Nervous-Tissue-Specific Elimination of Microtubule-Actin Crosslinking Factor 1a Results in Multiple Developmental Defects in the Mouse Brain

PubMed Central

Goryunov, Dmitry; He, Cui-Zhen; Lin, Chyuan-Sheng; Leung, Conrad L.; Liem, Ronald K. H.

2010-01-01

The microtubule-actin crosslinking factor 1 (MACF1) is a ubiquitous cytoskeletal linker protein with multiple spliced isoforms expressed in different tissues. The MACF1a isoform contains microtubule and actin binding regions and is expressed at high levels in the nervous system. Macf1−/− mice are early embryonic lethal and hence the role of MACF1 in the nervous system could not be determined. We have specifically knocked out MACF1a in the developing mouse nervous system using Cre/loxP technology. Mutant mice died within 24–36 hrs after birth of apparent respiratory distress. Their brains displayed a disorganized cerebral cortex with a mixed layer structure, heterotopia in the pyramidal layer of the hippocampus, disorganized thalamocortical and corticofugal fibers, and aplastic anterior and hippocampal commissures. Embryonic neurons showed a defect in traversing the cortical plate. Our data suggest a critical role for MACF1 in neuronal migration that is dependent on its ability to interact with both microfilaments and microtubules. PMID:20170731

Nervous-tissue-specific elimination of microtubule-actin crosslinking factor 1a results in multiple developmental defects in the mouse brain.

PubMed

Goryunov, Dmitry; He, Cui-Zhen; Lin, Chyuan-Sheng; Leung, Conrad L; Liem, Ronald K H

2010-05-01

The microtubule-actin crosslinking factor 1 (MACF1) is a ubiquitous cytoskeletal linker protein with multiple spliced isoforms expressed in different tissues. The MACF1a isoform contains microtubule and actin-binding regions and is expressed at high levels in the nervous system. Macf1-/- mice are early embryonic lethal and hence the role of MACF1 in the nervous system could not be determined. We have specifically knocked out MACF1a in the developing mouse nervous system using Cre/loxP technology. Mutant mice died within 24-36h after birth of apparent respiratory distress. Their brains displayed a disorganized cerebral cortex with a mixed layer structure, heterotopia in the pyramidal layer of the hippocampus, disorganized thalamocortical and corticofugal fibers, and aplastic anterior and hippocampal commissures. Embryonic neurons showed a defect in traversing the cortical plate. Our data suggest a critical role for MACF1 in neuronal migration that is dependent on its ability to interact with both microfilaments and microtubules. Copyright 2010 Elsevier Inc. All rights reserved.

Multiple cerebral and cerebellar infarcts as the first clinical manifestation in a patient with Churg-Strauss syndrome: case report and literature review.

PubMed

Cheng, Meng-Ju; Huang, Pai-Hao; Liao, Pin-Wen; Chen, Jen-Tse; Chiang, Tsuey-Ru

2012-12-01

Churg-Strauss syndrome (CSS) is a rare autoimmune disease with small-vessel vasculitis. Neurological manifestation of CSS is common. Central nervous system is less frequently involved than that of peripheral nervous system. We report a case of 60-year-old man who presented with acute onset of right hemiparesis and impaired cognition. The presence of hypereosinophilia, asthma, sinusitis and extravascular eosinophil accumulation led to the diagnosis of Churg-Strauss syndrome. Brain magnetic resonance imaging (MRI) revealed multiple infarcts in bilateral cerebral and cerebellar hemispheres. The neurophysiology study did not reveal peripheral neuropathy. The patient was effectively treated with methylprednisolone, cyclophosphamide and warfarin. Symptoms and signs of central nervous system can be the initial neurological manifestation of CSS patients. CSS should be considered while patients have stroke and hypereosinophilia. In our patient, there is a good response to timely steroid, immunosuppressant and anticoagulant therapies.

Evoked potentials in multiple sclerosis.

PubMed

Kraft, George H

2013-11-01

Before the development of magnetic resonance imaging (MRI), evoked potentials (EPs)-visual evoked potentials, somatosensory evoked potentials, and brain stem auditory evoked responses-were commonly used to determine a second site of disease in patients being evaluated for possible multiple sclerosis (MS). The identification of an area of the central nervous system showing abnormal conduction was used to supplement the abnormal signs identified on the physical examination-thus identifying the "multiple" in MS. This article is a brief overview of additional ways in which central nervous system (CNS) physiology-as measured by EPs-can still contribute value in the management of MS in the era of MRIs. Copyright © 2013 Elsevier Inc. All rights reserved.

Mechanisms of developmental neurite pruning.

PubMed

Schuldiner, Oren; Yaron, Avraham

2015-01-01

The precise wiring of the nervous system is a combined outcome of progressive and regressive events during development. Axon guidance and synapse formation intertwined with cell death and neurite pruning sculpt the mature circuitry. It is now well recognized that pruning of dendrites and axons as means to refine neuronal networks, is a wide spread phenomena required for the normal development of vertebrate and invertebrate nervous systems. Here we will review the arising principles of cellular and molecular mechanisms of neurite pruning. We will discuss these principles in light of studies in multiple neuronal systems, and speculate on potential explanations for the emergence of neurite pruning as a mechanism to sculpt the nervous system.

Intranasal Insulin: A Novel Treatment for Gulf War Multisymptom Illness

DTIC Science & Technology

2017-10-01

nervous system (CNS). Over the years it has been found that cognitive complaints have been particularly troublesome to GWV. Recent studies have shown a...central nervous system (CNS). Over the years it has been found that cognitive complaints have been particularly troublesome to GWV. Recent studies...GWV may reflect executive system dysfunction (Tillman et al., 2010) as reflected by slower motor responses across multiple cognitive domains (RAC

Cell-based therapeutic strategies for multiple sclerosis

PubMed Central

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A; Atkins, Harold; Banwell, Brenda; Bar-Or, Amit; Bebo, Bruce; Bowen, James; Burt, Richard; Calabresi, Peter; Cohen, Jeffrey; Comi, Giancarlo; Connick, Peter; Cross, Anne; Cutter, Gary; Derfuss, Tobias; Ffrench-Constant, Charles; Freedman, Mark; Galipeau, Jacques; Goldman, Myla; Goldman, Steven; Goodman, Andrew; Green, Ari; Griffith, Linda; Hartung, Hans-Peter; Hemmer, Bernhard; Hyun, Insoo; Iacobaeus, Ellen; Inglese, Matilde; Jubelt, Burk; Karussis, Dimitrios; Küry, Patrick; Landsman, Douglas; Laule, Cornelia; Liblau, Roland; Mancardi, Giovanni; Ann Marrie, Ruth; Miller, Aaron; Miller, Robert; Miller, David; Mowry, Ellen; Muraro, Paolo; Nash, Richard; Ontaneda, Daniel; Pasquini, Marcelo; Pelletier, Daniel; Peruzzotti-Jametti, Luca; Pluchino, Stefano; Racke, Michael; Reingold, Stephen; Rice, Claire; Ringdén, Olle; Rovira, Alex; Saccardi, Riccardo; Sadiq, Saud; Sarantopoulos, Stefanie; Savitz, Sean; Scolding, Neil; Soelberg Sorensen, Per; Pia Sormani, Maria; Stuve, Olaf; Tesar, Paul; Thompson, Alan; Trojano, Maria; Uccelli, Antonio; Uitdehaag, Bernard; Utz, Ursula; Vukusic, Sandra; Waubant, Emmanuelle; Wilkins, Alastair

2017-01-01

Abstract The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. PMID:29053779

Capability of Virtual Environments to Meet Military Requirements

DTIC Science & Technology

2000-11-01

Hettinger, 1992). These symptoms, now called cybersickness (McCauley & Sharkey, 1992), could retard development of VE technology and limit its use as a... cybersickness may involve multiple functional pathways. The first pathway is related to ill-effects upon the autonomic nervous system or ANS (Money...avoided by obtaining a better understanding of the ANS mechanism. Another cybersickness pathway involves adaptation within the central nervous system

Mechanisms of developmental neurite pruning

PubMed Central

Schuldiner, Oren; Yaron, Avraham

2016-01-01

The precise wiring of the nervous system is a combined outcome of progressive and regressive events during development. Axon guidance and synapse formation intertwined with cell death and neurite pruning sculpt the mature circuitry. It is now well recognized that pruning of dendrites and axons as means to refine neuronal networks, is a wide spread phenomena required for the normal development of vertebrate and invertebrate nervous systems. Here we will review the arising principles of cellular and molecular mechanisms of neurite pruning. We will discuss these principles in light of studies in multiple neuronal systems, and speculate on potential explanations for the emergence of neurite pruning as a mechanism to sculpt the nervous system. PMID:25213356

Notes on the Epidemiology of Multiple Sclerosis, with Special Reference to Dietary Habits

PubMed Central

Lauer, Klaus

2014-01-01

A hypothesis, based primarily on the occurrence of multiple sclerosis (MS) in the Faroe Islands and supported by numerous analytical epidemiological studies, is described. It proposes that MS is caused by the interaction of a virus disease with intestinal pathology, e.g., infectious mononucleosis, and application of smoked and nitrate/nitrite-cured meat products in the diet during circumscribed time intervals. The biological mechanisms might involve a break of tolerance by an alteration of self within the central nervous system, by nitrophenylated compounds conjugated to animal tissue, in particular to proteins occurring in the central nervous system. Further research is needed. PMID:24577315

[Indications for percutaneous endoscopic gastrostomy in patients with disorders of the nervous system].

PubMed

Ehler, E; Geier, P; Dostál, V; Novotná, A; Vyhnálek, P; Hájek, J; Sákra, L

2002-05-01

Percutaneous endoscopic gastrostomy (PEG) is an efficient endoscopic method that ensures enteral nutrition for a longer period of time in patients who cannot take food per os. This method is also indicated in patients suffering from disorders of the central or peripheral nervous system which developed suddenly, such as a stroke or craniocerebral injuries, or gradually, such as amyotrophic lateral sclerosis (ALS), dementia, and multiple sclerosis. It has become common practice in the cooperation between neurologists and a gastroenterologists to use PEG in patients hospitalized in a neurological ward with encephalomalacy and haemorrhage, or craniocerebral injuries (after the patient recovers from the acute stage of the disease and is transferred to a neurological ICU), as well as in patients with ALS in a progressive stage. We gradually extend the indications of PEG for other patients with neurological disorders such as patients suffering from dementia, progressive multiple sclerosis, Parkinson's disease, and progressive polyneuropathy. Of 62 patients hospitalized in a neurological ward during a period of 4.5 years, 56 patients suffered from sudden disorders of the nervous system (strokes and craniocerebral injuries) and 6 patients had gradually progressing neurological diseases (ALS, multiple sclerosis, Parkinson's disease, dementia, and polyneuropathy).

Cancer risk among patients with multiple sclerosis: A cohort study in Isfahan, Iran.

PubMed

Etemadifar, Masoud; Jahanbani-Ardakani, Hamidreza; Ghaffari, Sara; Fereidan-Esfahani, Maboobeh; Changaei, Hossein; Aghadoost, Nazila; Jahanbani Ardakani, Ameneh; Moradkhani, Negin

2017-01-01

Multiple sclerosis (MS), a central nervous system (CNS) autoimmune disorder, affects 2.3 million people around the world. Cancer kills around 7.5 million people annually. Both diseases have similar risks and intertwining molecular causes. Most studies focusing on MS and cancer have found an insignificant difference or reduction in the amount of cancer found in the MS community. We performed a cohort study using data from Isfahan Multiple Sclerosis Society (IMSS) and Isfahan cancer society and followed-up for 8 years on average (2006-2014). All of the 1718 MS patients were diagnosed according to McDonald's criteria, then standardized incidence ratio and the numbers of expected cancer case were calculated. While patients had an insignificant change in cancer prevalence, men had fewer cancer cases and women showed an increased prevalence of cancer. Certain types of cancer proved statistically significant. Breast cancer, nervous system cancers, and lymphoma were elevated in the cohort. Our results support the hypothesis that MS significantly affects certain cancers in a protective or associative manner. All cancer rates, except breast cancer, cancers located in the nervous system, and lymphomas were reduced in cohort, suggesting that unregulated immune function may provide protective effects to MS patients against cancer.

Blood pressure normalization post-jugular venous balloon angioplasty.

PubMed

Sternberg, Zohara; Grewal, Prabhjot; Cen, Steven; DeBarge-Igoe, Frances; Yu, Jinhee; Arata, Michael

2015-05-01

This study is the first in a series investigating the relationship between autonomic nervous system dysfunction and chronic cerebrospinal venous insufficiency in multiple sclerosis patients. We screened patients for the combined presence of the narrowing of the internal jugular veins and symptoms of autonomic nervous system dysfunction (fatigue, cognitive dysfunction, sleeping disorders, headache, thermal intolerance, bowel/bladder dysfunction) and determined systolic and diastolic blood pressure responses to balloon angioplasty. The criteria for eligibility for balloon angioplasty intervention included ≥ 50% narrowing in one or both internal jugular veins, as determined by the magnetic resonance venography, and ≥ 3 clinical symptoms of autonomic nervous system dysfunction. Blood pressure was measured at baseline and post-balloon angioplasty. Among patients who were screened, 91% were identified as having internal jugular veins narrowing (with obstructing lesions) combined with the presence of three or more symptoms of autonomic nervous system dysfunction. Balloon angioplasty reduced the average systolic and diastolic blood pressure. However, blood pressure categorization showed a biphasic response to balloon angioplasty. The procedure increased blood pressure in multiple sclerosis patients who presented with baseline blood pressure within lower limits of normal ranges (systolic ≤ 105 mmHg, diastolic ≤ 70 mmHg) but decreased blood pressure in patients with baseline blood pressure above normal ranges (systolic ≥ 130 mmHg, diastolic ≥ 80 mmHg). In addition, gender differences in baseline blood pressure subcategories were observed. The coexistence of internal jugular veins narrowing and symptoms of autonomic nervous system dysfunction suggests that the two phenomena may be related. Balloon angioplasty corrects blood pressure deviation in multiple sclerosis patients undergoing internal jugular vein dilation. Further studies should investigate the association between blood pressure deviation and internal jugular veins narrowing, and whether blood pressure normalization affects Patient's clinical outcomes. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Risk of central nervous system defects in offspring of women with and without mental illness.

PubMed

Ayoub, Aimina; Fraser, William D; Low, Nancy; Arbour, Laura; Healy-Profitós, Jessica; Auger, Nathalie

2018-02-22

We sought to determine the relationship between maternal mental illness and the risk of having an infant with a central nervous system defect. We analyzed a cohort of 654,882 women aged less than 20 years between 1989 and 2013 who later delivered a live born infant in any hospital in Quebec, Canada. The primary exposure was mental illness during pregnancy or hospitalization for mental illness before pregnancy. The outcomes were neural and non-neural tube defects of the central nervous system in any offspring. We computed risk ratios (RR) and 95% confidence intervals (CI) for the association between mental disorders and risk of central nervous system defects in log-binomial regression models adjusted for age at delivery, total parity, comorbidity, socioeconomic deprivation, place of residence, and time period. Maternal mental illness was associated with an increased risk of nervous system defects in offspring (RR 1.76, 95% CI 1.64-1.89). Hospitalization for any mental disorder was more strongly associated with non-neural tube (RR 1.84, 95% CI 1.71-1.99) than neural tube defects (RR 1.31, 95% CI 1.08-1.59). Women at greater risk of nervous system defects in offspring tended to be diagnosed with multiple mental disorders, have more than one hospitalization for mental disease, or be 17 or older at first hospitalization. A history of mental illness is associated with central nervous system defects in offspring. Women hospitalized for mental illness may merit counseling at first symptoms to prevent central nervous system defects at pregnancy.

Intravascular lymphoma involving the central and peripheral nervous systems in a dog.

PubMed

Bush, William W; Throop, Juliene L; McManus, Patricia M; Kapatkin, Amy S; Vite, Charles H; Van Winkle, Tom J

2003-01-01

A 5-year-old, castrated male mixed-breed dog was presented for paraparesis, ataxia, hyperesthesia, and thrombocytopenia of 5 months' duration and recurrent seizures during the preceding 2 weeks. Multifocal neurological, ophthalmological, pulmonary, and cardiac diseases were identified. Magnetic resonance imaging and cerebrospinal fluid analysis supported a tentative diagnosis of neoplastic or inflammatory disease. A computed tomography-guided biopsy provided both cytopathological and histopathological evidence of intravascular lymphoma. The disease progressed despite chemotherapy with prednisone, L-asparginase, and vincristine. Postmortem histopathological examinations suggested intravascular lymphoma in the central and peripheral nervous systems as well as in multiple other organ systems. This is the first description of an antemortem diagnosis and treatment of intravascular lymphoma involving the central nervous system of a dog.

Cell-based therapeutic strategies for multiple sclerosis.

PubMed

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

2017-11-01

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

On the morphology of the central nervous system in larval stages of Carcinus maenas L. (Decapoda, Brachyura)

NASA Astrophysics Data System (ADS)

Harzsch, S.; Dawirs, R. R.

1993-02-01

We investigated the morphology of the central nervous system throughout the larval development of Carcinus maenas. For that purpose single larvae were reared in the laboratory from hatching through metamorphosis. Complete series of whole mout semithin sections were obtained from individuals of all successive larval stages and analysed with a light microscope. Morphological feature and spatial arrangement of discernable neural cell clusters, fibre tracts and neuropile are described and compared with the adult pattern. We found that most of the morphological features characterizing the adult nervous system are already present in the zoea-1. Nevertheless, there are marked differences with respect to the arrangement of nerve cell bodies, organization of cerebral neuropile, and disposition of ganglia in the ventral nerve cord. It appears that complexity of the central nervous neuropile is selectively altered during postmetamorphotic development, probably reflecting adaptive changes of sensory-motor integration in response to behavioural maturation. In contrast, during larval development there was little change in the overall structural organization of the central nervous system despite some considerable growth. However, the transition from zoea-4 to megalopa brings about multiple fundamental changes in larval morphology and behavioural pattern. Since central nervous integration should properly adapt to the altered behavioural repertoire of the megalopa, it seems necessary to ask in which respect synaptic rearrangement might characterize development of the central nervous system.

Autonomic nervous system involvement in pulmonary arterial hypertension.

PubMed

Vaillancourt, Mylène; Chia, Pamela; Sarji, Shervin; Nguyen, Jason; Hoftman, Nir; Ruffenach, Gregoire; Eghbali, Mansoureh; Mahajan, Aman; Umar, Soban

2017-12-04

Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disease characterized by increased pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Autonomic nervous system involvement in the pathogenesis of PAH has been demonstrated several years ago, however the extent of this involvement is not fully understood. PAH is associated with increased sympathetic nervous system (SNS) activation, decreased heart rate variability, and presence of cardiac arrhythmias. There is also evidence for increased renin-angiotensin-aldosterone system (RAAS) activation in PAH patients associated with clinical worsening. Reduction of neurohormonal activation could be an effective therapeutic strategy for PAH. Although therapies targeting adrenergic receptors or RAAS signaling pathways have been shown to reverse cardiac remodeling and improve outcomes in experimental pulmonary hypertension (PH)-models, the effectiveness and safety of such treatments in clinical settings have been uncertain. Recently, novel direct methods such as cervical ganglion block, pulmonary artery denervation (PADN), and renal denervation have been employed to attenuate SNS activation in PAH. In this review, we intend to summarize the multiple aspects of autonomic nervous system involvement in PAH and overview the different pharmacological and invasive strategies used to target autonomic nervous system for the treatment of PAH.

Vitamin D and the central nervous system.

PubMed

Wrzosek, Małgorzata; Łukaszkiewicz, Jacek; Wrzosek, Michał; Jakubczyk, Andrzej; Matsumoto, Halina; Piątkiewicz, Paweł; Radziwoń-Zaleska, Maria; Wojnar, Marcin; Nowicka, Grażyna

2013-01-01

Vitamin D is formed in human epithelial cells via photochemical synthesis and is also acquired from dietary sources. The so-called classical effect of this vitamin involves the regulation of calcium homeostasis and bone metabolism. Apart from this, non-classical effects of vitamin D have recently gained renewed attention. One important yet little known of the numerous functions of vitamin D is the regulation of nervous system development and function. The neuroprotective effect of vitamin D is associated with its influence on neurotrophin production and release, neuromediator synthesis, intracellular calcium homeostasis, and prevention of oxidative damage to nervous tissue. Clinical studies suggest that vitamin D deficiency may lead to an increased risk of disease of the central nervous system (CNS), particularly schizophrenia and multiple sclerosis. Adequate intake of vitamin D during pregnancy and the neonatal period seems to be crucial in terms of prevention of these diseases.

Seven-pass transmembrane cadherins: roles and emerging mechanisms in axonal and dendritic patterning.

PubMed

Berger-Müller, Sandra; Suzuki, Takashi

2011-12-01

The Flamingo/Celsr seven-transmembrane cadherins represent a conserved subgroup of the cadherin superfamily involved in multiple aspects of development. In the developing nervous system, Fmi/Celsr control axonal blueprint and dendritic morphogenesis from invertebrates to mammals. As expected from their molecular structure, seven-transmembrane cadherins can induce cell-cell homophilic interactions but also intracellular signaling. Fmi/Celsr is known to regulate planar cell polarity (PCP) through interactions with PCP proteins. In the nervous system, Fmi/Celsr can function in collaboration with or independently of other PCP genes. Here, we focus on recent studies which show that seven-transmembrane cadherins use distinct molecular mechanisms to achieve diverse functions in the development of the nervous system.

Distribution and function of voltage-gated sodium channels in the nervous system.

PubMed

Wang, Jun; Ou, Shao-Wu; Wang, Yun-Jie

2017-11-02

Voltage-gated sodium channels (VGSCs) are the basic ion channels for neuronal excitability, which are crucial for the resting potential and the generation and propagation of action potentials in neurons. To date, at least nine distinct sodium channel isoforms have been detected in the nervous system. Recent studies have identified that voltage-gated sodium channels not only play an essential role in the normal electrophysiological activities of neurons but also have a close relationship with neurological diseases. In this study, the latest research findings regarding the structure, type, distribution, and function of VGSCs in the nervous system and their relationship to neurological diseases, such as epilepsy, neuropathic pain, brain tumors, neural trauma, and multiple sclerosis, are reviewed in detail.

Cancer risk among patients with multiple sclerosis: A cohort study in Isfahan, Iran

PubMed Central

Etemadifar, Masoud; Jahanbani-Ardakani, Hamidreza; Ghaffari, Sara; Fereidan-Esfahani, Maboobeh; Changaei, Hossein; Aghadoost, Nazila; Jahanbani Ardakani, Ameneh; Moradkhani, Negin

2017-01-01

Background: Multiple sclerosis (MS), a central nervous system (CNS) autoimmune disorder, affects 2.3 million people around the world. Cancer kills around 7.5 million people annually. Both diseases have similar risks and intertwining molecular causes. Most studies focusing on MS and cancer have found an insignificant difference or reduction in the amount of cancer found in the MS community. Methods: We performed a cohort study using data from Isfahan Multiple Sclerosis Society (IMSS) and Isfahan cancer society and followed-up for 8 years on average (2006-2014). All of the 1718 MS patients were diagnosed according to McDonald’s criteria, then standardized incidence ratio and the numbers of expected cancer case were calculated. Results: While patients had an insignificant change in cancer prevalence, men had fewer cancer cases and women showed an increased prevalence of cancer. Certain types of cancer proved statistically significant. Breast cancer, nervous system cancers, and lymphoma were elevated in the cohort. Conclusion: Our results support the hypothesis that MS significantly affects certain cancers in a protective or associative manner. All cancer rates, except breast cancer, cancers located in the nervous system, and lymphomas were reduced in cohort, suggesting that unregulated immune function may provide protective effects to MS patients against cancer. PMID:28932368

Neuromuscular Disorders

MedlinePlus

... become unhealthy or die, communication between your nervous system and muscles breaks down. As a result, your muscles weaken ... Amyotrophic lateral sclerosis Multiple sclerosis Myasthenia ... your genes. Sometimes, an immune system disorder can cause them. Most of them have ...

TRPA1 deficiency is protective in cuprizone-induced demyelination-A new target against oligodendrocyte apoptosis.

PubMed

Sághy, Éva; Sipos, Éva; Ács, Péter; Bölcskei, Kata; Pohóczky, Krisztina; Kemény, Ágnes; Sándor, Zoltán; Szőke, Éva; Sétáló, György; Komoly, Sámuel; Pintér, Erika

2016-12-01

Multiple sclerosis is a chronic inflammatory, demyelinating degenerative disease of the central nervous system. Current treatments target pathological immune responses to counteract the inflammatory processes. However, these drugs do not restrain the long-term progression of clinical disability. For this reason, new therapeutic approaches and identification of novel target molecules are needed to prevent demyelination or promote repair mechanisms. Transient Receptor Potential Ankyrin 1 (TRPA1) is a nonselective cation channel with relatively high Ca 2+ permeability. Its pathophysiological role in central nervous system disorders has not been elucidated yet. In the present study, we aimed to assess the distribution of TRPA1 in the mouse brain and reveal its regulatory role in the cuprizone-induced demyelination. This toxin-induced model, characterized by oligodendrocyte apoptosis and subsequent primary demyelination, allows us to investigate the nonimmune aspects of multiple sclerosis. We found that TRPA1 is expressed on astrocytes in the mouse central nervous system. Interestingly, TRPA1 deficiency significantly attenuated cuprizone-induced demyelination by reducing the apoptosis of mature oligodendrocytes. Our data suggest that TRPA1 regulates mitogen-activated protein kinase pathways, as well as transcription factor c-Jun and a proapoptotic Bcl-2 family member (Bak) expression resulting in enhanced oligodendrocyte apoptosis. In conclusion, we propose that TRPA1 receptors enhancing the intracellular Ca 2+ concentration modulate astrocyte functions, and influence the pro or anti-apoptotic pathways in oligodendrocytes. Inhibition of TRPA1 receptors might successfully diminish the degenerative pathology in multiple sclerosis and could be a promising therapeutic target to limit central nervous system damage in demyelinating diseases. GLIA 2016;64:2166-2180. © 2016 Wiley Periodicals, Inc.

Role of the autonomic nervous system in tumorigenesis and metastasis

PubMed Central

Magnon, Claire

2015-01-01

Convergence of multiple stromal cell types is required to develop a tumorigenic niche that nurtures the initial development of cancer and its dissemination. Although the immune and vascular systems have been shown to have strong influences on cancer, a growing body of evidence points to a role of the nervous system in promoting cancer development. This review discusses past and current research that shows the intriguing role of autonomic nerves, aided by neurotrophic growth factors and axon cues, in creating a favorable environment for the promotion of tumor formation and metastasis. PMID:27308436

Role of the autonomic nervous system in tumorigenesis and metastasis.

PubMed

Magnon, Claire

2015-01-01

Convergence of multiple stromal cell types is required to develop a tumorigenic niche that nurtures the initial development of cancer and its dissemination. Although the immune and vascular systems have been shown to have strong influences on cancer, a growing body of evidence points to a role of the nervous system in promoting cancer development. This review discusses past and current research that shows the intriguing role of autonomic nerves, aided by neurotrophic growth factors and axon cues, in creating a favorable environment for the promotion of tumor formation and metastasis.

Statin Therapy Inhibits Remyelination in the Central Nervous System

PubMed Central

Miron, Veronique E.; Zehntner, Simone P.; Kuhlmann, Tanja; Ludwin, Samuel K.; Owens, Trevor; Kennedy, Timothy E.; Bedell, Barry J.; Antel, Jack P.

2009-01-01

Remyelination of lesions in the central nervous system contributes to neural repair following clinical relapses in multiple sclerosis. Remyelination is initiated by recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Simvastatin, a blood-brain barrier-permeable statin in multiple sclerosis clinical trials, has been shown to impact the in vitro processes that have been implicated in remyelination. Animals were fed a cuprizone-supplemented diet for 6 weeks to induce localized demyelination in the corpus callosum; subsequent return to normal diet for 3 weeks stimulated remyelination. Simvastatin was injected intraperitoneally during the period of coincident demyelination and OPC maturation (weeks 4 to 6), throughout the entire period of OPC responses (weeks 4 to 9), or during the remyelination-only phase (weeks 7 to 9). Simvastatin treatment (weeks 4 to 6) caused a decrease in myelin load and both Olig2strong and Nkx2.2strong OPC numbers. Simvastatin treatment (weeks 4 to 9 and 7 to 9) caused a decrease in myelin load, which was correlated with a reduction in Nkx2.2strong OPCs and an increase in Olig2strong cells, suggesting that OPCs were maintained in an immature state (Olig2strong/Nkx2.2weak). NogoA+ oligodendrocyte numbers were decreased during all simvastatin treatment regimens. Our findings suggest that simvastatin inhibits central nervous system remyelination by blocking progenitor differentiation, indicating the need to monitor effects of systemic immunotherapies that can access the central nervous system on brain tissue-repair processes. PMID:19349355

Pazopanib efficacy in recurrent central nervous system hemangiopericytomas.

PubMed

Apra, Caroline; Alentorn, Agusti; Mokhtari, Karima; Kalamarides, Michel; Sanson, Marc

2018-04-26

There is currently no treatment for solitary fibrous tumors/hemangiopericytomas (SFT/H) of the central nervous system recurring after multiple surgeries and radiotherapies. The NAB2-STAT6 gene fusion is the hallmark of these tumors, and upregulates Early Growth Factor, activating several growth pathways. We treated two patients presenting pluri-recurrent meningeal SFT/H with Pazopanib, a broad-spectrum tyrosine kinase inhibitor. We analyzed the exome and RNA sequencing data of one of them and, in addition to another meningeal SFT/H, compared it to the transcriptomic profiling of 5 systemic SFT/H. A dramatic clinical and radiological response was observed in both cases, respectively 84 and 43% decrease after 3 months. As a comparison, Pazopanib has only a stabilizing effect in systemic SFT/H. Indeed, central nervous system SFT/H show overexpression of different tyrosine kinases targeted by Pazopanib. Two consecutive patients with untreatable central nervous system SFT/H showed a spectacular partial response to Pazopanib, an unprecedented result in SFT/H. This result could be explained by differences in expression profiles and calls for a confirmation in a larger cohort of patients.

Ultrasound diagnosis of central nervous system anomalies (bifid choroid plexus, ventriculomegaly, Dandy-Walker malformation) associated with multicystic dysplastic kidney disease in a trisomy 9 fetus: case report with literature review.

PubMed

Tonni, Gabriele; Grisolia, Giampaolo

2013-09-01

Trisomy 9 is a lethal chromosomal abnormality that rarely progresses beyond the second trimester of pregnancy. Multiple central nervous system anomalies, including bifid choroid plexus, ventriculomegaly, and Dandy-Walker malformation, associated with multicystic dysplastic kidney disease in a trisomy 9 fetus are reported. The prenatal ultrasound diagnosis has been aided by novel three-dimensional ultrasound software. Copyright © 2012 Wiley Periodicals, Inc.

Central nervous system remyelination in culture--a tool for multiple sclerosis research.

PubMed

Zhang, Hui; Jarjour, Andrew A; Boyd, Amanda; Williams, Anna

2011-07-01

Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. Copyright © 2011 Elsevier Inc. All rights reserved.

Central nervous system remyelination in culture — A tool for multiple sclerosis research

PubMed Central

Zhang, Hui; Jarjour, Andrew A.; Boyd, Amanda; Williams, Anna

2011-01-01

Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. PMID:21515259

Emerging Role for Methylation in Multiple Sclerosis: Beyond DNA.

PubMed

Webb, Lindsay M; Guerau-de-Arellano, Mireia

2017-06-01

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The inflammatory and neurodegenerative pathways driving MS are modulated by DNA, lysine, and arginine methylation, as evidenced by studies made possible by novel tools for methylation detection or loss of function. We present evidence that MS is associated with genetic variants and metabolic changes that impact on methylation. Further, we comprehensively review current understanding of how methylation can impact on central nervous system (CNS) resilience and neuroregenerative potential, as well as inflammatory versus regulatory T helper (Th) cell balance. These findings are discussed in the context of therapeutic relevance for MS, with broad implications in other neurologic and immune-mediated diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inflammation, Iron, Energy Failure, and Oxidative Stress in the Pathogenesis of Multiple Sclerosis

PubMed Central

Haider, Lukas

2015-01-01

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Different trigger pathologies have been suggested by the primary cytodegenerative “inside-out” and primary inflammation-driven “outside-in” hypotheses. Recent data indicate that mitochondrial injury and subsequent energy failure are key factors in the induction of demyelination and neurodegeneration. The brain weighs only a few percent of the body mass but accounts for approximately 20% of the total basal oxygen consumption of mitochondria. Oxidative stress induces mitochondrial injury in patients with multiple sclerosis and energy failure in the central nervous system of susceptible individuals. The interconnected mechanisms responsible for free radical production in patients with multiple sclerosis are as follows: (i) inflammation-induced production of free radicals by activated immune cells, (ii) liberation of iron from the myelin sheets during demyelination, and (iii) mitochondrial injury and thus energy failure-related free radical production. In the present review, the different sources of oxidative stress and their relationships to patients with multiple sclerosis considering tissue injury mechanisms and clinical aspects have been discussed. PMID:26106458

Dysarthria

MedlinePlus

... on the central nervous system, such as narcotics, phenytoin, or carbamazepine Symptoms Depending on its cause, dysarthria ... lose the ability to speak. Some people with Parkinson disease or multiple sclerosis lose the ability to ...

Childhood Multiple Sclerosis: A Review

ERIC Educational Resources Information Center

Waldman, Amy; O'Connor, Erin; Tennekoon, Gihan

2006-01-01

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) that is increasingly recognized as a disease that affects children. Similar to adult-onset MS, children present with visual and sensory complaints, as well as weakness, spasticity, and ataxia. A lumbar puncture can be helpful in diagnosing MS when…

Neuronopathic Lysosomal Storage Diseases: Clinical and Pathologic Findings

ERIC Educational Resources Information Center

Prada, Carlos E.; Grabowski, Gregory A.

2013-01-01

Background: The lysosomal--autophagocytic system diseases (LASDs) affect multiple body systems including the central nervous system (CNS). The progressive CNS pathology has its onset at different ages, leading to neurodegeneration and early death. Methods: Literature review provided insight into the current clinical neurological findings,…

Relapsing remitting multiple sclerosis in x-linked charcot-marie-tooth disease with central nervous system involvement.

PubMed

Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

PubMed Central

Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis. PMID:25883816

Cerebrospinal Fluid Cytokine Expression Profile in Multiple Sclerosis and Chronic Inflammatory Demyelinating Polyneuropathy.

PubMed

Bonin, Serena; Zanotta, Nunzia; Sartori, Arianna; Bratina, Alessio; Manganotti, Paolo; Trevisan, Giusto; Comar, Manola

2018-02-01

Cerebrospinal fluid (CSF) analysis in patients with particular neurologic disorders is a powerful tool to evaluate specific central nervous system inflammatory markers for diagnostic needs, because CSF represents the specific immune micro-environment to the central nervous system. CSF samples from 49 patients with multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), and non-inflammatory neurologic disorders (NIND) as controls were submitted to protein expression profiles of 47 inflammatory biomarkers by multiplex Luminex bead assay to investigate possible differences in the inflammatory process for MS and CIDP. Our results showed differences in CSF cytokine levels in MS and CIDP; in particular, IL12 (p40) was significantly highly expressed in MS in comparison with CIDP and NIND, while SDF-1α and SCGF-β were significantly highly expressed in CIDP cohort when compared to MS and NIND. IL-9, IL-13, and IL-17 had higher expression levels in NIND if compared with the other groups. Our study showed that, despite some common pathogenic mechanisms, central and peripheral nervous system demyelinating diseases, such as MS and CIDP, differ in some specific inflammatory soluble proteins in CSF, underlining differences in the immune response involved in those autoimmune diseases.

Application of Targeted Mass Spectrometry for the Quantification of Sirtuins in the Central Nervous System

NASA Astrophysics Data System (ADS)

Jayasena, T.; Poljak, A.; Braidy, N.; Zhong, L.; Rowlands, B.; Muenchhoff, J.; Grant, R.; Smythe, G.; Teo, C.; Raftery, M.; Sachdev, P.

2016-10-01

Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7). Quantification of all peptides was by multiple reaction monitoring (MRM) using three mass transitions per protein-specific peptide, two specific peptides for each sirtuin and a stable isotope labelled internal standard. The assay was applied to a variety of samples including cultured brain cells, mammalian brain tissue, CSF and plasma. All sirtuin peptides were detected in the human brain, with SIRT2 being the most abundant. Sirtuins were also detected in human CSF and plasma, and guinea pig and mouse tissues. In conclusion, we have successfully applied MRM mass spectrometry for the detection and quantification of sirtuin proteins in the central nervous system, paving the way for more quantitative and functional studies.

The role of TAM family receptors and ligands in the nervous system: From development to pathobiology.

PubMed

Shafit-Zagardo, Bridget; Gruber, Ross C; DuBois, Juwen C

2018-03-04

Tyro3, Axl, and Mertk, referred to as the TAM family of receptor tyrosine kinases, are instrumental in maintaining cell survival and homeostasis in mammals. TAM receptors interact with multiple signaling molecules to regulate cell migration, survival, phagocytosis and clearance of metabolic products and cell debris called efferocytosis. The TAMs also function as rheostats to reduce the expression of proinflammatory molecules and prevent autoimmunity. All three TAM receptors are activated in a concentration-dependent manner by the vitamin K-dependent growth arrest-specific protein 6 (Gas6). Gas6 and the TAMs are abundantly expressed in the nervous system. Gas6, secreted by neurons and endothelial cells, is the sole ligand for Axl. ProteinS1 (ProS1), another vitamin K-dependent protein functions mainly as an anti-coagulant, and independent of this function can activate Tyro3 and Mertk, but not Axl. This review will focus on the role of the TAM receptors and their ligands in the nervous system. We highlight studies that explore the function of TAM signaling in myelination, the visual cortex, neural cancers, and multiple sclerosis (MS) using Gas6 -/- and TAM mutant mice models. Copyright © 2018. Published by Elsevier Inc.

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

Biology of GDNF and its receptors - Relevance for disorders of the central nervous system.

PubMed

Ibáñez, Carlos F; Andressoo, Jaan-Olle

2017-01-01

A targeted effort to identify novel neurotrophic factors for midbrain dopaminergic neurons resulted in the isolation of GDNF (glial cell line-derived neurotrophic factor) from the supernatant of a rat glial cell line in 1993. Over two decades and 1200 papers later, the GDNF ligand family and their different receptor systems are now recognized as one of the major neurotrophic networks in the nervous system, important for the development, maintenance and function of a variety of neurons and glial cells. The many ways in which the four members of the GDNF ligand family can signal and function allow these factors to take part in the control of multiple types of processes, from neuronal survival to axon guidance and synapse formation in the developing nervous system, to synaptic function and regenerative responses in the adult. In this review, we will briefly summarize basic aspects of GDNF signaling mechanisms and receptor systems and then review our current knowledge of the physiology of GDNF activities in the central nervous system, with an eye to its relevance for neurodegenerative and neuropsychiatric diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Blood-brain barrier-on-a-chip: Microphysiological systems that capture the complexity of the blood-central nervous system interface.

PubMed

Phan, Duc Tt; Bender, R Hugh F; Andrejecsk, Jillian W; Sobrino, Agua; Hachey, Stephanie J; George, Steven C; Hughes, Christopher Cw

2017-11-01

The blood-brain barrier is a dynamic and highly organized structure that strictly regulates the molecules allowed to cross the brain vasculature into the central nervous system. The blood-brain barrier pathology has been associated with a number of central nervous system diseases, including vascular malformations, stroke/vascular dementia, Alzheimer's disease, multiple sclerosis, and various neurological tumors including glioblastoma multiforme. There is a compelling need for representative models of this critical interface. Current research relies heavily on animal models (mostly mice) or on two-dimensional (2D) in vitro models, neither of which fully capture the complexities of the human blood-brain barrier. Physiological differences between humans and mice make translation to the clinic problematic, while monolayer cultures cannot capture the inherently three-dimensional (3D) nature of the blood-brain barrier, which includes close association of the abluminal side of the endothelium with astrocyte foot-processes and pericytes. Here we discuss the central nervous system diseases associated with blood-brain barrier pathology, recent advances in the development of novel 3D blood-brain barrier -on-a-chip systems that better mimic the physiological complexity and structure of human blood-brain barrier, and provide an outlook on how these blood-brain barrier-on-a-chip systems can be used for central nervous system disease modeling. Impact statement The field of microphysiological systems is rapidly evolving as new technologies are introduced and our understanding of organ physiology develops. In this review, we focus on Blood-Brain Barrier (BBB) models, with a particular emphasis on how they relate to neurological disorders such as Alzheimer's disease, multiple sclerosis, stroke, cancer, and vascular malformations. We emphasize the importance of capturing the three-dimensional nature of the brain and the unique architecture of the BBB - something that until recently had not been well modeled by in vitro systems. Our hope is that this review will provide a launch pad for new ideas and methodologies that can provide us with truly physiological BBB models capable of yielding new insights into the function of this critical interface.

Expression profiling of peroxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissue microarray.

PubMed

Higashiyama, Hiroyuki; Billin, Andrew N; Okamoto, Yuji; Kinoshita, Mine; Asano, Satoshi

2007-05-01

Peroxisome proliferator-activated receptor-delta (PPAR-delta) is known as a transcription factor involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in several tissues, such as skeletal muscle, liver and adipose tissues. In this study, to elucidate systemic physiological functions of PPAR-delta, we examined the tissue distribution and localization of PPAR-delta in adult mouse tissues using tissue microarray (TMA)-based immunohistochemistry. PPAR-delta positive signals were observed on variety of tissues/cells in multiple systems including cardiovascular, urinary, respiratory, digestive, endocrine, nervous, hematopoietic, immune, musculoskeletal, sensory and reproductive organ systems. In these organs, PPAR-delta immunoreactivity was generally localized on the nucleus, although cytoplasmic localization was observed on several cell types including neurons in the nervous system and cells of the islet of Langerhans. These expression profiling data implicate various physiological roles of PPAR-delta in multiple organ systems. TMA-based immunohistochemistry enables to profile comprehensive protein localization and distribution in a high-throughput manner.

Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair

PubMed Central

Luo, Lihua; Wang, Xiaoyan; Key, Brian; Lee, Bae Hoon

2018-01-01

This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases. PMID:29853908

Coexistence of multiple sclerosis and ankylosing spondylitis: Report of four cases from Russia and review of the literature.

PubMed

Fominykh, Vera; Shevtsova, Tatyana; Arzumanian, Narine; Brylev, Lev

2017-10-01

Multiple sclerosis is a chronic demyelinating disorder of the central nervous system. There are many cases of multiple sclerosis - like syndrome and demyelinating disorders in systemic lupus erythematosus, Sjogren disease, Behcet disease and other autoimmune conditions. Coexistence of ankylosing spondylitis and multiple sclerosis usually is rare but in this article we report 4 Russian patients with concomitant multiple sclerosis and ankylosing spondylitis diseases. None of these patients received anti-tumor necrosis factor alpha therapy prior to diagnosis of multiple sclerosis. Pathogenesis, diagnostic and treatment challenges are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis.

PubMed

Tran, Khiem A; Zhang, Xianming; Predescu, Dan; Huang, Xiaojia; Machado, Roberto F; Göthert, Joachim R; Malik, Asrar B; Valyi-Nagy, Tibor; Zhao, You-Yang

2016-01-12

The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients. These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation. © 2015 American Heart Association, Inc.

Numerous Fusiform and Saccular Cerebral Aneurysms in Central Nervous System Lupus Presenting with Ischemic Stroke.

PubMed

Majidi, Shahram; Leon Guerrero, Christopher R; Gandhy, Shreya; Burger, Kathleen M; Sigounas, Dimitri

2017-07-01

Central nervous system (CNS) involvement occurs in up to 50% of patients with systemic lupus erythematosus (SLE). Cerebral aneurysm formation is a rare complication of CNS lupus. The majority of these patients present with subarachnoid hemorrhage. We report a patient with an active SLE flare who presented with a recurrent ischemic stroke and was found to have numerous unruptured fusiform and saccular aneurysms in multiple vascular territories. He was treated with high-dose steroid and rituximab along with aspirin and blood pressure control for stroke prevention. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Central nervous system aspergillosis in an immunocompetent patient: cure in a hospice setting with very high-dose itraconazole.

PubMed

Palanisamy, Akilesh; Chao, Stephanie D; Fouts, Michelle; Kerr, Derek

2005-01-01

Aspergillosis of the central nervous system (CNS) is a rare condition with exceedingly high mortality. This study describes the case of an immunocompetent 42-year-old man with a history of intravenous drug use and hepatitis C who developed multiple Aspergillus lesions in the cerebellum. Despite neurosurgery and antifungal therapy with amphotericin B, he had a protracted hospital course with multiple complications, eventually developing cognitive and motor impairment due to progressive cerebellar lesions. After transfer to hospice and palliative care service, oral itraconazole was escalated to 1600 mg/day with the hope of palliating headache, nausea, and cognitive impairment. Remarkably, the patient stabilized and improved over time. After 14 months, this unprecedented high-dose regimen was discontinued, and the patient was discharged home with only mild cerebellar motor impairment.

From the "little brain" gastrointestinal infection to the "big brain" neuroinflammation: a proposed fast axonal transport pathway involved in multiple sclerosis.

PubMed

Deretzi, Georgia; Kountouras, Jannis; Grigoriadis, Nikolaos; Zavos, Christos; Chatzigeorgiou, Stavros; Koutlas, Evangelos; Tsiptsios, Iakovos

2009-11-01

The human central nervous system (CNS) is targeted by different pathogens which, apart from pathogens' intranasal inoculation or trafficking into the brain through infected blood cells, may use a distinct pathway to bypass the blood-brain barrier by using the gastrointestinal tract (GIT) retrograde axonal transport through sensory or motor fibres. The recent findings regarding the enteric nervous system (often called the "little brain") similarities with CNS and GIT axonal transport of infections resulting in CNS neuroinflammation are mainly reviewed in this article. We herein propose that the GIT is the vulnerable area through which pathogens (such as Helicobacter pylori) may influence the brain and induce multiple sclerosis pathologies, mainly via the fast axonal transport by the afferent neurones connecting the GIT to brain.

Positive or negative involvement of heat shock proteins in multiple sclerosis pathogenesis: an overview.

PubMed

Turturici, Giuseppina; Tinnirello, Rosaria; Sconzo, Gabriella; Asea, Alexzander; Savettieri, Giovanni; Ragonese, Paolo; Geraci, Fabiana

2014-12-01

Multiple sclerosis (MS) is the most diffuse chronic inflammatory disease of the central nervous system. Both immune-mediated and neurodegenerative processes apparently play roles in the pathogenesis of this disease. Heat shock proteins (HSPs) are a family of highly evolutionarily conserved proteins; their expression in the nervous system is induced in a variety of pathologic states, including cerebral ischemia, neurodegenerative diseases, epilepsy, and trauma. To date, investigators have observed protective effects of HSPs in a variety of brain disease models (e.g. of Alzheimer disease and Parkinson disease). In contrast, unequivocal data have been obtained for their roles in MS that depend on the HSP family and particularly on their localization (i.e. intracellular or extracellular). This article reviews our current understanding of the involvement of the principal HSP families in MS.

Current progress in use of adipose derived stem cells in peripheral nerve regeneration

PubMed Central

Zack-Williams, Shomari DL; Butler, Peter E; Kalaskar, Deepak M

2015-01-01

Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair. PMID:25621105

Spatial signal correlation from an III-nitride synaptic device

NASA Astrophysics Data System (ADS)

Zhang, Shuai; Zhu, Bingcheng; Shi, Zheng; Yuan, Jialei; Jiang, Yuan; Shen, Xiangfei; Cai, Wei; Yang, Yongchao; Wang, Yongjin

2017-10-01

The mechanism by which the external environment affects the internal nervous system is investigated via the spatial correlation of an III-nitride synaptic device, which combines in-plane and out-of-plane illumination. The InGaN/GaN multiple-quantum-well collector (MQW-collector) demonstrates a simultaneous light emission and light detection mode due to the unique property of the MQW-diode. The MQW-collector absorbs the internal incoming light and the external illumination at the same time to generate an integration of the excitatory postsynaptic voltages (EPSVs). Signal cognition can be distinctly decoded from the integrated EPSVs because the signal differences are maintained, which is in good agreement with the simulation results. These results suggest that the nervous system can simultaneously amplify the EPSV amplitude and achieve signal cognition by spatial EPSV summation, which can be further optimized to explore the connections between the internal nervous system and the external environment.

Neural Stem Cells: Implications for the Conventional Radiotherapy of Central Nervous System Malignancies

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

Barani, Igor J.; Benedict, Stanley H.; Lin, Peck-Sun

Advances in basic neuroscience related to neural stem cells and their malignant counterparts are challenging traditional models of central nervous system tumorigenesis and intrinsic brain repair. Neurogenesis persists into adulthood predominantly in two neurogenic centers: subventricular zone and subgranular zone. Subventricular zone is situated adjacent to lateral ventricles and subgranular zone is confined to the dentate gyrus of the hippocampus. Neural stem cells not only self-renew and differentiate along multiple lineages in these regions, but also contribute to intrinsic brain plasticity and repair. Ionizing radiation can depopulate these exquisitely sensitive regions directly or impair in situ neurogenesis by indirect, dose-dependentmore » and inflammation-mediated mechanisms, even at doses <2 Gy. This review discusses the fundamental neural stem cell concepts within the framework of cumulative clinical experience with the treatment of central nervous system malignancies using conventional radiotherapy.« less

Will PEDF Therapy Reverse Chronic Demyelination and Prevent Axon Loss in a Murine Model of Progressive Multiple Sclerosis

DTIC Science & Technology

2015-12-01

Multiple Sclerosis ? PRINCIPAL INVESTIGATOR: David Pleasure MD CONTRACTING ORGANIZATION: University of California Davis, CA 95618 REPORT DATE...Murine Model of Progressive Multiple Sclerosis ? 5b. GRANT NUMBER W81XWH-12-1-0566 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David Pleasure MD 5d...enhance central nervous system (CNS) remyelination and preserve CNS axons in mouse models of multiple sclerosis models. After determining the dosage of

Top 10 Research Questions Related to Physical Activity and Multiple Sclerosis

ERIC Educational Resources Information Center

Motl, Robert W.; Learmonth, Yvonne C.; Pilutti, Lara A.; Gappmaier, Eduard; Coote, Susan

2015-01-01

An estimated 2.5 million people worldwide are living with multiple sclerosis (MS), and this disease may be increasing in prevalence. MS is a disease of the central nervous system that is associated with heterogeneous symptoms and functional consequences, and the current first-line disease-modifying therapies often become ineffective later in the…

3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer

ClinicalTrials.gov

2017-12-05

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unspecified Adult Solid Tumor, Protocol Specific

Nerve supply to the pelvis (image)

MedlinePlus

The nerves that branch off the central nervous system (CNS) provide messages to the muscles and organs for normal ... be compromised. In multiple sclerosis, the demyelinization of nerve cells may lead to bowel incontinence, bladder problems ...

Mechlorethamine-based drug structures for intervention of central nervous system tumors.

PubMed

Bartzatt, Ronald

2013-06-01

Tumors of the central nervous system are the third most common type of childhood cancers. Brain tumors occur in children and adults; however pediatric patients require a different treatment process. Thirteen drugs similar to mechlorethamine are analyzed in this study. These drugs possess molecular properties enabling substantial and successful access to tumors of the central nervous system. All drugs exhibit zero violations of the Rule of 5, which indicate favorable bioavailability. Ranges in Log P, formula weight, and polar surface area for these drugs are: 1.554 to 3.52, 156.06 to 460.45, and 3.238 Angstroms(2) to 45.471 Angstroms(2), respectively. Hierarchical cluster analysis determined that agents 7 and 12 are most similar to the parent compound mechlorethamine. The mean values of Log P, formula weight, polar surface area, and molecular volume are 2.25, 268.51, 16.57 Angstroms(2), and 227.01 Angstroms(3), respectively. Principal component analysis indicates that agents 7 and 12 are most similar to mechlorethamine and multiple regression analysis of molecular properties produced a model to enable the design of similar alkylating agents. Values of Log (Cbrain/Cblood) indicate these agents will have very high permeation into the central nervous system.

Microglia in the developing brain: a potential target with lifetime effects

PubMed Central

Harry, G. Jean; Kraft, Andrew D.

2012-01-01

Microglia are a heterogeneous group of monocyte-derived cells serving multiple roles within the brain, many of which are associated with immune and macrophage like properties. These cells are known to serve a critical role during brain injury and to maintain homeostasis; yet, their defined roles during development have yet to be elucidated. Microglial actions appear to influence events associated with neuronal proliferation and differentiation during development, as well as, contribute to processes associated with the removal of dying neurons or cellular debris and management of synaptic connections. These long-lived cells display changes during injury and with aging that are critical to the maintenance of the neuronal environment over the lifespan of the organism. These processes may be altered by changes in the colonization of the brain or by inflammatory events during development. This review addresses the role of microglia during brain development, both structurally and functionally, as well as the inherent vulnerability of the developing nervous system. A framework is presented considering microglia as a critical nervous system-specific cell that can influence multiple aspects of brain development (e.g., vascularization, synaptogenesis, and myelination) and have a long term impact on the functional vulnerability of the nervous system to a subsequent insult, whether environmental, physical, age-related, or disease-related. PMID:22322212

Nervous System Sensitization as a Predictor of Outcome in the Treatment of Peripheral Musculoskeletal Conditions: A Systematic Review.

