Koch, Klaus P; Hoffmann, Klaus P; Lang, Hauke
The aim of this prospective study was to assess internal anal sphincter (IAS) innervation in patients undergoing total mesorectal excision (TME) by intraoperative neuromonitoring (IONM). Fourteen patients underwent TME. IONM was carried out through pelvic splanchnic nerve stimulation under continuous electromyography of the IAS. Anorectal function was assessed with the digital rectal examination scoring system and a standardized questionnaire. Nine of 11 patients who underwent low anterior resection had positive IONM results, with stimulation-induced increased IAS electromyographic amplitudes (median 0.23 μV (interquartile range [IQR] 0.05, 0.56) vs median 0.89 μV (IQR 0.64, 1.88), p < 0.001) after TME. The patients with the positive IONM results were continent after stoma closure. Of 2 patients with negative IONM results, 1 had fecal incontinence after closure of the defunctioning stoma and received a permanent sigmoidostomy. In the other patient the defunctioning stoma was deemed permanent due to decreased anal sphincter function. In 3 patients who underwent abdominoperineal excision, IONM assessed denervation of the IAS after performance of the abdominal part. This study demonstrated that IONM of IAS innervation in rectal cancer patients is feasible and may predict neurogenic fecal incontinence. Copyright Â© 2012. Published by Elsevier Inc.
Utkan, T; Sarioglu, Y; Yazir, Y
The present study was conducted to investigate the reactivity of the corpus cavernosum smooth muscle after unilateral cavernous nerve neurotomy in rabbits. Rabbits (18) were randomly divided into two groups: sham-operated (n = 9) and those subjected to unilateral neurotomy of a 5-mm segment of the cavernous nerve (n = 9). The reactivity of the corpus cavernosum tissue from the neurotomized and sham groups was studied in organ chambers at 4 weeks postoperation. In the neurotomized group, endothelium-dependent relaxation of the corpus cavernosum smooth muscle to carbachol was significantly increased when compared to the sham group. In addition, the sensitivity (i.e., pD(2)) of neurotomized strips to carbachol was also increased when compared to controls. Electrical field stimulation-induced neurogenic relaxation was significantly reduced in the neurotomized group. Relaxation to the nitric oxide (NO) donor sodium nitroprusside and to papaverine was similar in the cavernosal tissue of both groups. There was no change in agonist potency. Furthermore, neurotomy had no effect on KCl-induced contractile responses. When tissue contraction was induced with phenylephrine to study relaxation to various stimuli, the tension induced was similar in the neurotomized and the sham control groups. We conclude that unilateral, chronic cavernous nerve neurotomy causes significant functional changes to the penile erectile tissue of rabbits, which may contribute to the development of impotence. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.
Abo Youssef, Nadim; Schneider, Marc P; Mordasini, Livio; Ineichen, Benjamin V; Bachmann, Lucas M; Chartier-Kastler, Emmanuel; Panicker, Jalesh N; Kessler, Thomas M
To review systematically all the available evidence on efficacy and safety of cannabinoids for treating neurogenic lower urinary tract dysfunction (NLUTD) in patients with multiple sclerosis (MS). The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of the Cochrane register, Embase, Medline, Scopus (last search on 11 November 2016). After screening 8 469 articles, we included two randomized controlled trials and one open-label study, in which a total of 426 patients were enrolled. Cannabinoids relevantly decreased the number of incontinence episodes in all three studies. Pooling data showed the mean difference in incontinence episodes per 24 h to be -0.35 (95% confidence interval -0.46 to -0.24). Mild adverse events were frequent (38-100%), but only two patients (0.7%) reported a serious adverse event. Preliminary data imply that cannabinoids might be an effective and safe treatment option for NLUTD in patients with MS; however, the evidence base is poor and more high-quality, well-designed and adequately powered and sampled studies are urgently needed to reach definitive conclusions. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.
Caicedo, Alexander; Varon, Carolina; Thewissen, Liesbeth; Naulaers, Gunnar; Lemmers, Petra; Van Bel, Frank; Van Huffel, Sabine
Labetalol is a drug used in the treatment of hypertensive disorders of pregnancy (HDP). In a previous study we investigated the influence of the maternal use of labetalol on the cerebral autoregulation (CA) mechanism of neonates. In that study, we found that labetalol induces impaired CA during the first day of life, with CA returning to a normal status by the third day after birth. This effect was hypothesized to be caused by labetalol-induced vasodilation. However, no strong evidence for this claim was found. In this study we aim to find stronger evidence for the vasodilation effect caused by labetalol, by investigating its effect on the neurogenic mechanism (NM) involved in CA. The status of the NM was assessed by means of transfer function analysis between the low frequency content of the autonomic control activity (LFA), obtained by processing of the heart rate (HR), and the regional cerebral oxygen saturation (rScO₂). We found that neonates from mothers treated with labetalol presented a lower LFA and an impaired NM response during the first day of life, with values returning to normal by the end of the third day. These results reflect a vasodilation effect caused by labetalol, and indicate that the impaired CA observed in the previous study is caused by vasodilation.
Fang, H; Lu, B; Wang, X; Zheng, L; Sun, K; Cai, W
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.
Zhao, Min-Zhu; Li, Yong-Guo; Zhang, Peng; Xiong, Jin-Cheng; Zhu, Shi-Sheng; Xiao, Xuan; Li, Jian-Bo
In forensic medicine, the diagnosis of death due to neurogenic shock is considered to be an aporia, as lacking objective indicators and presenting atypical symptoms in autopsy. Medico-legal disputes and complaints occasionally result from this ambiguity. To explore potential objective indicators of neurogenic shock, we set up a model of neurogenic shock by applying an external mechanical force on the carotid sinus baroreceptor in rabbits. The serum atrial natriuretic peptide (ANP) level was measured by radioimmunoassay in the control group (n = 8), survival group (n = 15) and death group (n = 5) both before and after the insult. The serum ANP level showed a significant increase after the insult in the death group compared with the serum obtained before the insult (P = 0.006), while the serum ANP level after the insult in the survival group and control group was not statistically significant compared with the serum obtained before the insult (P = 0.332 and P = 0.492, respectively). To verify the repeatability of the model and the postmortem behavior of serum ANP, five healthy adult rabbits underwent the same procedure as the experimental group. The mortality rate was consistent with the former experiment (20 %). There were no significant changes in serum ANP level in vitro and in vivo (within 48 and 24 h, respectively). But there was a significant decrease in serum ANP level at 48 h postmortem in vivo (P = 0.001). A female patient who expired due to neurogenic shock during a hysteroscopy was reported. Neither fatal primary disease nor evidence for mechanical injuries or intoxication was found according to the autopsy. The serum ANP level was assayed as a supplementary indicator and was found to be three-fold higher than the normal maximum limit. Combined with the animal experiment, this case highlights that serum ANP has the potential to be an objective indicator for the diagnosis of death due to neurogenic shock.
