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Sample records for nervous system cancers

  1. Cancer stem cells in nervous system tumors.

    PubMed

    Singh, Sheila K; Clarke, Ian D; Hide, Takuichiro; Dirks, Peter B

    2004-09-20

    Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, evidence in leukemia and more recently in solid tumors such as breast cancer suggests that the tumor cell population is heterogeneous with respect to proliferation and differentiation. Recently, several groups have described the existence of a cancer stem cell population in human brain tumors of different phenotypes from both children and adults. The finding of brain tumor stem cells (BTSCs) has been made by applying the principles for cell culture and analysis of normal neural stem cells (NSCs) to brain tumor cell populations and by identification of cell surface markers that allow for isolation of distinct tumor cell populations that can then be studied in vitro and in vivo. A population of brain tumor cells can be enriched for BTSCs by cell sorting of dissociated suspensions of tumor cells for the NSC marker CD133. These CD133+ cells, which also expressed the NSC marker nestin, but not differentiated neural lineage markers, represent a minority fraction of the entire brain tumor cell population, and exclusively generate clonal tumor spheres in suspension culture and exhibit increased self-renewal capacity. BTSCs can be induced to differentiate in vitro into tumor cells that phenotypically resembled the tumor from the patient. Here, we discuss the evidence for and implications of the discovery of a cancer stem cell in human brain tumors. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC. Specific genetic and molecular analyses of the BTSC will further our understanding of the mechanisms of brain tumor growth, reinforcing parallels between normal neurogenesis and brain tumorigenesis.

  2. Report from the Fifth National Cancer Institute Mouse Models of Human Cancers Consortium Nervous System Tumors Workshop

    PubMed Central

    Gutmann, David H.; Stiles, Charles D.; Lowe, Scott W.; Bollag, Gideon E.; Furnari, Frank B.; Charest, Al

    2011-01-01

    Cancers of the nervous system are clinically challenging tumors that present with varied histopathologies and genetic etiologies. While the prognosis for the most malignant of these tumors is essentially unchanged despite decades of basic and translational science research, the past few years have witnessed the identification of numerous targetable molecular alterations in these cancers. With the advent of advanced genomic sequencing methodologies and the development of accurate small-animal models of these nervous system cancers, we are now ideally positioned to develop personalized therapies that target the unique cellular and molecular changes that define their formation and drive their continued growth. Recently, the National Cancer Institute convened a workshop to advance our understanding of nervous system cancer mouse models and to inform clinical trials by reconsidering these neoplasms as complex biological systems characterized by heterogeneity at all levels. PMID:21727208

  3. Clinical trial aims to study immunotherapy for central nervous system tumors | Center for Cancer Research

    Cancer.gov

    A new clinical trial aims to determine whether nivolumab, an immune checkpoint inhibitor, can improve control of cancer for patients with several types of tumors of the central nervous system (CNS). The CNS is composed of the brain and spinal cord and the cause of most CNS tumors in adults is unknown. Learn more...

  4. 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 and ... blood vessels. When something goes wrong in this system, it can cause serious problems, including Blood pressure ...

  5. Progress in the Biological Understanding and Management of Breast Cancer-Associated Central Nervous System Metastases

    PubMed Central

    Gonzalez-Angulo, Ana M.

    2013-01-01

    Metastasis to the central nervous system (CNS) is a devastating neurological complication of systemic cancer. Brain metastases from breast cancer have been documented to occur in approximately 10%–16% of cases over the natural course of the disease with leptomeningeal metastases occurring in approximately 2%–5% of cases of breast cancer. CNS metastases among women with breast cancer tend to occur among those who are younger, have larger tumors, and have a more aggressive histological subtype such as the triple negative and HER2-positive subtypes. Treatment of CNS metastases involves various combinations of whole brain radiation therapy, surgery, stereotactic radiosurgery, and chemotherapy. We will discuss the progress made in the treatment and prevention of breast cancer-associated CNS metastases and will delve into the biological underpinnings of CNS metastases including evaluating the role of breast tumor subtype on the incidence, natural history, prognostic outcome, and impact of therapeutic efficacy. PMID:23740934

  6. 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.

  7. A case report of gastric cancer with brain metastasis: Rare peripheral nervous system symptoms.

    PubMed

    Yang, Ge-Liang; Luo, Tian-Hang; Zhang, Hui-Qing; Ling, Chang-Quan; Li, Bai

    2016-04-01

    Gastric cancer with brain metastasis is rare. The present study reports a case of gastric cancer with isolated brain metastasis 1 year after gastrectomy. To the best of our knowledge, there have been no prior reports of solitary brain metastasis from gastric cancer with peripheral nervous system symptoms. A distal gastrectomy was performed on a 60-year-old male patient with gastric cancer in November 2012. Postoperative pathological analysis revealed a moderately differentiated adenocarcinoma with tumor invasion into the serosa and metastasis to one dissected lymph node. No abnormalities were found at follow-up examination. However, a tumor representing metastasis to the brain was recognized by a cranial enhanced magnetic resonance imaging examination 1 year after gastrectomy, which was performed when the patient exhibited numbness and thigmesthesia. The patient was administered 30 Gy of stereotactic radiotherapy, delivered in 5 fractions. The patient succumbed to disease 10 months subsequent to undergoing radiotherapy. This case report suggests that gastric cancer may re-present as brain metastasis with peripheral nervous system symptoms.

  8. Semaphorin 5A mediated cellular navigation: connecting nervous system and cancer

    PubMed Central

    Purohit, Abhilasha; Sadanandam, Anguraj; Myneni, Pavan; Singh, Rakesh K.

    2014-01-01

    The ultraprecise wiring of neurons banks on the instructions provided by guidance cue proteins that steer them to their appropriate target tissue during neuronal development. Semaphorins are one such family of proteins. Semaphorins are known to play major physiological roles during the development of various organs including nervous system, cardiovascular, and immune systems. Their role in different pathologies including cancer remains an intense area of investigation. This review focuses on a novel member of this family of proteins, semaphorin 5A, which is much less explored in comparison to its other affiliates. Recent reports suggest that semaphorins play important roles in the pathology of cancer by affecting angiogenesis, tumor growth and metastasis. We will firstly give a general overview of the semaphorin family and its receptors. Next, we discuss their roles in cellular movements and how that makes them a connecting link between nervous system and cancer. Finally, we focus our discussion on semaphorin 5A to summarize the prevailing knowledge for this molecule in developmental biology and carcinogenesis. PMID:25263940

  9. Semaphorin 5A mediated cellular navigation: connecting nervous system and cancer.

    PubMed

    Purohit, Abhilasha; Sadanandam, Anguraj; Myneni, Pavan; Singh, Rakesh K

    2014-12-01

    The ultraprecise wiring of neurons banks on the instructions provided by guidance cue proteins that steer them to their appropriate target tissue during neuronal development. Semaphorins are one such family of proteins. Semaphorins are known to play major physiological roles during the development of various organs including the nervous, cardiovascular, and immune systems. Their role in different pathologies including cancer remains an intense area of investigation. This review focuses on a novel member of this family of proteins, semaphorin 5A, which is much less explored in comparison to its other affiliates. Recent reports suggest that semaphorins play important roles in the pathology of cancer by affecting angiogenesis, tumor growth and metastasis. We will firstly give a general overview of the semaphorin family and its receptors. Next, we discuss their roles in cellular movements and how that makes them a connecting link between the nervous system and cancer. Finally, we focus our discussion on semaphorin 5A to summarize the prevailing knowledge for this molecule in developmental biology and carcinogenesis.

  10. The Complex Diagnostic Challenge in Children With Non-Central Nervous System Cancer and Cerebellar Mutism.

    PubMed

    Helton, Kathleen; Patterson, Amy L; Khan, Raja B; Sadighi, Zsila S

    2017-08-01

    Multiple etiologies should be considered in the differential diagnosis of immunocompromised patients with non-central nervous system cancer and viral infections who develop mutism. Acute cerebellitis, caused by infections or by neurotoxicity resulting from chemotherapy; paraneoplastic cerebellar degeneration; atypical posterior reversible encephalopathy syndrome; and acute disseminated encephalomyelitis may all cause mutism in such patients. This condition warrants prompt recognition and may require treatment with immunotherapy, as it may be an immune-mediated process. We present 2 patients with leukemia and viral illness who developed cerebellar mutism in the setting of acute cerebellitis and responded to immunotherapy, suggesting that the condition involved a parainfectious immune-mediated response.

  11. Clinical Characteristics, Pathophysiology, and Management of Noncentral Nervous System Cancer-Related Cognitive Impairment in Adults

    PubMed Central

    Wefel, Jeffrey S.; Kesler, Shelli R.; Noll, Kyle R.; Schagen, Sanne B.

    2014-01-01

    Over the past few decades, a body of research has emerged confirming what many adult patients with noncentral nervous system cancer have long reported—that cancer and its treatment are frequently associated with cancer-related cognitive impairment (CRCI). The severity of CRCI varies, and symptoms can emerge early or late in the disease course. Nonetheless, CRCI is typically mild to moderate in nature and primarily involves the domains of memory, attention, executive functioning, and processing speed. Animal models and novel neuroimaging techniques have begun to unravel the pathophysiologic mechanisms underlying CRCI, including the role of inflammatory cascades, direct neurotoxic effects, damage to progenitor cells, white matter abnormalities, and reduced functional connectivity, among others. Given the paucity of research on CRCI with other cancer populations, this review synthesizes the current literature with a deliberate focus on CRCI within the context of breast cancer. A hypothetical case-study approach is used to illustrate how CRCI often presents clinically and how current science can inform practice. While the literature regarding intervention for CRCI is nascent, behavioral and pharmacologic approaches are discussed. PMID:25483452

  12. SUBSEQUENT NEOPLASMS OF THE CENTRAL NERVOUS SYSTEM AMONG SURVIVORS OF CHILDHOOD CANCER: A SYSTEMATIC REVIEW

    PubMed Central

    Bowers, Daniel C.; Nathan, Paul C.; Constine, Louis; Woodman, Catherine; Bhatia, Smita; Keller, Karen; Bashore, Lisa

    2015-01-01

    Childhood cancer survivors are at risk for development of subsequent neoplasms of the central nervous system (CNS). Better understanding of the rates, risk factors for and outcomes of subsequent neoplasms of the CNS among survivors of childhood cancer may lead to the development of more informed screening guidelines. Two independent investigators independently performed a systematic search of studies from the MEDLINE and EMBASE databases (1966 – 2012) for studies examining subsequent neoplasms of the CNS among childhood cancer survivors. Articles were selected to answer 3 questions: What is the risk of CNS tumors following radiation to the cranium for a pediatric cancer as compared with the general population? What are the outcomes in children with subsequent neoplasms of the CNS who have been treated with CNS directed radiation for a pediatric cancer? Are outcomes of subsequent neoplasms different from primary neoplasms of the same histology? Our search identified 72 reports, of which 18 publications were included in this review. These studies reported that childhood cancer survivors have an 8.1 – 52.3 times higher incidence of subsequent CNS neoplasms compared with the general population. Nearly all cancer survivors who developed a CNS neoplasm had been exposed to cranial radiation; some studies demonstrate a correlation between radiation dose and risk of subsequent CNS tumors. Five year survival rates for subsequent high-grade gliomas and meningiomas range from 0 – 19.5% and 73 – 100%, respectively, which are similar to those observed in patients with primary gliomas or meningiomas. The quality of evidence was limited by variation in study design, heterogeneity of details regarding treatment and outcomes, limited follow-up and relatively small sample sizes. We concluded that survivors of childhood cancer who were treated with cranial radiation therapy have an elevated risk for subsequent CNS neoplasms. The current literature is insufficient to comment

  13. Nervous System Lyme Disease.

    PubMed

    Halperin, John J

    2015-12-01

    Nervous system involvement occurs in 10% to 15% of patients infected with the tick-borne spirochetes Borrelia burgdorferi, B afzelii, and B garinii. Peripheral nervous system involvement is common. Central nervous system (CNS) involvement, most commonly presenting with lymphocytic meningitis, causes modest cerebrospinal fluid (CSF) pleocytosis. Parenchymal CNS infection is rare. If the CNS is invaded, however, measuring local production of anti-B burgdorferi antibodies in the CSF provides a useful marker of infection. Most cases of neuroborreliosis can be cured with oral doxycycline; parenteral regimens should be reserved for patients with particularly severe disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Brain and Nervous System

    MedlinePlus

    ... such as the beating of your heart, the digestion of your food, and yes, even the amount ... functions, like breathing, heart rate, blood pressure, swallowing, digestion, and blinking. previous continue How the Nervous System ...

  15. DNA damage response in peripheral nervous system: coping with cancer therapy-induced DNA lesions.

    PubMed

    Englander, Ella W

    2013-08-01

    In the absence of blood brain barrier (BBB) the DNA of peripheral nervous system (PNS) neurons is exposed to a broader spectrum of endogenous and exogenous threats compared to that of the central nervous system (CNS). Hence, while CNS and PNS neurons cope with many similar challenges inherent to their high oxygen consumption and vigorous metabolism, PNS neurons are also exposed to circulating toxins and inflammatory mediators due to relative permeability of PNS blood nerve barrier (BNB). Consequently, genomes of PNS neurons incur greater damage and the question awaiting investigation is whether specialized repair mechanisms for maintenance of DNA integrity have evolved to meet the additional needs of PNS neurons. Here, I review data showing how PNS neurons manage collateral DNA damage incurred in the course of different anti-cancer treatments designed to block DNA replication in proliferating tumor cells. Importantly, while PNS neurotoxicity and concomitant chemotherapy-induced peripheral neuropathy (CIPN) are among major dose limiting barriers in achieving therapy goals, CIPN is partially reversible during post-treatment nerve recovery. Clearly, cell recovery necessitates mobilization of the DNA damage response and underscores the need for systematic investigation of the scope of DNA repair capacities in the PNS to help predict post-treatment risks to recovering neurons.

  16. Progressive central nervous system metastases in responder patients for outside central nervous system metastases on trastuzumab-based therapy--report of two cases of refractory breast cancer.

    PubMed

    Okita, Riki; Saeki, Toshiaki; Takashima, Shigemitsu; Aogi, Kenjiro; Ohsumi, Shozo

    2005-03-01

    We report two cases of central nervous system (CNS) metastases during systemic response to trastuzumab in combination with chemotherapy for refractory breast cancer. The patients responded to trastuzumab in combination with chemotherapy. During combination treatment, the patients developed cerebellar metastases. A follow-up computed tomography scan revealed that their diseases continued to respond outside the CNS. These cases suggest that the failure of trastuzumab to cross the blood-brain barrier may compromise its overall effectiveness and raises the possibility that CNS metastasis may become clinically more significant in patients receiving antibody-based therapies, including patients responding to therapy outside the CNS. Additionally, repeated stereotactic radiosurgery as gammaknife combination therapy synchronously with systematic trastuzumab-based therapy was useful for the treatment of metastatic breast carcinoma.

  17. Descriptive epidemiology of brain and central nervous system cancers in Central and South America.

    PubMed

    Piñeros, Marion; Sierra, Mónica S; Izarzugaza, M Isabel; Forman, David

    2016-09-01

    Although malignant tumors of the brain and central nervous system (CNS) represent less than 3% of new cancer cases estimated worldwide, they cause significant morbidity and in the case of gliomas, the most common histological type, have a poor prognosis. We describe patterns and trends in brain and CNS incidence and mortality in Central and South America. We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries and cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence rates (ASRs) and mortality rates (ASMRs) per 100,000 person-years, and present incidence by histological subtypes. In general, incidence rates were higher in males than in females. The highest incidence ASRs were observed for Cuba (5.1 males, 3.6 females) in Central America, and for Brazil (6.4 males, 4.8 females) and Uruguay (6.2 and 4.0) in South America. Mortality rates closely followed the pattern of incidence rates. Argentina, Brazil and Chile showed increasing mortality trends, although these were not statistically significant. Glioma and unspecified tumors were the most common histological types, accounting for 55.4% and 32.8%, respectively. The proportion of microscopically verified diagnoses was 47-70% in most countries. Although incidence and mortality rates in general were low, some countries displayed high- to intermediate-level incidence rates; under-reporting and under-ascertainment of cases could contribute to the geographic variations observed. There is a need to improve both the ascertainment of cases and the accuracy of histological diagnosis. Monitoring of brain and CNS cancers along with etiological research remain priorities. Copyright © 2016 International Agency for Research on Cancer. Published by Elsevier Ltd.. All rights reserved.

  18. Preclinical Modeling and Therapeutic Avenues for Cancer Metastasis to the Central Nervous System.

    PubMed

    Singh, Mohini; Bakhshinyan, David; Venugopal, Chitra; Singh, Sheila K

    2017-01-01

    Metastasis is the dissemination of cells from the primary tumor to other locations within the body, and continues to be the predominant cause of death among cancer patients. Metastatic progression within the adult central nervous system is 10 times more frequent than primary brain tumors. Metastases affecting the brain parenchyma and leptomeninges are associated with grave prognosis, and even after successful control of the primary tumor the median survival is a dismal 2-3 months with treatment options typically limited to palliative care. Current treatment options for brain metastases (BM) and disseminated brain tumors are scarce, and the improvement of novel targeted therapies requires a broader understanding of the biological complexity that characterizes metastatic progression. In this review, we provide insight into patterns of BM progression and leptomeningeal spread, outlining the development of clinically relevant in vivo models and their contribution to the discovery of innovative cancer therapies. In vivo models paired with manipulation of in vitro methods have expanded the tools available for investigators to develop agents that can be used to prevent or treat metastatic disease. The knowledge gained from the use of such models can ultimately lead to the prevention of metastatic dissemination and can extend patient survival by transforming a uniformly fatal systemic disease into a locally controlled and eminently more treatable one.

  19. Cancer risks in children with congenital malformations in the nervous and circulatory system-A population based cohort study.

    PubMed

    Sun, Yuelian; Overvad, Kim; Olsen, Jørn

    2014-08-01

    We estimated the age and organ-specific cancer risk for children with a congenital malformation (CM) in the nervous or in the circulatory system. We identified 1,709,456 live born singletons in Denmark between 1 January 1977 and 31 December 2007 and excluded children with chromosomal birth defects. Information on CMs was obtained from the Danish National Hospital Register. Information on cancer occurrence was obtained from the Danish Cancer Registry. We applied Cox proportional hazards regression model to estimate hazard ratios (HR) for cancer. Children entered into the CM cohort on the day of birth regardless of when the CM was diagnosed or on the day of CM diagnosis in an alternative analysis. Overall, 4484 (0.26%) and 24,643 (1.44%) children were diagnosed with a CM in the nervous and in the circulatory system, respectively. Compared with children without any CM, children with a CM in the nervous system had a 5.97 fold (95%CI [confidence interval]: 4.66-7.64) higher risk of cancer, including cancer in the central nervous system (HR=18.84, 95%CI: 12.67-28.01), in the mesothelial and soft tissue (HR=15.64, 95%CI: 7.99-30.60), in the skin (HR=4.91, 95%CI: 2.19-11.0). The associations were stronger early in life. Children with a CM in the circulatory system had a 2.64 fold (95%CI: 2.21-3.16) higher risk of cancer, including cancer in the lymphatic and haematopoietic tissues (HR=3.22, 95%CI: 2.43-4.27) and cancer in the CNS (HR=2.40, 95%CI: 1.43-4.02). Some of these associations were weaker in the alternative analysis. Children with subtypes of CM in the two systems showed a higher cancer risk. Children who were diagnosed with a CM in the nervous system had a substantially higher cancer risk especially early in life. Children diagnosed with a CM in the circulatory system had a moderately higher cancer risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Consensus Conference on Cancer Registration of Brain and Central Nervous System Tumors1

    PubMed Central

    McCarthy, Bridget J.; Kruchko, Carol

    2005-01-01

    The passage of Public Law 107–260, the Benign Brain Tumor Cancer Registries Amendment Act, in October 2002 has made the collection of all primary brain tumors a reality. However, at the first Consensus Conference on Brain Tumor Definition for Registration in 2002, and during the development of training materials for benign brain tumor collection, several issues were identified that were tabled for future discussion. These and other issues were addressed at the subsequent 2003 Consensus Conference on Cancer Registration of Brain and Central Nervous System Tumors, at which the Central Brain Tumor Registry of the United States facilitated a discussion among epidemiologists, neurosurgeons, and neuro-pathologists. Multidisciplinary consensus was reached on four points, for which the following recommendations were made: (1) amend the histology coding scheme for cysts and tumor-like lesions that currently have a code in the third edition of the International Classification of Disease for Oncology (ICDO), (2) collect data on all instances of specific cysts and tumor-like lesions that are located in brain and other CNS sites but currently lack ICDO codes, (3) establish a new ICDO topography site for skull base tumors for the brain and CNS, and (4) collect data on genetic syndromes in patients diagnosed with brain or CNS tumors. We view this conference as part of a continuing process. Because classification of primary intracranial and other CNS tumors is dynamic, and the registration and coding of these tumors will need to be periodically reviewed. PMID:15831238

  1. The Nervous System Game

    ERIC Educational Resources Information Center

    Corbitt, Cynthia; Carpenter, Molly

    2006-01-01

    For many children, especially those with reading difficulties, a motor-kinesthetic learning activity may be an effective tool to teach complex concepts. With this in mind, the authors developed and tested a game designed to teach fourth- to sixth-grade children some basic principles of nervous system function by allowing the children themselves to…

  2. The Nervous System Game

    ERIC Educational Resources Information Center

    Corbitt, Cynthia; Carpenter, Molly

    2006-01-01

    For many children, especially those with reading difficulties, a motor-kinesthetic learning activity may be an effective tool to teach complex concepts. With this in mind, the authors developed and tested a game designed to teach fourth- to sixth-grade children some basic principles of nervous system function by allowing the children themselves to…

  3. Anti-angiogenetic therapies for central nervous system metastases from non-small cell lung cancer

    PubMed Central

    Buttigliero, Consuelo; Novello, Silvia

    2016-01-01

    Central nervous system (CNS) metastases are common in patients with advanced non-small cell lung cancer (NSCLC), occurring in 24% to 44% of patients in the course of their disease and confer significant morbidity and mortality. Systemic therapies have been deemed ineffective in brain metastases (BM) under the hypothesis that the blood-brain barrier (BBB) limits their delivery to the brain. Angiogenesis, which is mainly mediated by vascular endothelial growth factor (VEGF) pathway, is crucial for tumor survival, growth and invasion both in primary and metastatic brain lesions. Two major categories of agents have been developed to target this pathway: antibody-based agents and VEGF receptor tyrosine kinase inhibitors (TKIs). Clinical benefits have been shown with anti-angiogenetic therapies in the treatment of metastatic NSCLC. However, patients with CNS metastases were often excluded from trials with these agents, due to concerns about a potentially greater risk of cerebral haemorrhage and thromboembolic disease. Therefore, the overall efficacy and safety of angiogenetic agents in patients with BM from NSCLC are yet to be clarified. This paper aims to review available data about the efficacy and safety of anti-angiogenetic therapies for CNS metastases in NSCLC patients. PMID:28149756

  4. Developmental therapeutics for patients with breast cancer and central nervous system metastasis: current landscape and future perspectives.

    PubMed

    Costa, R; Carneiro, B A; Wainwright, D A; Santa-Maria, C A; Kumthekar, P; Chae, Y K; Gradishar, W J; Cristofanilli, M; Giles, F J

    2016-10-03

    Breast cancer is the second-leading cause of metastatic disease in the central nervous system (CNS). Recent advances in the biological understanding of breast cancer have facilitated an unprecedented increase of survival in a subset of patients presenting with metastatic breast cancer. Patients with HER2 positive (HER2+) or triple negative breast cancer are at highest risk of developing CNS metastasis, and typically experience a poor prognosis despite treatment with local and systemic therapies. Among the obstacles ahead in the realm of developmental therapeutics for breast cancer CNS metastasis is the improvement of our knowledge on its biological nuances and on the interaction of the blood brain barrier with new compounds. This manuscript reviews recent discoveries related to the underlying biology of breast cancer brain metastases, clinical progress to date and suggests rational approaches for investigational therapies.

  5. Imaging nervous system activity.

    PubMed

    Fields, Douglas R; Shneider, Neil; Mentis, George Z; O'Donovan, Michael J

    2009-10-01

    This unit describes methods for loading ion- and voltage-sensitive dyes into neurons, with a particular focus on the spinal cord as a model system. In addition, we describe the use of these dyes to visualize neural activity. Although the protocols described here concern spinal networks in culture or an intact in vitro preparation, they can be, and have been, widely used in other parts of the nervous system.

  6. Clinical outcomes of a cohort of patients with central nervous system metastases from thyroid cancer

    PubMed Central

    Macedo, Daniel; Bugalho, Maria João

    2016-01-01

    Introduction Metastases to central nervous system (M1-CNS) are rarely reported in thyroid cancer (TC) patients. We aimed to characterize patients with M1-CNS from TC followed in our department. Methods Review of the medical records of 27 patients with TC-related M1-CNS. Results Mean age at TC diagnosis was 56.9 ± 19.1 years. Papillary TC (55.6%) was the commonest histological type, followed by poorly differentiated (18.5%), medullary (11.1%), follicular (7.4%) and Hürthle cell (7.4%) carcinomas. Angioinvasion and extrathyroidal extension were observed in a high number of patients. At M1-CNS diagnosis, other distant metastases were already present in 77.8% of the patients. Treatment directed to M1-CNS was offered to 20 (74%) patients: 1 was submitted to surgery, 18 to radiotherapy (either whole-brain radiotherapy or stereotaxic radiosurgery or both) and 4 to surgery and radiotherapy. Four patients received cytotoxic chemotherapy and one was submitted to 131I. Median survival since M1-CNS detection was 5.0 months. The only factor associated with better survival was surgery to brain metastases (P = 0.012). Conclusions The management of these patients is very challenging given the inexistence of effective treatments, except for brain surgery in selected cases. PMID:27856495

  7. Malignant involvement of the peripheral nervous system in patients with cancer: multimodality imaging and pathologic correlation.

    PubMed

    Crush, Andrew Bryce; Howe, Benjamin Matthew; Spinner, Robert J; Amrami, Kimberly K; Hunt, Christopher Harker; Johnson, Geoffrey B; Murphy, Robert C; Morreale, Robert F; Peller, Patrick J

    2014-01-01

    The clinical and imaging evaluation of peripheral neuropathies in patients with cancer is challenging. It is critically important to differentiate malignant invasion of the peripheral nervous system from nonmalignant causes, such as radiation-induced neuritis, neuropathy associated with chemotherapy, and inflammatory neuropathies. Contrast material-enhanced magnetic resonance (MR) imaging is the initial noninvasive test of choice; however, interpretation can be challenging when the anatomic features are distorted by prior surgery, radiation, or both. Fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an imaging adjunct to MR imaging that is particularly helpful for evaluating peripheral nerves because the metabolic activity depicted with (18)F-FDG PET/CT helps differentiate malignant from benign disease and assists in making certain management decisions. For example, sites of high (18)F-FDG activity in a peripheral nerve can be targeted to increase the diagnostic yield of a biopsy because malignant involvement of peripheral nerves can be patchy. Of note, (18)F-FDG PET/CT can show clinically unsuspected metastases elsewhere in the body. If cancer is found, (18)F-FDG PET/CT allows excellent assessment of treatment response. (18)F-FDG PET/CT is also useful in evaluating primary nerve sheath tumors in that such tumors with low metabolic activity on FDG PET/CT images are unlikely to be malignant, although the specificity is limited. It is essential to have a good understanding of the imaging characteristics of benign and malignant causes of peripheral neuropathy if (18)F-FDG PET/CT is to be used effectively for accurate diagnosis.

  8. Central nervous system toxicity.

    PubMed

    Ruha, Anne-Michelle; Levine, Michael

    2014-02-01

    Central nervous system toxicity caused by xenobiotic exposure is a common reason for presentation to the emergency department. Sources of exposure may be medicinal, recreational, environmental, or occupational; the means of exposure may be intentional or unintended. Toxicity may manifest as altered thought content resulting in psychosis or confusion; may affect arousal, resulting in lethargy, stupor, or coma; or may affect both elements of consciousness. Seizures may also occur. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. NASA Models of Space Radiation Induced Cancer, Circulatory Disease, and Central Nervous System Effects

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Chappell, Lori J.; Kim, Myung-Hee Y.

    2013-01-01

    The risks of late effects from galactic cosmic rays (GCR) and solar particle events (SPE) are potentially a limitation to long-term space travel. The late effects of highest concern have significant lethality including cancer, effects to the central nervous system (CNS), and circulatory diseases (CD). For cancer and CD the use of age and gender specific models with uncertainty assessments based on human epidemiology data for low LET radiation combined with relative biological effectiveness factors (RBEs) and dose- and dose-rate reduction effectiveness factors (DDREF) to extrapolate these results to space radiation exposures is considered the current "state-of-the-art". The revised NASA Space Risk Model (NSRM-2014) is based on recent radio-epidemiology data for cancer and CD, however a key feature of the NSRM-2014 is the formulation of particle fluence and track structure based radiation quality factors for solid cancer and leukemia risk estimates, which are distinct from the ICRP quality factors, and shown to lead to smaller uncertainties in risk estimates. Many persons exposed to radiation on earth as well as astronauts are life-time never-smokers, which is estimated to significantly modify radiation cancer and CD risk estimates. A key feature of the NASA radiation protection model is the classification of radiation workers by smoking history in setting dose limits. Possible qualitative differences between GCR and low LET radiation increase uncertainties and are not included in previous risk estimates. Two important qualitative differences are emerging from research studies. The first is the increased lethality of tumors observed in animal models compared to low LET radiation or background tumors. The second are Non- Targeted Effects (NTE), which include bystander effects and genomic instability, which has been observed in cell and animal models of cancer risks. NTE's could lead to significant changes in RBE and DDREF estimates for GCR particles, and the potential

  10. Characteristics of breast cancer patients with central nervous system metastases: a single-center experience.

    PubMed

    Harputluoglu, Hakan; Dizdar, Omer; Aksoy, Sercan; Kilickap, Saadettin; Dede, Didem S; Ozisik, Yavuz; Guler, Nilufer; Barista, Ibrahim; Gullu, Ibrahim; Hayran, Mutlu; Selek, Ugur; Cengiz, Mustafa; Zorlu, Faruk; Tekuzman, Gulten; Altundag, Kadri

    2008-05-01

    The aim of this study was to assess the characteristics of breast cancer patients with central nervous system (CNS) metastases and factors associated with survival after development of CNS metastasis. One-hundred-forty-four patients with brain metastases were retrospectively analyzed. Median age at the time of brain metastasis diagnosis was 48.9. Median time between initial diagnosis and development of brain metastasis was 36 months. Fourteen cases had leptomeningeal involvement. Twenty-two patients (15.3%) had single metastasis. Ten percent of the patients had surgery, 94% had radiotherapy and 63% had chemotherapy. Median survival after development of brain metastasis was 7.4 months. Survival of patients with single metastasis was significantly longer than those with multiple metastases (33.5 vs. 6.5 months, p = 0.0006). Survival of patients who received chemotherapy was significantly longer than those who received radiotherapy alone (9.9 vs. 2 months, p < 0.0001). In multivariate Cox regression analyses, presence of single metastasis and application of chemotherapy were the only significant factors associated with better survival (p = 0.047 and p < 0.0001, respectively). Age at initial diagnosis or at the time of brain metastasis, time from initial diagnosis to development of brain metastasis, menopausal status, tumor stage, grade, hormone receptor or HER2 status individually were not associated with survival. In this study, survival after the diagnosis of CNS metastases appeared to be affected by patient characteristics rather than biologic characteristics of the tumor. This is probably secondary to the lack of effective treatment options in these patients and overall poor prognosis.

  11. Central nervous system metastasis secondary to colorectal cancer: a retrospective cohort study of 20 cases

    PubMed Central

    Mondaca, Sebastián; Hornig, Valentina; Munoz-Schuffenegger, Pablo; Acevedo, Francisco; Garrido, Marcelo; Nervi, Bruno

    2016-01-01

    Introduction Involvement of the central nervous system (CNS) secondary to colorectal cancer is infrequent and associated with a poor prognosis. Its treatment is extrapolated from metastases of other origins as the information available on this scenario is limited. The goal of this study is to assess the clinical characteristics of a series of patients and determine the results in terms of progression-free survival (PFS) and global survival. Method The records of patients with CNS metastasis of colorectal origin who were treated in this facility between the years 2001 and 2016 were reviewed retrospectively. Results 20 patients with CNS lesions of this origin were identified. Of these, 45% were male and 55% were female (average age 65.5 years). The histology corresponded to tubular adenocarcinoma in 95% of cases. Around 85% of the patients showed a neurological deficit, and their recursive partitioning analysis (RPA) classifications were 1 in 20%, 2 in 55%, and 3 in 25% of the cases studied. The treatments provided were: holocerebral radiotherapy (45%), stereotactic radiosurgery (25%), surgery followed by holocerebral radiotherapy (25%), and exclusively palliative care (5%). The PFS was 2.6 months from treatment of the CNS lesion, while the median survival was 3.8 months. The survival times for patients receiving different treatments were as follows: surgery plus holocerebral radiotherapy 16.2 months, stereotactic radiotherapy 12 months, and holocerebral radiotherapy 2.4 months (p = 0.003). Conclusion The prognosis for patients with metastasis of colorectal origin is poor. The patients treated with surgery or stereotactic radiotherapy can have a greater survival. PMID:28105076

  12. Your Brain and Nervous System

    MedlinePlus

    ... Room? What Happens in the Operating Room? Your Brain & Nervous System KidsHealth > For Kids > Your Brain & Nervous ... The coolest wetsuit? Nope — he needs his cerebellum! Brain Stem Keeps You Breathing — and More Another brain ...

  13. Your Brain and Nervous System

    MedlinePlus

    ... los dientes Video: Getting an X-ray Your Brain & Nervous System KidsHealth > For Kids > Your Brain & Nervous ... The coolest wetsuit? Nope — he needs his cerebellum! Brain Stem Keeps You Breathing — and More Another brain ...