PubMed

O'Leary, Helen; Smart, Keith M; Moloney, Niamh A; Doody, Catherine M

2017-02-01

Research suggests that peripheral and central nervous system sensitization can contribute to the overall pain experience in peripheral musculoskeletal (MSK) conditions. It is unclear, however, whether sensitization of the nervous system results in poorer outcomes following the treatment. This systematic review investigated whether nervous system sensitization in peripheral MSK conditions predicts poorer clinical outcomes in response to a surgical or conservative intervention. Four electronic databases were searched to identify the relevant studies. Eligible studies had a prospective design, with a follow-up assessing the outcome in terms of pain or disability. Studies that used baseline indices of nervous system sensitization were included, such as quantitative sensory testing (QST) or questionnaires that measured centrally mediated symptoms. Thirteen studies met the inclusion criteria, of which six were at a high risk of bias. The peripheral MSK conditions investigated were knee and hip osteoarthritis, shoulder pain, and elbow tendinopathy. QST parameters indicative of sensitization (lower electrical pain thresholds, cold hyperalgesia, enhanced temporal summation, lower punctate sharpness thresholds) were associated with negative outcome (more pain or disability) in 5 small exploratory studies. Larger studies that accounted for multiple confounders in design and analysis did not support a predictive relationship between QST parameters and outcome. Two studies used self-report measures to capture comorbid centrally mediated symptoms, and found higher questionnaire scores were independently predictive of more persistent pain following a total joint arthroplasty. This systematic review found insufficient evidence to support an independent predictive relationship between QST measures of nervous system sensitization and treatment outcome. Self-report measures demonstrated better predictive ability. Further high-quality prognostic research is warranted. © 2016 World Institute of Pain.

Heart rate variability is differentially altered in multiple sclerosis: implications for acute, worsening and progressive disability.

PubMed

Studer, Valeria; Rocchi, Camilla; Motta, Caterina; Lauretti, Benedetta; Perugini, Jacopo; Brambilla, Laura; Pareja-Gutierrez, Lorena; Camera, Giorgia; Barbieri, Francesca Romana; Marfia, Girolama A; Centonze, Diego; Rossi, Silvia

2017-01-01

Sympathovagal imbalance has been associated with poor prognosis in chronic diseases, but there is conflicting evidence in multiple sclerosis. The objective of this study was to investigate the autonomic nervous system dysfunction correlation with inflammation and progression in multiple sclerosis. Heart rate variability was analysed in 120 multiple sclerosis patients and 60 healthy controls during supine rest and head-up tilt test; the normalised units of low frequency and high frequency power were considered to assess sympathetic and vagal components, respectively. Correlation analyses with clinical and radiological markers of disease activity and progression were performed. Sympathetic dysfunction was closely related to the progression of disability in multiple sclerosis: progressive patients showed altered heart rate variability with respect to healthy controls and relapsing-remitting patients, with higher rest low frequency power and lacking the expected low frequency power increase during the head-up tilt test. In relapsing-remitting patients, disease activity, even subclinical, was associated with lower rest low frequency power, whereas stable relapsing-remitting patients did not differ from healthy controls. Less sympathetic reactivity and higher low frequency power at rest were associated with incomplete recovery from relapse. Autonomic balance appears to be intimately linked with both the inflammatory activity of multiple sclerosis, which is featured by an overall hypoactivity of the sympathetic nervous system, and its compensatory plastic processes, which appear inefficient in case of worsening and progressive multiple sclerosis.

Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

ClinicalTrials.gov

2017-03-15

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Metastatic Cancer; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Secondary Myelofibrosis; Unspecified Adult Solid Tumor, Protocol Specific

Methadone, Morphine, or Oxycodone in Treating Pain in Patients With Cancer

ClinicalTrials.gov

2012-11-09

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

Influenza Vaccine in Preventing Flu in Patients Who Have Undergone Stem Cell Transplant and in Healthy Volunteers

ClinicalTrials.gov

2015-06-03

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nonmalignant Neoplasm; Viral Infection

Donor Natural Killer Cells After Donor Stem Cell Transplant in Treating Patients With Advanced Cancer

ClinicalTrials.gov

2013-02-18

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unspecified Adult Solid Tumor, Protocol Specific

Severe brachial plexopathy after an ultrasound-guided single-injection nerve block for total shoulder arthroplasty in a patient with multiple sclerosis.

PubMed

Koff, Matthew D; Cohen, Jeffrey A; McIntyre, John J; Carr, Charles F; Sites, Brian D

2008-02-01

DESPITE the known benefits of regional anesthesia for patients undergoing joint arthroplasty, the performance of peripheral nerve blocks in patients with multiple sclerosis (MS) remains controversial. MS has traditionally been described as an isolated disease of the central nervous system, without involvement of the peripheral nerves, and peripheral nerve blockade has been suggested to be safe. However, careful review of the literature suggests that MS may also be associated with involvement of the peripheral nervous system, challenging traditional teachings. There is a paucity of evidence with regard to safety in using peripheral nerve regional anesthesia in these patients. This makes it difficult to provide adequate "informed consent" to these patients. This case report describes a patient with MS who sustained a severe brachial plexopathy after a total shoulder arthroplasty during combined general anesthesia and interscalene nerve block.

Neuronal intrinsic regenerative capacity: The impact of microtubule organization and axonal transport.

PubMed

Murillo, Blanca; Sousa, Mónica Mendes

2018-05-08

In the adult vertebrate central nervous system, axons generally fail to regenerate. In contrast, peripheral nervous system axons are able to form a growth cone and regenerate upon lesion. Among the multiple intrinsic mechanisms leading to the formation of a new growth cone and to successful axon regrowth, cytoskeleton organization and dynamics is central. Here we discuss how multiple pathways that define the regenerative capacity converge into the regulation of the axonal microtubule cytoskeleton and transport. We further explore the use of dorsal root ganglion neurons as a model to study the neuronal regenerative ability. Finally, we address some of the unanswered questions in the field, including the mechanisms by which axonal transport might be modulated by injury, and the relationship between microtubule organization, dynamics, and axonal transport. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.

Disease Modifying Therapy in Multiple Sclerosis

PubMed Central

Williams, U. E.; Oparah, S. K.; Philip-Ephraim, E. E.

2014-01-01

Multiple sclerosis is an autoimmune disease of the central nervous system characterized by inflammatory demyelination and axonal degeneration. It is the commonest cause of permanent disability in young adults. Environmental and genetic factors have been suggested in its etiology. Currently available disease modifying drugs are only effective in controlling inflammation but not prevention of neurodegeneration or accumulation of disability. Search for an effective neuroprotective therapy is at the forefront of multiple sclerosis research. PMID:27355035

The Orphan Nuclear Receptor TLX/NR2E1 in Neural Stem Cells and Diseases.

PubMed

Wang, Tao; Xiong, Jian-Qiong

2016-02-01

The human TLX gene encodes an orphan nuclear receptor predominantly expressed in the central nervous system. Tailess and Tlx, the TLX homologues in Drosophila and mouse, play essential roles in body-pattern formation and neurogenesis during early embryogenesis and perform crucial functions in maintaining stemness and controlling the differentiation of adult neural stem cells in the central nervous system, especially the visual system. Multiple target genes and signaling pathways are regulated by TLX and its homologues in specific tissues during various developmental stages. This review aims to summarize previous studies including many recent updates from different aspects concerning TLX and its homologues in Drosophila and mouse.

Multiparametric Imaging of Organ System Interfaces

PubMed Central

Vandoorne, Katrien; Nahrendorf, Matthias

2017-01-01

Cardiovascular diseases are a consequence of genetic and environmental risk factors that together generate arterial wall and cardiac pathologies. Blood vessels connect multiple systems throughout the entire body and allow organs to interact via circulating messengers. These same interactions facilitate nervous and metabolic system influence on cardiovascular health. Multiparametric imaging offers the opportunity to study these interfacing systems’ distinct processes, to quantify their interactions and to explore how these contribute to cardiovascular disease. Noninvasive multiparametric imaging techniques are emerging tools that can further our understanding of this complex and dynamic interplay. PET/MRI and multichannel optical imaging are particularly promising because they can simultaneously sample multiple biomarkers. Preclinical multiparametric diagnostics could help discover clinically relevant biomarker combinations pivotal for understanding cardiovascular disease. Interfacing systems important to cardiovascular disease include the immune, nervous and hematopoietic systems. These systems connect with ‘classical’ cardiovascular organs, like the heart and vasculature, and with the brain. The dynamic interplay between these systems and organs enables processes such as hemostasis, inflammation, angiogenesis, matrix remodeling, metabolism and fibrosis. As the opportunities provided by imaging expand, mapping interconnected systems will help us decipher the complexity of cardiovascular disease and monitor novel therapeutic strategies. PMID:28360260

Sarcocystosis in a stillborn lamb

USDA-ARS?s Scientific Manuscript database

Confirmed congenital sarcocystosis has not been reported in sheep and extremely rarely in other domestic ruminants. Sarcocystosis was diagnosed in a stillborn lamb with microscopic lesions predominantly in the central nervous system and placenta. Encephalitis was characterized by multiple foci of gl...

Collecting and Storing Blood Samples From Patients With Cancer

ClinicalTrials.gov

2011-12-08

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nonmalignant Neoplasm; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

Personalized Information or Basic Information in Helping Patients Make Decisions About Participating in a Clinical Trial

ClinicalTrials.gov

2013-08-20

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unspecified Adult Solid Tumor, Protocol Specific

Opioid Titration Order Sheet or Standard Care in Treating Patients With Cancer Pain

ClinicalTrials.gov

2012-08-04

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

The Yin and Yang of YY1 in the nervous system

PubMed Central

He, Ye; Casaccia-Bonnefil, Patrizia

2008-01-01

The transcription factor Yin Yang 1 (YY1) is a multifunctional protein that can activate or repress gene expression depending on the cellular context. YY1 is ubiquitously expressed and highly conserved between species. However its role varies in diverse cell types and includes proliferation, differentiation and apoptosis. This review will focus on the function of YY1 in the nervous system including its role in neural development, neuronal function, developmental myelination and neurological disease. The multiple functions of YY1 in distinct cell types are reviewed and the possible mechanisms underlying the cell specificity for these functions are discussed. PMID:18485096

Compensating for intersegmental dynamics across the shoulder, elbow, and wrist joints during feedforward and feedback control.

PubMed

Maeda, Rodrigo S; Cluff, Tyler; Gribble, Paul L; Pruszynski, J Andrew

2017-10-01

Moving the arm is complicated by mechanical interactions that arise between limb segments. Such intersegmental dynamics cause torques applied at one joint to produce movement at multiple joints, and in turn, the only way to create single joint movement is by applying torques at multiple joints. We investigated whether the nervous system accounts for intersegmental limb dynamics across the shoulder, elbow, and wrist joints during self-initiated planar reaching and when countering external mechanical perturbations. Our first experiment tested whether the timing and amplitude of shoulder muscle activity account for interaction torques produced during single-joint elbow movements from different elbow initial orientations and over a range of movement speeds. We found that shoulder muscle activity reliably preceded movement onset and elbow agonist activity, and was scaled to compensate for the magnitude of interaction torques arising because of forearm rotation. Our second experiment tested whether elbow muscles compensate for interaction torques introduced by single-joint wrist movements. We found that elbow muscle activity preceded movement onset and wrist agonist muscle activity, and thus the nervous system predicted interaction torques arising because of hand rotation. Our third and fourth experiments tested whether shoulder muscles compensate for interaction torques introduced by different hand orientations during self-initiated elbow movements and to counter mechanical perturbations that caused pure elbow motion. We found that the nervous system predicted the amplitude and direction of interaction torques, appropriately scaling the amplitude of shoulder muscle activity during self-initiated elbow movements and rapid feedback control. Taken together, our results demonstrate that the nervous system robustly accounts for intersegmental dynamics and that the process is similar across the proximal to distal musculature of the arm as well as between feedforward (i.e., self-initiated) and feedback (i.e., reflexive) control. NEW & NOTEWORTHY Intersegmental dynamics complicate the mapping between applied joint torques and the resulting joint motions. We provide evidence that the nervous system robustly predicts these intersegmental limb dynamics across the shoulder, elbow, and wrist joints during reaching and when countering external perturbations. Copyright © 2017 the American Physiological Society.

Advances in neuroimmunology

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

Raine, C.S.

1988-01-01

This volume presents the proceedings of the Second International Congress of Neuroimmunology. It brought together basic researchers and clinicians involved in the application of immunologic methodologies to the elucidation of problems related to nervous system development and disease. Neuroimmunology as a discipline is still in its infancy although its roots date back more than 50 years when it was realized that certain neurologic disorders were related to allergic reactions. Since then, it has been shown that immunological mechanisms are involved not only in a growing number of disease processes of the nervous system, but also in the development of nervousmore » tissue. It is now widely accepted that the nervous system shares a unique relationship with the immune system, sometimes through shared receptors, and possesses a large repertoire of specific antigens. Thus, with the continuing and intensive application of immunologic techniques to the neurologic sciences, the specialty of neuroimmunology has evolved. The major diseases that now fall into its realm include multiple sclerosis, myasthenia gravis, peripheral neuropathy, systemic lupus erythematosus, AIDS, leprosy, narcolepsy, tumors, viral encephalitis, and their experimental counterparts.« less

Perceptions of Burden in Patients With Late-Stage Cancer and Their Caregivers

ClinicalTrials.gov

2015-05-27

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Depression; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Psychosocial Effects of Cancer and Its Treatment; Unspecified Adult Solid Tumor, Protocol Specific

The Application of Nanomaterials in Stem Cell Therapy for Some Neurological Diseases.

PubMed

Zhang, Guilong; Khan, Ahsan Ali; Wu, Hao; Chen, Lukui; Gu, Yuchun; Gu, Ning

2018-02-08

Stem cell therapy provides great promising therapeutic benefits for various neurological disorders. Cell transplantation has emerged as cell replacement application for nerve damage. Recently, nanomaterials obtain wide development in various industrial and medical fields, and nanoparticles have been applied in the neurological field for tracking and treating nervous system diseases. Combining stem cells with nanotechnology has raised more and more attentions; and it has demonstrated that the combination has huge effects on clinical diagnosis and therapeutics in multiple central nervous system diseases, meanwhile, improves prognosis. The aim of this review was to give a brief overview of the application of nanomaterials in stem cell therapy for neurological diseases. Nanoparticles not only promote stem cell proliferation and differentiation in vitro or in vivo, but also play dominant roles on stem cell imaging and tracking. Furthermore, via delivering genes or drugs, nanoparticles can participate in stem cell therapeutic applications for various neurological diseases, such as ischemic stroke, spinal cord injury (SCI), multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD) and gliomas. However, nanoparticles have potential cytotoxic effects on nerve cells, which are related to their physicochemical properties. Nano-stem cell-based therapy as a promising strategy has the ability to affect neuronal repair and regeneration in the central nervous system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Neuroprotection for the new millennium. Matchmaking pharmacology and technology

NASA Technical Reports Server (NTRS)

Andrews, R. J.

2001-01-01

A major theme of the 1990s in the pathophysiology of nervous system injury has been the multifactorial etiology of irreversible injury. Multiple causes imply multiple opportunities for therapeutic intervention--hence the abandonment of the "magic bullet" single pharmacologic agent for neuroprotection in favor of pharmacologic "cocktails". A second theme of the 1990s has been the progress in technology for neuroprotection, minimally- or non-invasive monitoring as well as treatment. Cardiac stenting has eliminated the need, in many cases, for open heart surgery; deep brain stimulation for Parkinson's disease has offered significant improvement in quality of life for many who had exhausted cocktail drug treatment for their disease. Deep brain stimulation of the subthalamic nucleus offers a novel treatment for Parkinson's disease where a technological advance may actually be an intervention with effects that are normally expected from pharmacologic agents. Rather than merely "jamming" the nervous system circuits involved in Parkinson's disease, deep brain stimulation of the subthalamic nucleus appears to improve the neurotransmitter imbalance that lies at the heart of Parkinson's disease. It may also slow the progression of the disease. Given the example of deep brain stimulation of the subthalamic nucleus for Parkinson's disease, in future one may expect other technological or "hardware" interventions to influence the programming or "software" of the nervous system's physiologic response in certain disease states.

Chemokine receptor binding and signal transduction in native cells of the central nervous system.

PubMed

Davis, Christopher N; Chen, Shuzhen; Boehme, Stefen A; Bacon, Kevin B; Harrison, Jeffrey K

2003-04-01

Chemokine receptors belong to the superfamily of seven-transmembrane-spanning, G-protein-coupled receptors, and their expression by central nervous system cells is clearly documented. As this gene family has become the target of novel therapeutic development, the analysis of these receptors requires radioligand binding techniques as well as methods that entail assessing receptor stimulation of signal transduction pathways. Herein, we describe specific protocols for measuring radiolabeled chemokine binding to their cognate receptors on cultured glial cells as well as to receptors expressed in heterologous cell systems. Multiple downstream signaling pathways, including intracellular calcium influx and receptor-dependent kinase activation, are associated with chemokine receptor stimulation. Protocols for measuring these signaling events in chemokine-receptor-expressing cells are also presented.

A Tol2 Gateway-Compatible Toolbox for the Study of the Nervous System and Neurodegenerative Disease.

PubMed

Don, Emily K; Formella, Isabel; Badrock, Andrew P; Hall, Thomas E; Morsch, Marco; Hortle, Elinor; Hogan, Alison; Chow, Sharron; Gwee, Serene S L; Stoddart, Jack J; Nicholson, Garth; Chung, Roger; Cole, Nicholas J

2017-02-01

Currently there is a lack in fundamental understanding of disease progression of most neurodegenerative diseases, and, therefore, treatments and preventative measures are limited. Consequently, there is a great need for adaptable, yet robust model systems to both investigate elementary disease mechanisms and discover effective therapeutics. We have generated a Tol2 Gateway-compatible toolbox to study neurodegenerative disorders in zebrafish, which includes promoters for astrocytes, microglia and motor neurons, multiple fluorophores, and compatibility for the introduction of genes of interest or disease-linked genes. This toolbox will advance the rapid and flexible generation of zebrafish models to discover the biology of the nervous system and the disease processes that lead to neurodegeneration.

Multiple Sclerosis and the Family Physician

PubMed Central

Sky, Ruth

1977-01-01

Multiple sclerosis is difficult to diagnose since it develops over a period of time and the symptoms and signs are scattered throughout the central nervous system. Because there is no specific treatment, the problems of management are especially challenging. Case histories are presented to support the concept that multiple sclerosis is a family and community concern. Family physicians are urged to maintain a supportive role and an interested attitude towards patients with multiple sclerosis. These patients and their families have urgent and continuing needs for their doctors' skills. PMID:21304869

Sunitinib in Treating Young Patients With Refractory Solid Tumors

ClinicalTrials.gov

2014-01-27

Central Nervous System Metastases; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Recurrent Childhood Central Nervous System Embryonal Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

Caloric restriction and intermittent fasting: Two potential diets for successful brain aging

PubMed Central

Martin, Bronwen; Mattson, Mark P.; Maudsley, Stuart

2008-01-01

The vulnerability of the nervous system to advancing age is all too often manifest in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review article we describe evidence suggesting that two dietary interventions, caloric restriction (CR) and intermittent fasting (IF), can prolong the health-span of the nervous system by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span. CR and IF affect energy and oxygen radical metabolism, and cellular stress response systems, in ways that protect neurons against genetic and environmental factors to which they would otherwise succumb during aging. There are multiple interactive pathways and molecular mechanisms by which CR and IF benefit neurons including those involving insulin-like signaling, FoxO transcription factors, sirtuins and peroxisome proliferator-activated receptors. These pathways stimulate the production of protein chaperones, neurotrophic factors and antioxidant enzymes, all of which help cells cope with stress and resist disease. A better understanding of the impact of CR and IF on the aging nervous system will likely lead to novel approaches for preventing and treating neurodegenerative disorders. PMID:16899414

Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.

PubMed

De Luca, Ciro; Virtuoso, Assunta; Maggio, Nicola; Papa, Michele

2017-10-12

Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix. The pleiotropy of these effects is produced through different receptors, expressed in various cell types, in a dose- and time-dependent pattern. We reviewed how these pathways may be involved in neurodegenerative diseases (amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases), multiple sclerosis, ischemic stroke and post-ischemic epilepsy, CNS cancer, addiction, and mental health. These data open up a new path for the potential therapeutic use of the agonist/antagonist of these proteins in the management of several central nervous system diseases.

Cnidarian Nerve Nets and Neuromuscular Efficiency.

PubMed

Satterlie, Richard A

2015-12-01

Cnidarians are considered "nerve net animals" even though their nervous systems include various forms of condensation and centralization. Yet, their broad, two-dimensional muscle sheets are innervated by diffuse nerve nets. Do the motor nerve nets represent a primitive organization of multicellular nervous systems, do they represent a consequence of radial symmetry, or do they offer an efficient way to innervate a broad, two-dimensional muscle sheet, in which excitation of the muscle sheet can come from multiple sites of initiation? Regarding the primitive nature of cnidarian nervous systems, distinct neuronal systems exhibit some adaptations that are well known in higher animals, such as the use of oversized neurons with increased speed of conduction, and condensation of neurites into nerve-like tracts. A comparison of neural control of two-dimensional muscle sheets in a mollusc and jellyfish suggests that a possible primitive feature of cnidarian neurons may be a lack of regional specialization into conducting and transmitting regions. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Test Pool Questions, Area III.

ERIC Educational Resources Information Center

Sloan, Jamee Reid

This manual contains multiple choice questions to be used in testing students on nurse training objectives. Each test includes several questions covering each concept. The concepts in section A, medical surgical nursing, are diseases of the following systems: musculoskeletal; central nervous; cardiovascular; gastrointestinal; urinary and male…

Predictors of Outcome following Acquired Brain Injury in Children

ERIC Educational Resources Information Center

Johnson, Abigail R.; DeMatt, Ellen; Salorio, Cynthia F.

2009-01-01

Acquired brain injury (ABI) in children and adolescents can result from multiple causes, including trauma, central nervous system infections, noninfectious disorders (epilepsy, hypoxia/ischemia, genetic/metabolic disorders), tumors, and vascular abnormalities. Prediction of outcomes is important, to target interventions, allocate resources,…

Introduction to 'Homology and convergence in nervous system evolution'.

PubMed

Strausfeld, Nicholas J; Hirth, Frank

2016-01-05

The origin of brains and central nervous systems (CNSs) is thought to have occurred before the Palaeozoic era 540 Ma. Yet in the absence of tangible evidence, there has been continued debate whether today's brains and nervous systems derive from one ancestral origin or whether similarities among them are due to convergent evolution. With the advent of molecular developmental genetics and genomics, it has become clear that homology is a concept that applies not only to morphologies, but also to genes, developmental processes, as well as to behaviours. Comparative studies in phyla ranging from annelids and arthropods to mammals are providing evidence that corresponding developmental genetic mechanisms act not only in dorso-ventral and anterior-posterior axis specification but also in segmentation, neurogenesis, axogenesis and eye/photoreceptor cell formation that appear to be conserved throughout the animal kingdom. These data are supported by recent studies which identified Mid-Cambrian fossils with preserved soft body parts that present segmental arrangements in brains typical of modern arthropods, and similarly organized brain centres and circuits across phyla that may reflect genealogical correspondence and control similar behavioural manifestations. Moreover, congruence between genetic and geological fossil records support the notion that by the 'Cambrian explosion' arthropods and chordates shared similarities in brain and nervous system organization. However, these similarities are strikingly absent in several sister- and outgroups of arthropods and chordates which raises several questions, foremost among them: what kind of natural laws and mechanisms underlie the convergent evolution of such similarities? And, vice versa: what are the selection pressures and genetic mechanisms underlying the possible loss or reduction of brains and CNSs in multiple lineages during the course of evolution? These questions were addressed at a Royal Society meeting to discuss homology and convergence in nervous system evolution. By integrating knowledge ranging from evolutionary theory and palaeontology to comparative developmental genetics and phylogenomics, the meeting covered disparities in nervous system origins as well as correspondences of neural circuit organization and behaviours, all of which allow evidence-based debates for and against the proposition that the nervous systems and brains of animals might derive from a common ancestor. © 2015 The Author(s).

Astrocytic TYMP and VEGFA drive blood–brain barrier opening in inflammatory central nervous system lesions

PubMed Central

Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M.; Mariani, John N.; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S.

2015-01-01

In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood–brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood–brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood–brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood–brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood–brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood–brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an astrocyte-derived permeability factor, and suggest TYMP and VEGFA together promote blood–brain barrier breakdown. PMID:25805644

In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR-dCas9-activator transgenic mice.

PubMed

Zhou, Haibo; Liu, Junlai; Zhou, Changyang; Gao, Ni; Rao, Zhiping; Li, He; Hu, Xinde; Li, Changlin; Yao, Xuan; Shen, Xiaowen; Sun, Yidi; Wei, Yu; Liu, Fei; Ying, Wenqin; Zhang, Junming; Tang, Cheng; Zhang, Xu; Xu, Huatai; Shi, Linyu; Cheng, Leping; Huang, Pengyu; Yang, Hui

2018-03-01

Despite rapid progresses in the genome-editing field, in vivo simultaneous overexpression of multiple genes remains challenging. We generated a transgenic mouse using an improved dCas9 system that enables simultaneous and precise in vivo transcriptional activation of multiple genes and long noncoding RNAs in the nervous system. As proof of concept, we were able to use targeted activation of endogenous neurogenic genes in these transgenic mice to directly and efficiently convert astrocytes into functional neurons in vivo. This system provides a flexible and rapid screening platform for studying complex gene networks and gain-of-function phenotypes in the mammalian brain.

Feeling good: autonomic nervous system responding in five positive emotions.

PubMed

Shiota, Michelle N; Neufeld, Samantha L; Yeung, Wan H; Moser, Stephanie E; Perea, Elaine F

2011-12-01

Although dozens of studies have examined the autonomic nervous system (ANS) aspects of negative emotions, less is known about ANS responding in positive emotion. An evolutionary framework was used to define five positive emotions in terms of fitness-enhancing function, and to guide hypotheses regarding autonomic responding. In a repeated measures design, participants viewed sets of visual images eliciting these positive emotions (anticipatory enthusiasm, attachment love, nurturant love, amusement, and awe) plus an emotionally neutral state. Peripheral measures of sympathetic and vagal parasympathetic activation were assessed. Results indicated that the emotion conditions were characterized by qualitatively distinct profiles of autonomic activation, suggesting the existence of multiple, physiologically distinct positive emotions. (c) 2011 APA, all rights reserved.

A Review of Cardiac Autonomic Measures: Considerations for Examination of Physiological Response in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Benevides, Teal W.; Lane, Shelly J.

2015-01-01

The autonomic nervous system (ANS) is responsible for multiple physiological responses, and dysfunction of this system is often hypothesized as contributing to cognitive, affective, and behavioral responses in children. Research suggests that examination of ANS activity may provide insight into behavioral dysregulation in children with autism…

NeuroLex.org: an online framework for neuroscience knowledge

PubMed Central

Larson, Stephen D.; Martone, Maryann E.

2013-01-01

The ability to transmit, organize, and query information digitally has brought with it the challenge of how to best use this power to facilitate scientific inquiry. Today, few information systems are able to provide detailed answers to complex questions about neuroscience that account for multiple spatial scales, and which cross the boundaries of diverse parts of the nervous system such as molecules, cellular parts, cells, circuits, systems and tissues. As a result, investigators still primarily seek answers to their questions in an increasingly densely populated collection of articles in the literature, each of which must be digested individually. If it were easier to search a knowledge base that was structured to answer neuroscience questions, such a system would enable questions to be answered in seconds that would otherwise require hours of literature review. In this article, we describe NeuroLex.org, a wiki-based website and knowledge management system. Its goal is to bring neurobiological knowledge into a framework that allows neuroscientists to review the concepts of neuroscience, with an emphasis on multiscale descriptions of the parts of nervous systems, aggregate their understanding with that of other scientists, link them to data sources and descriptions of important concepts in neuroscience, and expose parts that are still controversial or missing. To date, the site is tracking ~25,000 unique neuroanatomical parts and concepts in neurobiology spanning experimental techniques, behavioral paradigms, anatomical nomenclature, genes, proteins and molecules. Here we show how the structuring of information about these anatomical parts in the nervous system can be reused to answer multiple neuroscience questions, such as displaying all known GABAergic neurons aggregated in NeuroLex or displaying all brain regions that are known within NeuroLex to send axons into the cerebellar cortex. PMID:24009581

Changes of procalcitonin level in multiple trauma patients.

PubMed

Wojtaszek, Marek; Staśkiewicz, Grzegorz; Torres, Kamil; Jakubowski, Krzysztof; Rácz, Oliver; Cipora, Elżbieta

2014-01-01

Some aspects of the pathophysiology of complications in multiple-trauma patients still remain unclear. Mediators of inflammation have been postulated as playing a key role in being responsible for life threatening complications of multiple trauma patients. The objective of this study was to evaluate the prognostic value of procalcitonin (PCT) level in multiple trauma patients. A prospective study took place including patients with multiple trauma hospitalised in several hospital units. PCT level was measured in blood from 45 patients, aged 18-70 years using enzyme-linked immunoassay. The patients were divided into three groups: group I - individuals with multiple trauma with central nervous system injury; group II - those with multiple trauma without CNS injury; and group III - patients with isolated central nervous system injury. Initial PCT levels were below 0.5 ng mL(-1) regardless of the cause of trauma. In the 24th hour of observation, a statistically significant increase of PCT concentration vs. initial levels was recorded in all groups of patients. Then PCT levels decreased significantly at the 3rd measurement point in all groups, and they remained unchanged until the last measurement. The highest levels of PCT were observed in multiple trauma patients without CNS injury (group II). In this group of patients, a significantly longer duration of surgery in the post-trauma period affected PCT levels. PCT concentrations in patients who died were significantly greater than in survivors. A long lasting elevated concentration of procalcitonin in the post-traumatic period, or its repeated increase, is a good marker of developing complications observed earlier than clinical manifestations.

Combination Chemotherapy in Treating Young Patients With Advanced Solid Tumors

ClinicalTrials.gov

2013-05-01

Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

Cellular and Molecular Actions of Methylene Blue in the Nervous System

PubMed Central

Oz, Murat; Lorke, Dietrich E.; Hasan, Mohammed; Petroianu, George A.

2010-01-01

Methylene Blue (MB), following its introduction to biology in the 19th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide-induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimer's disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system. PMID:19760660

[Cannabis: Effects in the Central Nervous System. Therapeutic, societal and legal consequences].

PubMed

Rivera-Olmos, Víctor Manuel; Parra-Bernal, Marisela C

2016-01-01

The consumption of marijuana extracted from Cannabis sativa and indica plants involves an important cultural impact in Mexico. Their psychological stimulatory effect is widely recognized; their biochemical and molecular components interact with CB1 and CB2 (endocannabinoid system) receptors in various central nervous system structures (CNS) and immune cells. The psychoactive element Δ-9-tetrahydrocannabinol (THC) can be reproduced synthetically. Systematic reviews show evidence of therapeutic effectiveness of therapeutic marijuana only for certain symptoms of multiple sclerosis (spasticity, spasms and pain), despite attempts for its widespread use, including refractory childhood epilepsy. Evidence indicates significant adverse effects of smoked marijuana on the structure, functioning and brain connectivity. Cannabis exposure during pregnancy affects fetal brain development, potentially leading to later behavioral problems in children. Neuropsychological tests and advanced imaging techniques show involvement in the learning process in adolescents with substance use. Also, marijuana increases the cognitive impairment in patients with multiple sclerosis. Social and ethical consequences to legally free marijuana for recreational use may be deleterious transcendentally. The medicinal or psychoactive cannabinol no addictive effect requires controlled proven efficacy and safety before regulatory approval studies.

The Dilemmas of the Gourmet Fly: The Molecular and Neuronal Mechanisms of Feeding and Nutrient Decision Making in Drosophila

PubMed Central

Itskov, Pavel M.; Ribeiro, Carlos

2012-01-01

To survive and successfully reproduce animals need to maintain a balanced intake of nutrients and energy. The nervous system of insects has evolved multiple mechanisms to regulate feeding behavior. When animals are faced with the choice to feed, several decisions must be made: whether or not to eat, how much to eat, what to eat, and when to eat. Using Drosophila melanogaster substantial progress has been achieved in understanding the neuronal and molecular mechanisms controlling feeding decisions. These feeding decisions are implemented in the nervous system on multiple levels, from alterations in the sensitivity of peripheral sensory organs to the modulation of memory systems. This review discusses methodologies developed in order to study insect feeding, the effects of neuropeptides and neuromodulators on feeding behavior, behavioral evidence supporting the existence of internal energy sensors, neuronal and molecular mechanisms controlling protein intake, and finally the regulation of feeding by circadian rhythms and sleep. From the discussed data a conceptual framework starts to emerge which aims to explain the molecular and neuronal processes maintaining the stability of the internal milieu. PMID:23407678

Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues

PubMed Central

Zhang, Sharon; Ratliff, Eric P.; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W.; Achal, Madhulika; Mauntz, Ruth E.; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A.; Macias, Andrew M.; Daugherty, Daniel; Harris, Greg L.; Edwards, Robert A.; Finley, Kim D.

2018-01-01

The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system. PMID:29642630

Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues.

PubMed

Zhang, Sharon; Ratliff, Eric P; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W; Achal, Madhulika; Mauntz, Ruth E; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A; Macias, Andrew M; Daugherty, Daniel; Harris, Greg L; Edwards, Robert A; Finley, Kim D

2018-04-10

The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system.

Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

PubMed Central

Ortiz, Genaro G.; Pacheco-Moisés, Fermín P.; Bitzer-Quintero, Oscar K.; Ramírez-Anguiano, Ana C.; Flores-Alvarado, Luis J.; Ramírez-Ramírez, Viridiana; Macias-Islas, Miguel A.; Torres-Sánchez, Erandis D.

2013-01-01

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle. PMID:24174971

The Complete Remission of Acquired Immunodeficiency Syndrome-associated Isolated Central Nervous System Lymphomatoid Granulomatosis: A Case Report and Review of the Literature.

PubMed

Kano, Yasuhiro; Kodaira, Minori; Ushiki, Atsuhito; Kosaka, Makoto; Yamada, Mitsunori; Shingu, Kunihiko; Nishihara, Hiroshi; Hanaoka, Masayuki; Sekijima, Yoshiki

2017-09-15

A 49-year-old man presented with gradually progressive aphasia one month after being diagnosed with acquired immunodeficiency syndrome (AIDS). Brain magnetic resonance imaging showed multiple brain lesions with punctate and linear enhancement. A polymerase chain reaction detected Epstein-Barr virus (EBV) in the patient's cerebrospinal fluid. A diagnosis of isolated central nervous system lymphomatoid granulomatosis (CNS-LYG) was made based on the brain biopsy findings. The complete remission of CNS-LYG was achieved by anti-retroviral therapy (ART) alone. In the present case, the development of AIDS-associated CNS-LYG was considered to have been initiated by the reactivation of EBV in the CNS under immunosuppressive conditions. The patient's condition improved with the reconstitution of the patient's immune system.

Cerebral pyogranuloma associated with systemic coronavirus infection in a ferret.

PubMed

Gnirs, K; Quinton, J F; Dally, C; Nicolier, A; Ruel, Y

2016-01-01

A 2-year-old male ferret was presented with central nervous system signs. Computed tomography (CT) of the brain revealed a well-defined contrast-enhancing lesion on the rostral forebrain that appeared extraparenchymal. Surgical excision of the mass was performed and the ferret was euthanised during the procedure. Histopathology of the excised mass showed multiple meningeal nodular lesions with infiltrates of epithelioid macrophages, occasionally centred on degenerated neutrophils and surrounded by a broad rim of plasma cells, features consistent with pyogranulomatous meningitis. The histopathological features in this ferret were similar to those in cats with feline infectious peritonitis. Definitive diagnosis was assessed by immunohistochemistry, confirming a ferret systemic coronavirus (FSCV) associated disease. This is the first case of coronavirus granuloma described on CT-scan in the central nervous system of a ferret. © 2015 British Small Animal Veterinary Association.

Ncam1a and Ncam1b: two carriers of polysialic acid with different functions in the developing zebrafish nervous system.

PubMed

Langhauser, Melanie; Ustinova, Jana; Rivera-Milla, Eric; Ivannikov, Darja; Seidl, Carmen; Slomka, Christin; Finne, Jukka; Yoshihara, Yoshihiro; Bastmeyer, Martin; Bentrop, Joachim

2012-02-01

Polysialic acid (polySia) is mainly described as a glycan modification of the neural cell adhesion molecule NCAM1. PolySia-NCAM1 has multiple functions during the development of vertebrate nervous systems including axon extension and fasciculation. Phylogenetic analyses reveal the presence of two related gene clusters, NCAM1 and NCAM2, in tetrapods and fishes. Within the ncam1 cluster, teleost fishes express ncam1a (ncam) and ncam1b (pcam) as duplicated paralogs which arose from a second round of ray-finned fish-specific genome duplication. Tetrapods, in contrast, express a single NCAM1 gene. Using the zebrafish model, we identify Ncam1b as a novel major carrier of polySia in the nervous system. PolySia-Ncam1a is expressed predominantly in rostral regions of the developing nervous system, whereas polySia-Ncam1b prevails caudally. We show that ncam1a and ncam1b have different expression domains which only partially overlap. Furthermore, Ncam1a and Ncam1b and their polySia modifications serve different functions in axon guidance. Formation of the posterior commissure at the forebrain/midbrain junction requires polySia-Ncam1a on the axons for proper fasciculation, whereas Ncam1b, expressed by midbrain cell bodies, serves as an instructive guidance cue for the dorso-medially directed growth of axons. Spinal motor axons, on the other hand, depend on axonally expressed Ncam1b for correct growth toward their target region. Collectively, these findings suggest that the genome duplication in the teleost lineage has provided the basis for a functional diversification of polySia carriers in the nervous system.

Neuropeptides shaping the central nervous system development: Spatiotemporal actions of VIP and PACAP through complementary signaling pathways.

PubMed

Maduna, Tando; Lelievre, Vincent

2016-12-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are neuropeptides with wide, complementary, and overlapping distributions in the central and peripheral nervous systems, where they exert important regulatory roles in many physiological processes. VIP and PACAP display a large range of biological cellular targets and functions in the adult nervous system including regulation of neurotransmission and neuroendocrine secretion and neuroprotective and neuroimmune responses. As the main focus of the present review, VIP and PACAP also have been long implicated in nervous system development and maturation through their interaction with the seven transmembrane domain G protein-coupled receptors, PAC1, VPAC1, and VPAC2, initiating multiple signaling pathways. Compared with PAC1, which solely binds PACAP with very high affinity, VPACs exhibit high affinities for both VIP and PACAP but differ from each other because of their pharmacological profile for both natural accessory peptides and synthetic or chimeric molecules, with agonistic and antagonistic properties. Complementary to initial pharmacological studies, transgenic animals lacking these neuropeptides or their receptors have been used to further characterize the neuroanatomical, electrophysiological, and behavioral roles of PACAP and VIP in the developing central nervous system. In this review, we recapitulate the critical steps and processes guiding/driving neurodevelopment in vertebrates and superimposing the potential contribution of PACAP and VIP receptors on the given timeline. We also describe how alterations in VIP/PACAP signaling may contribute to both (neuro)developmental and adult pathologies and suggest that tuning of VIP/PACAP signaling in a spatiotemporal manner may represent a novel avenue for preventive therapies of neurological and psychiatric disorders. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Immunosenescence of microglia and macrophages: impact on the ageing central nervous system.

PubMed

Rawji, Khalil S; Mishra, Manoj K; Michaels, Nathan J; Rivest, Serge; Stys, Peter K; Yong, V Wee

2016-03-01

Ageing of the central nervous system results in a loss of both grey and white matter, leading to cognitive decline. Additional injury to both the grey and white matter is documented in many neurological disorders with ageing, including Alzheimer's disease, traumatic brain and spinal cord injury, stroke, and multiple sclerosis. Accompanying neuronal and glial damage is an inflammatory response consisting of activated macrophages and microglia, innate immune cells demonstrated to be both beneficial and detrimental in neurological repair. This article will propose the following: (i) infiltrating macrophages age differently from central nervous system-intrinsic microglia; (ii) several mechanisms underlie the differential ageing process of these two distinct cell types; and (iii) therapeutic strategies that selectively target these diverse mechanisms may rejuvenate macrophages and microglia for repair in the ageing central nervous system. Most responses of macrophages are diminished with senescence, but activated microglia increase their expression of pro-inflammatory cytokines while diminishing chemotactic and phagocytic activities. The senescence of macrophages and microglia has a negative impact on several neurological diseases, and the mechanisms underlying their age-dependent phenotypic changes vary from extrinsic microenvironmental changes to intrinsic changes in genomic integrity. We discuss the negative effects of age on neurological diseases, examine the response of senescent macrophages and microglia in these conditions, and propose a theoretical framework of therapeutic strategies that target the different mechanisms contributing to the ageing phenotype in these two distinct cell types. Rejuvenation of ageing macrophage/microglia may preserve neurological integrity and promote regeneration in the ageing central nervous system. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The role of MACF1 in nervous system development and maintenance.

PubMed

Moffat, Jeffrey J; Ka, Minhan; Jung, Eui-Man; Smith, Amanda L; Kim, Woo-Yang

2017-09-01

Microtubule-actin crosslinking factor 1 (MACF1), also known as actin crosslinking factor 7 (ACF7), is essential for proper modulation of actin and microtubule cytoskeletal networks. Most MACF1 isoforms are expressed broadly in the body, but some are exclusively found in the nervous system. Consequentially, MACF1 is integrally involved in multiple neural processes during development and in adulthood, including neurite outgrowth and neuronal migration. Furthermore, MACF1 participates in several signaling pathways, including the Wnt/β-catenin and GSK-3 signaling pathways, which regulate key cellular processes, such as proliferation and cell migration. Genetic mutation or dysregulation of the MACF1 gene has been associated with neurodevelopmental and neurodegenerative diseases, specifically schizophrenia and Parkinson's disease. MACF1 may also play a part in neuromuscular disorders and have a neuroprotective role in the optic nerve. In this review, the authors seek to synthesize recent findings relating to the roles of MACF1 within the nervous system and explore potential novel functions of MACF1 not yet examined. Copyright © 2017 Elsevier Ltd. All rights reserved.

The impact of occurrence of exceptional solar events on mortality from diseases of the nervous system

NASA Astrophysics Data System (ADS)

Podolska, Katerina

2015-04-01

The aim of this conference paper is to analyse relationships between strong changes of solar, geomagnetic and ionospheric physical parameters, and mortality by medical cause of death from diagnosis group Diseases of the nervous system by ICD-10 WHO. The aggregated daily number of deaths of 6 largest individual causes of death of group VI. Diseases of the nervous system on the occurrence of exceptional solar and geomagnetic events is investigated. Analysis is performed for the period of the solar cycles No. 23 and 24 (years 1994-2013) in the Czech Republic. The correlation between the intensity of mortality from diseases Multiple sclerosis, Epilepsy, Cerebral palsy, Parkinson disease, Secondary parkinsonism and Alzheimer disease and the solar, geomagnetic and ionospheric physical parameters is examined using stochastic method of graphical models of conditional dependences. We study the daily number of deaths separately for both sexes at the age groups under 39 and 40+. Differences are found for maximum solar activity and during the ascending and descending epoch of the solar cycles.

Prevalence and distribution of congenital abnormalities in Turkey: differences between the prenatal and postnatal periods.

PubMed

Oztarhan, Kazim; Gedikbasi, Ali; Yildirim, Dogukan; Arslan, Oguz; Adal, Erdal; Kavuncuoglu, Sultan; Ozbek, Sibel; Ceylan, Yavuz

2010-12-01

The aim of this study was to determine the distribution of cases associated with congenital abnormalities during the following three periods: pregnancy, birth, and the neonatal period. This was a retrospective study of cases between 2002 and 2006. All abnormal pregnancies, elective terminations of pregnancies, stillbirths, and births with congenital abnormalities managed in the Neonatology Unit were classified based on the above distribution scheme. During the 5-year study period, 1906 cases with congenital abnormalities were recruited, as follows: 640 prenatally detected and terminated cases, with most abnormalities related to the central nervous system, chromosomes, and urogenital system (56.7%, 12.7%, and 8.9%, respectively); 712 neonates with congenital abnormalities (congenital heart disease [49.2%], central nervous system abnormalities [14.7%], and urogenital system abnormalities [12.9%]); and hospital stillbirths, of which 34.2% had malformations (220 prenatal cases [34.4%] had multiple abnormalities, whereas 188 liveborn cases [26.4%] had multiple abnormalities). The congenital abnormalities rate between 2002 and 2006 was 2.07%. Systematic screening for fetal anomalies is the primary means for identification of affected pregnancies. © 2010 The Authors. Congenital Anomalies © 2010 Japanese Teratology Society.

Chaos theory for clinical manifestations in multiple sclerosis.

PubMed

Akaishi, Tetsuya; Takahashi, Toshiyuki; Nakashima, Ichiro

2018-06-01

Multiple sclerosis (MS) is a demyelinating disease which characteristically shows repeated relapses and remissions irregularly in the central nervous system. At present, the pathological mechanism of MS is unknown and we do not have any theories or mathematical models to explain its disseminated patterns in time and space. In this paper, we present a new theoretical model from a viewpoint of complex system with chaos model to reproduce and explain the non-linear clinical and pathological manifestations in MS. First, we adopted a discrete logistic equation with non-linear dynamics to prepare a scalar quantity for the strength of pathogenic factor at a specific location of the central nervous system at a specific time to reflect the negative feedback in immunity. Then, we set distinct minimum thresholds in the above-mentioned scalar quantity for demyelination possibly causing clinical relapses and for cerebral atrophy. With this simple model, we could theoretically reproduce all the subtypes of relapsing-remitting MS, primary progressive MS, and secondary progressive MS. With the sensitivity to initial conditions and sensitivity to minute change in parameters of the chaos theory, we could also reproduce the spatial dissemination. Such chaotic behavior could be reproduced with other similar upward-convex functions with appropriate set of initial conditions and parameters. In conclusion, by applying chaos theory to the three-dimensional scalar field of the central nervous system, we can reproduce the non-linear outcome of the clinical course and explain the unsolved disseminations in time and space of the MS patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pazopanib Hydrochloride in Treating Young Patients With Solid Tumors That Have Relapsed or Not Responded to Treatment

ClinicalTrials.gov

2013-09-27

Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Metastatic Childhood Soft Tissue Sarcoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Visual Pathway Glioma; Unspecified Childhood Solid Tumor, Protocol Specific

Visceral larva migrans presenting as multiple intracranial and intraspinal abscesses.

PubMed

Moiyadi, Alefia; Mahadevan, Anita; Anandh, Balasubramaniam; Shivashankar, Ravi Shankar; Chickabasavaiah, Yasha Thagadur; Shankar, Susarla Krishna

2007-08-01

Involvement of nervous system by toxocariasis is rare and can produce a spectrum of pathology that includes eosinophillic meningoencephalitis, meningomyelitis, space occupying lesions, vasculitis causing seizures or behavioral abnormalities posing diagnostic dilemmas. We describe a 38-year-old man who presented with multiple intracranial and intramedullary abscesses caused by visceral larva migrans. Neurohelminthiasis as a cause of multiple abscesses, though rare, should be entertained as a differential diagnosis particularly in tropical South-east Asian countries where helminthiasis is still an epidemiological concern prevalent in the pediatric age group.

Mediators of Oligodendrocyte Differentiation During Remyelination

PubMed Central

Patel, Jigisha R.; Klein, Robyn S.

2011-01-01

Myelin, a dielectric sheath that wraps large axons in the central and peripheral nervous systems, is essential for proper conductance of axon potentials. In multiple sclerosis (MS), autoimmune-mediated damage to myelin within the central nervous system (CNS) leads to progressive disability primarily due to limited endogenous repair of demyelination with associated axonal pathology. While treatments are available to limit demyelination, no treatments are available to promote myelin repair. Studies examining the molecular mechanisms that promote remyelination are therefore essential for identifying therapeutic targets to promote myelin repair and thereby limit disability in MS. Here, we present our current understanding of the critical extracellular and intracellular pathways that regulate the remyelinating capabilities of oligodendrocyte precursor cells (OPCs) within the adult CNS. PMID:21539842

Multiplexed Molecular Diagnostics for Respiratory, Gastrointestinal, and Central Nervous System Infections.

PubMed

Hanson, Kimberly E; Couturier, Marc Roger

2016-11-15

The development and implementation of highly multiplexed molecular diagnostic tests have allowed clinical microbiology laboratories to more rapidly and sensitively detect a variety of pathogens directly in clinical specimens. Current US Food and Drug Administration-approved multiplex panels target multiple different organisms simultaneously and can identify the most common pathogens implicated in respiratory viral, gastrointestinal, or central nervous system infections. This review summarizes the test characteristics of available assays, highlights the advantages and limitations of multiplex technology for infectious diseases, and discusses potential utilization of these new tests in clinical practice. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

The Caenorhabditis Elegans Unc-31 Gene Affects Multiple Nervous System-Controlled Functions

PubMed Central

Avery, L.; Bargmann, C. I.; Horvitz, H. R.

1993-01-01

We have devised a method for selecting Caenorhabditis elegans mutants that execute feeding motions in the absence of food. One mutation isolated in this way is an allele of the gene unc-31, first discovered by S. Brenner in 1974, because of its effects on locomotion. We find that strong unc-31 mutations cause defects in four functions controlled by the nervous system. Mutant worms are lethargic, feed constitutively, are defective in egg-laying and produce dauer larvae that fail to recover. We discuss two extreme models to explain this pleiotropy: either unc-31 affects one or a few neurons that coordinately control several different functions, or it affects many neurons that independently control different functions. PMID:8325482

Neuronal Rap1 regulates energy balance, glucose homeostasis, and leptin actions

USDA-ARS?s Scientific Manuscript database

The Central Nervous System (CNS) contributes to obesity and metabolic disease; however, the underlying neurobiological pathways remain to be fully established. Here, we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in...

Challenges of Developing Communicative Interaction in Individuals with Congenital Profound Intellectual and Multiple Disabilities

ERIC Educational Resources Information Center

Blain-Moraes, Stefanie; Chau, Tom

2012-01-01

Background: Physiological responses have been used in individuals with acquired disability to enable communicative interaction without motor movement. This study explored four autonomic nervous system (ANS) signals--electrodermal activity, skin temperature, cardiac patterns and respiratory patterns--to enable interaction with individuals born with…

Reduced lentivirus susceptibility in sheep with TMEM154 mutations

USDA-ARS?s Scientific Manuscript database

Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the U.S., is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine g...

Analysis of the U.S. Air Force Flying Class Waiver Outcomes of the Aeromedical Consultation Service and Major Command Units in Neuropsychiatry

DTIC Science & Technology

2011-11-01

bacterial meningitis , multiple sclerosis, cerebral stroke) 42 77 Obstructive Sleep Apnea 104 72 Headaches 15 67 Decompression...history of closed head injury, headaches, obstructive sleep apnea, central nervous system illness/injury (e.g., bacterial meningitis , stroke), and

Difference in effect of single immunosuppressive agents (cyclophosphamide, CCNU, 5-FU) on peripheral blood immune cell parameters and central nervous system immunoglobulin synthesis rate in patients with multiple sclerosis.

PubMed Central

Shih, W W; Baumhefner, R W; Tourtellotte, W W; Haskell, C M; Korn, E L; Fahey, J L

1983-01-01

Cyclophosphamide (CY), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-fluorouracil (5-FU) were given in single course schedules to chronic progressive multiple sclerosis (MS) patients clinically stable for 6 months. The following peripheral immune cellular parameters were measured before, during and after each drug administration: white blood count (WBC), polymorphonuclear count (PMN), lymphocyte count, percentage of T cells, T cell response to phytohaemagglutinin (PHA), percentage of B cells, percentage of cells bearing receptors for the Fc portion of immunoglobulin (% FcR cells), killer (K) cell activity defined by antibody-dependent cellular cytotoxicity (ADCC), and natural killer (NK) cell activity. Central nervous system (CNS) immunoglobulin G (IgG) synthesis was also measured. The patients were followed carefully by both quantitative and qualitative methods for any change in their neurologic condition. Selective reduction in NK activity was observed with CY and 5-FU while no significant alteration was seen in %FcR cells and K activity. CY differed from 5-FU in reducing lymphocyte count and B cell percentage while 5-FU decreased the percentage of T cells. CCNU, but not the other drugs, reduced T cell proliferative response to PHA. In addition, CCNU, which is known to penetrate well into the nervous system, caused a modest reduction in CNS IgG synthesis, while 5-FU had an uncertain effect. Clinically the patients were unchanged or continued to progress in their disability. The results suggest an independence of the CNS immune from the systemic immune system in MS in response to many immunosuppressive drugs. PMID:6603303

Neuromodulation and Synaptic Plasticity for the Control of Fast Periodic Movement: Energy Efficiency in Coupled Compliant Joints via PCA.