Comer, Christine M; Johnson, Mark I; Marchant, Paul R; Redmond, Anthony C; Bird, Howard A; Conaghan, Philip G
Comer CM, Johnson MI, Marchant PR, Redmond AC, Bird HA, Conaghan PG. The effectiveness of walking stick use for neurogenic claudication: results from a randomized trial and the effects on walking tolerance and posture. To determine the immediate effects of using a stick on walking tolerance and on the potential explanatory variable of posture, and to provide a preliminary evaluation of the effects of daily walking stick use on symptoms and function for people with neurogenic claudication. A 2-phase study of neurogenic claudication patients comprising a randomized trial of 2 weeks of home use of a walking stick and a crossover study comparing walking tolerance and posture with and without a walking stick. A primary care-based musculoskeletal service. Patients aged 50 years or older with neurogenic claudication symptoms (N=46; 24 women, 22 men, mean age=71.26y) were recruited. Walking stick. Phase 1 of the trial used the Zurich Claudication Questionnaire symptom severity and physical function scores to measure outcome. The total walking distance during a shuttle walking test and the mean lumbar spinal posture (measured by using electronic goniometry) were used as the primary outcome measurements in the second phase. Forty of the participants completed phase 1 of the trial, and 40 completed phase 2. No significant differences in symptom severity or physical function were shown in score improvements for walking stick users (stick user scores - control scores) in the 2-week trial (95% confidence interval [CI], -.24 to .28 and -.10 to .26, respectively). In the second phase of the trial, the ratio of the shuttle walking distance with a stick to without a stick showed no significance (95% CI, .959-1.096) between the groups. Furthermore, the use of a walking stick did not systematically promote spinal flexion; no significant difference was shown for mean lumbar spinal flexion for stick use versus no stick (95% CI, .351 degrees -.836 degrees ). The prescription of a walking
Fung, Eva Lai-Wah; Tsung, Lilian Li-Yan; Dale, Russell C
Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease often associated with a highly specific autoantibody, aquaporin-4 antibody. Although the classic syndrome involves the optic nerves and spinal cord, aquaporin-4 antibody has been important in defining the true spectrum of NMO, which now includes brain lesions in areas of high aquaporin-4 expression. Brainstem involvement, specifically area postrema involvement in the medulla, has been associated with intractable vomiting in some patients with NMO. We describe a 14-year-old female with positive aquaporin-4 antibody whose clinical course was dominated by severe anorexia with associated weight loss (from 68-41kg; body mass index 25.2-15.6). Magnetic resonance imaging showed lesions in the medulla, pons, and thalami. Although she had asymptomatic radiological longitudinally extensive transverse myelitis, she never had symptoms or signs referable to the spinal cord or the optic nerves. We propose that anorexia and weight loss should be considered part of the NMO spectrum, probably related to area postrema involvement. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.
Maria del Carmen Cardenas-Aguayo
Full Text Available The level of brain-derived neurotrophic factor (BDNF, a member of the neurotrophin family, is down regulated in Alzheimer's disease (AD, Parkinson's disease (PD, depression, stress, and anxiety; conversely the level of this neurotrophin is increased in autism spectrum disorders. Thus, modulating the level of BDNF can be a potential therapeutic approach for nervous system pathologies. In the present study, we designed five different tetra peptides (peptides B-1 to B-5 corresponding to different active regions of BDNF. These tetra peptides were found to be non-toxic, and they induced the expression of neuronal markers in mouse embryonic day 18 (E18 primary hippocampal neuronal cultures. Additionally, peptide B-5 induced the expression of BDNF and its receptor, TrkB, suggesting a positive feedback mechanism. The BDNF peptides induced only a moderate activation (phosphorylation at Tyr 706 of the TrkB receptor, which could be blocked by the Trk's inhibitor, K252a. Peptide B-3, when combined with BDNF, potentiated the survival effect of this neurotrophin on H(2O(2-treated E18 hippocampal cells. Peptides B-3 and B-5 were found to work as partial agonists and as partial antagonists competing with BDNF to activate the TrkB receptor in a dose-dependent manner. Taken together, these results suggest that the described BDNF tetra peptides are neurotrophic, can modulate BDNF signaling in a partial agonist/antagonist way, and offer a novel therapeutic approach to neural pathologies where BDNF levels are dysregulated.
Full Text Available Transcription factor Runx1 (Runt Related Transcription Factor 1, plays an important role in the differentiation of hematopoetic stem cells, angiogenesis and the development of nociceptive neurons. These known functions have in common that they relate to lineage decisions. We thus asked whether such role might also be found for Runx1 in adult hippocampal neurogenesis as a process, in which such decisions have to be regulated lifelong. Runx1 shows a widespread low expression in the adult mouse brain, not particularly prominent in the hippocampus and the resident neural precursor cells. Isoforms 1 and 2 of Runx1 (but not 3 to 5 driven by the proximal promoter were expressed in hippocampal precursor cells ex vivo, albeit again at very low levels, and were markedly increased after stimulation with TGF-β1. Under differentiation conditions (withdrawal of growth factors Runx1 became down-regulated. Overexpression of Runx1 in vitro reduced proliferation, increased survival of precursor cells by reducing apoptosis, and increased neuronal differentiation, while slightly reducing dendritic morphology and complexity. Transfection with dominant-negative Runx1 in hippocampal precursor cells in vitro did not result in differences in neurogenesis. Hippocampal expression of Runx1 correlated with adult neurogenesis (precursor cell proliferation across BXD recombinant strains of mice and covarying transcripts enriched in the GO categories "neural precursor cell proliferation" and "neuron differentiation". Runx1 is thus a plausible candidate gene to be involved in regulating initial differentiation-related steps of adult neurogenesis. It seems, however, that the relative contribution of Runx1 to such effect is complementary and will explain only small parts of the cell-autonomous pro-differentiation effect.