  14. Imaging nervous system activity.

    PubMed

    Fields, R D; O'Donovan, M J

    2001-05-01

    Optical imaging methods rely upon visualization of three types of signals: (1) intrinsic optical signals, including light scattering and reflectance, birefringence, and spectroscopic changes of intrinsic molecules, such as NADH or oxyhemoglobin; (2) changes in fluorescence or absorbance of voltage-sensitive membrane dyes; and (3) changes in fluorescence or absorbance of calcium-sensitive indicator dyes. Of these, the most widely used approach is fluorescent microscopy of calcium-sensitive dyes. This unit describes protocols for the use of calcium-sensitive dyes and voltage-dependent dyes for studies of neuronal activity in culture, tissue slices, and en-bloc preparations of the central nervous system.

  15. Aquaporins in Nervous System.

    PubMed

    Xu, Mengmeng; Xiao, Ming; Li, Shao; Yang, Baoxue

    2017-01-01

    Aquaporins (AQPs ) mediate water flux between the four distinct water compartments in the central nervous system (CNS). In the present chapter, we mainly focus on the expression and function of the 9 AQPs expressed in the CNS, which include five members of aquaporin subfamily: AQP1, AQP4, AQP5, AQP6, and AQP8; three members of aquaglyceroporin subfamily: AQP3, AQP7, and AQP9; and one member of superaquaporin subfamily: AQP11. In addition, AQP1, AQP2 and AQP4 expressed in the peripheral nervous system (PNS) are also reviewed. AQP4, the predominant water channel in the CNS, is involved both in the astrocyte swelling of cytotoxic edema and the resolution of vasogenic edema, and is of pivotal importance in the pathology of brain disorders such as neuromyelitis optica , brain tumors and Alzheimer's disease. Other AQPs are also involved in a variety of important physiological and pathological process in the brain. It has been suggested that AQPs could represent an important target in treatment of brain disorders like cerebral edema. Future investigations are necessary to elucidate the pathological significance of AQPs in the CNS.

  16. Brain and central nervous system cancer incidence in navarre (Spain), 1973-2008 and projections for 2014.

    PubMed

    Etxeberria, J; Román, E San; Burgui, R; Guevara, M; Moreno-Iribas, C; Urbina, M J; Ardanaz, E

    2015-01-01

    Different studies have pointed out Navarre as one of the regions of Spain with the highest incidence rates of brain and other central nervous system (CNS) cancer. Trend analysis for cancer incidence rates for long periods of time, might help determining risk factors as well as, assessing prevention actions involved in this disease. The objective of this study was to describe the incidence of brain and CNS cancer using data from the population-based cancer registry of Navarre, (Spain) during the period 1973-2008 and provide forecast figures up to-2014. Crude and age-standardized (world population) incidence rates of brain cancer per 100,000 person-years were calculated by the direct method separately by gender, area (Pamplona and others), and age-groups. Penalized splines for smoothing rates in the temporal dimensions were applied in order to estimate and forecast cancer incidence rates. Age-adjusted incidence rates showed an increase over the study and forecast periods in both sexes more marked in women than in men. Higher incidence rates were observed in men compared with women but the differences became smaller with time. The increase was due to the rise of rates in the oldest age groups since the rates for younger age groups remained stable or decreased over time. As the entire aetiology of brain and other CNS cancer is not still clear, keep promoting healthful lifestyles for cancer primary prevention among the whole population is necessary.

  17. Immunotherapy for cancer in the central nervous system: Current and future directions.

    PubMed

    Binder, David C; Davis, Andrew A; Wainwright, Derek A

    2016-02-01

    Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and still remains incurable. Although immunotherapeutic vaccination against GBM has demonstrated immune-stimulating activity with some promising survival benefits, tumor relapse is common, highlighting the need for additional and/or combinatorial approaches. Recently, antibodies targeting immune checkpoints were demonstrated to generate impressive clinical responses against advanced melanoma and other malignancies, in addition to showing potential for enhancing vaccination and radiotherapy (RT). Here, we summarize the current knowledge of central nervous system (CNS) immunosuppression, evaluate past and current immunotherapeutic trials and discuss promising future immunotherapeutic directions to treat CNS-localized malignancies.

  18. Immunotherapy for cancer in the central nervous system: Current and future directions

    PubMed Central

    Binder, David C.; Davis, Andrew A.; Wainwright, Derek A.

    2016-01-01

    ABSTRACT Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and still remains incurable. Although immunotherapeutic vaccination against GBM has demonstrated immune-stimulating activity with some promising survival benefits, tumor relapse is common, highlighting the need for additional and/or combinatorial approaches. Recently, antibodies targeting immune checkpoints were demonstrated to generate impressive clinical responses against advanced melanoma and other malignancies, in addition to showing potential for enhancing vaccination and radiotherapy (RT). Here, we summarize the current knowledge of central nervous system (CNS) immunosuppression, evaluate past and current immunotherapeutic trials and discuss promising future immunotherapeutic directions to treat CNS-localized malignancies. PMID:27057463

  19. Moderate swimming suppressed the growth and metastasis of the transplanted liver cancer in mice model: with reference to nervous system.

    PubMed

    Zhang, Q-B; Zhang, B-H; Zhang, K-Z; Meng, X-T; Jia, Q-A; Zhang, Q-B; Bu, Y; Zhu, X-D; Ma, D-N; Ye, B-G; Zhang, N; Ren, Z-G; Sun, H-C; Tang, Z-Y

    2016-08-04

    Physical activity has been shown to suppress tumor initiation and progression. The neurotransmitter dopamine (DA) is closely related to movement and exhibits antitumor properties. However, whether the suppressive effects of physical activity on tumors was mediated by the nervous system via increased DA level remains unknowns. Here we show that regular moderate swimming (8 min/day, 9 weeks) raised DA levels in the prefrontal cortex, serum and tumor tissue, suppressed growth, reduced lung metastasis of transplanted liver cancer, and prolonged survival in a C57BL/6 mouse model, while overload swimming (16 and 32 min/day, 9 weeks) had the opposite effect. In nude mice that were orthotopically implanted with human liver cancer cell lines, DA treatment significantly suppressed growth and lung metastasis by acting on the D2 receptor (DR2). Furthermore, DR2 blockade attenuated the suppressive effect of moderate swimming on liver cancer. Both moderate swimming and DA treatment suppressed the transforming growth factor-beta (TGF-β1)-induced epithelial-mesenchymal transition of transplanted liver cancer cells. At the molecular level, DR2 signaling inhibited extracellular signal-regulated kinase phosphorylation and expression of TGF-β1 in vitro. Together, these findings demonstrated a novel mechanism by which the moderate exercise suppressed liver cancer through boosting DR2 activity, while overload exercise had the opposite effect, highlighting the possible importance of the dopaminergic system in tumor growth and metastasis of liver cancer.

  20. Nervous System Complexity Baffles Scientists.

    ERIC Educational Resources Information Center

    Fox, Jeffrey L.

    1982-01-01

    New research findings about how nerve cells transmit signals are forcing researchers to overhaul their simplistic ideas about the nervous system. Topics highlighted include the multiple role of peptides in the nervous system, receptor molecules, and molecules that form ion channels within membranes. (Author/JN)

  1. Nervous System Complexity Baffles Scientists.

    ERIC Educational Resources Information Center

    Fox, Jeffrey L.

    1982-01-01

    New research findings about how nerve cells transmit signals are forcing researchers to overhaul their simplistic ideas about the nervous system. Topics highlighted include the multiple role of peptides in the nervous system, receptor molecules, and molecules that form ion channels within membranes. (Author/JN)

  2. 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.

  3. Noise in the nervous system.

    PubMed

    Faisal, A Aldo; Selen, Luc P J; Wolpert, Daniel M

    2008-04-01

    Noise--random disturbances of signals--poses a fundamental problem for information processing and affects all aspects of nervous-system function. However, the nature, amount and impact of noise in the nervous system have only recently been addressed in a quantitative manner. Experimental and computational methods have shown that multiple noise sources contribute to cellular and behavioural trial-to-trial variability. We review the sources of noise in the nervous system, from the molecular to the behavioural level, and show how noise contributes to trial-to-trial variability. We highlight how noise affects neuronal networks and the principles the nervous system applies to counter detrimental effects of noise, and briefly discuss noise's potential benefits.

  4. Brain and nervous system (image)

    MedlinePlus

    The nervous system controls the many complicated and interconnected functions of the body and mind. Motor, sensory cognitive and autonomic function are all coordinated and driven by the brain and nerves. As people age, ...

  5. Risk of leukaemia or cancer in the central nervous system among children living in an area with high indoor radon concentrations: results from a cohort study in Norway.

    PubMed

    Del Risco Kollerud, R; Blaasaas, K G; Claussen, B

    2014-09-23

    Over the past few years, there has been growing interest in assessing the relationship between exposure to radon at home and the risk of childhood cancer. Previous studies have produced conflicting results, probably because of limitations assessing radon exposure, too few cancer cases and poorly documented health statistics. We used a cohort approach of 0-15-year-old children to examine whether residential radon exposure was associated with childhood leukaemia and cancer in the central nervous system in the Oslo region. The study was based on Norwegian population registers and identified cancer cases from The Cancer Registry of Norway. The residence of every child was geo-coded and assigned a radon exposure. In all, 712 674 children were followed from 1967 to 2009 from birth to date of cancer diagnosis, death, emigration or 15 years of age. A total of 864 cancer cases were identified, 437 children got leukaemia and 427 got cancer in the central nervous system.Conclusions or interpretation:No association was found for childhood leukaemia. An elevated nonsignificant risk for cancer in the central nervous system was observed. This association should be interpreted with caution owing to the crude exposure assessment and possibilities of confounding.

  6. Risk of leukaemia or cancer in the central nervous system among children living in an area with high indoor radon concentrations: results from a cohort study in Norway

    PubMed Central

    Del Risco Kollerud, R; Blaasaas, K G; Claussen, B

    2014-01-01

    Background: Over the past few years, there has been growing interest in assessing the relationship between exposure to radon at home and the risk of childhood cancer. Previous studies have produced conflicting results, probably because of limitations assessing radon exposure, too few cancer cases and poorly documented health statistics. Methods: We used a cohort approach of 0–15-year-old children to examine whether residential radon exposure was associated with childhood leukaemia and cancer in the central nervous system in the Oslo region. The study was based on Norwegian population registers and identified cancer cases from The Cancer Registry of Norway. The residence of every child was geo-coded and assigned a radon exposure. Results: In all, 712 674 children were followed from 1967 to 2009 from birth to date of cancer diagnosis, death, emigration or 15 years of age. A total of 864 cancer cases were identified, 437 children got leukaemia and 427 got cancer in the central nervous system. Conclusions or interpretation: No association was found for childhood leukaemia. An elevated nonsignificant risk for cancer in the central nervous system was observed. This association should be interpreted with caution owing to the crude exposure assessment and possibilities of confounding. PMID:25117818

  7. Symptomatic diagnosis of cancer of the brain and central nervous system in primary care: a systematic review.

    PubMed

    Schmidt-Hansen, Mia; Berendse, Sabine; Hamilton, William

    2015-12-01

    We performed a systematic review of diagnostic studies of symptomatic patients in primary care to quantify the risk of brain/central nervous system (CNS) cancer in patients presenting in primary care with symptoms that may indicate brain/CNS cancer. To quantify the risk of brain/CNS cancer in symptomatic patients presenting in primary care. We searched Medline, Premedline, Embase, the Cochrane Library, Web of Science and ISI Proceedings (1980 to August 2014) and PsychInfo (1980 to February 2013) for diagnostic studies of symptomatic adult patients in primary care. Study quality was assessed using QUADAS-II and data were extracted to calculate the positive predictive values (PPVs) of symptoms, singly or in combination, for brain/CNS cancer. Six studies with 159938 patients were included. The PPVs of single symptoms were very low with only 'new-onset seizure' being above 1% in patients aged 18 years and above, rising to 2.3% in patients aged 60-69 years. In patients aged 15-24 years, the PPVs for the individual symptoms were also very low, with the highest, also for seizure, being 0.024%, similar to that in children aged 0-14 years of 0.02%. For symptom combinations, none of the PPVs were above 0.39%. All the symptoms of brain tumours are individually low risk, apart from new-onset epilepsy. This provides a real diagnostic problem, as brain tumours have all the expected features seen with cancer diagnostic delay, with high proportions presenting as an emergency and having had multiple primary care consultations before referral, and the prognosis is poor. Improving these metrics can only be done by liberalizing investigation, although the health economics of that strategy is undetermined. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Radiation exposure and central nervous system cancers: A case-control study among workers at two nuclear facilities

    SciTech Connect

    Carpenter, A.V.; Flanders, W.D.; Frome, E.L.; Crawford-Brown, D.J.; Fry, S.A.

    1987-03-01

    A nested case-control study was conducted among workers employed between 1943 and 1977 at two nuclear facilities to investigate the possible association of primary malignant neoplasms of the central nervous system (CNS) with occupational exposure to ionizing radiation from external and internal sources. Eighty-nine white male and female workers, who according to the information on death certificates dies of primary CNS cancers, were identified as cases. Four matched controls were selected for each case. External radiation exposure data were available from film badge readings for individual workers, whereas radiation dose to lung from internally deposited radionuclides, mainly uranium, was estimated from area and personnel monitoring data and was used in analyses in lieu of the dose to the brain. Matched sets were included in the analyses only if information was available for the case and at least one of the corresponding controls. Thus, the analyses of external radiation included 27 cases and 90 matched controls, and 47 cases and 120 matched controls were analyzed for the effects of radiation from internally deposited uranium. No association was observed between deaths fron CNS cancers and occupational exposure to ionizing radiation from external or internal sources. However, due to the small number of monitored subjects and low doses, a weak association could not be ruled out. 43 refs., 1 fig., 15 tabs.

  9. Harvey Cushing's operative treatment of metastatic breast cancer to the central nervous system in the early 1900s.

    PubMed

    Latimer, Katherine; Pendleton, Courtney; Cohen-Gadol, Aaron A; Gokaslan, Ziya L; Quinones-Hinojosa, Alfredo

    2011-08-01

    A review of the surgical cases of Harvey Cushing, MD, at The Johns Hopkins Hospital provided insight into his early work treating breast cancer metastasis to the central nervous system (CNS). At the time, neurologic surgery was in its infancy. Metastases of breast carcinoma to the CNS were recognized; however, many surgeons of the era adhered to a general principle of not operating in these situations. The Johns Hopkins Hospital surgical records from 1896 to 1912 were reviewed. Four cases in which Cushing treated patients with a history of breast cancer who were diagnosed as having CNS metastasis were selected for further study. Cushing performed surgery on 4 patients with suspected CNS metastasis in the early 1900s. For a spinal metastasis, Cushing performed a laminectomy and intradural exploratory surgery. His treatments in cerebral cases sought to relieve increased intracranial pressure through decompression. He resected the lesions when they could be located. From the start of his career as a neurosurgeon, Cushing chose to perform surgery on patients with suspected CNS metastasis in an attempt to palliate some of their symptoms. Although his patients did not survive long after the procedures, they did experience temporary relief of symptoms that likely encouraged Cushing's continued operations in such situations and laid the foundation for future therapies for these patients.

  10. [Mitophagy and nervous system disease].

    PubMed

    Li, Ming-Xi; Mu, De-Zhi

    2017-06-01

    Mitophagy is a process during which the cell selectively removes the mitochondria via the mechanism of autophagy. It is crucial to the functional completeness of the whole mitochondrial network and determines cell survival and death. On the one hand, the damaged mitochondria releases pro-apoptotic factors which induce cell apoptosis; on the other hand, the damaged mitochondria eliminates itself via autophagy, which helps to maintain cell viability. Mitophagy is of vital importance for the development and function of the nervous system. Neural cells rely on autophagy to control protein quality and eliminate the damaged mitochondria, and under normal circumstances, mitophagy can protect the neural cells. Mutations in genes related to mitophagy may cause the development and progression of neurodegenerative diseases. An understanding of the role of mitophagy in nervous system diseases may provide new theoretical bases for clinical treatment. This article reviews the research advances in the relationship between mitophagy and different types of nervous system diseases.

  11. 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

  12. Settling a Nervous Stomach: The Neural Regulation of Enteric Cancer.

    PubMed

    Monje, Michelle

    2017-01-09

    The nervous system is emerging as a regulator of malignancy. In this issue of Cancer Cell, Hayakawa et al. demonstrate a feedforward signaling loop in which tumor-derived nerve growth factor promotes enteric tumor innervation, and recruited nerves drive cancer growth through acetylcholine-regulated Wnt signaling and stimulation of further NGF release. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Novel central nervous system drug delivery systems.

    PubMed

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.

  14. Human nervous system function emulator.

    PubMed

    Frenger, P

    2000-01-01

    This paper describes a modular, extensible, open-systems design for a multiprocessor network which emulates the major functions of the human nervous system. Interchangeable hardware/software components, a socketed software bus with plug-and-play capability and self diagnostics are included. The computer hardware is based on IEEE P996.1 bus cards. Its operating system utilizes IEEE 1275 standard software. Object oriented design techniques and programming are featured. A machine-independent high level script-based command language was created for this project. Neural anatomical structures which were emulated include the cortex, brainstem, cerebellum, spinal cord, autonomic and peripheral nervous systems. Motor, sensory, autoregulatory, and higher cognitive artificial intelligence, behavioral and emotional functions are provided. The author discusses how he has interfaced this emulator to machine vision, speech recognition/speech synthesis, an artificial neural network and a dexterous hand to form an android robotic platform.

  15. Infections of the nervous system

    PubMed Central

    Parikh, Vevek; Tucci, Veronica; Galwankar, Sagar

    2012-01-01

    Glycemic control is an important aspect of patient care in the surgical Infections of the nervous system are among the most difficult infections in terms of the morbidity and mortality posed to patients, and thereby require urgent and accurate diagnosis. Although viral meningitides are more common, it is the bacterial meningitides that have the potential to cause a rapidly deteriorating condition that the physician should be familiar with. Viral encephalitis frequently accompanies viral meningitis, and can produce focal neurologic findings and cognitive difficulties that can mimic other neurologic disorders. Brain abscesses also have the potential to mimic and present like other neurologic disorders, and cause more focal deficits. Finally, other infectious diseases of the central nervous system, such as prion disease and cavernous sinus thrombosis, are explored in this review. PMID:22837896

  16. 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,…

  17. 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,…

  18. 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

  19. Characterisation of the triple negative breast cancer phenotype associated with the development of central nervous system metastases

    PubMed Central

    Laimito, Katerin Rojas; Gámez-Pozo, Angelo; Sepúlveda, Juan; Manso, Luis; López-Vacas, Rocío; Pascual, Tomás; Fresno Vara, Juan A; Ciruelos, Eva

    2016-01-01

    Aims Breast cancer (BC) is the most frequent tumour in women, representing 20–30% of all malignancies, and continues to be the leading cause of cancer deaths among European women. Triple-negative (TN) BC biological aggressiveness is associated with a higher dissemination rate, with central nervous system (CNS) metastases common. This study aims to elucidate the association between gene expression profiles of PTGS2, HBEGF and ST6GALNAC5 and the development of CNS metastases in TNBC. Methods This is a case-controlled retrospective study comparing patients (pts) with CNS metastases versus patients without them after adjuvant treatment. The selection of the samples was performed including 30 samples in both case and control groups. Formalin-fixed, paraffin-embedded samples were retrieved from the Hospital 12 de Octubre Biobank. Five 10 µm sections from each FFPE sample were deparaffinised with xylene and washed with ethanol, and the RNA was then extracted with the RecoverAll Kit (Ambion). Gene expression was assessed using TaqMan assays. Results A total of 53 patients were included in the study. The average age was 55 years (range 25–85). About 47 patients (88.67%) had ductal histology and presented high grade (III) tumours (40 patients; 75.47%). Eight women in the case group presented first distant recurrence in the CNS (34.80%), local recurrence (three patients, 13.04%), lungs (two patients; 8.7%), bone (one patient; 4.34%) and other locations (seven patients; 30.38%). In the control group, first distant recurrence occurred locally (six patients; 46.1%), in bone (two patients; 15.4%), lungs (one patient; 7.7%) and other sites (four patients; 23.1%). RNA was successfully obtained from 53 out of 60 samples. PTGS2, HBEGF, and ST6GALNAC5 expression values were not related to metastasis location. Conclusion TN tumours frequently metastasise to the visceral organs, particularly lungs and brain, and are less common in bone. The literature suggests that expression of

  20. Lavender and the Nervous System

    PubMed Central

    Koulivand, Peir Hossein; Khaleghi Ghadiri, Maryam; Gorji, Ali

    2013-01-01

    Lavender is traditionally alleged to have a variety of therapeutic and curative properties, ranging from inducing relaxation to treating parasitic infections, burns, insect bites, and spasm. There is growing evidence suggesting that lavender oil may be an effective medicament in treatment of several neurological disorders. Several animal and human investigations suggest anxiolytic, mood stabilizer, sedative, analgesic, and anticonvulsive and neuroprotective properties for lavender. These studies raised the possibility of revival of lavender therapeutic efficacy in neurological disorders. In this paper, a survey on current experimental and clinical state of knowledge about the effect of lavender on the nervous system is given. PMID:23573142

  1. Bioterrorism and the nervous system.

    PubMed

    Han, M H; Zunt, J R

    2003-11-01

    Recent events of war, terrorist attacks, and mail-borne anthrax exposure have produced increasing awareness of potential bioterrorism attacks in the United States and other parts of the world. Physicians and healthcare personnel play a key role in identifying potential bioterrorist attacks. Early recognition and preparedness for bioterrorism-associated illnesses is especially important for neurologists because most bioterrorism agents can directly or indirectly affect the nervous system. This article reviews the neurologic manifestations, diagnosis, and treatments of syndromes caused by potential bioterrorism agents, as well as the potential side effects of vaccines against some of these agents.

  2. Cocaine and the nervous system.

    PubMed

    Prakash, A; Das, G

    1993-12-01

    Cocaine abuse today has reached greater heights than it did during the first cocaine epidemic in the late nineteenth century. It is estimated that one out of every four Americans has used cocaine and some six million people in the US use it regularly. Although cocaine affects all systems in the body, the central nervous system (CNS) is the primary target. Cocaine blocks the reuptake of neurotransmitters in the neuronal synapses. Almost all CNS effects of cocaine can be attributed to this mechanism. Euphoria, pharmacological pleasure and intense cocaine craving share basis in this system. The effects of cocaine on other organ systems, in addition to its effects on the CNS, account for the majority of the complications associated with cocaine abuse. In this paper, the CNS effects following cocaine administration and their treatment are discussed.

  3. Population-based risks of central nervous system tumours in childhood cancer survivors: the British Childhood Cancer Survivor Study

    PubMed Central

    Taylor, Aliki J; Little, Mark P; Winter, David L; Sugden, Elaine; Ellison, David W; Stiller, Charles A; Stovall, Marilyn; Frobisher, Clare; Lancashire, Emma R; Reulen, Raoul C; Hawkins, Michael M

    2016-01-01

    Purpose CNS tumours are the most common second primary neoplasm observed after childhood cancer in Britain, but the relationship of risk to dose of previous radiotherapy and chemotherapy is uncertain. Methods The British Childhood Cancer Survivor Study is a national population-based cohort study of 17980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national population-based cancer registries identified 247 second primary neoplasms of the CNS. Cohort and nested case-control studies were undertaken. Results There were 137 meningiomas, 73 gliomas and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01-9.99,10.00-19.99,20.00-29.99,30.00-39.99 and ≥40Gy had a risk 2,8,52,568 and 479-fold that experienced by those whose meningeal tissue was unexposed, respectively. The risk of meningioma among individuals receiving 1-39,40-69 and at least 70mg/m2 of intrathecal methotrexate was 15,11 and 36-fold that experienced by those unexposed, respectively. The standardised incidence ratio for gliomas was 10·8 (95% confidence interval: 8·5, 13·6). The risk of glioma/primitive neuroectodermal tumours increased linearly with dose of radiation and those with CNS tissue exposed to at least 40Gy experienced a risk 4-fold that experienced by those with CNS tissue unexposed. Conclusion The largest ever study of CNS tumours in childhood cancer survivors indicates the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and increased dose of intrathecal methotrexate. PMID:21079138

  4. Aquaporin Biology and Nervous System

    PubMed Central

    Barbara, Buffoli

    2010-01-01

    Our understanding of the movement of water through cell membranes has been greatly advanced by the discovery of a family of water-specific, membrane-channel proteins: the Aquaporins (AQPs). These proteins are present in organisms at all levels of life, and their unique permeability characteristics and distribution in numerous tissues indicate diverse roles in the regulation of water homeostasis. Phenotype analysis of AQP knock-out mice has confirmed the predicted role of AQPs in osmotically driven transepithelial fluid transport, as occurs in the urinary concentrating mechanism and glandular fluid secretion. Regarding their expression in nervous system, there are evidences suggesting that AQPs are differentially expressed in the peripheral versus central nervous system and that channel-mediated water transport mechanisms may be involved in cerebrospinal fluid formation, neuronal signal transduction and information processing. Moreover, a number of recent studies have revealed the importance of mammalian AQPs in both physiological and pathophysiological mechanisms and have suggested that pharmacological modulation of AQP expression and activity may provide new tools for the treatment of variety of human disorders in which water and small solute transport may be involved. For all the AQPs, new contributions to physiological functions are likely to be discovered with ongoing work in this rapidly expanding field of research. PMID:21119880

  5. Trends in central nervous system tumor incidence relative to other common cancers in adults, adolescents, and children in the United States, 2000 to 2010

    PubMed Central

    Gittleman, Haley R; Ostrom, Quinn T; Rouse, Chaturia D; Dowling, Jacqueline A; de Blank, Peter M; Kruchko, Carol A; Elder, J Bradley; Rosenfeld, Steven S; Selman, Warren R; Sloan, Andrew E; Barnholtz-Sloan, Jill S

    2015-01-01

    BACKGROUND Time trends in cancer incidence rates (IR) are important to measure the changing burden of cancer on a population over time. The overall IR of cancer in the United States is declining. Although central nervous system tumors (CNST) are rare, they contribute disproportionately to mortality and morbidity. In this analysis, the authors examined trends in the incidence of the most common cancers and CNST between 2000 and 2010. METHODS The current analysis used data from the United States Cancer Statistics publication and the Central Brain Tumor Registry of the United States. Age-adjusted IR per 100,000 population with 95% confidence intervals and the annual percent change (APC) with 95% confidence intervals were calculated for selected common cancers and CNST overall and by age, sex, race/ethnicity, selected histologies, and malignancy status. RESULTS In adults, there were significant decreases in colon (2000-2010: APC, −3.1), breast (2000-2010: APC, −0.8), lung (2000-2010: APC, −1.1), and prostate (2000-2010: APC, −2.4) cancer as well as malignant CNST (2008-2010: APC, −3.1), but a significant increase was noted in nonmalignant CNST (2004-2010: APC, 2.7). In adolescents, there were significant increases in malignant CNST (2000-2008: APC, 1.0) and nonmalignant CNST (2004-2010: APC, 3.9). In children, there were significant increases in acute lymphocytic leukemia (2000-2010: APC, 1.0), non-Hodgkin lymphoma (2000-2010: APC, 0.6), and malignant CNST (2000-2010: APC, 0.6). CONCLUSIONS Surveillance of IR trends is an important way to measure the changing public health and economic burden of cancer. In the current study, there were significant decreases noted in the incidence of adult cancer, whereas adolescent and childhood cancer IR were either stable or increasing. Cancer 2015;121:102–112. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Time trends in cancer incidence rates are important to

  6. Functional analysis of [methyl-(3)H]choline uptake in glioblastoma cells: Influence of anti-cancer and central nervous system drugs.

    PubMed

    Taguchi, Chiaki; Inazu, Masato; Saiki, Iwao; Yara, Miki; Hara, Naomi; Yamanaka, Tsuyoshi; Uchino, Hiroyuki

    2014-04-01

    Positron emission tomography (PET) and PET/computed tomography (PET-CT) studies with (11)C- or (18)F-labeled choline derivatives are used for PET imaging in glioblastoma patients. However, the nature of the choline transport system in glioblastoma is poorly understood. In this study, we performed a functional characterization of [methyl-(3)H]choline uptake and sought to identify the transporters that mediate choline uptake in the human glioblastoma cell lines A-172 and U-251MG. In addition, we examined the influence of anti-cancer drugs and central nervous system drugs on the transport of [methyl-(3)H]choline. High- and low-affinity choline transport systems were present in A-172 cells, U-251MG cells and astrocytes, and these were Na(+)-independent and pH-dependent. Cell viability in A-172 cells was not affected by choline deficiency. However, cell viability in U-251MG cells was significantly inhibited by choline deficiency. Both A-172 and U-251MG cells have two different choline transporters, choline transporter-like protein 1 (CTL1) and CTL2. In A-172 cells, CTL1 is predominantly expressed, whereas in U-251MG cells, CTL2 is predominantly expressed. Treatment with anti-cancer drugs such as cisplatin, etoposide and vincristine influenced [methyl-(3)H]choline uptake in U-251MG cells, but not A-172 cells. Central nervous system drugs such as imipramine, fluvoxamine, paroxetine, reboxetine, citalopram and donepezil did not affect cell viability or [methyl-(3)H]choline uptake. The data presented here suggest that CTL1 and CTL2 are functionally expressed in A-172 and U-251MG cells and are responsible for [methyl-(3)H]choline uptake that relies on a directed H(+) gradient as a driving force. Furthermore, while anti-cancer drugs altered [methyl-(3)H]choline uptake, central nervous system drugs did not affect [methyl-(3)H]choline uptake.

  7. What Are the Parts of the Nervous System?

    MedlinePlus

    ... and Publications What are the parts of the nervous system? Skip sharing on social media links Share this: ... the central nervous system and the peripheral nervous system: The central nervous system is made up of the brain and ...

  8. Long-term health experience of jet engine manufacturing workers: IV. A comparison of central nervous system cancer ascertainment using mortality and incidence data.

    PubMed

    Buchanich, Jeanine M; Youk, Ada O; Marsh, Gary M; Kennedy, Kathleen J; Esmen, Nurtan A; Lacey, Steven E; Hancock, Roger; Cunningham, Michael A; Lieberman, Frank S; Fleissner, Mary Lou

    2010-10-01

    To compare ascertainment of central nervous system (CNS) neoplasms with the use of mortality and incidence data as part of an occupational epidemiology study. Deaths were identified by matching the cohort of 223,894 jet engine manufacturing employees to the U.S. Social Security Administration death files and the National Death Index. Incident cancer cases were identified by matching the cohort to 19 state cancer registries. We identified 718 cases overall: 59% by the use of both mortality and cancer incidence tracing; 24% by the use of only mortality tracing, and 17% by the use of only cancer incidence tracing. Compared with state cancer registries, death certificates missed 38% of the malignant, more than six times the benign and nearly 1.5 times the unspecified CNS cases. The positive predictive value of death certificates, with cancer registry as gold standard, was 6% for unspecified, 35% for benign, and 86% for malignant histologies. Death certificates seriously underascertained benign and unspecified CNS tumors; analyses determined with mortality data would not accurately capture the true extent of disease among the cohort. Most state cancer registries have only collected nonmalignant CNS tumor information since 2004, which currently limits the usefulness of state cancer registries as a source of nonmalignant CNS tumor identification. Underascertainment of CNS deaths could seriously affect interpretation of results, more so if examining nonmalignant CNS. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Autonomic nervous system and immune system interactions.

    PubMed

    Kenney, M J; Ganta, C K

    2014-07-01

    The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological, and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines, and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease

  10. Autonomic Nervous System and Immune System Interactions

    PubMed Central

    Kenney, MJ; Ganta, CK

    2015-01-01

    The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease development

  11. Trends in central nervous system tumor incidence relative to other common cancers in adults, adolescents, and children in the United States, 2000 to 2010.

    PubMed

    Gittleman, Haley R; Ostrom, Quinn T; Rouse, Chaturia D; Dowling, Jacqueline A; de Blank, Peter M; Kruchko, Carol A; Elder, J Bradley; Rosenfeld, Steven S; Selman, Warren R; Sloan, Andrew E; Barnholtz-Sloan, Jill S

    2015-01-01

    Time trends in cancer incidence rates (IR) are important to measure the changing burden of cancer on a population over time. The overall IR of cancer in the United States is declining. Although central nervous system tumors (CNST) are rare, they contribute disproportionately to mortality and morbidity. In this analysis, the authors examined trends in the incidence of the most common cancers and CNST between 2000 and 2010. The current analysis used data from the United States Cancer Statistics publication and the Central Brain Tumor Registry of the United States. Age-adjusted IR per 100,000 population with 95% confidence intervals and the annual percent change (APC) with 95% confidence intervals were calculated for selected common cancers and CNST overall and by age, sex, race/ethnicity, selected histologies, and malignancy status. In adults, there were significant decreases in colon (2000-2010: APC, -3.1), breast (2000-2010: APC, -0.8), lung (2000-2010: APC, -1.1), and prostate (2000-2010: APC, -2.4) cancer as well as malignant CNST (2008-2010: APC, -3.1), but a significant increase was noted in nonmalignant CNST (2004-2010: APC, 2.7). In adolescents, there were significant increases in malignant CNST (2000-2008: APC, 1.0) and nonmalignant CNST (2004-2010: APC, 3.9). In children, there were significant increases in acute lymphocytic leukemia (2000-2010: APC, 1.0), non-Hodgkin lymphoma (2000-2010: APC, 0.6), and malignant CNST (2000-2010: APC, 0.6). Surveillance of IR trends is an important way to measure the changing public health and economic burden of cancer. In the current study, there were significant decreases noted in the incidence of adult cancer, whereas adolescent and childhood cancer IR were either stable or increasing. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  12. Sympathetic nervous system regulation of the tumour microenvironment

    PubMed Central

    Cole, Steven W.; Nagaraja, Archana S.; Lutgendorf, Susan K.; Green, Paige A.; Sood, Anil K.