PubMed

Stratmann, Philipp; Lakatos, Dominic; Albu-Schäffer, Alin

2016-01-01

There are multiple indications that the nervous system of animals tunes muscle output to exploit natural dynamics of the elastic locomotor system and the environment. This is an advantageous strategy especially in fast periodic movements, since the elastic elements store energy and increase energy efficiency and movement speed. Experimental evidence suggests that coordination among joints involves proprioceptive input and neuromodulatory influence originating in the brain stem. However, the neural strategies underlying the coordination of fast periodic movements remain poorly understood. Based on robotics control theory, we suggest that the nervous system implements a mechanism to accomplish coordination between joints by a linear coordinate transformation from the multi-dimensional space representing proprioceptive input at the joint level into a one-dimensional controller space. In this one-dimensional subspace, the movements of a whole limb can be driven by a single oscillating unit as simple as a reflex interneuron. The output of the oscillating unit is transformed back to joint space via the same transformation. The transformation weights correspond to the dominant principal component of the movement. In this study, we propose a biologically plausible neural network to exemplify that the central nervous system (CNS) may encode our controller design. Using theoretical considerations and computer simulations, we demonstrate that spike-timing-dependent plasticity (STDP) for the input mapping and serotonergic neuromodulation for the output mapping can extract the dominant principal component of sensory signals. Our simulations show that our network can reliably control mechanical systems of different complexity and increase the energy efficiency of ongoing cyclic movements. The proposed network is simple and consistent with previous biologic experiments. Thus, our controller could serve as a candidate to describe the neural control of fast, energy-efficient, periodic movements involving multiple coupled joints.

Neuromodulation and Synaptic Plasticity for the Control of Fast Periodic Movement: Energy Efficiency in Coupled Compliant Joints via PCA

PubMed Central

Stratmann, Philipp; Lakatos, Dominic; Albu-Schäffer, Alin

2016-01-01

There are multiple indications that the nervous system of animals tunes muscle output to exploit natural dynamics of the elastic locomotor system and the environment. This is an advantageous strategy especially in fast periodic movements, since the elastic elements store energy and increase energy efficiency and movement speed. Experimental evidence suggests that coordination among joints involves proprioceptive input and neuromodulatory influence originating in the brain stem. However, the neural strategies underlying the coordination of fast periodic movements remain poorly understood. Based on robotics control theory, we suggest that the nervous system implements a mechanism to accomplish coordination between joints by a linear coordinate transformation from the multi-dimensional space representing proprioceptive input at the joint level into a one-dimensional controller space. In this one-dimensional subspace, the movements of a whole limb can be driven by a single oscillating unit as simple as a reflex interneuron. The output of the oscillating unit is transformed back to joint space via the same transformation. The transformation weights correspond to the dominant principal component of the movement. In this study, we propose a biologically plausible neural network to exemplify that the central nervous system (CNS) may encode our controller design. Using theoretical considerations and computer simulations, we demonstrate that spike-timing-dependent plasticity (STDP) for the input mapping and serotonergic neuromodulation for the output mapping can extract the dominant principal component of sensory signals. Our simulations show that our network can reliably control mechanical systems of different complexity and increase the energy efficiency of ongoing cyclic movements. The proposed network is simple and consistent with previous biologic experiments. Thus, our controller could serve as a candidate to describe the neural control of fast, energy-efficient, periodic movements involving multiple coupled joints. PMID:27014051

Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice.

PubMed

Douris, Nicholas; Stevanovic, Darko M; Fisher, Ffolliott M; Cisu, Theodore I; Chee, Melissa J; Nguyen, Ngoc L; Zarebidaki, Eleen; Adams, Andrew C; Kharitonenkov, Alexei; Flier, Jeffrey S; Bartness, Timothy J; Maratos-Flier, Eleftheria

2015-07-01

Fibroblast growth factor 21 (FGF21) has multiple metabolic actions, including the induction of browning in white adipose tissue. Although FGF21 stimulated browning results from a direct interaction between FGF21 and the adipocyte, browning is typically associated with activation of the sympathetic nervous system through cold exposure. We tested the hypothesis that FGF21 can act via the brain, to increase sympathetic activity and induce browning, independent of cell-autonomous actions. We administered FGF21 into the central nervous system via lateral ventricle infusion into male mice and found that the central treatment increased norepinephrine turnover in target tissues that include the inguinal white adipose tissue and brown adipose tissue. Central FGF21 stimulated browning as assessed by histology, expression of uncoupling protein 1, and the induction of gene expression associated with browning. These effects were markedly attenuated when mice were treated with a β-blocker. Additionally, neither centrally nor peripherally administered FGF21 initiated browning in mice lacking β-adrenoceptors, demonstrating that an intact adrenergic system is necessary for FGF21 action. These data indicate that FGF21 can signal in the brain to activate the sympathetic nervous system and induce adipose tissue thermogenesis.

Gut commensalism, cytokines, and central nervous system demyelination.

PubMed

Telesford, Kiel; Ochoa-Repáraz, Javier; Kasper, Lloyd H

2014-08-01

There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination.

Test-retest reliability of the multiple sleep latency test in narcolepsy without cataplexy and idiopathic hypersomnia.

PubMed

Trotti, Lynn Marie; Staab, Beth A; Rye, David B

2013-08-15

Differentiation of narcolepsy without cataplexy from idiopathic hypersomnia relies entirely upon the multiple sleep latency test (MSLT). However, the test-retest reliability for these central nervous system hypersomnias has never been determined. Patients with narcolepsy without cataplexy, idiopathic hypersomnia, and physiologic hypersomnia who underwent two diagnostic multiple sleep latency tests were identified retrospectively. Correlations between the mean sleep latencies on the two studies were evaluated, and we probed for demographic and clinical features associated with reproducibility versus change in diagnosis. Thirty-six patients (58% women, mean age 34 years) were included. Inter -test interval was 4.2 ± 3.8 years (range 2.5 months to 16.9 years). Mean sleep latencies on the first and second tests were 5.5 (± 3.7 SD) and 7.3 (± 3.9) minutes, respectively, with no significant correlation (r = 0.17, p = 0.31). A change in diagnosis occurred in 53% of patients, and was accounted for by a difference in the mean sleep latency (N = 15, 42%) or the number of sleep onset REM periods (N = 11, 31%). The only feature predictive of a diagnosis change was a history of hypnagogic or hypnopompic hallucinations. The multiple sleep latency test demonstrates poor test-retest reliability in a clinical population of patients with central nervous system hypersomnia evaluated in a tertiary referral center. Alternative diagnostic tools are needed.

Heart rate variability regression and risk of sudden unexpected death in epilepsy.

PubMed

Galli, Alessio; Lombardi, Federico

2017-02-01

The exact mechanisms of sudden unexpected death in epilepsy remain elusive, despite there is consensus that SUDEP is associated with severe derangements in the autonomic control to vital functions as breathing and heart rate regulation. Heart rate variability (HRV) has been advocated as biomarker of autonomic control to the heart. Cardiac dysautonomia has been found in diseases where other branches of the autonomous nervous system are damaged, as Parkinson disease and multiple system atrophy. In this perspective, an impaired HRV not only is a risk factor for sudden cardiac death mediated by arrhythmias, but also a potential biomarker for monitoring a progressive decline of the autonomous nervous system. This slope may lead to an acute imbalance of the regulatory pathways of vital functions after seizure and then to SUDEP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Harnessing the capacity of cell-penetrating peptides for drug delivery to the central nervous system.

PubMed

Kang, Ting; Gao, Xiaoling; Chen, Jun

2014-01-01

The existence of blood-brain barrier (BBB) represents the most formidable challenge for drug delivery to the central nervous system (CNS). Modern breakthrough in biology offers multiple choices for overcoming this barrier but yields modest outcomes for clinical application due to various problems such as safety concerns, insufficient delivery efficiency and poor penetration. Cell penetrating peptides (CPPs) possessing powerful transmembrane capacity have been shown to be effective transport vectors for bioactive molecules and an attractive alternative to traditional active targeting approaches. However, the non-specificity of CPPs has hindered them from targeting a desired site of action. Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with specific targeting property may extricate CPPs from the dilemma. In this review, both the traditional and novel applications of CPPs-based strategies for CNS drug delivery will be discussed.

The Complete Remission of Acquired Immunodeficiency Syndrome-associated Isolated Central Nervous System Lymphomatoid Granulomatosis: A Case Report and Review of the Literature

PubMed Central

Kano, Yasuhiro; Kodaira, Minori; Ushiki, Atsuhito; Kosaka, Makoto; Yamada, Mitsunori; Shingu, Kunihiko; Nishihara, Hiroshi; Hanaoka, Masayuki; Sekijima, Yoshiki

2017-01-01

A 49-year-old man presented with gradually progressive aphasia one month after being diagnosed with acquired immunodeficiency syndrome (AIDS). Brain magnetic resonance imaging showed multiple brain lesions with punctate and linear enhancement. A polymerase chain reaction detected Epstein-Barr virus (EBV) in the patient's cerebrospinal fluid. A diagnosis of isolated central nervous system lymphomatoid granulomatosis (CNS-LYG) was made based on the brain biopsy findings. The complete remission of CNS-LYG was achieved by anti-retroviral therapy (ART) alone. In the present case, the development of AIDS-associated CNS-LYG was considered to have been initiated by the reactivation of EBV in the CNS under immunosuppressive conditions. The patient's condition improved with the reconstitution of the patient's immune system. PMID:28824078

Anticholinergics and Central Nervous System Effects: Are We Confused?

PubMed Central

Staskin, David R; Zoltan, Edward

2007-01-01

The central nervous system (CNS) effects of anticholinergic agents have been documented in various patient populations and to varying degrees in case reports, brain-activity surrogates, and computerized cognitive testing. The older patient population with overactive bladder represents a group at increased risk of cognitive impairment and other CNS side effects associated with antimuscarinic agents. The complexity of the effect of anticholinergic agents on CNS function requires an increased level of careful investigation. Studies need to be performed in the at-risk population with multiple, validated tests at clinically prescribed doses in acute and chronic situations. These studies need to take into account the effect of commonly prescribed dosing regimens, with doses selected to represent with equivalent bladder potency. The alterations in the serum levels and parent/metabolite effects contributed by metabolic issues or drug delivery systems require special attention. PMID:18231615

Simpson-Golabi-Behmel syndrome types I and II.

PubMed

Tenorio, Jair; Arias, Pedro; Martínez-Glez, Víctor; Santos, Fernando; García-Miñaur, Sixto; Nevado, Julián; Lapunzina, Pablo

2014-09-20

Simpson-Golabi-Behmel syndrome (SGBS) is a rare overgrowth syndrome clinically characterized by multiple congenital abnormalities, pre/postnatal overgrowth, distinctive craniofacial features, macrocephaly, and organomegaly. Abnormalities of the skeletal system, heart, central nervous system, kidney, and gastrointestinal tract may also be observed. Intellectual disability, early motor milestones and speech delay are sometimes present; however, there are a considerable number of individuals with normal intelligence.

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation.

PubMed

Petra, Anastasia I; Panagiotidou, Smaro; Hatziagelaki, Erifili; Stewart, Julia M; Conti, Pio; Theoharides, Theoharis C

2015-05-01

Gut microbiota regulate intestinal function and health. However, mounting evidence indicates that they can also influence the immune and nervous systems and vice versa. This article reviews the bidirectional relationship between the gut microbiota and the brain, termed the microbiota-gut-brain (MGB) axis, and discusses how it contributes to the pathogenesis of certain disorders that may involve brain inflammation. Articles were identified with a search of Medline (starting in 1980) by using the key words anxiety, attention-deficit hypersensitivity disorder (ADHD), autism, cytokines, depression, gut, hypothalamic-pituitary-adrenal (HPA) axis, inflammation, immune system, microbiota, nervous system, neurologic, neurotransmitters, neuroimmune conditions, psychiatric, and stress. Various afferent or efferent pathways are involved in the MGB axis. Antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and essential metabolites all convey information to the central nervous system about the intestinal state. Conversely, the hypothalamic-pituitary-adrenal axis, the central nervous system regulatory areas of satiety, and neuropeptides released from sensory nerve fibers affect the gut microbiota composition directly or through nutrient availability. Such interactions seem to influence the pathogenesis of a number of disorders in which inflammation is implicated, such as mood disorder, autism-spectrum disorders, attention-deficit hypersensitivity disorder, multiple sclerosis, and obesity. Recognition of the relationship between the MGB axis and the neuroimmune systems provides a novel approach for better understanding and management of these disorders. Appropriate preventive measures early in life or corrective measures such as use of psychobiotics, fecal microbiota transplantation, and flavonoids are discussed. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Effect of partition board color on mood and autonomic nervous function.

PubMed

Sakuragi, Sokichi; Sugiyama, Yoshiki

2011-12-01

The purpose of this study was to evaluate the effects of the presence or absence (control) of a partition board and its color (red, yellow, blue) on subjective mood ratings and changes in autonomic nervous system indicators induced by a video game task. The increase in the mean Profile of Mood States (POMS) Fatigue score and mean Oppressive feeling rating after the task was lowest with the blue partition board. Multiple-regression analysis identified oppressive feeling and error scores on the second half of the task as statistically significant contributors to Fatigue. While explanatory variables were limited to the physiological indices, multiple-regression analysis identified a significant contribution of autonomic reactivity (assessed by heart rate variability) to Fatigue. These results suggest that a blue partition board would reduce task-induced subjective fatigue, in part by lowering the oppressive feeling of being enclosed during the task, possibly by increasing autonomic reactivity.

Overview of the Autonomic Nervous System

MedlinePlus

... be reversible or progressive. Anatomy of the autonomic nervous system The autonomic nervous system is the part of ... organs they connect with. Function of the autonomic nervous system The autonomic nervous system controls internal body processes ...

[Multiple myeloma (IgG-kappa) infiltrating central nervous system, lymph nodes, liver, and kidneys, and with elevation of IgE].

PubMed

Toyota, Shigeo; Nakamura, Norihiko; Dan, Kazuo

2004-05-01

A 63-year-old man was admitted because of general malaise, fever, headache, generalized lymphadenopathy and hepatomegaly in July 2002. He was diagnosed as having multiple myeloma (MM) (IgG-kappa type) with atypical plasma cells in the bone marrow, lymph nodes and cerebrospinal fluid. Systemic and intrathecal chemotherapy were effective. Because of an increase of polyclonal IgE, electrophoretic patterns revealed an M-peak which was not as sharp as that in IgG myeloma. IgE production is not impaired by the pathologic process in MM patients.

[Epidemiological, clinical and progressive aspects of neurological manifestations associated with retroviral infections: eleven year retrospective study].

PubMed

Sene-Diouf, F; Ndiaye, M; Diop, A G; Thiam, A; Ndao, A K; Diagne, M; Ndiaye, M M; Ndiaye, I P

2000-01-01

Through a cohort of 93 neuroaids which has been diagnosed at Dakar in our Neurology Department, the authors evaluated the hospital prevalence of retrovirus, detected socio-demographic factors, related AIDS outline the mean neurological picture and try to correlate survival and neurological involvement of these patients. Among 1151 patients who got retroviral blood test, 93 were seropositive (8.1%). On these repartitions 36 were females (38.7%) and 57 males (61.3%). The age goes from 19 to 76 years old. 45 patients (48.4%) have been found positive for HIV-1 blood test, 21 patients (22.6%) for HIV-2 blood test, 11 patients (11.8%) for both HIV2, 11 patients (11.8%) for HTLV1, 3 patients (3.2%) for both HIV-1 and HTLV1, and 2 patients (2.2%) for both HIV-2 and HTLV1. In our study the transmission of AIDS occur mainly through heterosexual inter course and multiple parternship is a high risk group. The central nervous system deseases represented 68.8% of cases. The pathology were dominated by stroke, myelopathies, meningoencephalotis and spinal cord compression. The peripheral nervous system desease were found in 7.5% of cases. The peripheral facial paralysis occupied the first place in HIV infections of peripheral nervous system deseases (57.1% of cases). When neurological involvement set up the letality is higher for HIV-1 (57% of global letality) and for central system nervous involvement (76.2%).

The Impact of Team-Based Learning on Nervous System Examination Knowledge of Nursing Students.

PubMed

Hemmati Maslakpak, Masomeh; Parizad, Naser; Zareie, Farzad

2015-12-01

Team-based learning is one of the active learning approaches in which independent learning is combined with small group discussion in the class. This study aimed to determine the impact of team-based learning in nervous system examination knowledge of nursing students. This quasi-experimental study was conducted on 3(rd) grade nursing students, including 5th semester (intervention group) and 6(th) semester (control group). The traditional lecture method and the team-based learning method were used for educating the examination of the nervous system for intervention and control groups, respectively. The data were collected by a test covering 40-questions (multiple choice, matching, gap-filling and descriptive questions) before and after intervention in both groups. Individual Readiness Assurance Test (RAT) and Group Readiness Assurance Test (GRAT) used to collect data in the intervention group. In the end, the collected data were analyzed by SPSS ver. 13 using descriptive and inferential statistical tests. In team-based learning group, mean and standard deviation was 13.39 (4.52) before the intervention, which had been increased to 31.07 (3.20) after the intervention and this increase was statistically significant. Also, there was a statistically significant difference between the scores of RAT and GRAT in team-based learning group. Using team-based learning approach resulted in much better improvement and stability in the nervous system examination knowledge of nursing students compared to traditional lecture method; therefore, this method could be efficiently used as an effective educational approach in nursing education.

Undiagnosed neurological disease as a potential cause of male lower urinary tract symptoms.

PubMed

Wei, Diana Y; Drake, Marcus J

2016-01-01

In the central nervous system there are many regulatory processes controlling the lower urinary tract. This review considers the possibility that urinary dysfunction may precede diagnosis of neurological disease. Lower urinary tract symptoms (LUTS) occur early in multiple system atrophy, Parkinson's disease and normal pressure hydrocephalus, and may present before neurological diagnosis. Some people present with LUTS and subsequently are diagnosed with multiple sclerosis or a spinal condition. In male LUTS, the symptoms could reflect early stages of a neurological disease, which has not yet been diagnosed ('occult neurology'). Key symptoms include erectile dysfunction, retrograde ejaculation, enuresis, loss of filling sensation or unexplained stress urinary incontinence. Directed questioning should enquire about visual symptoms, back pain, anosmia, bowel dysfunction and incontinence, or memory loss. Examination features can include resting tremor, 'croaky' speech, abnormal gait, orthostatic hypotension, ataxia, or altered perineal sensation. Imaging, such as MRI scan, should only be requested after expert neurological examination, to ensure the correct parts of the central nervous system are scanned with appropriate radiological protocols. Urologists should consider an undiagnosed neurological condition can be present in a few cases. Any finding should be further evaluated by colleagues with relevant expertise.

Cancer and central nervous system disorders: protocol for an umbrella review of systematic reviews and updated meta-analyses of observational studies.

PubMed

Catalá-López, Ferrán; Hutton, Brian; Driver, Jane A; Page, Matthew J; Ridao, Manuel; Valderas, José M; Alonso-Arroyo, Adolfo; Forés-Martos, Jaume; Martínez, Salvador; Gènova-Maleras, Ricard; Macías-Saint-Gerons, Diego; Crespo-Facorro, Benedicto; Vieta, Eduard; Valencia, Alfonso; Tabarés-Seisdedos, Rafael

2017-04-04

The objective of this study will be to synthesize the epidemiological evidence and evaluate the validity of the associations between central nervous system disorders and the risk of developing or dying from cancer. We will perform an umbrella review of systematic reviews and conduct updated meta-analyses of observational studies (cohort and case-control) investigating the association between central nervous system disorders and the risk of developing or dying from any cancer or specific types of cancer. Searches involving PubMed/MEDLINE, EMBASE, SCOPUS and Web of Science will be used to identify systematic reviews and meta-analyses of observational studies. In addition, online databases will be checked for observational studies published outside the time frames of previous reviews. Eligible central nervous system disorders will be Alzheimer's disease, anorexia nervosa, amyotrophic lateral sclerosis, autism spectrum disorders, bipolar disorder, depression, Down's syndrome, epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and schizophrenia. The primary outcomes will be cancer incidence and cancer mortality in association with a central nervous system disorder. Secondary outcome measures will be site-specific cancer incidence and mortality, respectively. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study quality/risk of bias will be appraised by two reviewers independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary observational studies will be conducted where appropriate. Parameters for exploring statistical heterogeneity are pre-specified. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes. Our study will establish the extent of the epidemiological evidence underlying the associations between central nervous system disorders and cancer and will provide a rigorous and updated synthesis of a range of important site-specific cancer outcomes. PROSPERO CRD42016052762.

A Case of Pseudo-Retardation.

ERIC Educational Resources Information Center

Stott, D. H.

Review of a case study of a 4-year-old girl who assumed the role of a retardate reveals that the girl probably suffered multiple congenital impairments of a minor character that affected the central nervous system and the structures governing social behavior and maturation. The stated basis for pseudo-retardation is the person's ability to…

Assessment of Cross-Chemical Predictibility for Changes in Serum Clinical Bioindicators and EEG Produced by Pesticides with Different Modes of Action

EPA Science Inventory

Electroencephalography (EEG) is often used as an apical measure of multiple types of central nervous system (CNS) changes, while biomarkers in blood may serve as predictors for adverse outcomes. Correlation between these two measures would suggest that certain changes in biomarke...

A COMPARISON OF MULTIPLE TOXICITIES FOLLOWING DEVELOPMENTAL EXPOSURE TO PESTICIDES: NEUROTOXICITY, IMMUNOTOXICITY, AND REPRODUCTIVE TOXICITY.

EPA Science Inventory

The NAS report (Pesticides in the Diets of Infants and Children, 1993) called for significant research effort into the long-term effects of perinatal pesticide exposure on the nervous, immune, and reproductive systems. In response, the US EPA and NIEHS collaborated on a series o...

Severe Neurologic Disorders in 2 Fetuses with Zika Virus Infection, Colombia.

PubMed

Acosta-Reyes, Jorge; Navarro, Edgar; Herrera, Maria José; Goenaga, Eloina; Ospina, Martha L; Parra, Edgar; Mercado, Marcela; Chaparro, Pablo; Beltran, Mauricio; Gunturiz, Maria Luz; Pardo, Lissethe; Valencia, Catalina; Huertas, Sandra; Rodríguez, Jorge; Ruiz, Germán; Valencia, Diana; Haddad, Lisa B; Tinker, Sarah C; Moore, Cynthia A; Baquero, Hernando

2017-06-01

We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus.

Severe Neurologic Disorders in 2 Fetuses with Zika Virus Infection, Colombia

PubMed Central

Navarro, Edgar; Herrera, Maria José; Goenaga, Eloina; Ospina, Martha L.; Parra, Edgar; Mercado, Marcela; Chaparro, Pablo; Beltran, Mauricio; Gunturiz, Maria Luz; Pardo, Lissethe; Valencia, Catalina; Huertas, Sandra; Rodríguez, Jorge; Ruiz, Germán; Valencia, Diana; Haddad, Lisa B.; Tinker, Sarah C.; Moore, Cynthia A.; Baquero, Hernando

2017-01-01

We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus. PMID:28296632

"Digit Anatomy": A New Technique for Learning Anatomy Using Motor Memory

ERIC Educational Resources Information Center

Oh, Chang-Seok; Won, Hyung-Sun; Kim, Kyong-Jee; Jang, Dong-Su

2011-01-01

Gestural motions of the hands and fingers are powerful tools for expressing meanings and concepts, and the nervous system has the capacity to retain multiple long-term motor memories, especially including movements of the hands. We developed many sets of successive movements of both hands, referred to as "digit anatomy," and made…

Vocational identity, positive affect, and career thoughts in a group of young adult central nervous system cancer survivors.

PubMed

Lange, Dustin D; Wong, Alex W K; Strauser, David R; Wagner, Stacia

2014-12-01

The aims of this study were as follows: (a) to compare levels of career thoughts and vocational identity between young adult childhood central nervous system (CNS) cancer survivors and noncancer peers and (b) to investigate the contribution of vocational identity and affect on career thoughts among cancer survivors. Participants included 45 young adult CNS cancer survivors and a comparison sample of 60 college students. Participants completed Career Thoughts Inventory, My Vocational Situation, and the Positive and Negative Affect Schedule. Multivariate analysis of variance and multiple regression analysis were used to analyze the data in this study. CNS cancer survivors had a higher level of decision-making confusion than the college students. Multiple regression analysis indicated that vocational identity and positive affect significantly predicted the career thoughts of CNS survivors. The differences in decision-making confusion suggest that young adult CNS survivors would benefit from interventions that focus on providing knowledge of how to make decisions, while increasing vocational identity and positive affect for this specific population could also be beneficial.

An autopsy case of chronic active Epstein-Barr virus infection (CAEBV): distribution of central nervous system (CNS) lesions.

PubMed

Kobayashi, Zen; Tsuchiya, Kuniaki; Takahashi, Makoto; Yokota, Osamu; Sasaki, Atsushi; Bhunchet, Ekapot; Arai, Tetsuaki; Akiyama, Haruhiko; Kamoshita, Masaharu; Kotera, Minoru; Mizusawa, Hidehiro

2008-12-15

A 27-year-old Japanese man developed recurrent respiratory and central nervous system (CNS) symptoms, and hemophagocytic syndromes with a clinical course of 6 years. CT demonstrated multiple nodular lesions in the bilateral lungs, and MRI revealed multiple abnormal intensity areas in the brain and spinal cord. Cerebrospinal fluid (CSF) examination disclosed mild pleocytosis and the presence of Epstein-Barr virus (EBV)-DNA detected by polymerase chain reaction (PCR). The patient died of a hemorrhagic shock associated with a hemophagocytic syndrome. A postmortem study revealed massive hemorrhage in the abdominal cavity and iliopsoas muscles, as well as diffuse infiltration of lymphocytes and/or macrophages into the lungs, liver, kidneys, spleen, cardiac muscle, bone marrow, and CNS. The severe involvement was demonstrated in the CNS, especially in the spinal cord and brainstem. The CD3 positive cells of the brainstem were EBV-encoded RNA 1 positive. This is the first autopsy case of chronic active EBV infection (CAEBV) in which severe and extensive CNS involvement was demonstrated.

Effects of whole body vibration on muscle spasticity for people with central nervous system disorders: a systematic review.

PubMed

Huang, Meizhen; Liao, Lin-Rong; Pang, Marco Yc

2017-01-01

To examine the effects of whole-body vibration on spasticity among people with central nervous system disorders. Electronic searches were conducted using CINAHL, Cochrane Library, MEDLINE, Physiotherapy Evidence Database, PubMed, PsycINFO, SPORTDiscus and Scopus to identify randomized controlled trials that investigated the effect of whole-body vibration on spasticity among people with central nervous system disorders (last search in August 2015). The methodological quality and level of evidence were rated using the PEDro scale and guidelines set by the Oxford Centre for Evidence-Based Medicine. Nine trials with totally 266 subjects (three in cerebral palsy, one in multiple sclerosis, one in spinocerebellar ataxia, and four in stroke) fulfilled all selection criteria. One study was level 1b (PEDro⩾6 and sample size>50) and eight were level 2b (PEDro<6 or sample size ⩽50). All three cerebral palsy trials (level 2b) reported some beneficial effects of whole-body vibration on reducing leg muscle spasticity. Otherwise, the results revealed no consistent benefits on spasticity in other neurological conditions studied. There is little evidence that change in spasticity was related to change in functional performance. The optimal protocol could not be identified. Many reviewed studies were limited by weak methodological and reporting quality. Adverse events were minor and rare. Whole-body vibration may be useful in reducing leg muscle spasticity in cerebral palsy but this needs to be verified by future high quality trials. There is insufficient evidence to support or refute the notion that whole-body vibration can reduce spasticity in stroke, spinocerebellar ataxia or multiple sclerosis.

The application of Fourier transform infrared microspectroscopy for the study of diseased central nervous system tissue.

PubMed

Caine, Sally; Heraud, Philip; Tobin, Mark J; McNaughton, Donald; Bernard, Claude C A

2012-02-15

In the last two decades the field of infrared spectroscopy has seen enormous advances in both instrumentation and the development of bioinformatic methods for spectral analysis, allowing the examination of a large variety of healthy and diseased samples, including biological fluids, isolated cells, whole tissues, and tissue sections. The non-destructive nature of the technique, together with the ability to directly probe biochemical changes without the addition of stains or contrast agents, enables a range of complementary analyses. This review focuses on the application of Fourier transform infrared (FTIR) microspectroscopy to analyse central nervous system tissues, with the aim of understanding the biochemical and structural changes associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathies, multiple sclerosis, as well as brain tumours. Modern biospectroscopic methods that combine FTIR microspectroscopy with bioinformatic analysis constitute a powerful new methodology that can discriminate pathology from normal healthy tissue in a rapid, unbiased fashion, with high sensitivity and specificity. Notably, the ability to detect protein secondary structural changes associated with Alzheimer's plaques, neurons in Parkinson's disease, and in some spectra from meningioma, as well as in the animal models of Alzheimer's disease, transmissible spongiform encephalopathies, and multiple sclerosis, illustrates the power of this technology. The capacity to offer insight into the biochemical and structural changes underpinning aetio-pathogenesis of diseases in tissues provides both a platform to investigate early pathologies occurring in a variety of experimentally induced and naturally occurring central nervous system diseases, and the potential to evaluate new therapeutic approaches. Copyright © 2011 Elsevier Inc. All rights reserved.

From fish to man: understanding endogenous remyelination in central nervous system demyelinating diseases.

PubMed

Dubois-Dalcq, Monique; Williams, Anna; Stadelmann, Christine; Stankoff, Bruno; Zalc, Bernard; Lubetzki, Catherine

2008-07-01

In the central nervous system (CNS) of man, evolutionary pressure has preserved some capability for remyelination while axonal regeneration is very limited. In contrast, two efficient programmes of regeneration exist in the adult fish CNS, neurite regrowth and remyelination. The rapidity of CNS remyelination is critical since it not only restores fast conduction of nerve impulses but also maintains axon integrity. If myelin repair fails, axons degenerate, leading to increased disability. In the human CNS demyelinating disease multiple sclerosis (MS), remyelination often takes place in the midst of inflammation. Here, we discuss recent studies that address the innate repair capabilities of the axon-glia unit from fish to man. We propose that expansion of this research field will help find ways to maintain or enhance spontaneous remyelination in man.

Cardiomyocyte-released factors stimulate oligodendrocyte precursor cells proliferation

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

Kuroda, Mariko; Muramatsu, Rieko; Precursory Research for Embryonic Science and Technology

The heart produces multiple diffusible factors that are involved in a number of physiological processes, but the action of these factors on the central nervous system is not well understood. In this study, we found that one or more factors released by cardiomyocytes promote oligodendrocyte precursor cell (OPC) proliferation in vitro. Mouse OPCs co-cultured with mouse cardiomyocytes showed higher proliferative ability than OPCs cultured alone. In addition, cardiomyocyte-conditioned media was sufficient to promote OPC proliferation. The phosphorylation of phosphatidylinositol (PI) 3-kinase and extracellular signal-regulated kinase (ERK) in OPCs is necessary for the enhancement of OPC proliferation by cardiomyocyte-conditioned media. These datamore » indicate that heart-derived factors have the ability to directly regulate the function of central nervous system (CNS) cells.« less

Optimized optical clearing method for imaging central nervous system

NASA Astrophysics Data System (ADS)

Yu, Tingting; Qi, Yisong; Gong, Hui; Luo, Qingming; Zhu, Dan

2015-03-01

The development of various optical clearing methods provides a great potential for imaging entire central nervous system by combining with multiple-labelling and microscopic imaging techniques. These methods had made certain clearing contributions with respective weaknesses, including tissue deformation, fluorescence quenching, execution complexity and antibody penetration limitation that makes immunostaining of tissue blocks difficult. The passive clarity technique (PACT) bypasses those problems and clears the samples with simple implementation, excellent transparency with fine fluorescence retention, but the passive tissue clearing method needs too long time. In this study, we not only accelerate the clearing speed of brain blocks but also preserve GFP fluorescence well by screening an optimal clearing temperature. The selection of proper temperature will make PACT more applicable, which evidently broaden the application range of this method.

Programmed Cell Death and Caspase Functions During Neural Development.

PubMed

Yamaguchi, Yoshifumi; Miura, Masayuki

2015-01-01

Programmed cell death (PCD) is a fundamental component of nervous system development. PCD serves as the mechanism for quantitative matching of the number of projecting neurons and their target cells through direct competition for neurotrophic factors in the vertebrate peripheral nervous system. In addition, PCD plays roles in regulating neural cell numbers, canceling developmental errors or noise, and tissue remodeling processes. These findings are mainly derived from genetic studies that prevent cells from dying by apoptosis, which is a major form of PCD and is executed by activation of evolutionarily conserved cysteine protease caspases. Recent studies suggest that caspase activation can be coordinated in time and space at multiple levels, which might underlie nonapoptotic roles of caspases in neural development in addition to apoptotic roles. © 2015 Elsevier Inc. All rights reserved.

Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen.

PubMed

Braak, H; Rüb, U; Gai, W P; Del Tredici, K

2003-05-01

The progressive, neurodegenerative process underlying idiopathic Parkinson's disease is associated with the formation of proteinaceous inclusion bodies that involve a few susceptible neuronal types of the human nervous system. In the lower brain stem, the process begins in the dorsal motor nucleus of the vagus nerve and advances from there essentially upwards through susceptible regions of the medulla oblongata, pontine tegmentum, midbrain, and basal forebrain until it reaches the cerebral cortex. With time, multiple components of the autonomic, limbic, and motor systems become severely impaired. All of the vulnerable subcortical grays and cortical areas are closely interconnected. Incidental cases of idiopathic Parkinson's disease may show involvement of both the enteric nervous system and the dorsal motor nucleus of the vagus nerve. This observation, combined with the working hypothesis that the stereotypic topographic expansion pattern of the lesions may resemble that of a falling row of dominos, prompts the question whether the disorder might originate outside of the central nervous system, caused by a yet unidentified pathogen that is capable of passing the mucosal barrier of the gastrointestinal tract and, via postganglionic enteric neurons, entering the central nervous system along unmyelinated praeganglionic fibers generated from the visceromotor projection cells of the vagus nerve. By way of retrograde axonal and transneuronal transport, such a causative pathogen could reach selectively vulnerable subcortical nuclei and, unimpeded, gain access to the cerebral cortex. The here hypothesized mechanism offers one possible explanation for the sequential and apparently uninterrupted manner in which vulnerable brain regions, subcortical grays and cortical areas become involved in idiopathic Parkinson's disease.

[Persistent Bilateral Vocal Cord Paralysis after General Anesthesia in a Patient with Multiple System Atrophy: A Case Report].

PubMed

Konishi, Hanako; Mizota, Toshiyuki; Fukuda, Kazuhiko

2015-06-01

We report a case of persistent bilateral vocal cord paralysis which developed after spine surgery under general anesthesia in a patient with multiple system atrophy. A 64-year-old woman was scheduled to receive spinal fusion surgery for kyphoscoliosis. She did not have apparent symptoms of vocal cord paralysis such as hoarseness before surgery. The surgery was performed smoothly under general anesthesia with endotracheal intubation. However, immediately after extubation, the patient developed severe upper airway obstruction and was re-intubated. Fiberoptic laryngoscopy revealed bilateral vocal cord abductor paralysis. Vocal cord paralysis did not improve and she received tracheotomy on the 12th day after surgery. She also showed symptoms of autonomic nervous system dysfunction and cerebellar ataxia, and was diagnosed as multiple system atrophy on postoperative day 64. We discuss differential diagnosis of persistent vocal cord paralysis after general anesthesia, and anesthetic management of a patient with multiple system atrophy.

Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions.

PubMed

Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M; Mariani, John N; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S; John, Gareth R

2015-06-01

In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood-brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood-brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood-brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood-brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood-brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood-brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an astrocyte-derived permeability factor, and suggest TYMP and VEGFA together promote blood-brain barrier breakdown. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Identification of Ind transcription activation and repression domains required for dorsoventral patterning of the CNS.

PubMed

Von Ohlen, Tonia L; Moses, Cade

2009-07-01

Specification of cell fates across the dorsoventral axis of the central nervous system in Drosophila involves the subdivision of the neuroectoderm into three domains that give rise to three columns of neural precursor cells called neuroblasts. Ventral nervous system defective (Vnd), intermediate neuroblasts defective (Ind) and muscle segment homeobox (Msh) are expressed in the three columns from ventral to dorsal, respectively. The products of these genes play multiple important roles in formation and specification of the embryonic nervous system. Ind, for example, is known to play roles in two important processes. First, Ind is essential for formation of neuroblasts conjunction with SoxB class transcription factors. Sox class transcription factors are known to specify neural stem cells in vertebrates. Second, Ind plays an important role in patterning the CNS in conjunction with, vnd and msh, which is also similar to how vertebrates pattern their neural tube. This work focuses two important aspects of Ind function. First, we used multiple approaches to identify and characterize specific domains within the protein that confer repressor or activator ability. Currently, little is known about the presence of activation or repression domains within Ind. Here, we show that transcriptional repression by Ind requires multiple conserved domains within the protein, and that Ind has a transcriptional activation domain. Specifically, we have identified a novel domain, the Pst domain, that has transcriptional repression ability and appears to act independent of interaction with the co-repressor Groucho. This domain is highly conserved among insect species, but is not found in vertebrate Gsh class homeodomain proteins. Second, we show that Ind can and does repress vnd expression, but does so in a stage specific manner. We conclude from this that the function of Ind in regulating vnd expression is one of refinement and maintenance of the dorsal border.

Immunotherapeutics in Pediatric Autoimmune Central Nervous System Disease: Agents and Mechanisms.

PubMed

Nosadini, Margherita; Sartori, Stefano; Sharma, Suvasini; Dale, Russell C

2017-08-01

Beyond the major advances produced by careful clinical-radiological phenotyping and biomarker development in autoimmune central nervous system disorders, a comprehensive knowledge of the range of available immune therapies and a deeper understanding of their action should benefit therapeutic decision-making. This review discusses the agents used in neuroimmunology and their mechanisms of action. First-line treatments typically include corticosteroids, intravenous immunoglobulin, and plasmapheresis, while for severe disease second-line "induction" agents such as rituximab or cyclophosphamide are used. Steroid-sparing agents such as mycophenolate, azathioprine, or methotrexate are often used in potentially relapsing or corticosteroid-dependent diseases. Lessons from adult neuroimmunology and rheumatology could be translated into pediatric autoimmune central nervous system disease in the future, including the potential utility of monoclonal antibodies targeting lymphocytes, adhesion molecules for lymphocytic migration, cytokines or their receptors, or complement. Finally, many agents used in other fields have multiple mechanisms of action, including immunomodulation, with potential usefulness in neuroimmunology, such as antibiotics, psychotropic drugs, probiotics, gut health, and ketogenic diet. All currently accepted and future potential agents have adverse effects, which can be severe; therefore, a "risk-versus-benefit" determination should guide therapeutic decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk of defeats in the central nervous system during deep space missions.

PubMed

Kokhan, Viktor S; Matveeva, Marina I; Mukhametov, Azat; Shtemberg, Andrey S

2016-12-01

Space flight factors (SFF) significantly affect the operating activity of astronauts during deep space missions. Gravitational overloads, hypo-magnetic field and ionizing radiation are the main SFF that perturb the normal activity of the central nervous system (CNS). Acute and chronic CNS risks include alterations in cognitive abilities, reduction of motor functions and behavioural changes. Multiple experimental works have been devoted to the SFF effects on integrative functional activity of the brain; however, the model parameters utilized have not always been ideal and consistent. Even less is known regarding the combined effects of these SFF in a real interplanetary mission, for example to Mars. Our review aims to systemize and analyse the last advancements in astrobiology, with a focus on the combined effects of SFF; as well as to discuss on unification of the parameters for ground-based models of deep space missions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acquired toxoplasmosis. A neglected cause of treatable nervous system disease.

PubMed

Townsend, J J; Wolinsky, J S; Baringer, J R; Johnson, P C

1975-05-01

The neurological manifestations of six cases of acquired central nervous system toxoplasmosis are compared with the 39 well-documented cases from the literature. Half of the patients had underlying systemic diseases (18 malignant neoplasms, two renal transplants, three collagen vascular diseases) treated with intensive immunosuppressive therapy. The remainder had primary toxoplasmosis. Three major neurological patterns were seen: (1) diffuse encephalopathy with or without seizures, (2) meningoencephalitis, and (3) singular or multiple progressive mass lesions. Routine neurological diagnostic studies were not helpful. The Sabin-Feldman dye test or IgM indirect fluorescent antibody test or both were effective in confirming the diagnosis. Twenty-seven patients died without a clinical diagnosis of toxoplasmosis. The diagnosis was made terminally in four additional patients. Thirteen of fourteen patients who received a full course of sulfadiazine or pyrimethamine or both did well. Toxoplasmosis should be considered in the immunosuppressed patient who appears with neurological involvement.

Anti-inflammatory genes associated with multiple sclerosis: a gene expression study.

PubMed

Perga, S; Montarolo, F; Martire, S; Berchialla, P; Malucchi, S; Bertolotto, A

2015-02-15

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system caused by a complex interaction between multiple genes and environmental factors. HLA region is the strongest susceptibility locus, but recent huge genome-wide association studies identified new susceptibility genes. Among these, BACH2, PTGER4, RGS1 and ZFP36L1 were highlighted. Here, a gene expression analysis revealed that three of them, namely BACH2, PTGER4 and ZFP36L1, are down-regulated in MS patients' blood cells compared to healthy subjects. Interestingly, all these genes are involved in the immune system regulation with predominant anti-inflammatory role and their reduction could predispose to MS development. Copyright © 2015 Elsevier B.V. All rights reserved.

77 FR 56133 - Dinotefuran; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-12

... is the nervous system but effects on the nervous system were only observed at high doses. Nervous... cholinergic nervous system seen after repeated dosing. Typically, low to moderate levels of neonicotinoids... peripheral nervous system (PNS). High levels of neonicotinoids can over stimulate the PNS, maintaining cation...

Drosophila Importin-α2 Is Involved in Synapse, Axon and Muscle Development

PubMed Central

Mosca, Timothy J.; Schwarz, Thomas L.

2010-01-01

Nuclear import is required for communication between the cytoplasm and the nucleus and to enact lasting changes in gene transcription following stimuli. Binding to an Importin-α molecule in the cytoplasm is often required to mediate nuclear entry of a signaling protein. As multiple isoforms of Importin-α exist, some may be responsible for the entry of distinct cargoes rather than general nuclear import. Indeed, in neuronal systems, Importin-α isoforms can mediate very specific processes such as axonal tiling and communication of an injury signal. To study nuclear import during development, we examined the expression and function of Importin-α2 in Drosophila melanogaster. We found that Importin-α2 was expressed in the nervous system where it was required for normal active zone density at the NMJ and axonal commissure formation in the central nervous system. Other aspects of synaptic morphology at the NMJ and the localization of other synaptic markers appeared normal in importin-α2 mutants. Importin-α2 also functioned in development of the body wall musculature. Mutants in importin-α2 exhibited errors in muscle patterning and organization that could be alleviated by restoring muscle expression of Importin-α2. Thus, Importin-α2 is needed for some processes in the development of both the nervous system and the larval musculature. PMID:21151903

21 CFR 882.5550 - Central nervous system fluid shunt and components.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Central nervous system fluid shunt and components... Central nervous system fluid shunt and components. (a) Identification. A central nervous system fluid... central nervous system to an internal delivery site or an external receptacle for the purpose of relieving...

21 CFR 882.5550 - Central nervous system fluid shunt and components.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Central nervous system fluid shunt and components... Central nervous system fluid shunt and components. (a) Identification. A central nervous system fluid... central nervous system to an internal delivery site or an external receptacle for the purpose of relieving...

21 CFR 882.5550 - Central nervous system fluid shunt and components.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Central nervous system fluid shunt and components... Central nervous system fluid shunt and components. (a) Identification. A central nervous system fluid... central nervous system to an internal delivery site or an external receptacle for the purpose of relieving...

21 CFR 882.5550 - Central nervous system fluid shunt and components.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Central nervous system fluid shunt and components... Central nervous system fluid shunt and components. (a) Identification. A central nervous system fluid... central nervous system to an internal delivery site or an external receptacle for the purpose of relieving...

21 CFR 882.5550 - Central nervous system fluid shunt and components.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Central nervous system fluid shunt and components... Central nervous system fluid shunt and components. (a) Identification. A central nervous system fluid... central nervous system to an internal delivery site or an external receptacle for the purpose of relieving...

The NEO-FFI in Multiple Sclerosis: Internal Consistency, Factorial Validity, and Correspondence between Self and Informant Reports

ERIC Educational Resources Information Center

Schwartz, Eben S.; Chapman, Benjamin P.; Duberstein, Paul R.; Weinstock-Guttman, Bianca; Benedict, Ralph H. B.

2011-01-01

Personality assessment is a potentially important component of clinical and empirical work with neurological patients because (a) individual differences in personality may be associated with different neurological outcomes and (b) central nervous system changes may give rise to alteration in personality. For personality assessment to be useful to…

Primary Sjogren's syndrome with central nervous system involvement.

PubMed

Alhomoud, Iftetah A; Bohlega, Saeed A; Alkawi, Mohammed Z; Alsemari, Abdulaziz M; Omer, Saleh M; Alsenani, Fahmi M

2009-08-01

To describe the clinical, laboratory, and radiological features of Primary Sjogren's syndrome (PSS) with central nervous system (CNS) involvement. A retrospective case series of 12 female patients with PSS and CNS involvement at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia from 1991-2009. The diagnosis of PSS is defined by the American-European Diagnostic Criteria. We analyzed the clinical, radiological, and immunological features. The mean age was 40 years (range 16-58 years); all patient were females and presented with active neurological symptoms. The neurological involvement preceded the classic sicca symptoms (33%). Eight patients (66%) presented with myelopathy, 9 patients (75%) had optic neuritis, and the rest had variable neurological signs. Immunological tests (anti-Sjogren's syndrome A and anti-Sjogren's syndrome B) were high in 7 patients (58%). Minor salivary gland biopsy revealed inflammatory cell infiltrate in 11 patients (92%). Brain MRI showed scattered white matter changes in 7 patients (58%). Spine MRI showed multiple foci of hyperintensity in T2-weighted image in 6 patients (50%), and long segment of hyperintensity at the cervical spinal cord in 2 patients (16%). Our findings demonstrate that CNS involvements in PSS have great clinical variability and could precede the classic sicca symptoms by years. Primary Sjogren's syndrome can mimic multiple sclerosis (primary progressive multiple sclerosis or relapsing remitting multiple sclerosis), therefore a screening test for PSS should be considered in suspected cases. A well-defined management protocol awaits studies with larger case numbers.

Nature, nurture, and microbes: The development of multiple sclerosis.

PubMed

Wekerle, H

2017-11-01

This paper argues that multiple sclerosis (MS) is the result of an autoimmune attack against components of the central nervous system (CNS). The effector cells involved in the pathogenic process are CNS-autoreactive T cells present in the healthy immune system in a resting state. Upon activation, these cells cross the blood-brain barrier and attack the CNS target tissue. Recent evidence indicates that autoimmune activation may happen in the intestine, following an interaction of bacterial components of the gut flora with local CNS autoreactive T cells. The consequences of this concept are discussed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transcriptomic changes throughout post-hatch development in Gallus gallus pituitary

PubMed Central

Lamont, Susan J; Schmidt, Carl J

2016-01-01

The pituitary gland is a neuroendocrine organ that works closely with the hypothalamus to affect multiple processes within the body including the stress response, metabolism, growth and immune function. Relative tissue expression (rEx) is a transcriptome analysis method that compares the genes expressed in a particular tissue to the genes expressed in all other tissues with available data. Using rEx, the aim of this study was to identify genes that are uniquely or more abundantly expressed in the pituitary when compared to all other collected chicken tissues. We applied rEx to define genes enriched in the chicken pituitaries at days 21, 22 and 42 post-hatch. rEx analysis identified 25 genes shared between all time points, 295 genes shared between days 21 and 22 and 407 genes unique to day 42. The 25 genes shared by all time points are involved in morphogenesis and general nervous tissue development. The 295 shared genes between days 21 and 22 are involved in neurogenesis and nervous system development and differentiation. The 407 unique day 42 genes are involved in pituitary development, endocrine system development and other hormonally related gene ontology terms. Overall, rEx analysis indicates a focus on nervous system/tissue development at days 21 and 22. By day 42, in addition to nervous tissue development, there is expression of genes involved in the endocrine system, possibly for maturation and preparation for reproduction. This study defines the transcriptome of the chicken pituitary gland and aids in understanding the expressed genes critical to its function and maturation. PMID:27856505

AAV-PHP.B-Mediated Global-Scale Expression in the Mouse Nervous System Enables GBA1 Gene Therapy for Wide Protection from Synucleinopathy.

PubMed

Morabito, Giuseppe; Giannelli, Serena G; Ordazzo, Gabriele; Bido, Simone; Castoldi, Valerio; Indrigo, Marzia; Cabassi, Tommaso; Cattaneo, Stefano; Luoni, Mirko; Cancellieri, Cinzia; Sessa, Alessandro; Bacigaluppi, Marco; Taverna, Stefano; Leocani, Letizia; Lanciego, José L; Broccoli, Vania

2017-12-06

The lack of technology for direct global-scale targeting of the adult mouse nervous system has hindered research on brain processing and dysfunctions. Currently, gene transfer is normally achieved by intraparenchymal viral injections, but these injections target a restricted brain area. Herein, we demonstrated that intravenous delivery of adeno-associated virus (AAV)-PHP.B viral particles permeated and diffused throughout the neural parenchyma, targeting both the central and the peripheral nervous system in a global pattern. We then established multiple procedures of viral transduction to control gene expression or inactivate gene function exclusively in the adult nervous system and assessed the underlying behavioral effects. Building on these results, we established an effective gene therapy strategy to counteract the widespread accumulation of α-synuclein deposits throughout the forebrain in a mouse model of synucleinopathy. Transduction of A53T-SCNA transgenic mice with AAV-PHP.B-GBA1 restored physiological levels of the enzyme, reduced α-synuclein pathology, and produced significant behavioral recovery. Finally, we provided evidence that AAV-PHP.B brain penetration does not lead to evident dysfunctions in blood-brain barrier integrity or permeability. Altogether, the AAV-PHP.B viral platform enables non-invasive, widespread, and long-lasting global neural expression of therapeutic genes, such as GBA1, providing an invaluable approach to treat neurodegenerative diseases with diffuse brain pathology such as synucleinopathies. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Meninges-derived cues control axon guidance.

PubMed

Suter, Tracey A C S; DeLoughery, Zachary J; Jaworski, Alexander

2017-10-01

The axons of developing neurons travel long distances along stereotyped pathways under the direction of extracellular cues sensed by the axonal growth cone. Guidance cues are either secreted proteins that diffuse freely or bind the extracellular matrix, or membrane-anchored proteins. Different populations of axons express distinct sets of receptors for guidance cues, which results in differential responses to specific ligands. The full repertoire of axon guidance cues and receptors and the identity of the tissues producing these cues remain to be elucidated. The meninges are connective tissue layers enveloping the vertebrate brain and spinal cord that serve to protect the central nervous system (CNS). The meninges also instruct nervous system development by regulating the generation and migration of neural progenitors, but it has not been determined whether they help guide axons to their targets. Here, we investigate a possible role for the meninges in neuronal wiring. Using mouse neural tissue explants, we show that developing spinal cord meninges produce secreted attractive and repulsive cues that can guide multiple types of axons in vitro. We find that motor and sensory neurons, which project axons across the CNS-peripheral nervous system (PNS) boundary, are attracted by meninges. Conversely, axons of both ipsi- and contralaterally projecting dorsal spinal cord interneurons are repelled by meninges. The responses of these axonal populations to the meninges are consistent with their trajectories relative to meninges in vivo, suggesting that meningeal guidance factors contribute to nervous system wiring and control which axons are able to traverse the CNS-PNS boundary. Copyright © 2017 Elsevier Inc. All rights reserved.

Central Nervous System Vasculitis

MedlinePlus

... of Vasculitis / Central Nervous System (CNS) Vasculitis Central Nervous System (CNS) Vasculitis Swap out your current Facebook Profile ... Facebook personal page. Replace with this image. Central nervous system (CNS) vasculitis is inflammation of blood vessel walls ...

Subacute combined degeneration

MedlinePlus

... SCD Images Central nervous system and peripheral nervous system Central nervous system References Pytel P, Anthony DC. Peripheral nerves and ... chap 27. So YT. Deficiency diseases of the nervous system. In: Daroff RB, Jankovic J, Mazziotta JC, Pomeroy ...

Neurocutaneous Disorders.

PubMed

Rosser, Tena

2018-02-01

This article presents an up-to-date summary of the genetic etiology, diagnostic criteria, clinical features, and current management recommendations for the most common neurocutaneous disorders encountered in clinical adult and pediatric neurology practices. The phakomatoses are a phenotypically and genetically diverse group of multisystem disorders that primarily affect the skin and central nervous system. A greater understanding of the genetic and biological underpinnings of numerous neurocutaneous disorders has led to better clinical characterization, more refined diagnostic criteria, and improved treatments in neurofibromatosis type 1, Legius syndrome, neurofibromatosis type 2, Noonan syndrome with multiple lentigines, tuberous sclerosis complex, Sturge-Weber syndrome, and incontinentia pigmenti. Neurologists require a basic knowledge of and familiarity with a wide variety of neurocutaneous disorders because of the frequent involvement of the central and peripheral nervous systems. A simple routine skin examination can often open a broad differential diagnosis and lead to improved patient care.