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Green Tea Polyphenols Precondition against Cell Death Induced by Oxygen-Glucose Deprivation via Stimulation of Laminin Receptor, Generation of Reactive Oxygen Species, and Activation of Protein Kinase Cϵ
Gundimeda, Usha; McNeill, Thomas H.; Elhiani, Albert A.; Schiffman, Jason E.; Hinton, David R.; Gopalakrishna, Rayudu
As the development of synthetic drugs for the prevention of stroke has proven challenging, utilization of natural products capable of preconditioning neuronal cells against ischemia-induced cell death would be a highly useful complementary approach. In this study using an oxygen-glucose deprivation and reoxygenation (OGD/R) model in PC12 cells, we show that 2-day pretreatment with green tea polyphenols (GTPP) and their active ingredient, epigallocatechin-3-gallate (EGCG), protects cells from subsequent OGD/R-induced cell death. A synergistic interaction was observed between GTPP constituents, with unfractionated GTPP more potently preconditioning cells than EGCG. GTPP-induced preconditioning required the 67-kDa laminin receptor (67LR), to which EGCG binds with high affinity. 67LR also mediated the generation of reactive oxygen species (ROS) via activation of NADPH oxidase. An exogenous ROS-generating system bypassed 67LR to induce preconditioning, suggesting that sublethal levels of ROS are indeed an important mediator in GTPP-induced preconditioning. This role for ROS was further supported by the fact that antioxidants blocked GTPP-induced preconditioning. Additionally, ROS induced an activation and translocation of protein kinase C (PKC), particularly PKCϵ from the cytosol to the membrane/mitochondria, which was also blocked by antioxidants. The crucial role of PKC in GTPP-induced preconditioning was supported by use of its specific inhibitors. Preconditioning was increased by conditional overexpression of PKCϵ and decreased by its knock-out with siRNA. Collectively, these results suggest that GTPP stimulates 67LR and thereby induces NADPH oxidase-dependent generation of ROS, which in turn induces activation of PKC, particularly prosurvival isoenzyme PKCϵ, resulting in preconditioning against cell death induced by OGD/R. PMID:22879598
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Full Text Available ... early brain development. It may also assist in learning and memory. Problems in making or using glutamate have been ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain involved in ...
Full Text Available ... affect many aspects of life. Scientists are continually learning more about how the brain grows and works in healthy people, and how ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain involved in creating and filing new memories. hypothalmic- ...
Full Text Available ... including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain Regions Just as many neurons working together form ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman ...
Full Text Available ... pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah ... having trouble coping with the stresses in her life. She began to think of suicide because she ...
Full Text Available ... These circuits control specific body functions such as sleep and speech. The brain continues maturing well into a person's early 20s. ... that regulates many functions, including mood, appetite, and sleep. synapse —The tiny gap between neurons, where nerve impulses are sent from one neuron to ... of Deep Brain Stimulation Brain’s Alertness Circuitry Revealed New BRAIN Grants ...
... inside of the brain (ventricles) or surrounding your brain and spinal cord to drain the excess fluid into an external bag. Sometimes it may then be necessary to introduce a shunt system — which consists of a ... brain and ending in your abdominal cavity. Rehabilitative therapy. ...
Full Text Available ... brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain growth in children with autism appears to peak early. And as they grow there are differences in ...
Full Text Available ... another important research tool in understanding how the brain functions. Another type of brain scan called magnetoencephalography, or ... highly developed area at the front of the brain that, in humans, plays a role in executive functions such as judgment, decision making and problem solving, ...
Farmer, Lesley S. J.
As the United States student population is becoming more diverse, library media specialists need to find ways to address these distinctive needs. However, some of these differences transcend culture, touching on variations in the brain itself. Most people have a dominant side of the brain, which can affect their personality and learning style.…
Jiao, Qian; Du, Xixun; Li, Yong; Gong, Bing; Shi, Limin; Tang, Tingting; Jiang, Hong
Ghrelin, a peptide released by the stomach that plays a major role in regulating energy metabolism, has recently been shown to have effects on neurobiological behaviors. Ghrelin enhances neuronal survival by reducing apoptosis, alleviating inflammation and oxidative stress, and accordingly improving mitochondrial function. Ghrelin also stimulates the proliferation, differentiation and migration of neural stem/progenitor cells (NS/PCs). Additionally, the ghrelin is benefit for the recovery of memory, mood and cognitive dysfunction after stroke or traumatic brain injury. Because of its neuroprotective and neurogenic roles, ghrelin may be used as a therapeutic agent in the brain to combat neurodegenerative disease. In this review, we highlight the pre-clinical evidence and the proposed mechanisms underlying the role of ghrelin in physiological and pathological brain function. Copyright © 2016 Elsevier Ltd. All rights reserved.
Galarza, Marcelo; Fabrizi, Anthony P; Maina, Raffaella; Gazzeri, Roberto; Martínez-Lage, Juan F
The aim of this study was to evaluate whether clinical improvement is noticeable after a minimally invasive procedure such as that used with the Aperius PercLID System in patients with degenerative lumbar spinal stenosis (DLSS) and neurogenic intermittent claudication (NIC). The patients were treated with the aforementioned system at 3 different centers. The initial requirement to be included in the study was a minimum follow-up of 12 months. The authors studied 40 cases of DLSS in patients with NIC (age 72.7 +/- 8.08 years). Symptom severity, physical function, quality of life, and self-rated pain were assessed preoperatively and at the 12-month follow-up using the Zurich Claudication Questionnaire (ZCQ) and a visual analog scale. The procedure was conducted under spinal (35 patients) or local (5 patients) anesthesia, using biplanar fluoroscopy for visualization. Single-level treatment was performed in 28 patients and 2-level treatment was performed in 12 patients. Based on time recordings in 24 cases, the mean procedural time was 19.9 +/- 5.0 minutes. The mean pain visual analog scale score improved significantly from 8.1 +/- 2.19 at baseline to 3.44 +/- 2.89 at the 1-year follow-up. The ZCQ score for patient satisfaction showed 90% of the patients being satisfied with the procedure. The mean rates of improvement in ZCQ score for symptom severity and physical function at 1 year were 38.7 +/- 33.3% and 33.8 +/- 29.7%, respectively, and both proved to be statistically significant. Most improvement was seen in mobility, pain/discomfort, and ability for self-care. In this preliminary study, the Aperius system provided clinically significant improvement after 1 year of follow-up in patients older than 65 years with DLSS and NIC.