    2016-01-01

    The peripheral autonomic nervous system (ANS) is known to regulate gene expression in primary tumours and their surrounding microenvironment. Activation of the sympathetic division of the ANS in particular modulates gene expression programs that promote metastasis of solid tumours by stimulating macrophage infiltration, inflammation, angiogenesis, epithelial-mesenchymal transition, and tumour invasion, and by inhibiting cellular immune responses and programmed cell death. Haematological cancers are modulated by sympathetic nervous system (SNS) regulation of stem cell biology and hematopoietic differentiation programs. In addition to identifying a molecular basis for physiologic stress effects on cancer, these findings have also identified new pharmacologic strategies to inhibit cancer progression in vivo. PMID:26299593

  13. Annual Report to the Nation on the Status of Cancer, 1975–2007, Featuring Tumors of the Brain and Other Nervous System

    PubMed Central

    Ward, Elizabeth; McCarthy, Bridget J.; Schymura, Maria J.; Eheman, Christie; Jemal, Ahmedin; Anderson, Robert N.; Ajani, Umed A.; Edwards, Brenda K.

    2011-01-01

    Background The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute, and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year’s report highlights brain and other nervous system (ONS) tumors, including nonmalignant brain tumors, which became reportable on a national level in 2004. Methods Cancer incidence data were obtained from the National Cancer Institute, CDC, and NAACCR, and information on deaths was obtained from the CDC’s National Center for Health Statistics. The annual percentage changes in age-standardized incidence and death rates (2000 US population standard) for all cancers combined and for the top 15 cancers for men and for women were estimated by joinpoint analysis of long-term (1992–2007 for incidence; 1975–2007 for mortality) trends and short-term fixed interval (1998–2007) trends. Analyses of malignant neuroepithelial brain and ONS tumors were based on data from 1980–2007; data on nonmalignant tumors were available for 2004–2007. All statistical tests were two-sided. Results Overall cancer incidence rates decreased by approximately 1% per year; the decrease was statistically significant (P < .05) in women, but not in men, because of a recent increase in prostate cancer incidence. The death rates continued to decrease for both sexes. Childhood cancer incidence rates continued to increase, whereas death rates continued to decrease. Lung cancer death rates decreased in women for the first time during 2003–2007, more than a decade after decreasing in men. During 2004–2007, more than 213 500 primary brain and ONS tumors were diagnosed, and 35.8% were malignant. From 1987–2007, the incidence of neuroepithelial malignant brain and ONS tumors decreased by 0.4% per year in men and women combined. Conclusions The decrease in cancer incidence and

  14. Annual report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system.

    PubMed

    Kohler, Betsy A; Ward, Elizabeth; McCarthy, Bridget J; Schymura, Maria J; Ries, Lynn A G; Eheman, Christie; Jemal, Ahmedin; Anderson, Robert N; Ajani, Umed A; Edwards, Brenda K

    2011-05-04

    The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute, and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year's report highlights brain and other nervous system (ONS) tumors, including nonmalignant brain tumors, which became reportable on a national level in 2004. Cancer incidence data were obtained from the National Cancer Institute, CDC, and NAACCR, and information on deaths was obtained from the CDC's National Center for Health Statistics. The annual percentage changes in age-standardized incidence and death rates (2000 US population standard) for all cancers combined and for the top 15 cancers for men and for women were estimated by joinpoint analysis of long-term (1992-2007 for incidence; 1975-2007 for mortality) trends and short-term fixed interval (1998-2007) trends. Analyses of malignant neuroepithelial brain and ONS tumors were based on data from 1980-2007; data on nonmalignant tumors were available for 2004-2007. All statistical tests were two-sided. Overall cancer incidence rates decreased by approximately 1% per year; the decrease was statistically significant (P < .05) in women, but not in men, because of a recent increase in prostate cancer incidence. The death rates continued to decrease for both sexes. Childhood cancer incidence rates continued to increase, whereas death rates continued to decrease. Lung cancer death rates decreased in women for the first time during 2003-2007, more than a decade after decreasing in men. During 2004-2007, more than 213 500 primary brain and ONS tumors were diagnosed, and 35.8% were malignant. From 1987-2007, the incidence of neuroepithelial malignant brain and ONS tumors decreased by 0.4% per year in men and women combined. The decrease in cancer incidence and mortality reflects progress in cancer prevention, early detection

  15. Distribution and physiological effects of B-type allatostatins (myoinhibitory peptides, MIPs) in the stomatogastric nervous system of the crab, Cancer borealis

    PubMed Central

    Szabo, Theresa M.; Chen, Ruibing; Goeritz, Marie L.; Maloney, Ryan T.; Tang, Lamont S.; Li, Lingjun; Marder, Eve

    2011-01-01

    The crustacean stomatogastric ganglion (STG) is modulated by a large number of amines and neuropeptides that are found in descending pathways from anterior ganglia or reach the STG via the hemolymph. Among these are the allatostatin (AST) – B types also known as myoinhibitory peptides (MIPs). We used mass spectrometry to determine the sequences of nine members of the AST-B family of peptides that were found in the stomatogastric nervous system of the crab, Cancer borealis. We raised an antibody against Cancer borealis Allatostatin-B1 (CbAST-B1) (VPNDWAHFRGSWa) and used it to map the distribution of CbAST-B1-like immunoreactivity (-LI) in the stomatogastric nervous system. CbAST-B1-LI was found in neurons and neuropil in the commissural ganglia (CoGs), in somata in the esophageal ganglion (OG), in fibers in the stomatogastric nerve (stn), and in neuropilar processes in the STG. CbAST-B1-LI was blocked by preincubation with 10-6 M CbAST-B1, and partially blocked by lower concentrations. Electrophysiological recordings of the effects of CbAST-B1, CbAST-B2, and CbAST-B3 on the pyloric rhythm of the STG showed that all three peptides inhibited the pyloric rhythm in a state-dependent manner. Specifically, all three peptides at 10-8 M significantly decreased the frequency of the pyloric rhythm when the initial frequency of the pyloric rhythm was below 0.6 Hz. These data suggest important neuromodulatory roles for the CbAST-B family in the stomatogastric nervous system. PMID:21491432

  16. Distribution and physiological effects of B-type allatostatins (myoinhibitory peptides, MIPs) in the stomatogastric nervous system of the crab Cancer borealis.

    PubMed

    Szabo, Theresa M; Chen, Ruibing; Goeritz, Marie L; Maloney, Ryan T; Tang, Lamont S; Li, Lingjun; Marder, Eve

    2011-09-01

    The crustacean stomatogastric ganglion (STG) is modulated by a large number of amines and neuropeptides that are found in descending pathways from anterior ganglia or reach the STG via the hemolymph. Among these are the allatostatin (AST) B types, also known as myoinhibitory peptides (MIPs). We used mass spectrometry to determine the sequences of nine members of the AST-B family of peptides that were found in the stomatogastric nervous system of the crab Cancer borealis. We raised an antibody against Cancer borealis allatostatin-B1 (CbAST-B1; VPNDWAHFRGSWa) and used it to map the distribution of CbAST-B1-like immunoreactivity (-LI) in the stomatogastric nervous system. CbAST-B1-LI was found in neurons and neuropil in the commissural ganglia (CoGs), in somata in the esophageal ganglion (OG), in fibers in the stomatogastric nerve (stn), and in neuropilar processes in the STG. CbAST-B1-LI was blocked by preincubation with 10(-6) M CbAST-B1 and was partially blocked by lower concentrations. Electrophysiological recordings of the effects of CbAST-B1, CbAST-B2, and CbAST-B3 on the pyloric rhythm of the STG showed that all three peptides inhibited the pyloric rhythm in a state-dependent manner. Specifically, all three peptides at 10(-8) M significantly decreased the frequency of the pyloric rhythm when the initial frequency of the pyloric rhythm was below 0.6 Hz. These data suggest important neuromodulatory roles for the CbAST-B family in the stomatogastric nervous system.

  17. Primary central nervous system lymphoma.

    PubMed

    Pels, Hendrik; Schlegel, Uwe

    2006-07-01

    There is no class I evidence for any therapeutic option in primary central nervous system lymphoma (PCNSL). When possible, patients should be included in clinical trials. The role of surgery is restricted to stereotactic biopsy in order to gain material for histopathologic diagnosis. Radiotherapy alone is associated with a median survival of no more than 1.5 years; cure is exceptional. However, in patients aged younger than 60 years, cure is the therapeutic aim. Polychemotherapy based on high-dose methotrexate with deferred radiation results in long-term survival in most of these patients and possibly cure in a substantial fraction of these patients. With regard to chemotherapy in PCNSL, the following must be considered: 1) the most efficient drug in PCNSL is methotrexate at a dosage of at least 1.5 g/m(2) per single dose; 2) methotrexate alone will lead to complete remission in only some patients, whereas the combination of methotrexate with other drugs is more efficient; and 3) the value of additional intraventricular chemotherapy and the necessity of "consolidation" radiotherapy after response to chemotherapy are not yet defined. For patients aged older than 60 years, no curative regimen with acceptable toxicity has yet been established. The combination of radiotherapy with methotrexate-based chemotherapy leads to severe long-term neurotoxic sequelae, ie, cognitive dysfunction, in most older patients and in some patients aged younger than 60 years.

  18. Sympathetic nervous system and spaceflight

    NASA Astrophysics Data System (ADS)

    Cooke, William H.; Convertino, Victor A.

    2007-02-01

    Purpose: Orthostatic stability on Earth is maintained through sympathetic nerve activation sufficient to increase peripheral vascular resistance and defend against reductions of blood pressure. Orthostatic instability in astronauts upon return from space missions has been linked to blunted vascular resistance responses to standing, introducing the possibility that spaceflight alters normal function between sympathetic efferent traffic and vascular reactivity. Methods: We evaluated published results of spaceflight and relevant ground-based microgravity simulations in an effort to determine responses of the sympathetic nervous system and consequences for orthostatic stability. Results: Direct microneurographic recordings from humans in space revealed that sympathetic nerve activity is increased and preserved in the upright posture after return to Earth (STS-90). However, none of the astronauts studied during STS-90 presented with presyncope postflight, leaving unanswered the question of whether postflight orthostatic intolerance is associated with blunted sympathetic nerve responses or inadequate translation into vascular resistance. Conclusions: There is little evidence to support the concept that spaceflight induces fundamental sympathetic neuroplasticity. The available data seem to support the hypothesis that regardless of whether or not sympathetic traffic is altered during flight, astronauts return with reduced blood volumes and consequent heightened baseline sympathetic activity. Because of this, the ability to withstand an orthostatic challenge postflight is directly proportional to an astronaut's maximal sympathetic activation capacity and remaining sympathetic reserve.

  19. Curation of the Mammalian Palmitoylome Indicates a Pivotal Role for Palmitoylation in Diseases and Disorders of the Nervous System and Cancers

    PubMed Central

    Butland, Stefanie L.; Lavallée-Adam, Mathieu; Calzolari, Diego; Kay, Chris; Yates, John R.; Hayden, Michael R.

    2015-01-01

    Palmitoylation involves the reversible posttranslational addition of palmitate to cysteines and promotes membrane binding and subcellular localization. Recent advancements in the detection and identification of palmitoylated proteins have led to multiple palmitoylation proteomics studies but these datasets are contained within large supplemental tables, making downstream analysis and data mining time-consuming and difficult. Consequently, we curated the data from 15 palmitoylation proteomics studies into one compendium containing 1,838 genes encoding palmitoylated proteins; representing approximately 10% of the genome. Enrichment analysis revealed highly significant enrichments for Gene Ontology biological processes, pathway maps, and process networks related to the nervous system. Strikingly, 41% of synaptic genes encode a palmitoylated protein in the compendium. The top disease associations included cancers and diseases and disorders of the nervous system, with Schizophrenia, HD, and pancreatic ductal carcinoma among the top five, suggesting that aberrant palmitoylation may play a pivotal role in the balance of cell death and survival. This compendium provides a much-needed resource for cell biologists and the palmitoylation field, providing new perspectives for cancer and neurodegeneration. PMID:26275289

  20. The Challenge of Cancer Genomics in Rare Nervous System Neoplasms: Malignant Peripheral Nerve Sheath Tumors as a Paradigm for Cross-Species Comparative Oncogenomics.

    PubMed

    Carroll, Steven L

    2016-03-01

    Comprehensive genomic analyses of common nervous system cancers provide new insights into their pathogenesis, diagnosis, and treatment. Although analogous studies of rare nervous system tumors are needed, there are major barriers to performing such studies. Cross-species comparative oncogenomics, identifying driver mutations in mouse cancer models and validating them in human tumors, is a promising alternative. Although still in its infancy, this approach is being applied to malignant peripheral nerve sheath tumors (MPNSTs), rare Schwann cell-derived malignancies that occur sporadically, after radiotherapy, and in neurofibromatosis type 1. Studies of human neurofibromatosis type 1-associated tumors suggest that NF1 tumor suppressor loss in Schwann cells triggers cell-autonomous and intercellular changes, resulting in development of benign neurofibromas; subsequent neurofibroma-MPNST progression is caused by aberrant growth factor signaling and mutations affecting the p16(INK4A)-cyclin D1-CDK4-Rb and p19(ARF)-Mdm2-p53 cell cycle pathways. Mice with Nf1, Trp53, and/or Cdkn2a mutations that overexpress the Schwann cell mitogen neuregulin-1 or overexpress the epidermal growth factor receptor validate observations in human tumors and, to various degrees, model human tumorigenesis. Genomic analyses of MPNSTs arising in neuregulin-1 and epidermal growth factor receptor-overexpressing mice and forward genetic screens with Sleeping Beauty transposons implicate additional signaling cascades in MPNST pathogenesis. These studies confirm the utility of mouse models for MPNST driver gene discovery and provide new insights into the complexity of MPNST pathogenesis.

  1. Environmental Chemicals and Nervous System Dysfunction 1

    PubMed Central

    Damstra, Terri

    1978-01-01

    Selected examples of associations between nervous system diseases and exposures to occupational and environmental chemicals have been reviewed. Recent outbreaks of human neurotoxicity from both wellknown and previously unknown toxicants reemphasize the need for the medical community to give increased attention to chemical causes of nervous system dysfunction. PMID:87062

  2. Neurogenesis in the adult peripheral nervous system.

    PubMed

    Czaja, Krzysztof; Fornaro, Michele; Geuna, Stefano

    2012-05-15

    Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system.

  3. 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.

  4. Poverty and the risk of leukemia and cancer in the central nervous system in children: A cohort study in a high-income country.

    PubMed

    Del Risco Kollerud, Ruby; Blaasaas, Karl Gerhard; Claussen, Bjørgulf

    2015-11-01

    The association between childhood cancer and socioeconomic status is inconclusive. Family income has seldom been included in large population-based studies, and the specific contributions of it remain unknown. A total of 712,674 children born between 1967 and 2009 in the Oslo region were included. Of these, 864 were diagnosed with leukemia or cancer in the central nervous system before the age of 15 years. The association between poverty and childhood leukemia or brain cancer was analyzed using logistic regression and Cox proportional hazards models. Family income was stratified according to poverty lines. Parents' educational level and several perinatal variables were also examined. Family poverty during the first 2 years of life was associated with lymphoid leukemia before the age of 15 years: odds ratio 1.72, 95% confidence interval 1.11-2.64. In the same age group we found a significant dose response, with a 21% increased risk of lymphoid leukemia with increasing poverty. The risk for intracranial and intraspinal embryonal tumors in the whole study period was lower for children in the middle family income category. For astrocytomas there was a more than 70% increased risk in the medium income category when analyzing the two first years of life. The observed increase was reduced when all years each child contributed to the study were included. The risk of cancer in the central nervous system overall was 20% higher in the medium income category compared to the high-income category. Being born into a household of low family income the first 2 years of life was found to be a risk factor for development of lymphoid leukemia. For astrocytomas we observed an increased risk among children born into the medium income category throughout the first two years of life. © 2015 the Nordic Societies of Public Health.

  5. Paraneoplastic disorders of the peripheral nervous system.

    PubMed

    Antoine, Jean-Christophe; Camdessanché, Jean-Philippe

    2013-06-01

    Paraneoplastic neurological syndromes are rare but can affect any part of the peripheral nervous system (PNS) including motor neurons, sensory ganglia, nerve roots, plexuses, cranial and peripheral nerves, and neuromuscular junctions. The type of cancer, lymphoma or solid tumour, is a determinant factor of the underlying mechanism. With solid tumour, antibodies directed to intracellular (anti-Hu or anti-CV2/CRMP5 antibodies) or surface antigens (anti-VGCC,or LGI1 and Caspr2 antibodies) have been identified while with lymphoma, the neuropathy is usually linked to a monoclonal gammopathy. This review discusses the different etiologies and mechanisms of paraneoplastic disorders of the PNS in patients emphasising their evaluation, diagnosis and treatment.

  6. Radiation injury to the nervous system

    SciTech Connect

    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.

  7. [Functional anatomy of the central nervous system].

    PubMed

    Krainik, A; Feydy, A; Colombani, J M; Hélias, A; Menu, Y

    2003-03-01

    The central nervous system (CNS) has a particular regional functional anatomy. The morphological support of cognitive functions can now be depicted using functional imaging. Lesions of the central nervous system may be responsible of specific symptoms based on their location. Current neuroimaging techniques are able to show and locate precisely macroscopic lesions. Therefore, the knowledge of functional anatomy of the central nervous system is useful to link clinical disorders to symptomatic lesions. Using radio-clinical cases, we present the functional neuro-anatomy related to common cognitive impairments.

  8. [Enteric nervous system and Parkinson's disease].

    PubMed

    Paillusson, S; Lebouvier, T; Pouclet, H; Coron, E; Bruley des Varannes, S; Damier, P; Neunlist, M; Derkinderen, P

    2012-06-01

    It has become increasingly evident over the last years that Parkinson's disease is a multicentric neurodegenerative disease that affects several neuronal structures outside the substantia nigra, among which is the enteric nervous system. The aims of the present article are to discuss the role of the enteric nervous system lesions in pathology spreading (Braak's hypothesis) and in the gastrointestinal dysfunction encountered in Parkinson's disease. Owing to its accessibility to biopsies, we further discuss the use of the enteric nervous system as an original source of biomarker in Parkinson's disease.

  9. Extracellular Matrix: Functions in the Nervous System

    PubMed Central

    Barros, Claudia S.; Franco, Santos J.; Müller, Ulrich

    2011-01-01

    An astonishing number of extracellular matrix glycoproteins are expressed in dynamic patterns in the developing and adult nervous system. Neural stem cells, neurons, and glia express receptors that mediate interactions with specific extracellular matrix molecules. Functional studies in vitro and genetic studies in mice have provided evidence that the extracellular matrix affects virtually all aspects of nervous system development and function. Here we will summarize recent findings that have shed light on the specific functions of defined extracellular matrix molecules on such diverse processes as neural stem cell differentiation, neuronal migration, the formation of axonal tracts, and the maturation and function of synapses in the peripheral and central nervous system. PMID:21123393

  10. Sites of Distant Relapse and Clinical Outcomes in Patients with Metastatic Triple-Negative Breast Cancer: High Incidence of Central Nervous System Metastases

    PubMed Central

    Claus, Elizabeth; Sohl, Jessica; Razzak, Abdul R.; Arnaout, Amal; Winer, Eric P.

    2008-01-01

    Purpose To characterize the outcomes of patients with metastatic triple negative breast cancers, including the risk and clinical consequences of central nervous system (CNS) relapse. Patients and Methods Using pharmacy and pathology records, a study group of 116 patients treated for metastatic triple negative breast cancer at Dana-Farber Cancer Institute from January 2000 to June 2006 was identified. Results The median survival from time of metastatic diagnosis was 13.3 months. Sixteen patients (14%) were diagnosed with CNS involvement at the time of initial metastatic diagnosis; overall, 46% of patients were diagnosed with CNS metastases prior to death. Median survival after a diagnosis of CNS metastasis was 4.9 months. The age and race-adjusted rate of death for patients whose first presentation included a CNS metastasis was 3.4 times (95%CI:1.9, 6.1) that of patients without a CNS lesion at first metastatic presentation. Of 53 patients who developed brain metastases, only 3 patients were judged to have stable or responsive systemic disease in the face of progressive CNS disease at the last follow up prior to death. Conclusion Triple negative breast cancer is associated with poor survival after recurrence. CNS relapse is common, but death as a direct consequence of CNS progression in the setting of controlled systemic disease is uncommon. Thus, it does not appear that the high rate of CNS involvement is due to a sanctuary effect, but rather to the lack of effective therapies in general for this aggressive subtype of breast cancer. New treatment strategies are needed. PMID:18833576

  11. Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of central nervous system metastases from non-small cell lung cancer: the present and the future.

    PubMed

    Proto, Claudia; Imbimbo, Martina; Gallucci, Rosaria; Brissa, Angela; Signorelli, Diego; Vitali, Milena; Macerelli, Marianna; Corrao, Giulia; Ganzinelli, Monica; Greco, Francesca Gabriella; Garassino, Marina Chiara; Lo Russo, Giuseppe

    2016-12-01

    Lung cancer is one of the major causes of cancer related mortality worldwide. Brain metastases (BM) complicate clinical evolution of non-small cell lung cancer (NSCLC) in approximately 25-40% of cases, adversely influencing quality of life (QoL) and overall survival (OS). Systemic therapy remains the standard strategy for metastatic disease. Nevertheless, the blood-brain barrier (BBB) makes central nervous system (CNS) a sanctuary site. To date, the combination of chemotherapy with whole brain radiation therapy (WBRT), surgery and/or stereotactic radiosurgery (SRS) represents the most used treatment for patients (pts) with intracranial involvement. However, due to their clinical conditions, many pts are not able to undergo local treatments. Targeted therapies directed against epidermal growth factor receptor (EGFR), such as gefitinib, erlotinib and afatinib, achieved important improvements in EGFR mutated NSCLC with favorable toxicity profile. Although their role is not well defined, the reported objective response rate (ORR) and the good tolerance make EGFR-tyrosine kinase inhibitors (TKIs) an interesting valid alternative for NSCLC pts with BM, especially for those harboring EGFR mutations. Furthermore, new-generation TKIs, such as osimertinib and rociletinib, have already shown important activity on intracranial disease and several trials are still ongoing to evaluate their efficacy. In this review we want to highlight literature data about the use and the effectiveness of EGFR-TKIs in pts with BM from NSCLC.

  12. Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of central nervous system metastases from non-small cell lung cancer: the present and the future

    PubMed Central

    Proto, Claudia; Imbimbo, Martina; Gallucci, Rosaria; Brissa, Angela; Signorelli, Diego; Vitali, Milena; Macerelli, Marianna; Corrao, Giulia; Ganzinelli, Monica; Greco, Francesca Gabriella; Garassino, Marina Chiara

    2016-01-01

    Lung cancer is one of the major causes of cancer related mortality worldwide. Brain metastases (BM) complicate clinical evolution of non-small cell lung cancer (NSCLC) in approximately 25–40% of cases, adversely influencing quality of life (QoL) and overall survival (OS). Systemic therapy remains the standard strategy for metastatic disease. Nevertheless, the blood-brain barrier (BBB) makes central nervous system (CNS) a sanctuary site. To date, the combination of chemotherapy with whole brain radiation therapy (WBRT), surgery and/or stereotactic radiosurgery (SRS) represents the most used treatment for patients (pts) with intracranial involvement. However, due to their clinical conditions, many pts are not able to undergo local treatments. Targeted therapies directed against epidermal growth factor receptor (EGFR), such as gefitinib, erlotinib and afatinib, achieved important improvements in EGFR mutated NSCLC with favorable toxicity profile. Although their role is not well defined, the reported objective response rate (ORR) and the good tolerance make EGFR-tyrosine kinase inhibitors (TKIs) an interesting valid alternative for NSCLC pts with BM, especially for those harboring EGFR mutations. Furthermore, new-generation TKIs, such as osimertinib and rociletinib, have already shown important activity on intracranial disease and several trials are still ongoing to evaluate their efficacy. In this review we want to highlight literature data about the use and the effectiveness of EGFR-TKIs in pts with BM from NSCLC. PMID:28149752

  13. Aging changes in the nervous system

    MedlinePlus

    ... article/004023.htm Aging changes in the nervous system To use the sharing features on this page, ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  14. Congenital defects of the ruminant nervous system.

    PubMed

    Washburn, Kevin E; Streeter, Robert N

    2004-07-01

    Abnormalities of the nervous system are common occurrences among congenital defects and have been reported in most ruminant species. From a clinical standpoint, the signs of such defects create difficulty in arriving at an antemortem etiology through historical and physical examination alone. By first localizing clinical signs to their point of origin in the nervous system, however, a narrower differential list can be generated so that the clinician can pursue a definitive diagnosis. This article categorizes defects of the ruminant nervous system by location of salient clinical signs into dysfunction of one of more of the following regions: cerebrum, cerebellum,and spinal cord. A brief review of some of the more recognized etiologies of these defects is also provided. It is important to make every attempt to determine the cause of nervous system defects because of the impact that an inherited condition would have on a breeding program and for prevention of defects caused by infectious or toxic teratogen exposure.

  15. State of the art of chemotherapy for the treatment of central nervous system metastases from non-small cell lung cancer

    PubMed Central

    Di Noia, Vincenzo; D’Argento, Ettore; Modena, Alessandra; Gori, Stefania

    2016-01-01

    Chemotherapy is the mainstay of treatment of advanced non-small cell lung cancer (NSCLC) without molecular drivers. Despite a low penetration of central nervous system (CNS), chemotherapy drugs demonstrated encouraging activity against CNS metastases from NSCLC. Based on the available data, chemotherapy should be considered as an important part of the multidisciplinary treatment of CNS metastases. Particularly, platinum-based regimens represent the most active combinations and pemetrexed is associated with a meaningful clinical benefit for patients with non-squamous histology. How to integrate chemotherapy and radiotherapy for newly diagnosed brain metastases (BMs) is still debated. Although flawed by some limitations, the available evidence suggests a role for upfront chemotherapy for the treatment of NSCLC patients with synchronous, asymptomatic BMs, thus allowing a delay of radiotherapy. Despite the introduction of modern and more effective chemotherapy, however, the prognosis of NSCLC patients with CNS metastases remains poor, especially for those with progressive BMs or leptomeningeal carcinomatosis (LC). PMID:28149755

  16. [Drug allergy and nervous system disorders].

    PubMed

    Gerasimova, M M

    2005-01-01

    The article presents data on involvement of the nervous system of patients with medicamentous allergy characterized by allergic lesions of body vessels. Cerebral allergic vasculitis is often masked by other vascular conditions such as the following: atherosclerosis, high blood pressure, rheumatism and vegetovascular dystonia. The use of the reaction of a specific injury of basophilic leukocytes exposed to penicillin, streptomycin may be a diagnostic test in the determination of the damage of the nervous system in patients with medicamentous allergy.

  17. 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.

  18. [Parasitic diseases of the central nervous system].

    PubMed

    Schmutzhard, E

    2010-02-01

    Central nervous system infections and infestations by protozoa and helminths constitute a problem of increasing importance throughout all of central European and northern/western countries. This is partially due to the globalisation of our society, tourists and business people being more frequently exposed to parasitic infection/infestation in tropical countries than in moderate climate countries. On top of that, migrants may import chronic infestations and infections with parasitic pathogens, eventually also--sometimes exclusively--involving the nervous system. Knowledge of epidemiology, initial clinical signs and symptoms, diagnostic procedures as well as specific chemotherapeutic therapies and adjunctive therapeutic strategies is of utmost important in all of these infections and infestations of the nervous systems, be it by protozoa or helminths. This review lists, mainly in the form of tables, all possible infections and infestations of the nervous systems by protozoa and by helminths. Besides differentiating parasitic diseases of the nervous system seen in migrants, tourists etc., it is very important to have in mind that disease-related (e.g. HIV) or iatrogenic immunosuppression has led to the increased occurrence of a wide variety of parasitic infections and infestations of the nervous system (e. g. babesiosis, Chagas disease, Strongyloides stercoralis infestation, toxoplasmosis, etc.).

  19. 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.

  20. Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the childhood cancer survivor study.

    PubMed

    Patterson, Briana C; Chen, Yan; Sklar, Charles A; Neglia, Joseph; Yasui, Yutaka; Mertens, Ann; Armstrong, Gregory T; Meadows, Anna; Stovall, Marilyn; Robison, Leslie L; Meacham, Lillian R

    2014-06-01

    Cranial radiation therapy (CRT) predisposes to GH deficiency and subsequent neoplasms (SNs) of the central nervous system (CNS). Increased rates of SNs have been reported in GH-treated survivors. The objective of the study was to evaluate the association between GH treatment and the development of CNS-SNs. The study was designed with a retrospective cohort with longitudinal follow-up. The setting of the study was multiinstitutional. A total of 12 098 5-year pediatric cancer survivors from the Childhood Cancer Survivor Study, diagnosed with cancer prior to age 21 years, of whom 338 self-reported GH treatment, which was verified through medical record review. INTERVENTIONS included subject surveys, medical records abstraction, and pathological review. Incidence of meningioma, glioma, and other CNS-SNs was measured. Among GH-treated survivors, 16 (4.7%) developed CNS-SN, including 10 with meningioma and six with glioma. Two hundred three survivors without GH treatment (1.7%) developed CNS-SN, including 138 with meningioma, 49 with glioma, and 16 with other CNS-SNs. The adjusted rate ratio in GH-treated compared with untreated survivors for development of any CNS-SN was 1.0 [95% confidence interval (CI) 0.6-1.8, P = .94], for meningiomas, 0.8 (95% CI 0.4-1.7, P = .61), and for gliomas, 1.9 (95% CI 0.7-4.8, P = .21). Factors associated with meningioma development included female gender (P = .001), younger age at primary cancer diagnosis (P < .001), and CRT/longer time since CRT (P < .001). Glioma was associated with CRT/shorter time since CRT (P < .001). There was no statistically significant increased overall risk of the occurrence of a CNS-SN associated with GH exposure. Specifically, occurrence of meningiomas and gliomas were not associated with GH treatment.

  1. Central nervous system complications after liver transplantation.

    PubMed

    Kim, Jeong-Min; Jung, Keun-Hwa; Lee, Soon-Tae; Chu, Kon; Roh, Jae-Kyu

    2015-08-01

    We investigated the diversity of central nervous system complications after liver transplantation in terms of clinical manifestations and temporal course. Liver transplantation is a lifesaving option for end stage liver disease patients but post-transplantation neurologic complications can hamper recovery. Between 1 January 2001 and 31 December 2010, patients who had undergone liver transplantation at a single tertiary university hospital were included. We reviewed their medical records and brain imaging data and classified central nervous system complications into four categories including vascular, metabolic, infectious and neoplastic. The onset of central nervous system complications was grouped into five post-transplantation intervals including acute (within 1 month), early subacute (1-3 months), late subacute (3-12 months), chronic (1-3 years), and long-term (after 3 years). During follow-up, 65 of 791 patients (8.2%) experienced central nervous system complications, with 30 occurring within 1 month after transplantation. Vascular etiology was the most common (27 patients; 41.5%), followed by metabolic (23; 35.4%), infectious (nine patients; 13.8%), and neoplastic (six patients). Metabolic encephalopathy with altered consciousness was the most common etiology during the acute period, followed by vascular disorders. An initial focal neurologic deficit was detected in vascular and neoplastic complications, whereas metabolic and infectious etiologies presented with non-focal symptoms. Our study shows that the etiology of central nervous system complications after liver transplantation changes over time, and initial symptoms can help to predict etiology.

  2. Compassionate intention as a therapeutic intervention by partners of cancer patients: effects of distant intention on the patients' autonomic nervous system.

    PubMed

    Radin, Dean; Stone, Jerome; Levine, Ellen; Eskandarnejad, Shahram; Schlitz, Marilyn; Kozak, Leila; Mandel, Dorothy; Hayssen, Gail

    2008-01-01

    This double-blind study investigated the effects of intention on the autonomic nervous system of a human "sender" and distant "receiver" of those intentions, and it explored the roles that motivation and training might have in modulating these effects. Skin conductance level was measured in each member of a couple, both of whom were asked to feel the presence of the other. While the receiving person relaxed in a distant shielded room for 30 minutes, the sending person directed intention toward the receiver during repeated 10-second epochs separated by random interepoch periods. Thirty-six couples participated in 38 test sessions. In 22 couples, one of the pair was a cancer patient. In 12 of those couples, the healthy person was trained to direct intention toward the patient and asked to practice that intention daily for three months prior to the experiment (trained group). In the other 10 couples, the pair was tested before the partner was trained (wait group). Fourteen healthy couples received no training (control group). Using nonparametric bootstrap procedures, normalized skin conductance means recorded during the intention epochs were compared with the same measures recorded during randomly selected interepoch periods, used as controls. The preplanned difference examined the intention versus control means at the end of the intention epoch. Overall, receivers' skin conductance increased during the intention epochs (z = 3.9; P = .00009, two-tailed). Planned differences in skin conductance among the three groups were not significant, but a post hoc analysis showed that peak deviations were largest and most sustained in the trained group, followed by more moderate effects in the wait group, and still smaller effects in the control group. Directing intention toward a distant person is correlated with activation of that person's autonomic nervous system. Strong motivation to heal and to be healed, and training on how to cultivate and direct compassionate intention

  3. Clinical impact of continued crizotinib administration after isolated central nervous system progression in patients with lung cancer positive for ALK rearrangement.