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury*

PubMed Central

van Niekerk, Erna A.; Tuszynski, Mark H.; Lu, Paul; Dulin, Jennifer N.

2016-01-01

Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. PMID:26695766

K-Cl cotransporters, cell volume homeostasis, and neurological disease

PubMed Central

Kahle, Kristopher T.; Khanna, Arjun R.; Alper, Seth L.; Adragna, Norma C.; Lauf, Peter K.; Sun, Dandan; Delpire, Eric

2016-01-01

K+-Cl− cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. PMID:26142773

K-Cl cotransporters, cell volume homeostasis, and neurological disease.

PubMed

Kahle, Kristopher T; Khanna, Arjun R; Alper, Seth L; Adragna, Norma C; Lauf, Peter K; Sun, Dandan; Delpire, Eric

2015-08-01

K(+)-Cl(-) cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Robotics, motor learning, and neurologic recovery.

PubMed

Reinkensmeyer, David J; Emken, Jeremy L; Cramer, Steven C

2004-01-01

Robotic devices are helping shed light on human motor control in health and injury. By using robots to apply novel force fields to the arm, investigators are gaining insight into how the nervous system models its external dynamic environment. The nervous system builds internal models gradually by experience and uses them in combination with impedance and feedback control strategies. Internal models are robust to environmental and neural noise, generalized across space, implemented in multiple brain regions, and developed in childhood. Robots are also being used to assist in repetitive movement practice following neurologic injury, providing insight into movement recovery. Robots can haptically assess sensorimotor performance, administer training, quantify amount of training, and improve motor recovery. In addition to providing insight into motor control, robotic paradigms may eventually enhance motor learning and rehabilitation beyond the levels possible with conventional training techniques.

Coexpression network analysis identifies transcriptional modules associated with genomic alterations in neuroblastoma.

PubMed

Yang, Liulin; Li, Yun; Wei, Zhi; Chang, Xiao

2018-06-01

Neuroblastoma is a highly complex and heterogeneous cancer in children. Acquired genomic alterations including MYCN amplification, 1p deletion and 11q deletion are important risk factors and biomarkers in neuroblastoma. Here, we performed a co-expression-based gene network analysis to study the intrinsic association between specific genomic changes and transcriptome organization. We identified multiple gene coexpression modules which are recurrent in two independent datasets and associated with functional pathways including nervous system development, cell cycle, immune system process and extracellular matrix/space. Our results also indicated that modules involved in nervous system development and cell cycle are highly associated with MYCN amplification and 1p deletion, while modules responding to immune system process are associated with MYCN amplification only. In summary, this integrated analysis provides novel insights into molecular heterogeneity and pathogenesis of neuroblastoma. This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang. Copyright © 2017. Published by Elsevier B.V.

Molecular Regulation of Alternative Polyadenylation (APA) within the Drosophila Nervous System.

PubMed

Vallejos Baier, Raul; Picao-Osorio, Joao; Alonso, Claudio R

2017-10-27

Alternative polyadenylation (APA) is a widespread gene regulatory mechanism that generates mRNAs with different 3'-ends, allowing them to interact with different sets of RNA regulators such as microRNAs and RNA-binding proteins. Recent studies have shown that during development, neural tissues produce mRNAs with particularly long 3'UTRs, suggesting that such extensions might be important for neural development and function. Despite this, the mechanisms underlying neural APA are not well understood. Here, we investigate this problem within the Drosophila nervous system, focusing on the roles played by general cleavage and polyadenylation factors (CPA factors). In particular, we examine the model that modulations in CPA factor concentration may affect APA during development. For this, we first analyse the expression of the Drosophila orthologues of all mammalian CPA factors and note that their expression decreases during embryogenesis. In contrast to this global developmental decrease in CPA factor expression, we see that cleavage factor I (CFI) expression is actually elevated in the late embryonic central nervous system, suggesting that CFI might play a special role in neural tissues. To test this, we use the UAS/Gal4 system to deplete CFI proteins from neural tissue and observe that in this condition, multiple genes switch their APA patterns, demonstrating a role of CFI in APA control during Drosophila neural development. Furthermore, analysis of genes with 3'UTR extensions of different length leads us to suggest a novel relation between 3'UTR length and sensitivity to CPA factor expression. Our work thus contributes to the understanding of the mechanisms of APA control within the developing central nervous system. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Autonomic Nervous System Disorders

MedlinePlus

Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

Source characterization of nervous system active pharmaceutical ingredients in healthcare wastewaters

EPA Science Inventory

Nervous system active pharmaceutical ingredients (APIs), including anti-depressants and opioids, are important clinically administered pharmaceuticals within healthcare facilities. Concentrations and mass loadings of ten nervous system APIs and three nervous system API metaboli...

Stressful life events and the risk of initial central nervous system demyelination.

PubMed

Saul, Alice; Ponsonby, Anne-Louise; Lucas, Robyn M; Taylor, Bruce V; Simpson, Steve; Valery, Patricia; Dwyer, Terence; Kilpatrick, Trevor J; Pender, Michael P; van der Mei, Ingrid Af

2017-06-01

There is substantial evidence that stress increases multiple sclerosis disease activity, but limited evidence on its association with the onset of multiple sclerosis. To examine the association between stressful life events and risk of first demyelinating event (FDE). This was a multicentre incident case-control study. Cases ( n = 282 with first diagnosis of central nervous system (CNS) demyelination, including n = 216 with 'classic FDE') were aged 18-59 years. Controls without CNS demyelination ( n = 558) were matched to cases on age, sex and study region. Stressful life events were assessed using a questionnaire based on the Social Readjustment Rating Scale. Those who suffered from a serious illness in the previous 12 months were more likely to have an FDE (odds ratio (OR) = 2.35 (1.36, 4.06), p = 0.002), and when we limited our reference group to those who had no stressful life events, the magnitude of effect became stronger (OR = 5.41 (1.80, 16.28)). The total stress number and stress load were not convincingly associated with the risk of an FDE. Cases were more likely to report a serious illness in the previous 12 months, which could suggest that a non-specific illness provides an additional strain to an already predisposed immune system.

Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria

PubMed Central

Polman, Chris H; Reingold, Stephen C; Banwell, Brenda; Clanet, Michel; Cohen, Jeffrey A; Filippi, Massimo; Fujihara, Kazuo; Havrdova, Eva; Hutchinson, Michael; Kappos, Ludwig; Lublin, Fred D; Montalban, Xavier; O'Connor, Paul; Sandberg-Wollheim, Magnhild; Thompson, Alan J; Waubant, Emmanuelle; Weinshenker, Brian; Wolinsky, Jerry S

2011-01-01

New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use. Ann Neurol 2011 PMID:21387374

Human radiation tolerance

NASA Technical Reports Server (NTRS)

Lushbaugh, C. C.

1974-01-01

The acute radiation syndrome in man is clinically bounded by death at high dose levels and by the prodromal syndrome of untoward physiological effects at minimal levels of clinically effective exposure. As in lower animals, man experiences principally three acute modes of death from radiation exposure (Bond et al., 1965). These are known collectively as the lethal radiation syndromes: central nervous system death, gastrointestinal death, and hematopoietic death. The effect of multiple exposure on lethality, the effect of multiple exposure on hematopoietic recovery, and quantitative aspects of cell and tissue repair are discussed.

Gorlin syndrome.

PubMed

Devi, Basanti; Behera, Binodini; Patro, Sibasish; Pattnaik, Subhransu S; Puhan, Manas R

2013-05-01

Gorlin Syndrome, a rare genodermatosis, otherwise known as Nevoid basal cell carcinoma syndrome (NBCCS) is a multisystem disease affecting skin, nervous system, eyes, endocrine glands, and bones. It is characterized by multiple basal cell carcinomas, palmoplantar pits, jaw cysts, and bony deformities like kyphoscoliosis and frontal bossing. We would like to report a case of Gorlin syndrome with classical features, as this is a rare genodermatosis.

Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient.

PubMed

Graves, Tracey D; Condon, Marie; Loucaidou, Marina; Perry, Richard J

2009-10-15

Metronidazole-induced central nervous system (CNS) toxicity causes a spectrum of neurological symptoms including ataxia, encephalopathy and peripheral neuropathy. It is associated with characteristic MRI changes of high signal intensity in the dentate nuclei. Given the increasing use of metronidazole, it is import to recognise this drug as a cause of ataxia, as it is entirely reversible on drug withdrawal.

Role of the blood-brain barrier in multiple sclerosis.

PubMed

Ortiz, Genaro Gabriel; Pacheco-Moisés, Fermín Paul; Macías-Islas, Miguel Ángel; Flores-Alvarado, Luis Javier; Mireles-Ramírez, Mario A; González-Renovato, Erika Daniela; Hernández-Navarro, Vanessa Elizabeth; Sánchez-López, Angélica Lizeth; Alatorre-Jiménez, Moisés Alejandro

2014-11-01

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system associated with demyelination and axonal loss eventually leading to neurodegeneration. MS exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB). The BBB is a complex organization of cerebral endothelial cells, pericytes and their basal lamina, which are surrounded and supported by astrocytes and perivascular macrophages. In pathological conditions, lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Cytotoxic factors including pro-inflammatory cytokines, proteases, and reactive oxygen and nitrogen species accumulate and may contribute to myelin destruction. Dysregulation of the BBB and transendothelial migration of activated leukocytes are among the earliest cerebrovascular abnormalities seen in MS brains and parallel the release of inflammatory cytokines. In this review we establish the importance of the role of the BBB in MS. Improvements in our understanding of molecular mechanism of BBB functioning in physiological and pathological conditions could lead to improvement in the quality of life of MS patients. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

The expanding universe of neurotrophic factors: therapeutic potential in aging and age-associated disorders.

PubMed

Lanni, C; Stanga, S; Racchi, M; Govoni, S

2010-01-01

Multiple molecular, cellular, structural and functional changes occur in the brain during aging. Neural cells may respond to these changes adaptively by employing multiple mechanisms in order to maintain the integrity of nerve cell circuits and to facilitate responses to environmental demands. Otherwise, they may succumb to neurodegenerative cascades that result in disorders such as Alzheimer's and Parkinson's diseases. An important role in this balancement is played by neurotrophic factors, which are central to many aspects of nervous system function since they regulate the development, maintenance and survival of neurons and neuron-supporting cells such as glia and oligodendrocytes. A vast amount of evidence indicates that alterations in levels of neurotrophic factors or their receptors can lead to neuronal death and contribute to aging as well as to the pathogenesis of diseases of abnormal trophic support (such as neurodegenerative diseases and depression) and diseases of abnormal excitability (such as epilepsy and central pain sensitization). Cellular and molecular mechanisms by which neurotrophic factors may influence cell survival and excitability are also critically examined to provide novel concepts and targets for the treatment of physiological changes bearing detrimental functional alterations and of different diseases affecting the central nervous system during aging.

[Peripheral neuropathy in systemic lupus erythematosus with epineural vasculitis and antiphospholipid antibodies].

PubMed

Rafai, M A; Fadel, H; Boulaajaj, F Z; Gam, I; El Moutawakkil, B; Karkouri, M; Hakim, K; Slassi, I

2007-01-01

Neurological manifestations of systemic lupus erythematosus are frequent and polymorphic. Their frequency varies according to authors (24-75p.cent). Central nervous system complications predominate; peripheral features are rare, classically symmetrical polyneuropathy, multiple mononeuropathies or cranial nerve involvement. We report a case of a 48-year-old woman presenting a histologically documented sensitivo-motor polyneuropathy with severe motor involvement complicating lupus associated with antiphospholipides antibodies. Outcome was good after cyclophosphamid pulse. We discuss the frequency of peripheral involvement in systemic lupus erythematosus, pathogenic mechanisms, therapeutic possibilities and outcome of this complication.

Integrated defense system overlaps as a disease model: with examples for multiple chemical sensitivity.

PubMed Central

Rowat, S C

1998-01-01

The central nervous, immune, and endocrine systems communicate through multiple common messengers. Over evolutionary time, what may be termed integrated defense system(s) (IDS) have developed to coordinate these communications for specific contexts; these include the stress response, acute-phase response, nonspecific immune response, immune response to antigen, kindling, tolerance, time-dependent sensitization, neurogenic switching, and traumatic dissociation (TD). These IDSs are described and their overlap is examined. Three models of disease production are generated: damage, in which IDSs function incorrectly; inadequate/inappropriate, in which IDS response is outstripped by a changing context; and evolving/learning, in which the IDS learned response to a context is deemed pathologic. Mechanisms of multiple chemical sensitivity (MCS) are developed from several IDS disease models. Model 1A is pesticide damage to the central nervous system, overlapping with body chemical burdens, TD, and chronic zinc deficiency; model 1B is benzene disruption of interleukin-1, overlapping with childhood developmental windows and hapten-antigenic spreading; and model 1C is autoimmunity to immunoglobulin-G (IgG), overlapping with spreading to other IgG-inducers, sudden spreading of inciters, and food-contaminating chemicals. Model 2A is chemical and stress overload, including comparison with the susceptibility/sensitization/triggering/spreading model; model 2B is genetic mercury allergy, overlapping with: heavy metals/zinc displacement and childhood/gestational mercury exposures; and model 3 is MCS as evolution and learning. Remarks are offered on current MCS research. Problems with clinical measurement are suggested on the basis of IDS models. Large-sample patient self-report epidemiology is described as an alternative or addition to clinical biomarker and animal testing. Images Figure 1 Figure 2 Figure 3 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9539008

[Progressive multifocal leukoencephalitis complicating polymyositis].

PubMed

Elloumi, Mohamed; Ayadi, Nada; Mhiri, Chokri; Jlidi, Rachid; Baklouti, Soufiène

2003-02-01

Progressive multifocal leukoencephalitis (PML) must be evoked in patients presenting with a systemic disease during which multiple neurological deficiencies rapidly worsen. A 17 year-old girl suffering from histologically confirmed polymyositis was treated with corticosteroids. Two years after the diagnosis she exhibited global signs of cerebral damage with fever and magnetic resonance imaging evoked leukoencephalitis. An affection of the central nervous system, PML is characterised by the existence of multiple areas of demyelination in the hemispheric white substance of the cerebral trunk and sometimes the cerebellum, whereas the grey substance is usually spared. This entity occurs more frequently in HIV-infected patients, but also in patients in whom the immunodeficiency may have other causes, such as the treatment for a systemic disease for example.

What Health-Related Functions Are Regulated by the Nervous System?

MedlinePlus

... What health-related functions are regulated by the nervous system? The nervous system plays a role in nearly every aspect of ... feeling emotions. Functions that are regulated by the nervous system include (but are not limited to): Brain growth ...

Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy.

PubMed

Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Boccara, A Claude; Bourdieu, Laurent

2011-11-01

Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy

NASA Astrophysics Data System (ADS)

Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Claude Boccara, A.; Bourdieu, Laurent

2011-11-01

Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

The human natural killer-1 (HNK-1) glycan mimetic ursolic acid promotes functional recovery after spinal cord injury in mouse.

PubMed

Sahu, Sudhanshu; Li, Rong; Kadeyala, Praveen Kumar; Liu, Shisong; Schachner, Melitta

2018-05-01

Human natural killer-1 (HNK-1) cell antigen is a glycan epitope involved in several neural events, such as neuritogenesis, myelination, synaptic plasticity and regeneration of the nervous system after injury. We have recently identified the small organic compound ursolic acid (UA) as a HNK-1 mimetic with the aim to test its therapeutic potential in the central nervous system. UA, a plant-derived pentacyclic triterpenoid, is well known for its multiple biological functions, including neuroprotective, antioxidant and anti-inflammatory activities. In the present study, we evaluated its functions in a mouse model of spinal cord injury (SCI) and explored the molecular mechanisms underlying its positive effects. Oral administration of UA to mice 1 h after SCI and thereafter once daily for 6 weeks enhanced the regaining of motor functions and axonal regrowth, and decreased astrogliosis. UA administration decreased levels of proinflammatory markers, including interleukin-6 and tumor necrosis factor-α, in the injured spinal cord at the acute phase of inflammation and activated the mitogen-activated protein kinase and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways in the injured spinal cord. Taken together, these results suggest that UA may be a candidate for treatment of nervous system injuries. Copyright © 2017. Published by Elsevier Inc.

Neuroanatomy of the Vestimentiferan Tubeworm Lamellibrachia satsuma Provides Insights into the Evolution of the Polychaete Nervous System

PubMed Central

Miyamoto, Norio; Shinozaki, Ayuta; Fujiwara, Yoshihiro

2013-01-01

Vestimentiferan tubeworms are marine invertebrates that inhabit chemosynthetic environments, and although recent molecular phylogenetic analyses have suggested that vestimentiferan tubeworms are derived from polychaete annelids, they show some morphological features that are different from other polychaetes. For example, vestimentiferans lack a digestive tract and have less body segments and comparative neuroanatomy can provide essential insight into the vestimentiferan body plan and its evolution. In the present study, we investigated the adult nervous system in the vestimentiferan Lamellibrachia satsuma using antibodies against synapsin, serotonin, FMRMamide and acetylated α-tubulin. We also examined the expressions of neural marker genes, elav and synaptotagmin to reveal the distribution of neuronal cell bodies. Brain anatomy shows simple organization in Lamellibrachia compared to other polychaetes. This simplification is probably due to the loss of the digestive tract, passing through the body between the brain and the subesophageal ganglion. In contrast, the ventral nerve cord shows a repeated organizational structure as in the other polychaetes, despite the absence of the multiple segmentation of the trunk. These results suggest that the brain anatomy is variable depending on the function and the condition of surrounding tissues, and that the formation of the rope ladder-like nervous system of the ventral nerve cord is independent from segmentation in polychaetes. PMID:23372830

Control of Bone Remodeling by the Peripheral Sympathetic Nervous System

PubMed Central

Campbell, Preston; Ma, Yun

2013-01-01

The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last two decades, a more complete picture of the multiple functions of the skeleton has emerged, and its interactions with a growing number of apparently unrelated organs have become evident. The skeleton not only reacts to mechanical loading and inflammatory, hormonal, and mineral challenges, but also acts of its own accord by secreting factors controlling the function of other tissues, including the kidney and possibly the pancreas and gonads. It is thus becoming widely recognized that it is by nature an endocrine organ, in addition to a structural organ and site of mineral storage and hematopoiesis. Consequently and by definition, bone homeostasis must be tightly regulated and integrated with the biology of other organs to maintain whole body homeostasis, and data uncovering the involvement of the central nervous system (CNS) in the control of bone remodeling support this concept. The sympathetic nervous system (SNS) represents one of the main links between the CNS and the skeleton, based on a number of anatomic, pharmacologic, and genetic studies focused on β-adrenergic receptor (βAR) signaling in bone cells. The goal of this report was to review the data supporting the role of the SNS and βAR signaling in the regulation of skeletal homeostasis. PMID:23765388

An option space for early neural evolution.

PubMed

Jékely, Gáspár; Keijzer, Fred; Godfrey-Smith, Peter

2015-12-19

The origin of nervous systems has traditionally been discussed within two conceptual frameworks. Input-output models stress the sensory-motor aspects of nervous systems, while internal coordination models emphasize the role of nervous systems in coordinating multicellular activity, especially muscle-based motility. Here we consider both frameworks and apply them to describe aspects of each of three main groups of phenomena that nervous systems control: behaviour, physiology and development. We argue that both frameworks and all three aspects of nervous system function need to be considered for a comprehensive discussion of nervous system origins. This broad mapping of the option space enables an overview of the many influences and constraints that may have played a role in the evolution of the first nervous systems. © 2015 The Author(s).

Test-Retest Reliability of the Multiple Sleep Latency Test in Narcolepsy without Cataplexy and Idiopathic Hypersomnia

PubMed Central

Trotti, Lynn Marie; Staab, Beth A.; Rye, David B.

2013-01-01

Study Objectives: Differentiation of narcolepsy without cataplexy from idiopathic hypersomnia relies entirely upon the multiple sleep latency test (MSLT). However, the test-retest reliability for these central nervous system hypersomnias has never been determined. Methods: Patients with narcolepsy without cataplexy, idiopathic hypersomnia, and physiologic hypersomnia who underwent two diagnostic multiple sleep latency tests were identified retrospectively. Correlations between the mean sleep latencies on the two studies were evaluated, and we probed for demographic and clinical features associated with reproducibility versus change in diagnosis. Results: Thirty-six patients (58% women, mean age 34 years) were included. Inter -test interval was 4.2 ± 3.8 years (range 2.5 months to 16.9 years). Mean sleep latencies on the first and second tests were 5.5 (± 3.7 SD) and 7.3 (± 3.9) minutes, respectively, with no significant correlation (r = 0.17, p = 0.31). A change in diagnosis occurred in 53% of patients, and was accounted for by a difference in the mean sleep latency (N = 15, 42%) or the number of sleep onset REM periods (N = 11, 31%). The only feature predictive of a diagnosis change was a history of hypnagogic or hypnopompic hallucinations. Conclusions: The multiple sleep latency test demonstrates poor test-retest reliability in a clinical population of patients with central nervous system hypersomnia evaluated in a tertiary referral center. Alternative diagnostic tools are needed. Citation: Trotti LM; Staab BA; Rye DB. Test- retest reliability of the multiple sleep latency test in narcolepsy without cataplexy and idiopathic hypersomnia. J Clin Sleep Med 2013;9(8):789-795. PMID:23946709

78 FR 9311 - Hazard Communication; Corrections and Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-08

... Column for Standard No. 1910.1051. ``Cancer; eye and respiratory tract irritation; center nervous system... irritation; central nervous system effects; and flammability.'' The following table contains a summary of the... (l)(1)(ii) ``center nervous system effects'' is paragraph. corrected to ``central nervous system...

The Nervous System and Gastrointestinal Function

ERIC Educational Resources Information Center

Altaf, Muhammad A.; Sood, Manu R.

2008-01-01

The enteric nervous system is an integrative brain with collection of neurons in the gastrointestinal tract which is capable of functioning independently of the central nervous system (CNS). The enteric nervous system modulates motility, secretions, microcirculation, immune and inflammatory responses of the gastrointestinal tract. Dysphagia,…

A review of Neuropharmacology Effects of Nigella sativa and Its Main Component, Thymoquinone.

PubMed

Javidi, Soheila; Razavi, Bibi Marjan; Hosseinzadeh, Hossein

2016-08-01

Neuropharmacology is the scientific study of drug effect on nervous system. In the last few years, different natural plants and their active constituents have been used in neurological therapy. The availability, lower price, and less toxic effects of herbal medicines compared with synthetic agents make them as simple and excellent choice in the treatment of nervous diseases. Nigella sativa, which belongs to the botanical family of Ranunculaceae, is a widely used medicinal plant all over the world. In traditional and modern medicines several beneficial properties have been attributed to N. sativa and its main component, thymoquinone (TQ). In this review, various studies in scientific databases regarding the neuropharmacological aspects of N. sativa and TQ have been introduced. Results of these studies showed that N. sativa and TQ have several properties including anticonvulsant, antidepressant, anxiolytic, anti-ischemic, analgesic, antipsychotic, and memory enhancer. Furthermore, its protective effects against neurodegenerative diseases such as Alzheimer, Parkinson and multiple sclerosis have been discussed. Although there are many studies indicating the beneficial actions of this plant in nervous system, the number of research projects relating to the human reports is rare. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Genetic predisposition to peripheral nerve neoplasia: Diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes

PubMed Central

Rodriguez, Fausto J.; Stratakis, Constantine A.; Evans, D Gareth

2013-01-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately a third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney Complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia. PMID:22210082

Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes.

PubMed

Rodriguez, Fausto J; Stratakis, Constantine A; Evans, D Gareth

2012-03-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately one-third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET, respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.

Peripheral nervous system involvement in primary burning mouth syndrome--results of a pilot study.

PubMed

Puhakka, A; Forssell, H; Soinila, S; Virtanen, A; Röyttä, M; Laine, M; Tenovuo, O; Teerijoki-Oksa, T; Jääskeläinen, S K

2016-05-01

The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, but recent studies suggest pathology within the nervous system at multiple levels. This study aimed to investigate in detail the contribution of either focal or generalized alterations within the peripheral nervous system (PNS) in the etiopathogenesis of BMS. Intraepithelial nerve fiber density (IENFD) of tongue mucosa was assessed in 10 carefully characterized BMS, and the results were compared to 19 age- and gender-matched cadaver controls, 6 with lifetime diabetes. Extensive neurophysiologic and psychophysical examinations of the trigeminal system and distal extremities were performed to profile PNS function in BMS. Patients with BMS had significantly fewer intraepithelial nerve fibers (0,27, s.e. 0,18 mm(-1); P = 0.0253) than non-diabetic controls (0,92, s.e. 0,15 mm(-1)). In the subepithelial space, the amount of nerve fibers did not differ between the groups. The majority (9/10) of patients with BMS showed neurophysiologic or psychophysical signs of a more generalized PNS dysfunction. Our results in neurophysiologically optimally characterized BMS patients confirm that pure focal small fiber neuropathy of the oral mucosa has a role in the pathophysiology of primary BMS. Furthermore, BMS may be related to a more generalized, yet subclinical peripheral neuropathy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Primary central nervous system lymphoma in an human immunodeficiency virus-infected patient mimicking bilateral eye sign in brain seen in fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography.

PubMed

Kamaleshwaran, Koramadai Karuppusany; Thirugnanam, Rajasekar; Shibu, Deepu; Kalarikal, Radhakrishnan Edathurthy; Shinto, Ajit Sugunan

2014-04-01

Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) has proven useful in the diagnosis, staging, and detection of metastasis and posttreatment monitoring of several malignancies in human immunodeficiency virus (HIV)-infected patients. It also has the ability to make the important distinction between malignancy and infection in the evaluation of central nervous system (CNS) lesions, leading to the initiation of the appropriate treatment and precluding the need for invasive biopsy. We report an interesting case of HIV positive 35-year-old woman presented with headache, disorientation, and decreased level of consciousness. She underwent whole body PET/CT which showed multiple lesions in the cerebrum which mimics bilateral eye in brain. A diagnosis of a primary CNS lymphoma was made and patient was started on chemotherapy.

Review: the role of vitamin D in nervous system health and disease.

PubMed

DeLuca, G C; Kimball, S M; Kolasinski, J; Ramagopalan, S V; Ebers, G C

2013-08-01

Vitamin D and its metabolites have pleomorphic roles in both nervous system health and disease. Animal models have been paramount in contributing to our knowledge and understanding of the consequences of vitamin D deficiency on brain development and its implications for adult psychiatric and neurological diseases. The conflation of in vitro, ex vivo, and animal model data provide compelling evidence that vitamin D has a crucial role in proliferation, differentiation, neurotrophism, neuroprotection, neurotransmission, and neuroplasticity. Vitamin D exerts its biological function not only by influencing cellular processes directly, but also by influencing gene expression through vitamin D response elements. This review highlights the epidemiological, neuropathological, experimental and molecular genetic evidence implicating vitamin D as a candidate in influencing susceptibility to a number of psychiatric and neurological diseases. The strength of evidence varies for schizophrenia, autism, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and is especially strong for multiple sclerosis. © 2013 British Neuropathological Society.

Molecular Magnetic Resonance Imaging of Endothelial Activation in the Central Nervous System

PubMed Central

Gauberti, Maxime; Fournier, Antoine P.; Docagne, Fabian; Vivien, Denis; Martinez de Lizarrondo, Sara

2018-01-01

Endothelial cells of the central nervous system over-express surface proteins during neurological disorders, either as a cause, or a consequence, of the disease. Since the cerebral vasculature is easily accessible by large contrast-carrying particles, it constitutes a target of choice for molecular magnetic resonance imaging (MRI). In this review, we highlight the most recent advances in molecular MRI of brain endothelial activation and focus on the development of micro-sized particles of iron oxide (MPIO) targeting adhesion molecules including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), P-Selectin and E-Selectin. We also discuss the perspectives and challenges for the clinical application of this technology in neurovascular disorders (ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage, diabetes mellitus), neuroinflammatory disorders (multiple sclerosis, brain infectious diseases, sepsis), neurodegenerative disorders (Alzheimer's disease, vascular dementia, aging) and brain cancers (primitive neoplasms, metastasis). PMID:29507614

Mouse forward genetics in the study of the peripheral nervous system and human peripheral neuropathy

PubMed Central

Douglas, Darlene S.; Popko, Brian

2009-01-01

Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics. PMID:18481175

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury.

PubMed

van Niekerk, Erna A; Tuszynski, Mark H; Lu, Paul; Dulin, Jennifer N

2016-02-01

Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Tau Kinetics in Neurons and the Human Central Nervous System.

PubMed

Sato, Chihiro; Barthélemy, Nicolas R; Mawuenyega, Kwasi G; Patterson, Bruce W; Gordon, Brian A; Jockel-Balsarotti, Jennifer; Sullivan, Melissa; Crisp, Matthew J; Kasten, Tom; Kirmess, Kristopher M; Kanaan, Nicholas M; Yarasheski, Kevin E; Baker-Nigh, Alaina; Benzinger, Tammie L S; Miller, Timothy M; Karch, Celeste M; Bateman, Randall J

2018-03-21

We developed stable isotope labeling and mass spectrometry approaches to measure the kinetics of multiple isoforms and fragments of tau in the human central nervous system (CNS) and in human induced pluripotent stem cell (iPSC)-derived neurons. Newly synthesized tau is truncated and released from human neurons in 3 days. Although most tau proteins have similar turnover, 4R tau isoforms and phosphorylated forms of tau exhibit faster turnover rates, suggesting unique processing of these forms that may have independent biological activities. The half-life of tau in control human iPSC-derived neurons is 6.74 ± 0.45 days and in human CNS is 23 ± 6.4 days. In cognitively normal and Alzheimer's disease participants, the production rate of tau positively correlates with the amount of amyloid plaques, indicating a biological link between amyloid plaques and tau physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

Concise Review: Dental Pulp Stem Cells: A Novel Cell Therapy for Retinal and Central Nervous System Repair.

PubMed

Mead, Ben; Logan, Ann; Berry, Martin; Leadbeater, Wendy; Scheven, Ben A

2017-01-01

Dental pulp stem cells (DPSC) are neural crest-derived ecto-mesenchymal stem cells that can relatively easily and non-invasively be isolated from the dental pulp of extracted postnatal and adult teeth. Accumulating evidence suggests that DPSC have great promise as a cellular therapy for central nervous system (CNS) and retinal injury and disease. The mode of action by which DPSC confer therapeutic benefit may comprise multiple pathways, in particular, paracrine-mediated processes which involve a wide array of secreted trophic factors and is increasingly regarded as the principal predominant mechanism. In this concise review, we present the current evidence for the use of DPSC to repair CNS damage, including recent findings on retinal ganglion cell neuroprotection and regeneration in optic nerve injury and glaucoma. Stem Cells 2017;35:61-67. © 2016 AlphaMed Press.

The pathogenesis of Hirschsprung's disease-associated enterocolitis.

PubMed

Austin, Kelly Miller

2012-11-01

Hirschsprung's disease-associated enterocolitis (HAEC) remains the most life-threatening complication in Hirschsprung disease (HD) patients. The pathogenesis of HAEC has not been determined and many hypotheses regarding the etiology of HAEC have been proposed. These include a possible causal relationship between the abnormal enteric nervous system development in HD and the development of enterocolitis. Based on the complex genetic causes of HD that have been discovered and the resultant heterogeneous group of patients that exists, the causes of HAEC are likely multiple. New insights regarding the relationship of the role of the enteric nervous system and its interaction between intestinal barrier function, innate host immunity, and commensal microflora have been discovered, which may shed light on this perplexing problem. This review presents current known risk factors of HAEC and the proposed theories and supporting evidence for the potential etiologies of HAEC. Copyright © 2012. Published by Elsevier Inc.

77 FR 70908 - Dinotefuran; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-28

... level of skin irritation. The main target of toxicity is the nervous system but effects on the nervous system were only observed at high doses. Nervous system toxicity was manifested as clinical signs and... motor activity which are consistent with effects on the nicotinic cholinergic nervous system seen after...

78 FR 21267 - Dinotefuran; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-10

... causes a low level of skin irritation. The main target of toxicity is the nervous system, but effects on the nervous system were only observed at high doses. Nervous system toxicity was manifested as... in motor activity which are consistent with effects on the nicotinic cholinergic nervous system seen...

The Effect of Head Massage on the Regulation of the Cardiac Autonomic Nervous System: A Pilot Randomized Crossover Trial.

PubMed

Fazeli, Mir Sohail; Pourrahmat, Mir-Masoud; Liu, Mailan; Guan, Ling; Collet, Jean-Paul

2016-01-01

To evaluate the effect of a single 10-minute session of Chinese head massage on the activity of the cardiac autonomic nervous system via measurement of heart rate variability (HRV). In this pilot randomized crossover trial, each participant received both head massage and the control intervention in a randomized fashion. The study was conducted at Children's & Women's Health Centre of British Columbia between June and November 2014. Ten otherwise healthy adults (6 men and 4 women) were enrolled in this study. The intervention comprised 10 minutes of head massage therapy (HMT) in a seated position compared with a control intervention of sitting quietly on the same chair with eyes closed for an equal amount of time (no HMT). The primary outcome measures were the main parameters of HRV, including total power (TP), high frequency (HF), HF as a normalized unit, pre-ejection period, and heart rate (HR). A single short session (10 minutes) of head massage demonstrated an increase in TP continuing up to 20 minutes after massage and reaching statistical significance at 10 minutes after massage (relative change from baseline, 66% for HMT versus -6.6% for no HMT; p = 0.017). The effect on HF also peaked up to 10 minutes after massage (59.4% for HMT versus 4% for no HMT; p = 0.139). Receiving head massage also decreased HR by more than three-fold compared to the control intervention. This study shows the potential benefits of head massage by modulating the cardiac autonomic nervous system through an increase in the total variability and a shift toward higher parasympathetic nervous system activity. Randomized controlled trials with larger sample size and multiple sessions of massage are needed to substantiate these findings.

Localization of Tyrosine Hydroxylase-like Immunoreactivity in the Nervous Systems of Biomphalaria glabrata and Biomphalaria alexandrina, Intermediate Hosts for Schistosomiasis

PubMed Central

Vallejo, Deborah; Habib, Mohammed R.; Delgado, Nadia; Vaasjo, Lee O.; Croll, Roger P.; Miller, Mark W.

2014-01-01

Planorbid snails of the genus Biomphalaria are major intermediate hosts for the digenetic trematode parasite Schistosoma mansoni. Evidence suggests that levels of the neurotransmitter dopamine (DA) are reduced during the course of S. mansoni multiplication and transformation within the snail. This investigation used immunohistochemical methods to localize tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamines, in the nervous system of Biomphalaria. The two species examined, Biomphalaria glabrata and Biomphalaria alexandrina, are the major intermediate hosts for S. mansoni in sub-Saharan Africa, where more than 90% of global cases of human intestinal schistosomiasis occur. TH-like immunoreactive (THli) neurons were distributed throughout the central nervous system (CNS) and labeled fibers were present in all commissures, connectives, and nerves. Some asymmetries were observed, including a large distinctive neuron (LPeD1) in the pedal ganglion described previously in several pulmonates. The majority of TH-like immunoreactive neurons were detected in the peripheral nervous system (PNS), especially in lip and foot regions of the anterior integument. Independent observations supporting the dopaminergic phenotype of THli neurons included 1) block of LPeD1 synaptic signaling by the D2/3 antagonist sulpiride, and 2) the similar localization of aqueous aldehyde (FaGlu) induced fluorescence. The distribution of THli neurons indicates that, as in other gastropods, dopamine functions as a sensory neurotransmitter and in the regulation of feeding and reproductive behaviors in Biomphalaria. It is hypothesized that infection could stimulate transmitter release from dopaminergic sensory neurons and that dopaminergic signaling could contribute to modifications of both host and parasite behavior. PMID:24477836

A distal modular enhancer complex acts to control pituitary- and nervous system-specific expression of the LHX3 regulatory gene.

PubMed

Mullen, Rachel D; Park, Soyoung; Rhodes, Simon J

2012-02-01

Lin-11, Isl-1, and Mec-3 (LIM)-homeodomain (HD)-class transcription factors are critical for many aspects of mammalian organogenesis. Of these, LHX3 is essential for pituitary gland and nervous system development. Pediatric patients with mutations in coding regions of the LHX3 gene have complex syndromes, including combined pituitary hormone deficiency and nervous system defects resulting in symptoms such as dwarfism, thyroid insufficiency, infertility, and developmental delay. The pathways underlying early pituitary development are poorly understood, and the mechanisms by which the LHX3 gene is regulated in vivo are not known. Using bioinformatic and transgenic mouse approaches, we show that multiple conserved enhancers downstream of the human LHX3 gene direct expression to the developing pituitary and spinal cord in a pattern consistent with endogenous LHX3 expression. Several transferable cis elements can individually guide nervous system expression. However, a single 180-bp minimal enhancer is sufficient to confer specific expression in the developing pituitary. Within this sequence, tandem binding sites recognized by the islet-1 (ISL1) LIM-HD protein are essential for enhancer activity in the pituitary and spine, and a pituitary homeobox 1 (PITX1) bicoid class HD element is required for spatial patterning in the developing pituitary. This study establishes ISL1 as a novel transcriptional regulator of LHX3 and describes a potential mechanism for regulation by PITX1. Moreover, these studies suggest models for analyses of the transcriptional pathways coordinating the expression of other LIM-HD genes and provide tools for the molecular analysis and genetic counseling of pediatric patients with combined pituitary hormone deficiency.

A Distal Modular Enhancer Complex Acts to Control Pituitary- and Nervous System-Specific Expression of the LHX3 Regulatory Gene

PubMed Central

Mullen, Rachel D.; Park, Soyoung

2012-01-01

Lin-11, Isl-1, and Mec-3 (LIM)-homeodomain (HD)-class transcription factors are critical for many aspects of mammalian organogenesis. Of these, LHX3 is essential for pituitary gland and nervous system development. Pediatric patients with mutations in coding regions of the LHX3 gene have complex syndromes, including combined pituitary hormone deficiency and nervous system defects resulting in symptoms such as dwarfism, thyroid insufficiency, infertility, and developmental delay. The pathways underlying early pituitary development are poorly understood, and the mechanisms by which the LHX3 gene is regulated in vivo are not known. Using bioinformatic and transgenic mouse approaches, we show that multiple conserved enhancers downstream of the human LHX3 gene direct expression to the developing pituitary and spinal cord in a pattern consistent with endogenous LHX3 expression. Several transferable cis elements can individually guide nervous system expression. However, a single 180-bp minimal enhancer is sufficient to confer specific expression in the developing pituitary. Within this sequence, tandem binding sites recognized by the islet-1 (ISL1) LIM-HD protein are essential for enhancer activity in the pituitary and spine, and a pituitary homeobox 1 (PITX1) bicoid class HD element is required for spatial patterning in the developing pituitary. This study establishes ISL1 as a novel transcriptional regulator of LHX3 and describes a potential mechanism for regulation by PITX1. Moreover, these studies suggest models for analyses of the transcriptional pathways coordinating the expression of other LIM-HD genes and provide tools for the molecular analysis and genetic counseling of pediatric patients with combined pituitary hormone deficiency. PMID:22194342

Calm Merino ewes have a higher ovulation rate and more multiple pregnancies than nervous ewes.

PubMed

van Lier, E; Hart, K W; Viñoles, C; Paganoni, B; Blache, D

2017-07-01

In 1990, two selection lines of Merino sheep were established for low and high behavioural reactivity (calm and nervous temperament) at the University of Western Australia. Breeding records consistently showed that calm ewes weaned 10% to 19% more lambs than the nervous ewes. We hypothesise that calm ewes could have a higher ovulation rate than nervous ewes and/or calm ewes could have a lower rate of embryo mortality than nervous ewes. We tested these hypotheses by comparing the ovulation rate and the rate of embryo mortality between the calm and nervous lines before and after synchronisation and artificial insemination. Merino ewes from the temperament selection lines (calm, n=100; nervous, n=100) were synchronised (early breeding season) for artificial insemination (day 0) (intravaginal sponges containing fluogestone acetate and eCG immediately after sponge withdrawal). On day-17 and 11 ovarian cyclicity and corpora lutea, and on days 30 and 74 pregnancies and embryos/foetuses were determined by ultrasound. Progesterone, insulin and leptin concentrations were determined in blood plasma samples from days 5, 12 and 17. Ovarian cyclicity before and after oestrus synchronisation did not differ between the lines, but ovulation rate did (day-17: calm 1.63; nervous 1.26; P<0.01; day 11: calm 1.83; nervous 1.57; P<0.05). Ovulation rate on day 11 in nervous ewes was higher than on day-17. Loss of embryos by day 30 was high (calm: 71/150; nervous: 68/130); but nervous ewes had a lower proportion (15/47) of multiple pregnancies compared with calm ewes (30/46; P<0.01). Reproductive loss between days 30 and 74 represented 7.3% of the overall loss. Temperament did not affect concentrations of progesterone, but nervous ewes had higher insulin (32.0 pmol/l±1.17 SEM; P=0.013) and lower leptin (1.18 μg/l±0.04 SEM; P=0.002) concentrations than calm ewes (insulin: 27.8 pmol/l±1.17 SEM; leptin: 1.35 μg/l±0.04 SEM). The differences in reproductive outcomes between the calm and nervous ewes were mainly due to a higher ovulation rate in calm ewes. We suggest that reproduction in nervous ewes is compromised by factors leading up to ovulation and conception, or the uterine environment during early pregnancy, that reflect differences in energy utilisation.

The Homogeneity of Optimal Sensor Placement Across Multiple Winged Insect Species

NASA Astrophysics Data System (ADS)

Jenkins, Abigail L.

Taking inspiration from biology, control algorithms can be implemented to imitate the naturally occurring control systems present in nature. This research is primarily concerned with insect flight and optimal wing sensor placement. Many winged insects with halteres are equipped with mechanoreceptors termed campaniform sensilla. Although the exact information these receptors provide to the insect's nervous system is unknown, it is thought to have the capability of measuring inertial rotation forces. During flight, when the wing bends, the information measured by the campaniform sensilla is received by the central nervous system, and provides the insect necessary data to control flight. This research compares three insect species - the hawkmoth Manduca sexta, the honeybee Apis mellifera, and the fruit fly Drosophila melanogaster. Using an observability-based sensor placement algorithm, the optimal sensor placement for these three species is determined. Simulations resolve if this optimal sensor placement corresponds to the insect's campaniform sensilla, as well as if placement is homogeneous across species.

Determining the IgM and IgG antibody titer against CMV and helicobacter pylori in the serum of multiple sclerosis patients comparing to the control group in Hamadan.

PubMed

Salim, Masome Afiati; Eftekharian, Mohammad Mahdi; Taheri, Mohammad; Yousef Alikhani, Mohammad

2017-07-19

Multiple sclerosis (MS) is a chronic autoimmune disease that disables central nervous system (CNS) system. Cytomegalovirus (CMV) probably has an important role in the MS pathology. The infection with helicobacter pylori also is recognized as a protective agent against MS in female. Serum samples were isolated and frozen at -70∘C. The earlier mentioned anti-virus antibodies and antibacterial antibodies were quantified by Elisa kit. The results showed that IgG antibody average value against cytomegalovirus in the blood of multiple sclerosis patients not only decreased but also was significant statistically (p< 0.05). IgM and IgG antibodies average value in the blood of multiple sclerosis patients against helicobacter pylori shown a statistically significant decrease (p< 0.05). Therefore it may be considered that probably helicobacter pylori presence in the individuals especially in female can alleviate MS signs. CMV infection can intensify the symptoms in multiple sclerosis patients.

Axonal Elongation into Peripheral Nervous System ``Bridges'' after Central Nervous System Injury in Adult Rats

NASA Astrophysics Data System (ADS)

David, Samuel; Aguayo, Albert J.

1981-11-01

The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as ``bridges'' between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.

The NUP98 Gene as a Potential Modifier of NF2 Associated Tumors

DTIC Science & Technology

2017-06-01

limited to observation, surgical removal, and stereotactic radiation [ 1 ]. However, surgery may not be possible if the tumor is inaccessible or when...there are too many tumors. Radiation treatment may cause malignant transformation and/or growth acceleration of benign tumor cells. In addition...genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas

Parenchymal Neurocutaneous Melanosis in Association with Intraventricular Dermoid and Dandy-Walker Variant: A Case Report

PubMed Central

Won, Yoo Dong; Kim, Ki Tae; Chang, Eun Deok; Huh, Pil Woo

2006-01-01

Neurocutaneous melanosis (NCM) is a rare congenital disease that is characterized by the presence of large or multiple congenital melanocytic nevi and melanotic lesions of the central nervous system. We report here on the CT and MR imaging findings of an unusual case of NCM that was associated with intraventricular dermoid and Dandy-Walker malformation. PMID:16799276

Naive CD8 T-Cells Initiate Spontaneous Autoimmunity to a Sequestered Model Antigen of the Central Nervous System

ERIC Educational Resources Information Center

Na, Shin-Young; Cao, Yi; Toben, Catherine; Nitschke, Lars; Stadelmann, Christine; Gold, Ralf; Schimpl, Anneliese; Hunig, Thomas

2008-01-01

In multiple sclerosis, CD8 T-cells are thought play a key pathogenetic role, but mechanistic evidence from rodent models is limited. Here, we have tested the encephalitogenic potential of CD8 T-cells specific for the model antigen ovalbumin (OVA) sequestered in oligodendrocytes as a cytosolic molecule. We show that in these "ODC-OVA" mice, the…

Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

ClinicalTrials.gov

2013-07-01

Childhood Burkitt Lymphoma; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Medulloepithelioma; Childhood Meningioma; Childhood Mixed Glioma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Oligodendroglioma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Cystic Fibrosis and the Nervous System.

PubMed

Reznikov, Leah R

2017-05-01

Cystic fibrosis (CF) is a life-shortening autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an anion channel that conducts bicarbonate and chloride across cell membranes. Although defective anion transport across epithelial cells is accepted as the basic defect in CF, many of the features observed in people with CF and organs affected by CF are modulated by the nervous system. This is of interest because CFTR expression has been reported in both the peripheral and central nervous systems, and it is well known that the transport of anions, such as chloride, greatly modulates neuronal excitability. Thus it is predicted that in CF, lack of CFTR in the nervous system affects neuronal function. Consistent with this prediction, several nervous system abnormalities and nervous system disorders have been described in people with CF and in animal models of CF. The goal of this special feature article is to highlight the expression and function of CFTR in the nervous system. Special emphasis is placed on nervous system abnormalities described in people with CF and in animal models of CF. Finally, features of CF that may be modulated by or attributed to faulty nervous system function are discussed. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

The Central Nervous System and Bone Metabolism: An Evolving Story.

PubMed

Dimitri, Paul; Rosen, Cliff

2017-05-01

Our understanding of the control of skeletal metabolism has undergone a dynamic shift in the last two decades, primarily driven by our understanding of energy metabolism. Evidence demonstrating that leptin not only influences bone cells directly, but that it also plays a pivotal role in controlling bone mass centrally, opened up an investigative process that has changed the way in which skeletal metabolism is now perceived. Other central regulators of bone metabolism have since been identified including neuropeptide Y (NPY), serotonin, endocannabinoids, cocaine- and amphetamine-regulated transcript (CART), adiponectin, melatonin and neuromedin U, controlling osteoblast and osteoclast differentiation, proliferation and function. The sympathetic nervous system was originally identified as the predominant efferent pathway mediating central signalling to control skeleton metabolism, in part regulated through circadian genes. More recent evidence points to a role of the parasympathetic nervous system in the control of skeletal metabolism either through muscarinic influence of sympathetic nerves in the brain or directly via nicotinic receptors on osteoclasts, thus providing evidence for broader autonomic skeletal regulation. Sensory innervation of bone has also received focus again widening our understanding of the complex neuronal regulation of bone mass. Whilst scientific advance in this field of bone metabolism has been rapid, progress is still required to understand how these model systems work in relation to the multiple confounders influencing skeletal metabolism, and the relative balance in these neuronal systems required for skeletal growth and development in childhood and maintaining skeletal integrity in adulthood.

Is Multiple Sclerosis an Autoimmune Disease?

PubMed Central

Wootla, Bharath; Eriguchi, Makoto; Rodriguez, Moses

2012-01-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS. PMID:22666554

Multiple Sclerosis: Epidemiologic, Clinical, and Therapeutic Aspects.

PubMed

Vidal-Jordana, Angela; Montalban, Xavier

2017-05-01

Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system that affects young people. MS develops in genetically susceptible individuals exposed to different unknown triggering factors. Different phenotypes are described. About 15% of patients present with a primary progressive course and 85% with a relapsing-remitting course. An increasing number of disease-modifying treatments has emerged. Although encouraging, the number of drugs challenges the neurologist because each treatment has its own risk-benefit profile. Patients should be involved in the decision-making process to ensure good treatment and safety monitoring adherence. Copyright © 2016 Elsevier Inc. All rights reserved.

Green Tea Extracts Epigallocatechin-3-gallate for Different Treatments

PubMed Central

Chu, Chenyu; Deng, Jia

2017-01-01

Epigallocatechin-3-gallate (EGCG), a component extracted from green tea, has been proved to have multiple effects on human pathological and physiological processes, and its mechanisms are discrepant in cancer, vascularity, bone regeneration, and nervous system. Although there are multiple benefits associated with EGCG, more and more challenges are still needed to get through. For example, EGCG shows low bioactivity via oral administration. This review focuses on effects of EGCG, including anti-cancer, antioxidant, anti-inflammatory, anticollagenase, and antifibrosis effects, to express the potential of EGCG and necessity of further studies in this field. PMID:28884125

Mechanisms responsible for postmenopausal hypertension in a rat model: Roles of the renal sympathetic nervous system and the renin-angiotensin system.

PubMed

Maranon, Rodrigo O; Reckelhoff, Jane F

2016-02-01

Hypertension in postmenopausal women is less well controlled than in age-matched men. The aging female SHR is a model of postmenopausal hypertension that is mediated in part by activation of the renin-angiotensin system (RAS) and by the renal sympathetic nervous system. In this study, the hypothesis was tested that renal denervation would lower the blood pressure in old female SHR and would attenuate the antihypertensive effects of AT1 receptor antagonism. Retired breeder female SHR were subjected to right uninephrectomy (UNX) and left renal denervation (RD) or UNX and sham, and 2 weeks later, baseline mean arterial pressure (MAP; radiotelemetry) was measured for 4 days, and then rats were treated with angiotensin (AT1) receptor antagonist, losartan (40 mg/kg/day po) for 6 days. Renal denervation reduced MAP in old females compared to sham (172 ± 6 vs. 193 ± 6 mm Hg; P < 0.05). Losartan reduced MAP in both sham and RD rats similarly (numerically and by percentage) (142 ± 10 vs. 161 ± 6 mm Hg; P < 0.05 vs. RD, P < 0.05 vs. baseline). However, female SHR rats remained significantly hypertensive despite both pharmacological intervention and RD. The data suggest that both the renal sympathetic nervous system and the RAS have independent effects to control the blood pressure in old female SHR. Since the denervated rats treated with losartan remained hypertensive, the data also suggest that other mechanisms than the RAS and renal sympathetic nervous system contribute to the hypertension in old female SHR. The data also suggest that multiple mechanisms may mediate the elevated blood pressure in postmenopausal women. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Testosterone Plus Finasteride Treatment After Spinal Cord Injury

ClinicalTrials.gov

2018-05-16

Spinal Cord Injury; Spinal Cord Injuries; Trauma, Nervous System; Wounds and Injuries; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Genital Diseases, Male

Management of disease-modifying treatments in neurological autoimmune diseases of the central nervous system.

PubMed

Salmen, A; Gold, R; Chan, A

2014-05-01

The therapeutic armamentarium for autoimmune diseases of the central nervous system, specifically multiple sclerosis and neuromyelitis optica, is steadily increasing, with a large spectrum of immunomodulatory and immunosuppressive agents targeting different mechanisms of the immune system. However, increasingly efficacious treatment options also entail higher potential for severe adverse drug reactions. Especially in cases failing first-line treatment, thorough evaluation of the risk-benefit profile of treatment alternatives is necessary. This argues for the need of algorithms to identify patients more likely to benefit from a specific treatment. Moreover, paradigms to stratify the risk for severe adverse drug reactions need to be established. In addition to clinical/paraclinical measures, biomarkers may aid in individualized risk-benefit assessment. A recent example is the routine testing for anti-John Cunningham virus antibodies in natalizumab-treated multiple sclerosis patients to assess the risk for the development of progressive multi-focal leucoencephalopathy. Refined algorithms for individualized risk assessment may also facilitate early initiation of induction treatment schemes in patient groups with high disease activity rather than classical escalation concepts. In this review, we will discuss approaches for individiualized risk-benefit assessment both for newly introduced agents as well as medications with established side-effect profiles. In addition to clinical parameters, we will also focus on biomarkers that may assist in patient selection. © 2013 British Society for Immunology.