Lyle, Samantha; Williamson, Esther; Darton, Frances; Griffiths, Frances; Lamb, Sarah E
The aim of this study was to explore older people's experiences of living with neurogenic claudication (NC), their preferences for physiotherapy treatment provision and associated outcomes in order to inform an intervention to be tested in a clinical trial. Patients with a diagnosis of NC and/or lumbar spinal stenosis were recruited through a UK NHS tertiary care center. Semi-structured interviews and self-report questionnaires were used to obtain data. A thematic analysis was conducted. 15 participants were recruited; half were classed as frail older adults. Pain and the threat of pain was a prominent feature of participants' experience of NC. This led to a loss of engagement in meaningful activities and sense of self. Discourses of ageing influenced experiences as well as treatment preferences, particularly the acceptability of walking aids. A combination of one-to-one and group setting for treatment was preferred. Outcome preferences related to re-engagement in meaningful activities and pain reduction. Limitations relate to generalisability of the findings for NC patients not under physiotherapy treatment. We have obtained important findings about older people's experiences of living with NC and preferences for physiotherapy treatment and outcomes. These will be incorporated into an evidence-based intervention and evaluated in a randomized controlled trial. Implications for rehabilitation Older people living with NC want to get back to meaningful activities and learn how to live with the threat of pain. Allied health professionals (AHPs) should be sensitive to the complex and ambiguous ways in which older people live with ageing and age-related decline. AHPs are in a position to support patients' successful transition to the use of walking aids thereby reducing stigmatizing effects and increasing activity. AHPs should consider a mixture of one-to-one and group classes to enable rehabilitation for older NC patients.
Cho, Young Jae; Lee, Hyuk Jin; Gong, Hyun Sik; Rhee, Seung Hwan; Park, Sang Jae; Baek, Goo Hyun
Neurogenic thoracic outlet syndrome (NTOS) is produced by compression of the brachial plexus in the thoracic outlet. The lower position of the shoulder girdle relative to the upper thorax may be related to NTOS. We investigated this hypothesis using plain cervical radiographs. We conducted this case-control study using plain cervical anteroposterior and lateral radiographs in 63 NTOS patients and 126 carpal tunnel syndrome patients who were matched for age and sex. To estimate the position of the shoulder girdle relative to the upper thorax, we analyzed the level of the clavicle using 2 parameters: the number of vertebrae visible in a lateral radiograph and the number of vertebrae above the line connecting both sternal ends of the clavicles in an anteroposterior radiograph. The number of vertebrae visible in a lateral radiograph was the parameter for the level of the lateral part of the clavicle relative to the upper thorax, whereas we used the number of vertebrae above the line connecting both sternal ends of the clavicles in an anteroposterior radiograph to determine the level of the medial part of the clavicle. Both parameters were greater in the NTOS group than in the control group, which suggests that the level of the shoulder girdle was lower in the NTOS group than in the control group. In addition, the risk of NTOS was increased in patients with lower shoulder girdle position. The lower placement of the shoulder girdle relative to the upper thorax was related to NTOS. Physicians may be able to estimate the position of the shoulder girdle using plain cervical radiographs when NTOS is clinically suspected. Diagnostic IV. Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.
Krebs, Jörg; Bartel, Peter; Pannek, Jürgen
To investigate the functional outcome after supratrigonal cystectomy and augmentation ileocystoplasty in adult patients with refractory neurogenic lower urinary tract dysfunction (NLUTD). Retrospective follow-up investigation in a single spinal cord injury rehabilitation center. In 29 patients, urodynamic data before and after supratrigonal cystectomy and augmentation ileocystoplasty, clinical outcome and post-operative complications were evaluated. The median age of the 29 patients at the time of surgery was 31 years, a median 14 years after NLUTD had occurred. At the last follow-up visit (median 2.4, range 0.4-9.0 years post-operatively), 20/29 patients (69%) were continent compared to 2/29 pre-operatively (P = 0.001). Furthermore, 16 patients required no or less detrusor relaxation therapy after augmentation ileocystoplasty. Augmentation cystoplasty resulted in a significant (P = 0.001) increase in the median bladder capacity (from 240 ml to 500 ml) and compliance (from 13 ml/cm H2 O to 50 ml/cm H2 O). The median maximum detrusor pressure had decreased significantly (P = 0.001) from 38 cm H2 O to 15 cm H2 O. Significantly (P = 0.001) fewer patients presented with a risk for renal damage (1 vs. 15 with maximum detrusor pressure >40 cm H2 O and 1 vs. 12 with detrusor compliance <20 ml/cm H2 O) at the last follow-up. The following complications were observed in 11/29 (38%) patients: paralytic and obstructive ileus, impaired bowel function, bladder stones, dehiscence, metabolic acidosis and autonomic dysreflexia. Protection of renal function, adequate bladder capacity and low detrusor pressure can be achieved using supratrigonal cystectomy and augmentation ileocystoplasty in patients suffering from refractory NLUTD. © 2014 Wiley Periodicals, Inc.
Full Text Available Abstract Objective: To characterize a cohort of children with non-neurogenic daytime urinary incontinence followed-up in a tertiary center. Methods: Retrospective analysis of 50 medical records of children who had attained bladder control or minimum age of 5 years, using a structured protocol that included lower urinary tract dysfunction symptoms, comorbidities, associated manifestations, physical examination, voiding diary, complementary tests, therapeutic options, and clinical outcome, in accordance with the 2006 and 2014 International Children's Continence Society standardizations. Results: Female patients represented 86.0% of this sample. Mean age was 7.9 years and mean follow-up was 4.7 years. Urgency (56.0%, urgency incontinence (56.0%, urinary retention (8.0%, nocturnal enuresis (70.0%, urinary tract infections (62.0%, constipation (62.0%, and fecal incontinence (16.0% were the most prevalent symptoms and comorbidities. Ultrasound examinations showed alterations in 53.0% of the cases; the urodynamic study showed alterations in 94.7%. At the last follow-up, 32.0% of patients persisted with urinary incontinence. When assessing the diagnostic methods, 85% concordance was observed between the predictive diagnosis of overactive bladder attained through medical history plus non-invasive exams and the diagnosis of detrusor overactivity achieved through the invasive urodynamic study. Conclusions: This subgroup of patients with clinical characteristics of an overactive bladder, with no history of urinary tract infection, and normal urinary tract ultrasound and uroflowmetry, could start treatment without invasive studies even at a tertiary center. Approximately one-third of the patients treated at the tertiary level remained refractory to treatment.
Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta
Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients.
Full Text Available Objective: To analyze the effect of α-lipoic acid combined with mecobalamine therapy on urodynamics and oxidative damage of nerve in patients with diabetic neurogenic bladder. Methods: A total of 78 patients with diabetic neurogenic bladder were randomly divided into observation group and control group (n=39, control group received conventional therapy and observation group received conventional therapy + α-lipoic acid combined with mecobalamine therapy. Before treatment and after one course of treatment, urodynamic indexes, peripheral nerve conduction latency time and serum indexes of two groups were detected respectively. Results: After one course of treatment, RUV, Pdet, FS, T and C value as well as ROS, MDA, SP, NPY and ChAT content of both groups were significantly lower than those before treatment, MFR value as well as GSH, SOD, BDNF and CNTF content was significantly higher than those before treatment, and the sensory conduction latency time of median nerve and ulnar nerve as well as motor conduction latency time of median nerve and peroneal nerve were shorter than those before treatment (P<0.05; RUV, Pdet, FS, T and C value as well as ROS, MDA, SP, NPY and ChAT content of observation group were significantly lower than those of control group, MFR value as well as GSH, SOD, BDNF and CNTF content was significantly higher than those of control group, and the sensory conduction latency time of median nerve and ulnar nerve as well as motor conduction latency time of median nerve and peroneal nerve were significantly shorter than those of control group (P<0.05. Conclusions: α-lipoic acid combined with mecobalamine therapy can optimize the urodynamics in patients with diabetic neurogenic bladder and also reduce the oxidative damage of nerve, and it is an effective solution for treatment of such disease.
Su, Liling; Wei, Xiaoxia; Xu, Zhengping; Chen, Guangdi
Despite many years of studies, the debate on genotoxic effects of radiofrequency electromagnetic fields (RF-EMF) continues. To systematically evaluate genotoxicity of RF-EMF, this study examined effects of RF-EMF on DNA damage and cellular behavior in different neurogenic cells. Neurogenic A172, U251, and SH-SY5Y cells were intermittently (5 min on/10 min off) exposed to 1800 MHz RF-EMF at an average specific absorption rate (SAR) of 4.0 W/kg for 1, 6, or 24 h. DNA damage was evaluated by quantification of γH2AX foci, an early marker of DNA double-strand breaks. Cell cycle progression, cell proliferation, and cell viability were examined by flow cytometry, hemocytometer, and cell counting kit-8 assay, respectively. Results showed that exposure to RF-EMF at an SAR of 4.0 W/kg neither significantly induced γH2AX foci formation in A172, U251, or SH-SY5Y cells, nor resulted in abnormal cell cycle progression, cell proliferation, or cell viability. Furthermore, prolonged incubation of these cells for up to 48 h after exposure did not significantly affect cellular behavior. Our data suggest that 1800 MHz RF-EMF exposure at 4.0 W/kg is unlikely to elicit DNA damage or abnormal cellular behaviors in neurogenic cells. Bioelectromagnetics. 38:175-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Muralidharan, Bhavana; Keruzore, Marc; Pradhan, Saurabh J; Roy, Basabdatta; Shetty, Ashwin S; Kinare, Veena; D'Souza, Leora; Maheshwari, Upasana; Karmodiya, Krishanpal; Suresh, Agasthya; Galande, Sanjeev; Bellefroid, Eric J; Tole, Shubha
Regulation of the neuron-glia cell-fate switch is a critical step in the development of the CNS. Previously, we demonstrated that Lhx2 is a necessary and sufficient regulator of this process in the mouse hippocampal primordium, such that Lhx2 overexpression promotes neurogenesis and suppresses gliogenesis, whereas loss of Lhx2 has the opposite effect. We tested a series of transcription factors for their ability to mimic Lhx2 overexpression and suppress baseline gliogenesis, and also to compensate for loss of Lhx2 and suppress the resulting enhanced level of gliogenesis in the hippocampus. Here, we demonstrate a novel function of Dmrt5/Dmrta2 as a neurogenic factor in the developing hippocampus. We show that Dmrt5, as well as known neurogenic factors Neurog2 and Pax6, can each not only mimic Lhx2 overexpression, but also can compensate for loss of Lhx2 to different extents. We further uncover a reciprocal regulatory relationship between Dmrt5 and Lhx2, such that each can compensate for loss of the other. Dmrt5 and Lhx2 also have opposing regulatory control on Pax6 and Neurog2, indicating a complex bidirectionally regulated network that controls the neuron-glia cell-fate switch.SIGNIFICANCE STATEMENT We identify Dmrt5 as a novel regulator of the neuron-glia cell-fate switch in the developing hippocampus. We demonstrate Dmrt5 to be neurogenic, and reciprocally regulated by Lhx2: loss of either factor promotes gliogenesis; overexpression of either factor suppresses gliogenesis and promotes neurogenesis; each can substitute for loss of the other. Furthermore, each factor has opposing effects on established neurogenic genes Neurog2 and Pax6 Dmrt5 is known to suppress their expression, and we show that Lhx2 is required to maintain it. Our study reveals a complex regulatory network with bidirectional control of a fundamental feature of CNS development, the control of the production of neurons versus astroglia in the developing hippocampus.Finally, we confirm that Lhx2
Jongen, Peter; Blok, Bertil; Heesakkers, John P.; Heerings, Marco; Lemmens, Wim A.; Donders, Rogier
textabstractBackground: The Actionable questionnaire is an 8-item tool to screen patients with multiple sclerosis (MS) for neurogenic bladder problems, identifying those patients who might benefit from urological referral and bladder-specific treatment. The original scoring yields a total score of 0 to 24 with cut-off point 6. A simplified scoring, yielding a total score of 0 to 8 with cut-off point 3, has been developed in urogynaecological patients, but has not been investigated in MS. Meth...