    PubMed

    Takeda, Masayuki; Okamoto, Isamu; Nakagawa, Kazuhiko

    2013-05-01

    Although crizotinib manifests marked antitumor activity in individuals with non-small-cell lung cancer positive for ALK abnormalities, all treated patients ultimately develop resistance to this drug. The central nervous system (CNS) is a frequent site of disease progression in such patients, with palliative radiotherapy usually being administered for the CNS metastasis. However, subsequent chemotherapy has not been optimized in these patients. We retrospectively evaluated the continuation of crizotinib treatment after radiotherapy for isolated CNS progression in ALK-rearrangement-positive non-small-cell lung cancer patients. Among 21 ALK-rearrangement-positive patients treated with crizotinib, seven individuals resumed daily crizotinib administration after the completion of radiotherapy for isolated CNS failure. All these patients continued to receive crizotinib for at least 4 months after radiotherapy without disease progression. One patient experienced a recurrent isolated CNS failure during the second period of crizotinib administration but subsequently resumed crizotinib treatment again for at least 8.5 months after another application of radiotherapy. Development of isolated CNS metastasis is emerging as a clinical concern for patients treated with crizotinib. Our data suggest that continued administration of crizotinib after radiotherapy for isolated CNS progression is a potential treatment option for such patients.

  4. The mechanical control of nervous system development.

    PubMed

    Franze, Kristian

    2013-08-01

    The development of the nervous system has so far, to a large extent, been considered in the context of biochemistry, molecular biology and genetics. However, there is growing evidence that many biological systems also integrate mechanical information when making decisions during differentiation, growth, proliferation, migration and general function. Based on recent findings, I hypothesize that several steps during nervous system development, including neural progenitor cell differentiation, neuronal migration, axon extension and the folding of the brain, rely on or are even driven by mechanical cues and forces.

  5. Hydrogels for central nervous system therapeutic strategies.

    PubMed

    Russo, Teresa; Tunesi, Marta; Giordano, Carmen; Gloria, Antonio; Ambrosio, Luigi

    2015-12-01

    The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described.

  6. Comparative anatomy of the autonomic nervous system.

    PubMed

    Nilsson, Stefan

    2011-11-16

    This short review aims to point out the general anatomical features of the autonomic nervous systems of non-mammalian vertebrates. In addition it attempts to outline the similarities and also the increased complexity of the autonomic nervous patterns from fish to tetrapods. With the possible exception of the cyclostomes, perhaps the most striking feature of the vertebrate autonomic nervous system is the similarity between the vertebrate classes. An evolution of the complexity of the system can be seen, with the segmental ganglia of elasmobranchs incompletely connected longitudinally, while well developed paired sympathetic chains are present in teleosts and the tetrapods. In some groups the sympathetic chains may be reduced (dipnoans and caecilians), and have yet to be properly described in snakes. Cranial autonomic pathways are present in the oculomotor (III) and vagus (X) nerves of gnathostome fish and the tetrapods, and with the evolution of salivary and lachrymal glands in the tetrapods, also in the facial (VII) and glossopharyngeal (IX) nerves.

  7. Novel markers identify nervous system components of the holothurian nervous system

    PubMed Central

    Díaz-Balzac, Carlos A.; Vázquez-Figueroa, Lionel D.; García-Arrarás, José E.

    2014-01-01

    Echinoderms occupy a key position in the evolution of deuterostomes. As such, the study of their nervous system can shed important information on the evolution of the vertebrate nervous system. However, the study of the echinoderm nervous system has lagged behind when compared to that of other invertebrates due to the lack of tools available. In this study, we tested three commercially available antibodies as markers of neural components in holothurians. Immunohistological experiments with antibodies made against the mammalian transcription factors Pax6 and Nurr1, and against phosphorylated histone H3 showed that these markers identified cells and fibers within the nervous system of Holothuria glaberrima. Most of the fibers recognized by these antibodies were co-labeled with the well-known neural marker, RN1. Additional experiments showed that similar immunoreactivity was found in the nervous tissue of three other holothurian species (Holothuria mexicana, Leptosynapta clarki and Sclerodactyla briareus), thus extending our findings to the three orders of Holothuroidea. Furthermore, these markers identified different subdivisions of the holothurian nervous system. Our study presents three additional markers of the holothurian nervous system, expanding the available toolkit to study the anatomy, physiology, development and evolution of the echinoderm nervous system. PMID:24740637

  8. Chemical exposures and central nervous system cancers: a case-control study among workers at two nuclear facilities

    SciTech Connect

    Carpenter, A.V.; Flanders, W.D.; Frome, E.L.; Tankersley, W.G.; Fry, S.A.

    1988-01-01

    In a nested case-control study of workers employed between 1943 and 1977 at two nuclear facilities, we evaluated the possible association of primary CNS cancers with occupational exposure to chemicals. Seventy-two white male and 17 white female workers who, according to the information on death certificates, died of primary CNS cancers were identified as cases. For each case, four controls were matched on race, sex, facility at which initially employed (cohort), year of birth, and year of hire. Each job title/department combination was subjectively evaluated for potential exposure to each of 26 chemicals or chemical groups. Statistically significant associations were not found between CNS cancer deaths and any of the 26 chemicals. An increased risk of CNS cancer occurrence was observed among subjects employed for more than 20 yr (OR = 7.0, 95% CI = 1.2,41.1, cases = 9).

  9. Embryonic Development of the Central Nervous System.

    PubMed

    de Lahunta, Alexander; Glass, Eric N; Kent, Marc

    2016-03-01

    Ultimately, it is only with an understanding of normal embryologic development that there can be an understanding of why and how a specific malformation develops. Knowing from where and when a specific part of the nervous system develops and what morphogens are at play will enable us to identify undescribed malformation as well as better define causality. The following article reviews the normal embryologic development of the mammalian nervous system and is intended to serve as a foundation for the understanding of the various malformations presented in this issue.

  10. Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab

    PubMed Central

    Olson, E. M.; Abdel-Rasoul, M.; Maly, J.; Wu, C. S.; Lin, N. U.; Shapiro, C. L.

    2013-01-01

    Background Central nervous system (CNS) disease as the site of first relapse after exposure to adjuvant trastuzumab has been reported. We carried out comprehensive meta-analysis to determine the risk of CNS metastases as the first site of recurrence in patients with HER2-positive breast cancer who received adjuvant trastuzumab. Methods Eligible studies include randomized trials of adjuvant trastuzumab administered for 1 year to patients with HER2-positive breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the incidence, relative risk (RR), and 95% confidence intervals (CIs) using fixed-effects inverse variance and random-effects models. Results A total of 9020 patients were included. The incidence of CNS metastases as first site of disease recurrence in HER2-positive patients receiving adjuvant trastuzumab was 2.56% (95% CI 2.07% to 3.01%) compared with 1.94% (95% CI 1.54% to 2.38%) in HER2-positive patients who did not receive adjuvant trastuzumab. The RR of the CNS as first site of relapse in trastuzumab-treated patients was 1.35 (95% CI 1.02–1.78, P = 0.038) compared with control arms without trastuzumab therapy. The ratio of CNS metastases to total number of recurrence events was 16.94% (95% CI 10.85% to 24.07%) and 8.33% (95% CI 6.49% to 10.86%) for the trastuzumab-treated and control groups, respectively. No statistically significant differences were found based on trastuzumab schedule or median follow-up time. No evidence of publication bias was observed. Conclusions Adjuvant trastuzumab is associated with a significant increased risk of CNS metastases as the site of first recurrence in HER2-positive breast cancer patients. PMID:23463626

  11. Central nervous system and computation.

    PubMed

    Guidolin, Diego; Albertin, Giovanna; Guescini, Michele; Fuxe, Kjell; Agnati, Luigi F

    2011-12-01

    Computational systems are useful in neuroscience in many ways. For instance, they may be used to construct maps of brain structure and activation, or to describe brain processes mathematically. Furthermore, they inspired a powerful theory of brain function, in which the brain is viewed as a system characterized by intrinsic computational activities or as a "computational information processor. "Although many neuroscientists believe that neural systems really perform computations, some are more cautious about computationalism or reject it. Thus, does the brain really compute? Answering this question requires getting clear on a definition of computation that is able to draw a line between physical systems that compute and systems that do not, so that we can discern on which side of the line the brain (or parts of it) could fall. In order to shed some light on the role of computational processes in brain function, available neurobiological data will be summarized from the standpoint of a recently proposed taxonomy of notions of computation, with the aim of identifying which brain processes can be considered computational. The emerging picture shows the brain as a very peculiar system, in which genuine computational features act in concert with noncomputational dynamical processes, leading to continuous self-organization and remodeling under the action of external stimuli from the environment and from the rest of the organism.

  12. Evolving specialization of the arthropod nervous system.

    PubMed

    Jarvis, Erin; Bruce, Heather S; Patel, Nipam H

    2012-06-26

    The diverse array of body plans possessed by arthropods is created by generating variations upon a design of repeated segments formed during development, using a relatively small "toolbox" of conserved patterning genes. These attributes make the arthropod body plan a valuable model for elucidating how changes in development create diversity of form. As increasingly specialized segments and appendages evolved in arthropods, the nervous systems of these animals also evolved to control the function of these structures. Although there is a remarkable degree of conservation in neural development both between individual segments in any given species and between the nervous systems of different arthropod groups, the differences that do exist are informative for inferring general principles about the holistic evolution of body plans. This review describes developmental processes controlling neural segmentation and regionalization, highlighting segmentation mechanisms that create both ectodermal and neural segments, as well as recent studies of the role of Hox genes in generating regional specification within the central nervous system. We argue that this system generates a modular design that allows the nervous system to evolve in concert with the body segments and their associated appendages. This information will be useful in future studies of macroevolutionary changes in arthropod body plans, especially in understanding how these transformations can be made in a way that retains the function of appendages during evolutionary transitions in morphology.

  13. Peripheral nervous system manifestations in systemic autoimmune diseases.

    PubMed

    Cojocaru, Inimioara Mihaela; Cojocaru, Manole; Silosi, Isabela; Vrabie, Camelia Doina

    2014-09-01

    The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. Systemic autoimmune diseases can affect both the central and peripheral nervous systems in a myriad of ways and through a heterogeneous number of mechanisms leading to many different clinical manifestations. As a result, neurological complications of these disorders can result in significant morbidity and mortality. The most common complication of peripheral nervous system (PNS) involvement is peripheral neuropathy, with symptoms of numbness, sensory paresthesias, weakness, or gait imbalance. The neuropathy may be multifocal and asymmetric or, less frequently, distal and symmetric.

  14. Nervous system examination on YouTube.

    PubMed

    Azer, Samy A; Aleshaiwi, Sarah M; Algrain, Hala A; Alkhelaif, Rana A

    2012-12-22

    Web 2.0 sites such as YouTube have become a useful resource for knowledge and are used by medical students as a learning resource. This study aimed at assessing videos covering the nervous system examination on YouTube. A research of YouTube was conducted from 2 November to 2 December 2011 using the following key words "nervous system examination", "nervous system clinical examination", "cranial nerves examination", "CNS examination", "examination of cerebellum", "balance and coordination examination". Only relevant videos in the English language were identified and related URL recorded. For each video, the following information was collected: title, author/s, duration, number of viewers, number of posted comments, and total number of days on YouTube. Using criteria comprising content, technical authority and pedagogy parameters, videos were rated independently by three assessors and grouped into educationally useful and non-educationally useful. A total of 2240 videos were screened; 129 were found to have relevant information to nervous system examination. Analysis revealed that 61 (47%) of the videos provided useful information on the nervous system examination. These videos scored (mean ± SD, 14.9 ± 0.2) and mainly covered examination of the whole nervous system (8 videos, 13%), cranial nerves (42 videos, 69%), upper limbs (6 videos, 10%), lower limbs (3 videos, 5%), balance and co-ordination (2 videos, 3%). The other 68 (53%) videos were not useful educationally; scoring (mean ± SD, 11.1 ± 3.0). The total viewers of all videos was 2,189,434. Useful videos were viewed by 1,050,445 viewers (48% of total viewers). The total viewership per day for useful videos was 1,794.5 and for non-useful videos 1,132.0. The differences between the three assessors were insignificant (less than 0.5 for the mean and 0.3 for the SD). Currently, YouTube provides an adequate resource for learning nervous system examination, which can be used by medical students

  15. Nervous system examination on YouTube

    PubMed Central

    2012-01-01

    Background Web 2.0 sites such as YouTube have become a useful resource for knowledge and are used by medical students as a learning resource. This study aimed at assessing videos covering the nervous system examination on YouTube. Methods A research of YouTube was conducted from 2 November to 2 December 2011 using the following key words “nervous system examination”, “nervous system clinical examination”, “cranial nerves examination”, “CNS examination”, “examination of cerebellum”, “balance and coordination examination”. Only relevant videos in the English language were identified and related URL recorded. For each video, the following information was collected: title, author/s, duration, number of viewers, number of posted comments, and total number of days on YouTube. Using criteria comprising content, technical authority and pedagogy parameters, videos were rated independently by three assessors and grouped into educationally useful and non-educationally useful. Results A total of 2240 videos were screened; 129 were found to have relevant information to nervous system examination. Analysis revealed that 61 (47%) of the videos provided useful information on the nervous system examination. These videos scored (mean ± SD, 14.9 ± 0.2) and mainly covered examination of the whole nervous system (8 videos, 13%), cranial nerves (42 videos, 69%), upper limbs (6 videos, 10%), lower limbs (3 videos, 5%), balance and co-ordination (2 videos, 3%). The other 68 (53%) videos were not useful educationally; scoring (mean ± SD, 11.1 ± 3.0). The total viewers of all videos was 2,189,434. Useful videos were viewed by 1,050,445 viewers (48% of total viewers). The total viewership per day for useful videos was 1,794.5 and for non-useful videos 1,132.0. The differences between the three assessors were insignificant (less than 0.5 for the mean and 0.3 for the SD). Conclusions Currently, YouTube provides an adequate resource for learning

  16. Measures of Autonomic Nervous System

    DTIC Science & Technology

    2011-04-01

    optimal level of the individual’s lung function is measured by using three color-coded peak flow zones. The individual monitoring and peak flow monitor... monoamine oxidase inhibitors, which may interfere with accurate measurements of catecholamine metabolites. Three tools for measuring catecholamine...monitoring system for patient transport . IEEE Trans Inf Technol Biomed. 2004;8(4):439. 25. Blank JM, Altman DG. Statistical methods for assessing

  17. Evolution of basal deuterostome nervous systems.

    PubMed

    Holland, Linda Z

    2015-02-15

    Understanding the evolution of deuterostome nervous systems has been complicated by the by the ambiguous phylogenetic position of the Xenocoelomorpha (Xenoturbellids, acoel flat worms, nemertodermatids), which has been placed either as basal bilaterians, basal deuterostomes or as a sister group to the hemichordate/echinoderm clade (Ambulacraria), which is a sister group of the Chordata. None of these groups has a single longitudinal nerve cord and a brain. A further complication is that echinoderm nerve cords are not likely to be evolutionarily related to the chordate central nervous system. For hemichordates, opinion is divided as to whether either one or none of the two nerve cords is homologous to the chordate nerve cord. In chordates, opposition by two secreted signaling proteins, bone morphogenetic protein (BMP) and Nodal, regulates partitioning of the ectoderm into central and peripheral nervous systems. Similarly, in echinoderm larvae, opposition between BMP and Nodal positions the ciliary band and regulates its extent. The apparent loss of this opposition in hemichordates is, therefore, compatible with the scenario, suggested by Dawydoff over 65 years ago, that a true centralized nervous system was lost in hemichordates.

  18. [Neuropeptide Y and autonomic nervous system].

    PubMed

    Nozdrachev, A D; Masliukov, P M

    2011-01-01

    Neuropeptide Y (NPY) containing 36 amino acid residues belongs to peptides widely spread in the central and peripheral nervous system. NPY and its receptors play an extremely diverse role in the nervous system, including regulation of satiety, of emotional state, of vascular tone, and of gastrointestinal secretion. In mammals, NPY has been revealed in the majority of sympathetic ganglion neurons, in a high number of neurons of parasympathetic cranial ganglia as well as of intramural ganglia of the metasympathetic nervous system. At present, six types of receptors to NPY (Y1-Y6) have been identified. All receptors to NPY belong to the family of G-bound proteins. Action of NPY on peripheral organs-targets is predominantly realized through postsynaptic receptors Y1, Y3-Y5, and presynaptic receptors of the Y2 type. NPY is present in large electron-dense vesicles and is released at high-frequency stimulation. NPY affects not only vascular tone, frequency and strength of heart contractions, motorics and secretion of the gastrointestinal tract, but also has trophic effect and produces proliferation of cells of organs-targets, specifically of vessels, myocardium, and adipose tissue. In early postnatal ontogenesis the percent of the NPY-containing neurons in ganglia of the autonomic nervous system increases. In adult organisms, this parameter decreases. This seems to be connected with the trophic NPY effect on cells-targets as well as with regulation of their functional state.

  19. Electrophysiological studies of the nervous system

    NASA Technical Reports Server (NTRS)

    Galambos, R.

    1972-01-01

    The electrophysiology of the nervous system is studied using cats and human subjects. Data cover effects of chlorolose on evoked potential, the evoked resistance shift that accompanies evoked potentials, and the relationship of eye movements to potentials aroused by visual stimulation.

  20. Mergeable nervous systems for robots.

    PubMed

    Mathews, Nithin; Christensen, Anders Lyhne; O'Grady, Rehan; Mondada, Francesco; Dorigo, Marco

    2017-09-12

    Robots have the potential to display a higher degree of lifetime morphological adaptation than natural organisms. By adopting a modular approach, robots with different capabilities, shapes, and sizes could, in theory, construct and reconfigure themselves as required. However, current modular robots have only been able to display a limited range of hardwired behaviors because they rely solely on distributed control. Here, we present robots whose bodies and control systems can merge to form entirely new robots that retain full sensorimotor control. Our control paradigm enables robots to exhibit properties that go beyond those of any existing machine or of any biological organism: the robots we present can merge to form larger bodies with a single centralized controller, split into separate bodies with independent controllers, and self-heal by removing or replacing malfunctioning body parts. This work takes us closer to robots that can autonomously change their size, form and function.Robots that can self-assemble into different morphologies are desired to perform tasks that require different physical capabilities. Mathews et al. design robots whose bodies and control systems can merge and split to form new robots that retain full sensorimotor control and act as a single entity.

  1. Influence of thyroid in nervous system growth.

    PubMed

    Mussa, G C; Mussa, F; Bretto, R; Zambelli, M C; Silvestro, L

    2001-08-01

    Nervous system growth and differentiation are closely correlated with the presence of iodine and thyroid hormones in initial development stages. In the human species, encephalon maturation during the first quarter of pregnancy is affected according to recent studies by the transplacenta passage of maternal thyroid hormones while it depends on initial iodiothyronin secretion by the foetal gland after the 12th week of pregnancy. Thyroid hormone deficiency during nervous system development causes altered noble nervous cells, such as the pyramidal cortical and Purkinje cells, during glial cell proliferation and differentiation alike. Neurons present cell hypoplasia with reduced axon count, dendritic branching, synaptic spikes and interneuron connections. Oligodendrocytes decrease in number and average myelin content consequently drops. Biochemical studies on hypothyroid rats have demonstrated alterations to neuron intraplasmatic microtubule content and organisation, changed mitochondria number and arrangement and anomalies in T3 nuclear and citoplasmatic receptor maturation. Alterations to microtubules are probably responsible for involvement of the axon-dendrite system, and are the consequence of deficient thyroid hormone action on the mitochondria, the mitochondria enzymes and proteins associated with microtubules. Nuclear and citoplasmatic receptors have been identified and gene clonation studies have shown two families of nuclear receptors that include several sub-groups in their turn. A complex scheme of temporal and spatial expression of these receptors exists, so they probably contribute with one complementary function, although their physiological role differs. The action of thyroid hormones occurs by changing cell protein levels because of their regulation at the transcriptional or post-transcriptional level. Genes submitted to thyroid hormone control are either expressed by oligodendrytes, which are myelin protein coders or glial differentiation mediators, or

  2. German Cancer Society Neuro-Oncology Working Group NOA-03 multicenter trial of single-agent high-dose methotrexate for primary central nervous system lymphoma.

    PubMed

    Herrlinger, Ulrich; Schabet, Martin; Brugger, Wolfram; Kortmann, Rolf-Dieter; Küker, Wilhelm; Deckert, Martina; Engel, Corinna; Schmeck-Lindenau, Hans-Jürgen; Mergenthaler, Hans-Günther; Krauseneck, Peter; Benöhr, Christian; Meisner, Christoph; Wiestler, Otmar D; Dichgans, Johannes; Kanz, Lothar; Bamberg, Michael; Weller, Michael

    2002-02-01

    The prospective multicenter NOA-03 trial, conducted by the Neuro-Oncology Working Group (NOA) of the German Cancer Society, was initiated to define the feasibility and efficacy of single-agent high-dose methotrexate therapy without concomitant radiotherapy in immunocompetent patients with primary central nervous system lymphoma. Thirty-seven patients (median age, 60 years) received 179 biweekly courses of 8 g/m2 methotrexate. Response was assessed after 3 and 6 courses. We had planned to enter 105 patients into the trial. Since fewer than the projected 18 of 37 patients achieved a complete response after an intermediate analysis, the trial was closed. In intention-to-treat analysis, 11 of 37 patients (29.7%) achieved complete response, whereas 14 of 37 patients (37.8%) were found to have progressive disease. The median relapse-free survival among complete response patients was 13.7 months. Multivariate logistic regression analysis revealed that corticosteroid application during the first methotrexate course was associated with complete response. The regimen was well tolerated, but, unlike previously reported results, the activity of high-dose methotrexate was only moderate.

  3. Illuminating viral infections in the nervous system

    PubMed Central

    McGavern, Dorian B.; Kang, Silvia S.

    2016-01-01

    Viral infections are a major cause of human disease. Although most viruses replicate in peripheral tissues, some have developed unique strategies to move into the nervous system, where they establish acute or persistent infections. Viral infections in the central nervous system (CNS) can alter homeostasis, induce neurological dysfunction and result in serious, potentially life-threatening inflammatory diseases. This Review focuses on the strategies used by neurotropic viruses to cross the barrier systems of the CNS and on how the immune system detects and responds to viral infections in the CNS. A special emphasis is placed on immune surveillance of persistent and latent viral infections and on recent insights gained from imaging both protective and pathogenic antiviral immune responses. PMID:21508982

  4. Assessment of Real-World Central Nervous System Events in Patients with Advanced Prostate Cancer Using Abiraterone Acetate, Bicalutamide, Enzalutamide, or Chemotherapy.

    PubMed

    Pilon, Dominic; Behl, Ajay S; Ellis, Lorie A; Robitaille, Marie-Noëlle; Lefebvre, Patrick; Dawson, Nancy A

    2017-05-01

    Central nervous system (CNS) events are frequently reported among patients with advanced prostate cancer as a consequence of the treatments used in this patient population. To assess the incidence of CNS events in patients with advanced prostate cancer who initiated treatment with abiraterone acetate, bicalutamide, enzalutamide, or chemotherapy. The Truven Health MarketScan Research databases were used to retrospectively identify patients with prostate cancer who initiated treatment with abiraterone acetate, enzalutamide, bicalutamide, or chemotherapy after September 1, 2012 (ie, the index date). The chemotherapy agents included cabazitaxel, docetaxel, mitoxantrone hydrochloride, and estramustine, and were used as monotherapy or as combination therapy. Patients were followed until December 31, 2014, the end of exposure to treatment, or until loss to follow-up. Kaplan-Meier rates and adjusted Cox proportional hazard models were used to compare the incidence of CNS events between the abiraterone acetate cohort and the other cohorts. A sensitivity analysis of patients with a diagnosis of metastasis was also conducted. A total of 1067 patients receiving abiraterone acetate, 5524 receiving bicalutamide, 592 receiving enzalutamide, and 256 receiving chemotherapy were identified. After 12 months, patients who received abiraterone acetate were less likely to have a CNS event than patients who received enzalutamide (39.5% vs 46.0%, respectively; P = .0036) or chemotherapy (39.5% vs 51.1%, respectively; P = .0277), and were more likely to have a CNS event than patients who received bicalutamide (39.5% vs 34.2%, respectively; P = .0397). After multivariate adjustment, at 12 months, patients who initiated abiraterone acetate treatment had 20% (P = .0388) reduction in the risk for a CNS event compared with patients who initiated enzalutamide; 8% (P = .3622) versus bicalutamide; and 27% (P = .0456) versus chemotherapy. The sensitivity analysis yielded similar results. The

  5. A patient previously treated with ALK inhibitors for central nervous system lesions from ALK rearranged lung cancer: a case report

    PubMed Central

    Kashima, Jumpei; Okuma, Yusuke; Hishima, Tsunekazu

    2016-01-01

    Background Patients with anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) are now preferentially treated with tyrosine kinase inhibitors (TKIs). However, patients treated with ALK inhibitors end up with acquired resistance. Case presentation We present a patient with recurrent ALK-rearranged NSCLC that developed multiple brain metastases and meningitis carcinomatosa after sequential treatment with several lines of cytotoxic chemotherapy, crizotinib, and alectinib. After the patient underwent retreatment with crizotinib as salvage therapy because of poor performance status, the intracranial metastatic foci and meningeal thickening were shrank within 1 week. Conclusion Our experience with this case suggests that alectinib may restore sensitivity to crizotinib or amplified pathway such as MET which bestowed alectinib resistance was inhibited with crizotinib. PMID:27785052

  6. Gravitational Study of the Central Nervous System

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.

    1983-01-01

    A series of experiments conducted at 1G are discussed with reference to the role of calcium ions in information processing by the central nervous system. A technique is described which allows thin sections of a mammalian hippocampus to be isolated while maintaining neural activity. Two experiments carried out in hypergravic fields are also addressed; one investigating altered stimulation in the auditory system, the other determining temperature regulation responses in hypergravic fields.

  7. Gravitational Study of the Central Nervous System

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.

    1983-01-01

    A series of experiments conducted at 1G are discussed with reference to the role of calcium ions in information processing by the central nervous system. A technique is described which allows thin sections of a mammalian hippocampus to be isolated while maintaining neural activity. Two experiments carried out in hypergravic fields are also addressed; one investigating altered stimulation in the auditory system, the other determining temperature regulation responses in hypergravic fields.

  8. CENTRAL NERVOUS SYSTEM INFECTION DURING IMMUNOSUPPRESSION

    PubMed Central

    Zunt, Joseph R.

    2009-01-01

    The central nervous system (CNS) is susceptible to bacterial, viral, and fungal infections. Suppression of the immune system by human immunodeficiency virus (HIV) infection or immunosuppressive therapy after transplantation increases susceptibility to CNS infection and modifies the presentation, diagnosis, and recommended treatment of various CNS infections. This chapter discusses how suppression of the host immune status modifies the presentation, diagnosis, and treatment of selected CNS infections. PMID:11754299

  9. Homarus Americanus Stomatogastric Nervous System Dissection

    PubMed Central

    Tobin, Anne-Elise; Bierman, Hilary S.

    2009-01-01

    With the goal of understanding how nervous systems produce activity and respond to the environment, neuroscientists turn to model systems that exhibit the activity of interest and are accessible and amenable to experimental methods. The stomatogastric nervous system (STNS) of the American lobster (Homarus americanus; also know was the Atlantic or Maine lobster) has been established as a model system for studying rhythm generating networks and neuromodulation of networks. The STNS consists of 3 anterior ganglia (2 commissural ganglia and an oesophageal ganglion), containing modulatory neurons that project centrally to the stomatogastric ganglion (STG). The STG contains approximately 30 neurons that comprise two central pattern generating networks, the pyloric and gastric networks that underlie feeding behaviors in crustaceans1,2. While it is possible to study this system in vivo3, the STNS continues to produce its rhythmic activity when isolated in vitro. Physical isolation of the STNS in a dish allows for easy access to the somata in the ganglia for intracellular electrophysiological recordings and to the nerves of the STNS for extracellular recordings. Isolating the STNS is a two-part process. The first part, dissecting the stomach from the animal, is described in an accompanying video article4. In this video article, fine dissection techniques are used to isolate the STNS from the stomach. This procedure results in a nervous system preparation that is available for electrophysiological recordings. PMID:19483669

  10. Autonomic nervous system dysregulation in pediatric hypertension.

    PubMed

    Feber, Janusz; Ruzicka, Marcel; Geier, Pavel; Litwin, Mieczyslaw

    2014-05-01

    Historically, primary hypertension (HTN) has been prevalent typically in adults. Recent data however, suggests an increasing number of children diagnosed with primary HTN, mainly in the setting of obesity. One of the factors considered in the etiology of HTN is the autonomous nervous system, namely its dysregulation. In the past, the sympathetic nervous system (SNS) was regarded as a system engaged mostly in buffering major acute changes in blood pressure (BP), in response to physical and emotional stressors. Recent evidence suggests that the SNS plays a much broader role in the regulation of BP, including the development and maintenance of sustained HTN by a chronically elevated central sympathetic tone in adults and children with central/visceral obesity. Consequently, attempts have been made to reduce the SNS hyperactivity, in order to intervene early in the course of the disease and prevent HTN-related complications later in life.

  11. Atypical nervous system manifestations of HIV.

    PubMed

    Lyons, Jennifer; Venna, Nagagopal; Cho, Tracey A

    2011-07-01

    Despite the widespread success of combination antiretroviral therapy (cART) in reducing morbidity and mortality in human immunodeficiency virus 1 (HIV-1) infection, HIV-associated neurologic disease remains prevalent. Although the virus is unable to infect neurons or muscle fibers directly, it can still injure these structures by a variety of mechanisms, many of which are yet to be elucidated. Additionally, antiretroviral medications used to treat HIV infection can cause damage to the nervous system both by direct toxicity and via modulation of host-virus interactions. Some neurologic complications of HIV infection are rarely seen and are poorly understood; nevertheless, they are important to recognize. In this review article, the authors focus on the uncommon neurologic manifestations of HIV infection, including mononeuropathies, inflammatory demyelinating polyneuropathies, motor neuron disease, polymyositis, diffuse infiltrative lymphocytosis syndrome, mononeuritis multiplex, HIV-associated neuromuscular weakness syndrome, immune reconstitution inflammatory syndrome, and central nervous system HIV-escape meningoencephalomyelitis and myelitis. © Thieme Medical Publishers.

  12. Regeneration in the nervous system with erythropoietin

    PubMed Central

    Maiese, Kenneth

    2015-01-01

    Globally, greater than 30 million individuals are afflicted with disorders of the nervous system accompanied by tens of thousands of new cases annually with limited, if any, treatment options. Erythropoietin (EPO) offers an exciting and novel therapeutic strategy to address both acute and chronic neurodegenerative disorders. EPO governs a number of critical protective and regenerative mechanisms that can impact apoptotic and autophagic programmed cell death pathways through protein kinase B (Akt), sirtuins, mammalian forkhead transcription factors, and wingless signaling. Translation of the cytoprotective pathways of EPO into clinically effective treatments for some neurodegenerative disorders has been promising, but additional work is necessary. In particular, development of new treatments with erythropoiesis-stimulating agents such as EPO brings several important challenges that involve detrimental vascular outcomes and tumorigenesis. Future work that can effectively and safely harness the complexity of the signaling pathways of EPO will be vital for the fruitful treatment of disorders of the nervous system. PMID:26549969

  13. Maintaining Genome Stability in the Nervous System

    PubMed Central

    McKinnon, Peter J.

    2014-01-01

    Active maintenance of genome stability is a prerequisite for the development and function of the nervous system. The high replication index during neurogenesis and the long life of mature neurons highlight the need for efficient cellular programs to safeguard genetic fidelity. Multiple DNA damage response pathways ensure that replication stress and other types of DNA lesions such as oxidative damage do not impact neural homeostasis. Numerous human neurologic syndromes result from defective DNA damage signaling and compromised genome integrity. These syndromes can involve different neuropathology, which highlights the diverse maintenance roles required for genome stability in the nervous system. Understanding how DNA damage signaling pathways promote neural development and preserve homeostasis is essential for understanding fundamental brain function. PMID:24165679

  14. [Central nervous system malformations: neurosurgery correlates].

    PubMed

    Jiménez-León, Juan C; Betancourt-Fursow, Yaline M; Jiménez-Betancourt, Cristina S

    2013-09-06

    Congenital malformations of the central nervous system are related to alterations in neural tube formation, including most of the neurosurgical management entities, dysraphism and craniosynostosis; alterations of neuronal proliferation; megalencefaly and microcephaly; abnormal neuronal migration, lissencephaly, pachygyria, schizencephaly, agenesis of the corpus callosum, heterotopia and cortical dysplasia, spinal malformations and spinal dysraphism. We expose the classification of different central nervous system malformations that can be corrected by surgery in the shortest possible time and involving genesis mechanisms of these injuries getting better studied from neurogenic and neuroembryological fields, this involves connecting innovative knowledge areas where alteration mechanisms in dorsal induction (neural tube) and ventral induction (telencephalization) with the current way of correction, as well as the anomalies of cell proliferation and differentiation of neuronal migration and finally the complex malformations affecting the posterior fossa and current possibilities of correcting them.

  15. Regeneration in the nervous system with erythropoietin.

    PubMed

    Maiese, Kenneth

    2016-01-01

    Globally, greater than 30 million individuals are afflicted with disorders of the nervous system accompanied by tens of thousands of new cases annually with limited, if any, treatment options. Erythropoietin (EPO) offers an exciting and novel therapeutic strategy to address both acute and chronic neurodegenerative disorders. EPO governs a number of critical protective and regenerative mechanisms that can impact apoptotic and autophagic programmed cell death pathways through protein kinase B (Akt), sirtuins, mammalian forkhead transcription factors, and wingless signaling. Translation of the cytoprotective pathways of EPO into clinically effective treatments for some neurodegenerative disorders has been promising, but additional work is necessary. In particular, development of new treatments with erythropoiesis-stimulating agents such as EPO brings several important challenges that involve detrimental vascular outcomes and tumorigenesis. Future work that can effectively and safely harness the complexity of the signaling pathways of EPO will be vital for the fruitful treatment of disorders of the nervous system.

  16. Virus Infections in the Nervous System

    PubMed Central

    Koyuncu, Orkide O.; Hogue, Ian B.; Enquist, Lynn W.