Ferritin Is Required in Multiple Tissues during Drosophila melanogaster Development.

PubMed

González-Morales, Nicanor; Mendoza-Ortíz, Miguel Ángel; Blowes, Liisa M; Missirlis, Fanis; Riesgo-Escovar, Juan R

2015-01-01

In Drosophila melanogaster, iron is stored in the cellular endomembrane system inside a protein cage formed by 24 ferritin subunits of two types (Fer1HCH and Fer2LCH) in a 1:1 stoichiometry. In larvae, ferritin accumulates in the midgut, hemolymph, garland, pericardial cells and in the nervous system. Here we present analyses of embryonic phenotypes for mutations in Fer1HCH, Fer2LCH and in both genes simultaneously. Mutations in either gene or deletion of both genes results in a similar set of cuticular embryonic phenotypes, ranging from non-deposition of cuticle to defects associated with germ band retraction, dorsal closure and head involution. A fraction of ferritin mutants have embryonic nervous systems with ventral nerve cord disruptions, misguided axonal projections and brain malformations. Ferritin mutants die with ectopic apoptotic events. Furthermore, we show that ferritin maternal contribution, which varies reflecting the mother's iron stores, is used in early development. We also evaluated phenotypes arising from the blockage of COPII transport from the endoplasmic reticulum to the Golgi apparatus, feeding the secretory pathway, plus analysis of ectopically expressed and fluorescently marked Fer1HCH and Fer2LCH. Overall, our results are consistent with insect ferritin combining three functions: iron storage, intercellular iron transport, and protection from iron-induced oxidative stress. These functions are required in multiple tissues during Drosophila embryonic development.

Localization of multiple neurotransmitters in surgically derived specimens of human atrial ganglia.

PubMed

Hoover, D B; Isaacs, E R; Jacques, F; Hoard, J L; Pagé, P; Armour, J A

2009-12-15

Dysfunction of the intrinsic cardiac nervous system is implicated in the genesis of atrial and ventricular arrhythmias. While this system has been studied extensively in animal models, far less is known about the intrinsic cardiac nervous system of humans. This study was initiated to anatomically identify neurotransmitters associated with the right atrial ganglionated plexus (RAGP) of the human heart. Biopsies of epicardial fat containing a portion of the RAGP were collected from eight patients during cardiothoracic surgery and processed for immunofluorescent detection of specific neuronal markers. Colocalization of markers was evaluated by confocal microscopy. Most intrinsic cardiac neuronal somata displayed immunoreactivity for the cholinergic marker choline acetyltransferase and the nitrergic marker neuronal nitric oxide synthase. A subpopulation of intrinsic cardiac neurons also stained for noradrenergic markers. While most intrinsic cardiac neurons received cholinergic innervation evident as punctate immunostaining for the high affinity choline transporter, some lacked cholinergic inputs. Moreover, peptidergic, nitrergic, and noradrenergic nerves provided substantial innervation of intrinsic cardiac ganglia. These findings demonstrate that the human RAGP has a complex neurochemical anatomy, which includes the presence of a dual cholinergic/nitrergic phenotype for most of its neurons, the presence of noradrenergic markers in a subpopulation of neurons, and innervation by a host of neurochemically distinct nerves. The putative role of multiple neurotransmitters in controlling intrinsic cardiac neurons and mediating efferent signaling to the heart indicates the possibility of novel therapeutic targets for arrhythmia prevention.

Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome

PubMed Central

Vodopiutz, Julia; Zoller, Heinz; Fenwick, Aimée L.; Arnhold, Richard; Schmid, Max; Prayer, Daniela; Müller, Thomas; Repa, Andreas; Pollak, Arnold; Aufricht, Christoph; Wilkie, Andrew O.M.; Janecke, Andreas R.

2013-01-01

Objective To delineate a novel autosomal recessive multiple congenital anomaly-mental retardation (MCA-MR) syndrome in 2 female siblings of a consanguineous pedigree and to identify the disease-causing mutation. Study design Both siblings were clinically characterized and homozygosity mapping and sequencing of candidate genes were applied. The contribution of nonsense-mediated messenger RNA (mRNA) decay to the expression of mutant mRNA in fibroblasts of a healthy carrier and a control was studied by pyrosequencing. Results We identified the first homozygous SALL1 mutation, c.3160C > T (p.R1054*), in 2 female siblings presenting with multiple congenital anomalies, central nervous system defects, cortical blindness, and absence of psychomotor development (ie, a novel recognizable, autosomal recessive MCA-MR). The mutant SALL1 transcript partially undergoes nonsense-mediated mRNA decay and is present at 43% of the normal transcript level in the fibroblasts of a healthy carrier. Conclusion Previously heterozygous SALL1 mutations and deletions have been associated with dominantly inherited anal-renal-radial-ear developmental anomalies. We identified an allelic recessive SALL1-related MCA-MR. Our findings imply that quantity and quality of SALL1 transcript are important for SALL1 function and determine phenotype, and mode of inheritance, of allelic SALL1-related disorders. This novel MCA-MR emphasizes SALL1 function as critical for normal central nervous system development and warrants a detailed neurologic investigation in all individuals with SALL1 mutations. PMID:23069192

Highly elevated serum lactate dehydrogenase is associated with central nervous system relapse in patients with diffuse large B-cell lymphoma: Results of a multicenter prospective cohort study.

PubMed

Kim, Seok Jin; Hong, Jun Sik; Chang, Myung Hee; Kim, Jeong-A; Kwak, Jae-Yong; Kim, Jin Seok; Yoon, Dok Hyun; Lee, Won Sik; Do, Young Rok; Kang, Hye Jin; Eom, Hyeon-Seok; Park, Yong; Won, Jong-Ho; Mun, Yeung-Chul; Kim, Hyo Jung; Kwon, Jung Hye; Kong, Jee Hyun; Oh, Sung Yong; Lee, Sunah; Bae, Sung Hwa; Yang, Deok-Hwan; Jun, Hyun Jung; Kim, Yang Soo; Yun, Hwan Jung; Lee, Soon Il; Kim, Min Kyoung; Park, Eun Kyung; Kim, Won Seog; Suh, Cheolwon

2016-11-01

Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4-29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448.

Highly elevated serum lactate dehydrogenase is associated with central nervous system relapse in patients with diffuse large B-cell lymphoma: Results of a multicenter prospective cohort study

PubMed Central

Kim, Seok Jin; Hong, Jun Sik; Chang, Myung Hee; Kim, Jeong-A; Kwak, Jae-Yong; Kim, Jin Seok; Yoon, Dok Hyun; Lee, Won Sik; Do, Young Rok; Kang, Hye Jin; Eom, Hyeon-Seok; Park, Yong; Won, Jong-Ho; Mun, Yeung-Chul; Kim, Hyo Jung; Kwon, Jung Hye; Kong, Jee Hyun; Oh, Sung Yong; Lee, Sunah; Bae, Sung Hwa; Yang, Deok-Hwan; Jun, Hyun Jung; Kim, Yang Soo; Yun, Hwan Jung; Il Lee, Soon; Kim, Min Kyoung; Park, Eun Kyung; Kim, Won Seog; Suh, Cheolwon

2016-01-01

Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4–29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448. PMID:27713132

Central nervous system considerations in the use of beta-blockers, angiotensin-converting enzyme inhibitors, and thiazide diuretics in managing essential hypertension.

PubMed

Gengo, F M; Gabos, C

1988-07-01

The most common mild side effects occurring with use of beta-blockers, thiazide diuretics, and angiotensin-converting enzyme inhibitors for blood pressure control are central nervous system symptoms, specifically lethargy, sedation, and fatigue. These symptoms affect 5% to 10% of patients taking these drugs. The mechanism by which beta-blockers may induce central nervous system effects is uncertain. Relative lipophilicity as a factor affecting penetrance of the blood-brain barrier has not proved to be a reliable predictor of whether the drug will cause such disturbances. Comparisons of atenolol (hydrophilic) and metoprolol (lipophilic) have shown no differences between these drugs with respect to side effects of the central nervous system. The incidence of central nervous system effects with angiotensin-converting enzyme inhibitors is similar to that for most beta-blockers. The precise role of the angiotensin-converting enzyme in the central nervous system is not well defined. Most thiazide diuretics are not associated with major complications of the central nervous system, although electrolyte imbalance may occasionally lead to complaints of neurologic symptoms. Because the incidence of central nervous system effects with these three classes of drugs is so low, concern for the side effects of the central nervous system is not a prime consideration in the choice of an initial antihypertensive agent.

Influence of laser irradiation on demyelination of nervous fibers

NASA Astrophysics Data System (ADS)

Melnik, Nataly O.; Plaksij, Yu. S.; Mamilov, Serge A.

2000-11-01

Problem demyelinating diseases from actual in modern of neurology. Main disease of this group - multiple sclerosis, which morphological manifestation is the process demyelineation - disintegration of myelin, which covers axial cylinders of nervous filaments. The outcome of such damage is violation of realization of nervous impulses, dissonance of implement and coordination functions. Most typical the feature of a multiple sclerosis is origin of repeated remissions, which compact with indication remyelination. In development of disease the large role is played by modifications of immunological of a reactivity of an organism. The purpose of the title is development of new methods of treatment of a multiple sclerosis because of lasertherapy. For thsi purpose the influence of a laser exposure on demyelination and remyelination processes will be investigated, is investigated pathological fabrics at microscopic and submicroscopic levels. The study of proceses demyelination and remyelination will be conducted on experimental animals (rats), which are sick experimental allergic encephalomyelitis (EAE), that is the most adequate model of a multiple sclerosis. The patients' EAE animals will be subjected to treatment by a laser exposure. For want of it there will be determinate optimum lengths of waves, dozes and modes of laser radiation.

Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

ClinicalTrials.gov

2013-05-01

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Extra-adrenal Paraganglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

[ASSESSMENT OF PEFORMANCE IN STUDENTS WITH DIFFERENT TYPES OF THE NERVOUS SYSTEM WITH THE USE OF THE DEVELOPED SOFTWARE FOR PC "TAPPING-TEST"].

PubMed

Shumskikh, D S; Rakhmanov, R S; Orlov, A L

2015-01-01

There was developed the PC software, which demonstrates the type of nervous system, allows us to differentiate people according to the empirical coefficient within groups with the same type of nervous system, provides information on the severity of the asymmetry of the hemispheres of the brain and shows the results of performance of the work It does not require additional calculations. With its use there were examined 1 and 2 courses students of the institution. Ehpyky was performed the comparative analysis of the progress of students with different types of nervous system. The academic performance in the examinees with a strong type of nervous system was significantly higher than in those with a weak type. In order to improve professional training the assessment of the type of the nervous system can be used in the educational process for the identification and correction of students with a weak nervous system.

Erdheim-Chester Disease Involving the Central Nervous System with the Unique Appearance of a Coated Vertebral Artery.

PubMed

Suzuki, Hime; Wanibuchi, Masahiko; Komatsu, Katsuya; Akiyama, Yukinori; Mikami, Takeshi; Sugita, Shintaro; Hasegawa, Tadashi; Kaya, Mitsunori; Takada, Kohichi; Mikuni, Nobuhiro

2016-10-01

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. It is characterized by multiple xanthogranulomatous masses throughout the body, predominantly in the tibia. One of the characteristic radiological findings of the lesions associated with ECD is a "coated artery," which is often observed in the aorta. Although approximately one-fourth of ECD cases involve the central nervous system (CNS), an intracranial-coated artery has only been reported in four cases. We report a case of ECD that involves the CNS and has the unique appearance of a coated vertebral artery (VA). These tumors entirely encase the bilateral VAs without stenosis and are attached to the dura. Cranial magnetic resonance imaging also showed multiple extra-axial tumors in the cavernous sinus, the frontal convexity, and the orbital cavity. Further investigation revealed additional extracranial lesions around the cervical carotid artery, at the bilateral tibia, and at the elbow joint. A biopsy of the cervical and tibial lesions confirmed ECD. Steroid therapy resulted in a month-long improvement of preoperative symptoms. However, the patient's condition gradually progressed and he died of pneumonia 1 year after ECD diagnosis. The encasement of the intracranial artery by the tumor without stenosis and the dural attachment suggest ECD, which requires whole body investigation.

Erdheim-Chester Disease Involving the Central Nervous System with the Unique Appearance of a Coated Vertebral Artery

PubMed Central

Suzuki, Hime; Wanibuchi, Masahiko; Komatsu, Katsuya; Akiyama, Yukinori; Mikami, Takeshi; Sugita, Shintaro; Hasegawa, Tadashi; Kaya, Mitsunori; Takada, Kohichi; Mikuni, Nobuhiro

2016-01-01

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. It is characterized by multiple xanthogranulomatous masses throughout the body, predominantly in the tibia. One of the characteristic radiological findings of the lesions associated with ECD is a “coated artery,” which is often observed in the aorta. Although approximately one-fourth of ECD cases involve the central nervous system (CNS), an intracranial-coated artery has only been reported in four cases. We report a case of ECD that involves the CNS and has the unique appearance of a coated vertebral artery (VA). These tumors entirely encase the bilateral VAs without stenosis and are attached to the dura. Cranial magnetic resonance imaging also showed multiple extra-axial tumors in the cavernous sinus, the frontal convexity, and the orbital cavity. Further investigation revealed additional extracranial lesions around the cervical carotid artery, at the bilateral tibia, and at the elbow joint. A biopsy of the cervical and tibial lesions confirmed ECD. Steroid therapy resulted in a month-long improvement of preoperative symptoms. However, the patient’s condition gradually progressed and he died of pneumonia 1 year after ECD diagnosis. The encasement of the intracranial artery by the tumor without stenosis and the dural attachment suggest ECD, which requires whole body investigation. PMID:28664013

Na-coupled bicarbonate transporters of the Slc4 family in the nervous system: function, localization, and relevance to neurologic function

PubMed Central

Majumdar, Debeshi; Bevensee, Mark O.

2010-01-01

Many cellular processes including neuronal activity are sensitive to changes in intracellular and/or extracellular pH— both of which are regulated by acid-base transporter activity. HCO3−-dependent transporters are particularly potent regulators of intracellular pH in neurons and astrocytes, and also contribute to the composition of the cerebrospinal fluid (CSF). The molecular physiology of HCO3− transporters has advanced considerably over the past ~14 years as investigators have cloned and characterized the function and localization of many Na-Coupled Bicarbonate Transporters of the Slc4 family (NCBTs). In this review, we provide an updated overview of the function and localization of NCBTs in the nervous system. Multiple NCBTs are expressed in neurons and astrocytes in various brain regions, as well as in epithelial cells of the choroid plexus. Characteristics of human patients with SLC4 gene mutations/deletions and results from recent studies on mice with Slc4 gene disruptions highlight the functional importance of NCBTs in neuronal activity, somatosensory function, and CSF production. Furthermore, energy-deficient states (e.g., hypoxia and ischemia) lead to altered expression and activity of NCBTs. Thus, recent studies expand our understanding of the role of NCBTs in regulating the pH and ionic composition of the nervous system that can modulate neuronal activity. PMID:20884330

Birth weight and order as risk factors for childhood central nervous system tumors.

PubMed

MacLean, Jane; Partap, Sonia; Reynolds, Peggy; Von Behren, Julie; Fisher, Paul Graham

2010-09-01

To determine whether birth characteristics related to maternal-fetal health in utero are associated with the development of childhood central nervous system tumors. We identified, from the California Cancer Registry, 3733 children under age 15 diagnosed with childhood central nervous system tumors between 1988 and 2006 and linked these cases to their California birth certificates. Four controls per case, matched on birth date and sex, were randomly selected from the same birth files. We evaluated associations of multiple childhood CNS tumor subtypes with birth weight and birth order. Low birth weight was associated with a reduced risk of low-grade gliomas (OR=0.67; 95% CI, 0.46 to 0.97) and high birth weight was associated with increased risk of high-grade gliomas (OR=1.57; 95% CI, 1.16 to 2.12). High birth order (fourth or higher) was associated with decreased risk of low-grade gliomas (OR=0.75; 95% CI, 0.56 to 0.99) and increased risk of high-grade gliomas (OR=1.32; 95% CI, 1.01 to 1.72 for second order). Factors that drive growth in utero may increase the risk of low-grade gliomas. There may be a similar relationship in high-grade gliomas, although other factors, such as early infection, may modify this association. Additional investigation is warranted to validate and further define these findings. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Nerve Regeneration in the Peripheral Nervous System versus the Central Nervous System and the Relevance to Speech and Hearing after Nerve Injuries

ERIC Educational Resources Information Center

Gordon, Tessa; Gordon, Karen

2010-01-01

Schwann cells normally form myelin sheaths around axons in the peripheral nervous system (PNS) and support nerve regeneration after nerve injury. In contrast, nerve regeneration in the central nervous system (CNS) is not supported by the myelinating cells known as oligodendrocytes. We have found that: 1) low frequency electrical stimulation can be…

Neurological diseases and pain

PubMed Central

2012-01-01

Chronic pain is a frequent component of many neurological disorders, affecting 20–40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). Chronic pain should thus be considered a brain disease in which alterations in neural networks affect multiple aspects of brain function, structure and chemistry. The study and treatment of this disease is greatly complicated by the lack of objective measures for either the symptoms or the underlying mechanisms of chronic pain. In pain associated with neurological disease, it is sometimes difficult to obtain even a subjective evaluation of pain, as is the case for patients in a vegetative state or end-stage Alzheimer's disease. It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain. PMID:22067541

Central nervous system

MedlinePlus

The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

[A case of severe asthma exacerbation complicated with cerebral edema and diffuse multiple cerebral micro-bleeds].

PubMed

Ohkura, Noriyuki; Fujimura, Masaki; Sakai, Asao; Fujita, Kentaro; Katayama, Nobuyuki

2009-08-01

A 36-year-old woman was admitted to the Intensive Care Unit for the treatment of severe asthma exacerbation. Her condition of asthma improved with systemic glucocorticosteroids, inhaled beta2-agonist, intravenous theophylline and inhaled anesthesia (isoflurane) under mechanical ventilation. Her consciousness was disturbed even after terminating isoflurane. Brain CT and MRI scan showed cerebral edema and diffuse multiple cerebral micro-bleeds. Glyceol, a hyperosmotic diuretic solution consisting of 10% glycerol and 5% fructose in saline, was administered to decrease cerebral edema. Her consciousness disturbance gradually recovered. Cerebral edema and hemorrhage improved. On the 69th hospital day, she was discharged from hospital without sequelae. This case is a rare one in which severe asthma exacerbation was complicated with cerebral edema and diffuse multiple cerebral hemorrhage. Inhaled anesthesia for asthma exacerbation should be used carefully to avoid delay of diagnosis of central nervous system complications.

Role of endothelial-to-mesenchymal transition in the pathogenesis of central nervous system hemangioblastomas.

PubMed

Takada, Shigeki; Hojo, Masato; Takebe, Noriyoshi; Tanigaki, Kenji; Miyamoto, Susumu

2018-06-07

Hemangioblastomas (HBs) are benign vascular tumors of the central nervous system and histologically contain abundant microvessels. Therefore, they clinically exhibit vascular malformation-like characteristics. It has been described that endothelial-to-mesenchymal transition (EndMT) contributes to the pathogenesis of cerebral cavernous malformations. However, it remains unknown whether EndMT contributes to the pathogenesis of central nervous system HBs. The aim of our study was to investigate whether EndMT occurs in central nervous system HBs. Ten central nervous system HBs were immunohistochemically investigated. CD31 (an endothelial marker) and EndMT markers, such as α-smooth muscle actin (a mesenchymal marker) and CD44 (a mesenchymal stem cell marker), were expressed in the endothelial layer of microvessels in all cases. These findings suggest that endothelial cells (ECs) of microvessels in central nervous system HBs have acquired mesenchymal and stem-cell-like characteristics and undergone EndMT. In all cases, both ephrin-B2 and EphB4, which are not detected in adult normal brain vessels, were expressed in the endothelial layer of microvessels. These data suggest that ECs of microvessels in central nervous system HBs are immature or malformed cells and have both arterial and venous characteristics. This is the first report showing the possibility that EndMT contributes to the pathogenesis of central nervous system HBs. It is likely that ECs of microvessels in central nervous system HBs are immature or malformed cells and have both arterial and venous characteristics. EndMT is expected to be a new therapeutic target in central nervous system HBs. Copyright © 2018 Elsevier Inc. All rights reserved.

The Human Sympathetic Nervous System Response to Spaceflight

NASA Technical Reports Server (NTRS)

Ertl, Andrew C.; Diedrich, Andre; Paranjape, Sachin Y.; Biaggioni, Italo; Robertson, Rose Marie; Lane, Lynda D.; Shiavi, Richard; Robertson, David

2003-01-01

The sympathetic nervous system is an important part of the autonomic (or automatic) nervous system. When an individual stands up, the sympathetic nervous system speeds the heart and constricts blood vessels to prevent a drop in blood pressure. A significant number of astronauts experience a drop in blood pressure when standing for prolonged periods after they return from spaceflight. Difficulty maintaining blood pressure with standing is also a daily problem for many patients. Indirect evidence available before the Neurolab mission suggested the problem in astronauts while in space might be due partially to reduced sympathetic nervous system activity. The purpose of this experiment was to identify whether sympathetic activity was reduced during spaceflight. Sympathetic nervous system activity can be determined in part by measuring heart rate, nerve activity going to blood vessels, and the release of the hormone norepinephrine into the blood. Norepinephrine is a neurotransmitter discharged from active sympathetic nerve terminals, so its rate of release can serve as a marker of sympathetic nervous system action. In addition to standard cardiovascular measurements (heart rate, blood pressure), we determined sympathetic nerve activity as well as norepinephrine release and clearance on four crewmembers on the Neurolab mission. Contrary to our expectation, the results demonstrated that the astronauts had mildly elevated resting sympathetic nervous system activity in space. Sympathetic nervous system responses to stresses that simulated the cardiovascular effects of standing (lower body negative pressure) were brisk both during and after spaceflight. We concluded that, in the astronauts tested, the activity and response of the sympathetic nervous system to cardiovascular stresses appeared intact and mildly elevated both during and after spaceflight. These changes returned to normal within a few days.

Evaluation of a Multivariate Syndromic Surveillance System for West Nile Virus.

PubMed

Faverjon, Céline; Andersson, M Gunnar; Decors, Anouk; Tapprest, Jackie; Tritz, Pierre; Sandoz, Alain; Kutasi, Orsolya; Sala, Carole; Leblond, Agnès

2016-06-01

Various methods are currently used for the early detection of West Nile virus (WNV) but their outputs are not quantitative and/or do not take into account all available information. Our study aimed to test a multivariate syndromic surveillance system to evaluate if the sensitivity and the specificity of detection of WNV could be improved. Weekly time series data on nervous syndromes in horses and mortality in both horses and wild birds were used. Baselines were fitted to the three time series and used to simulate 100 years of surveillance data. WNV outbreaks were simulated and inserted into the baselines based on historical data and expert opinion. Univariate and multivariate syndromic surveillance systems were tested to gauge how well they detected the outbreaks; detection was based on an empirical Bayesian approach. The systems' performances were compared using measures of sensitivity, specificity, and area under receiver operating characteristic curve (AUC). When data sources were considered separately (i.e., univariate systems), the best detection performance was obtained using the data set of nervous symptoms in horses compared to those of bird and horse mortality (AUCs equal to 0.80, 0.75, and 0.50, respectively). A multivariate outbreak detection system that used nervous symptoms in horses and bird mortality generated the best performance (AUC = 0.87). The proposed approach is suitable for performing multivariate syndromic surveillance of WNV outbreaks. This is particularly relevant, given that a multivariate surveillance system performed better than a univariate approach. Such a surveillance system could be especially useful in serving as an alert for the possibility of human viral infections. This approach can be also used for other diseases for which multiple sources of evidence are available.

Stages of Childhood Soft Tissue Sarcoma

MedlinePlus

... lymph nodes or to the lungs. Peripheral nervous system tumors Peripheral nervous system tumors include the following ... and surgery with or without chemotherapy . Peripheral Nervous System Tumors Ectomesenchymoma Treatment of ectomesenchymoma may include the ...

Treatment Options for Childhood Soft Tissue Sarcoma

MedlinePlus

... lymph nodes or to the lungs. Peripheral nervous system tumors Peripheral nervous system tumors include the following ... and surgery with or without chemotherapy . Peripheral Nervous System Tumors Ectomesenchymoma Treatment of ectomesenchymoma may include the ...

The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.

PubMed

van Riel, Debby; Verdijk, Rob; Kuiken, Thijs

2015-01-01

The olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (CNS). Each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. Viruses that can use the olfactory nerve as a shortcut into the CNS include influenza A virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatitis virus, rabies virus, parainfluenza virus, adenoviruses, Japanese encephalitis virus, West Nile virus, chikungunya virus, La Crosse virus, mouse hepatitis virus, and bunyaviruses. However, mechanisms of transport via the olfactory nerve and subsequent spread through the CNS are poorly understood. Proposed mechanisms are either infection of olfactory receptor neurons themselves or diffusion through channels formed by olfactory ensheathing cells. Subsequent virus spread through the CNS could occur by multiple mechanisms, including trans-synaptic transport and microfusion. Viral infection of the CNS can lead to damage from infection of nerve cells per se, from the immune response, or from a combination of both. Clinical consequences range from nervous dysfunction in the absence of histopathological changes to severe meningoencephalitis and neurodegenerative disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Radiculopathy in neuromyelitis optica. How does anti-AQP4 Ab involve PNS?

PubMed

Kim, Seungyeon; Park, Joonghyun; Kwon, Bum Sun; Park, Jin-Woo; Lee, Ho Jun; Choi, Jin-Ho; Nam, Kiyeun

2017-11-01

Until recently, the peripheral nervous system (PNS) had been known to be spared in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, some studies of late have reported PNS damage in demyelination diseases of the central nervous system (CNS) such as MS and NMOSD. Although multiple studies have reported characteristics reminiscent of peripheral neuropathy in MS, there have been limited reports in NMOSD. To investigate the incidence and pathology of peripheral neuropathy in NMOSD, we reviewed articles describing such cases including our own case. We performed a search of all clinical studies of peripheral neuropathy in NMOSD published up to December 17, 2016. We put no restrictions on language or year of publication in our search. The following keywords were searched: radiculopathy, peripheral nervous system diseases, neuromyelitis optica, neuromyelitis optica septrum disorder, aquaporin 4, electrodiagnosis, neural conduction and electromyography. We review ten cases (nine published reports and our own case study) of peripheral neuropathy in NMOSD. Each case could be confirmed as radiculopathy by electrodiagnostic (EDX) testing. Presently, there are two disparate viewpoints on peripheral neuropathy in NMOSD. In the first, aquaporin 4, which exists in the transitional zone of the CNS-PNS at the root level, may be the target of radiculitis in NMOSD. In the second, there may be some other unknown antibody to an axoglial antigen or something else that may play an active role in PNS damage. In our survey of ten case studies, the EDX results confirmed mixed axonal loss as well as demyelination type radiculopathy, which lends support to the first viewpoint. Pathophysiology of PNS damage in NMOSD might be due to radiculopathy. Although it seems to be rare, radiculopathy may actually be underestimated, and correspondingly underreported, due to its overlap with symptoms of myelitis. Therefore, further evaluation is needed to establish the incidence and pathophysiology of radiculopathy in NMOSD. Copyright © 2017 Elsevier B.V. All rights reserved.

[Axonopathy in the pathogenesis of multiple sclerosis, peripheral diffuse and local motor neuropathies and motor neuron disease].

PubMed

Merkulov, Iu A; Merkulova, D M; Iosifova, O A; Zavalishin, I A

2010-01-01

Two hundreds and seventy-six patients including 43 patients with multiple sclerosis, 24 - with acute inflammatory demyelinating polyneuropathy (AIDP), 144 - with chronic inflammatory demyelinating polyneuropathy (CIDP), 27 - with motor multifocal neuropathy (MMN), 38 - with lateral amyotrophic sclerosis (LAS) have been examined. Symptoms of axonal degeneration, manifested in denervation phenomena in both clinical and instrumental studies (electromyography, transcranial magnetic stimulation, MRT), were revealed in all groups of patients. The formation of excitation conduction blocks is an universal pathophysiological mechanism of the axonopathy development in AIDP, CIDP, MMN and LAS. Symptoms of axonopathy and peripheral demyelinization in patients with multiple sclerosis and LAS suggest the possibility of transformation of immunopathological process from the central nervous system to the peripheral one.

A history of the autonomic nervous system: part II: from Reil to the modern era.

PubMed

Oakes, Peter C; Fisahn, Christian; Iwanaga, Joe; DiLorenzo, Daniel; Oskouian, Rod J; Tubbs, R Shane

2016-12-01

The history of the study of the autonomic nervous system is rich. At the beginning of the nineteenth century, scientists were beginning to more firmly grasp the reality of this part of the human nervous system. The evolution of our understanding of the autonomic nervous system has a rich history. Our current understanding is based on centuries of research and trial and error.

Evolution of eumetazoan nervous systems: insights from cnidarians.

PubMed

Kelava, Iva; Rentzsch, Fabian; Technau, Ulrich

2015-12-19

Cnidarians, the sister group to bilaterians, have a simple diffuse nervous system. This morphological simplicity and their phylogenetic position make them a crucial group in the study of the evolution of the nervous system. The development of their nervous systems is of particular interest, as by uncovering the genetic programme that underlies it, and comparing it with the bilaterian developmental programme, it is possible to make assumptions about the genes and processes involved in the development of ancestral nervous systems. Recent advances in sequencing methods, genetic interference techniques and transgenic technology have enabled us to get a first glimpse into the molecular network underlying the development of a cnidarian nervous system-in particular the nervous system of the anthozoan Nematostella vectensis. It appears that much of the genetic network of the nervous system development is partly conserved between cnidarians and bilaterians, with Wnt and bone morphogenetic protein (BMP) signalling, and Sox genes playing a crucial part in the differentiation of neurons. However, cnidarians possess some specific characteristics, and further studies are necessary to elucidate the full regulatory network. The work on cnidarian neurogenesis further accentuates the need to study non-model organisms in order to gain insights into processes that shaped present-day lineages during the course of evolution. © 2015 The Authors.

75 FR 69005 - Flumioxazin; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-10

... reproduction studies indicated an effect on the nervous systems. Based on the lack of evidence of... flumioxazin does not directly impact the nervous system or directly target the immune system. The Agency does... to indicate that flumioxazin targets the nervous system or the immune system. Further, EPA has...

Treatment Option Overview (Childhood Soft Tissue Sarcoma)

MedlinePlus

... nearby lymph nodes or to the lungs. Peripheral nervous system tumors Peripheral nervous system tumors include the following ... therapy , and surgery with or without chemotherapy . Peripheral Nervous System Tumors Ectomesenchymoma Treatment of ectomesenchymoma may include the ...

Hypotonia

MedlinePlus

... will include a detailed examination of the nervous system and muscle function. In most cases, a neurologist (specialist in ... require ongoing care and support. Alternative Names Decreased muscle tone; Floppy infant ... Central nervous system and peripheral nervous system References Burnette WB. Hypotonic ( ...

Sweating

MedlinePlus

... the autonomic nervous system. This is the part of the nervous system that is not under your control. Sweating is ... Skin layers References Chelimsky T, Chelimsky G. Disorders of the autonomic nervous system. In: Daroff RB, Jankovic J, Mazziotta JC, Pomeroy ...

The central nervous system phenotype of X-linked Charcot-Marie-Tooth disease: a transient disorder of children and young adults.

PubMed

Al-Mateen, Majeed; Craig, Alexa Kanwit; Chance, Phillip F

2014-03-01

We describe 2 patients with X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) disease and central nervous system manifestations and review 19 cases from the literature. Our first case had not been previously diagnosed with Charcot-Marie-Tooth disease, and the second case, although known to have Charcot-Marie-Tooth disease, was suspected of having CMTX1 after presentation with central nervous system manifestations. The most common central nervous system manifestations were transient and included dysarthria, ataxia, hemiparesis, and tetraparesis resembling periodic paralysis. Of the 21 patients, 19 presented at 21 years of age or younger, implicating CMTX1 with transient central nervous system manifestations as a disorder that predominantly affects children and adolescents. CMTX1 should be included in the differential diagnosis of patients who present with transient central nervous system phenomena, including stroke-like episodes, tetraparesis suggestive of periodic paralysis, dysarthria, ataxia, or combinations of these deficits. Reversible, bilateral, nonenhancing white matter lesions and restricted diffusion on magnetic resonance imaging are characteristic features of the central nervous system phenotype of CMTX1.

[Effects of inflammation and stimulant diets on functions of autonomic nervous system (author's transl)].

PubMed

Akaeda, H; Nagai, K; Okuda, Y; Shinoto, M; Okuda, H

1981-06-01

In usual medical consultation, we have been met a lot of female patients suffering from disturbances of autonomic nervous system such as headache, shoulder-ache and so on. Experiments were designed to elucidate whether or not these disturbances of autonomic nervous system were induced by inflammation and accelerated by stimulant diets. Functions of autonomic nervous system were examined by lipolysis in rat epididymal adipose tissue which was partly controlled by sympathetic nervous system. It was found that free fatty acid release from the epididymal adipose tissue was considerably elevated by inflammation which was formed in abdominal wall or in abdominal cavity or oral administration of stimulant diets such as red pepper and white pepper, and that such elevation of lipolysis was significantly reduced by resection of the autonomic nerve. These results indicated that the inflammation and the stimulant diets induced excitement of sympathetic nerve which controlled the epididymal adipose tissue. Experiments were now in progress to clarify relationship between such excitement of sympathetic nervous system induced by the inflammation or by the stimulant diet and irregular complaints due to disturbances of autonomic nervous system.

Rhabdomyolysis following interferon-beta treatment in a patient with multiple sclerosis - A case report.

PubMed

Dalbjerg, Sara Maria; Tsakiri, Anna; Frederiksen, Jette Lautrup

2016-07-01

Multiple sclerosis is an inflammatory disease of the central nervous system for which there is currently no cure. Interferon-beta-1-alpha is worldwide one of the most widely used treatments in multiple sclerosis. To our knowledge there is one previous reported case of rhabdomyolysis associated with Interferon-beta treatment. We describe a 30 year old man with relapsing remitting multiple sclerosis who developed rhabdomyolysis and increased creatine kinase following Interferon-beta-1-alpha therapy. After the medication was discontinued, the patient rapidly improved. Clinicians should be aware of the possibility of rhabdomyolysis occurring during Interferon-beta-1-alpha therapy. In cases where patients complain of severe myalgia, and in particular if weakness is reported, creatine kinase activity should be measured to prevent irreversible rhabdomyolysis during Interferon-beta-1-alpha therapy in patients with multiple sclerosis. Copyright © 2016 Elsevier B.V. All rights reserved.

The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps.

PubMed

Casper, T Charles; Rose, John W; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

2015-09-01

Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. © The Author(s) 2014.

The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps

PubMed Central

Casper, T. Charles; Rose, John W.; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E.; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

2014-01-01

Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. PMID:25270659

The effect of space radiation of the nervous system

NASA Astrophysics Data System (ADS)

Gauger, Grant E.; Tobias, Cornelius A.; Yang, Tracy; Whitney, Monroe

The long-term effects of irradiation by accelerated heavy ions on the structure and function of the nervous system have not been studied extensively. Although the adult brain is relatively resistant to low LET radiation, cellular studies indicate that individual heavy ions can produce serious membrane lesions and multiple chromatin breaks. Capillary hemorrhages may follow high LET particle irradiation of the developing brain as high RBE effects. Evidence has been accumulating that the glial system and blood-brain barrier (BBB) are relatively sensitive to injury by ionizing radiation. While DNA repair is active in neural systems, it may be assumed that a significant portion of this molecular process is misrepair. Since the expression of cell lethality usually requires cell division, and nerve cells have an extremely low rate of division, it is possible that some of the characteristic changes of premature aging may represent a delayed effect of chromatin misrepair in brain. Altered microcirculation, decreased local metabolism, entanglement and reduction in synaptic density, premature loss of neurons, myelin degeneration, and glial proliferation are late signs of such injuries. HZE particles are very efficient in producing carcinogenic cell transformation, reaching a peak for iron particles. The promotion of viral transformation is also efficient up to an energy transfer of approximately 300 keV/micron. The RBE for carcinogenesis in nerve tissues remains unknown. On the basis of available information concerning HZE particle flux in interplanetary space, only general estimates of the magnitude of the effects of long-term spaceflight on some nervous system parameters may be constructed.

Isolated Myocysticercosis.

PubMed

Vignesh, S; Bhole, Chetan; Bafna, Chander; Nirala, Neeraj; Prajapati, Mehul; Samar, Neera; Meena, R L

2016-03-01

Cysticercosis, a parasitic disease caused by larval form of Taenia solium, is a major health concern in the developing world. The encysted larval stage can affect any part of the body, but are most frequently detected in brain, eye, skeletal muscle and subcutaneous tissue. Most muscular cysticercosis are almost always associated with central nervous system involvement or with multiple intramuscular cysts or both. Here we report an unusual case of cysticercosis in right rectus muscle which was an isolated muscle involvement without any other systemic manifestation. © Journal of the Association of Physicians of India 2011.

Vaccines and Autism: A Tale of Shifting Hypotheses

PubMed Central

Gerber, Jeffrey S.; Offit, Paul A.

2010-01-01

Although child vaccination rates remain high, some parental concern persists that vaccines might cause autism. Three specific hypotheses have been proposed: (1) the combination measles-mumps-rubella vaccine causes autism by damaging the intestinal lining, which allows the entrance of encephalopathic proteins; (2) thimerosal, an ethylmercury-containing preservative in some vaccines, is toxic to the central nervous system; and (3) the simultaneous administration of multiple vaccines overwhelms or weakens the immune system. We will discuss the genesis of each of these theories and review the relevant epidemiological evidence. PMID:19128068

Vaccines and autism: a tale of shifting hypotheses.

PubMed

Gerber, Jeffrey S; Offit, Paul A

2009-02-15

Although child vaccination rates remain high, some parental concern persists that vaccines might cause autism. Three specific hypotheses have been proposed: (1) the combination measles-mumps-rubella vaccine causes autism by damaging the intestinal lining, which allows the entrance of encephalopathic proteins; (2) thimerosal, an ethylmercury-containing preservative in some vaccines, is toxic to the central nervous system; and (3) the simultaneous administration of multiple vaccines overwhelms or weakens the immune system. We will discuss the genesis of each of these theories and review the relevant epidemiological evidence.

The New Neurobiology of Autism

PubMed Central

Minshew, Nancy J.; Williams, Diane L.

2008-01-01

This review covers a fraction of the new research developments in autism but establishes the basic elements of the new neurobiologic understanding of autism. Autism is a polygenetic developmental neurobiologic disorder with multiorgan system involvement, though it predominantly involves central nervous system dysfunction. The evidence supports autism as a disorder of the association cortex, both its neurons and their projections. In particular, it is a disorder of connectivity, which appears, from current evidence, to primarily involve intrahemispheric connectivity. The focus of connectivity studies thus far has been on white matter, but alterations in functional magnetic resonance imaging activation suggest that intracortical connectivity is also likely to be disturbed. Furthermore, the disorder has a broad impact on cognitive and neurologic functioning. Deficits in high-functioning individuals occur in processing that places high demands on integration of information and coordination of multiple neural systems. Intact or enhanced abilities share a dependence on low information-processing demands and local neural connections. This multidomain model with shared characteristics predicts an underlying pathophysiologic mechanism that impacts the brain broadly, according to a common neurobiologic principle. The multiorgan system involvement and diversity of central nervous system findings suggest an epigenetic mechanism. PMID:17620483

Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-1-0586 TITLE: Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring PRINCIPAL INVESTIGATOR...Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH- 14-1-0586 5c. PROGRAM ELEMENT...cavitations that are not spontaneously repaired. Early after injury, blood enters the central nervous system (CNS) and directly kills brain cells but also

Immunostaining to visualize murine enteric nervous system development.

PubMed

Barlow-Anacker, Amanda J; Erickson, Christopher S; Epstein, Miles L; Gosain, Ankush

2015-04-29

The enteric nervous system is formed by neural crest cells that proliferate, migrate and colonize the gut. Following colonization, neural crest cells must then differentiate into neurons with markers specific for their neurotransmitter phenotype. Cholinergic neurons, a major neurotransmitter phenotype in the enteric nervous system, are identified by staining for choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine. Historical efforts to visualize cholinergic neurons have been hampered by antibodies with differing specificities to central nervous system versus peripheral nervous system ChAT. We and others have overcome this limitation by using an antibody against placental ChAT, which recognizes both central and peripheral ChAT, to successfully visualize embryonic enteric cholinergic neurons. Additionally, we have compared this antibody to genetic reporters for ChAT and shown that the antibody is more reliable during embryogenesis. This protocol describes a technique for dissecting, fixing and immunostaining of the murine embryonic gastrointestinal tract to visualize enteric nervous system neurotransmitter expression.

Multiple-Task Performance: A Critical Review of the Literature and a Cognitive Neuroscience Framework

DTIC Science & Technology

1994-03-10

determine capacity variations as shown in dual-task performance. In addition, neurobiology and psychological evidence shows that the nervous system is...do we perform complex tasks requiring two or more activities in a short period of time and what determines the quality of performance? Psychological ...definition for these kinds of entities. Introduction of the computer metaphor in cognitive psychology , ascribing behavioral capacity limitations to a kind

Variables Affecting the Reporting of Pain Following an Acute Myocardial Infarction

DTIC Science & Technology

1991-05-01

research found which investigated the phenomenon of unreported CP. The experience of pain is a highly complex human experience with a multiplicity of...occur, and is persistent (Greer & Hoyt, 1990). Nociceptive fibers have cell bodies in the spinal ganglia , which enter the dorsal horn posteriorly, and...via the spinothalamic pathway, and stimulate somatic motor neurons on the anterior horn, or preganglionic neurons of the autonomic nervous system in the

Neural-endocrine-immune complex in the central modulation of tumorigenesis: facts, assumptions, and hypotheses.

PubMed

Mravec, Boris; Gidron, Yori; Kukanova, Barbara; Bizik, Jozef; Kiss, Alexander; Hulin, Ivan

2006-11-01

For the precise coordination of systemic functions, the nervous system uses a variety of peripherally and centrally localized receptors, which transmit information from internal and external environments to the central nervous system. Tight interconnections between the immune, nervous, and endocrine systems provide a base for monitoring and consequent modulation of immune system functions by the brain and vice versa. The immune system plays an important role in tumorigenesis. On the basis of rich interconnections between the immune, nervous and endocrine systems, the possibility that the brain may be informed about tumorigenesis is discussed in this review article. Moreover, the eventual modulation of tumorigenesis by central nervous system is also considered. Prospective consequences of the interactions between tumor and brain for diagnosis and therapy of cancer are emphasized.

A Rare Presentation of Isolated CNS Posttransplantation Lymphoproliferative Disorder

PubMed Central

Smith, Casey; Streicher, Andrew; Magnuson, Allison; Newman, Susan; Bertoli, Robert

2017-01-01

Posttransplantation lymphoproliferative disorder (PTLD) is a recognized and extremely morbid complication of solid organ transplantation, but central nervous system involvement, particularly in isolation, is rare. There are no standardized treatment strategies for PTLD, though commonly used strategies include reduction of immunosuppression, chemotherapy, rituximab, radiation, and surgery. We present a case of an unusual morphologic variant of primary central nervous system PTLD with successful response to rituximab and cranial radiation. A 69-year-old Asian male, who underwent postrenal transplant nine years earlier, presented with a one-month history of new onset seizure activity. His evaluation revealed multiple brain lesions on magnetic resonance imaging (MRI), as well as serologic and cerebrospinal fluid studies which were positive for Epstein-Barr Virus (EBV) infection. Ultimately, he underwent craniotomy with tissue biopsy with the final pathology report showing posttransplant lymphoproliferative disorder, polymorphic type. The patient was managed with reduction in immunosuppression, rituximab therapy, and cranial radiation treatments. He had demonstrated marked improvement in his neurologic function and was ultimately discharged to inpatient rehabilitation facility. PMID:28116196

A Rare Presentation of Isolated CNS Posttransplantation Lymphoproliferative Disorder.

PubMed

Morris, Jaime; Smith, Casey; Streicher, Andrew; Magnuson, Allison; Newman, Susan; Bertoli, Robert

2017-01-01

Posttransplantation lymphoproliferative disorder (PTLD) is a recognized and extremely morbid complication of solid organ transplantation, but central nervous system involvement, particularly in isolation, is rare. There are no standardized treatment strategies for PTLD, though commonly used strategies include reduction of immunosuppression, chemotherapy, rituximab, radiation, and surgery. We present a case of an unusual morphologic variant of primary central nervous system PTLD with successful response to rituximab and cranial radiation. A 69-year-old Asian male, who underwent postrenal transplant nine years earlier, presented with a one-month history of new onset seizure activity. His evaluation revealed multiple brain lesions on magnetic resonance imaging (MRI), as well as serologic and cerebrospinal fluid studies which were positive for Epstein-Barr Virus (EBV) infection. Ultimately, he underwent craniotomy with tissue biopsy with the final pathology report showing posttransplant lymphoproliferative disorder, polymorphic type. The patient was managed with reduction in immunosuppression, rituximab therapy, and cranial radiation treatments. He had demonstrated marked improvement in his neurologic function and was ultimately discharged to inpatient rehabilitation facility.

The Effects of Different Factors on the Behavior of Neural Stem Cells

PubMed Central

Huang, Lixiang

2017-01-01

The repair of central nervous system (CNS) injury has been a worldwide problem in the biomedical field. How to reduce the damage to the CNS and promote the reconstruction of the damaged nervous system structure and function recovery has always been the concern of nerve tissue engineering. Multiple differentiation potentials of neural stem cell (NSC) determine the application value for the repair of the CNS injury. Thus, how to regulate the behavior of NSCs becomes the key to treating the CNS injury. So far, a large number of researchers have devoted themselves to searching for a better way to regulate the behavior of NSCs. This paper summarizes the effects of different factors on the behavior of NSCs in the past 10 years, especially on the proliferation and differentiation of NSCs. The final purpose of this review is to provide a more detailed theoretical basis for the clinical repair of the CNS injury by nerve tissue engineering. PMID:29358957

Nasopharyngeal carcinoma with central nervous system metastases: Two case reports and a review of the literature.

PubMed

Shen, Chunying; Ying, Hongmei; Lu, Xueguan; Hu, Chaosu

2017-12-01

Central nervous system (CNS) metastases are rarely seen in patients with nasopharyngeal carcinoma (NPC). Two NPC patients developed CNS metastases were collected in Fudan University Shanghai Cancer Center. The medical records were reviewed to document patients' characteristics, treatment, and outcomes. In addition, we also provide an overview of the literature concerning this scenario. Both patients were staged T4N1M0 with pathologically confirmed CNS metastases from nasopharyngeal carcinoma. After the completion of initial chemoradiotherapy, metastases to CNS including brain and/or spine occurred during follow-up. Surgical resection combined with palliative chemoradiation was offered to alleviate the symptoms. Although multiple treatment modalities were given, both patients succumbed to disease progression. The mechanism for CNS metastases is postulated through hematogenous route or cerebral spinal fluid spread. Good symptoms amelioration can be achieved with aggressive treatments such as surgery followed by palliative chemoradiation, but prognoses are ominous due to systematic disease dissemination.

Mitochondria in the nervous system: From health to disease, Part I.

PubMed

Polster, Brian M; Carrì, Maria Teresa; Beart, Philip M

2017-10-01

In Part I of this Special Issue on "Mitochondria in the Nervous System: From Health to Disease", the editors bring together contributions from experts in brain mitochondrial research to provide an up-to-date overview of mitochondrial functioning in physiology and pathology. The issue provides cutting edge reviews on classical areas of mitochondrial biology that include energy substrate utilization, calcium handling, mitochondria-endoplasmic reticulum communication, and cell death regulation. Additional reviews and original research articles touch upon key mitochondrial defects seen across multiple neurodegenerative conditions, including fragmentation, loss of respiratory capacity, calcium overload, elevated reactive oxygen species generation, perturbed NAD + metabolism, altered protein acetylation, and compromised mitophagy. Emerging links between the genetics of neurodegenerative disorders and disruption in mitochondrial function are discussed, and a new mouse model of Complex I deficiency is described. Finally, novel ways to rescue mitochondrial structure and function in acute and chronic brain injury are explored. Copyright © 2017. Published by Elsevier Ltd.

Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit in C. elegans.

PubMed

Kim, Byunghyuk; Emmons, Scott W

2017-09-13

Nervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in C. elegans , we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG. A third, basal pathway results in considerable HOA-AVG fasciculation and synapse formation in the absence of the other two. The features of this multiplexed mechanism help to explain how complex connectivity is encoded and robustly established during nervous system development.

Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system

PubMed Central

Gonzalez, Ginez A.; Hofer, Matthias P.; Syed, Yasir A.; Amaral, Ana I.; Rundle, Jon; Rahman, Saifur; Zhao, Chao; Kotter, Mark R. N.

2016-01-01

Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models. PMID:27554391

Spinal cord infarction as a rare complication of fat embolism syndrome following bilateral intramedullary nailing of femur fractures.

PubMed

Kearsley, RoseMarie; Galbraith, John; Dalton, David; Motherway, Catherine

2016-09-13

Fat embolism syndrome (FES) is a rare and potentially fatal complication occurring most often after long bone or pelvic fractures and orthopaedic procedures. It can consist of pulmonary, central nervous system and cutaneous manifestations. The exact pathophysiology of emboli reaching the arterial circulation is poorly understood.1 It is suggested that this may occur by either 'paradoxical' embolism or microembolism.2 3 Its true incidence is unknown but increases in the presence of multiple closed fractures. It can be a diagnostic dilemma for clinicians and if suspected diffusion-weighted MRI is the modality of choice for the investigation of the central nervous system.4 We present the case of a 22-year-old man who developed multifocal cerebral infarcts, a right-sided cerebellar infarct and an infarct in the anterior cord bilaterally at the level of C5-C6 as a result of FES. 2016 BMJ Publishing Group Ltd.

[Research progress in the role of aquaproin-4 and inward rectifying potassium channel 4.1 in spinal cord edema].

PubMed

Chen, Tiege; Dang, Yuexiu; Wang, Ming; Zhang, Dongliang; Guo, Yongqiang; Zhang, Haihong

2018-05-28

Spinal edema is a very important pathophysiological basis for secondary spinal cord injury, which affects the repair and prognosis of spinal cord injury. Aquaporin-4 is widely distributed in various organs of the body, and is highly expressed in the brain and spinal cord. Inward rectifying potassium channel 4.1 is a protein found in astrocytes of central nervous system. It interacts with aquaporins in function. Aquaporin-4 and inward rectifying potassium channel 4.1 play an important role in the formation and elimination of spinal cord edema, inhibition of glial scar formation and promotion of excitotoxic agents exclusion. The distribution and function of aquaporin-4 and inward rectifying potassium channel 4.1 in the central nervous system and their expression after spinal cord injury have multiple effects on spinal edema. Studies of aquaporin-4 and inward rectifying potassium channel 4.1 in the spinal cord may provide new ideas for the elimination and treatment of spinal edema.

Pulsatile crizotinib treatment for brain metastasis in a patient with non-small-cell lung cancer.

PubMed

Wang, S; Chen, J; Xie, Z; Xia, L; Luo, W; Li, J; Li, Q; Yang, Z

2017-10-01

Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is a distinct subtype with patients showing peculiar clinicopathological features and dramatic responses to the ALK tyrosine kinase inhibitor crizotinib. Patients with this cancer variant have a dismal prognosis and limited treatment options when it has progressed to intracranial metastasis because of inadequate drug penetration into the central nervous system (CNS). Factors associated with response to TKI therapy have been reported to include pharmacokinetic and biodynamic resistance phenomena. In our NSCLC patient with multiple intracranial metastases, we administered high-dose pulsatile crizotinib therapy (1000 mg/d) on a one-day-on/one-day-off basis. A significant central nervous system (CNS) response was achieved, and time to neurological progression was prolonged to 6 months. High-dose pulsatile therapy may be an effective dosing strategy for crizotinib in NSCLC showing progression to metastasis in the brain. © 2017 John Wiley & Sons Ltd.

Drug-resistant tuberculosis in two children in Greece: report of the first extensively drug-resistant case.

PubMed

Katragkou, Aspasia; Antachopoulos, Charalampos; Hatziagorou, Elpis; Sdougka, Maria; Roilides, Emmanuel; Tsanakas, John

2013-04-01

Extensively drug-resistant (XDR) tuberculosis (TB) represents a serious and growing problem in both endemic and non-endemic countries. We describe a 2.5-year-old girl with XDR-pulmonary TB and an 18-month-old boy with pre-XDR-central nervous system TB. Patients received individualized treatment with second-line anti-TB agents based on genotypic and phenotypic drug susceptibility testing results. Both children achieved culture conversion 3 months and 1 month after treatment initiation, respectively. The child with XDR-pulmonary TB showed evidence of cure while treatment adverse events were managed without treatment interruption. The child with pre-XDR-central nervous system TB after 6-month hospitalization with multiple infectious complications had a dismal end due to hepatic insufficiency possibly related to anti-TB treatment. This is the first report of children with pre-XDR and XDR TB in Greece, emphasizing the public health dimensions and management complexity of XDR TB.