Full Text Available Here, we present a case of dorsal medulla oblongata hemangioblastoma with fourth ventricular hemorrhage. A 23-year-old female developed sudden consciousness disturbance, and CT revealed hemorrhage in all cerebral ventricles and a hyperdense mass in the cisterna magna. Although the reddish tumor located in the dorsal medulla oblongata was successfully removed, she suffered from severe tako-tsubo cardiomyopathy (TTC and neurogenic pulmonary edema (NPE because of baroreflex failure and damage to the solitary tract nuclei. After intensive care for 12 weeks following surgery, she was discharged without any neurological or radiological deficits. Pathogenesis of TTC/NPE is discussed in this paper.
Obel, Linea Lykke Frimodt; Müller, Margit S; Walls, Anne B
Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia....... In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies-it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic...... activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms...
Beresford, H R
Current law in the United States authorizes physicians to diagnose brain death by applying generally accepted neurologic criteria for determining loss of function of the entire brain. This article offers a medical-legal perspective on problems that may arise with respect to the determination of brain death. These include the possibility of diagnostic error, conceptual disagreements that may constrain the use of neurologic criteria to diagnose death, and the conflation of brain death and loss of consciousness. This article also addresses legal aspects of the debate over whether to expand the definition of brain death to include permanent unconsciousness. Although existing laws draw a clear distinction between brain death and the persistent vegetative state, many courts have authorized removal of life support from individuals whose unconsciousness is believed to be permanent on proof that removal accords with preferences expressed before sentience was lost.
Full Text Available ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain Regions Just as many neurons working together form ...
de Kloet, Annette D; Steckelings, Ulrike M; Sumners, Colin
The goal of this review is to assess the evidence that activation of angiotensin type 2 receptors (AT2R) in the brain can lower blood pressure and possibly constitute an endogenous anti-hypertensive mechanism. Recent studies that detail the location of AT2R in the brain, particularly within or near cardiovascular control centers, mesh well with findings from pharmacological and gene transfer studies which demonstrate that activation of central AT2R can influence cardiovascular regulation. Collectively, these studies indicate that selective activation of brain AT2R causes moderate decreases in blood pressure in normal animals and more profound anti-hypertensive effects, along with restoration of baroreflex function, in rodent models of neurogenic hypertension. These findings have opened the door to studies that can (i) assess the role of specific AT2R neuron populations in depressing blood pressure, (ii) determine the relevance of such mechanisms, and (iii) investigate interactions between AT2R and depressor angiotensin-(1-7)/Mas mechanisms in the brain.
Olivera-Pasilio, Valentina; Lasserre, Moira; Castelló, María E.
Adult neurogenesis, an essential mechanism of brain plasticity, enables brain development along postnatal life, constant addition of new neurons, neuronal turnover, and/or regeneration. It is amply distributed but negatively modulated during development and along evolution. Widespread cell proliferation, high neurogenic, and regenerative capacities are considered characteristics of teleost brains during adulthood. These anamniotes are promising models to depict factors that modulate cell proliferation, migration, and neurogenesis, and might be intervened to promote brain plasticity in mammals. Nevertheless, the migration path of derived cells to their final destination was not studied in various teleosts, including most weakly electric fish. In this group adult brain morphology is attributed to sensory specialization, involving the concerted evolution of peripheral electroreceptors and electric organs, encompassed by the evolution of neural networks involved in electrosensory information processing. In wave type gymnotids adult brain morphology is proposed to result from lifelong region specific cell proliferation and neurogenesis. Consistently, pulse type weakly electric gymnotids and mormyrids show widespread distribution of proliferation zones that persists in adulthood, but their neurogenic potential is still unknown. Here we studied the migration process and differentiation of newborn cells into the neuronal phenotype in the pulse type gymnotid Gymnotus omarorum. Pulse labeling of S-phase cells with 5-Chloro-2′-deoxyuridine thymidine followed by 1 to 180 day survivals evidenced long distance migration of newborn cells from the rostralmost telencephalic ventricle to the olfactory bulb, and between layers of all cerebellar divisions. Shorter migration appeared in the tectum opticum and torus semicircularis. In many brain regions, derived cells expressed early neuronal markers doublecortin (chase: 1–30 days) and HuC/HuD (chase: 7–180 days). Some newborn
Full Text Available Adult neurogenesis, an essential mechanism of brain plasticity, enables brain development along postnatal life, constant addition of new neurons, neuronal turnover, and/or regeneration. It is amply distributed but negatively modulated during development and along evolution. Widespread cell proliferation, high neurogenic, and regenerative capacities are considered characteristics of teleost brains during adulthood. These anamniotes are promising models to depict factors that modulate cell proliferation, migration, and neurogenesis, and might be intervened to promote brain plasticity in mammals. Nevertheless, the migration path of derived cells to their final destination was not studied in various teleosts, including most weakly electric fish. In this group adult brain morphology is attributed to sensory specialization, involving the concerted evolution of peripheral electroreceptors and electric organs, encompassed by the evolution of neural networks involved in electrosensory information processing. In wave type gymnotids adult brain morphology is proposed to result from lifelong region specific cell proliferation and neurogenesis. Consistently, pulse type weakly electric gymnotids and mormyrids show widespread distribution of proliferation zones that persists in adulthood, but their neurogenic potential is still unknown. Here we studied the migration process and differentiation of newborn cells into the neuronal phenotype in the pulse type gymnotid Gymnotus omarorum. Pulse labeling of S-phase cells with 5-Chloro-2′-deoxyuridine thymidine followed by 1 to 180 day survivals evidenced long distance migration of newborn cells from the rostralmost telencephalic ventricle to the olfactory bulb, and between layers of all cerebellar divisions. Shorter migration appeared in the tectum opticum and torus semicircularis. In many brain regions, derived cells expressed early neuronal markers doublecortin (chase: 1–30 days and HuC/HuD (chase: 7–180 days
Full Text Available Alterations in cerebral cortex connectivity lead to intellectual disability and in Down syndrome, this is associated with a deficit in cortical neurons that arises during prenatal development. However, the pathogenic mechanisms that cause this deficit have not yet been defined. Here we show that the human DYRK1A kinase on chromosome 21 tightly regulates the nuclear levels of Cyclin D1 in embryonic cortical stem (radial glia cells, and that a modest increase in DYRK1A protein in transgenic embryos lengthens the G1 phase in these progenitors. These alterations promote asymmetric proliferative divisions at the expense of neurogenic divisions, producing a deficit in cortical projection neurons that persists in postnatal stages. Moreover, radial glial progenitors in the Ts65Dn mouse model of Down syndrome have less Cyclin D1, and Dyrk1a is the triplicated gene that causes both early cortical neurogenic defects and decreased nuclear Cyclin D1 levels in this model. These data provide insights into the mechanisms that couple cell cycle regulation and neuron production in cortical neural stem cells, emphasizing that the deleterious effect of DYRK1A triplication in the formation of the cerebral cortex begins at the onset of neurogenesis, which is relevant to the search for early therapeutic interventions in Down syndrome.