    2013-01-01

    Virus infections usually begin in peripheral tissues and can invade the mammalian nervous system (NS), spreading into the peripheral (PNS) and more rarely the central nervous systems (CNS). The CNS is protected from most virus infections by effective immune responses and multi-layer barriers. However, some viruses enter the NS with high efficiency via the bloodstream or by directly infecting nerves that innervate peripheral tissues, resulting in debilitating direct and immune-mediated pathology. Most viruses in the NS are opportunistic or accidental pathogens, but a few, most notably the alpha herpesviruses and rabies virus, have evolved to enter the NS efficiently and exploit neuronal cell biology. Remarkably, the alpha herpesviruses can establish quiescent infections in the PNS, with rare but often fatal CNS pathology. Here we review how viruses gain access to and spread in the well-protected CNS, with particular emphasis on alpha herpesviruses, which establish and maintain persistent NS infections. PMID:23601101

  17. Incidence Patterns and Trends of non-Central Nervous System Solid Tumours in Children and Adolescents. A Collaborative Study of the Spanish Population Based Cancer Registries.

    PubMed

    Larrañaga, Nerea; Sanchez, M José; Ardanaz, Eva; Felipe, Saray; Marcos-Gragera, Rafael; Ramos, María; Carulla, Marià; Chirlaque, M Dolores; Argüelles, Marcial V; Martos, Carmen; Mateo, Antonio; Peris-Bonet, Rafael

    2016-01-01

    To describe incidence patterns and trends in children (0-14 years) and adolescents (15-19 age-range) with solid tumours, except those of central nervous system (CNS), in Spain. Cases were drawn from eleven Spanish population-based cancer registries. Incidence was estimated for the period 1983-2007 and trends were evaluated using Joinpoint regression analysis. The studied tumour groups accounted for 36% of total childhood cancers and 47.6% of those diagnosed in adolescence with annual rates per million of 53.5 and 89.3 respectively. In children 0 to 14 years of age, Neuroblastoma (NB) was the commonest (7.8%) followed by Soft-tissue sarcomas (STS) (6.3%), bone tumours (BT) (6.2%) and renal tumours (RT) (4.5%). NB was the most frequently diagnosed tumour before the 5th birthday, while STS and BT were the commonest at 5-9 years of age, and BT and Carcinoma and other epithelial tumours (COET) at 10-14. COET presented the highest incidence in adolescents, followed by germ-cell tumours (GCT), BT and STS. These four diagnostic groups accounted for 94% of total non-CNS solid tumours, in adolescents. Overall incidence rates increased significantly in children up to 1996 with an annual percentage change (APC) of 2.6% (95%CI: 1.7; 3.6). NB and COET showed significant time trend (APCs: 1.4% and 3.8% respectively) while other tumour groups such as RT, STS, BT or GCT had no significant changes over time. A significant increase was present in NB under the age of 5 and in BT and STS in children aged 10-14 years. In adolescents there were significant increases for all tumours combined (APC=2.7; 95%CI: 1.8-3.6) and for STS, GCT and COET (APCs: 3.2%, 4.4% and 3.5% respectively), while other tumour groups such as hepatic tumours, BT or thyroid carcinomas showed a decreasing trend or no increase. Overall, the incidence of the studied cancers in children increased along the period 1983-1996 with no posterior significant rise, while the incidence in adolescents increased significantly

  18. Incidence Patterns and Trends of non-Central Nervous System Solid Tumours in Children and Adolescents. A Collaborative Study of the Spanish Population Based Cancer Registries

    PubMed Central

    Larrañaga, Nerea; Sanchez, Mª José; Ardanaz, Eva; Felipe, Saray; Marcos-Gragera, Rafael; Ramos, María; Carulla, Marià; Chirlaque, Mª Dolores; Argüelles, Marcial V.; Martos, Carmen; Mateo, Antonio; Peris-Bonet, Rafael

    2016-01-01

    Objective: To describe incidence patterns and trends in children (0-14 years) and adolescents (15-19 age-range) with solid tumours, except those of central nervous system (CNS), in Spain. Methods: Cases were drawn from eleven Spanish population-based cancer registries. Incidence was estimated for the period 1983-2007 and trends were evaluated using Joinpoint regression analysis. Results: The studied tumour groups accounted for 36% of total childhood cancers and 47.6% of those diagnosed in adolescence with annual rates per million of 53.5 and 89.3 respectively. In children 0 to 14 years of age, Neuroblastoma (NB) was the commonest (7.8%) followed by Soft-tissue sarcomas (STS) (6.3%), bone tumours (BT) (6.2%) and renal tumours (RT) (4.5%). NB was the most frequently diagnosed tumour before the 5th birthday, while STS and BT were the commonest at 5-9 years of age, and BT and Carcinoma and other epithelial tumours (COET) at 10-14. COET presented the highest incidence in adolescents, followed by germ-cell tumours (GCT), BT and STS. These four diagnostic groups accounted for 94% of total non-CNS solid tumours, in adolescents. Overall incidence rates increased significantly in children up to 1996 with an annual percentage change (APC) of 2.6% (95%CI: 1.7; 3.6). NB and COET showed significant time trend (APCs: 1.4% and 3.8% respectively) while other tumour groups such as RT, STS, BT or GCT had no significant changes over time. A significant increase was present in NB under the age of 5 and in BT and STS in children aged 10-14 years. In adolescents there were significant increases for all tumours combined (APC=2.7; 95%CI: 1.8-3.6) and for STS, GCT and COET (APCs: 3.2%, 4.4% and 3.5% respectively), while other tumour groups such as hepatic tumours, BT or thyroid carcinomas showed a decreasing trend or no increase. Conclusions: Overall, the incidence of the studied cancers in children increased along the period 1983-1996 with no posterior significant rise, while the incidence

  19. [Nervous system involvement in Madelung's syndrome].

    PubMed

    Tolubaev, N S; Gerasimovich, L A; Tolubaeva, N I

    1992-04-01

    Due to proliferation of the fatty tissue in the neck and depending on the degree of compression of the pharynx, larynx, vessels, nerve trunks the patients show, respiratory disorders, swallowing disturbances, dysarthria, stenocardia, neck and occipital pain, scalenus syndrome, cervicobrachialgia, posterior cervical sympathetic syndrome, disorders of the cerebral and spinal blood circulation. Involvement of both the central and peripheral nervous system are observed in Madelung's disease.

  20. Development of Central Nervous System Radioprotectors.

    DTIC Science & Technology

    1982-05-01

    accompanied ionizing radiation exposure of the central nervous system (CNS). Implicit in this objective is the requirement that this.. drug be...CNS injury either 27?’ concentrate on the late consequences of radio therapeutic exposures , or involve large mammals which would not lend themselves to...assays in which the rats are anesthetized with ketamine at the time of exposure and assayed for sensitivity to anesthesia induced by sodium

  1. Peripheral Nervous System Manifestations of Infectious Diseases

    PubMed Central

    Brizzi, Kate T.

    2014-01-01

    Infectious causes of peripheral nervous system (PNS) disease are underrecognized but potentially treatable. Heightened awareness educed by advanced understanding of the presentations and management of these infections can aid diagnosis and facilitate treatment. In this review, we discuss the clinical manifestations, diagnosis, and treatment of common bacterial, viral, and parasitic infections that affect the PNS. We additionally detail PNS side effects of some frequently used antimicrobial agents. PMID:25360209

  2. Rhabdoid tumors of the central nervous system.

    PubMed

    Reinhardt, D; Behnke-Mursch, J; Weiss, E; Christen, H J; Kühl, J; Lakomek, M; Pekrun, A

    2000-04-01

    Rhabdoid tumors of the central nervous system are rare malignancies with a still almost uniformly fatal outcome. There is still no proven curative therapy available. We report our experience with nine patients with central nervous system rhabdoid tumors. Gross complete surgical removal of the tumor was achieved in six patients. Seven patients received intensive chemotherapy. Four of these were treated in addition with both neuroaxis radiotherapy and a local boost directed to the tumor region, while two patients received local radiotherapy only. The therapy was reasonably well tolerated in most cases. Despite the aggressive therapy, eight of the nine patients died from progressive tumor disease, and one patient died from hemorrhagic brain stem lesions of unknown etiology. The mean survival time was 10 months after diagnosis. Conventional treatment, although aggressive, cannot change the fatal prognosis of central nervous system rhabdoid tumors. As these neoplasms are so rare, a coordinated register would probably be a good idea, offering a means of learning more about the tumor's biology and possible strategies of treatment.

  3. Metal toxicity in the central nervous system.

    PubMed Central

    Clarkson, T W

    1987-01-01

    The nervous system is the principal target for a number of metals. Inorganic compounds of aluminum, arsenic, lead, lithium, manganese, mercury, and thallium are well known for their neurological and behavioral effects in humans. The alkyl derivatives of certain metals--lead, mercury and tin--are specially neurotoxic. Concern over human exposure and in some cases, outbreaks of poisoning, have stimulated research into the toxic action of these metals. A number of interesting hypotheses have been proposed for the mechanism of lead toxicity on the nervous system. Lead is known to be a potent inhibitor of heme synthesis. A reduction in heme-containing enzymes could compromise energy metabolism. Lead may affect brain function by interference with neurotransmitters such as gamma-amino-isobutyric acid. There is mounting evidence that lead interferes with membrane transport and binding of calcium ions. Methylmercury produces focal damage to specific areas in the adult brain. One hypothesis proposes that certain cells are susceptible because they cannot repair the initial damage to the protein sythesis machinery. The developing nervous system is especially susceptible to damage by methylmercury. It has been discovered that microtubules are destroyed by this form of mercury and this effect may explain the inhibition of cell division and cell migration, processes that occur only in the developmental stages. These and other hypotheses will stimulate considerable experimental challenges in the future. PMID:3319566

  4. LGI proteins in the nervous system.

    PubMed

    Kegel, Linde; Aunin, Eerik; Meijer, Dies; Bermingham, John R

    2013-06-25

    The development and function of the vertebrate nervous system depend on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. LGI1-4 (leucine-rich glioma inactivated proteins) play important roles in these processes. They are secreted proteins consisting of an LRR (leucine-rich repeat) domain and a so-called epilepsy-associated or EPTP (epitempin) domain. Both domains are thought to function in protein-protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in ADLTE (autosomal dominant lateral temporal (lobe) epilepsy) also referred to as ADPEAF (autosomal dominant partial epilepsy with auditory features). LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodelling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here, we review our current knowledge about this important family of proteins, and the progress made towards understanding their functions.

  5. Tuberculoma of the central nervous system.

    PubMed

    DeLance, Arthur R; Safaee, Michael; Oh, Michael C; Clark, Aaron J; Kaur, Gurvinder; Sun, Matthew Z; Bollen, Andrew W; Phillips, Joanna J; Parsa, Andrew T

    2013-10-01

    Tuberculosis is among the oldest and most devastating infectious diseases worldwide. Nearly one third of the world's population has active or latent disease, resulting in 1.5 million deaths annually. Central nervous system involvement, while rare, is the most severe form of tuberculosis. Manifestations include tuberculoma and tuberculous meningitis, with the majority of cases occurring in children and immunocompromised patients. Despite advancements in imaging and laboratory diagnostics, tuberculomas of the central nervous system remain a diagnostic challenge due to their insidious nature and nonspecific findings. On imaging studies tuberculous meningitis is characterized by diffuse basal enhancement, but tuberculomas may be indistinguishable from neoplasms. Early diagnosis is imperative, since clinical outcomes are largely dependent on timely treatment. Stereotactic biopsy with histopathological analysis can provide a definitive diagnosis, but is only recommended when non-invasive methods are inconclusive. Standard medical treatment includes rifampicin, isoniazid, pyrazinamide, and streptomycin or ethambutol. In cases of drug resistance, revision of the treatment regimen with second-line agents is recommended over the addition of a single drug to the first-line regimen. Advances in genomics have identified virulent strains of tuberculosis and are improving our understanding of host susceptibility. Neurosurgical referral is advised for patients with elevated intracranial pressure, seizures, or brain or spinal cord compression. This review synthesizes pertinent findings in the literature surrounding central nervous system tuberculoma in an effort to highlight recent advances in pathophysiology, diagnosis, and treatment.

  6. The BIRN Project: Imaging the Nervous System

    SciTech Connect

    Ellisman, Mark

    2006-05-22

    The grand goal in neuroscience research is to understand how the interplay of structural, chemical and electrical signals in nervous tissue gives rise to behavior. Experimental advances of the past decades have given the individual neuroscientist an increasingly powerful arsenal for obtaining data, from the level of molecules to nervous systems. Scientists have begun the arduous and challenging process of adapting and assembling neuroscience data at all scales of resolution and across disciplines into computerized databases and other easily accessed sources. These databases will complement the vast structural and sequence databases created to catalogue, organize and analyze gene sequences and protein products. The general premise of the neuroscience goal is simple; namely that with "complete" knowledge of the genome and protein structures accruing rapidly we next need to assemble an infrastructure that will facilitate acquisition of an understanding for how functional complexes operate in their cell and tissue contexts.

  7. The BIRN Project: Imaging the Nervous System

    SciTech Connect

    Ellisman, Mark

    2006-05-22

    The grand goal in neuroscience research is to understand how the interplay of structural, chemical and electrical signals in nervous tissue gives rise to behavior. Experimental advances of the past decades have given the individual neuroscientist an increasingly powerful arsenal for obtaining data, from the level of molecules to nervous systems. Scientists have begun the arduous and challenging process of adapting and assembling neuroscience data at all scales of resolution and across disciplines into computerized databases and other easily accessed sources. These databases will complement the vast structural and sequence databases created to catalogue, organize and analyze gene sequences and protein products. The general premise of the neuroscience goal is simple; namely that with 'complete' knowledge of the genome and protein structures accruing rapidly we next need to assemble an infrastructure that will facilitate acquisition of an understanding for how functional complexes operate in their cell and tissue contexts.

  8. 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)

  9. Childhood Central Nervous System Germ Cell Tumors Treatment

    MedlinePlus

    ... Ependymoma Treatment Research Childhood Central Nervous System Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Childhood Central Nervous System (CNS) Germ Cell Tumors Go to Health Professional Version Key Points ...

  10. 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)

  11. Treatment patterns, clinical outcomes and health care costs associated with her2-positive breast cancer with central nervous system metastases: a French multicentre observational study

    PubMed Central

    2013-01-01

    Background The population of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) who develop central nervous system (CNS) metastases is growing. Treatment strategies in this population are highly diverse. The objective of the study was to assess health care costs for the management of HER2 positive BC with CNS metastases. Methods This multicentre, retrospective, observational study was conducted on HER2-positive BC patients diagnosed with CNS metastases between 2006 and 2008. Data were extracted from patient medical records to estimate health care resource use. A partitioned estimator was used to adjust censoring costs by use of the Kaplan-Meier survival estimate. Results 218 patients were included and costs were estimated for 200 patients. The median time to detection of CNS metastases was 37.6 months. The first metastatic event involved the CNS in 39 patients, and this was the unique first metastatic site in 31 of these patients. Two years following diagnosis of CNS metastases, 70.3% of patients had died. The mean per capita cost of HER2-positive BC with CNS metastases in the first year following diagnosis was €35,735 [95% CI: 31,716-39,898]. The proportion of costs attributed to expensive drugs and those arising from hospitalisation were in the same range. Conclusion A range of individualised disease management strategies are used in HER2-positive BC patients with CNS metastases and the treatments used in the first months following diagnosis are expensive. The understanding of cost drivers may help optimise healthcare expenditure and inform the development of appropriate prevention policies. PMID:24176086

  12. Screening for ALK abnormalities in central nervous system metastases of non-small-cell lung cancer: ALK abnormalities in CNS metastases of NSCLC.

    PubMed

    Nicoś, Marcin; Jarosz, Bożena; Krawczyk, Paweł; Wojas-Krawczyk, Kamila; Kucharczyk, Tomasz; Sawicki, Marek; Pankowski, Juliusz; Trojanowski, Tomasz; Milanowski, Janusz

    2016-11-23

    Anaplastic lymphoma kinase (ALK) gene rearrangement was reported in 3-7% of primary non-small-cell lung cancer (NSCLC) and its presence is commonly associated with adenocarcinoma (AD) type and non-smoking history. ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, alectinib and ceritinib showed efficiency in patients with primary NSCLC harboring ALK gene rearrangement. Moreover, response to ALK TKIs was observed in central nervous system (CNS) metastatic lesions of NSCLC. However, there are no reports concerning the frequency of ALK rearrangement in CNS metastases. We assessed the frequency of ALK abnormalities in 145 formalin fixed paraffin embedded (FFPE) tissue samples from CNS metastases of NSCLC using immunohistochemical (IHC) automated staining (BenchMark GX, Ventana, USA) and fluorescence in situ hybridization (FISH) technique (Abbot Molecular, USA). The studied group was heterogeneous in terms of histopathology and smoking status. ALK abnormalities were detected in 4.8% (7/145) of CNS metastases. ALK abnormalities were observed in six AD (7.5%; 6/80) and in single patients with adenosuqamous lung carcinoma. Analysis of clinical and demographic factors indicated that expression of abnormal ALK was significantly more frequently observed (p=0.0002; χ(2) =16.783) in former-smokers. Comparison of IHC and FISH results showed some discrepancies, which were caused by unspecific staining of macrophages and glial/nerve cells, which constitute the background of CNS tissues. Our results indicate high frequency of ALK gene rearrangement in CNS metastatic sites of NSCLC that are in line with prior studies concerning evaluation of the presence of ALK abnormalities in such patients. However, we showed that assessment of ALK by IHC and FISH methods in CNS tissues require additional standardizations. This article is protected by copyright. All rights reserved.

  13. Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

    SciTech Connect

    Gan, Gregory N.; Weickhardt, Andrew J.; Scheier, Benjamin; Doebele, Robert C.; Gaspar, Laurie E.; Kavanagh, Brian D.; Camidge, D. Ross

    2014-03-15

    Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progression meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival.

  14. [Radiation-induced tumors of the nervous system in man].

    PubMed

    Hubert, D; Bertin, M

    1993-11-01

    The risk of developing a tumor of the nervous system in humans is analysed in several studies of populations, exposed to ionising radiation for medical reasons, or exposed to military or occupational radiation. The main data come from series of patients who underwent radiotherapy during childhood: a high incidence of tumors of the nervous system is found after irradiation of one to a few grays as treatment of a benign disease (especially tinea capitis), as well as after irradiation at higher doses of a few tens of grays for the treatment of cancer (in particular cerebral irradiation in acute lymphoblastic leukaemia). The type of radiation-induced tumors is variable, but meningioma is more frequent after low doses and glioma and sarcoma after higher doses used in the treatment of neoplastic diseases. A dose-effect relationship appeared between the risk of tumor of the nervous system and the radiation dose. The risk was higher when radiation was delivered at a younger age. Much less data are available after radiotherapy in the adulthood, but an increased risk of cerebral tumor appears in the series of ankylosing spondylitis patients. As for the exposures to radiodiagnosis exams, the main problem is the risk of cerebral tumor in children whose mother has undergone abdominal or pelvic X-rays during pregnancy. No risk of neurologic tumor was found in the A-bomb survivors irradiated at Hiroshima and Nagasaki. Occupational exposure to ionising radiation has been incriminated in the first radiologists exposed to high doses. In nuclear industry workers, the results of epidemiological studies are contradictory and at the present time it is not possible to link their radiologic exposure with a risk of tumor of the nervous system. In populations living near nuclear plants, mortality due to tumors of the nervous system was not increased.

  15. Monoclonal Antibodies against the Drosophila Nervous System

    NASA Astrophysics Data System (ADS)

    Fujita, Shinobu C.; Zipursky, Stephen L.; Benzer, Seymour; Ferrus, Alberto; Shotwell, Sandra L.

    1982-12-01

    A panel of 148 monoclonal antibodies directed against Drosophila neural antigens has been prepared by using mice immunized with homogenates of Drosophila tissue. Antibodies were screened immunohistochemically on cryostat sections of fly heads. A large diversity of staining patterns was observed. Some antigens were broadly distributed among tissues; others were highly specific to nerve fibers, neuropil, muscle, the tracheal system, cell nuclei, photoreceptors, or other structures. The antigens for many of the antibodies have been identified on immunoblots. Monoclonal antibodies that identify specific molecules within the nervous system should prove useful in the study of the molecular genetics of neural development.

  16. HCV-Related Nervous System Disorders

    PubMed Central

    Monaco, Salvatore; Ferrari, Sergio; Gajofatto, Alberto; Zanusso, Gianluigi; Mariotto, Sara

    2012-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a wide spectrum of extrahepatic manifestations, affecting different organ systems. Neurological complications occur in a large number of patients and range from peripheral neuropathy to cognitive impairment. Pathogenetic mechanisms responsible for nervous system dysfunction are mainly related to the upregulation of the host immune response with production of autoantibodies, immune complexes, and cryoglobulins. Alternative mechanisms include possible extrahepatic replication of HCV in neural tissues and the effects of circulating inflammatory cytokines and chemokines. PMID:22899946

  17. Chaperone Proteins in the Central Nervous System and Peripheral Nervous System after Nerve Injury

    PubMed Central

    Ousman, Shalina S.; Frederick, Ariana; Lim, Erin-Mai F.

    2017-01-01

    Injury to axons of the central nervous system (CNS) and the peripheral nervous system (PNS) is accompanied by the upregulation and downregulation of numerous molecules that are involved in mediating nerve repair, or in augmentation of the original damage. Promoting the functions of beneficial factors while reducing the properties of injurious agents determines whether regeneration and functional recovery ensues. A number of chaperone proteins display reduced or increased expression following CNS and PNS damage (crush, transection, contusion) where their roles have generally been found to be protective. For example, chaperones are involved in mediating survival of damaged neurons, promoting axon regeneration and remyelination and, improving behavioral outcomes. We review here the various chaperone proteins that are involved after nervous system axonal damage, the functions that they impact in the CNS and PNS, and the possible mechanisms by which they act. PMID:28270745

  18. Chaperone Proteins in the Central Nervous System and Peripheral Nervous System after Nerve Injury.

    PubMed

    Ousman, Shalina S; Frederick, Ariana; Lim, Erin-Mai F

    2017-01-01

    Injury to axons of the central nervous system (CNS) and the peripheral nervous system (PNS) is accompanied by the upregulation and downregulation of numerous molecules that are involved in mediating nerve repair, or in augmentation of the original damage. Promoting the functions of beneficial factors while reducing the properties of injurious agents determines whether regeneration and functional recovery ensues. A number of chaperone proteins display reduced or increased expression following CNS and PNS damage (crush, transection, contusion) where their roles have generally been found to be protective. For example, chaperones are involved in mediating survival of damaged neurons, promoting axon regeneration and remyelination and, improving behavioral outcomes. We review here the various chaperone proteins that are involved after nervous system axonal damage, the functions that they impact in the CNS and PNS, and the possible mechanisms by which they act.

  19. Central nervous system systemic lupus erythematosus mimicking progressive multifocal leucoencephalopathy.

    PubMed Central

    Kaye, B R; Neuwelt, C M; London, S S; DeArmond, S J

    1992-01-01

    The case is reported of a patient with central nervous system systemic lupus erythematosus (SLE) with features of progressive multifocal leucoencephalopathy (PML) seen clinically and by magnetic resonance imaging. A brain biopsy sample showed microinfarcts. The use of magnetic resonance imaging and IgG synthesis rates in evaluating central nervous system lupus, the co-occurrence of SLE and PML, and the differentiation of these entities by magnetic resonance imaging and by histology are considered. Images PMID:1444628

  20. Autopsy proven peripheral nervous system neurolymphomatosis despite negative bilateral sural nerve biopsy.

    PubMed

    Ramirez-Zamora, Adolfo; Morales-Vidal, Sarkis; Chawla, Jasvinder; Biller, José

    2013-01-01

    Neurolymphomatosis (NL) refers to a lymphomatous infiltration of peripheral nerves associated with central nervous system or systemic lymphoma, or alternatively, neurodiagnostic evidence of nerve enhancement and/or enlargement beyond the dural sleeve in the setting of primary central nervous system lymphoma or systemic lymphoma. NL is a rare complication of systemic cancer with heterogeneous clinical presentations and an elusive diagnosis. Diagnosis usually requires the demonstration of infiltrating malignant lymphocytes in the peripheral nerve. Infiltration of brain parenchyma, meninges or Virchow-Robin spaces is characteristic of systemic disease at autopsy. We describe a patient presenting with biopsy negative NL affecting exclusively the peripheral nervous system at autopsy.

  1. Microglia: Architects of the Developing Nervous System.

    PubMed

    Frost, Jeffrey L; Schafer, Dorothy P

    2016-08-01

    Microglia are resident macrophages of the central nervous system (CNS), representing 5-10% of total CNS cells. Recent findings reveal that microglia enter the embryonic brain, take up residence before the differentiation of other CNS cell types, and become critical regulators of CNS development. Here, we discuss exciting new work implicating microglia in a range of developmental processes, including regulation of cell number and spatial patterning of CNS cells, myelination, and formation and refinement of neural circuits. Furthermore, we review studies suggesting that these cellular functions result in the modulation of behavior, which has important implications for a variety of neurological disorders.

  2. Physiology of the Autonomic Nervous System

    PubMed Central

    2007-01-01

    This manuscript discusses the physiology of the autonomic nervous system (ANS). The following topics are presented: regulation of activity; efferent pathways; sympathetic and parasympathetic divisions; neurotransmitters, their receptors and the termination of their activity; functions of the ANS; and the adrenal medullae. In addition, the application of this material to the practice of pharmacy is of special interest. Two case studies regarding insecticide poisoning and pheochromocytoma are included. The ANS and the accompanying case studies are discussed over 5 lectures and 2 recitation sections during a 2-semester course in Human Physiology. The students are in the first-professional year of the doctor of pharmacy program. PMID:17786266

  3. Did the ctenophore nervous system evolve independently?

    PubMed

    Ryan, Joseph F

    2014-08-01

    Recent evidence supports the placement of ctenophores as the most distant relative to all other animals. This revised animal tree means that either the ancestor of all animals possessed neurons (and that sponges and placozoans apparently lost them) or that ctenophores developed them independently. Differentiating between these possibilities is important not only from a historical perspective, but also for the interpretation of a wide range of neurobiological results. In this short perspective paper, I review the evidence in support of each scenario and show that the relationship between the nervous system of ctenophores and other animals is an unsolved, yet tractable problem. Copyright © 2014 Elsevier GmbH. All rights reserved.

  4. Mold Infections of the Central Nervous System

    PubMed Central

    McCarthy, Matthew; Rosengart, Axel; Schuetz, Audrey N.; Kontoyiannis, Dimitrios P.; Walsh, Thomas J.

    2016-01-01

    The recent outbreak of exserohilum rostratum meningitis linked to epidural injections of methylprednisolone acetate has brought renewed attention to mold infections of the central nervous system (CNS).1 Although uncommon, these infections are often devastating and difficult to treat. This focused review of the epidemiologic aspects, clinical characteristics, and treatment of mold infections of the CNS covers a group of common pathogens: aspergillus, fusarium, and scedosporium species, molds in the order Mucorales, and dematiaceous molds. Infections caused by these pathogen groups have distinctive epidemiologic profiles, clinical manifestations, microbiologic characteristics, and therapeutic implications, all of which clinicians should understand. PMID:25006721

  5. Histoplasmosis of the central nervous system.

    PubMed Central

    Tan, V; Wilkins, P; Badve, S; Coppen, M; Lucas, S; Hay, R; Schon, F

    1992-01-01

    Histoplasma capsulatum infection of the central nervous system is extremely rare in the United Kingdom partly because the organism is not endemic. However, because the organism can remain quiescent in the lungs or the adrenal glands for over 40 years before dissemination, it increasingly needs to be considered in unexplained neurological disease particularly in people who lived in endemic areas as children. In this paper a rapidly progressive fatal myelopathy in an English man brought up in India was shown at necropsy to be due to histoplasmosis. The neurological features of this infection are reviewed. Images PMID:1640242

  6. Sarcoidosis of the peripheral nervous system.

    PubMed

    Said, Gérard

    2013-01-01

    Neurological manifestations of sarcoidosis are relatively rare but constitute a treatable cause of central and peripheral neurological manifestations. Regarding the peripheral nervous system, cranial nerves are predominantly affected, and peripheral facial nerve palsy, often bilateral, is the most common neurological manifestation of sarcoidosis. Multifocal peripheral neuropathy is a rare event in sarcoidosis. In some cases, however, peripheral neuropathy is the presenting manifestation and seemingly the only organ affected. Definite diagnosis of sarcoidosis rests ideally on histological demonstration of sarcoid granulomas in tissue biopsy specimens.

  7. Whipple's disease confined to the nervous system.

    PubMed Central

    Pollock, S; Lewis, P D; Kendall, B

    1981-01-01

    Whipple's disease confined to the nervous system occurred in a 36-year old woman who presented with grand mal seizures and dementia. There was no evidence of extracerebral involvement and the jejunal biopsy was negative before treatment. Multiple enhancing lesions on CT scan progressed despite therapy with minocycline and prednisone, but resolved on treatment with tetracycline. The dementia did not progress while she was on antibiotic therapy. Whipple's disease should be considered as a treatable cause of progressive dementia even in the absence of an abnormal jejunal biopsy. Images PMID:6174699

  8. Occurrence of nervous system involvement in SIRS.

    PubMed

    Marchiori, Paulo E; Lino, Angelina M M; Hirata, Maria T A; Carvalho, Nise B; Brotto, Mario W I; Scaff, Milberto

    2006-12-01

    Systemic inflammatory response syndrome (SIRS) is a medical condition in which the all-organ microcirculation is affected including nervous system. We describe neurological findings in 64 patients with SIRS at Hospital das Clínicas of Sao Paulo University School of Medicine; 45.3% were male and 54.7% female; their age ranged from 16 to 95 years old. SIRS was caused by infection in 68.8% of patients, trauma in 10.9%, burns in 7.8%, and elective surgery in 4.7%. The central nervous system involvement occurred in 56.3% of patients and was characterized as encephalopathy in 75%, seizures in 13.9%, non-epileptic myoclonus in 2.8%, and ischemic stroke in 8.3%. The magnetic resonance imaging, cerebrospinal fluid and electroencephalographic changes were unremarkable in encephalopathic patients. Neuromuscular disorders were diagnosed in 43.7%. Critical ill polyneuropathy was characterized in 57.1%, critical ill myopathy in 32.1%, demyelinating neuropathy in 7.2%, and pure motor neuropathy in 3.6%. Nerve and muscle pathological studies dismissed inflammatory abnormalities. The identification of these conditions has important economic implications and may change the critically ill patients' prognosis.

  9. Statins and the autonomic nervous system.

    PubMed

    Millar, Philip J; Floras, John S

    2014-03-01

    Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) reduce plasma cholesterol and improve endothelium-dependent vasodilation, inflammation and oxidative stress. A 'pleiotropic' property of statins receiving less attention is their effect on the autonomic nervous system. Increased central sympathetic outflow and diminished cardiac vagal tone are disturbances characteristic of a range of cardiovascular conditions for which statins are now prescribed routinely to reduce cardiovascular events: following myocardial infarction, and in hypertension, chronic kidney disease, heart failure and diabetes. The purpose of the present review is to synthesize contemporary evidence that statins can improve autonomic circulatory regulation. In experimental preparations, high-dose lipophilic statins have been shown to reduce adrenergic outflow by attenuating oxidative stress in central brain regions involved in sympathetic and parasympathetic discharge induction and modulation. In patients with hypertension, chronic kidney disease and heart failure, lipophilic statins, such as simvastatin or atorvastatin, have been shown to reduce MNSA (muscle sympathetic nerve activity) by 12-30%. Reports concerning the effect of statin therapy on HRV (heart rate variability) are less consistent. Because of their implications for BP (blood pressure) control, insulin sensitivity, arrhythmogenesis and sudden cardiac death, these autonomic nervous system actions should be considered additional mechanisms by which statins lower cardiovascular risk.

  10. Cardiac autonomic nervous system activity in obesity.

    PubMed

    Liatis, Stavros; Tentolouris, Nikolaos; Katsilambros, Nikolaos

    2004-08-01

    The development of obesity is caused by a disturbance of energy balance, with energy intake exceeding energy expenditure. As the autonomic nervous system (ANS) has a role in the regulation of both these variables, it has become a major focus of investigation in the fields of obesity pathogenesis. The enhanced cardiac sympathetic drive shown in most of the studies in obese persons might be due to an increase in their levels of circulating insulin. The role of leptin needs further investigation with studies in humans. There is a blunted response of the cardiac sympathetic nervous system (SNS) activity in obese subjects after consumption of a carbohydrate-rich meal as well as after insulin administration. This might be due to insulin resistance. It is speculated that increased SNS activity in obesity may contribute to the development of hypertension in genetically susceptible individuals. It is also speculated that the increase in cardiac SNS activity under fasting conditions in obesity may be associated with high cardiovascular morbidity and mortality.

  11. Progress in Central Nervous System Lymphomas

    PubMed Central

    Wang, Chia-Ching; Carnevale, Julia; Rubenstein, James L.