Physiological and pathological functions of acid-sensing ion channels in the central nervous system

PubMed Central

Chu, Xiang-Ping; Xiong, Zhi-Gang

2012-01-01

Protons are important signals for neuronal function. In the central nervous system (CNS), proton concentrations change locally when synaptic vesicles release their acidic contents into the synaptic cleft, and globally in ischemia, seizures, traumatic brain injury, and other neurological disorders due to lactic acid accumulation. The finding that protons gate a distinct family of ion channels, the acid-sensing ion channels (ASICs), has shed new light on the mechanism of acid signaling and acidosis-associated neuronal injury. Accumulating evidence has suggested that ASICs play important roles in physiological processes such as synaptic plasticity, learning/memory, fear conditioning, and retinal integrity, and in pathological conditions such as brain ischemia, multiple sclerosis, epileptic seizures, and malignant glioma. Thus, targeting these channels may lead to novel therapeutic interventions for neurological disorders. The goal of this review is to provide an update on recent advances in our understanding of the functions of ASICs in the CNS. PMID:22204324

Gut environment-induced intraepithelial autoreactive CD4+ T cells suppress central nervous system autoimmunity via LAG-3

PubMed Central

Kadowaki, Atsushi; Miyake, Sachiko; Saga, Ryoko; Chiba, Asako; Mochizuki, Hideki; Yamamura, Takashi

2016-01-01

The gut environment has been found to significantly influence autoimmune diseases such as multiple sclerosis; however, immune cell mechanisms are unclear. Here we show that the gut epithelium of myelin oligodendrocyte glycoprotein(35-55)-specific T-cell receptor transgenic mice contains environmental stimuli-induced intraepithelial lymphocytes (IELs) that inhibit experimental autoimmune encephalomyelitis on transfer. These cells express surface markers phenotypical of ‘induced' IELs, have a TH17-like profile and infiltrate the central nervous system (CNS). They constitutively express Ctla4 and Tgfb1 and markedly upregulate Lag3 expression in the CNS, thereby inhibiting inflammation. We also demonstrate the suppressive capability of CD4+ IELs with alternative antigen specificities, their proliferation in response to gut-derived antigens and contribution of the microbiota and dietary aryl hydrocarbon receptor ligands to their induction. Thus, the gut environment favours the generation of autoreactive CD4+ T cells with unique regulatory functions, potentially important for preventing CNS autoimmunity. PMID:27198196

Catastrophic secondary antiphospholipid syndrome with peripheral nervous system involvement: a case report.

PubMed

Erten, Nilgun; Saka, Bulent; Karan, M Akif; Parman, Yesim; Umman, Berrin; Tascioglu, Cemil

2004-04-01

A 34-year-old woman was admitted to our emergency room with a high fever, abdominal pain, dyspnea and confusion. High fever and abdominal pain had first occured after a cystocele operation 5 months earlier. Later, congestive heart failure with mural thrombus formation, peripheral polyneuropathy and ischemic cerebrovascular accident were identified in clinical follow-ups, and multiple arterial and venous thromboses were seen on cranial and abdominal magnetic resonance imaging angiography. The patient's symptoms improved with anticoagulant treatment. Antiphospholipid syndrome with elevated serum anticardiolipin IgG levels was diagnosed, and ischemic peripheral polyneuropathy with axonal degeneration was determined by sural nerve biopsy. In antiphospholipid syndrome, elevated anticardiolipin antibodies appear to be the most common acquired blood protein defect causing thrombosis. Disseminated vascular thrombosis in catastrophic antiphospholipid syndrome can result in multiorgan failure with increased morbidity and mortality. It rarely occurs secondary to various infections as in the case of our patient, who suffered postoperative intraabdominal infection. It is important to note that peripheral nervous system involvement is rare in antiphospholipid syndrome.

Advancing drug delivery systems for the treatment of multiple sclerosis.

PubMed

Tabansky, Inna; Messina, Mark D; Bangeranye, Catherine; Goldstein, Jeffrey; Blitz-Shabbir, Karen M; Machado, Suly; Jeganathan, Venkatesh; Wright, Paul; Najjar, Souhel; Cao, Yonghao; Sands, Warren; Keskin, Derin B; Stern, Joel N H

2015-12-01

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.

Clustering Multiple Sclerosis Subgroups with Multifractal Methods and Self-Organizing Map Algorithm

NASA Astrophysics Data System (ADS)

Karaca, Yeliz; Cattani, Carlo

Magnetic resonance imaging (MRI) is the most sensitive method to detect chronic nervous system diseases such as multiple sclerosis (MS). In this paper, Brownian motion Hölder regularity functions (polynomial, periodic (sine), exponential) for 2D image, such as multifractal methods were applied to MR brain images, aiming to easily identify distressed regions, in MS patients. With these regions, we have proposed an MS classification based on the multifractal method by using the Self-Organizing Map (SOM) algorithm. Thus, we obtained a cluster analysis by identifying pixels from distressed regions in MR images through multifractal methods and by diagnosing subgroups of MS patients through artificial neural networks.

Immunopharmacological role of the leukotriene receptor antagonists and inhibitors of leukotrienes generating enzymes in multiple sclerosis.

PubMed

Mirshafiey, Abbas; Jadidi-Niaragh, Farhad

2010-06-01

Multiple sclerosis (MS) is a chronic inflammatory disease that involves central nervous system, and is generally associated with demyelination and axonal lesion. The effective factors for initiation of the inflammatory responses have not been known precisely so far. Leukotrienes (LTs) are inflammatory mediators with increased levels in the cerebrospinal fluid of MS patients and in experimental models of multiple sclerosis. Inhibition of LT receptors with specific antagonists can decrease inflammatory responses. In this review article we try to clarify the role of LT receptor antagonists and also inhibitors of enzymes which are involved in LTs generating pathway for treating multiple sclerosis as new targets for MS therapy. Moreover, we suggest that blockage of LT receptors by potent specific antagonists and/or agonists can be as a novel useful method in treatment of MS.

Expanding Role of T Cells in Human Autoimmune Diseases of the Central Nervous System

PubMed Central

Pilli, Deepti; Zou, Alicia; Tea, Fiona; Dale, Russell C.; Brilot, Fabienne

2017-01-01

It is being increasingly recognized that a dysregulation of the immune system plays a vital role in neurological disorders and shapes the treatment of the disease. Aberrant T cell responses, in particular, are key in driving autoimmunity and have been traditionally associated with multiple sclerosis. Yet, it is evident that there are other neurological diseases in which autoreactive T cells have an active role in pathogenesis. In this review, we report on the recent progress in profiling and assessing the functionality of autoreactive T cells in central nervous system (CNS) autoimmune disorders that are currently postulated to be primarily T cell driven. We also explore the autoreactive T cell response in a recently emerging group of syndromes characterized by autoantibodies against neuronal cell-surface proteins. Common methodology implemented in T cell biology is further considered as it is an important determinant in their detection and characterization. An improved understanding of the contribution of autoreactive T cells expands our knowledge of the autoimmune response in CNS disorders and can offer novel methods of therapeutic intervention. PMID:28638382

[Central nervous system vasculitis and of the peripheral nerves in the elderly].

PubMed

Boddaert, Jacques; Verny, Marc

2002-11-01

Vasculitis of the nervous system are rare in the elderly. When present, they may constitute an urgent diagnosis and a therapeutic emergency. Clinical expression is rich and without specificity. Atypical signs (unusual course of dementia, systemic signs) or atypical laboratory results (inflammatory syndrome) may suggest the diagnosis of vasculitis. However, as multiple comorbidity is the rule in elderly subjects, searching for intercurrent factors (e.g. atrial fibrilation due to infectious disease causing embolic stroke) may be more contributive than searching for proof of a rare disease (vasculitis) with invasive procedures in this population. Giant cell (temporal) arteritis is the only vasculitis specifically related with age; the vital prognosis of vision may be compromised. Corticosterid therapy must be instituted without delay. Periartritis nodosa begins in 30% of cases after 60 years of age. The clinical features are the same as in younger subjects. Other vasculidis are rare in the elderly. In absence of specific studies in this population, therapeutic protocols are the same as in younger subjects but may have to be adjusted.

The Therapeutic Potential of Insulin-Like Growth Factor-1 in Central Nervous System Disorders

PubMed Central

Costales, Jesse; Kolevzon, Alexander

2016-01-01

Central nervous system (CNS) development is a finely tuned process that relies on multiple factors and intricate pathways to ensure proper neuronal differentiation, maturation, and connectivity. Disruption of this process can cause significant impairments in CNS functioning and lead to debilitating disorders that impact motor and language skills, behavior, and cognitive functioning. Recent studies focused on understanding the underlying cellular mechanisms of neurodevelopmental disorders have identified a crucial role for insulin-like growth factor-1 (IGF-1) in normal CNS development. Work in model systems has demonstrated rescue of pathophysiological and behavioral abnormalities when IGF-1 is administered, and several clinical studies have shown promise of efficacy in disorders of the CNS, including autism spectrum disorder (ASD). In this review, we explore the molecular pathways and downstream effects of IGF-1 and summarize the results of completed and ongoing pre-clinical and clinical trials using IGF-1 as a pharmacologic intervention in various CNS disorders. This aim of this review is to provide evidence for the potential of IGF-1 as a treatment for neurodevelopmental disorders and ASD. PMID:26780584

Exogenous administration of Substance P enhances wound healing in a novel skin-injury model.

PubMed

Delgado, Angel V; McManus, Albert T; Chambers, James P

2005-04-01

Soft tissue injury accounts for approximately 44% of all wounds in both the military and civilian populations. Following injury to soft tissue, Substance P (SP) and other neuropeptides are released by cutaneous neurons and modulate the function of immunocompetent and inflammatory cells, as well as epithelial and endothelial cells. The interaction between these components of the nervous system and multiple target cells affecting cutaneous repair is of increasing interest. In this report, we describe the effects of SP on wound repair in a novel, laser-induced, skin-wound model. Gross and histologic examination of laser-induced injury revealed that exogenously administered SP affects wound healing via neurite outgrowth, in addition to adhesion molecule and neurokinin-1 receptor involvement in vivo. All SP effects were decreased by pretreatment with Spantide II, an SP antagonist. The elucidation of SP-mediating mechanisms is crucial to firmly establishing the involvement and interaction of the peripheral nervous system and the immune system in cutaneous repair. Findings presented here suggest that SP participates in the complex network of mediators involved in cutaneous inflammation and wound healing.

Classical Neurotransmitters and their Significance within the Nervous System.

ERIC Educational Resources Information Center

Veca, A.; Dreisbach, J. H.

1988-01-01

Describes some of the chemical compounds involved in the nervous system and their roles in transmitting nerve signals. Discusses acetylcholine, dopamine, norepinephrine, serotonin, histamine, glycine, glutemate, and gamma-aminobutyric acid and their effects within the nervous system. (CW)

Complex Homology and the Evolution of Nervous Systems

PubMed Central

Liebeskind, Benjamin J.; Hillis, David M.; Zakon, Harold H.; Hofmann, Hans A.

2016-01-01

We examine the complex evolution of animal nervous systems and discuss the ramifications of this complexity for inferring the nature of early animals. Although reconstructing the origins of nervous systems remains a central challenge in biology, and the phenotypic complexity of early animals remains controversial, a compelling picture is emerging. We now know that the nervous system and other key animal innovations contain a large degree of homoplasy, at least on the molecular level. Conflicting hypotheses about early nervous system evolution are due primarily to differences in the interpretation of this homoplasy. We highlight the need for explicit discussion of assumptions and discuss the limitations of current approaches for inferring ancient phenotypic states. PMID:26746806

Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-1-0586 TITLE: Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring PRINCIPAL...Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring 5a. CONTRACT NUMBER W81XWH-14-1-0586 5b. GRANT NUMBER W81XWH- 14-1-0586 5c...barriers that prevent the optimal delivery of biologics and cells to the injured nervous system . A significant problem is the formation of scar tissue

Peptide-gated ion channels and the simple nervous system of Hydra.

PubMed

Gründer, Stefan; Assmann, Marc

2015-02-15

Neurons either use electrical or chemical synapses to communicate with each other. Transmitters at chemical synapses are either small molecules or neuropeptides. After binding to their receptors, transmitters elicit postsynaptic potentials, which can either be fast and transient or slow and longer lasting, depending on the type of receptor. Fast transient potentials are mediated by ionotropic receptors and slow long-lasting potentials by metabotropic receptors. Transmitters and receptors are well studied for animals with a complex nervous system such as vertebrates and insects, but much less is known for animals with a simple nervous system like Cnidaria. As cnidarians arose early in animal evolution, nervous systems might have first evolved within this group and the study of neurotransmission in cnidarians might reveal an ancient mechanism of neuronal communication. The simple nervous system of the cnidarian Hydra extensively uses neuropeptides and, recently, we cloned and functionally characterized an ion channel that is directly activated by neuropeptides of the Hydra nervous system. These results demonstrate the existence of peptide-gated ion channels in Hydra, suggesting they mediate fast transmission in its nervous system. As related channels are also present in the genomes of the cnidarian Nematostella, of placozoans and of ctenophores, it should be considered that the early nervous systems of cnidarians and ctenophores have co-opted neuropeptides for fast transmission at chemical synapses. © 2015. Published by The Company of Biologists Ltd.

A Bending Willow Tree: A Japanese (Morita Therapy) Model of Human Nature and Client Change.

ERIC Educational Resources Information Center

Ishiyama, F. Ishu

2003-01-01

Japanese Morita therapy is discussed to highlight its culturally and theoretically unique perspectives on human nature and client change. Key features of this theory are: theory of the nervous trait; multiple-dimensional model of causes and treatment of nervous neurosis; theory of mental attachment; reframing anxiety into constructive desires; and…

Learning and Memory... and the Immune System

ERIC Educational Resources Information Center

Marin, Ioana; Kipnis, Jonathan

2013-01-01

The nervous system and the immune system are two main regulators of homeostasis in the body. Communication between them ensures normal functioning of the organism. Immune cells and molecules are required for sculpting the circuitry and determining the activity of the nervous system. Within the parenchyma of the central nervous system (CNS),…

High-Affinity Binding of Remyelinating Natural Autoantibodies to Myelin-Mimicking Lipid Bilayers Revealed by Nanohole Surface Plasmon Resonance

PubMed Central

Wittenberg, Nathan J.; Im, Hyungsoon; Xu, Xiaohua; Wootla, Bharath; Watzlawik, Jens; Warrington, Arthur E.; Rodriguez, Moses; Oh, Sang-Hyun

2012-01-01

Multiple sclerosis is a progressive neurological disorder that results in the degradation of myelin sheaths that insulate axons in the central nervous system. Therefore promotion of myelin repair is a major thrust of multiple sclerosis treatment research. Two mouse monoclonal natural autoantibodies, O1 and O4, promote myelin repair in several mouse models of multiple sclerosis. Natural autoantibodies are generally polyreactive and predominantly of the IgM isotype. The prevailing paradigm is that because they are polyreactive, these antibodies bind antigens with low affinities. Despite their wide use in neuroscience and glial cell research, however, the affinities and kinetic constants of O1 and O4 antibodies have not been measured to date. In this work, we developed a membrane biosensing platform based on surface plasmon resonance in gold nanohole arrays with a series of surface modification techniques to form myelin-mimicking lipid bilayer membranes to measure both the association and dissociation rate constants for O1 and O4 antibodies binding to their myelin lipid antigens. The ratio of rate constants shows that O1 and O4 bind to galactocerebroside and sulfated galactocerebroside, respectively, with unusually small apparent dissociation constants (KD ~0.9 nM) for natural autoantibodies. This is approximately one to two orders of magnitude lower than typically observed for the highest affinity natural autoantibodies. We propose that the unusually high affinity of O1 and O4 to their targets in myelin contributes to the mechanism by which they signal oligodendrocytes and induce central nervous system repair. PMID:22762372

What have we learned about GPER function in physiology and disease from knockout mice?

PubMed Central

Prossnitz, Eric R.; Hathaway, Helen J.

2015-01-01

Estrogens, predominantly 17β-estradiol, exert diverse effects throughout the body in both normal and patho-physiology, during development and in reproductive, metabolic, endocrine, cardiovascular, nervous, musculoskeletal and immune systems. Estrogen and its receptors also play important roles in carcinogenesis and therapy, particularly for breast cancer. In addition to the classical nuclear estrogen receptors (ERα and ERβ) that traditionally mediate predominantly genomic signaling, the G protein-coupled estrogen receptor GPER has become recognized as a critical mediator of rapid signaling in response to estrogen. Mouse models, and in particular knockout (KO) mice, represent an important approach to understand the functions of receptors in normal physiology and disease. Whereas ERα KO mice display multiple significant defects in reproduction and mammary gland development, ERβ KO phenotypes are more limited, and GPER KO exhibit no reproductive deficits. However, the study of GPER KO mice over the last six years has revealed that GPER deficiency results in multiple physiological alterations including obesity, cardiovascular dysfunction, insulin resistance and glucose intolerance. In addition, the lack of estrogen-mediated effects in numerous tissues of GPER KO mice, studied in vivo or ex vivo, including those of the cardiovascular, endocrine, nervous and immune systems, reveals GPER as a genuine mediator of estrogen action. Importantly, GPER KO mice have also revealed roles for GPER in breast carcinogenesis and metastasis. In combination with the supporting effects of GPER-selective ligands and GPER knockdown approaches, GPER KO mice demonstrate the therapeutic potential of targeting GPER activity in diseases as diverse as obesity, diabetes, multiple sclerosis, hypertension, atherosclerosis, myocardial infarction, stroke and cancer. PMID:26189910

40 CFR 721.72 - Hazard communication program.

Code of Federal Regulations, 2011 CFR

2011-07-01

... irritation. (ii) Respiratory complications. (iii) Central nervous system effects. (iv) Internal organ effects... irritation (B) Respiratory complications (C) Central nervous system effects (D) Internal organ effects (E... irritation (B) Respiratory complications (C) Central nervous system effects (D) Internal organ effects (E...

40 CFR 721.72 - Hazard communication program.

Code of Federal Regulations, 2010 CFR

2010-07-01

... irritation. (ii) Respiratory complications. (iii) Central nervous system effects. (iv) Internal organ effects... irritation (B) Respiratory complications (C) Central nervous system effects (D) Internal organ effects (E... irritation (B) Respiratory complications (C) Central nervous system effects (D) Internal organ effects (E...

76 FR 5711 - Bispyribac-sodium; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-02

...- sodium has shown no indications of central or peripheral nervous system toxicity in any study and does not appear to be structurally related to any other chemical that causes adverse nervous system effects... the nervous system is a target for [[Page 5715

40 CFR 721.72 - Hazard communication program.

Code of Federal Regulations, 2012 CFR

2012-07-01

... irritation. (ii) Respiratory complications. (iii) Central nervous system effects. (iv) Internal organ effects... irritation (B) Respiratory complications (C) Central nervous system effects (D) Internal organ effects (E... irritation (B) Respiratory complications (C) Central nervous system effects (D) Internal organ effects (E...

40 CFR 721.72 - Hazard communication program.

Code of Federal Regulations, 2014 CFR

2014-07-01

... irritation. (ii) Respiratory complications. (iii) Central nervous system effects. (iv) Internal organ effects... irritation (B) Respiratory complications (C) Central nervous system effects (D) Internal organ effects (E... irritation (B) Respiratory complications (C) Central nervous system effects (D) Internal organ effects (E...

40 CFR 721.72 - Hazard communication program.

Code of Federal Regulations, 2013 CFR

2013-07-01

... irritation. (ii) Respiratory complications. (iii) Central nervous system effects. (iv) Internal organ effects... irritation (B) Respiratory complications (C) Central nervous system effects (D) Internal organ effects (E... irritation (B) Respiratory complications (C) Central nervous system effects (D) Internal organ effects (E...

Using Ferumoxytol-Enhanced MRI to Measure Inflammation in Patients With Brain Tumors or Other Conditions of the CNS

ClinicalTrials.gov

2017-08-30

Brain Injury; Central Nervous System Degenerative Disorder; Central Nervous System Infectious Disorder; Central Nervous System Vascular Malformation; Hemorrhagic Cerebrovascular Accident; Ischemic Cerebrovascular Accident; Primary Brain Neoplasm; Brain Cancer; Brain Tumors

Natural History Study of Children With Metachromatic Leukodystrophy

ClinicalTrials.gov

2016-04-19

Lipid Metabolism Disorders; Metachromatic Leukodystrophy (MLD); Nervous System Diseases; Brain Diseases; Central Nervous System Diseases; Demyelinating Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Sphingolipidoses; Hereditary Central Nervous System Demyelinating Diseases; Metabolic Inborn Brain Diseases; Lysosomal Storage Diseases; Metabolic Diseases; Sulfatidosis

Metabolic Dysfunction and Peroxisome Proliferator-Activated Receptors (PPAR) in Multiple Sclerosis.

PubMed

Ferret-Sena, Véronique; Capela, Carlos; Sena, Armando

2018-06-01

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) probably caused, in most cases, by the interaction of genetic and environmental factors. This review first summarizes some clinical, epidemiological and pathological characteristics of MS. Then, the involvement of biochemical pathways is discussed in the development and repair of the CNS lesions and the immune dysfunction in the disease. Finally, the potential roles of peroxisome proliferator-activated receptors (PPAR) in MS are discussed. It is suggested that metabolic mechanisms modulated by PPAR provide a window to integrate the systemic and neurological events underlying the pathogenesis of the disease. In conclusion, the reviewed data highlight molecular avenues of understanding MS that may open new targets for improved therapies and preventive strategies for the disease.

Kalrn plays key roles within and outside of the nervous system.

PubMed

Mandela, Prashant; Yankova, Maya; Conti, Lisa H; Ma, Xin-Ming; Grady, James; Eipper, Betty A; Mains, Richard E

2012-11-01

The human KALRN gene, which encodes a complex, multifunctional Rho GDP/GTP exchange factor, has been linked to cardiovascular disease, psychiatric disorders and neurodegeneration. Examination of existing Kalrn knockout mouse models has focused only on neuronal phenotypes. However, Kalirin was first identified through its interaction with an enzyme involved in the synthesis and secretion of multiple bioactive peptides, and studies in C.elegans revealed roles for its orthologue in neurosecretion. We used a broad array of tests to evaluate the effects of ablating a single exon in the spectrin repeat region of Kalrn (KalSR(KO/KO)); transcripts encoding Kalrn isoforms containing only the second GEF domain can still be produced from the single remaining functional Kalrn promoter. As expected, KalSR(KO/KO) mice showed a decrease in anxiety-like behavior and a passive avoidance deficit. No changes were observed in prepulse inhibition of acoustic startle or tests of depression-like behavior. Growth rate, parturition and pituitary secretion of growth hormone and prolactin were deficient in the KalSR(KO/KO) mice. Based on the fact that a subset of Kalrn isoforms is expressed in mouse skeletal muscle and the observation that muscle function in C.elegans requires its Kalrn orthologue, KalSR(KO/KO) mice were evaluated in the rotarod and wire hang tests. KalSR(KO/KO) mice showed a profound decrease in neuromuscular function, with deficits apparent in KalSR(+/KO) mice; these deficits were not as marked when loss of Kalrn expression was restricted to the nervous system. Pre- and postsynaptic deficits in the neuromuscular junction were observed, along with alterations in sarcomere length. Many of the widespread and diverse deficits observed both within and outside of the nervous system when expression of Kalrn is eliminated may reflect its role in secretory granule function and its expression outside of the nervous system.

Kalrn plays key roles within and outside of the nervous system

PubMed Central

2012-01-01

Background The human KALRN gene, which encodes a complex, multifunctional Rho GDP/GTP exchange factor, has been linked to cardiovascular disease, psychiatric disorders and neurodegeneration. Examination of existing Kalrn knockout mouse models has focused only on neuronal phenotypes. However, Kalirin was first identified through its interaction with an enzyme involved in the synthesis and secretion of multiple bioactive peptides, and studies in C.elegans revealed roles for its orthologue in neurosecretion. Results We used a broad array of tests to evaluate the effects of ablating a single exon in the spectrin repeat region of Kalrn (KalSRKO/KO); transcripts encoding Kalrn isoforms containing only the second GEF domain can still be produced from the single remaining functional Kalrn promoter. As expected, KalSRKO/KO mice showed a decrease in anxiety-like behavior and a passive avoidance deficit. No changes were observed in prepulse inhibition of acoustic startle or tests of depression-like behavior. Growth rate, parturition and pituitary secretion of growth hormone and prolactin were deficient in the KalSRKO/KO mice. Based on the fact that a subset of Kalrn isoforms is expressed in mouse skeletal muscle and the observation that muscle function in C.elegans requires its Kalrn orthologue, KalSRKO/KO mice were evaluated in the rotarod and wire hang tests. KalSRKO/KO mice showed a profound decrease in neuromuscular function, with deficits apparent in KalSR+/KO mice; these deficits were not as marked when loss of Kalrn expression was restricted to the nervous system. Pre- and postsynaptic deficits in the neuromuscular junction were observed, along with alterations in sarcomere length. Conclusions Many of the widespread and diverse deficits observed both within and outside of the nervous system when expression of Kalrn is eliminated may reflect its role in secretory granule function and its expression outside of the nervous system. PMID:23116210

Nutritional and metabolic diseases involving the nervous system.

PubMed

Kopcha, M

1987-03-01

This article will discuss eight diseases that alter normal nervous system function: hypovitaminosis A, water deprivation/salt toxicity, ammonia toxicosis, hypomagnesemia, hypocalcemia, nervous ketosis, hepatoencephalopathy, and rumen metabolic acidosis.

The glia of the adult Drosophila nervous system

PubMed Central

Kremer, Malte C.; Jung, Christophe; Batelli, Sara; Rubin, Gerald M.

2017-01-01

Glia play crucial roles in the development and homeostasis of the nervous system. While the GLIA in the Drosophila embryo have been well characterized, their study in the adult nervous system has been limited. Here, we present a detailed description of the glia in the adult nervous system, based on the analysis of some 500 glial drivers we identified within a collection of synthetic GAL4 lines. We find that glia make up ∼10% of the cells in the nervous system and envelop all compartments of neurons (soma, dendrites, axons) as well as the nervous system as a whole. Our morphological analysis suggests a set of simple rules governing the morphogenesis of glia and their interactions with other cells. All glial subtypes minimize contact with their glial neighbors but maximize their contact with neurons and adapt their macromorphology and micromorphology to the neuronal entities they envelop. Finally, glial cells show no obvious spatial organization or registration with neuronal entities. Our detailed description of all glial subtypes and their regional specializations, together with the powerful genetic toolkit we provide, will facilitate the functional analysis of glia in the mature nervous system. GLIA 2017 GLIA 2017;65:606–638 PMID:28133822

Serum neuron specific enolase - a novel indicator for neuropsychiatric systemic lupus erythematosus?

PubMed

Hawro, T; Bogucki, A; Krupińska-Kun, M; Maurer, M; Woźniacka, A

2015-12-01

Neuropsychiatric (NP) lupus, a common manifestation of systemic lupus erythematosus (SLE), is still insufficiently understood, in part, because of the lack of specific biomarkers. Neuron specific enolase (NSE), an important neuronal glycolytic enzyme, shows increased serum levels following acute brain injury, and decreased serum levels in several chronic disorders of the nervous system, including multi infarct dementia, multiple sclerosis and depression. The aim of the study was to evaluate serum NSE levels in SLE patients with and without nervous system involvement, and in healthy controls, and to assess the correlation of NSE serum levels of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) with clinical parameters. The study comprised 47 SLE patients and 28 controls. SLE activity was assessed using the Systemic Lupus Activity Measure (SLAM). A neurologist and a psychiatrist examined all patients. NP involvement was diagnosed according to strict NPSLE criteria proposed by Ainiala and coworkers, as modification to American College of Rheumatology (ACR) nomenclature and case definitions. NSE serum levels were determined by use of an immunoassay. Mean NSE serum concentrations in patients with NPSLE were significantly lower than in non-NPSLE patients (6.3 ± 2.6 µg/L vs. 9.7 ± 3.3 µg/L, p < 0.01) and in controls (8.8 ± 3.3 µg/L, p < 0.05). There were significant negative correlations between NSE serum levels and SLE activity (r = -0.42, p < 0.05) and the number of NPSLE manifestations diagnosed (-0.37; p = 0.001). Decreased serum concentrations of NSE may reflect chronic neuronal damage with declined metabolism of the nervous tissue in patients with NPSLE. © The Author(s) 2015.

[Involvement of the peripheral nervous system in systemic connective tissue diseases: report on clinical cases].

PubMed

Kujawska-Danecka, Hanna; Masiak, Anna; Smoleńska, Zaneta; Zdrojewski, Zbigniew

2011-01-01

The peripheral nervous system is usually involved in the majority of systemic connective tissue diseases, particularly in systemic lupus erythematosus, Sjögren's syndrome, vasculitis and systemic sclerosis. The pathogenesis of lesions in the peripheral nervous system associated with the autoimmune process is complex and it appears that two mechanisms, immunological and ischemic, are of greatest importance. Structures of the nervous system may be damaged by several autoantibodies (e.g. antineuronal, anti-nerve growth factor, anti-neurotrophins), by cytotoxic effects ofproinflammatory cytokines and by activated cells of the immune system. Local ischemia and hypoxia of neurons caused by inflammation of vasa nervosum represents the second significant mechanism leading to damage of nerve fibres in the peripheral nervous system. We present 3 cases with involvement of the peripheral nervous system as a dominant feature in the clinical picture of systemic connective tissue diseases. Clinical conditions in which the peripheral nervous system is involved include peripheral sensory and sensorimotor polyneuropathy, mononeuropathies, cranial neuropathies, acute inflammatory demyelinating polyneuropathy (Guillian-Barré syndrome), chronic inflammatory demyelinating polyneuropathy, plexopathy, myasthenia gravis, and dysfunctions of the autonomic nervous system. The diagnosis is based on clinical symptoms reported by the patient and disclosed during neurologic examination. The importance of electrophysiologic tests is advocated. Selection of treatment depends on the patient's clinical condition, as well as on the clinical form and type of disease. Treatment relies principally on glucocorticosteroids, intravenous immunoglobulins, cyclophosphamide, and other immunosuppressive drugs. Plasmapheresis and rituximab are administered in severe cases. Rehabilitation of the patient appears to be an important element of therapy. Cases with neurologic symptoms as the first and often the sole manifestation of systemic connective tissue disease are particularly problematic requiring a multidimensional approach; their process of diagnosis and treatment is usually long.

P17.05 Epidemiology and clinical in patients with primary and secondary lymphomas with a nervous system condition in the South Central Hospital of High Specialty from PEMEX in Mexico

PubMed Central

Cordoba Mosqueda, M.; Guerra Mora, J.; Hernandez Resendiz, R.; Loya Aguilar, I.; Vicuña Gonzalez, R.; Ibarra de la Torre, A.; Garcia Gonzalez, U.

2016-01-01

Abstract Introduction: Primary lymphomas of the central nervous system are a type of Non Hodgkin Lymphoma with high morbidity and mortality. They are frequently associated with HIV infection, nevertheless the prevalence in non HIV patients has been tripled recently without any justified cause. In occasions it is difficult to identify the difference between primary and secondary origin in the central nervous system, this is crucial since the prognosis also changes. Method and Materials: Observational study with a range of patients from March 1999- March 2016 with reported diagnosis of Non Hodgkin Lymphoma with Central Nervous System involvement inside the electronic files of the South Central Hospital of High Specialty PEMEX. A statistical analysis is made through the SPSS Statistics of the Disease in this Institution program. Results: There were a total of 20 patients found with the diagnosis of Non Hodgkin Lymphoma with Central Nervous System involvement with a media of 57.7 ± 16 years of age, 60% males. 45% were classified as primary; multiple variables were analyzed such as the histological subtype from which the most common was Giant B cell types in a 40%. Within the symptoms the most common was headheach and pyramidal syndrome with 25%. At the time of diagnosis we found that with most prevalence ECOG of the population was of 1 reported case of 55 % of patients, nevertheless the survival rate after diagnosis had a global media of 40.3 ± 21 months, being of 56 months in secondary lymphoma and of 16 months in primary lymphoma, there were no significant statistical differences in both groups. Conclusions: The clinical and epidemiological characteristics in both groups were similar to the ones reported in the literature, nonetheless compared with the time of diagnosis based on the ECOG the overall rate of survival in both groups is low, which brings a great challenge for medical and surgical management. It is important to denote that the clinical scenario of this pathology is quite unspecific, giving a large range of differential diagnosis, therefore making it harder to diagnose and treatment.

75 FR 4571 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-28

... peripheral nervous systems. Researchers at the National Cancer Institute (``NCI'')-Frederick investigating genetic influences on cancer susceptibility of the nervous system have synthesized novel analogues of.... Applications: Therapies for tumors associated with NF1 (including brain and peripheral nervous system tumors...

Emergency Department Visits Involving Nonmedical Use of Central Nervous System Stimulants among Adults Aged 18 to 34 ...

MedlinePlus

... Emergency Department Visits Involving Nonmedical Use of Central Nervous System Stimulants among Adults Aged 18 to 34 Increased between 2005 and 2011 Central nervous system (CNS) stimulants include prescription drugs, like those used ...

Strategies for Enhanced Drug Delivery to the Central Nervous System

PubMed Central

Dwibhashyam, V. S. N. M.; Nagappa, A. N.

2008-01-01

Treating central nervous system diseases is very challenging because of the presence of a variety of formidable obstacles that impede drug delivery. Physiological barriers like the blood-brain barrier and blood-cerebrospinal fluid barrier as well as various efflux transporter proteins make the entry of drugs into the central nervous system very difficult. The present review provides a brief account of the blood brain barrier, the P-glycoprotein efflux and various strategies for enhancing drug delivery to the central nervous system. PMID:20046703

Radiation injury to the nervous system

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

Gutin, P.H.; Leibel, S.A.; Sneline, G.E.

1991-01-01

This book is designed to describe to the radiation biologist, radiation oncologist, neurologist, neurosurgeon, medical oncologist, and neuro-oncologist, the current state of knowledge about the tolerance of the nervous system to various kinds of radiation, the mechanisms of radiation injury, and how nervous system tolerance and injury are related to the more general problem of radiation damage to normal tissue of all types. The information collected here should stimulate interest in and facilitate the growing research effort into radiation injury to the nervous system.

Biomedical Science, Unit IV: The Nervous System in Health and Medicine. The Nervous System; Disorders of the Brain and Nervous System; Application of Computer Science to Diagnosis; Drugs and Pharmacology; The Human Senses; Electricity. Laboratory Manual. Revised Version, 1976.

ERIC Educational Resources Information Center

Biomedical Interdisciplinary Curriculum Project, Berkeley, CA.

Designed to accompany the student text on the nervous system, this manual presents laboratory activities dealing with concepts presented in the text. Thirty-seven activities are described. Four supplementary activities dealing with concepts in electricity are also included. Laboratory activities are divided into several parts, each part covering a…

Biomedical Science, Unit IV: The Nervous System in Health and Medicine. The Nervous System; Disorders of the Brain and Nervous System; Application of Computer Science to Diagnosis; Drugs and Pharmacology; The Human Senses; Electricity. Instructor's Manual. Revised Version, 1976.

ERIC Educational Resources Information Center

Biomedical Interdisciplinary Curriculum Project, Berkeley, CA.

This volume contains the lesson plans and appropriate teacher background material for a 37-lesson sequence on the nervous system in health and medicine. Additional material is provided for supplementary lessons on concepts of electricity. Associated material, contained in separate volumes, include a student text and a student laboratory manual.…

Pharmacotherapy for Adults with Tumors of the Central Nervous System

PubMed Central

Schor, Nina F.

2009-01-01

Tumors of the adult central nervous system are among the most common and most chemoresistant neoplasms. Malignant tumors of the brain and spinal cord collectively account for approximately 1.3% of all cancers and 2.2% of all cancer-related deaths. Novel pharmacological approaches to nervous system tumors are urgently needed. This review presents the current approaches and challenges to successful pharmacotherapy of adults with malignant tumors of the central nervous system and discusses novel approaches aimed at overcoming these challenges. PMID:19091301

Endocannabinoids in the Retina: From Marijuana to Neuroprotection

PubMed Central

Yazulla, Stephen

2008-01-01

The active component of the marijuana plant Cannabis sativa, Δ9-tetrahydrocannabinol (THC), produces numerous beneficial effects, including analgesia, appetite stimulation and nausea reduction, in addition to its psychotropic effects. THC mimics the action of endogenous fatty acid derivatives, referred to as endocannabinoids. The effects of THC and the endocannabinoids are mediated largely by metabotropic receptors that are distributed throughout the nervous and peripheral organ systems. There is great interest in endocannabinoids for their role in neuroplasticity as well as for therapeutic use in numerous conditions, including pain, stroke, cancer, obesity, osteoporosis, fertility, neurodegenerative diseases, multiple sclerosis, glaucoma and inflammatory diseases, among others. However, there has been relatively far less research on this topic in the eye and retina compared with the brain and other organ systems. The purpose of this review is to introduce the “cannabinergic” field to the retinal community. All of the fundamental work on cannabinoids has been performed in non-retinal preparations, necessitating extensive dependence on this literature for background. Happily, the retinal cannabinoid system has much in common with other regions of the central nervous system. For example, there is general agreement that cannabinoids suppress dopamine release and presynaptically reduce transmitter release from cones and bipolar cells. How these effects relate to light and dark adaptation, receptive field formation, temporal properties of ganglion cells or visual perception are unknown. The presence of multiple endocannabinoids, degradative enzymes with their bioactive metabolites, and receptors provides a broad spectrum of opportunities for basic research and to identify targets for therapeutic application to retinal diseases. PMID:18725316

Endocannabinoids in the retina: from marijuana to neuroprotection.

PubMed

Yazulla, Stephen

2008-09-01

The active component of the marijuana plant Cannabis sativa, Delta9-tetrahydrocannabinol (THC), produces numerous beneficial effects, including analgesia, appetite stimulation and nausea reduction, in addition to its psychotropic effects. THC mimics the action of endogenous fatty acid derivatives, referred to as endocannabinoids. The effects of THC and the endocannabinoids are mediated largely by metabotropic receptors that are distributed throughout the nervous and peripheral organ systems. There is great interest in endocannabinoids for their role in neuroplasticity as well as for therapeutic use in numerous conditions, including pain, stroke, cancer, obesity, osteoporosis, fertility, neurodegenerative diseases, multiple sclerosis, glaucoma and inflammatory diseases, among others. However, there has been relatively far less research on this topic in the eye and retina compared with the brain and other organ systems. The purpose of this review is to introduce the "cannabinergic" field to the retinal community. All of the fundamental works on cannabinoids have been performed in non-retinal preparations, necessitating extensive dependence on this literature for background. Happily, the retinal cannabinoid system has much in common with other regions of the central nervous system. For example, there is general agreement that cannabinoids suppress dopamine release and presynaptically reduce transmitter release from cones and bipolar cells. How these effects relate to light and dark adaptations, receptive field formation, temporal properties of ganglion cells or visual perception are unknown. The presence of multiple endocannabinoids, degradative enzymes with their bioactive metabolites, and receptors provides a broad spectrum of opportunities for basic research and to identify targets for therapeutic application to retinal diseases.

THE PURINERGIC NEUROTRANSMITTER REVISITED: A SINGLE SUBSTANCE OR MULTIPLE PLAYERS?

PubMed Central

Mutafova-Yambolieva, Violeta N.; Durnin, Leonie

2014-01-01

The past half century has witnessed tremendous advances in our understanding of extracellular purinergic signaling pathways. Purinergic neurotransmission, in particular, has emerged as a key contributor in the efficient control mechanisms in the nervous system. The identity of the purine neurotransmitter, however, remains controversial. Identifying it is difficult because purines are present in all cell types, have a large variety of cell sources, and are released via numerous pathways. Moreover, studies on purinergic neurotransmission have relied heavily on indirect measurements of integrated postjunctional responses that do not provide direct information for neurotransmitter identity. This paper discusses experimental support for adenosine 5′-triphosphate (ATP) as a neurotransmitter and recent evidence for possible contribution of other purines, in addition to or instead of ATP, in chemical neurotransmission in the peripheral, enteric and central nervous systems. Sites of release and action of purines in model systems such as vas deferens, blood vessels, urinary bladder and chromaffin cells are discussed. This is preceded by a brief discussion of studies demonstrating storage of purines in synaptic vesicles. We examine recent evidence for cell type targets (e.g., smooth muscle cells, interstitial cells, neurons and glia) for purine neurotransmitters in different systems. This is followed by brief discussion of mechanisms of terminating the action of purine neurotransmitters, including extracellular nucleotide hydrolysis and possible salvage and reuptake in the cell. The significance of direct neurotransmitter release measurements is highlighted. Possibilities for involvement of multiple purines (e.g., ATP, ADP, NAD+, ADP-ribose, adenosine, and diadenosine polyphosphates) in neurotransmission are considered throughout. PMID:24887688

Anteroposterior patterning in hemichordates and the origins of the chordate nervous system

NASA Technical Reports Server (NTRS)

Lowe, Christopher J.; Wu, Mike; Salic, Adrian; Evans, Louise; Lander, Eric; Stange-Thomann, Nicole; Gruber, Christian E.; Gerhart, John; Kirschner, Marc

2003-01-01

The chordate central nervous system has been hypothesized to originate from either a dorsal centralized, or a ventral centralized, or a noncentralized nervous system of a deuterostome ancestor. In an effort to resolve these issues, we examined the hemichordate Saccoglossus kowalevskii and studied the expression of orthologs of genes that are involved in patterning the chordate central nervous system. All 22 orthologs studied are expressed in the ectoderm in an anteroposterior arrangement nearly identical to that found in chordates. Domain topography is conserved between hemichordates and chordates despite the fact that hemichordates have a diffuse nerve net, whereas chordates have a centralized system. We propose that the deuterostome ancestor may have had a diffuse nervous system, which was later centralized during the evolution of the chordate lineage.

Complex Homology and the Evolution of Nervous Systems.

PubMed

Liebeskind, Benjamin J; Hillis, David M; Zakon, Harold H; Hofmann, Hans A

2016-02-01

We examine the complex evolution of animal nervous systems and discuss the ramifications of this complexity for inferring the nature of early animals. Although reconstructing the origins of nervous systems remains a central challenge in biology, and the phenotypic complexity of early animals remains controversial, a compelling picture is emerging. We now know that the nervous system and other key animal innovations contain a large degree of homoplasy, at least on the molecular level. Conflicting hypotheses about early nervous system evolution are due primarily to differences in the interpretation of this homoplasy. We highlight the need for explicit discussion of assumptions and discuss the limitations of current approaches for inferring ancient phenotypic states. Copyright © 2015. Published by Elsevier Ltd.

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.

Code of Federal Regulations, 2012 CFR

2012-10-01

... of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia virus is isolated from the central nervous system. Manifestations usually occur abruptly and may include fever... spinal cord (myelitis) such as paralysis or meningismus. Long term central nervous system impairments...

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.

Code of Federal Regulations, 2013 CFR

2013-10-01

... of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia virus is isolated from the central nervous system. Manifestations usually occur abruptly and may include fever... spinal cord (myelitis) such as paralysis or meningismus. Long term central nervous system impairments...

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.

Code of Federal Regulations, 2011 CFR

2011-10-01

... of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia virus is isolated from the central nervous system. Manifestations usually occur abruptly and may include fever... spinal cord (myelitis) such as paralysis or meningismus. Long term central nervous system impairments...

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.

Code of Federal Regulations, 2014 CFR

2014-10-01

... of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia virus is isolated from the central nervous system. Manifestations usually occur abruptly and may include fever... spinal cord (myelitis) such as paralysis or meningismus. Long term central nervous system impairments...

The octopus genome and the evolution of cephalopod neural and morphological novelties.

PubMed

Albertin, Caroline B; Simakov, Oleg; Mitros, Therese; Wang, Z Yan; Pungor, Judit R; Edsinger-Gonzales, Eric; Brenner, Sydney; Ragsdale, Clifton W; Rokhsar, Daniel S

2015-08-13

Coleoid cephalopods (octopus, squid and cuttlefish) are active, resourceful predators with a rich behavioural repertoire. They have the largest nervous systems among the invertebrates and present other striking morphological innovations including camera-like eyes, prehensile arms, a highly derived early embryogenesis and a remarkably sophisticated adaptive colouration system. To investigate the molecular bases of cephalopod brain and body innovations, we sequenced the genome and multiple transcriptomes of the California two-spot octopus, Octopus bimaculoides. We found no evidence for hypothesized whole-genome duplications in the octopus lineage. The core developmental and neuronal gene repertoire of the octopus is broadly similar to that found across invertebrate bilaterians, except for massive expansions in two gene families previously thought to be uniquely enlarged in vertebrates: the protocadherins, which regulate neuronal development, and the C2H2 superfamily of zinc-finger transcription factors. Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions. We identified hundreds of cephalopod-specific genes, many of which showed elevated expression levels in such specialized structures as the skin, the suckers and the nervous system. Finally, we found evidence for large-scale genomic rearrangements that are closely associated with transposable element expansions. Our analysis suggests that substantial expansion of a handful of gene families, along with extensive remodelling of genome linkage and repetitive content, played a critical role in the evolution of cephalopod morphological innovations, including their large and complex nervous systems.

38 CFR 4.88b - Schedule of ratings-infectious diseases, immune disorders and nutritional deficiencies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... disease 100 Thereafter rate residuals such as liver or spleen damage or central nervous system involvement... complications of nervous system, vascular system, eyes or ears. (See DC 7004, syphilitic heart disease, DC 8013... associated with central nervous system syphilis) 6311Tuberculosis, miliary: As active disease 100 Inactive...

38 CFR 4.88b - Schedule of ratings-infectious diseases, immune disorders and nutritional deficiencies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... disease 100 Thereafter rate residuals such as liver or spleen damage or central nervous system involvement... complications of nervous system, vascular system, eyes or ears. (See DC 7004, syphilitic heart disease, DC 8013... associated with central nervous system syphilis) 6311Tuberculosis, miliary: As active disease 100 Inactive...

38 CFR 4.88b - Schedule of ratings-infectious diseases, immune disorders and nutritional deficiencies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... disease 100 Thereafter rate residuals such as liver or spleen damage or central nervous system involvement... complications of nervous system, vascular system, eyes or ears. (See DC 7004, syphilitic heart disease, DC 8013... associated with central nervous system syphilis) 6311Tuberculosis, miliary: As active disease 100 Inactive...

38 CFR 4.88b - Schedule of ratings-infectious diseases, immune disorders and nutritional deficiencies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... disease 100 Thereafter rate residuals such as liver or spleen damage or central nervous system involvement... complications of nervous system, vascular system, eyes or ears. (See DC 7004, syphilitic heart disease, DC 8013... associated with central nervous system syphilis) 6311Tuberculosis, miliary: As active disease 100 Inactive...

38 CFR 4.88b - Schedule of ratings-infectious diseases, immune disorders and nutritional deficiencies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... disease 100 Thereafter rate residuals such as liver or spleen damage or central nervous system involvement... complications of nervous system, vascular system, eyes or ears. (See DC 7004, syphilitic heart disease, DC 8013... associated with central nervous system syphilis) 6311Tuberculosis, miliary: As active disease 100 Inactive...

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

PubMed Central

Bernstock, Joshua D.; Pluchino, Stefano

2015-01-01

Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one’s genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis. PMID:25802011

Fahr's Syndrome and Secondary Hypoparathyroidism.

PubMed

Dos Santos, Vitorino Modesta; Da Mata, Ana Medeiros De Farias; Ribeiro, Kelle Regina Alves; Calvo, Isadora Cartaxo De Sousa

2016-01-01

A typical case of Fahr's syndrome is described in a 76-year-old Brazilian female who underwent a total thyroidectomy three decades ago. Six years before the current admission, she started with generalized tonic-clonic seizures. Associated disorders involved extra-pyramidal, cognitive, nocturnal terror and mood changes. With suspicion of hypocalcemia due to secondary hypoparathyroidism, laboratory determinations confirmed the diagnoses. Furthermore, imaging studies of the central nervous system detected multiple calcifications, with characteristic distribution of Fahr's syndrome. Clinical management was successful.

Molecular Cloning of the Human Genes(s) Directing the Synthesis of Nervous System Cholinesterases.

DTIC Science & Technology

1985-12-01

anesthesia (1) This clinical om~pli- cation ould be diagnosed by a rapid method to detect such deficiencies or preventeod by injecting, as a scavenger...the enzyme could hence be employed to develop a method for the clinical diagnosis of this dims. Thus both for basic research and multiple clinical...translation, crossed imunoelec- trophoresis, and atoiradiogar t. This approach gives a method of high sensitivity and low back . It has the advantage over

Associated malformations among infants with anophthalmia and microphthalmia.

PubMed

Stoll, Claude; Dott, Beatrice; Alembik, Yves; Roth, Marie-Paule

2012-03-01

Infants with anophthalmia and microphthalmia frequently have other associated congenital anomalies. The reported frequency and types of associated malformations vary among different studies. The purpose of this investigation was to assess the frequency and types of associated malformations among infants with anophthalmia and microphthalmia in a geographically well defined population from 1979 to 2004 of 346,831 consecutive births. Of the 87 infants with anophthalmia and microphthalmia born during this period (prevalence at birth, 2.5 per 10,000), 90% had associated malformations. Infants with associated malformation were divided into recognizable conditions (22 infants [25%] with chromosomal and 15 infants [17%] with nonchromosomal conditions), and nonrecognizable conditions (41 infants [47%] with multiple malformations). Trisomies 13 and 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, CHARGE syndrome, Meckel-Gruber syndrome, and VACTERL association were most often present in recognizable nonchromosomal conditions. Malformations in the musculoskeletal, cardiovascular, and central nervous systems were the most common other anomalies in infants with multiple malformations and nonrecognizable conditions. The frequency of associated malformations in infants with anophthalmia or microphthalmia emphasizes the need for a thorough investigation of these infants. Routine screening for other malformations-especially musculoskeletal, cardiac, and central nervous system anomalies-may need to be considered in infants with anophthalmia or microphthalmia, and referral of these infants for genetics evaluation and counseling seems warranted. Copyright © 2012 Wiley Periodicals, Inc.

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system.

PubMed

Kim, Hee Jin; Kim, Pitna; Shin, Chan Young

2013-03-01

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng's therapeutic effects. These include Alzheimer's disease, Parkinson's disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng.

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system

PubMed Central

Kim, Hee Jin; Kim, Pitna; Shin, Chan Young

2013-01-01

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng’s therapeutic effects. These include Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng. PMID:23717153

The nature of the autonomic dysfunction in multiple system atrophy

NASA Technical Reports Server (NTRS)

Parikh, Samir M.; Diedrich, Andre; Biaggioni, Italo; Robertson, David

2002-01-01

The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

Vestibular system: the many facets of a multimodal sense.

PubMed

Angelaki, Dora E; Cullen, Kathleen E

2008-01-01

Elegant sensory structures in the inner ear have evolved to measure head motion. These vestibular receptors consist of highly conserved semicircular canals and otolith organs. Unlike other senses, vestibular information in the central nervous system becomes immediately multisensory and multimodal. There is no overt, readily recognizable conscious sensation from these organs, yet vestibular signals contribute to a surprising range of brain functions, from the most automatic reflexes to spatial perception and motor coordination. Critical to these diverse, multimodal functions are multiple computationally intriguing levels of processing. For example, the need for multisensory integration necessitates vestibular representations in multiple reference frames. Proprioceptive-vestibular interactions, coupled with corollary discharge of a motor plan, allow the brain to distinguish actively generated from passive head movements. Finally, nonlinear interactions between otolith and canal signals allow the vestibular system to function as an inertial sensor and contribute critically to both navigation and spatial orientation.

Monitoring the autonomic nervous activity as the objective evaluation of music therapy for severely and multiply disabled children.

PubMed

Orita, Makiko; Hayashida, Naomi; Shinkawa, Tetsuko; Kudo, Takashi; Koga, Mikitoshi; Togo, Michita; Katayama, Sotetsu; Hiramatsu, Kozaburo; Mori, Shunsuke; Takamura, Noboru

2012-07-01

Severely and multiply disabled children (SMDC) are frequently affected in more than one area of development, resulting in multiple disabilities. The aim of the study was to evaluate the efficacy of music therapy in SMDC using monitoring changes in the autonomic nervous system, by the frequency domain analysis of heart rate variability. We studied six patients with SMDC (3 patients with cerebral palsy, 1 patient with posttraumatic syndrome after head injury, 1 patient with herpes encephalitis sequelae, and 1 patient with Lennox-Gastaut syndrome characterized by frequent seizures, developmental delay and psychological and behavioral problems), aged 18-26 (mean 22.5 ± 3.5). By frequency domain method using electrocardiography, we measured the high frequency (HF; with a frequency ranging from 0.15 to 0.4 Hz), which represents parasympathetic activity, the low frequency/high frequency ratio, which represents sympathetic activity between the sympathetic and parasympathetic activities, and heart rate. A music therapist performed therapy to all patients through the piano playing for 50 min. We monitored each study participant for 150 min before therapy, 50 min during therapy, and 10 min after therapy. Interestingly, four of 6 patients showed significantly lower HF components during music therapy than before therapy, suggesting that these four patients might react to music therapy through the suppression of parasympathetic nervous activities. Thus, music therapy can suppress parasympathetic nervous activities in some patients with SMDC. The monitoring changes in the autonomic nervous activities could be a powerful tool for the objective evaluation of music therapy in patients with SMDC.