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
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.
Full Text Available ... the brain, which is linked to thought and emotion. It is also linked to reward systems in the brain. Problems in producing dopamine can result in Parkinson's disease, a disorder that affects a person's ability to move as they want to, resulting in ...
Full Text Available ... The brain's "fear hub," which activates our natural "fight-or-flight" response to confront or escape from a dangerous ... The brain's "fear hub," which helps activate the fight-or-flight response and is also involved in emotions and ...
Full Text Available ... will fire. This enhances the electrical flow among brain cells required for normal function and plays an important ... of neurons and their interconnections. neuron —A nerve cell that is the basic, working unit of the brain and nervous system, which processes and transmits information. ...
Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in understanding ...
Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in understanding ...
Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... MSC 9663 Bethesda, MD 20892-9663 Follow Us Facebook Twitter YouTube Google Plus NIMH Newsletter NIMH RSS ...
Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman who seemed to have it all. She was happily married and successful in business. Then, after a serious setback at work, she ...
Full Text Available ... to the front of the brain, which is linked to thought and emotion. It is also linked to reward systems in the brain. Problems in ... Problems in making or using glutamate have been linked to many mental disorders, including autism , obsessive compulsive ...
Full Text Available ... little dopamine or problems using dopamine in the thinking and feeling regions of the brain may play ... axis —A brain-body circuit which plays a critical role in the body's response to stress. impulse — ...
Full Text Available ... And as they grow there are differences in brain development in children who develop bipolar disorder than children who do not. Studies comparing such children to those with normal brain development may help scientists to pinpoint when and where ...
Full Text Available ... These circuits control specific body functions such as sleep and speech. The brain continues maturing well into a person's early 20s. ... Basics in Real Life—How Depression affects the Brain Meet Sarah ... had problems getting to sleep and generally felt tired, listless, and had no ...
Full Text Available ... in brain development in children who develop bipolar disorder than children who do not. Studies comparing such children to those with normal brain development may help scientists to pinpoint when and where mental disorders begin and perhaps how to slow or stop ...
Full Text Available ... as they grow there are differences in brain development in children who develop bipolar disorder than children who do not. Studies comparing such children to those with normal brain development may help scientists to pinpoint when and where ...
Full Text Available ... thinking and feeling regions of the brain may play a role in disorders like schizophrenia or attention deficit hyperactivity ... the front of the brain that, in humans, plays a role in executive functions such as judgment, decision making ...
Full Text Available ... PTSD) . Prefrontal cortex (PFC) —Seat of the brain's executive functions, such as judgment, decision making, and problem solving. ... brain that, in humans, plays a role in executive functions such as judgment, decision making and problem solving, ...
Full Text Available ... our physical surroundings but also factors that can affect our bodies, such as sleep, diet, or stress. These factors may act alone ... Life Brain Basics in Real Life—How Depression affects the Brain ... had problems getting to sleep and generally felt tired, listless, and had no ...
Full Text Available ... her symptoms were not caused by a stroke, brain tumor, or similar conditions, Sarah's doctor referred her to a psychiatrist, a type of medical doctor who is an expert on mental ... of serotonin in the brain and help reduce symptoms of depression. Sarah also ...
Full Text Available ... begun to chart how the brain develops over time in healthy people and are working to compare that with brain development in ... Other medical professionals who can diagnose mental disorders are psychologists or ... gets "the blues" from time to time. In contrast, major depression is a ...
Full Text Available ... such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies ... imaging (MRI) mdash;An imaging technique that uses magnetic fields to take pictures of the brain's structure. mutation — ...
Henry, Rebecca A; Hughes, Stephanie M; Connor, Bronwen
Brain-derived neurotrophic factor (BDNF) plays a major role in regulating the survival and fate of progenitor cells in the adult brain. In order to extend previous observations in the normal adult brain and advance our knowledge regarding the effect of BDNF on neurogenesis in the injured brain, this study directly compared the effect of BDNF on basal and injury-induced neurogenesis in relation to progenitor cell distribution and levels of neuronal differentiation and survival. BDNF was overexpressed in the subventricular zone (SVZ) via recombinant adeno-associated virus (AAV(1/2)) delivery, and newly generated cells were identified using bromodeoxyuridine (BrdU) labelling. Selective striatal cell loss was induced in a subgroup of rats by unilateral striatal injection of quinolinic acid (QA) 21 days after AAV(1/2) injection. In the normal brain, BDNF overexpression significantly increased BrdU-positive cell numbers in the rostral migratory stream, indicating enhanced progenitor cell migration. Following QA lesioning, we observed a reduction in BrdU immunoreactivity in the SVZ. Overexpression of BDNF restored BrdU-positive cell numbers in the QA-lesioned SVZ to that observed in the normal brain. Most significantly, BDNF enhanced the recruitment of progenitor cells to the QA-lesioned striatum and promoted neuronal differentiation in both the normal and QA-lesioned striatum. Our findings indicate that BDNF augments the recruitment, neuronal differentiation and survival of progenitor cells in both neurogenic and non-neurogenic regions of the normal or QA-lesioned brain. Enhanced expression of BDNF may therefore be a viable strategy for augmenting neurogenesis from endogenous progenitor cells.