    2014-01-01

    Until recently, primary central nervous system lymphoma (PCNSL) was associated with a uniformly dismal prognosis. It is now reasonable to anticipate long-term survival and possibly cure for a significant proportion of patients diagnosed with PCNSL. Accumulated data generated over the past ten years has provided evidence that long-term progression-free survival (PFS) can reproducibly be attained in a significant fraction of PCNSL patients that receive dose-intensive chemotherapy consolidation, without whole brain radiotherapy. One consolidative regimen that has reproducibly demonstrated promise is the combination of infusional etoposide plus high-dose cytarabine (EA), administered in first complete remission after methotrexate, temozolomide and rituximab-based induction. Given evolving principles of management and the mounting evidence for reproducible improvements in survival rates in prospective clinical series, our goal in this review is to highlight and update principles in diagnosis, staging and management as well as to review data regarding the pathogenesis of central nervous system lymphomas, information that is likely to constitute a basis for the implementation of novel therapies that are requisite for further progress in this unique phenotype of non-Hodgkin lymphoma. PMID:24837460

  12. Redox Signaling Mechanisms in Nervous System Development.

    PubMed

    Olguín-Albuerne, Mauricio; Morán, Julio

    2017-09-21

    Numerous studies have demonstrated the actions of reactive oxygen species (ROS) as regulators of several physiological processes. In this study, we discuss how redox signaling mechanisms operate to control different processes such as neuronal differentiation, oligodendrocyte differentiation, dendritic growth, and axonal growth. Recent Advances: Redox homeostasis regulates the physiology of neural stem cells (NSCs). Notably, the neuronal differentiation process of NSCs is determined by a change toward oxidative metabolism, increased levels of mitochondrial ROS, increased activity of NADPH oxidase (NOX) enzymes, decreased levels of Nrf2, and differential regulation of different redoxins. Furthermore, during the neuronal maturation processes, NOX and MICAL produce ROS to regulate cytoskeletal dynamics, which control the dendritic and axonal growth, as well as the axonal guidance. The redox homeostasis changes are, in part, attributed to cell metabolism and compartmentalized production of ROS, which is regulated, sensed, and transduced by different molecules such as thioredoxins, glutaredoxins, peroxiredoxins, and nucleoredoxin to control different signaling pathways in different subcellular regions. The study of how these elements cooperatively act is essential for the understanding of nervous system development, as well as the application of regenerative therapies that recapitulate these processes. The information about these topics in the last two decades leads us to the conclusion that the role of ROS signaling in development of the nervous system is more important than it was previously believed and makes clear the importance of exploring in more detail the mechanisms of redox signaling. Antioxid. Redox Signal. 00, 000-000.

  13. Central nervous system vasculitis in children.

    PubMed

    Cellucci, Tania; Benseler, Susanne M

    2010-09-01

    To review the current literature of childhood primary and secondary central nervous system (CNS) vasculitis and to evaluate the growing differential diagnosis of inflammatory and noninflammatory brain diseases. Primary angiitis of the central nervous system in children (cPACNS) is a reversible cause of severe neurological deficits and/or psychiatric symptoms. This disease is classified into subtypes based on distinct clinical and radiological features, treatment strategies, and disease trajectories. Also, the increased diagnostic yield from elective brain biopsies in children has improved our ability to diagnose angiography-negative cPACNS. Over the past few years, the differential diagnosis for cPACNS has rapidly expanded due to the characterization of novel inflammatory and noninflammatory brain diseases. Specifically, vasoconstrictive disorders and neuronal antibody-associated conditions have now been described in children and have overlapping clinical features with cPACNS. This review summarizes the recent data on diagnosis, treatment, and prognosis of cPACNS. It also addresses the evolving differential diagnosis for CNS vasculitis. Our improved understanding of these disorders allows a tailored diagnostic approach leading to rapid diagnosis and initiation of therapy in these potentially reversible conditions.

  14. Diagnosing central nervous system vasculitis in children.

    PubMed

    Cellucci, Tania; Benseler, Susanne M

    2010-12-01

    To review the current literature of childhood central nervous system vasculitis, and to discuss a tailored approach to diagnosis and treatment based on recent evidence. Primary angiitis of the central nervous system in children (cPACNS) is an increasingly recognized inflammatory brain disease with potentially devastating neurological consequences. The diagnostic approach should be tailored to the clinical presentation of the child with suspected cPACNS and should address the expanding spectrum of inflammatory and noninflammatory brain diseases with overlapping clinical features. New evidence has confirmed that elective brain biopsies in children have a higher diagnostic yield than in adults and improve our ability to diagnose angiography-negative cPACNS. Finally, observational studies have shown that early diagnosis and aggressive treatment lead to improved neurological outcomes and lower mortality rates in patients with cPACNS. This review summarizes the recent data on diagnosis, classification, treatment, and outcomes in cPACNS. Our improved understanding of cPACNS facilitates a tailored diagnostic approach that results in earlier diagnosis and initiation of therapy for this potentially reversible condition.

  15. Parasympathetic nervous system activity and children's sleep.

    PubMed

    El-Sheikh, Mona; Erath, Stephen A; Bagley, Erika J

    2013-06-01

    We examined indices of children's parasympathetic nervous system activity (PNS), including respiratory sinus arrhythmia during baseline (RSAB) and RSA reactivity (RSAR), to a laboratory challenge, and importantly the interaction between RSAB and RSAR as predictors of multiple parameters of children's sleep. Lower RSAR denotes increased vagal withdrawal (reductions in RSA between baseline and task) and higher RSAR represents decreased vagal withdrawal or augmentation (increases in RSA between baseline and task). A community sample of school-attending children (121 boys and 103 girls) participated [mean age = 10.41 years; standard deviation (SD) = 0.67]. Children's sleep parameters were examined through actigraphy for 7 consecutive nights. Findings demonstrate that RSAB and RSAR interact to predict multiple sleep quality parameters (activity, minutes awake after sleep onset and long wake episodes). The overall pattern of effects illustrates that children who exhibit more disrupted sleep (increased activity, more minutes awake after sleep onset and more frequent long wake episodes) are those with lower RSAB in conjunction with lower RSAR. This combination of low RSAB and low RSAR probably reflects increased autonomic nervous system arousal, which interferes with sleep. Results illustrate the importance of individual differences in physiological regulation indexed by interactions between PNS baseline activity and PNS reactivity for a better understanding of children's sleep quality.

  16. Autoimmune channelopathies of the nervous system.

    PubMed

    Kleopa, Kleopas A

    2011-09-01

    Ion channels are complex transmembrane proteins that orchestrate the electrical signals necessary for normal function of excitable tissues, including the central nervous system, peripheral nerve, and both skeletal and cardiac muscle. Progress in molecular biology has allowed cloning and expression of genes that encode channel proteins, while comparable advances in biophysics, including patch-clamp electrophysiology and related techniques, have made the functional assessment of expressed proteins at the level of single channel molecules possible. The role of ion channel defects in the pathogenesis of numerous disorders has become increasingly apparent over the last two decades. Neurological channelopathies are frequently genetically determined but may also be acquired through autoimmune mechanisms. All of these autoimmune conditions can arise as paraneoplastic syndromes or independent from malignancies. The pathogenicity of autoantibodies to ion channels has been demonstrated in most of these conditions, and patients may respond well to immunotherapies that reduce the levels of the pathogenic autoantibodies. Autoimmune channelopathies may have a good prognosis, especially if diagnosed and treated early, and if they are non-paraneoplastic. This review focuses on clinical, pathophysiologic and therapeutic aspects of autoimmune ion channel disorders of the nervous system.

  17. Central nervous system toxicity of metallic nanoparticles

    PubMed Central

    Feng, Xiaoli; Chen, Aijie; Zhang, Yanli; Wang, Jianfeng; Shao, Longquan; Wei, Limin

    2015-01-01

    Nanomaterials (NMs) are increasingly used for the therapy, diagnosis, and monitoring of disease- or drug-induced mechanisms in the human biological system. In view of their small size, after certain modifications, NMs have the capacity to bypass or cross the blood–brain barrier. Nanotechnology is particularly advantageous in the field of neurology. Examples may include the utilization of nanoparticle (NP)-based drug carriers to readily cross the blood–brain barrier to treat central nervous system (CNS) diseases, nanoscaffolds for axonal regeneration, nanoelectromechanical systems in neurological operations, and NPs in molecular imaging and CNS imaging. However, NPs can also be potentially hazardous to the CNS in terms of nano-neurotoxicity via several possible mechanisms, such as oxidative stress, autophagy, and lysosome dysfunction, and the activation of certain signaling pathways. In this review, we discuss the dual effect of NMs on the CNS and the mechanisms involved. The limitations of the current research are also discussed. PMID:26170667

  18. Space exploration, Mars, and the nervous system.

    PubMed

    Kalb, Robert; Solomon, David

    2007-04-01

    When human beings venture back to the moon and then on to Mars in the coming decade or so, we will be riding on the accumulated data and experience from approximately 50 years of manned space exploration. Virtually every organ system functions differently in the absence of gravity, and some of these changes are maladaptive. From a biologic perspective, long duration spaceflight beyond low Earth orbit presents many unique challenges. Astronauts traveling to Mars will live in the absence of gravity for more than 1 year en route and will have to transition between weightlessness and planetary gravitational forces at the beginning, middle, and end of the mission. We discuss some of what is known about the effects of spaceflight on nervous system function, with emphasis on the neuromuscular and vestibular systems because success of a Mars mission will depend on their proper functioning.

  19. Investigation of the Role of Breast Cancer Resistance Protein (Bcrp/Abcg2) on Pharmacokinetics and Central Nervous System Penetration of Abacavir and Zidovudine in the Mouse

    PubMed Central

    Giri, Nagdeep; Shaik, Naveed; Pan, Guoyu; Terasaki, Tetsuya; Mukai, Chisato; Kitagaki, Shinji; Miyakoshi, Naoki; Elmquist, William F.

    2016-01-01

    Many anti-human immunodeficiency virus 1 nucleoside reverse-transcriptase inhibitors have low central nervous system (CNS) distribution due in part to active efflux transport at the blood-brain barrier. We have previously shown that zidovudine (AZT) and abacavir (ABC) are in vitro substrates for the efflux transport protein breast cancer resistance protein (Bcrp) 1. We evaluated the influence of Bcrp1 on plasma pharmacokinetics and brain penetration of zidovudine and abacavir in wild-type and Bcrp1-deficient (Bcrp1−/−) FVB mice. There was no difference in either area under the concentration-time profiles for plasma (AUCplasma) or brain (AUCbrain) for zidovudine between the wild-type and Bcrp1−/− mice. The AUCplasma of abacavir was 20% lower in the Bcrp1−/− mice, whereas the AUCbrain was 20% greater. This difference resulted in a 1.5-fold increase in abacavir brain exposure in the Bcrp1−/− mice. The effect of selective and nonselective transport inhibitors on the ABC brain/plasma ratio at a single time point was evaluated. 3-(6-Isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indol-3-yl)-propionicacid tert-butyl ester (Ko143), N[4[2-(6, 7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]-5-methoxy-9-oxo-10H-acridine-4-carboxamide (GF120918), probenecid, and Pluronic P85 increased abacavir plasma concentrations in the wild-type mice. Abacavir plasma concentrations in Bcrp1−/− mice were increased by (R)-4-((1aR,6R,10bS)-1,2-difluoro-1,1a,6,10b-tetrahydrodibenzo(a,e)cyclopropa(c)cycloheptan-6-yl)-α-((5-quinoloyloxy)methyl)-1-piperazineethanol trihydrochloride (LY335979), GF120918, and probenecid, but not by Ko143. Brain/plasma concentration ratios in both the wild-type and Bcrp1−/− mice were increased by the P-glycoprotein inhibitors LY335979 and GF120918, but not by BCRP-selective inhibitors. These data indicate that deletion of Bcrp1 has little influence on the pharmacokinetics or brain

  20. Detection of MGMT, RASSF1A, p15INK4B, and p14ARF promoter methylation in circulating tumor-derived DNA of central nervous system cancer patients.

    PubMed

    Majchrzak-Celińska, Aleksandra; Paluszczak, Jarosław; Kleszcz, Robert; Magiera, Marta; Barciszewska, Anna-Maria; Nowak, Stanisław; Baer-Dubowska, Wanda

    2013-08-01

    Despite the growing understanding of the mechanisms of carcinogenesis, cancers of the central nervous system are usually associated with unfavorable prognosis. The use of an appropriate molecular marker may improve the treatment outcome by allowing early diagnosis and treatment susceptibility monitoring. Since methylation of tumor-derived DNA can be detected in the serum of cancer patients, this makes DNA methylation-based biomarkers one of the most promising diagnostic strategies. In this study, the methylation profiles of MGMT, RASSF1A, p15INK4B, and p14ARF genes were evaluated in serum free-circulating DNA and the corresponding tumor tissue in a group of 33 primary or metastatic central nervous system cancer patients. Gene promoter methylation was assessed using methylation-specific polymerase chain reaction (PCR). All the tested genes were found to be methylated to a different extent in both serum and tumor samples. In comparison to metastatic brain tumor patients, the patients with glial tumors were characterized by a higher frequency of gene hypermethylation. The hypermethylation of RASSF1A differentiated primary from metastatic brain cancers. Moreover, the gene methylation profiles observed in serum, in most cases, matched the methylation profiles detected in paired tumor samples.

  1. Extracellular vesicles round off communication in the nervous system

    PubMed Central

    Budnik, Vivian; Ruiz-Cañada, Catalina; Wendler, Franz

    2016-01-01

    Functional neural competence and integrity require interactive exchanges among sensory and motor neurons, interneurons and glial cells. Recent studies have attributed some of the tasks needed for these exchanges to extracellular vesicles (such as exosomes and microvesicles), which are most prominently involved in shuttling reciprocal signals between myelinating glia and neurons, thus promoting neuronal survival, the immune response mediated by microglia, and synapse assembly and plasticity. Such vesicles have also been identified as important factors in the spread of neurodegenerative disorders and brain cancer. These extracellular vesicle functions add a previously unrecognized level of complexity to transcellular interactions within the nervous system. PMID:26891626

  2. Novel nervous system mechanisms in visceral pain.

    PubMed

    De Winter, B Y; Deiteren, A; De Man, J G

    2016-03-01

    Visceral hypersensitivity is an important factor underlying abdominal pain in functional gastrointestinal disorders such as irritable bowel syndrome (IBS) and can result from aberrant signaling from the gut to the brain or vice versa. Over the last two decades, research has identified several selective, intertwining pathways that underlie IBS-related visceral nociception, including specific receptors on afferent and efferent nerve fibers such as transient receptor potential channels (TRP) channels, opioid, and cannabinoid receptors. In this issue of Neurogastroenterology and Motility Gil et al. demonstrate that in an animal model with reduced descending inhibitory control, the sympathetic nervous system outflow is enhanced, contributing to visceral and somatic hypersensitivity. They also provide evidence that interfering with the activation of adrenergic receptors on sensory nerves can be an interesting new strategy to treat visceral pain in IBS. This mini-review places these findings in a broader perspective by providing an overview of promising novel mechanisms to alter the nervous control of visceral pain interfering with afferent or efferent neuronal signaling. © 2016 John Wiley & Sons Ltd.

  3. The evolution of the serotonergic nervous system.

    PubMed Central

    Hay-Schmidt, A

    2000-01-01

    The pattern of development of the serotonergic nervous system is described from the larvae of ctenophores, platyhelminths, nemerteans, entoprocts, ectoprocts (bryozoans), molluscs, polychaetes, brachiopods, phoronids, echinoderms, enteropneusts and lampreys. The larval brain (apical ganglion) of spiralian protostomes (except nermerteans) generally has three serotonergic neurons and the lateral pair always innervates the ciliary band of the prototroch. In contrast, brachiopods, phoronids, echinoderms and enteropneusts have numerous serotonergic neurons in the apical ganglion from which the ciliary band is innervated. This pattern of development is much like the pattern seen in lamprey embryos and larvae, which leads the author to conclude that the serotonergic raphe system found in vertebrates originated in the larval brain of deuterostome invertebrates. Further, the neural tube of chordates appears to be derived, at least in part, from the ciliary band of deuterostome invertebrate larvae. The evidence shows no sign of a shift in the dorsal ventral orientation within the line leading to the chordates. PMID:10885511

  4. Gravity sensing in the central nervous system.

    PubMed

    Wiedemann, Meike; Hanke, Wolfgang

    2002-07-01

    For human based space research it is of high importance to understand the influence of gravity on the properties of the central nervous system (CNS). Until now it is not much known about how neuronal tissue can sense gravity. The aim of this study was to find out weather and how the CNS, as a complex system, can percept and react to changes in gravity. Neuronal tissue and especially the CNS fulfils all the requirements for excitable media. Consequently, self-organisation, pattern formation and propagating excitation waves as typical events of excitable media have been observed in such tissue. The spreading depression (SD), an excitation depression wave is the most obvious and best described of these phenomena in the CNS. In our experiments we showed that the properties of the SD and therefore the CNS in its properties as an excitable medium reacts very sensitive to changes in gravity.

  5. [Tumors of the central nervous system].

    PubMed

    Alegría-Loyola, Marco Antonio; Galnares-Olalde, Javier Andrés; Mercado, Moisés

    2017-01-01

    Central nervous system (CNS) tumors constitute a heterogeneous group of neoplasms that share a considerable morbidity and mortality rate. Recent advances in the underlying oncogenic mechanisms of these tumors have led to new classification systems, which, in turn, allow for a better diagnostic approach and therapeutic planning. Most of these neoplasms occur sporadically and several risk factors have been found to be associated with their development, such as exposure to ionizing radiation or electromagnetic fields and the concomitant presence of conditions like diabetes, hypertension and Parkinson's disease. A relatively minor proportion of primary CNS tumors occur in the context of hereditary syndromes. The purpose of this review is to analyze the etiopathogenesis, clinical presentation, diagnosis and therapy of CNS tumors with particular emphasis in the putative risk factors mentioned above.

  6. Exercise and the autonomic nervous system.

    PubMed

    Fu, Qi; Levine, Benjamin D

    2013-01-01

    The autonomic nervous system plays a crucial role in the cardiovascular response to acute (dynamic) exercise in animals and humans. During exercise, oxygen uptake is a function of the triple-product of heart rate and stroke volume (i.e., cardiac output) and arterial-mixed venous oxygen difference (the Fick principle). The degree to which each of the variables can increase determines maximal oxygen uptake (V˙O2max). Both "central command" and "the exercise pressor reflex" are important in determining the cardiovascular response and the resetting of the arterial baroreflex during exercise to precisely match systemic oxygen delivery with metabolic demand. In general, patients with autonomic disorders have low levels of V˙O2max, indicating reduced physical fitness and exercise capacity. Moreover, the vast majority of the patients have blunted or abnormal cardiovascular response to exercise, especially during maximal exercise. There is now convincing evidence that some of the protective and therapeutic effects of chronic exercise training are related to the impact on the autonomic nervous system. Additionally, training induced improvement in vascular function, blood volume expansion, cardiac remodeling, insulin resistance and renal-adrenal function may also contribute to the protection and treatment of cardiovascular, metabolic and autonomic disorders. Exercise training also improves mental health, helps to prevent depression, and promotes or maintains positive self-esteem. Moderate-intensity exercise at least 30 minutes per day and at least 5 days per week is recommended for the vast majority of people. Supervised exercise training is preferable to maximize function capacity, and may be particularly important for patients with autonomic disorders.

  7. Autonomic nervous system and cardiovascular disease.

    PubMed

    Deschamps, Alain; Denault, André

    2009-06-01

    Because anesthesia affects the integrity of the autonomic nervous system, anesthesiologists use vital signs to maintain respiratory and circulatory homeostasis. However, patients with genetic predispositions or with autonomic dysfunctions are at risk of severe complications from anesthesia. For these patients, the monitoring of vital signs may not give sufficient warning to avoid complications. The development of methods to measure autonomic tone could be of interest to anesthesiologists because they could warn of changes in autonomic tone before vital signs are affected. New noninvasive methods are being developed to obtain measurements of parasympathetic and sympathetic output allowing for the monitoring of perioperative autonomic tone. These measurements are based on analysis of heart rate and blood pressure variability. In this report, the principals of the analysis of heart rate and blood pressure variability will be explained and the usefulness of these methods to anesthesiologists will be discussed.

  8. Scaffolds for central nervous system tissue engineering

    NASA Astrophysics Data System (ADS)

    He, Jin; Wang, Xiu-Mei; Spector, Myron; Cui, Fu-Zhai

    2012-03-01

    Traumatic injuries to the brain and spinal cord of the central nervous system (CNS) lead to severe and permanent neurological deficits and to date there is no universally accepted treatment. Owing to the profound impact, extensive studies have been carried out aiming at reducing inflammatory responses and overcoming the inhibitory environment in the CNS after injury so as to enhance regeneration. Artificial scaffolds may provide a suitable environment for axonal regeneration and functional recovery, and are of particular importance in cases in which the injury has resulted in a cavitary defect. In this review we discuss development of scaffolds for CNS tissue engineering, focusing on mechanism of CNS injuries, various biomaterials that have been used in studies, and current strategies for designing and fabricating scaffolds.

  9. [Idiopathic hypersomnia of the central nervous system].

    PubMed

    Bové-Ribé, A

    Idiopathic hypersomnia of the central nervous system is a cause of excessive diurnal somnolence which affects 5-10% of the patients who attend sleep clinics for this reason. We describe three male patients who consulted for excessive diurnal somnolence. Nocturnal polysomnographic studies followed by tests for multiple latencies of sleep were done. In all cases there was confirmation of lengthening of the time of nocturnal sleep with normal phases of sleep and an increase in the number of sleep spindles in phase II. Similarly there was an average latency of sleep of less than 10 minutes and fewer than two phases of REM in the multiple latencies test. All patients improved with drugs stimulating vigil, two of them with centramine and the third with methilphenidate. We consider the clinical data the polysomnographic criteria which help to establish the diagnosis.

  10. Environmentally related disorders of the nervous system

    SciTech Connect

    Baker, E.L.; Feldman, R.G.; French, J.G. )

    1990-03-01

    Specific physical and chemical agents found in the workplace and in the general environment are responsible for characteristic pathologic processes within the nervous system. It has been shown that many neurotoxic agents produce a dose-related spectrum of impairment ranging from mild slowing of nerve conducting velocity or prolongation in reaction time to neuropathy and frank encephalopathy. Clinical manifestations are determined by the agent involved, by the dose of exposure, the vulnerability of the cellular target, the ability of the organism to metabolize and excrete the agent, and the ability to repair damage. An occupational history, including evaluation of evidence of specific agents and job history, is a critical component in the clinical management of individuals with suspect neurotoxic disease. Environmentally-induced disorders can be prevented by appropriate environmental controls. Prevention of neurotoxic disease is a complex process requiring continuous involvement of public health agencies and strong scientific research.

  11. Central nervous system nocardiosis in Queensland

    PubMed Central

    Rafiei, Nastaran; Peri, Anna Maria; Righi, Elda; Harris, Patrick; Paterson, David L.

    2016-01-01

    Abstract Nocardia infection of the central nervous system (CNS) is an uncommon but clinically important disease, often occurring in immunocompromised individuals and carrying a high mortality rate. We present 20 cases of microbiologically proven CNS nocardiosis diagnosed in Queensland from 1997 to 2015 and review the literature from 1997 to 2016. Over 50% of cases occurred in immunocompromised individuals, with corticosteroid use posing a particularly significant risk factor. Nine (45%) patients were immunocompetent and 3 had no comorbidities at time of diagnosis. Nocardia farcinica was the most frequently isolated species (8/20) and resistance to trimethoprim–sulfamethoxazole (TMP-SMX) was found in 2 isolates. Overall, 35% of our patients died within 1 year, with the majority of deaths occurring in the first month following diagnosis. Interestingly, of the 7 deaths occurring at 1 year, 6 were attributed to N farcinica with the seventh isolate being unspeciated, suggesting the virulence of the N farcinica strain. PMID:27861348

  12. The sympathetic nervous system in obesity hypertension.

    PubMed

    Lohmeier, Thomas E; Iliescu, Radu

    2013-08-01

    Abundant evidence supports a role of the sympathetic nervous system in the pathogenesis of obesity-related hypertension. However, the nature and temporal progression of mechanisms underlying this sympathetically mediated hypertension are incompletely understood. Recent technological advances allowing direct recordings of renal sympathetic nerve activity (RSNA) in conscious animals, together with direct suppression of RSNA by renal denervation and reflex-mediated global sympathetic inhibition in experimental animals and human subjects have been especially valuable in elucidating these mechanisms. These studies strongly support the concept that increased RSNA is the critical mechanism by which increased central sympathetic outflow initiates and maintains reductions in renal excretory function, causing obesity hypertension. Potential determinants of renal sympathoexcitation and the differential mechanisms mediating the effects of renal-specific versus reflex-mediated, global sympathetic inhibition on renal hemodynamics and cardiac autonomic function are discussed. These differential mechanisms may impact the efficacy of current device-based approaches for hypertension therapy.

  13. BK Channels in the Central Nervous System

    PubMed Central

    Contet, C.; Goulding, S. P.; Kuljis, D. A.; Barth, A. L.

    2016-01-01

    Large conductance Ca2+- and voltage-activated K+ (BK) channels are widely distributed in the postnatal central nervous system (CNS). BK channels play a pleiotropic role in regulating the activity of brain and spinal cord neural circuits by providing a negative feedback mechanism for local increases in intracellular Ca2+ concentrations. In neurons, they regulate the timing and duration of K+ influx such that they can either increase or decrease firing depending on the cellular context, and they can suppress neurotransmitter release from presynaptic terminals. In addition, BK channels located in astrocytes and arterial myocytes modulate cerebral blood flow. Not surprisingly, both loss and gain of BK channel function have been associated with CNS disorders such as epilepsy, ataxia, mental retardation, and chronic pain. On the other hand, the neuroprotective role played by BK channels in a number of pathological situations could potentially be leveraged to correct neurological dysfunction. PMID:27238267

  14. VIIP: Central Nervous System (CNS) Modeling

    NASA Technical Reports Server (NTRS)

    Vera, Jerry; Mulugeta, Lealem; Nelson, Emily; Raykin, Julia; Feola, Andrew; Gleason, Rudy; Samuels, Brian; Ethier, C. Ross; Myers, Jerry

    2015-01-01

    Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.

  15. Neuroactive steroids and central nervous system disorders.

    PubMed

    Wang, M; Bäckström, T; Sundström, I; Wahlström, G; Olsson, T; Zhu, D; Johansson, I M; Björn, I; Bixo, M

    2001-01-01

    Steroid hormones are vital for the cell life and affect a number of neuroendocrine and behavioral functions. In contrast to their endocrine actions, certain steroids have been shown to rapidly alter brain excitability and to produce behavioral effects within seconds to minutes. In this article we direct attention to this issue of neuroactive steroids by outlining several aspects of current interest in the field of steroid research. Recent advances in the neurobiology of neuroactive are described along with the impact of advances on drug design for central nervous system (CNS) disorders provoked by neuroactive steriods. The theme was selected in association with the clinical aspects and therapeutical potentials of the neuroactive steroids in CNS disorders. A wide range of topics relating to the neuroactive steroids are outlined, including steroid concentrations in the brain, premenstrual syndrome, estrogen and Alzheimer's disease, side effects of oral contraceptives, mental disorder in menopause, hormone replacement therapy, Catamenial epilepsy, and neuractive steroids in epilepsy treatment.

  16. Calcium pumps in the central nervous system.

    PubMed

    Mata, Ana M; Sepúlveda, M Rosario

    2005-09-01

    Two families of Ca2+ transport ATPases are involved in the maintenance of Ca2+ homeostasis in the nervous system, the plasma membrane Ca2+-ATPase that pumps Ca2+ to the extracellular medium and the intracellular sarco/endoplasmic reticulum Ca2+-ATPase that transports Ca2+ from the cytosol to the endoplasmic reticulum. Both types of calcium pumps show precise regulatory properties and they are localized in specific subcellular regions. In this review, we describe the functional and regulatory properties of both families of calcium pumps, their distribution in nerve cells, and their involvement in neurological disorders. The functional characterization of neuronal calcium pumps is very important in order to understand the biochemical processes involved in the maintenance of intracellular calcium in synaptic terminals.

  17. Autonomic complications following central nervous system injury.

    PubMed

    Baguley, Ian J

    2008-11-01

    Severe sympathetic overactivity occurs in several conditions that are recognized as medical emergencies. Following central nervous system injury, a small proportion of individuals develop severe paroxysmal sympathetic and motor overactivity. These individuals have a high attendant risk of unnecessary secondary morbidity. Following acquired brain injury, the syndrome is known by a number of names including dysautonomia and sympathetic storm. Dysautonomia is currently a diagnosis of exclusion and often goes unrecognized. The evidence base for management is almost entirely anecdotal in nature; there has been little structured or prospective research. In contrast, the evidence base for autonomic dysreflexia following spinal cord injury is much stronger, with level 1 evidence for many treatment interventions. This review presents a current understanding of each condition and suggests simple management protocols. With the marked disparity in the literature for the two conditions, the main focus is on the literature for dysautonomia. The similarity between these two conditions and the other autonomic emergency conditions is discussed.

  18. Navigating Intermediate Targets: The Nervous System Midline

    PubMed Central

    Dickson, Barry J.; Zou, Yimin

    2010-01-01

    In a bilaterally symmetric animal, the midline plays a key role in directing axon growth during wiring of the nervous system. Midline cells provide a variety of guidance cues for growing axons, to which different types of axons respond in different ways and at different times. For some axons, the midline is an intermediate target. They first seek it out, but then move on towards their final targets on the opposite side. For others, the midline is a repulsive barrier that keeps them on their own side of the midline. And for many of these axons the midline provides signals that guide them along specific lateral pathways or up and down the longitudinal axis. PMID:20534708

  19. The autonomic nervous system and perinatal metabolism.

    PubMed

    Milner, R D; De Gasparo, M

    1981-01-01

    The development of the autonomic nervous system in relation to perinatal metabolism is reviewed with particular attention given to the adipocyte, hepatocyte and the A and B cells of the islets of Langerhans. Adrenergic receptors develop in the B cell independently of normal innervation and by the time of birth, in most species studied, the pancreas, liver and adipose tissue respond appropriately to autonomic signals. Birth is associated with a huge surge in circulating catecholamines which is probably responsible for the early postnatal rise in free fatty acids and glucagon concentrations in plasma. beta-Blocking drugs such as propranolol have an adverse effect on fetal growth and neonatal metabolism, being responsible for hypoglycemia and for impairing the thermogenic response to cold exposure. beta-Mimetic drugs are commonly used to prevent premature labour and may help the fetus in other ways, for example, by improving the placental blood supply and the delivery of nutrients by increasing maternal fat and carbohydrate mobilization.

  20. Subcortical cytoskeleton periodicity throughout the nervous system.

    PubMed

    D'Este, Elisa; Kamin, Dirk; Velte, Caroline; Göttfert, Fabian; Simons, Mikael; Hell, Stefan W

    2016-03-07

    Superresolution fluorescence microscopy recently revealed a ~190 nm periodic cytoskeleton lattice consisting of actin, spectrin, and other proteins underneath the membrane of cultured hippocampal neurons. Whether the periodic cytoskeleton lattice is a structural feature of all neurons and how it is modified when axons are ensheathed by myelin forming glial cells is not known. Here, STED nanoscopy is used to demonstrate that this structure is a commonplace of virtually all neuron types in vitro. To check how the subcortical meshwork is modified during myelination, we studied sciatic nerve fibers from adult mice. Periodicity of both actin and spectrin was uncovered at the internodes, indicating no substantial differences between unmyelinated and myelinated axons. Remarkably, the actin/spectrin pattern was also detected in glial cells such as cultured oligodendrocyte precursor cells. Altogether our work shows that the periodic subcortical cytoskeletal meshwork is a fundamental characteristic of cells in the nervous system and is not a distinctive feature of neurons, as previously thought.

  1. Varicella Zoster Virus in the Nervous System

    PubMed Central

    Gilden, Don; Nagel, Maria; Cohrs, Randall; Mahalingam, Ravi; Baird, Nicholas

    2015-01-01

    Varicella zoster virus (VZV) is a ubiquitous, exclusively human alphaherpesvirus. Primary infection usually results in varicella (chickenpox), after which VZV becomes latent in ganglionic neurons along the entire neuraxis. As VZV-specific cell-mediated immunity declines in elderly and immunocompromised individuals, VZV reactivates and causes herpes zoster (shingles), frequently complicated by postherpetic neuralgia. VZV reactivation also produces multiple serious neurological and ocular diseases, such as cranial nerve palsies, meningoencephalitis, myelopathy, and VZV vasculopathy, including giant cell arteritis, with or without associated rash. Herein, we review the clinical, laboratory, imaging, and pathological features of neurological complications of VZV reactivation as well as diagnostic tests to verify VZV infection of the nervous system. Updates on the physical state of VZV DNA and viral gene expression in latently infected ganglia, neuronal, and primate models to study varicella pathogenesis and immunity are presented along with innovations in the immunization of elderly individuals to prevent VZV reactivation. PMID:26918131

  2. [Viral infections of human central nervous system].

    PubMed

    Agut, Henri

    2016-01-01

    The viruses that can infect the central nervous system of humans are numerous and form a heterogeneous group with respect to their structural, functional and epidemiological properties. The pathophysiological mechanisms leading to associated neurological diseases, mainly meningitis and encephalitis, also are complex and often intertwined. Overall, neurological clinical symptoms correspond either to acute viral diseases associated with primary infections or to acute, subacute or chronic diseases associated with persistent viral infections. The frequent severity of the clinical situation requires in all cases the practice of virological diagnosis for which the PCR techniques applied to cerebrospinal fluid samples occupy a prominent place. The severity of clinical manifestations justifies the use of prophylactic vaccination when available and antiviral treatment as soon as the causative virus is identified or suspected.

  3. Adenosine receptors and the central nervous system.

    PubMed

    Sebastião, Ana M; Ribeiro, Joaquim A

    2009-01-01

    The adenosine receptors (ARs) in the nervous system act as a kind of "go-between" to regulate the release of neurotransmitters (this includes all known neurotransmitters) and the action of neuromodulators (e.g., neuropeptides, neurotrophic factors). Receptor-receptor interactions and AR-transporter interplay occur as part of the adenosine's attempt to control synaptic transmission. A(2A)ARs are more abundant in the striatum and A(1)ARs in the hippocampus, but both receptors interfere with the efficiency and plasticity-regulated synaptic transmission in most brain areas. The omnipresence of adenosine and A(2A) and A(1) ARs in all nervous system cells (neurons and glia), together with the intensive release of adenosine following insults, makes adenosine a kind of "maestro" of the tripartite synapse in the homeostatic coordination of the brain function. Under physiological conditions, both A(2A) and A(1) ARs play an important role in sleep and arousal, cognition, memory and learning, whereas under pathological conditions (e.g., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, stroke, epilepsy, drug addiction, pain, schizophrenia, depression), ARs operate a time/circumstance window where in some circumstances A(1)AR agonists may predominate as early neuroprotectors, and in other circumstances A(2A)AR antagonists may alter the outcomes of some of the pathological deficiencies. In some circumstances, and depending on the therapeutic window, the use of A(2A)AR agonists may be initially beneficial; however, at later time points, the use of A(2A)AR antagonists proved beneficial in several pathologies. Since selective ligands for A(1) and A(2A) ARs are now entering clinical trials, the time has come to determine the role of these receptors in neurological and psychiatric diseases and identify therapies that will alter the outcomes of these diseases, therefore providing a hopeful future for the patients who suffer from these diseases.