Neuromorphic neural interfaces: from neurophysiological inspiration to biohybrid coupling with nervous systems

NASA Astrophysics Data System (ADS)

Broccard, Frédéric D.; Joshi, Siddharth; Wang, Jun; Cauwenberghs, Gert

2017-08-01

Objective. Computation in nervous systems operates with different computational primitives, and on different hardware, than traditional digital computation and is thus subjected to different constraints from its digital counterpart regarding the use of physical resources such as time, space and energy. In an effort to better understand neural computation on a physical medium with similar spatiotemporal and energetic constraints, the field of neuromorphic engineering aims to design and implement electronic systems that emulate in very large-scale integration (VLSI) hardware the organization and functions of neural systems at multiple levels of biological organization, from individual neurons up to large circuits and networks. Mixed analog/digital neuromorphic VLSI systems are compact, consume little power and operate in real time independently of the size and complexity of the model. Approach. This article highlights the current efforts to interface neuromorphic systems with neural systems at multiple levels of biological organization, from the synaptic to the system level, and discusses the prospects for future biohybrid systems with neuromorphic circuits of greater complexity. Main results. Single silicon neurons have been interfaced successfully with invertebrate and vertebrate neural networks. This approach allowed the investigation of neural properties that are inaccessible with traditional techniques while providing a realistic biological context not achievable with traditional numerical modeling methods. At the network level, populations of neurons are envisioned to communicate bidirectionally with neuromorphic processors of hundreds or thousands of silicon neurons. Recent work on brain-machine interfaces suggests that this is feasible with current neuromorphic technology. Significance. Biohybrid interfaces between biological neurons and VLSI neuromorphic systems of varying complexity have started to emerge in the literature. Primarily intended as a computational tool for investigating fundamental questions related to neural dynamics, the sophistication of current neuromorphic systems now allows direct interfaces with large neuronal networks and circuits, resulting in potentially interesting clinical applications for neuroengineering systems, neuroprosthetics and neurorehabilitation.

46 CFR Appendix C to Subpart C of... - Medical Surveillance Guidelines for Benzene

Code of Federal Regulations, 2014 CFR

2014-10-01

... depression of the hematopoietic system, pancytopenia, aplastic anemia, and leukemia. Inhalation of high concentrations may affect the functioning of the central nervous system. Aspiration of small amounts of liquid... an initial stimulatory effect on the central nervous system characterized by exhilaration, nervous...

46 CFR Appendix C to Subpart C to... - Medical Surveillance Guidelines for Benzene

Code of Federal Regulations, 2011 CFR

2011-10-01

... depression of the hematopoietic system, pancytopenia, aplastic anemia, and leukemia. Inhalation of high concentrations may affect the functioning of the central nervous system. Aspiration of small amounts of liquid... an initial stimulatory effect on the central nervous system characterized by exhilaration, nervous...

46 CFR Appendix C to Subpart C of... - Medical Surveillance Guidelines for Benzene

Code of Federal Regulations, 2013 CFR

2013-10-01

... depression of the hematopoietic system, pancytopenia, aplastic anemia, and leukemia. Inhalation of high concentrations may affect the functioning of the central nervous system. Aspiration of small amounts of liquid... an initial stimulatory effect on the central nervous system characterized by exhilaration, nervous...

46 CFR Appendix C to Subpart C of... - Medical Surveillance Guidelines for Benzene

Code of Federal Regulations, 2012 CFR

2012-10-01

... depression of the hematopoietic system, pancytopenia, aplastic anemia, and leukemia. Inhalation of high concentrations may affect the functioning of the central nervous system. Aspiration of small amounts of liquid... an initial stimulatory effect on the central nervous system characterized by exhilaration, nervous...

Extraversion, Neuroticism and Strength of the Nervous System

ERIC Educational Resources Information Center

Frigon, Jean-Yves

1976-01-01

The hypothesized identity of the dimensions of extraversion-introversion and strength of the nervous system was tested on four groups of nine subjects (neurotic extraverts, stable extraverts, neurotic introverts, stable introverts). Strength of the subjects' nervous system was estimated using the electroencephalographic (EEG) variant of extinction…

Multiple System Atrophy: An Oligodendroglioneural Synucleinopathy1

PubMed Central

Jellinger, Kurt A.

2017-01-01

Multiple system atrophy (MSA) is an orphan, fatal, adult-onset neurodegenerative disorder of uncertain etiology that is clinically characterized by various combinations of parkinsonism, cerebellar, autonomic, and motor dysfunction. MSA is an α-synucleinopathy with specific glioneuronal degeneration involving striatonigral, olivopontocerebellar, and autonomic nervous systems but also other parts of the central and peripheral nervous systems. The major clinical variants correlate with the morphologic phenotypes of striatonigral degeneration (MSA-P) and olivopontocerebellar atrophy (MSA-C). While our knowledge of the molecular pathogenesis of this devastating disease is still incomplete, updated consensus criteria and combined fluid and imaging biomarkers have increased its diagnostic accuracy. The neuropathologic hallmark of this unique proteinopathy is the deposition of aberrant α-synuclein in both glia (mainly oligodendroglia) and neurons forming glial and neuronal cytoplasmic inclusions that cause cell dysfunction and demise. In addition, there is widespread demyelination, the pathogenesis of which is not fully understood. The pathogenesis of MSA is characterized by propagation of misfolded α-synuclein from neurons to oligodendroglia and cell-to-cell spreading in a “prion-like” manner, oxidative stress, proteasomal and mitochondrial dysfunction, dysregulation of myelin lipids, decreased neurotrophic factors, neuroinflammation, and energy failure. The combination of these mechanisms finally results in a system-specific pattern of neurodegeneration and a multisystem involvement that are specific for MSA. Despite several pharmacological approaches in MSA models, addressing these pathogenic mechanisms, no effective neuroprotective nor disease-modifying therapeutic strategies are currently available. Multidisciplinary research to elucidate the genetic and molecular background of the deleterious cycle of noxious processes, to develop reliable biomarkers and targets for effective treatment of this hitherto incurable disorder is urgently needed. PMID:28984582

Multiple Spatial Coherence Resonances and Spatial Patterns in a Noise-Driven Heterogeneous Neuronal Network

NASA Astrophysics Data System (ADS)

Li, Yu-Ye; Ding, Xue-Li

2014-12-01

Heterogeneity of the neurons and noise are inevitable in the real neuronal network. In this paper, Gaussian white noise induced spatial patterns including spiral waves and multiple spatial coherence resonances are studied in a network composed of Morris—Lecar neurons with heterogeneity characterized by parameter diversity. The relationship between the resonances and the transitions between ordered spiral waves and disordered spatial patterns are achieved. When parameter diversity is introduced, the maxima of multiple resonances increases first, and then decreases as diversity strength increases, which implies that the coherence degrees induced by noise are enhanced at an intermediate diversity strength. The synchronization degree of spatial patterns including ordered spiral waves and disordered patterns is identified to be a very low level. The results suggest that the nervous system can profit from both heterogeneity and noise, and the multiple spatial coherence resonances are achieved via the emergency of spiral waves instead of synchronization patterns.

76 FR 18915 - Ethiprole; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-06

... homeostasis and the developing nervous system in the young is not available. Based on a battery of... of the nervous system, the Agency is requiring a developmental thyroid toxicity study to assess for... nervous system, the Agency is requiring the developmental thyroid toxicity study in lieu of the DNT. iii...

75 FR 10867 - Determinations Concerning Illnesses Discussed in the Institute of Medicine Report on Gulf War and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-09

... cancer; nervous system disease; reproductive or developmental dysfunction; non-malignant respiratory... nervous system cancers, stomach cancer, prostatic cancer and testicular cancer. The non-malignant diseases... and bladder cancer exists. G. Brain and Other Central Nervous System Cancers Of the 20 published...

75 FR 37301 - Exempt Chemical Mixtures Containing Gamma-Butyrolactone

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-29

... their central nervous system (CNS) depressant effect. An overdose from GBL or GHB may result in... the central nervous system that is substantially similar to or greater than the stimulant, depressant, or hallucinogenic effect on the central nervous system of a controlled substance in schedule I or II...

77 FR 65582 - Pfizer Therapeutic Research, Pfizer Worldwide Reasearch & Development Division, Formerly Known as...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-29

..., Central Nervous System Research Unit (Currently Known as Neuroscience Research Unit), Global External... as Warner Lambert Company, Central Nervous System Research Unit, Global External Supply Department... Central Nervous System Research Unit was renamed the Neuroscience Research Unit. In order to ensure proper...

76 FR 44595 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug... Committee: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee...

Marital Conflict and Growth in Children's Internalizing Symptoms: The Role of Autonomic Nervous System Activity

ERIC Educational Resources Information Center

El-Sheikh, Mona; Keiley, Margaret; Erath, Stephen; Dyer, W. Justin

2013-01-01

We assessed trajectories of children's internalizing symptoms, indexed through anxiety and depression, with a focus on the role of interactions between interparental marital conflict, children's sympathetic nervous system activity indexed by skin conductance level (SCL), and parasympathetic nervous system activity indexed by respiratory sinus…

Mitochondria in the nervous system: From health to disease, part II.

PubMed

Carrì, Maria Teresa; Polster, Brian M; Beart, Philip M

2018-04-10

In Part II of this Special Issue on "Mitochondria in the Nervous System: From Health to Disease", the editors bring together more reviews and original articles from researchers in the field of mitochondrial metabolism in the healthy and diseased nervous system. Subjects span from basic mitochondrial physiology to papers on mitochondrial dynamics and to those altered states of the nervous system that can be considered "mitopathologies". Finally, a few papers approach aspects of mitochondrial biology linked to the feasibility and validity of a mitochondrial therapy. Copyright © 2018. Published by Elsevier Ltd.

Diagnosis abnormalities of limb movement in disorders of the nervous system

NASA Astrophysics Data System (ADS)

Tymchik, Gregory S.; Skytsiouk, Volodymyr I.; Klotchko, Tatiana R.; Bezsmertna, Halyna; Wójcik, Waldemar; Luganskaya, Saule; Orazbekov, Zhassulan; Iskakova, Aigul

2017-08-01

The paper deals with important issues of diagnosis early signs of diseases of the nervous system, including Parkinson's disease and other specific diseases. Small quantities of violation trajectory of spatial movement of the extremities of human disease at the primary level as the most appropriate features are studied. In modern medical practice is very actual the control the emergence of diseases of the nervous system, including Parkinson's disease. In work a model limbs with six rotational kinematic pairs for diagnosis of early signs of diseases of the nervous system is considered. subject.

Understanding the mind of a worm: hierarchical network structure underlying nervous system function in C. elegans.

PubMed

Chatterjee, Nivedita; Sinha, Sitabhra

2008-01-01

The nervous system of the nematode C. elegans provides a unique opportunity to understand how behavior ('mind') emerges from activity in the nervous system ('brain') of an organism. The hermaphrodite worm has only 302 neurons, all of whose connections (synaptic and gap junctional) are known. Recently, many of the functional circuits that make up its behavioral repertoire have begun to be identified. In this paper, we investigate the hierarchical structure of the nervous system through k-core decomposition and find it to be intimately related to the set of all known functional circuits. Our analysis also suggests a vital role for the lateral ganglion in processing information, providing an essential connection between the sensory and motor components of the C. elegans nervous system.

Towards sensor array materials: can failure be delayed?

PubMed Central

Mekid, Samir; Saheb, Nouari; Khan, Shafique M A; Qureshi, Khurram K

2015-01-01

Further to prior development in enhancing structural health using smart materials, an innovative class of materials characterized by the ability to feel senses like humans, i.e. ‘nervous materials’, is discussed. Designed at all scales, these materials will enhance personnel and public safety, and secure greater reliability of products. Materials may fail suddenly, but any system wishes that failure is known in good time and delayed until safe conditions are reached. Nervous materials are expected to be the solution to this statement. This new class of materials is based on the novel concept of materials capable of feeling multiple structural and external stimuli, e.g. stress, force, pressure and temperature, while feeding information back to a controller for appropriate real-time action. The strain–stress state is developed in real time with the identified and characterized source of stimulus, with optimized time response to retrieve initial specified conditions, e.g. shape and strength. Sensors are volumetrically embedded and distributed, emulating the human nervous system. Immediate applications are in aircraft, cars, nuclear energy and robotics. Such materials will reduce maintenance costs, detect initial failures and delay them with self-healing. This article reviews the common aspects and challenges surrounding this new class of materials with types of sensors to be embedded seamlessly or inherently, including appropriate embedding manufacturing techniques with modeling and simulation methods. PMID:27877794

Towards sensor array materials: can failure be delayed?

NASA Astrophysics Data System (ADS)

Mekid, Samir; Saheb, Nouari; Khan, Shafique M. A.; Qureshi, Khurram K.

2015-06-01

Further to prior development in enhancing structural health using smart materials, an innovative class of materials characterized by the ability to feel senses like humans, i.e. ‘nervous materials’, is discussed. Designed at all scales, these materials will enhance personnel and public safety, and secure greater reliability of products. Materials may fail suddenly, but any system wishes that failure is known in good time and delayed until safe conditions are reached. Nervous materials are expected to be the solution to this statement. This new class of materials is based on the novel concept of materials capable of feeling multiple structural and external stimuli, e.g. stress, force, pressure and temperature, while feeding information back to a controller for appropriate real-time action. The strain-stress state is developed in real time with the identified and characterized source of stimulus, with optimized time response to retrieve initial specified conditions, e.g. shape and strength. Sensors are volumetrically embedded and distributed, emulating the human nervous system. Immediate applications are in aircraft, cars, nuclear energy and robotics. Such materials will reduce maintenance costs, detect initial failures and delay them with self-healing. This article reviews the common aspects and challenges surrounding this new class of materials with types of sensors to be embedded seamlessly or inherently, including appropriate embedding manufacturing techniques with modeling and simulation methods.

General pharmacology of loracarbef in animals.

PubMed

Shetler, T; Bendele, A; Buening, M; Clemens, J; Colbert, W; Deldar, A; Helton, D; McGrath, J; Shannon, H; Turk, J

1993-01-01

Loracarbef ((6R, 7S)-7-[(R)-2-amino-2-phenyl-acetamido]-3-chloro-8-oxo-1- azabicyclo [4.2.0]oct-2-ene-2-carboxylic acid, monohydrate, LY 163892, CAS 121961-22-6) is a carbacephem antibiotic targeted for use in the treatment of infectious disease. The potential pharmacological effects of this agent were examined on cardiovascular, respiratory, gastrointestinal, central nervous and autonomic nervous systems. Also examined were local anesthetic activity, effects on platelet aggregation, circulating blood glucose, primary antibody production, renal function, blood coagulation, ocular irritation, and the acute inflammatory response. Doses of 100, 1000, and 2000 mg/kg given by the oral route were selected for most in vivo studies. Concentrations up to 3 x 10(-3) mol/l were used in vitro. Loracarbef was essentially inactive in the tests of central and autonomic nervous system function, platelet aggregation, renal function, blood hemolysis, primary antibody production, blood coagulation, and ocular irritation. It had no local anesthetic activity. At high oral or intravenous doses, representing significant multiples of the therapeutic dose, loracarbef caused changes in gastrointestinal (decrease in gastric acid production and gastric fluid volume; increased biliary output), cardiovascular (increased mean pressure, cardiac output, heart rate, and femoral flow), blood glucose (increased glucose levels), and anti-inflammatory tests (suppressed acute inflammatory response). In summary, loracarbef exhibited minimal activity in these pharmacodynamic studies. These results indicate loracarbef has a low potential to produce adverse effects at therapeutic doses.

Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System.

PubMed

Wehrwein, Erica A; Orer, Hakan S; Barman, Susan M

2016-06-13

Comprised of the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system, the autonomic nervous system (ANS) provides the neural control of all parts of the body except for skeletal muscles. The ANS has the major responsibility to ensure that the physiological integrity of cells, tissues, and organs throughout the entire body is maintained (homeostasis) in the face of perturbations exerted by both the external and internal environments. Many commonly prescribed drugs, over-the-counter drugs, toxins, and toxicants function by altering transmission within the ANS. Autonomic dysfunction is a signature of many neurological diseases or disorders. Despite the physiological relevance of the ANS, most neuroscience textbooks offer very limited coverage of this portion of the nervous system. This review article provides both historical and current information about the anatomy, physiology, and pharmacology of the sympathetic and parasympathetic divisions of the ANS. The ultimate aim is for this article to be a valuable resource for those interested in learning the basics of these two components of the ANS and to appreciate its importance in both health and disease. Other resources should be consulted for a thorough understanding of the third division of the ANS, the enteric nervous system. © 2016 American Physiological Society. Compr Physiol 6:1239-1278, 2016. Copyright © 2016 John Wiley & Sons, Inc.

Mutations in spalt cause a severe but reversible neurodegenerative phenotype in the embryonic central nervous system of Drosophila melanogaster.

PubMed

Cantera, Rafael; Lüer, Karin; Rusten, Tor Erik; Barrio, Rosa; Kafatos, Fotis C; Technau, Gerhard M

2002-12-01

The gene spalt is expressed in the embryonic central nervous system of Drosophila melanogaster but its function in this tissue is still unknown. To investigate this question, we used a combination of techniques to analyse spalt mutant embryos. Electron microscopy showed that in the absence of spalt, the central nervous system cells are separated by enlarged extracellular spaces populated by membranous material at 60% of embryonic development. Surprisingly, the central nervous system from slightly older embryos (80% of development) exhibited almost wild-type morphology. An extensive survey by laser confocal microscopy revealed that the spalt mutant central nervous system has abnormal levels of particular cell adhesion and cytoskeletal proteins. Time-lapse analysis of neuronal differentiation in vitro, lineage analysis and transplantation experiments confirmed that the mutation causes cytoskeletal and adhesion defects. The data indicate that in the central nervous system, spalt operates within a regulatory pathway which influences the expression of the beta-catenin Armadillo, its ligand N-Cadherin, Notch, and the cell adhesion molecules Neuroglian, Fasciclin 2 and Fasciclin 3. Effects on the expression of these genes are persistent but many morphological aspects of the phenotype are transient, leading to the concept of sequential redundancy for stable organisation of the central nervous system.

Degenerative disease affecting the nervous system.

PubMed

Eadie, M J

1974-03-01

The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body. Copyright © 1974 Australian Physiotherapy Association. Published by . All rights reserved.

New tools for the analysis of glial cell biology in Drosophila.

PubMed

Awasaki, Takeshi; Lee, Tzumin

2011-09-01

Because of its genetic, molecular, and behavioral tractability, Drosophila has emerged as a powerful model system for studying molecular and cellular mechanisms underlying the development and function of nervous systems. The Drosophila nervous system has fewer neurons and exhibits a lower glia:neuron ratio than is seen in vertebrate nervous systems. Despite the simplicity of the Drosophila nervous system, glial organization in flies is as sophisticated as it is in vertebrates. Furthermore, fly glial cells play vital roles in neural development and behavior. In addition, powerful genetic tools are continuously being created to explore cell function in vivo. In taking advantage of these features, the fly nervous system serves as an excellent model system to study general aspects of glial cell development and function in vivo. In this article, we review and discuss advanced genetic tools that are potentially useful for understanding glial cell biology in Drosophila. Copyright © 2011 Wiley-Liss, Inc.

The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

PubMed

Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

2017-02-01

Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central nervous system positivity in T-cell acute lymphoblastic leukemia (odds ratio=11.00, 95% confidence interval, 2.00-60.62). We propose zeta-chain-associated protein kinase 70, CCR7 and CXCR4 as markers of central nervous system infiltration in acute lymphoblastic leukemia warranting prospective investigation. Copyright© Ferrata Storti Foundation.

Feasibility of Cell Therapy in Multiple Sclerosis: A Systematic Review of 83 Studies

PubMed Central

Ardeshiry lajimi, Abdolreza; Hagh, Majid Farshdousti; Saki, Najmaldin; Mortaz, Esmaeil; Soleimani, Masoud; Rahim, Fakher

2013-01-01

Multiple Sclerosis is an inflammatory disease of the central nervous system in which T cells experience a second phase of activation, which ultimately leads to axonal demyelination and neurological disability. The recent advances in stem cell therapies may serve as potential treatments for neurological disorders. There are broad types of stem cells such as neural, embryonic, mesenchymal and hematopoietic stem cells with unprecedented hope in treating many debilitating diseases. In this paper we will review the substantial literature regarding experimental and clinical use of these stem cells and possible mechanisms in the treatment of MS. These results may pave the road for the utilization of stem cells for the treatment of MS. PMID:24505515

Environmental Risk Factors for Multiple Sclerosis: A Review with a Focus on Molecular Mechanisms

PubMed Central

O’Gorman, Cullen; Lucas, Robyn; Taylor, Bruce

2012-01-01

Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system commonly affecting young adults. Pathologically, there are patches of inflammation (plaques) with demyelination of axons and oligodendrocyte loss. There is a global latitude gradient in MS prevalence, and incidence of MS is increasing (particularly in females). These changes suggest a major role for environmental factors in causation of disease. We have reviewed the evidence and potential mechanisms of action for three exposures: vitamin D, Epstein Barr virus and cigarette smoking. Recent advances supporting gene-environment interactions are reviewed. Further research is needed to establish mechanisms of causality in humans and to explore preventative strategies. PMID:23109880

Single nucleotide polymorphisms in multiple sclerosis: disease susceptibility and treatment response biomarkers.

PubMed

Pravica, Vera; Popadic, Dusan; Savic, Emina; Markovic, Milos; Drulovic, Jelena; Mostarica-Stojkovic, Marija

2012-04-01

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by unpredictable and variable clinical course. Etiology of MS involves both genetic and environmental factors. New technologies identified genetic polymorphisms associated with MS susceptibility among which immunologically relevant genes are significantly overrepresented. Although individual genes contribute only a small part to MS susceptibility, they might be used as biomarkers, thus helping to identify accurate diagnosis, predict clinical disease course and response to therapy. This review focuses on recent progress in research on MS genetics with special emphasis on the possibility to use single nucleotide polymorphism of candidate genes as biomarkers of susceptibility to disease and response to therapy.

Inflammation and therapeutic vaccination in CNS diseases

NASA Astrophysics Data System (ADS)

Weiner, Howard L.; Selkoe, Dennis J.

2002-12-01

The spectrum of inflammatory diseases of the central nervous system has been steadily expanding from classical autoimmune disorders such as multiple sclerosis to far more diverse diseases. Evidence now suggests that syndromes such as Alzheimer's disease and stroke have important inflammatory and immune components and may be amenable to treatment by anti-inflammatory and immunotherapeutic approaches. The notion of 'vaccinating' individuals against a neurodegenerative disorder such as Alzheimer's disease is a marked departure from classical thinking about mechanism and treatment, and yet therapeutic vaccines for both Alzheimer's disease and multiple sclerosis have been validated in animal models and are in the clinic. Such approaches, however, have the potential to induce unwanted inflammatory responses as well as to provide benefit.

Dysregulated MicroRNA Involvement in Multiple Sclerosis by Induction of T Helper 17 Cell Differentiation

PubMed Central

Chen, Chen; Zhou, Yifan; Wang, Jingqi; Yan, Yaping; Peng, Lisheng; Qiu, Wei

2018-01-01

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Growing evidence has proven that T helper 17 (Th17) cells are one of the regulators of neuroinflammation mechanisms in MS disease. Researchers have demonstrated that some microRNAs (miRNAs) are associated with disease activity and duration, even with different MS patterns. miRNAs regulate CD4+ T cells to differentiate toward various T cell subtypes including Th17 cells. In this review, we discuss the possible mechanisms of miRNAs in MS pathophysiology by regulating CD4+ T cell differentiation into Th17 cells, and potential miRNA targets for current disease-modifying treatments.

The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases.

PubMed

Chiurchiù, Valerio; van der Stelt, Mario; Centonze, Diego; Maccarrone, Mauro

2018-01-01

Multiple sclerosis is the most common inflammatory demyelinating disease of the central nervous system, caused by an autoimmune response against myelin that eventually leads to progressive neurodegeneration and disability. Although the knowledge on its underlying neurobiological mechanisms has considerably improved, there is a still unmet need for new treatment options, especially for the progressive forms of the disease. Both preclinical and clinical data suggest that cannabinoids, derived from the Cannabis sativa plant, may be used to control symptoms such as spasticity and chronic pain, whereas only preclinical data indicate that these compounds and their endogenous counterparts, i.e. the endocannabinoids, may also exert neuroprotective effects and slow down disease progression. Here, we review the preclinical and clinical studies that could explain the therapeutic action of cannabinoid-based medicines, as well as the medical potential of modulating endocannabinoid signaling in multiple sclerosis, with a link to other neuroinflammatory disorders that share common hallmarks and pathogenetic features. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

STP Position Paper: Recommended Practices for Sampling and Processing the Nervous System (Brain, Spinal Cord, Nerve, and Eye) during Nonclinical General Toxicity Studies

EPA Science Inventory

The Society of Toxicologic Pathology charged a Nervous System Sampling Working Group with devising recommended practices to routinely screen the central and peripheral nervous systems in Good Laboratory Practice-type nonclinical general toxicity studies. Brains should be trimmed ...

75 FR 17417 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

78 FR 63478 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

75 FR 36428 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

77 FR 20037 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

76 FR 77895 - Schedules of Controlled Substances: Placement of Ezogabine Into Schedule V

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-15

... ester, is a new chemical substance with central nervous system depressant properties and is classified... nervous system as an anticonvulsant and the potential side effects of the drug therein, warrant closer... the central nervous system is alone not enough to merit its inclusion into Schedule IV of the CSA, nor...

78 FR 63481 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

76 FR 3912 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

75 FR 12768 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

78 FR 19499 - Request for Information: The National Toxicology Program Requests Information On Assays and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

... means adverse outcomes to the nervous system resulting from exposure during any life stage. Special... critical to the development and/or function of the nervous system. The NTP is also interested in receiving... to act as toxicants to the developing or adult nervous systems. Request for Information 1...

[Process in menstrual blood-derived mesenchymal stem cells for treatment of central nervous system diseases].

PubMed

Liu, Mengmeng; Cheng, Xinran; Li, Kaikai; Xu, Mingrui; Wu, Yongji; Wang, Mengli; Zhang, Qianru; Yan, Wenyong; Luo, Chang; Zhao, Shanting

2018-05-25

Stem cell research has become a frontier in the field of life sciences, and provides an ideal model for exploring developmental biology problems such as embryogenesis, histiocytosis, and gene expression regulation, as well as opens up new doors for clinical tissue defective and inheritance diseases. Among them, menstrual blood-derived stem cells (MenSCs) are characterized by wide source, multi-directional differentiation potential, low immune rejection characteristics. Thus, MenSCs can achieve individual treatment and have the most advantage of the clinical application. The central nervous system, including brain and spinal cord, is susceptible to injury. And lethality and morbidity of them tops the list of all types of trauma. Compared to peripheral nervous system, recovery of central nervous system after damage remains extremely hard. However, the treatment of stem cells, especially MenSCs, is expected to solve this problem. Therefore, biological characteristics of MenSCs and their treatment in the respect of central nervous system diseases have been reviewed at home and abroad in recent years, so as to provide reference for the treatment of central nervous system diseases.

Improving and Accelerating Drug Development for Nervous System Disorders

PubMed Central

Pankevich, Diana E.; Altevogt, Bruce M.; Dunlop, John; Gage, Fred H.; Hyman, Steve E.

2014-01-01

Advances in the neurosciences have placed the field in the position where it is poised to significantly reduce the burden of nervous system disorders. However, drug discovery, development and translation for nervous system disorders still pose many unique challenges. The key scientific challenges can be summarized as follows: mechanisms of disease, target identification and validation, predictive models, biomarkers for patient stratification and as endpoints for clinical trials, clear regulatory pathways, reliability and reproducibility of published data, and data sharing and collaboration. To accelerate nervous system drug development the Institute of Medicine’s Forum on Neuroscience and Nervous System Disorders has hosted a series of public workshops that brought together representatives of industry, government (including both research funding and regulatory agencies), academia, and patient groups to discuss these challenges and offer potential strategies to improve the translational neuroscience. PMID:25442933

Programmed cell death acts at different stages of Drosophila neurodevelopment to shape the central nervous system

PubMed Central

Desplan, Claude

2016-01-01

Nervous system development is a process that integrates cell proliferation, differentiation and programmed cell death (PCD). PCD is an evolutionary conserved mechanism and a fundamental developmental process by which the final cell number in a nervous system is established. In vertebrates and invertebrates, PCD can be determined intrinsically by cell lineage and age, as well as extrinsically by nutritional, metabolic and hormonal states. Drosophila has been an instrumental model for understanding how this mechanism is regulated. We review the role of PCD in Drosophila central nervous system development from neural progenitors to neurons, its molecular mechanism and function, how it is regulated and implemented, and how it ultimately shapes the fly central nervous system from the embryo to the adult. Finally, we discuss ideas that emerge while integrating this information. PMID:27404003

Systemic control of brown fat thermogenesis: integration of peripheral and central signals.

PubMed

Schulz, Tim J; Tseng, Yu-Hua

2013-10-01

Brown adipose tissue (BAT) is of great scientific interest as a potential target to treat obesity. The development of novel strategies to quantify brown fat thermogenesis in adult humans now enables minimally invasive assessment of novel pharmacotherapeutics. Input from the central nervous system via sympathetic efferents is widely regarded as the key controller of BAT-mediated thermogenesis in response to changes in body temperature or nutrient availability. More recently, however, it has become clear that locally secreted signals and endocrine factors originating from multiple organs can control the recruitment of brown adipocytes and, more importantly, induce thermogenesis in brown fat. Thus, they provide an attractive strategy to fine-tune brown fat thermogenesis independent of classical temperature sensing. Here, we summarize recent findings on bone morphogenetic protein signaling as an example of secreted factors in the regulation of brown adipocyte formation and systemic control of energy metabolism. We further highlight endocrine communication routes between the different types of brown adipocytes and other organs that contribute to regulation of thermogenesis. Thus, emerging evidence suggests that the classical mechanisms of central temperature sensing and sympathetic nervous system-driven thermogenesis are complemented by local and endocrine signals to determine systemic energy homeostasis. © 2013 New York Academy of Sciences.

The Gut Microbiome and the Brain

PubMed Central

Galland, Leo

2014-01-01

Abstract The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics. PMID:25402818

Both physiology and epidemiology support zero tolerable blood lead levels.

PubMed

Shefa, Syeda T; Héroux, Paul

2017-10-05

Inorganic lead is one of the most common causes of environmental metal poisonings, and its adverse effects on multiple body systems are of great concern. The brain, along with the kidneys, are critically susceptible to lead toxicity for their hosting of high affinity lead binding proteins, and very sensitive physiology. Prolonged low-lead exposure frequently remains unrecognized, causes subtle changes in these organ systems, and manifests later at an irreversible stage. With the repeated documentation of "no safe blood lead level", the pernicious effects of lead at any measurable concentration need to be emphasized. In this review, we surveyed articles on chronic low-level lead exposures with a blood lead concentrations <10μg/dL and the development of neurobehavioral or renal disorders. The negative impacts of lead on both nervous and renal systems were obvious at a blood lead concentration of 2μg/dL, with the absence of any detectable threshold. The deleterious effect of lead on two different organ systems at such low concentrations drew our attention to the various extracellular and intracellular events that might be affected by minimal concentration of body lead, especially blood lead. Is there a true common ground between low-level lead toxicity in both the nervous system and the kidney? Copyright © 2017 Elsevier B.V. All rights reserved.

Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT

ClinicalTrials.gov

2018-06-22

Malignant Neoplasm of Breast; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

Severe excessive daytime sleepiness induced by hydroxyurea.

PubMed

Revol, Bruno; Joyeux-Faure, Marie; Albahary, Marie-Victoire; Gressin, Remy; Mallaret, Michel; Pepin, Jean-Louis; Launois, Sandrine H

2017-06-01

Excessive daytime sleepiness (EDS) has been reported with many drugs, either as an extension of a hypnotic effect (e.g. central nervous system depressants) or as an idiosyncratic response of the patient. Here, we report unexpected and severe subjective and objective EDS induced by hydroxyurea therapy, with a favorable outcome after withdrawal. Clinical history, sleep log, polysomnography, and multiple sleep latency tests confirming the absence of other EDS causes are presented. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Functional evaluation and rehabilitation engineering.

PubMed

Aliverti, Andrea; Frigo, C; Andreoni, G; Baroni, G; Bonarini, A; Cerveri, P; Crivellini, M; Dellaca, R; Ferrigno, G; Galli, M; Pedrocchi, A; Rodano, R; Santambrogio, G C; Tognola, G; Pedotti, A

2011-01-01

Life is complex and all about movement, which allows us to interact with the environment and communicate with each other. The human nervous system is capable of performing a simultaneous and integrated control of 100-150 mechanical degrees of freedom of movement in the body via tensions generated by about 700 muscles. In its widest context, movement is carried out by a sensory motor system comprising multiple sensors (visual,auditory, and proprioceptive),multiple actuators (muscles acting on the skeletal system),and an intermediary processor that can be summarized as a multiple-input–multiple-output nonlinear dynamic time-varying control system. This grand control system is capable of responding with remarkable accuracy,speed, appropriateness,versatility, and adaptability to a wide spectrum of continuous and discrete stimuli and conditions and is certainly orders of magnitude more complex and sophisticated than the most advanced robotic systems currently available. In the last decades,a great deal of research has been carried out in the fields of functional evaluation of human performance and rehabilitation engineering. These fields combine knowledge, concepts, and methods from across many disciplines (e.g., biomechanics,neuroscience, and physiology), with the aim of developing apparatuses and methods fort he measurement and analysis of complex sensory motor performance and the ultimate goal of enhancing the execution of different tasks in both healthy people and persons with reduced capabilities from different causes (injury, disease, amputation,and neural degeneration).

Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.

PubMed

Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

2016-04-01

Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic leukemia are due to other etiologies in approximately 80% of cases. Analysis of the cerebrospinal fluid has high sensitivity but limited specificity to distinguish clinically significant chronic lymphocytic leukemia involvement from other etiologies. Copyright© Ferrata Storti Foundation.

Nervous system development in lecithotrophic larval and juvenile stages of the annelid Capitella teleta.

PubMed

Meyer, Néva P; Carrillo-Baltodano, Allan; Moore, Richard E; Seaver, Elaine C

2015-01-01

Reconstructing the evolutionary history of nervous systems requires an understanding of their architecture and development across diverse taxa. The spiralians encompass diverse body plans and organ systems, and within the spiralians, annelids exhibit a variety of morphologies, life histories, feeding modes and associated nervous systems, making them an ideal group for studying evolution of nervous systems. We describe nervous system development in the annelid Capitella teleta (Blake JA, Grassle JP, Eckelbarger KJ. Capitella teleta, a new species designation for the opportunistic and experimental Capitella sp. I, with a review of the literature for confirmed records. Zoosymposia. 2009;2:25-53) using whole-mount in situ hybridization for a synaptotagmin 1 homolog, nuclear stains, and cross-reactive antibodies against acetylated α-tubulin, 5-HT and FMRFamide. Capitella teleta is member of the Sedentaria (Struck TH, Paul C, Hill N, Hartmann S, Hosel C, Kube M, et al. Phylogenomic analyses unravel annelid evolution. Nature. 2011;471:95-8) and has an indirectly-developing, lecithotrophic larva. The nervous system of C. teleta shares many features with other annelids, including a brain and a ladder-like ventral nerve cord with five connectives, reiterated commissures, and pairs of peripheral nerves. Development of the nervous system begins with the first neurons differentiating in the brain, and follows a temporal order from central to peripheral and from anterior to posterior. Similar to other annelids, neurons with serotonin-like-immunoreactivity (5HT-LIR) and FMRFamide-like-immunoreactivity (FMRF-LIR) are found throughout the brain and ventral nerve cord. A small number of larval-specific neurons and neurites are present, but are visible only after the central nervous system begins to form. These larval neurons are not visible after metamorphosis while the rest of the nervous system is largely unchanged in juveniles. Most of the nervous system that forms during larvogenesis in C. teleta persists into the juvenile stage. The first neurons differentiate in the brain, which contrasts with the early formation of peripheral, larval-specific neurons found in some spiralian taxa with planktotrophic larvae. Our study provides a clear indication that certain shared features among annelids - e.g., five connectives in the ventral nerve cord - are only visible during larval stages in particular species, emphasizing the need to include developmental data in ancestral character state reconstructions. The data provided in this paper will serve as an important comparative reference for understanding evolution of nervous systems, and as a framework for future molecular studies of development.

Central nervous system involvement in adults with haemophagocytic lymphohistiocytosis: a single-center study.

PubMed

Cai, Guilan; Wang, Yini; Liu, Xiaojing; Han, Yanfei; Wang, Zhao

2017-08-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder characterized by proliferation and diffuse infiltration multiple organs with histiocytes, including the central nervous system (CNS). Neurological manifestations of HLH have been recognized in different studies with children, but they remain relatively ill-defined in adults with HLH. From March 2008 to October 2014, 289 adult patients with HLH were admitted to our center. Clinical, radiological, and cerebral spinal fluid (CSF) data of the patients with CNS involvement were reviewed, and a retrospective study in our single-center was carried out. CNS involvement was observed in 29 patients (10%) either in their diagnosis process or during disease course. CNS symptoms included disturbance of consciousness, cranial nerve palsies, seizures, headache, limb paralysis, irritability, meningism, and memory loss. CSF analysis was conducted in 17 patients (59%). Among them, 11 patients (65%) were reported as having abnormal CSF. Neuroradiological studies were performed in 25 patients (86%). Among the 13 cases that underwent CT scan, one patient hemorrhaged. Single or multiple hypodense foci were detected in the other 2 patients. Magnetic resonance imaging (MRI) abnormalities were found in 15 patients, including focal lesions in cortical and adjacent subcortical regions with or without variable nodular or ring contrast-enhancement, multiple lesions in white matter, diffuse white matter signal changes, and meningeal enhancement. Basal ganglia, cerebellum, and brainstem lesions were also observed. CNS involvement could also be found in adult patients with HLH, but not as frequent as it was in children. The clinical manifestations could be diversified. By carrying out rigorous CNS examinations, an early diagnosis could be made and it was of the utmost importance for the prevention of further lesions.

Markers of sympathetic nervous system activity associate with complex plasma lipids in metabolic syndrome subjects.

PubMed

Nestel, Paul J; Khan, Anmar A; Straznicky, Nora E; Mellett, Natalie A; Jayawardana, Kaushala; Mundra, Piyushkumar A; Lambert, Gavin W; Meikle, Peter J

2017-01-01

Plasma sphingolipids including ceramides, and gangliosides are associated with insulin resistance (IR) through effects on insulin signalling and glucose metabolism. Our studies of subjects with metabolic syndrome (MetS) showed close relationships between IR and sympathetic nervous system (SNS) activity including arterial norepinephrine (NE). We have therefore investigated possible associations of IR and SNS activity with complex lipids that are involved in both insulin sensitivity and neurotransmission. We performed a cross-sectional assessment of 23 lipid classes/subclasses (total 339 lipid species) by tandem mass spectrometry in 94 overweight untreated subjects with IR (quantified by HOMA-IR, Matsuda index and plasma insulin). Independently of IR parameters, several circulating complex lipids associated significantly with arterial NE and NEFA (non-esterified fatty acids) and marginally with heart rate (HR). After accounting for BMI, HOMA-IR, systolic BP, age, gender, and correction for multiple comparisons, these associations were significant (p < 0.05): NE with ceramide, phosphatidylcholine, alkyl- and alkenylphosphatidylcholine and free cholesterol; NEFA with mono- di- and trihexosylceramide, G M3 ganglioside, sphingomyelin, phosphatidylcholine, alkyl- and alkenylphosphatidylcholine, phosphatidylinositol and free cholesterol; HR marginally (p = or <0.1>0.05) with ceramide, G M3 ganglioside, sphingomyelin, lysophosphatidylcholine, phosphatidylinositol, lysophosphatidylinositol and free cholesterol. Multiple subspecies of these lipids significantly associated with NE and NEFA. None of the IR biomarkers associated significantly with lipid classes/subclasses after correction for multiple comparisons. This is the first demonstration that arterial norepinephrine and NEFA, that reflect both SNS activity and IR, associate significantly with circulating complex lipids independently of IR, suggesting a role for such lipids in neural mechanisms operating in MetS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

What have we learned about GPER function in physiology and disease from knockout mice?

PubMed

Prossnitz, Eric R; Hathaway, Helen J

2015-09-01

Estrogens, predominantly 17β-estradiol, exert diverse effects throughout the body in both normal and pathophysiology, during development and in reproductive, metabolic, endocrine, cardiovascular, nervous, musculoskeletal and immune systems. Estrogen and its receptors also play important roles in carcinogenesis and therapy, particularly for breast cancer. In addition to the classical nuclear estrogen receptors (ERα and ERβ) that traditionally mediate predominantly genomic signaling, the G protein-coupled estrogen receptor GPER has become recognized as a critical mediator of rapid signaling in response to estrogen. Mouse models, and in particular knockout (KO) mice, represent an important approach to understand the functions of receptors in normal physiology and disease. Whereas ERα KO mice display multiple significant defects in reproduction and mammary gland development, ERβ KO phenotypes are more limited, and GPER KO exhibit no reproductive deficits. However, the study of GPER KO mice over the last six years has revealed that GPER deficiency results in multiple physiological alterations including obesity, cardiovascular dysfunction, insulin resistance and glucose intolerance. In addition, the lack of estrogen-mediated effects in numerous tissues of GPER KO mice, studied in vivo or ex vivo, including those of the cardiovascular, endocrine, nervous and immune systems, reveals GPER as a genuine mediator of estrogen action. Importantly, GPER KO mice have also demonstrated roles for GPER in breast carcinogenesis and metastasis. In combination with the supporting effects of GPER-selective ligands and GPER knockdown approaches, GPER KO mice demonstrate the therapeutic potential of targeting GPER activity in diseases as diverse as obesity, diabetes, multiple sclerosis, hypertension, atherosclerosis, myocardial infarction, stroke and cancer. Copyright © 2015. Published by Elsevier Ltd.

Iron oxide magnetic nanoparticles highlight early involvement of the choroid plexus in central nervous system inflammation

PubMed Central

Millward, Jason M.; Schnorr, Jörg; Taupitz, Matthias; Wagner, Susanne; Wuerfel, Jens T.; Infante-Duarte, Carmen

2013-01-01

Neuroinflammation during multiple sclerosis involves immune cell infiltration and disruption of the BBB (blood–brain barrier). Both processes can be visualized by MRI (magnetic resonance imaging), in multiple sclerosis patients and in the animal model EAE (experimental autoimmune encephalomyelitis). We previously showed that VSOPs (very small superparamagnetic iron oxide particles) reveal CNS (central nervous system) lesions in EAE which are not detectable by conventional contrast agents in MRI. We hypothesized that VSOP may help detect early, subtle inflammatory events that would otherwise remain imperceptible. To investigate the capacity of VSOP to reveal early events in CNS inflammation, we induced EAE in SJL mice using encephalitogenic T-cells, and administered VSOP prior to onset of clinical symptoms. In parallel, we administered VSOP to mice at peak disease, and to unmanipulated controls. We examined the distribution of VSOP in the CNS by MRI and histology. Prior to disease onset, in asymptomatic mice, VSOP accumulated in the choroid plexus and in spinal cord meninges in the absence of overt inflammation. However, VSOP was undetectable in the CNS of non-immunized control mice. At peak disease, VSOP was broadly distributed; we observed particles in perivascular inflammatory lesions with apparently preserved glia limitans. Moreover, at peak disease, VSOP was prominent in the choroid plexus and was seen in elongated endothelial structures, co-localized with phagocytes, and diffusely disseminated in the parenchyma, suggesting multiple entry mechanisms of VSOP into the CNS. Thus, using VSOP we were able to discriminate between inflammatory events occurring in established EAE and, importantly, we identified CNS alterations that appear to precede immune cell infiltration and clinical onset. PMID:23452162

Interleukin 35 and Hepatocyte Growth Factor; as a novel combined immune gene therapy for Multiple Sclerosis disease.

PubMed

Moghadam, Samira; Erfanmanesh, Maryam; Esmaeilzadeh, Abdolreza

2017-11-01

An autoimmune demyelination disease of the Central Nervous System, Multiple Sclerosis, is a chronic inflammation which mostly involves young adults. Suffering people face functional loss with a severe pain. Most current MS treatments are focused on the immune response suppression. Approved drugs suppress the inflammatory process, but factually, there is no definite cure for Multiple Sclerosis. Recently developed knowledge has demonstrated that gene and cell therapy as a hopeful approach in tissue regeneration. The authors propose a novel combined immune gene therapy for Multiple Sclerosis treatment using anti-inflammatory and remyelination of Interleukine-35 and Hepatocyte Growth Factor properties, respectively. In this hypothesis Interleukine-35 and Hepatocyte Growth Factor introduce to Mesenchymal Stem Cells of EAE mouse model via an adenovirus based vector. It is expected that Interleukine-35 and Hepatocyte Growth Factor genes expressed from MSCs could effectively perform in immunotherapy of Multiple Sclerosis. Copyright © 2017. Published by Elsevier Ltd.

Complex neural architecture in the diploblastic larva of Clava multicornis (Hydrozoa, Cnidaria).

PubMed

Piraino, Stefano; Zega, Giuliana; Di Benedetto, Cristiano; Leone, Antonella; Dell'Anna, Alessandro; Pennati, Roberta; Carnevali, Daniela Candia; Schmid, Volker; Reichert, Heinrich

2011-07-01

The organization of the cnidarian nervous system has been widely documented in polyps and medusae, but little is known about the nervous system of planula larvae, which give rise to adult forms after settling and metamorphosis. We describe histological and cytological features of the nervous system in planulae of the hydrozoan Clava multicornis. These planulae do not swim freely in the water column but rather crawl on the substrate by means of directional, coordinated ciliary movement coupled to lateral muscular bending movements associated with positive phototaxis. Histological analysis shows pronounced anteroposterior regionalization of the planula's nervous system, with different neural cell types highly concentrated at the anterior pole. Transmission electron microscopy of planulae shows the nervous system to be unusually complex, with a large, orderly array of sensory cells at the anterior pole. In the anterior half of the planula, the basiectodermal plexus of neurites forms an extensive orthogonal network, whereas more posteriorly neurites extend longitudinally along the body axis. Additional levels of nervous system complexity are uncovered by neuropeptide-specific immunocytochemistry, which reveals distinct neural subsets having specific molecular phenotypes. Together these observations imply that the nervous system of the planula of Clava multicornis manifests a remarkable level of histological, cytological, and functional organization, the features of which may be reminiscent of those present in early bilaterian animals. Copyright © 2011 Wiley-Liss, Inc.

Development of a brain monitoring system for multimodality investigation in awake rats.

PubMed

Limnuson, Kanokwan; Narayan, Raj K; Chiluwal, Amrit; Bouton, Chad; Ping Wang; Chunyan Li

2016-08-01

Multimodal brain monitoring is an important approach to gain insight into brain function, modulation, and pathology. We have developed a unique micromachined neural probe capable of real-time continuous monitoring of multiple physiological, biochemical and electrophysiological variables. However, to date, it has only been used in anesthetized animals due to a lack of an appropriate interface for awake animals. We have developed a versatile headstage for recording the small neural signal and bridging the sensors to the remote sensing units for multimodal brain monitoring in awake rats. The developed system has been successfully validated in awake rats by simultaneously measuring four cerebral variables: electrocorticography, oxygen tension, temperature and cerebral blood flow. Reliable signal recordings were obtained with minimal artifacts from movement and environmental noise. For the first time, multiple variables of cerebral function and metabolism were simultaneously recorded from awake rats using a single neural probe. The system is envisioned for studying the effects of pharmacologic treatments, mapping the development of central nervous system diseases, and better understanding normal cerebral physiology.

[Thyroid hormones and the development of the nervous system].

PubMed

Mussa, G C; Zaffaroni, M; Mussa, F

1990-09-01

The growth and differentiation of the central nervous system are closely related to the presence of iodine and thyroid hormones. During the first trimester of human pregnancy the development of the nervous system depends entirely on the availability of iodine; after 12 week of pregnancy it depends on the initial secretion of iodothyronine by the fetal thyroid gland. During the early stages of the development of the nervous system a thyroid hormone deficit may provoke alterations in the maturation of both noble nervous cells (cortical pyramidal cells, Purkinje cells) and glial cells. Hypothyroidism may lead to cellular hypoplasia and reduced dendritic ramification, gemmules and interneuronal connections. Experimental studies in hypothyroid rats have also shown alterations in the content and organization of neuronal intracytoplasmatic microtubules, the biochemical maturation of synaptosomes and the maturation of nuclear and cytoplasmatic T3 receptors. Excess thyroid hormones during the early stages of development may also cause permanent damage to the central nervous system. Hyperthyroidism may initially induce an acceleration of the maturation processes, including the migration and differentiation of cells, the extension of the dendritic processes and synaptogenesis. An excess of thyroid hormones therefore causes neuronal proliferation to end precociously leading to a reduction of the total number of gemmules. Experimental research and clinical studies have partially clarified the correlation between the maturation of the nervous system and thyroid function during the early stages of development; both a deficit and excess of thyroid hormones may lead to permanent anatomo-functional damage to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

The larval nervous system of the penis worm Priapulus caudatus (Ecdysozoa)

PubMed Central

2016-01-01

The origin and extreme diversification of the animal nervous system is a central question in biology. While most of the attention has traditionally been paid to those lineages with highly elaborated nervous systems (e.g. arthropods, vertebrates, annelids), only the study of the vast animal diversity can deliver a comprehensive view of the evolutionary history of this organ system. In this regard, the phylogenetic position and apparently conservative molecular, morphological and embryological features of priapulid worms (Priapulida) place this animal lineage as a key to understanding the evolution of the Ecdysozoa (i.e. arthropods and nematodes). In this study, we characterize the nervous system of the hatching larva and first lorica larva of the priapulid worm Priapulus caudatus by immunolabelling against acetylated and tyrosinated tubulin, pCaMKII, serotonin and FMRFamide. Our results show that a circumoral brain and an unpaired ventral nerve with a caudal ganglion characterize the central nervous system of hatching embryos. After the first moult, the larva attains some adult features: a neck ganglion, an introvert plexus, and conspicuous secondary longitudinal neurites. Our study delivers a neuroanatomical framework for future embryological studies in priapulid worms, and helps illuminate the course of nervous system evolution in the Ecdysozoa. PMID:26598729

Prognosis after treatment with multiple dental implants under general anesthesia and sedation in a cerebral palsy patient with mental retardation: A case report.

PubMed

Hong, Young-Joon; Dan, Jung-Bae; Kim, Myung-Jin; Kim, Hyun Jeong; Seo, Kwang-Suk

2017-06-01

Cerebral palsy is a non-progressive disorder resulting from central nervous system damage caused by multiple factors. Almost all cerebral palsy patients have a movement disorder that makes dental treatment difficult. Oral hygiene management is difficult and the risks for periodontitis, dental caries and loss of multiple teeth are high. Placement of dental implants for multiple missing teeth in cerebral palsy patients needs multiple rounds of general anesthesia, and the prognosis is poor despite the expense. Therefore, making the decision to perform multiple dental implant treatments on cerebral palsy patients is difficult. A 33-year-old female patient with cerebral palsy and mental retardation was scheduled for multiple implant treatments. She underwent computed tomography (CT) under sedation and the operation of nine dental implants under general anesthesia. Implant-supported fixed prosthesis treatment was completed. During follow-up, she had the anterior incisors extracted and underwent the surgery of 3 additional dental implants, completing the prosthetic treatment. Although oral parafunctions existed due to cerebral palsy, no implant failure was observed 9 years after the first implant surgery.

Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma

ClinicalTrials.gov

2017-08-28

B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Central Nervous System Lymphoma; Intraocular Lymphoma; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Recurrent Adult Diffuse Large Cell Lymphoma; Retinal Lymphoma

Metal-based nanoparticle interactions with the nervous system: The challenge of brain entry and the risk of retention in the organism

EPA Science Inventory

This review of metal and metal-oxide based nanoparticles focuses on factors that influence their distribution into the nervous system, evidence that they enter brain parenchyma, and nervous system responses. Emphasis is placed on gold as a model metal-based nanoparticle and for r...

75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug Safety... and Central Nervous System Drugs Advisory Committee and the Drug Safety and Risk Management Advisory...

Results from a Survey of Current Practices for Sampling of Nervous System in Rodents and Non-rodents in General Toxicity Studies

EPA Science Inventory

A survey of current practices for sampling and examination of the nervous system in rodents and non-rodents for general and neurotoxicity (NT) studies was conducted by the Nervous System Sampling Subcommittee of the STP. For general toxicity studies most of those surveyed (>63%) ...