Miyakoda, Keiichi (Yamashina Aiseikai Hospital, Kyoto (Japan)); Watanabe, Kousuke
In 45 patients (38 males and 7 females; average age:78 years) with brain bladder, who did not have any peripheral neuropathies and spinal disturbance, cerebral findings of MRI (1.5 T) T[sub 2] enhanced image were analyzed in comparison with those of 7 control patients with normal urination after BPH operations. Patients with neurogenic bladder were divided into three groups as follows: 33 patients with a chief complaint of urinary disturbance (Group I), 9 patients with urinary incontinence (Group II) and 3 patients with balanced bladder (Group III). High frequency of lacune (24%) of the globus pallidus and low signalling of the corpus striatum (30%) was found in Group I patients, but low frequency in other Group patients and control patients. Furthermore, pathologic changes with various grades in the globus pallidus were observed in 91% of Group I patients. In the treatment of urinary disturbance, a high improvement rate of micturition disorder (77%) was obtained in patients treated with a combination of dantrolene and TURp (TUIbn for females). However, patients who had clear lacune of the globus pallidus showed the low improvement rate. It should be possible that the globus pallidus contributes to control the movement of the external sphincter and the pelvic base muscles as well as other striated muscles. Moreover, lacune was rarely found in the urination center of the brain-stem on MRI. (author).
Amris, Kirstine; Jespersen, Anders
Fibromyalgia is characterised by chronic widespread pain and mechanical hyperalgesia. It is associated with a higher pain intensity, fewer pain-free intervals and more pronounced pain-related interference in function than other musculoskeletal pain conditions. Increasing evidence supports...... an underlying augmented central pain processing which includes sensitization of pain-transmitting neurons and dysfunction of pain inhibitory pathways. If this permanent change in the function of the nociceptive system is shown to equal fibromyalgia, the condition may be considered a neuropathic pain condition....
Amris, Kirstine; Jespersen, Anders
an underlying augmented central pain processing which includes sensitization of pain-transmitting neurons and dysfunction of pain inhibitory pathways. If this permanent change in the function of the nociceptive system is shown to equal fibromyalgia, the condition may be considered a neuropathic pain condition.......Fibromyalgia is characterised by chronic widespread pain and mechanical hyperalgesia. It is associated with a higher pain intensity, fewer pain-free intervals and more pronounced pain-related interference in function than other musculoskeletal pain conditions. Increasing evidence supports...
Amris, Kirstine; Jespersen, Anders
Fibromyalgia is characterised by chronic widespread pain and mechanical hyperalgesia. It is associated with a higher pain intensity, fewer pain-free intervals and more pronounced pain-related interference in function than other musculoskeletal pain conditions. Increasing evidence supports...
Biancardi, Vinicia Campana; Son, Sook Jin; Ahmadi, Sahra; Filosa, Jessica A; Stern, Javier E
Angiotensin II-mediated vascular brain inflammation emerged as a novel pathophysiological mechanism in neurogenic hypertension. However, the precise underlying mechanisms and functional consequences in relation to blood-brain barrier (BBB) integrity and central angiotensin II actions mediating neurohumoral activation in hypertension are poorly understood. Here, we aimed to determine whether BBB permeability within critical hypothalamic and brain stem regions involved in neurohumoral regulation was altered during hypertension. Using digital imaging quantification after intravascularly injected fluorescent dyes and immunohistochemistry, we found increased BBB permeability, along with altered key BBB protein constituents, in spontaneously hypertensive rats within the hypothalamic paraventricular nucleus, the nucleus of the solitary tract, and the rostral ventrolateral medulla, all critical brain regions known to contribute to neurohumoral activation during hypertension. BBB disruption, including increased permeability and downregulation of constituent proteins, was prevented in spontaneously hypertensive rats treated with the AT1 receptor antagonist losartan, but not with hydralazine, a direct vasodilator. Importantly, we found circulating angiotensin II to extravasate into these brain regions, colocalizing with neurons and microglial cells. Taken together, our studies reveal a novel angiotensin II-mediated feed-forward mechanism during hypertension, by which circulating angiotensin II evokes increased BBB permeability, facilitating in turn its access to critical brain regions known to participate in blood pressure regulation.
Pedersen, Bente K; Pedersen, Maria; Krabbe, Karen S
identifies BDNF as a player not only in central metabolism, but also in regulating energy metabolism in peripheral organs. Low levels of BDNF are found in patients with neurodegenerative diseases, including Alzheimer's disease and major depression. In addition, BDNF levels are low in obesity...... and independently so in patients with type 2 diabetes. Brain-derived neurotrophic factor is expressed in non-neurogenic tissues, including skeletal muscle, and exercise increases BDNF levels not only in the brain and in plasma, but in skeletal muscle as well. Brain-derived neurotrophic factor mRNA and protein...... expression was increased in muscle cells that were electrically stimulated, and BDNF increased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl coenzyme A carboxylase-beta (ACCbeta) and enhanced fatty oxidation both in vitro and ex vivo. These data identify BDNF as a contraction...
Pälvimäki, Esa-Pekka; Siironen, Jari; Pohjola, Juha; Hernesniemi, Juha
Brain concussion is a common disturbance caused by external forces or acceleration affecting the head. It may be accompanied by transient loss of consciousness and amnesia. Typical symptoms include headache, nausea and dizziness; these may remain for a week or two. Some patients may experience transient loss of inability to create new memories or other brief impairment of mental functioning. Treatment is symptomatic. Some patients may suffer from prolonged symptoms, the connection of which with brain concession is difficult to show. Almost invariably the prognosis of brain concussion is good.
Gonzalez-Perez, Oscar; Quiñones-Hinojosa, Alfredo
In the adult mammalian brain, bona fide neural stem cells were discovered in the subventricular zone (SVZ), the largest neurogenic niche lining the striatal wall of the lateral ventricles of the brain. In this region resides a subpopulation of astrocytes that express the glial fibrillary acidic protein (GFAP), nestin and LeX. Astonishingly, these GFAP-expressing progenitors display stem-cell-like features both in vivo and in vitro. Throughout life SVZ astrocytes give rise to interneurons and oligodendrocyte precursors, which populate the olfactory bulb and the white matter, respectively. The role of the progenies of SVZ astrocytes has not been fully elucidated, but some evidence indicates that the new neurons play a role in olfactory discrimination, whereas oligodendrocytes contribute to myelinate white matter tracts. In this chapter, we describe the astrocytic nature of adult neural stem cells, their organization into the SVZ and some of their molecular and genetic characteristics. PMID:23619383
Full Text Available Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia. Using a newly established in vitro system we show that calcium waves induced in an astrocytic monolayer spread to neural stem and progenitor cells and increase their self-renewal as well as migratory behavior. These changes are due to an upregulation of the Notch signaling pathway. This introduces the concept of propagating astrocytic calcium waves transmitting brain injury signals over long distances.