  4. Gangliosides of the Vertebrate Nervous System.

    PubMed

    Schnaar, Ronald L

    2016-08-14

    Gangliosides, sialylated glycosphingolipids, found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Composed of a sialylated glycan attached to a ceramide lipid, the same four structures-GM1, GD1a, GD1b, and GT1b-represent the vast majority (>90%) of gangliosides in the brains of all mammals and birds. Primarily found on the outer surface of the plasma membrane with their glycans facing outward, gangliosides associate laterally with each other, sphingomyelin, cholesterol, and select proteins in lipid rafts-the dynamic functional subdomains of the plasma membrane. The functions of gangliosides in the human nervous system are revealed by congenital mutations in ganglioside biosynthetic genes. Mutations in ST3GAL5, which codes for an enzyme early in brain ganglioside biosynthesis, result in an early-onset seizure disorder with profound motor and cognitive decay, whereas mutations in B4GALNT1, a gene encoding a later step, result in hereditary spastic paraplegia accompanied by intellectual deficits. The molecular functions of brain gangliosides include regulation of receptors in the same membrane via lateral (cis) associations and regulation of cell-cell recognition by trans interaction with ganglioside binding proteins on apposing cells. Gangliosides also affect the aggregation of Aβ (Alzheimer's disease) and α-synuclein (Parkinson's Disease). As analytical, biochemical, and genetic tools advance, research on gangliosides promises to reveal mechanisms of molecular control related to nerve and glial cell differentiation, neuronal excitability, axon outgrowth after nervous system injury, and protein folding in neurodegenerative diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Cnidarians and the evolutionary origin of the nervous system.

    PubMed

    Watanabe, Hiroshi; Fujisawa, Toshitaka; Holstein, Thomas W

    2009-04-01

    Cnidarians are widely regarded as one of the first organisms in animal evolution possessing a nervous system. Conventional histological and electrophysiological studies have revealed a considerable degree of complexity of the cnidarian nervous system. Thanks to expressed sequence tags and genome projects and the availability of functional assay systems in cnidarians, this simple nervous system is now genetically accessible and becomes particularly valuable for understanding the origin and evolution of the genetic control mechanisms underlying its development. In the present review, the anatomical and physiological features of the cnidarian nervous system and the interesting parallels in neurodevelopmental mechanisms between Cnidaria and Bilateria are discussed.

  6. Sialyltransferase regulates nervous system function in Drosophila

    PubMed Central

    Repnikova, Elena; Koles, Kate; Nakamura, Michiko; Pitts, Jared; Li, Haiwen; Ambavane, Apoorva; Zoran, Mark J.; Panin, Vladislav M.

    2012-01-01

    In vertebrates, sialylated glycans participate in a wide range of biological processes and affect nervous system’s development and function. While the complexity of glycosylation and the functional redundancy among sialyltransferases provide obstacles for revealing biological roles of sialylation in mammals, Drosophila possesses a sole vertebrate-type sialyltransferase, DSiaT, with significant homology to its mammalian counterparts, suggesting that Drosophila could be a suitable model to investigate the function of sialylation. To explore this possibility and investigate the role of sialylation in Drosophila, we inactivated DSiaT in vivo by gene targeting and analyzed phenotypes of DSiaT mutants using a combination of behavioural, immunolabeling, electrophysiological and pharmacological approaches. Our experiments demonstrated that DSiaT expression is restricted to a subset of CNS neurons throughout development. We found that DSiaT mutations result in significantly decreased life span, locomotor abnormalities, temperature-sensitive paralysis and defects of neuromuscular junctions. Our results indicate that DSiaT regulates neuronal excitability and affects the function of a voltage-gated sodium channel. Finally, we showed that sialyltransferase activity is required for DSiaT function in vivo, which suggests that DSiaT mutant phenotypes result from a defect in sialylation of N-glycans. This work provided the first evidence that sialylation has an important biological function in protostomes, while also revealing a novel, nervous system-specific function of α2,6 sialylation. Thus, our data shed light on one of the most ancient functions of sialic acids in metazoan organisms and suggest a possibility that this function is evolutionarily conserved between flies and mammals. PMID:20445073

  7. Central nervous system manifestations of neonatal lupus: a systematic review.

    PubMed

    Chen, C C; Lin, K-L; Chen, C-L; Wong, A May-Kuen; Huang, J-L

    2013-12-01

    Neonatal lupus is a rare and acquired autoimmune disease. Central nervous system abnormalities are potential manifestations in neonatal lupus. Through a systematic literature review, we analyzed the clinical features of previously reported neonatal lupus cases where central nervous system abnormalities had been identified. Most reported neonatal lupus patients with central nervous system involvement were neuroimaging-determined and asymptomatic. Only seven neonatal lupus cases were identified as having a symptomatic central nervous system abnormality which caused physical disability or required neurosurgery. A high percentage of these neurosymptomatic neonatal lupus patients had experienced a transient cutaneous skin rash and had no maternal history of autoimmune disease before pregnancy.

  8. Primary central nervous system posttransplant lymphoproliferative disorders.

    PubMed

    Castellano-Sanchez, Amilcar A; Li, Shiyong; Qian, Jiang; Lagoo, Anand; Weir, Edward; Brat, Daniel J

    2004-02-01

    Posttransplant lymphoproliferative disorders (PTLDs) represent a spectrum ranging from Epstein-Barr virus (EBV)-driven polyclonal lymphoid proliferations to EBV+ or EBV- malignant lymphomas. Central nervous system (CNS) PTLDs have not been characterized fully. We reviewed the clinical, radiologic, and pathologic features of 12 primary CNS PTLDs to define them more precisely. Patients included 10 males and 2 females (median age, 43.4 years) who were recipients of kidney (n = 5), liver (n = 2), heart (n = 2), peripheral blood stem cells (n = 2), or bone marrow (n = 1). All received immunosuppressive therapy. CNS symptoms developed 3 to 131 months (mean, 31 months) after transplantation. By neuroimaging, most showed multiple (3 to 9) intra-axial, contrast-enhancing lesions. Histologic sections showed marked expansion of perivascular spaces by large, cytologically malignant lymphoid cells that were CD45+, CD20+, EBV+ and showed light chain restriction or immunoglobulin gene rearrangement. In distinction to PTLDs in other organ systems, CNS PTLDs were uniformly high-grade lymphomas that fulfilled the World Health Organization criteria for monomorphic PTLDs. Extremely short survival periods were noted for each CNS PTLD that followed peripheral blood stem cell transplantation. Survival of others with CNS PTLD varied; some lived more than 2 years.

  9. Diverse Roles of Neurotensin Agonists in the Central Nervous System

    PubMed Central

    Boules, Mona; Li, Zhimin; Smith, Kristin; Fredrickson, Paul; Richelson, Elliott

    2013-01-01

    Neurotensin (NT) is a tridecapeptide that is found in the central nervous system (CNS) and the gastrointestinal tract. NT behaves as a neurotransmitter in the brain and as a hormone in the gut. Additionally, NT acts as a neuromodulator to several neurotransmitter systems including dopaminergic, sertonergic, GABAergic, glutamatergic, and cholinergic systems. Due to its association with such a wide variety of neurotransmitters, NT has been implicated in the pathophysiology of several CNS disorders such as schizophrenia, drug abuse, Parkinson’s disease (PD), pain, central control of blood pressure, eating disorders, as well as, cancer and inflammation. The present review will focus on the role that NT and its analogs play in schizophrenia, endocrine function, pain, psychostimulant abuse, and PD. PMID:23526754

  10. [Microbiological diagnosis of central nervous system infections].

    PubMed

    Codina, María Gema; de Cueto, Marina; Vicente, Diego; Echevarría, Juan Emilio; Prats, Guillem

    2011-02-01

    The infections of the central nervous system are associated with high morbidity and mortality. Several agents including bacteria, viruses, fungi and protozoa can invade the CNS. They are different clinical presentations of these infections: meningitis, encephalitis, brain and epidural abscesses and cerebrospinal fluid shunt infections. The clinical course could be acute, subacute or chronic depending on the infecting agent and the location of the infection. The travelling entails a risk of infection by exotic agents of meningo-encephalitis such as robovirus and arbovirus, which require new diagnostic and therapeutic methods. Despite some progress in the treatment of the CNS infections, the mortality is usually high. Rapid diagnosis and emergent interventions are necessary to improve the outcome of those patients, and early and targeted antimicrobial treatment and support measures are of paramount importance for a favourable clinical patient outcome. The antigen detection techniques and particularly those of genetic diagnosis by amplification (PCR and others) have advanced, and improved the diagnostic of those diseases. In this paper the clinical signs and symptoms and diagnostic procedures of CNS infections are presented.

  11. The autonomic nervous system and hypertension.

    PubMed

    Mancia, Giuseppe; Grassi, Guido

    2014-05-23

    Physiological studies have long documented the key role played by the autonomic nervous system in modulating cardiovascular functions and in controlling blood pressure values, both at rest and in response to environmental stimuli. Experimental and clinical investigations have tested the hypothesis that the origin, progression, and outcome of human hypertension are related to dysfunctional autonomic cardiovascular control and especially to abnormal activation of the sympathetic division. Here, we review the recent literature on the adrenergic and vagal abnormalities that have been reported in essential hypertension, with emphasis on their role as promoters and as amplifiers of the high blood pressure state. We also discuss the possible mechanisms underlying these abnormalities and their importance in the development and progression of the structural and functional cardiovascular damage that characterizes hypertension. Finally, we examine the modifications of sympathetic and vagal cardiovascular influences induced by current nonpharmacological and pharmacological interventions aimed at correcting elevations in blood pressure and restoring the normotensive state. © 2014 American Heart Association, Inc.

  12. Histology of the central nervous system.

    PubMed

    Garman, Robert H

    2011-01-01

    The intent of this article is to assist pathologists inexperienced in examining central nervous system (CNS) sections to recognize normal and abnormal cell types as well as some common artifacts. Dark neurons are the most common histologic artifact but, with experience, can readily be distinguished from degenerating (eosinophilic) neurons. Neuron degeneration stains can be useful in lowering the threshold for detecting neuron degeneration as well as for revealing degeneration within populations of neurons that are too small to show the associated eosinophilic cytoplasmic alteration within H&E-stained sections. Neuron degeneration may also be identified by the presence of associated macroglial and microglial reactions. Knowledge of the distribution of astrocyte cytoplasmic processes is helpful in determining that certain patterns of treatment-related neuropil vacuolation (as well as some artifacts) represent swelling of these processes. On the other hand, vacuoles with different distribution patterns may represent alterations of the myelin sheath. Because brains are typically undersampled for microscopic evaluation, many pathologists are unfamiliar with the circumventricuar organs (CVOs) that represent normal brain structures but are often mistaken for lesions. Therefore, the six CVOs found in the brain are also illustrated in this article.

  13. Plants and the central nervous system.

    PubMed

    Carlini, E A

    2003-06-01

    This review article draws the attention to the many species of plants possessing activity on the central nervous system (CNS). In fact, they cover the whole spectrum of central activity such as psychoanaleptic, psycholeptic and psychodysleptic effects, and several of these plants are currently used in therapeutics to treat human ailments. Among the psychoanaleptic (stimulant) plants, those utilized by human beings to reduce body weight [Ephedra spp. (Ma Huang), Paullinia spp. (guaraná), Catha edulis Forssk. (khat)] and plants used to improve general health conditions (plant adaptogens) were scrutinized. Many species of hallucinogenic (psychodysleptic) plants are used by humans throughout the world to achieve states of mind distortions; among those, a few have been used for therapeutic purposes, such as Cannabis sativa L., Tabernanthe iboga Baill. and the mixture of Psychotria viridis Ruiz and Pav. and Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton. Plants showing central psycholeptic activities, such as analgesic or anxiolytic actions (Passiflora incarnata L., Valeriana spp. and Piper methysticum G. Forst.), were also analysed.Finally, the use of crude or semipurified extracts of such plants instead of the active substances seemingly responsible for their therapeutic effect is discussed.

  14. Environmental effects on the central nervous system.

    PubMed Central

    Paulson, G W

    1977-01-01

    The central nervous system (CNS) is designed to respond to the environment and is peculiarly vulnerable to many of the influences found in the environment. Utilizing an anatomical classification (cortex, cerebellum, peripheral nerves) major toxins and stresses are reviewed with selections from recent references. Selective vulnerability of certain areas to particular toxins is apparent at all levels of the CNS, although the amount of damage produced by any noxious agent depends on the age and genetic substrate of the subject. It is apparent that the effects of certain well known and long respected environmental toxins such as lead, mercury, etc., deserve continued surveillance. In addition, the overwhelming impact on the CNS of social damages such as trauma, alcohol, and tobacco cannot be ignored by environmentalists. The effect of the hospital and therapeutic environment has become apparent in view of increased awareness of iatrogenic disorders. The need for particular laboratory tests, for example, examination of CSF and nerve conduction toxicity studies, is suggested. Epidemics such as the recent solvent neuropathies suggest a need for continued animal studies that are chronic, as well as acute evaluations when predicting the potential toxic effects of industrial compounds. PMID:202447

  15. Sympathetic nervous system behavior in human obesity.

    PubMed

    Davy, Kevin P; Orr, Jeb S

    2009-02-01

    The sympathetic nervous system (SNS) plays an essential role in the regulation of metabolic and cardiovascular homeostasis. Low SNS activity has been suggested to be a risk factor for weight gain and obesity development. In contrast, SNS activation is characteristic of a number of metabolic and cardiovascular diseases that occur more frequently in obese individuals. Until recently, the relation between obesity and SNS behavior has been controversial because previous approaches for assessing SNS activity in humans have produced inconsistent findings. Beginning in the early 1990s, many studies using state of the art neurochemical and neurophysiological techniques have provided important insight. The purpose of the present review is to provide an overview of our current understanding of the region specific alterations in SNS behavior in human obesity. We will discuss findings from our own laboratory which implicate visceral fat as an important depot linking obesity with skeletal muscle SNS activation. The influence of weight change on SNS behavior and the potential mechanisms and consequences of region specific SNS activation in obesity will also be considered.

  16. Bilastine and the central nervous system.

    PubMed

    Montoro, J; Mullol, J; Dávila, I; Ferrer, M; Sastre, J; Bartra, J; Jáuregui, I; del Cuvillo, A; Valero, A

    2011-01-01

    Antihistamines have been classifed as first or second generation drugs, according to their pharmacokinetic properties, chemical structure and adverse effects. The adverse effects of antihistamines upon the central nervous system (CNS) depend upon their capacity to cross the blood-brain barrier (BBB) and bind to the central H1 receptors (RH1). This in turn depends on the lipophilicity of the drug molecule, its molecular weight (MW), and affinity for P-glycoprotein (P-gp) (CNS xenobiotic substances extractor protein). First generation antihistamines show scant affinity for P-gp, unlike the second generation molecules which are regarded as P-gp substrates. Histamine in the brain is implicated in many functions (waking-sleep cycle, attention, memory and learning, and the regulation of appetite), with numerous and complex interactions with different types of receptors in different brain areas. Bilastine is a new H1 antihistamine that proves to be effective in treating allergic rhinoconjunctivitis (seasonal and perennial) and urticaria. The imaging studies made, as well as the objective psychomotor tests and subjective assessment of drowsiness, indicate the absence of bilastine action upon the CNS. This fact, and the lack of interaction with benzodiazepines and alcohol, define bilastine as a clinically promising drug with a good safety profile as regards adverse effects upon the CNS.

  17. Time Perception Mechanisms at Central Nervous System

    PubMed Central

    Fontes, Rhailana; Ribeiro, Jéssica; Gupta, Daya S.; Machado, Dionis; Lopes-Júnior, Fernando; Magalhães, Francisco; Bastos, Victor Hugo; Rocha, Kaline; Marinho, Victor; Lima, Gildário; Velasques, Bruna; Ribeiro, Pedro; Orsini, Marco; Pessoa, Bruno; Leite, Marco Antonio Araujo; Teixeira, Silmar

    2016-01-01

    The five senses have specific ways to receive environmental information and lead to central nervous system. The perception of time is the sum of stimuli associated with cognitive processes and environmental changes. Thus, the perception of time requires a complex neural mechanism and may be changed by emotional state, level of attention, memory and diseases. Despite this knowledge, the neural mechanisms of time perception are not yet fully understood. The objective is to relate the mechanisms involved the neurofunctional aspects, theories, executive functions and pathologies that contribute the understanding of temporal perception. Articles form 1980 to 2015 were searched by using the key themes: neuroanatomy, neurophysiology, theories, time cells, memory, schizophrenia, depression, attention-deficit hyperactivity disorder and Parkinson’s disease combined with the term perception of time. We evaluated 158 articles within the inclusion criteria for the purpose of the study. We conclude that research about the holdings of the frontal cortex, parietal, basal ganglia, cerebellum and hippocampus have provided advances in the understanding of the regions related to the perception of time. In neurological and psychiatric disorders, the understanding of time depends on the severity of the diseases and the type of tasks. PMID:27127597

  18. Central nervous system tumors in Mexican children.

    PubMed

    De la Torre Mondragón, L; Ridaura Sanz, C; Reyes Mujica, M; Rueda Franco, F

    1993-08-01

    Five hundred and seventy primary central nervous system (CNS) tumors from the Department of Pathology at the National Institute of Pediatrics in Mexico City, collected from 1970 to 1989, were histologically reclassified in order to find out their relative incidence as well as their outstanding features. With this, we could establish a frame of reference for our local population, contributing to the epidemiological analysis of these entities. All the tumors were examined independently by two pathologists (C.R. and M.R.), using the classification of Rorke et al. Histological type, patient age and sex, and tumor location were analyzed. CNS tumors were the secondmost frequently encountered solid tumors, after lymphomas, and were increasing in incidence at a rate of 2.2 annually. Children in the age group 0-9 years were most often affected, and there was a predominance of male patients. Astrocytoma and medulloblastoma were the most common tumor types. The infratentorial region was the most frequent tumor location in the 2- to 9-year age group. By contrast, in the under 2-year-olds a supratentorial location was more frequent, and the incidence of germ cell tumors was proportionally high. In general, some histological types seemed to be associated with particular age groups. Although we found primitive neuroectodermal tumors to be the fifth most common at all ages (except for medulloblastoma), many other authors do not report a similar finding.

  19. Time Perception Mechanisms at Central Nervous System.

    PubMed

    Fontes, Rhailana; Ribeiro, Jéssica; Gupta, Daya S; Machado, Dionis; Lopes-Júnior, Fernando; Magalhães, Francisco; Bastos, Victor Hugo; Rocha, Kaline; Marinho, Victor; Lima, Gildário; Velasques, Bruna; Ribeiro, Pedro; Orsini, Marco; Pessoa, Bruno; Leite, Marco Antonio Araujo; Teixeira, Silmar

    2016-04-01

    The five senses have specific ways to receive environmental information and lead to central nervous system. The perception of time is the sum of stimuli associated with cognitive processes and environmental changes. Thus, the perception of time requires a complex neural mechanism and may be changed by emotional state, level of attention, memory and diseases. Despite this knowledge, the neural mechanisms of time perception are not yet fully understood. The objective is to relate the mechanisms involved the neurofunctional aspects, theories, executive functions and pathologies that contribute the understanding of temporal perception. Articles form 1980 to 2015 were searched by using the key themes: neuroanatomy, neurophysiology, theories, time cells, memory, schizophrenia, depression, attention-deficit hyperactivity disorder and Parkinson's disease combined with the term perception of time. We evaluated 158 articles within the inclusion criteria for the purpose of the study. We conclude that research about the holdings of the frontal cortex, parietal, basal ganglia, cerebellum and hippocampus have provided advances in the understanding of the regions related to the perception of time. In neurological and psychiatric disorders, the understanding of time depends on the severity of the diseases and the type of tasks.

  20. Current approaches for drug delivery to central nervous system.

    PubMed

    Hossain, Sharif; Akaike, Toshihiro; Chowdhury, Ezharul Hoque

    2010-12-01

    Brain, the center of the nervous system in all vertebrate, plays the most vital role in every function of human body. However, many neurodegenerative diseases, cancer and infections of the brain become more prevalent as populations become older. In spite of the major advances in neuroscience, many potential therapeutics are still unable to reach the central nervous system (CNS) due to the blood-brain barrier (BBB) which is formed by the tight junctions within the capillary endothelium of the vertebrate brain. This results in the capillary wall behaving as a continuous lipid bilayer and preventing the passage of polar and lipid insoluble substances. Several approaches for delivering drugs to the CNS have been developed to enhance the capacity of therapeutic molecules to cross the BBB by modifying the drug itself, or by coupling it to a vector for receptor-mediated, carrier mediated or adsorption-mediated transcytosis. The current challenge is to develop drug delivery systems that ensure the safe and effective passage of drugs across the BBB. This review focuses on the strategies and approaches developed to enhance drug delivery to the CNS.

  1. Early animal evolution and the origins of nervous systems

    PubMed Central

    Budd, Graham E.

    2015-01-01

    Understanding the evolution of early nervous systems is hazardous because we lack good criteria for determining homology between the systems of distant taxa; the timing of the evolutionary events is contested, and thus the relevant ecological and geological settings for them are also unclear. Here I argue that no simple approach will resolve the first issue, but that it remains likely that animals evolved relatively late, and that their nervous systems thus arose during the late Ediacaran, in a context provided by the changing planktonic and benthic environments of the time. The early trace fossil provides the most concrete evidence for early behavioural diversification, but it cannot simply be translated into increasing nervous system complexity: behavioural complexity does not map on a one-to-one basis onto nervous system complexity, both because of possible limitations to behaviour caused by the environment and because we know that even organisms without nervous systems are capable of relatively complex behaviour. PMID:26554037

  2. Early animal evolution and the origins of nervous systems.

    PubMed

    Budd, Graham E

    2015-12-19

    Understanding the evolution of early nervous systems is hazardous because we lack good criteria for determining homology between the systems of distant taxa; the timing of the evolutionary events is contested, and thus the relevant ecological and geological settings for them are also unclear. Here I argue that no simple approach will resolve the first issue, but that it remains likely that animals evolved relatively late, and that their nervous systems thus arose during the late Ediacaran, in a context provided by the changing planktonic and benthic environments of the time. The early trace fossil provides the most concrete evidence for early behavioural diversification, but it cannot simply be translated into increasing nervous system complexity: behavioural complexity does not map on a one-to-one basis onto nervous system complexity, both because of possible limitations to behaviour caused by the environment and because we know that even organisms without nervous systems are capable of relatively complex behaviour. © 2015 The Authors.

  3. 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…

  4. [Primary central nervous system lymphoma: report of one case].

    PubMed

    Zhao, Peng; Su, Rong-Gang

    2002-04-01

    One case of primary central nervous system lymphoma was reported. The patient received comprehensive therapy, mainly the surgical treatment, with the survival time 12 months, and local recurrence was considered as the major cause of death. The pathology, imagine examination, diagnosis and treatment of primary central nervous system lymphoma were discussed.

  5. A gene catalogue of the amphioxus nervous system

    PubMed Central

    Benito-Gutiérrez, Èlia

    2006-01-01

    The elaboration of extremely complex nervous systems is a major success of evolution. However, at the dawn of the post-genomic era, few data have helped yet to unravel how a nervous system develops and evolves to complexity. On the evolutionary road to vertebrates, amphioxus occupies a key position to tackle this exciting issue. Its “simple” nervous system basically consists of a dorsal nerve cord and a diffuse net of peripheral neurons, which contrasts greatly with the complexity of vertebrate nervous systems. Notwithstanding, increasing data on gene expression has faced up this simplicity by revealing a mounting level of cryptic complexity, with unexpected levels of neuronal diversity, organisation and regionalisation of the central and peripheral nervous systems. Furthermore, recent gene expression data also point to the high neurogenic potential of the epidermis of amphioxus, suggestive of a skin-brain track for the evolution of the vertebrate nervous system. Here I attempt to catalogue and synthesise current gene expression data in the amphioxus nervous system. From this global point of view, I suggest scenarios for the evolutionary origin of complex features in the vertebrate nervous system, with special emphasis on the evolutionary origin of placodes and neural crest, and postulate a pre-patterned migratory pathway of cells, which, in the epidermis, may represent an intermediate state towards the deployment of one of the most striking innovative features of vertebrates: the neural crest and its derivatives. PMID:16763675

  6. Melatonin Metabolism in the Central Nervous System

    PubMed Central

    Hardeland, Rüdiger

    2010-01-01

    The metabolism of melatonin in the central nervous system is of interest for several reasons. Melatonin enters the brain either via the pineal recess or by uptake from the blood. It has been assumed to be also formed in some brain areas. Neuroprotection by melatonin has been demonstrated in numerous model systems, and various attempts have been undertaken to counteract neurodegeneration by melatonin treatment. Several concurrent pathways lead to different products. Cytochrome P450 subforms have been demonstrated in the brain. They either demethylate melatonin to N-acetylserotonin, or produce 6-hydroxymelatonin, which is mostly sulfated already in the CNS. Melatonin is deacetylated, at least in pineal gland and retina, to 5-methoxytryptamine. N1-acetyl-N2-formyl-5-methoxykynuramine is formed by pyrrole-ring cleavage, by myeloperoxidase, indoleamine 2,3-dioxygenase and various non-enzymatic oxidants. Its product, N1-acetyl-5-methoxykynuramine, is of interest as a scavenger of reactive oxygen and nitrogen species, mitochondrial modulator, downregulator of cyclooxygenase-2, inhibitor of cyclooxygenase, neuronal and inducible NO synthases. Contrary to other nitrosated aromates, the nitrosated kynuramine metabolite, 3-acetamidomethyl-6-methoxycinnolinone, does not re-donate NO. Various other products are formed from melatonin and its metabolites by interaction with reactive oxygen and nitrogen species. The relative contribution of the various pathways to melatonin catabolism seems to be influenced by microglia activation, oxidative stress and brain levels of melatonin, which may be strongly changed in experiments on neuroprotection. Many of the melatonin metabolites, which may appear in elevated concentrations after melatonin administration, possess biological or pharmacological properties, including N-acetylserotonin, 5-methoxytryptamine and some of its derivatives, and especially the 5-methoxylated kynuramines. PMID:21358968

  7. Extraversion, neuroticism and strength of the nervous system.

    PubMed

    Frigon, J Y

    1976-11-01

    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 with reinforcement. Introverted subjects were found to have weak nervous systems, according to the EEG index, while extraverted subjects had strong nervous systems, thus confirming the hypothesis. It was also found that the dimension of strength of the nervous system was unrelated to differences in neuroticism. The results are interpreted as adding support to Eysenck's theory relating differences in extraversion-introversion to differences in cortical arousal.

  8. Screening for medical disease--nervous system disorders.

    PubMed

    Cameron, Michelle H; Klein, Eve L

    2010-01-01

    NARRATIVE REVIEW: In general, nervous system disorders present with changes in sensation, strength, and cognitive function that must be recognized early for the timely referral often needed for optimal outcome. This article summarizes screening for nervous system disorders in patients who present to the hand therapist and the typical findings associated with common neurologic disorders. Recommendations for referral by the hand therapist of patients with a screening examination consistent with a nervous system disorder are also presented. Central nervous system (CNS) disorders discussed in this article include stroke, traumatic brain and spinal cord injury, CNS tumors, Parkinson disease, dementia, epilepsy, and multiple sclerosis. This is followed by a discussion of the peripheral nervous system (PNS) disorders of acquired and hereditary polyneuropathies, Guillain-Barré syndrome and myasthenia gravis. Lastly, there is a brief discussion of amyotrophic lateral sclerosis, a disorder affecting both the CNS and PNS. 5. Copyright 2010 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  9. Aging, the Central Nervous System, and Mobility

    PubMed Central

    2013-01-01

    Background. Mobility limitations are common and hazardous in community-dwelling older adults but are largely understudied, particularly regarding the role of the central nervous system (CNS). This has limited development of clearly defined pathophysiology, clinical terminology, and effective treatments. Understanding how changes in the CNS contribute to mobility limitations has the potential to inform future intervention studies. Methods. A conference series was launched at the 2012 conference of the Gerontological Society of America in collaboration with the National Institute on Aging and the University of Pittsburgh. The overarching goal of the conference series is to facilitate the translation of research results into interventions that improve mobility for older adults. Results. Evidence from basic, clinical, and epidemiological studies supports the CNS as an important contributor to mobility limitations in older adults without overt neurologic disease. Three main goals for future work that emerged were as follows: (a) develop models of mobility limitations in older adults that differentiate aging from disease-related processes and that fully integrate CNS with musculoskeletal contributors; (b) quantify the contribution of the CNS to mobility loss in older adults in the absence of overt neurologic diseases; (c) promote cross-disciplinary collaboration to generate new ideas and address current methodological issues and barriers, including real-world mobility measures and life-course approaches. Conclusions. In addition to greater cross-disciplinary research, there is a need for new approaches to training clinicians and investigators, which integrate concepts and methodologies from individual disciplines, focus on emerging methodologies, and prepare investigators to assess complex, multisystem associations. PMID:23843270

  10. Congenital tumors of the central nervous system.

    PubMed

    Severino, Mariasavina; Schwartz, Erin S; Thurnher, Majda M; Rydland, Jana; Nikas, Ioannis; Rossi, Andrea

    2010-06-01

    Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into "definitely congenital" (present or producing symptoms at birth), "probably congenital" (present or producing symptoms within the first week of life), and "possibly congenital" (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors, where aggressive surgical treatment leads to disease-free survival.

  11. Mechanosensitivity in the enteric nervous system

    PubMed Central

    Mazzuoli-Weber, Gemma; Schemann, Michael

    2015-01-01

    The enteric nervous system (ENS) autonomously controls gut muscle activity. Mechanosensitive enteric neurons (MEN) initiate reflex activity by responding to mechanical deformation of the gastrointestinal wall. MEN throughout the gut primarily respond to compression or stretch rather than to shear force. Some MEN are multimodal as they respond to compression and stretch. Depending on the region up to 60% of the entire ENS population responds to mechanical stress. MEN fire action potentials after mechanical stimulation of processes or soma although they are more sensitive to process deformation. There are at least two populations of MEN based on their sensitivity to different modalities of mechanical stress and on their firing pattern. (1) Rapidly, slowly and ultra-slowly adapting neurons which encode compressive forces. (2) Ultra-slowly adapting stretch-sensitive neurons encoding tensile forces. Rapid adaptation of firing is typically observed after compressive force while slow adaptation or ongoing spike discharge occurs often during tensile stress (stretch). All MEN have some common properties: they receive synaptic input, are low fidelity mechanoreceptors and are multifunctional in that some serve interneuronal others even motor functions. Consequently, MEN possess processes with mechanosensitive as well as efferent functions. This raises the intriguing hypothesis that MEN sense and control muscle activity at the same time as servo-feedback loop. The mechanosensitive channel(s) or receptor(s) expressed by the different MEN populations are unknown. Future concepts have to incorporate compressive and tensile-sensitive MEN into neural circuits that controls muscle activity. They may interact to control various forms of a particular motor pattern or regulate different motor patterns independently from each other. PMID:26528136

  12. 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…

  13. 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…

  14. [Systemic lupus erythematosus and the central nervous system].

    PubMed

    Rojas, E; Orrea Solano, M

    1993-01-01

    The central nervous system (CNS) manifestations of the chronic autoimmune disease systemic lupus erythematous (SLE) are reviewed. SLE-CNS dysfunction is broadly divided into neurologic and psychiatric clinical categories. The distinct clinical entities within these broad categories are fully described. Diagnostic criteria employed to verify the presence of SLE-CNS dysfunction, including laboratory serum and cerebral spinal fluid analyses as well as radiologic and other multimodality diagnostic tools, are compared and contrasted with respect to sensitivity and specificity.

  15. Animal–microbe interactions and the evolution of nervous systems

    PubMed Central

    2016-01-01

    Animals ubiquitously interact with environmental and symbiotic microbes, and the effects of these interactions on animal physiology are currently the subject of intense interest. Nevertheless, the influence of microbes on nervous system evolution has been largely ignored. We illustrate here how taking microbes into account might enrich our ideas about the evolution of nervous systems. For example, microbes are involved in animals' communicative, defensive, predatory and dispersal behaviours, and have likely influenced the evolution of chemo- and photosensory systems. In addition, we speculate that the need to regulate interactions with microbes at the epithelial surface may have contributed to the evolutionary internalization of the nervous system. PMID:26598731

  16. Calretinin in the peripheral nervous system of the adult zebrafish

    PubMed Central

    Levanti, M B; Montalbano, G; Laurà, R; Ciriaco, E; Cobo, T; García-Suarez, O; Germanà, A; Vega, J A

    2008-01-01

    Calretinin is a calcium-binding protein found widely distributed in the central nervous system and chemosensory cells of the teleosts, but its presence in the peripheral nervous system of fishes is unknown. In this study we used Western blot analysis and immunohistochemistry to investigate the occurrence and distribution of calretinin in the cranial nerve ganglia, dorsal root ganglia, sympathetic ganglia, and enteric nervous system of the adult zebrafish. By Western blotting a unique and specific protein band with an estimated molecular weight of around 30 kDa was detected, and it was identified as calretinin. Immunohistochemistry revealed that calretinin is selectively present in the cytoplasm of the neurons and never in the satellite glial cells. In both sensory and sympathetic ganglia the density of neurons that were immunolabelled, their size and morphology, as well as the intensity of immunostaining developed within the cytoplasm, were heterogeneous. In the enteric nervous system calretinin immunoreactivity was detected in a subset of enteric neurons as well as in a nerve fibre plexus localized inside the muscular layers. The present results demonstrate that in addition to the central nervous system, calretinin is also present in the peripheral nervous system of zebrafish, and contribute to completing the map of the distribution of this protein in the nervous system of teleosts. PMID:18173770

  17. 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.