Viral Oncolytic Therapeutics for Neoplastic Meningitis

DTIC Science & Technology

2012-07-01

the central nervous system (CNS). While several novel molecular approaches are being developed, many of them require delivery of macromolecu- lar or...nonhuman primates. Keywords PET Imaging . Pharmacokinetics . Biopharmaceuticals . Macromolecules . Brain . Central nervous system . Drug delivery...Iodine-124 Introduction The leptomeningeal route to the central nervous system (CNS) starts from drug administration (injection or in- fusion) into the

Vulnerability-Based Critical Neurons, Synapses, and Pathways in the Caenorhabditis elegans Connectome

PubMed Central

Kim, Seongkyun; Kim, Hyoungkyu; Kralik, Jerald D.; Jeong, Jaeseung

2016-01-01

Determining the fundamental architectural design of complex nervous systems will lead to significant medical and technological advances. Yet it remains unclear how nervous systems evolved highly efficient networks with near optimal sharing of pathways that yet produce multiple distinct behaviors to reach the organism’s goals. To determine this, the nematode roundworm Caenorhabditis elegans is an attractive model system. Progress has been made in delineating the behavioral circuits of the C. elegans, however, many details are unclear, including the specific functions of every neuron and synapse, as well as the extent the behavioral circuits are separate and parallel versus integrative and serial. Network analysis provides a normative approach to help specify the network design. We investigated the vulnerability of the Caenorhabditis elegans connectome by performing computational experiments that (a) “attacked” 279 individual neurons and 2,990 weighted synaptic connections (composed of 6,393 chemical synapses and 890 electrical junctions) and (b) quantified the effects of each removal on global network properties that influence information processing. The analysis identified 12 critical neurons and 29 critical synapses for establishing fundamental network properties. These critical constituents were found to be control elements—i.e., those with the most influence over multiple underlying pathways. Additionally, the critical synapses formed into circuit-level pathways. These emergent pathways provide evidence for (a) the importance of backward locomotion, avoidance behavior, and social feeding behavior to the organism; (b) the potential roles of specific neurons whose functions have been unclear; and (c) both parallel and serial design elements in the connectome—i.e., specific evidence for a mixed architectural design. PMID:27540747

Neural differentiation promoted by truncated trkC receptors in collaboration with p75(NTR).

PubMed

Hapner, S J; Boeshore, K L; Large, T H; Lefcort, F

1998-09-01

trkC receptors, which serve critical functions during the development of the nervous system, are alternatively spliced to yield isoforms containing the catalytic tyrosine kinase domain (TK+) and truncated isoforms which lack this domain (TK-). To test for potential differences in their roles during early stages of neural development, TK+ and TK- isoforms were ectopically expressed in cultures of neural crest, the stem cell population that gives rise to the vast majority of the peripheral nervous system. NT-3 activation of ectopically expressed trkC TK+ receptors promoted both proliferation of neural crest cells and neuronal differentiation. Strikingly, the trkC TK- isoform was significantly more effective at promoting neuronal differentiation, but had no effect on proliferation. Furthermore, the trkC TK- response was dependent on a conserved receptor cytoplasmic domain and required the participation of the p75(NTR) neurotrophin receptor. Antibody-mediated receptor dimerization of TK+ receptors, but not TK- receptors, was sufficient to stimulate differentiation. These data identify a phenotypic response to activation of the trkC TK- receptor and demonstrate a functional interaction with p75(NTR), indicating there may be multiple trkC receptor-mediated systems guiding neuronal differentiation. Copyright 1998 Academic Press.

Microcephaly, ectodermal dysplasia, multiple skeletal anomalies and distinctive facial appearance: delineation of cerebro-dermato-osseous-dysplasia.

PubMed

Castori, Marco; Pascolini, Giulia; Parisi, Valentina; Sana, Maria Elena; Novelli, Antonio; Nürnberg, Peter; Iascone, Maria; Grammatico, Paola

2015-04-01

In 1980, a novel multiple malformation syndrome has been described in a 17-year-old woman with micro- and turricephaly, intellectual disability, distinctive facial appearance, congenital atrichia, and multiple skeletal anomalies mainly affecting the limbs. Four further sporadic patients and a couple of affected sibs are also reported with a broad clinical variability. Here, we describe a 4-year-old girl strikingly resembling the original report. Phenotype comparison identified a recurrent pattern of multisystem features involving the central nervous system, and skin and bones in five sporadic patients (including ours), while the two sibs and a further sporadic case show significant phenotypic divergence. Marked clinical variability within the same entity versus syndrome splitting is discussed and the term "cerebro-dermato-osseous dysplasia" is introduced to define this condition. © 2015 Wiley Periodicals, Inc.

An Organ System Approach to Explore the Antioxidative, Anti-Inflammatory, and Cytoprotective Actions of Resveratrol

PubMed Central

Bath, Sundeep

2015-01-01

Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson's and Alzheimer's disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment. PMID:26180596

Combinatorial action of Grainyhead, Extradenticle and Notch in regulating Hox mediated apoptosis in Drosophila larval CNS

PubMed Central

Khandelwal, Risha; Govinda Rajan, Sriivatsan; Kumar, Raviranjan

2017-01-01

Hox mediated neuroblast apoptosis is a prevalent way to pattern larval central nervous system (CNS) by different Hox genes, but the mechanism of this apoptosis is not understood. Our studies with Abdominal-A (Abd-A) mediated larval neuroblast (pNB) apoptosis suggests that AbdA, its cofactor Extradenticle (Exd), a helix-loop-helix transcription factor Grainyhead (Grh), and Notch signaling transcriptionally contribute to expression of RHG family of apoptotic genes. We find that Grh, AbdA, and Exd function together at multiple motifs on the apoptotic enhancer. In vivo mutagenesis of these motifs suggest that they are important for the maintenance of the activity of the enhancer rather than its initiation. We also find that Exd function is independent of its known partner homothorax in this apoptosis. We extend some of our findings to Deformed expressing region of sub-esophageal ganglia where pNBs undergo a similar Hox dependent apoptosis. We propose a mechanism where common players like Exd-Grh-Notch work with different Hox genes through region specific enhancers to pattern respective segments of larval central nervous system. PMID:29023471

Combinatorial action of Grainyhead, Extradenticle and Notch in regulating Hox mediated apoptosis in Drosophila larval CNS.

PubMed

Khandelwal, Risha; Sipani, Rashmi; Govinda Rajan, Sriivatsan; Kumar, Raviranjan; Joshi, Rohit

2017-10-01

Hox mediated neuroblast apoptosis is a prevalent way to pattern larval central nervous system (CNS) by different Hox genes, but the mechanism of this apoptosis is not understood. Our studies with Abdominal-A (Abd-A) mediated larval neuroblast (pNB) apoptosis suggests that AbdA, its cofactor Extradenticle (Exd), a helix-loop-helix transcription factor Grainyhead (Grh), and Notch signaling transcriptionally contribute to expression of RHG family of apoptotic genes. We find that Grh, AbdA, and Exd function together at multiple motifs on the apoptotic enhancer. In vivo mutagenesis of these motifs suggest that they are important for the maintenance of the activity of the enhancer rather than its initiation. We also find that Exd function is independent of its known partner homothorax in this apoptosis. We extend some of our findings to Deformed expressing region of sub-esophageal ganglia where pNBs undergo a similar Hox dependent apoptosis. We propose a mechanism where common players like Exd-Grh-Notch work with different Hox genes through region specific enhancers to pattern respective segments of larval central nervous system.

Role of proteoglycans in neuro-inflammation and central nervous system fibrosis.

PubMed

Heindryckx, Femke; Li, Jin-Ping

2018-01-31

Fibrosis is defined as the thickening and scarring of connective tissue, usually as a consequence of tissue damage. The central nervous system (CNS) is special in the sense that fibrogenic cells are restricted to vascular and meningeal areas. Inflammation and the disruption of the blood-brain barrier can lead to the infiltration of fibroblasts and trigger fibrotic response. While the initial function of the fibrotic tissue is to restore the blood-brain barrier and to limit the site of injury, it also demolishes the structure of extracellular matrix and impedes the healing process by producing inhibitory molecules and forming a physical and biochemical barrier that prevents axon regeneration. As a major constituent in the extracellular matrix, proteoglycans participate in the neuro-inflammation, modulating the fibrotic process. In this review, we will discuss the pathophysiology of fibrosis during acute injuries of the CNS, as well as during chronic neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and age-related neurodegeneration with focus on the functional roles of proteoglycans. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Inside story of Group I Metabotropic Glutamate Receptors (mGluRs).

PubMed

Bhattacharyya, Samarjit

2016-08-01

Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors (GPCRs) that are activated by the neurotransmitter glutamate in the central nervous system. Among the eight subtypes, mGluR1 and mGluR5 belong to the group I family. These receptors play important roles in the brain and are believed to be involved in multiple forms of experience dependent synaptic plasticity including learning and memory. In addition, group I mGluRs also have been implicated in various neuropsychiatric disorders like Fragile X syndrome, autism etc. The normal signaling depends on the precise location of these receptors in specific region of the neuron and the process of receptor trafficking plays a crucial role in controlling this localization. Intracellular trafficking could also regulate the desensitization, resensitization, down-regulation and intracellular signaling of these receptors. In this review I focus on the current understanding of group I mGluR regulation in the central nervous system and also their role in neuropsychiatric disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical effects of air pollution on the central nervous system; a review.

PubMed

Babadjouni, Robin M; Hodis, Drew M; Radwanski, Ryan; Durazo, Ramon; Patel, Arati; Liu, Qinghai; Mack, William J

2017-09-01

The purpose of this review is to describe recent clinical and epidemiological studies examining the adverse effects of urban air pollution on the central nervous system (CNS). Air pollution and particulate matter (PM) are associated with neuroinflammation and reactive oxygen species (ROS). These processes affect multiple CNS pathways. The conceptual framework of this review focuses on adverse effects of air pollution with respect to neurocognition, white matter disease, stroke, and carotid artery disease. Both children and older individuals exposed to air pollution exhibit signs of cognitive dysfunction. However, evidence on middle-aged cohorts is lacking. White matter injury secondary to air pollution exposure is a putative mechanism for neurocognitive decline. Air pollution is associated with exacerbations of neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. Increases in stroke incidences and mortalities are seen in the setting of air pollution exposure and CNS pathology is robust. Large populations living in highly polluted environments are at risk. This review aims to outline current knowledge of air pollution exposure effects on neurological health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glossary

MedlinePlus

... effective, directed treatments. Central Nervous System The "central command system" of the body, it includes the brain, ... The central nervous system (CNS) is the "central command system" of the body, and includes the brain, ...

The complex simplicity of the brittle star nervous system.

PubMed

Zueva, Olga; Khoury, Maleana; Heinzeller, Thomas; Mashanova, Daria; Mashanov, Vladimir

2018-01-01

Brittle stars (Ophiuroidea, Echinodermata) have been increasingly used in studies of animal behavior, locomotion, regeneration, physiology, and bioluminescence. The success of these studies directly depends on good working knowledge of the ophiuroid nervous system. Here, we describe the arm nervous system at different levels of organization, including the microanatomy of the radial nerve cord and peripheral nerves, ultrastructure of the neural tissue, and localization of different cell types using specific antibody markers. We standardize the nomenclature of nerves and ganglia, and provide an anatomically accurate digital 3D model of the arm nervous system as a reference for future studies. Our results helped identify several general features characteristic to the adult echinoderm nervous system, including the extensive anatomical interconnections between the ectoneural and hyponeural components, neuroepithelial organization of the central nervous system, and the supporting scaffold of the neuroepithelium formed by radial glial cells. In addition, we provide further support to the notion that the echinoderm radial glia is a complex and diverse cell population. We also tested the suitability of a range of specific cell-type markers for studies of the brittle star nervous system and established that the radial glial cells are reliably labeled with the ERG1 antibodies, whereas the best neuronal markers are acetylated tubulin, ELAV, and synaptotagmin B. The transcription factor Brn1/2/4 - a marker of neuronal progenitors - is expressed not only in neurons, but also in a subpopulation of radial glia. For the first time, we describe putative ophiuroid proprioceptors associated with the hyponeural part of the central nervous system. Together, our data help establish both the general principles of neural architecture common to the phylum Echinodermata and the specific ophiuroid features.

Enteric nervous system abnormalities are present in human necrotizing enterocolitis: potential neurotransplantation therapy

PubMed Central

2013-01-01

Introduction Intestinal dysmotility following human necrotizing enterocolitis suggests that the enteric nervous system is injured during the disease. We examined human intestinal specimens to characterize the enteric nervous system injury that occurs in necrotizing enterocolitis, and then used an animal model of experimental necrotizing enterocolitis to determine whether transplantation of neural stem cells can protect the enteric nervous system from injury. Methods Human intestinal specimens resected from patients with necrotizing enterocolitis (n = 18), from control patients with bowel atresia (n = 8), and from necrotizing enterocolitis and control patients undergoing stoma closure several months later (n = 14 and n = 6 respectively) were subjected to histologic examination, immunohistochemistry, and real-time reverse-transcription polymerase chain reaction to examine the myenteric plexus structure and neurotransmitter expression. In addition, experimental necrotizing enterocolitis was induced in newborn rat pups and neurotransplantation was performed by administration of fluorescently labeled neural stem cells, with subsequent visualization of transplanted cells and determination of intestinal integrity and intestinal motility. Results There was significant enteric nervous system damage with increased enteric nervous system apoptosis, and decreased neuronal nitric oxide synthase expression in myenteric ganglia from human intestine resected for necrotizing enterocolitis compared with control intestine. Structural and functional abnormalities persisted months later at the time of stoma closure. Similar abnormalities were identified in rat pups exposed to experimental necrotizing enterocolitis. Pups receiving neural stem cell transplantation had improved enteric nervous system and intestinal integrity, differentiation of transplanted neural stem cells into functional neurons, significantly improved intestinal transit, and significantly decreased mortality compared with control pups. Conclusions Significant injury to the enteric nervous system occurs in both human and experimental necrotizing enterocolitis. Neural stem cell transplantation may represent a novel future therapy for patients with necrotizing enterocolitis. PMID:24423414

Metal-based nanoparticle interactions with the nervous system: the challenge of brain entry and the risk of retention in the organism.

PubMed

Yokel, Robert; Grulke, Eric; MacPhail, Robert

2013-01-01

This review of metal-based nanoparticles focuses on factors influencing their distribution into the nervous system, evidence they enter brain parenchyma, and nervous system responses. Gold is emphasized as a model metal-based nanoparticle and for risk assessment in the companion review. The anatomy and physiology of the nervous system, basics of colloid chemistry, and environmental factors that influence what cells see are reviewed to provide background on the biological, physical-chemical, and internal milieu factors that influence nervous system nanoparticle uptake. The results of literature searches reveal little nanoparticle research included the nervous system, which about equally involved in vitro and in vivo methods, and very few human studies. The routes of uptake into the nervous system and mechanisms of nanoparticle uptake by cells are presented with examples. Brain nanoparticle uptake inversely correlates with size. The influence of shape has not been reported. Surface charge has not been clearly shown to affect flux across the blood-brain barrier. There is very little evidence for metal-based nanoparticle distribution into brain parenchyma. Metal-based nanoparticle disruption of the blood-brain barrier and adverse brain changes have been shown, and are more pronounced for spheres than rods. Study concentrations need to be put in exposure contexts. Work with dorsal root ganglion cells and brain cells in vitro show the potential for metal-based nanoparticles to produce toxicity. Interpretation of these results must consider the ability of nanoparticles to distribute across the barriers protecting the nervous system. Effects of the persistence of poorly soluble metal-based nanoparticles are of particular concern. Copyright © 2013 Wiley Periodicals, Inc.

Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

PubMed Central

Cancela, Camila Silva Peres; Murao, Mitiko; Viana, Marcos Borato; de Oliveira, Benigna Maria

2012-01-01

Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count < 50 x 109/L (p-value = 0.0008). There was no difference in cumulative central nervous system relapse (isolated or combined) for the other analyzed variables: immunophenotype, traumatic lumbar puncture, interval between diagnosis and first lumbar puncture and place where the procedure was performed. Conclusions These results suggest that a leukocyte count > 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

NASA Astrophysics Data System (ADS)

Shumilov, V. N.; Syryamkin, V. I.; Syryamkin, M. V.

2015-11-01

The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervous systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of formation of connections between neurons in simplest biological objects. Based on the correspondence of function of the created models to function of biological nervous systems we suggest the use of computational and electronic models of the brain for the study of its function under normal and pathological conditions, because operating principles of the models are built on principles imitating the function of biological nervous systems and the brain.

Recent Understanding on Diagnosis and Management of Central Nervous System Vasculitis in Children

PubMed Central

Iannetti, Ludovico; Zito, Roberta; Bruschi, Simone; Papetti, Laura; Ulgiati, Fiorenza; Nicita, Francesco; Del Balzo, Francesca; Spalice, Alberto

2012-01-01

Central nervous system vasculitides in children may develop as a primary condition or secondary to an underlying systemic disease. Many vasculitides affect both adults and children, while some others occur almost exclusively in childhood. Patients usually present with systemic symptoms with single or multiorgan dysfunction. The involvement of central nervous system in childhood is not frequent and it occurs more often as a feature of subtypes like childhood polyarteritis nodosa, Kawasaki disease, Henoch Schönlein purpura, and Bechet disease. Primary angiitis of the central nervous system of childhood is a reversible cause of severe neurological impairment, including acute ischemic stroke, intractable seizures, and cognitive decline. The first line therapy of CNS vasculitides is mainly based on corticosteroids and immunosuppressor drugs. Other strategies include plasmapheresis, immunoglobulins, and biologic drugs. This paper discusses on current understanding of most frequent primary and secondary central nervous system vasculitides in children including a tailored-diagnostic approach and new evidence regarding treatment. PMID:23008735

Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.

PubMed

Maggi, Pietro; Absinta, Martina; Grammatico, Matteo; Vuolo, Luisa; Emmi, Giacomo; Carlucci, Giovanna; Spagni, Gregorio; Barilaro, Alessandro; Repice, Anna Maria; Emmi, Lorenzo; Prisco, Domenico; Martinelli, Vittorio; Scotti, Roberta; Sadeghi, Niloufar; Perrotta, Gaetano; Sati, Pascal; Dachy, Bernard; Reich, Daniel S; Filippi, Massimo; Massacesi, Luca

2018-02-01

In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294. © 2018 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

PubMed Central

Praticò, A.D.; Serra, A.; Maiolino, L.; Cocuzza, S.; Di Mauro, P.; Licciardello, L.; Milone, P.; Privitera, G.; Belfiore, G.; Di Pietro, M.; Di Raimondo, F.; Romano, A.; Chiarenza, A.; Muglia, M.; Polizzi, A.; Evans, D.G.

2016-01-01

SUMMARY Neurofibromatosis type 2 [NF2; MIM # 101000] is an autosomal dominant disorder characterised by the occurrence of vestibular schwannomas (VSs), schwannomas of other cranial, spinal and cutaneous nerves, cranial and spinal meningiomas and/or other central nervous system (CNS) tumours (e.g., ependymomas, astrocytomas). Additional features include early onset cataracts, optic nerve sheath meningiomas, retinal hamartomas, dermal schwannomas (i.e., NF2-plaques), and (few) café-au-lait spots. Clinically, NF2 children fall into two main groups: (1) congenital NF2 - with bilateral VSs detected as early as the first days to months of life, which can be stable/asymptomatic for one-two decades and suddenly progress; and (2) severe pre-pubertal (Wishart type) NF2- with multiple (and rapidly progressive) CNS tumours other-than-VS, which usually present first, years before VSs [vs. the classical adult (Gardner type) NF2, with bilateral VSs presenting in young adulthood, sometimes as the only disease feature]. Some individuals can develop unilateral VS associated with ipsilateral meningiomas or multiple schwannomas localised to one part of the peripheral nervous system [i.e., mosaic NF2] or multiple non-VS, non-intradermal cranial, spinal and peripheral schwannomas (histologically proven) [schwannomatosis]. NF2 is caused by mutations in the NF2 gene at chromosome 22q12.1, which encodes for a protein called merlin or schwannomin, most similar to the exrin-readixin-moesin (ERM) proteins; mosaicNF2 is due to mosaic phenomena for the NF2 gene, whilst schwannomatosis is caused by coupled germ-line and mosaic mutations either in the SMARCB1 gene [SWNTS1; MIM # 162091] or the LZTR1 gene [SWNTS2; MIM # 615670] both falling within the 22q region and the NF2 gene. Data driven from in vitro and animal studies on the merlin pathway [e.g., post-translational and upstream/downstream regulation] allowed biologically targeted treatment strategies [e.g., Lapatinib, Erlotinib, Bevacizumab] aimed to multiple tumour shrinkage and/or regression and tumour arrest of progression with functional improvement. PMID:27958595

A novel subset of enteric neurons revealed by ptf1a:GFP in the developing zebrafish enteric nervous system.

PubMed

Uribe, Rosa A; Gu, Tiffany; Bronner, Marianne E

2016-03-01

The enteric nervous system, the largest division of the peripheral nervous system, is derived from vagal neural crest cells that invade and populate the entire length of the gut to form diverse neuronal subtypes. Here, we identify a novel population of neurons within the enteric nervous system of zebrafish larvae that express the transgenic marker ptf1a:GFP within the midgut. Genetic lineage analysis reveals that enteric ptf1a:GFP(+) cells are derived from the neural crest and that most ptf1a:GFP(+) neurons express the neurotransmitter 5HT, demonstrating that they are serotonergic. This transgenic line, Tg(ptf1a:GFP), provides a novel neuronal marker for a subpopulation of neurons within the enteric nervous system, and highlights the possibility that Ptf1a may act as an important transcription factor for enteric neuron development. © 2016 Wiley Periodicals, Inc.

Evolution of the Human Nervous System Function, Structure, and Development.

PubMed

Sousa, André M M; Meyer, Kyle A; Santpere, Gabriel; Gulden, Forrest O; Sestan, Nenad

2017-07-13

The nervous system-in particular, the brain and its cognitive abilities-is among humans' most distinctive and impressive attributes. How the nervous system has changed in the human lineage and how it differs from that of closely related primates is not well understood. Here, we consider recent comparative analyses of extant species that are uncovering new evidence for evolutionary changes in the size and the number of neurons in the human nervous system, as well as the cellular and molecular reorganization of its neural circuits. We also discuss the developmental mechanisms and underlying genetic and molecular changes that generate these structural and functional differences. As relevant new information and tools materialize at an unprecedented pace, the field is now ripe for systematic and functionally relevant studies of the development and evolution of human nervous system specializations. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetically engineered mouse models shed new light on the pathogenesis of neurofibromatosis type I-related neoplasms of the peripheral nervous system.

PubMed

Brossier, Nicole M; Carroll, Steven L

2012-05-01

Neurofibromatosis type 1 (NF1), the most common genetic disorder affecting the human nervous system, is characterized by the development of multiple benign Schwann cell tumors in skin and large peripheral nerves. These neoplasms, which are termed dermal and plexiform neurofibromas respectively, have distinct clinical courses; of particular note, plexiform, but not dermal, neurofibromas often undergo malignant progression to form malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy occurring in NF1 patients. In recent years, a number of genetically engineered mouse models have been created to investigate the molecular mechanisms driving the pathogenesis of these tumors. These models have been designed to address key questions including: (1) whether NF1 loss in the Schwann cell lineage is essential for tumorigenesis; (2) what cell type(s) in the Schwann cell lineage gives rise to dermal neurofibromas, plexiform neurofibromas and MPNSTs; (3) how the tumor microenvironment contributes to neoplasia; (4) what additional mutations contribute to neurofibroma-MPNST progression; (5) what role different neurofibromin-regulated Ras proteins play in this process and (6) how dysregulated growth factor signaling facilitates PNS tumorigenesis. In this review, we summarize the major findings from each of these models and their limitations as well as how discrepancies between these models may be reconciled. We also discuss how information gleaned from these models can be synthesized to into a comprehensive model of tumor formation in peripheral nervous system and consider several of the major questions that remain unanswered about this process. Copyright © 2011 Elsevier Inc. All rights reserved.

Patients' Risk of Causing Traffic Violations and Traffic Accidents while Driving.

PubMed

Šestan, Nevenka; Dodič Fikfak, Metoda; Balantič, Zvone

2017-09-01

This study examines whether drivers suffering from epilepsy, chronic alcoholism and/or hazardous drinking, psychoactive substance abuse, other diseases of the nervous system, mental and behavioural disorders, cardiovascular diseases, severe diabetes, and severe eye diseases are at a greater risk of causing traffic accidents and traffic violations than drivers that cause accidents and violations without these diagnoses. A case control study was carried out. The cases were drivers checked by a special medical committee in the period observed suffering from the diseases listed above. Matched controls were taken from the cohort of those that caused accidents and violations during the same period observed. The descriptive statistics were followed by calculation of correlations, t-tests and χ 2 , and the odds ratio. Drivers with referrals for diseases of the nervous system are five times more likely to cause a traffic accident compared to controls (OR=5.18; 95% CI=2.59-10.34); in addition, a high risk is associated with drivers with mental and behavioural disorders (OR=3.64; 95% CI=1.91-6.94), drivers with epilepsy (OR=1.99; 95% CI=1.01-3.92), and drivers addicted to alcohol (OR=1.71; 95% CI=1.01-2.89). Drivers suffering from addiction, a disease of the nervous system, or epilepsy are more likely to cause a traffic accident, which is a contribution to the inconclusive findings of previous studies. The multiple reasons for risks of patients suffering from mental and behavioural disorders need to be further investigated. Copyright© by the National Institute of Public Health, Prague 2017

The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature

PubMed Central

Alawi, Khadija M.; Aubdool, Aisah A.; Liang, Lihuan; Wilde, Elena; Vepa, Abhinav; Psefteli, Maria-Paraskevi; Brain, Susan D.; Keeble, Julie E.

2015-01-01

Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the β-adrenoceptor antagonist propranolol, the mixed α-/β-adrenoceptor antagonist labetalol, and the α1-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. d-Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders.—Alawi, K. M., Aubdool, A. A., Liang, L., Wilde, E., Vepa, A., Psefteli, M.-P., Brain, S. D., Keeble, J. E. The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature. PMID:26136480

Polarity-specific high-level information propagation in neural networks.

PubMed

Lin, Yen-Nan; Chang, Po-Yen; Hsiao, Pao-Yueh; Lo, Chung-Chuan

2014-01-01

Analyzing the connectome of a nervous system provides valuable information about the functions of its subsystems. Although much has been learned about the architectures of neural networks in various organisms by applying analytical tools developed for general networks, two distinct and functionally important properties of neural networks are often overlooked. First, neural networks are endowed with polarity at the circuit level: Information enters a neural network at input neurons, propagates through interneurons, and leaves via output neurons. Second, many functions of nervous systems are implemented by signal propagation through high-level pathways involving multiple and often recurrent connections rather than by the shortest paths between nodes. In the present study, we analyzed two neural networks: the somatic nervous system of Caenorhabditis elegans (C. elegans) and the partial central complex network of Drosophila, in light of these properties. Specifically, we quantified high-level propagation in the vertical and horizontal directions: the former characterizes how signals propagate from specific input nodes to specific output nodes and the latter characterizes how a signal from a specific input node is shared by all output nodes. We found that the two neural networks are characterized by very efficient vertical and horizontal propagation. In comparison, classic small-world networks show a trade-off between vertical and horizontal propagation; increasing the rewiring probability improves the efficiency of horizontal propagation but worsens the efficiency of vertical propagation. Our result provides insights into how the complex functions of natural neural networks may arise from a design that allows them to efficiently transform and combine input signals.

Polarity-specific high-level information propagation in neural networks

PubMed Central

Lin, Yen-Nan; Chang, Po-Yen; Hsiao, Pao-Yueh; Lo, Chung-Chuan

2014-01-01

Analyzing the connectome of a nervous system provides valuable information about the functions of its subsystems. Although much has been learned about the architectures of neural networks in various organisms by applying analytical tools developed for general networks, two distinct and functionally important properties of neural networks are often overlooked. First, neural networks are endowed with polarity at the circuit level: Information enters a neural network at input neurons, propagates through interneurons, and leaves via output neurons. Second, many functions of nervous systems are implemented by signal propagation through high-level pathways involving multiple and often recurrent connections rather than by the shortest paths between nodes. In the present study, we analyzed two neural networks: the somatic nervous system of Caenorhabditis elegans (C. elegans) and the partial central complex network of Drosophila, in light of these properties. Specifically, we quantified high-level propagation in the vertical and horizontal directions: the former characterizes how signals propagate from specific input nodes to specific output nodes and the latter characterizes how a signal from a specific input node is shared by all output nodes. We found that the two neural networks are characterized by very efficient vertical and horizontal propagation. In comparison, classic small-world networks show a trade-off between vertical and horizontal propagation; increasing the rewiring probability improves the efficiency of horizontal propagation but worsens the efficiency of vertical propagation. Our result provides insights into how the complex functions of natural neural networks may arise from a design that allows them to efficiently transform and combine input signals. PMID:24672472

Neuroprotection trek--the next generation: the measurement is the message.

PubMed

Andrews, Russell J

2005-08-01

Animal trials of many pharmacological neuroprotective agents have been quite successful, whereas trials in humans have been uniformly disappointing. A major difference between laboratory research in animals and clinical research in humans is the amount and/or quality of data obtained. The goal of this presentation is to argue that when clinical studies consist of more valid, objective data--that is, as our measurement capabilities in clinical research become as robust as they are in laboratory research--we are likely to gain new insights into both (1) injury to the nervous system and (2) neuroprotective treatment strategies. Technological advances (in data acquisition and analysis)--often novel even in the laboratory--will be the "scale" that will enable progress in measurement. As examples of such technological advances, two projects initiated at NASA Ames Research Center are cited. The NASA Smart Probe Project, with the goal of combining multiple microsensors and neural networks for real-time tissue identification (e.g., for tumor detection), has recently moved into the clinical realm, with a prototype being used to diagnose breast cancer in women "on the spot". The NASA Nanoelectrode Array Project has fabricated nanoscale devices that can simultaneously monitor electrical activity and neurotransmitter concentrations, while providing electrical stimulation focally and precisely (and potentially in a closed-loop fashion based on the input from the nanosensors). The large amounts of data that such techniques can acquire and analyze--separated spatially and temporally throughout the nervous system, if necessary--will provide insights not only into neuroprotective strategies, but also into the workings of the nervous system itself.

Model of pediatric pituitary hormone deficiency separates the endocrine and neural functions of the LHX3 transcription factor in vivo.

PubMed

Colvin, Stephanie C; Malik, Raleigh E; Showalter, Aaron D; Sloop, Kyle W; Rhodes, Simon J

2011-01-04

The etiology of most pediatric hormone deficiency diseases is poorly understood. Children with combined pituitary hormone deficiency (CPHD) have insufficient levels of multiple anterior pituitary hormones causing short stature, metabolic disease, pubertal failure, and often have associated nervous system symptoms. Mutations in developmental regulatory genes required for the specification of the hormone-secreting cell types of the pituitary gland underlie severe forms of CPHD. To better understand these diseases, we have created a unique mouse model of CPHD with a targeted knockin mutation (Lhx3 W227ter), which is a model for the human LHX3 W224ter disease. The LHX3 gene encodes a LIM-homeodomain transcription factor, which has essential roles in pituitary and nervous system development in mammals. The introduced premature termination codon results in deletion of the carboxyl terminal region of the LHX3 protein, which is critical for pituitary gene activation. Mice that lack all LHX3 function do not survive beyond birth. By contrast, the homozygous Lhx3 W227ter mice survive, but display marked dwarfism, thyroid disease, and female infertility. Importantly, the Lhx3 W227ter mice have no apparent nervous system deficits. The Lhx3 W227ter mouse model provides a unique array of hormone deficits and facilitates experimental approaches that are not feasible with human patients. These experiments demonstrate that the carboxyl terminus of the LHX3 transcription factor is not required for viability. More broadly, this study reveals that the in vivo actions of a transcription factor in different tissues are molecularly separable.

The influence of body mass index and outdoor temperature on the autonomic response to eating in healthy young Japanese women.

PubMed

Okada, Masahiro; Kakehashi, Masayuki

2014-01-01

The influences of body weight and air temperature on the autonomic response to food intake have not been clarified. We measured heart rate variability before and after lunch, as well as the effects of outdoor temperature and increased body mass index (BMI), in healthy young Japanese women. We studied 55 healthy young female university students. Heart rate variability was measured before lunch, immediately after lunch, 30 min after lunch, and 1 h after lunch to determine any correlations between heart rate variability, outdoor temperature, and BMI. In addition, multiple regression analysis was performed to elucidate the relationship between heart rate variability and outdoor temperature before and after lunch. A simple slope test was conducted to show the relationship between the low-to-high frequency ratio (1 h after lunch) and outdoor temperature. Subjects were divided into a low BMI group (range: 16.6-20.3) and a high BMI group (range: 20.4-32.9). The very low frequency component of heart rate variability, an index of thermoregulatory vasomotor control exerted by the sympathetic nervous system, was significantly diminished after lunch in the high BMI group (P < 0.01). A significant decrease in the low-to-high frequency (LF/HF) ratio, which represents the balance between the parasympathetic and sympathetic nervous systems, was evident in the low BMI group after lunch, indicating parasympathetic system dominance (P = 0.001). In addition, a significant association was found between the LF/HF ratio and outdoor temperature after lunch with a lower BMI (P = 0.002), but this association disappeared with higher BMIs. Autonomic responses to eating showed clear differences according to BMI, indicating that the sensitivity of the autonomic nervous system may change with increases in BMI.

The octopus genome and the evolution of cephalopod neural and morphological novelties

PubMed Central

Albertin, Caroline B.; Simakov, Oleg; Mitros, Therese; Wang, Z. Yan; Pungor, Judit R.; Edsinger-Gonzalez, Eric; Brenner, Sydney; Ragsdale, Clifton W.; Rokhsar, Daniel S.

2016-01-01

Coleoid cephalopods (octopus, squid, and cuttlefish) are active, resourceful predators with a rich behavioral repertoire1. They have the largest nervous systems among the invertebrates2 and present other striking morphological innovations including camera-like eyes, prehensile arms, a highly derived early embryogenesis, and the most sophisticated adaptive coloration system among all animals1,3. To investigate the molecular bases of cephalopod brain and body innovations we sequenced the genome and multiple transcriptomes of the California two-spot octopus, Octopus bimaculoides. We found no evidence for hypothesized whole genome duplications in the octopus lineage4–6. The core developmental and neuronal gene repertoire of the octopus is broadly similar to that found across invertebrate bilaterians, except for massive expansions in two gene families formerly thought to be uniquely enlarged in vertebrates: the protocadherins, which regulate neuronal development, and the C2H2 superfamily of zinc finger transcription factors. Extensive mRNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described7, as well as in genes participating in a broad range of other cellular functions. We identified hundreds of cephalopod-specific genes, many of which showed elevated expression levels in such specialized structures as the skin, the suckers, and the nervous system. Finally, we found evidence for large-scale genomic rearrangements that are closely associated with transposable element expansions. Our analysis suggests that substantial expansion of a handful of gene families, along with extensive remodeling of genome linkage and repetitive content, played a critical role in the evolution of cephalopod morphological innovations, including their large and complex nervous systems. PMID:26268193

An Inflammation-Centric View of Neurological Disease: Beyond the Neuron

PubMed Central

Skaper, Stephen D.; Facci, Laura; Zusso, Morena; Giusti, Pietro

2018-01-01

Inflammation is a complex biological response fundamental to how the body deals with injury and infection to eliminate the initial cause of cell injury and effect repair. Unlike a normally beneficial acute inflammatory response, chronic inflammation can lead to tissue damage and ultimately its destruction, and often results from an inappropriate immune response. Inflammation in the nervous system (“neuroinflammation”), especially when prolonged, can be particularly injurious. While inflammation per se may not cause disease, it contributes importantly to disease pathogenesis across both the peripheral (neuropathic pain, fibromyalgia) and central [e.g., Alzheimer disease, Parkinson disease, multiple sclerosis, motor neuron disease, ischemia and traumatic brain injury, depression, and autism spectrum disorder] nervous systems. The existence of extensive lines of communication between the nervous system and immune system represents a fundamental principle underlying neuroinflammation. Immune cell-derived inflammatory molecules are critical for regulation of host responses to inflammation. Although these mediators can originate from various non-neuronal cells, important sources in the above neuropathologies appear to be microglia and mast cells, together with astrocytes and possibly also oligodendrocytes. Understanding neuroinflammation also requires an appreciation that non-neuronal cell—cell interactions, between both glia and mast cells and glia themselves, are an integral part of the inflammation process. Within this context the mast cell occupies a key niche in orchestrating the inflammatory process, from initiation to prolongation. This review will describe the current state of knowledge concerning the biology of neuroinflammation, emphasizing mast cell-glia and glia-glia interactions, then conclude with a consideration of how a cell's endogenous mechanisms might be leveraged to provide a therapeutic strategy to target neuroinflammation. PMID:29618972

Primary central nervous system B-cell lymphoma in a young dog

PubMed Central

Kim, Na-Hyun; Ciesielski, Thomas; Kim, Jung H.; Yhee, Ji-Young; Im, Keum-Soon; Nam, Hae-Mi; Kim, Il-Hwan; Kim, Jong-Hyuk; Sur, Jung-Hyang

2012-01-01

This report describes a primary central nervous system B-cell lymphoma in a 3-year-old intact female Maltese dog. Canine primary central nervous system lymphomas constitute about 4% of all intracranial primary neoplasms, but comprehensive histopathologic classifications have rarely been carried out. This is the first report of this disease in a young adult dog. PMID:23115372

Classification of neural tumors in laboratory rodents, emphasizing the rat.

PubMed

Weber, Klaus; Garman, Robert H; Germann, Paul-Georg; Hardisty, Jerry F; Krinke, Georg; Millar, Peter; Pardo, Ingrid D

2011-01-01

Neoplasms of the nervous system, whether spontaneous or induced, are infrequent in laboratory rodents and very rare in other laboratory animal species. The morphology of neural tumors depends on the intrinsic functions and properties of the cell type, the interactions between the neoplasm and surrounding normal tissue, and regressive changes. The incidence of neural neoplasms varies with sex, location, and age of tumor onset. Although the onset of spontaneous tumor development cannot be established in routine oncogenicity studies, calculations using the time of diagnosis (day of death) have revealed significant differences in tumor biology among different rat strains. In the central nervous system, granular cell tumors (a meningioma variant), followed by glial tumors, are the most common neoplasms in rats, whereas glial cell tumors are observed most frequently in mice. Central nervous system tumors usually affect the brain rather than the spinal cord. Other than adrenal gland pheochromocytomas, the most common neoplasms of the peripheral nervous system are schwannomas. Neural tumors may develop in the central nervous system and peripheral nervous system from other cell lineages (including extraneural elements like adipose tissue and lymphocytes), but such lesions are very rare in laboratory animals.

Dispatches from the Interface of Salivary Bioscience and Neonatal Research

PubMed Central

Voegtline, Kristin M.; Granger, Douglas A.

2014-01-01

The emergence of the interdisciplinary field of salivary bioscience has created opportunity for neonatal researchers to measure multiple components of biological systems non-invasively in oral fluids. The implications are profound and potentially high impact. From a single oral fluid specimen, information can be obtained about a vast array of biological systems (e.g., endocrine, immune, autonomic nervous system) and the genetic polymorphisms related to individual differences in their function. The purpose of this review is to describe the state of the art for investigators interested in integrating these unique measurement tools into the current and next generation of research on gonadal steroid exposure during the prenatal and neonatal developmental periods. PMID:24624119

Allelic imbalance of multiple sclerosis susceptibility genes IKZF3 and IQGAP1 in human peripheral blood.

PubMed

Keshari, Pankaj K; Harbo, Hanne F; Myhr, Kjell-Morten; Aarseth, Jan H; Bos, Steffan D; Berge, Tone

2016-04-14

Multiple sclerosis is a chronic inflammatory, demyelinating disease of the central nervous system. Recent genome-wide studies have revealed more than 110 single nucleotide polymorphisms as associated with susceptibility to multiple sclerosis, but their functional contribution to disease development is mostly unknown. Consistent allelic imbalance was observed for rs907091 in IKZF3 and rs11609 in IQGAP1, which are in strong linkage disequilibrium with the multiple sclerosis associated single nucleotide polymorphisms rs12946510 and rs8042861, respectively. Using multiple sclerosis patients and healthy controls heterozygous for rs907091 and rs11609, we showed that the multiple sclerosis risk alleles at IKZF3 and IQGAP1 are expressed at higher levels as compared to the protective allele. Furthermore, individuals homozygous for the multiple sclerosis risk allele at IQGAP1 had a significantly higher total expression of IQGAP1 compared to individuals homozygous for the protective allele. Our data indicate a possible regulatory role for the multiple sclerosis-associated IKZF3 and IQGAP1 variants. We suggest that such cis-acting mechanisms may contribute to the multiple sclerosis association of single nucleotide polymorphisms at IKZF3 and IQGAP1.

[Stress and autonomic dysregulation in patients with fibromyalgia syndrome].

PubMed

Friederich, H-C; Schellberg, D; Mueller, K; Bieber, C; Zipfel, S; Eich, W

2005-06-01

The aim of the present study was to evaluate to what extent the orthostatic dysregulation of FMS patients can be attributed primarily to reduced baroreceptor-mediated activation of the sympathetic nervous system and whether a hyporeactive sympathetic nervous system can also be confirmed for mental stress. A total of 28 patients with primary FMS were examined and compared with 15 healthy subjects. Diagnostic investigations of the autonomic nervous system were based on measuring HRV in frequency range and assessing spontaneous baroreflex sensitivity (sBRS) under mental stress and passive orthostatism. Both under orthostatic and mental stress FMS patients exhibited reduced activation of the sympathetic nervous system as measured by the spectral power of HRV in the low-frequency range and the mean arterial blood pressure or heart rate. The present study provided no indications for dysregulation of sBRS. The results obtained confirm the hypothesis of a hyporeactive stress system in FMS patients for both peripherally and centrally mediated stimulation of the sympathetic nervous system.

Central sympathoexcitatory actions of angiotensin II: role of type 1 angiotensin II receptors.

PubMed

DiBona, G F

1999-01-01

The role of the renin-angiotensin system in the control of sympathetic nerve activity is reviewed. Two general mechanisms are considered, one that involves the effects of circulating angiotensin II (AngII) on the central nervous system and a second that involves the central nervous system effects of AngII that originates within the central nervous system. The role of type 1 AngII receptors in discrete brain sites that mediate the sympathoexcitatory actions of AngII of either circulating or central nervous system origin is examined. AngII of circulating origin has ready access to the subfornical organ and area postrema, where it can bind to type 1 AngII receptors on neurons whose connections to the nucleus tractus solitarius and rostral ventrolateral medulla result in sympathoexcitation. In the rostral ventrolateral medulla, angiotensin peptides of central nervous system origin, likely involving angiotensin species in addition to AngII and binding to receptors other than type 1 or 2 AngII receptors, tonically support sympathetic nerve activity.

Connections of the Lateral Hypothalamic Area Juxtadorsomedial Region in the Male Rat

PubMed Central

Hahn, Joel D.; Swanson, Larry W.

2014-01-01

The connections of the lateral hypothalamic area juxtadorsomedial region (LHAjd) were investigated in a series of pathway-tracing experiments involving iontophoretic co-injection of the tracers Phaseolus vulgaris-leucoagglutinin (PHA-L; for outputs) and cholera toxin B subunit (CTB; for inputs). Results revealed that the LHAjd has connections with some 318 distinct gray matter regions encompassing all four subsystems—motor, sensory, cognitive, and behavioral state—included in a basic structure–function network model of the nervous system. Integration of these subsystems is necessary for the coordination and control of emotion and behavior, and in that regard the connections of the LHAjd indicate that it may have a prominent role. Furthermore, the LHAjd connections, together with the connections of other LHA differentiations studied similarly to date, indicate a distinct topographic organization that suggests each LHA differentiation has specifically differing degrees of involvement in the control of multiple behaviors. For the LHAjd, its involvement to a high degree in the control of defensive behavior, and to a lesser degree in the control of other behaviors, including ingestive and reproductive, is suggested. Moreover, the connections of the LHAjd suggest that its possible role in the control of these behaviors may be very broad in scope because they involve the somatic, neuroendocrine, and autonomic divisions of the nervous system. In addition, we suggest that connections between LHA differentiations may provide, at the level of the hypothalamus, a neuronal substrate for the coordinated control of multiple themes in the behavioral repertoire. PMID:22488503

Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors.

PubMed

Pediaditakis, Iosif; Iliopoulos, Ioannis; Theologidis, Ioannis; Delivanoglou, Nickoleta; Margioris, Andrew N; Charalampopoulos, Ioannis; Gravanis, Achille

2015-01-01

Dehydroepiandosterone (DHEA), the most abundant steroid in humans, affects multiple cellular functions of the endocrine, immune, and nervous systems. However, up to quite recently, no receptor has been described specifically for it, whereas most of its physiological actions have been attributed to its conversion to either androgens or estrogens. DHEA interacts and modulate a variety of membrane and intracellular neurotransmitter and steroid receptors. We have recently reported that DHEA protects neuronal cells against apoptosis, interacting with TrkA, the high-affinity prosurvival receptor of the neurotrophin, nerve growth factor. Intrigued by its pleiotropic effects in the nervous system of a variety of species, we have investigated the ability of DHEA to interact with the other two mammalian neurotrophin receptors, ie, the TrkB and TrkC, as well as their invertebrate counterparts (orthologs) in mollusks Lymnaea and Aplysia and in cephalochordate fish Amphioxus. Amazingly, DHEA binds to all Trk receptors, although with lower affinity by 2 orders of magnitude compared with that of the polypeptidic neurotrophins. DHEA effectively induced the first step of the TrkA and TrkC receptors activation (phosphorylation at tyrosine residues), including the vertebrate neurotrophin nonresponding invertebrate Lymnaea and Aplysia receptors. Based on our data, we hypothesize that early in evolution, DHEA may have acted as a nonspecific neurotrophic factor promoting neuronal survival. The interaction of DHEA with all types of neurotrophin receptors offers new insights into the largely unidentified mechanisms of its actions on multiple tissues and organs known to express neurotrophin receptors.

Bis-Benzimidazole Hits against Naegleria fowleri Discovered with New High-Throughput Screens

PubMed Central

Rice, Christopher A.; Colon, Beatrice L.; Alp, Mehmet; Göker, Hakan; Boykin, David W.

2015-01-01

Naegleria fowleri is a pathogenic free-living amoeba (FLA) that causes an acute fatal disease known as primary amoebic meningoencephalitis (PAM). The major problem for infections with any pathogenic FLA is a lack of effective therapeutics, since PAM has a case mortality rate approaching 99%. Clearly, new drugs that are potent and have rapid onset of action are needed to enhance the treatment regimens for PAM. Diamidines have demonstrated potency against multiple pathogens, including FLA, and are known to cross the blood-brain barrier to cure other protozoan diseases of the central nervous system. Therefore, amidino derivatives serve as an important chemotype for discovery of new drugs. In this study, we validated two new in vitro assays suitable for medium- or high-throughput drug discovery and used these for N. fowleri. We next screened over 150 amidino derivatives of multiple structural classes and identified two hit series with nM potency that are suitable for further lead optimization as new drugs for this neglected disease. These include both mono- and diamidino derivatives, with the most potent compound (DB173) having a 50% inhibitory concentration (IC50) of 177 nM. Similarly, we identified 10 additional analogues with IC50s of <1 μM, with many of these having reasonable selectivity indices. The most potent hits were >500 times more potent than pentamidine. In summary, the mono- and diamidino derivatives offer potential for lead optimization to develop new drugs to treat central nervous system infections with N. fowleri. PMID:25605363

Immunomodulatory Effects Mediated by Dopamine

PubMed Central

Alvarez-Herrera, Samantha; Pérez-Sánchez, Gilberto; Becerril-Villanueva, Enrique; Cruz-Fuentes, Carlos; Flores-Gutierrez, Enrique Octavio; Quintero-Fabián, Saray

2016-01-01

Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R). The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS), there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers. PMID:27795960

The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system.

PubMed

Mihm, Bernhard; Bergmann, Markus; Brück, Wolfgang; Probst-Cousin, Stefan

2014-06-01

To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14-positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8-positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process. © 2013 Japanese Society of Neuropathology.

Magnetic resonance imaging characteristics in four dogs with central nervous system neosporosis.

PubMed

Parzefall, Birgit; Driver, Colin J; Benigni, Livia; Davies, Emma

2014-01-01

Neosporosis is a polysystemic disease that can affect dogs of any age and can cause inflammation of the central nervous system. Antemortem diagnosis can be challenging, as clinical and conventional laboratory test findings are often nonspecific. A previous report described cerebellar lesions in brain MRI studies of seven dogs and proposed that these may be characteristic for central nervous system Neosporosis. The purpose of this retrospective study was to describe MRI characteristics in another group of dogs with confirmed central nervous system neosporosis and compare them with the previous report. The hospital's database was searched for dogs with confirmed central nervous system neosporosis and four observers recorded findings from each dog's MRI studies. A total of four dogs met inclusion criteria. Neurologic examination was indicative of a forebrain and cerebellar lesion in dog 2 and multifocal central nervous system disease in dogs 1, 3, and 4. Magnetic resonance imaging showed mild bilateral and symmetrical cerebellar atrophy in three of four dogs (dogs 2, 3, 4), intramedullary spinal cord changes in two dogs (dogs 3, 4) and a mesencephalic and metencephalic lesion in one dog (dog 2). Multifocal brain lesions were recognized in two dogs (dogs 1, 4) and were present in the thalamus, lentiform nucleus, centrum semiovale, internal capsule, brainstem and cortical gray matter of the frontal, parietal or temporal lobe. Findings indicated that central nervous system neosporosis may be characterized by multifocal MRI lesions as well as cerebellar involvement in dogs. © 2014 American College of Veterinary Radiology.

Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis

PubMed Central

Díaz-Balzac, Carlos A.; Lázaro-Peña, María I.; Vázquez-Figueroa, Lionel D.; Díaz-Balzac, Roberto J.; García-Arrarás, José E.

2016-01-01

The Echinodermata comprise an interesting branch in the phylogenetic tree of deuterostomes. Their radial symmetry which is reflected in their nervous system anatomy makes them a target of interest in the study of nervous system evolution. Until recently, the study of the echinoderm nervous system has been hindered by a shortage of neuronal markers. However, in recent years several markers of neuronal and fiber subpopulations have been described. These have been used to identify subpopulations of neurons and fibers, but an integrative study of the anatomical relationship of these subpopulations is wanting. We have now used eight commercial antibodies, together with three antibodies produced by our group to provide a comprehensive and integrated description and new details of the echinoderm neuroanatomy using the holothurian Holothuria glaberrima (Selenka, 1867) as our model system. Immunoreactivity of the markers used showed: (1) specific labeling patterns by markers in the radial nerve cords, which suggest the presence of specific nerve tracts in holothurians. (2) Nerves directly innervate most muscle fibers in the longitudinal muscles. (3) Similar to other deuterostomes (mainly vertebrates), their enteric nervous system is composed of a large and diverse repertoire of neurons and fiber phenotypes. Our results provide a first blueprint of the anatomical organization of cells and fibers that form the holothurian neural circuitry, and highlight the fact that the echinoderm nervous system shows unexpected diversity in cell and fiber types and their distribution in both central and peripheral nervous components. PMID:26987052

Is There Anything "Autonomous" in the Nervous System?

ERIC Educational Resources Information Center

Rasia-Filho, Alberto A.

2006-01-01

The terms "autonomous" or "vegetative" are currently used to identify one part of the nervous system composed of sympathetic, parasympathetic, and gastrointestinal divisions. However, the concepts that are under the literal meaning of these words can lead to misconceptions about the actual nervous organization. Some clear-cut examples indicate…

A map of terminal regulators of neuronal identity in Caenorhabditis elegans

PubMed Central

2016-01-01

Our present day understanding of nervous system development is an amalgam of insights gained from studying different aspects and stages of nervous system development in a variety of invertebrate and vertebrate model systems, with each model system making its own distinctive set of contributions. One aspect of nervous system development that has been among the most extensively studied in the nematode Caenorhabditis elegans is the nature of the gene regulatory programs that specify hardwired, terminal cellular identities. I first summarize a number of maps (anatomical, functional, and molecular) that describe the terminal identity of individual neurons in the C. elegans nervous system. I then provide a comprehensive summary of regulatory factors that specify terminal identities in the nervous system, synthesizing these past studies into a regulatory map of cellular identities in the C. elegans nervous system. This map shows that for three quarters of all neurons in the C. elegans nervous system, regulatory factors that control terminal identity features are known. In‐depth studies of specific neuron types have revealed that regulatory factors rarely act alone, but rather act cooperatively in neuron‐type specific combinations. In most cases examined so far, distinct, biochemically unlinked terminal identity features are coregulated via cooperatively acting transcription factors, termed terminal selectors, but there are also cases in which distinct identity features are controlled in a piecemeal fashion by independent regulatory inputs. The regulatory map also illustrates that identity‐defining transcription factors are reemployed in distinct combinations in different neuron types. However, the same transcription factor can drive terminal differentiation in neurons that are unrelated by lineage, unrelated by function, connectivity and neurotransmitter deployment. Lastly, the regulatory map illustrates the preponderance of homeodomain transcription factors in the control of terminal identities, suggesting that these factors have ancient, phylogenetically conserved roles in controlling terminal neuronal differentiation in the nervous system. WIREs Dev Biol 2016, 5:474–498. doi: 10.1002/wdev.233 For further resources related to this article, please visit the WIREs website. PMID:27136279