  18. 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.

  19. Evolution of eumetazoan nervous systems: insights from cnidarians

    PubMed Central

    Kelava, Iva; Rentzsch, Fabian; Technau, Ulrich

    2015-01-01

    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. PMID:26554048

  20. Electromagnetic fields and health effects--epidemiologic studies of cancer, diseases of the central nervous system and arrhythmia-related heart disease.

    PubMed

    Johansen, Christoffer

    2004-01-01

    cohort of mobile phone subscribers comprising some 420 000 persons. No increased risk was observed for the cancers considered a priori to be possibly associated with the radiofrequency fields emitted by mobile phones, which were brain tumors, including acoustic neuroma, salivary gland tumors, and leukemia. The data were analyzed by duration of phone use, latency, system used (NMT, GSM or both) and age at first subscription. A study of the incidence of ocular malignant melanoma in comparison with the annual increase among the mobile phone subscribers showed a highly stable incidence rate for this rare cancer in Denmark over close to 50 years of registration. On the basis of these studies and the scientific literature, it is concluded that occupational exposure to 50-Hz EMF is not associated with an increased risk of cancer, but that these fields, electric shocks, or some other unknown factor related to alternating current electricity may be associated with the risk of ALS. There is no clear evidence that 50-Hz EMF is associated with other neurodegenerative or cardiovascular diseases. At present, there is little, if any, evidence that the use of mobile phones is associated with cancer in adults, including brain tumors, acoustic neuroma, cancer of the salivary glands, leukemia, or malignant melanoma of the eye.

  1. Disseminated encephalomyelitis-like central nervous system neoplasm in childhood.

    PubMed

    Zhao, Jianhui; Bao, Xinhua; Fu, Na; Ye, Jintang; Li, Ting; Yuan, Yun; Zhang, Chunyu; Zhang, Yao; Zhang, Yuehua; Qin, Jiong; Wu, Xiru

    2014-08-01

    A malignant neoplasm in the central nervous system with diffuse white matter changes on magnetic resonance imaging (MRI) is rare in children. It could be misdiagnosed as acute disseminated encephalomyelitis. This report presents our experience based on 4 patients (3 male, 1 female; aged 7-13 years) whose MRI showed diffuse lesions in white matter and who were initially diagnosed with acute disseminated encephalomyelitis. All of the patients received corticosteroid therapy. After brain biopsy, the patients were diagnosed with gliomatosis cerebri, primitive neuroectodermal tumor and central nervous system lymphoma. We also provide literature reviews and discuss the differentiation of central nervous system neoplasm from acute disseminated encephalomyelitis.

  2. 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

  3. Reorganization of the human central nervous system.

    PubMed

    Schalow, G; Zäch, G A

    2000-10-01

    The key strategies on which the discovery of the functional organization of the central nervous system (CNS) under physiologic and pathophysiologic conditions have been based included (1) our measurements of phase and frequency coordination between the firings of alpha- and gamma-motoneurons and secondary muscle spindle afferents in the human spinal cord, (2) knowledge on CNS reorganization derived upon the improvement of the functions of the lesioned CNS in our patients in the short-term memory and the long-term memory (reorganization), and (3) the dynamic pattern approach for re-learning rhythmic coordinated behavior. The theory of self-organization and pattern formation in nonequilibrium systems is explicitly related to our measurements of the natural firing patterns of sets of identified single neurons in the human spinal premotor network and re-learned coordinated movements following spinal cord and brain lesions. Therapy induced cell proliferation, and maybe, neurogenesis seem to contribute to the host of structural changes during the process of re-learning of the lesioned CNS. So far, coordinated functions like movements could substantially be improved in every of the more than 100 patients with a CNS lesion by applying coordination dynamic therapy. As suggested by the data of our patients on re-learning, the human CNS seems to have a second integrative strategy for learning, re-learning, storing and recalling, which makes an essential contribution of the functional plasticity following a CNS lesion. A method has been developed by us for the simultaneous recording with wire electrodes of extracellular action potentials from single human afferent and efferent nerve fibres of undamaged sacral nerve roots. A classification scheme of the nerve fibres in the human peripheral nervous system (PNS) could be set up in which the individual classes of nerve fibres are characterized by group conduction velocities and group nerve fibre diameters. Natural impulse patterns

  4. Genomic scale profiling of autoimmune inflammation in the central nervous system: the nervous response to inflammation.

    PubMed

    Carmody, Ruaidhrí J; Hilliard, Brendan; Maguschak, Kimberly; Chodosh, Lewis A; Chen, Youhai H

    2002-12-01

    Using gene microarray technology, we found that inflammation in the central nervous system (CNS) not only induced the expression of many immune-related genes, but also significantly altered the gene expression profile of neural cells. Two unique groups of CNS genes were identified. The first group includes genes encoding ion channels, neural transmitters and growth factors. The second group includes genes that are important for nervous tissue regeneration. Additionally, a distinct pattern of gene expression was also identified in recovering animals. Thus, during autoimmune inflammation, the CNS actively responds to immune attacks by activating its own defense and repair genes.

  5. Neural circuit recording from an intact cockroach nervous system.

    PubMed

    Titlow, Josh S; Majeed, Zana R; Hartman, H Bernard; Burns, Ellen; Cooper, Robin L

    2013-11-04

    The cockroach ventral nerve cord preparation is a tractable system for neuroethology experiments, neural network modeling, and testing the physiological effects of insecticides. This article describes the scope of cockroach sensory modalities that can be used to assay how an insect nervous system responds to environmental perturbations. Emphasis here is on the escape behavior mediated by cerci to giant fiber transmission in Periplaneta americana. This in situ preparation requires only moderate dissecting skill and electrophysiological expertise to generate reproducible recordings of neuronal activity. Peptides or other chemical reagents can then be applied directly to the nervous system in solution with the physiological saline. Insecticides could also be administered prior to dissection and the escape circuit can serve as a proxy for the excitable state of the central nervous system. In this context the assays described herein would also be useful to researchers interested in limb regeneration and the evolution of nervous system development for which P. americana is an established model organism.

  6. 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

  7. Review: Glial lineages and myelination in the central nervous system

    PubMed Central

    COMPSTON, ALASTAIR; ZAJICEK, JOHN; SUSSMAN, JON; WEBB, ANNA; HALL, GILLIAN; MUIR, DAVID; SHAW, CHRISTOPHER; WOOD, ANDREW; SCOLDING, NEIL

    1997-01-01

    Oligodendrocytes, derived from stem cell precursors which arise in subventricular zones of the developing central nervous system, have as their specialist role the synthesis and maintenance of myelin. Astrocytes contribute to the cellular architecture of the central nervous system and act as a source of growth factors and cytokines; microglia are bone-marrow derived macrophages which function as primary immunocompetent cells in the central nervous system. Myelination depends on the establishment of stable relationships between each differentiated oligodendrocyte and short segments of several neighbouring axons. There is growing evidence, especially from studies of glial cell implantation, that oligodendrocyte precursors persist in the adult nervous system and provide a limited capacity for the restoration of structure and function in myelinated pathways damaged by injury or disease. PMID:9061442

  8. 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.

  9. Vasculitis Syndromes of the Central and Peripheral Nervous Systems

    MedlinePlus

    ... the Central and Peripheral Nervous Systems Fact Sheet Table of Contents (click to jump to sections) What ... Information Page NINDS Epilepsy Information Page NINDS Familial Periodic Paralyses Information Page NINDS Farber's Disease Information Page ...

  10. The sympathetic nervous system alterations in human hypertension.

    PubMed

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-03-13

    Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

  11. 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

  12. [Microglial cells and development of the embryonic central nervous system].

    PubMed

    Legendre, Pascal; Le Corronc, Hervé

    2014-02-01

    Microglia cells are the macrophages of the central nervous system with a crucial function in the homeostasis of the adult brain. However, recent studies showed that microglial cells may also have important functions during early embryonic central nervous system development. In this review we summarize recent works on the extra embryonic origin of microglia, their progenitor niche, the pattern of their invasion of the embryonic central nervous system and on interactions between embryonic microglia and their local environment during invasion. We describe microglial functions during development of embryonic neuronal networks, including their roles in neurogenesis, in angiogenesis and developmental cell death. These recent discoveries open a new field of research on the functions of neural-microglial interactions during the development of the embryonic central nervous system.

  13. 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.

  14. Central nervous system adaptation to exercise training

    NASA Astrophysics Data System (ADS)

    Kaminski, Lois Anne

    Exercise training causes physiological changes in skeletal muscle that results in enhanced performance in humans and animals. Despite numerous studies on exercise effects on skeletal muscle, relatively little is known about adaptive changes in the central nervous system. This study investigated whether spinal pathways that mediate locomotor activity undergo functional adaptation after 28 days of exercise training. Ventral horn spinal cord expression of calcitonin gene-related peptide (CGRP), a trophic factor at the neuromuscular junction, choline acetyltransferase (Chat), the synthetic enzyme for acetylcholine, vesicular acetylcholine transporter (Vacht), a transporter of ACh into synaptic vesicles and calcineurin (CaN), a protein phosphatase that phosphorylates ion channels and exocytosis machinery were measured to determine if changes in expression occurred in response to physical activity. Expression of these proteins was determined by western blot and immunohistochemistry (IHC). Comparisons between sedentary controls and animals that underwent either endurance training or resistance training were made. Control rats received no exercise other than normal cage activity. Endurance-trained rats were exercised 6 days/wk at 31m/min on a treadmill (8% incline) for 100 minutes. Resistance-trained rats supported their weight plus an additional load (70--80% body weight) on a 60° incline (3 x 3 min, 5 days/wk). CGRP expression was measured by radioimmunoassay (RIA). CGRP expression in the spinal dorsal and ventral horn of exercise-trained animals was not significantly different than controls. Chat expression measured by Western blot and IHC was not significantly different between runners and controls but expression in resistance-trained animals assayed by IHC was significantly less than controls and runners. Vacht and CaN immunoreactivity in motor neurons of endurance-trained rats was significantly elevated relative to control and resistance-trained animals. Ventral

  15. Introduction to 'Origin and evolution of the nervous system'.

    PubMed

    Strausfeld, Nicholas J; Hirth, Frank

    2015-12-19

    In 1665, Robert Hooke demonstrated in Micrographia the power of the microscope and comparative observations, one of which revealed similarities between the arthropod and vertebrate eyes. Utilizing comparative observations, Saint-Hilaire in 1822 was the first to propose that the ventral nervous system of arthropods corresponds to the dorsal nervous system of vertebrates. Since then, studies on the origin and evolution of the nervous system have become inseparable from studies about Metazoan origins and the origins of organ systems. The advent of genome sequence data and, in turn, phylogenomics and phylogenetics have refined cladistics and expanded our understanding of Metazoan phylogeny. However, the origin and evolution of the nervous system is still obscure and many questions and problems remain. A recurrent problem is whether and to what extent sequence data provide reliable guidance for comparisons across phyla. Are genetic data congruent with the geological fossil records? How can we reconcile evolved character loss with phylogenomic records? And how informative are genetic data in relation to the specification of nervous system morphologies? These provide some of the background and context for a Royal Society meeting to discuss new data and concepts that might achieve insights into the origin and evolution of brains and nervous systems.

  16. A simple analogy for nervous system plasticity after injury.

    PubMed

    Fouad, Karim; Forero, Juan; Hurd, Caitlin

    2015-04-01

    When considering plasticity, the central nervous system can be viewed as a building block house. After damage, building components might be lost or loosened and may be rearranged by renovation, analogous to neuroplasticity that occurs after central nervous system injury. In both scenarios, the location and severity of damage will determine the efficacy of renovation/rehabilitation and thus the quality of the adapted structure.

  17. Uropharmacology: X. Central nervous system stimulants and depressants.

    PubMed

    Bissada, N K; Finkbeiner, A E; Welch, L T

    1979-04-01

    Several drugs that are utilized primarily for their effects on the central nervous system also affect lower urinary tract function. Most of these effects are produced by the action of these drugs on adrenergic and cholinergic receptors or by direct action of lower urinary tract musculature. Central nervous system stimulants and depressants which are known to affect the storage or evacuation role of the lower urinary tract are discussed.

  18. Sympathetic Nervous System, Hypertension, Obesity and Metabolic Syndrome.

    PubMed

    Seravalle, Gino; Grassi, Guido

    2016-09-01

    Experimental and clinical studies have clearly shown the role of the sympathetic nervous system in the pathophysiology of several cardiovascular and non-cardiovascular diseases. This short review will be aimed at focusing and discussing the new information collected on two specific clinical conditions such as obesity and metabolic syndrome. The paper will briefly describe the four main mechanisms that represent the common link between these two pathophysiological conditions and that through the sympathetic nervous system contribute to increase the cardiovascular risk.

  19. 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...

  20. 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...

  1. Differential responses of components of the autonomic nervous system.

    PubMed

    Goldstein, David S

    2013-01-01

    This chapter conveys several concepts and points of view about the scientific and medical significance of differential alterations in activities of components of the autonomic nervous system in stress and disease. The use of terms such as "the autonomic nervous system," "autonomic failure," "dysautonomia," and "autonomic dysfunction" imply the existence of a single entity; however, the autonomic nervous system has functionally and neurochemically distinctive components, which are reflected in differential responses to stressors and differential involvement in pathophysiologic states. One can conceptualize the autonomic nervous system as having at least five components: the sympathetic noradrenergic system, the sympathetic cholinergic system, the parasympathetic cholinergic system, the sympathetic adrenergic system, and the enteric nervous system. Evidence has accumulated for differential noradrenergic vs. adrenergic responses in various situations. The largest sympathetic adrenergic system responses are seen when the organism encounters stressors that pose a global or metabolic threat. Sympathetic noradrenergic system activation dominates the responses to orthostasis, moderate exercise, and exposure to cold, whereas sympathetic adrenergic system activation dominates those to glucoprivation and emotional distress. There seems to be at least as good a justification for the concept of coordinated adrenocortical-adrenomedullary responses as for coordinated adrenomedullary-sympathoneural responses in stress. Fainting reactions involve differential adrenomedullary hormonal vs. sympathetic noradrenergic activation. Parkinson disease entails relatively selective dysfunction of the sympathetic noradrenergic system, with prominent loss of noradrenergic nerves in the heart, yet normal adrenomedullary function. Allostatic load links stress with degenerative diseases, and Parkinson disease may be a disease of the elderly because of allostatic load.

  2. 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

  3. Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis.

    PubMed

    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.

  4. 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

  5. Global research priorities for infections that affect the nervous system

    PubMed Central

    John, Chandy C.; Carabin, Hélène; Montano, Silvia M.; Bangirana, Paul; Zunt, Joseph R.; Peterson, Phillip K.

    2015-01-01

    Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries. PMID:26580325

  6. Global research priorities for infections that affect the nervous system.

    PubMed

    John, Chandy C; Carabin, Hélène; Montano, Silvia M; Bangirana, Paul; Zunt, Joseph R; Peterson, Phillip K

    2015-11-19

    Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries.

  7. 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

  8. Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia

    PubMed Central

    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.

    2016-01-01

    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

  9. [Necrotizing systemic sarcoidosis with pulmonary and central nervous system involvement].

    PubMed

    Ríos Fernández, R; Callejas-Rubio, J L; Guerrero Fernández, M; Serrano Falcón, M M; Ortego-Centeno, N

    2008-01-01

    Sarcoidosis is a multisystemic disease which diagnosis depends on the presence of nonnecrotizing granulomas in the biopsy. However there are variants such as necrotizing sarcoidal granulomas or nodular sarcoidosis which have atypical findings and make difficult the differential diagnosis with other infectious processes. We describe a case of a man who develops granulomas with extensive necrosis in a systemic sarcoidosis that affected the lung and the central nervous system. This finding made us to make the diagnosis of tuberculosis and delay the specific treatment.

  10. Blocking Action of Snake Venom Neurotoxins at Receptor Sites to Putative Central Nervous System Transmitters.

    DTIC Science & Technology

    SNAKES, *VENOMS, *PARASYMPATHOLYTIC AGENTS, PROBES, PRECURSORS, VERTEBRATES, NERVOUS SYSTEM, CENTRAL NERVOUS SYSTEM, TOXINS AND ANTITOXINS, CHOLINERGIC NERVES, NERVE TRANSMISSION, MOLLUSCA , EPINEPHRINE.

  11. Reactions of the nervous system to magnetic fields

    NASA Technical Reports Server (NTRS)

    Kholodov, Y. A.

    1974-01-01

    This magnetobiological survey considers sensory, nervous, stress and genetic effects of magnetic fields on man and animals. It is shown that the nervous system plays an important role in the reactions of the organism to magnetic fields; the final biological effect is a function of the strength of the magnetic fields, the gradient, direction of the lines of force, duration and location of the action, and the functional status of the organism.

  12. Structural and functional features of central nervous system lymphatic vessels.

    PubMed

    Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J; Eccles, Jacob D; Rouhani, Sherin J; Peske, J David; Derecki, Noel C; Castle, David; Mandell, James W; Lee, Kevin S; Harris, Tajie H; Kipnis, Jonathan

    2015-07-16

    One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

  13. Systemic delivery to central nervous system by engineered PLGA nanoparticles

    PubMed Central

    Cai, Qiang; Wang, Long; Deng, Gang; Liu, Junhui; Chen, Qianxue; Chen, Zhibiao

    2016-01-01

    Neurological disorders are an important global public health problem, but pharmaceutical treatments are limited due to drug access to the central nervous system being restricted by the blood-brain barrier (BBB). Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are one of the most promising drug and gene delivery systems for crossing the BBB. While these systems offer great promise, PLGA NPs also have some intrinsic drawbacks and require further engineering for clinical and research applications. Multiple strategies have been developed for using PLGA NPs to deliver compounds across the BBB. We classify these strategies into three categories according to the adaptations made to the PLGA NPs (1) to facilitate travel from the injection site (pre-transcytosis strategies); (2) to enhance passage across the brain endothelial cells (BBB transcytosis strategies) and (3) to achieve targeting of the impaired nervous system cells (post-transcytosis strategies). PLGA NPs modified according to these three strategies are denoted first, second, and third generation NPs, respectively. We believe that fusing these three strategies to engineer multifunctional PLGA NPs is the only way to achieve translational applications. PMID:27158367

  14. The polyvagal theory: phylogenetic substrates of a social nervous system.

    PubMed

    Porges, S W

    2001-10-01

    The evolution of the autonomic nervous system provides an organizing principle to interpret the adaptive significance of physiological responses in promoting social behavior. According to the polyvagal theory, the well-documented phylogenetic shift in neural regulation of the autonomic nervous system passes through three global stages, each with an associated behavioral strategy. The first stage is characterized by a primitive unmyelinated visceral vagus that fosters digestion and responds to threat by depressing metabolic activity. Behaviorally, the first stage is associated with immobilization behaviors. The second stage is characterized by the sympathetic nervous system that is capable of increasing metabolic output and inhibiting the visceral vagus to foster mobilization behaviors necessary for 'fight or flight'. The third stage, unique to mammals, is characterized by a myelinated vagus that can rapidly regulate cardiac output to foster engagement and disengagement with the environment. The mammalian vagus is neuroanatomically linked to the cranial nerves that regulate social engagement via facial expression and vocalization. As the autonomic nervous system changed through the process of evolution, so did the interplay between the autonomic nervous system and the other physiological systems that respond to stress, including the cortex, the hypothalamic-pituitary-adrenal axis, the neuropeptides of oxytocin and vasopressin, and the immune system. From this phylogenetic orientation, the polyvagal theory proposes a biological basis for social behavior and an intervention strategy to enhance positive social behavior.

  15. Survival of European patients with central nervous system tumors.

    PubMed

    Sant, Milena; Minicozzi, Pamela; Lagorio, Susanna; Børge Johannesen, Tom; Marcos-Gragera, Rafael; Francisci, Silvia

    2012-07-01

    We present estimates of population-based 5-year relative survival for adult Europeans diagnosed with central nervous system tumors, by morphology (14 categories based on cell lineage and malignancy grade), sex, age at diagnosis and region (UK and Ireland, Northern, Central, Eastern and Southern Europe) for the most recent period with available data (2000-2002). Sources were 39 EUROCARE cancer registries with continuous data from 1996 to 2002. Survival time trends (1988 to 2002) were estimated from 24 cancer registries with continuous data from 1988. Overall 5-year relative survival was 85.0% for benign, 19.9% for malignant tumors. Benign tumor survival ranged from 90.6% (Northern Europe) to 77.4% (UK and Ireland); for malignant tumors the range was 25.1% (Northern Europe) to 15.6% (UK and Ireland). Survival decreased with age at diagnosis and was slightly better for women (malignant tumors only). For glial tumors, survival varied from 83.5% (ependymoma and choroid plexus) to 2.7% (glioblastoma); and for non-glioma tumors from 96.5% (neurinoma) to 44.9% (primitive neuroectoderm tumor/medulloblastoma). Survival differences between regions narrowed after adjustment for morphology and age, and were mainly attributable to differences in morphology mix; however UK and Ireland and Eastern Europe patients still had 40% and 30% higher excess risk of death, respectively, than Northern Europe patients (reference). Survival for benign tumors increased from 69.3% (1988-1990) to 77.1% (2000-2002); but survival for malignant tumors did not improve indicating no useful advances in treatment over the 14-year study period, notwithstanding major improvement in the diagnosis and treatment of other solid cancers. Copyright © 2011 UICC.

  16. Designing and implementing nervous system simulations on LEGO robots.

    PubMed

    Blustein, Daniel; Rosenthal, Nikolai; Ayers, Joseph

    2013-05-25

    We present a method to use the commercially available LEGO Mindstorms NXT robotics platform to test systems level neuroscience hypotheses. The first step of the method is to develop a nervous system simulation of specific reflexive behaviors of an appropriate model organism; here we use the American Lobster. Exteroceptive reflexes mediated by decussating (crossing) neural connections can explain an animal's taxis towards or away from a stimulus as described by Braitenberg and are particularly well suited for investigation using the NXT platform.(1) The nervous system simulation is programmed using LabVIEW software on the LEGO Mindstorms platform. Once the nervous system is tuned properly, behavioral experiments are run on the robot and on the animal under identical environmental conditions. By controlling the sensory milieu experienced by the specimens, differences in behavioral outputs can be observed. These differences may point to specific deficiencies in the nervous system model and serve to inform the iteration of the model for the particular behavior under study. This method allows for the experimental manipulation of electronic nervous systems and serves as a way to explore neuroscience hypotheses specifically regarding the neurophysiological basis of simple innate reflexive behaviors. The LEGO Mindstorms NXT kit provides an affordable and efficient platform on which to test preliminary biomimetic robot control schemes. The approach is also well suited for the high school classroom to serve as the foundation for a hands-on inquiry-based biorobotics curriculum.

  17. Designing and Implementing Nervous System Simulations on LEGO Robots

    PubMed Central

    Blustein, Daniel; Rosenthal, Nikolai; Ayers, Joseph

    2013-01-01

    We present a method to use the commercially available LEGO Mindstorms NXT robotics platform to test systems level neuroscience hypotheses. The first step of the method is to develop a nervous system simulation of specific reflexive behaviors of an appropriate model organism; here we use the American Lobster. Exteroceptive reflexes mediated by decussating (crossing) neural connections can explain an animal's taxis towards or away from a stimulus as described by Braitenberg and are particularly well suited for investigation using the NXT platform.1 The nervous system simulation is programmed using LabVIEW software on the LEGO Mindstorms platform. Once the nervous system is tuned properly, behavioral experiments are run on the robot and on the animal under identical environmental conditions. By controlling the sensory milieu experienced by the specimens, differences in behavioral outputs can be observed. These differences may point to specific deficiencies in the nervous system model and serve to inform the iteration of the model for the particular behavior under study. This method allows for the experimental manipulation of electronic nervous systems and serves as a way to explore neuroscience hypotheses specifically regarding the neurophysiological basis of simple innate reflexive behaviors. The LEGO Mindstorms NXT kit provides an affordable and efficient platform on which to test preliminary biomimetic robot control schemes. The approach is also well suited for the high school classroom to serve as the foundation for a hands-on inquiry-based biorobotics curriculum. PMID:23728477

  18. 3D printed nervous system on a chip.

    PubMed

    Johnson, Blake N; Lancaster, Karen Z; Hogue, Ian B; Meng, Fanben; Kong, Yong Lin; Enquist, Lynn W; McAlpine, Michael C

    2016-04-21

    Bioinspired organ-level in vitro platforms are emerging as effective technologies for fundamental research, drug discovery, and personalized healthcare. In particular, models for nervous system research are especially important, due to the complexity of neurological phenomena and challenges associated with developing targeted treatment of neurological disorders. Here we introduce an additive manufacturing-based approach in the form of a bioinspired, customizable 3D printed nervous system on a chip (3DNSC) for the study of viral infection in the nervous system. Micro-extrusion 3D printing strategies enabled the assembly of biomimetic scaffold components (microchannels and compartmented chambers) for the alignment of axonal networks and spatial organization of cellular components. Physiologically relevant studies of nervous system infection using the multiscale biomimetic device demonstrated the functionality of the in vitro platform. We found that Schwann cells participate in axon-to-cell viral spread but appear refractory to infection, exhibiting a multiplicity of infection (MOI) of 1.4 genomes per cell. These results suggest that 3D printing is a valuable approach for the prototyping of a customized model nervous system on a chip technology.

  19. Evolution of flatworm central nervous systems: Insights from polyclads

    PubMed Central

    Quiroga, Sigmer Y.; Carolina Bonilla, E.; Marcela Bolaños, D.; Carbayo, Fernando; Litvaitis, Marian K.; Brown, Federico D.

    2015-01-01

    The nervous systems of flatworms have diversified extensively as a consequence of the broad range of adaptations in the group. Here we examined the central nervous system (CNS) of 12 species of polyclad flatworms belonging to 11 different families by morphological and histological studies. These comparisons revealed that the overall organization and architecture of polyclad central nervous systems can be classified into three categories (I, II, and III) based on the presence of globuli cell masses -ganglion cells of granular appearance-, the cross-sectional shape of the main nerve cords, and the tissue type surrounding the nerve cords. In addition, four different cell types were identified in polyclad brains based on location and size. We also characterize the serotonergic and FMRFamidergic nervous systems in the cotylean Boninia divae by immunocytochemistry. Although both neurotransmitters were broadly expressed, expression of serotonin was particularly strong in the sucker, whereas FMRFamide was particularly strong in the pharynx. Finally, we test some of the major hypothesized trends during the evolution of the CNS in the phylum by a character state reconstruction based on current understanding of the nervous system across different species of Platyhelminthes and on up-to-date molecular phylogenies. PMID:26500427

  20. 3D Printed Nervous System on a Chip

    PubMed Central

    Johnson, Blake N.; Lancaster, Karen Z.; Hogue, Ian B.; Meng, Fanben; Kong, Yong Lin; Enquist, Lynn W.; McAlpine, Michael C.

    2015-01-01

    Bioinspired organ-level in vitro platforms are emerging as effective technologies for fundamental research, drug discovery, and personalized healthcare. In particular, models for nervous system research are especially important, due to the complexity of neurological phenomena and challenges associated with developing targeted treatment of neurological disorders. Here we introduce an additive manufacturing-based approach in the form of a bioinspired, customizable 3D printed nervous system on a chip (3DNSC) for the study of viral infection in the nervous system. Micro-extrusion 3D printing strategies enabled the assembly of biomimetic scaffold components (microchannels and compartmented chambers) for the alignment of axonal networks and spatial organization of cellular components. Physiologically relevant studies of nervous system infection using the multiscale biomimetic device demonstrated the functionality of the in vitro platform. We found that Schwann cells participate in axon-to-cell viral spread but appear refractory to infection, exhibiting a multiplicity of infection (MOI) of 1.4 genomes per cell. These results suggest that 3D printing is a valuable approach for the prototyping of a customized model nervous system on a chip technology. PMID:26669842

  1. Monophyletic Origin of the Metazoan Nervous System: Characterizing

    NASA Astrophysics Data System (ADS)

    Watkins, Russell; Beckenbach, Andrew

    In the absence of additional cases to be studied, our understanding of the likelihood of intelligent life evolving elsewhere in the universe must be framed within the context of the evolution of intelligence on this planet. Towards this end a valid model of the evolution of animal life, and in particular of the nervous system, is key. Models which describe the development of complexity within the nervous system can be positively misleading if they are not grounded in an accurate model of the true relationships of the animal phyla. If fact the evolution of animal life at its earliest stages, from protists to the sponges, Cnidaria, and Ctenophora and onward to the bilateral animal phyla is poorly characterized. Recently numerous phylogenies of the early animal radiation have been published based upon DNA sequence data, with conflicting and poorly supported results. A polyphyletic origin for the animal nervous system has been implied by the results of several studies, which would lead to the conclusion that some characteristics of the nervous systems of higher and lower animals could be convergent. We show that an equally parsimonious interpretation of the molecular sequence data published thus far is that it reflects rapid speciation events early in animal evolution among the classical ``diploblast'' phyla, as well as accelerated DNA sequence divergence among the higher animals. This could be interpreted as support for a classical phylogeny of the animal kingdom, and thus of a strictly monophyletic origin for the nervous system.

  2. Evolution of flatworm central nervous systems: Insights from polyclads.

    PubMed

    Quiroga, Sigmer Y; Carolina Bonilla, E; Marcela Bolaños, D; Carbayo, Fernando; Litvaitis, Marian K; Brown, Federico D

    2015-01-01

    The nervous systems of flatworms have diversified extensively as a consequence of the broad range of adaptations in the group. Here we examined the central nervous system (CNS) of 12 species of polyclad flatworms belonging to 11 different families by morphological and histological studies. These comparisons revealed that the overall organization and architecture of polyclad central nervous systems can be classified into three categories (I, II, and III) based on the presence of globuli cell masses -ganglion cells of granular appearance-, the cross-sectional shape of the main nerve cords, and the tissue type surrounding the nerve cords. In addition, four different cell types were identified in polyclad brains based on location and size. We also characterize the serotonergic and FMRFamidergic nervous systems in the cotylean Boninia divae by immunocytochemistry. Although both neurotransmitters were broadly expressed, expression of serotonin was particularly strong in the sucker, whereas FMRFamide was particularly strong in the pharynx. Finally, we test some of the major hypothesized trends during the evolution of the CNS in the phylum by a character state reconstruction based on current understanding of the nervous system across different species of Platyhelminthes and on up-to-date molecular phylogenies.

  3. The alpha-herpesviruses: molecular pathfinders in nervous system circuits

    PubMed Central

    Ekstrand, Mats I.; Enquist, L.W.; Pomeranz, Lisa E.

    2012-01-01

    Several neuroinvasive viruses can be used to study the mammalian nervous system. In particular, infection by pseudorabies virus (PRV), an α-herpesvirus with broad host range, reveals chains of functionally connected neurons in the nervous systems of a variety of mammals. The specificity of PRV trans-neuronal spread has been established in several systems. One attenuated strain, PRV-Bartha, causes a reduced inflammatory response and also spreads only from infected post- to pre-synaptic neurons. We review the basics of PRV tracing and then discuss new developments and novel approaches that have enabled a more detailed understanding of the architecture of the nervous system. As questions and techniques evolve in the field of neuroscience, advances in PRV tracing will certainly follow. PMID:18280208

  4. [Molecular genetics of familial tumour syndromes of the central nervous system].

    PubMed

    Murnyák, Balázs; Szepesi, Rita; Hortobágyi, Tibor

    2015-02-01

    Although most of the central nervous system tumours are sporadic, rarely they are associated with familial tumour syndromes. These disorders usually present with an autosomal dominant inheritance and neoplasia develops at younger age than in sporadic cases. Most of these tumours are bilateral, multiplex or multifocal. The causative mutations occur in genes involved in cell cycle regulation, cell growth, differentiation and DNA repair. Studying these hereditary cancer predisposition syndromes associated with nervous system tumours can facilitate the deeper understanding of the molecular background of sporadic tumours and the development of novel therapeutic agents. This review is an update on hereditary tumour syndromes with nervous system involvement with emphasis on molecular genetic characteristics and their clinical implications.

  5. Current trends in autoimmunity and the nervous system.

    PubMed

    Selmi, Carlo; Barin, Jobert G; Rose, Noel R

    2016-12-01

    In the broad field of autoimmunity and clinical immunology, experimental evidence over the past few years have demonstrated several connections between the immune system and the nervous system, both central and peripheral, leading to the definition of neuroimmunology and of an immune-brain axis. Indeed, the central nervous system as an immune-privileged site, thanks to the blood-brain barrier, is no longer a dogma as the barrier may be altered during chronic inflammation with disruptive changes of endothelial cells and tight junctions, largely mediated by adenosine receptors and the expression of CD39/CD73. The diseases that encompass the neuroimmunology field vary from primary nervous diseases such as multiple sclerosis to systemic conditions with neuropsychiatric complications, such as systemic lupus erythematosus or vasculitidies. Despite potentially similar clinical manifestations, the pathogenesis of each condition is different, but the interaction between the ultra-specialized structure that is the nervous system and inflammation mediators are crucial. Two examples come from anti-dsDNA cross-reacting with anti-N-Methyl-d-Aspartate receptor (NMDAR) antibodies in neuropsychiatric lupus or the new family of antibody-associated neuronal autoimmune diseases including classic paraneoplastic syndromes with antibodies directed to intracellular antigens (Hu, Yo, Ri) and autoimmune encephalitis. In the case of multiple sclerosis, the T cell paradigm is now complicated by the growing evidence of a B cell involvement, particularly via aquaporin antibodies, and their influence on Th1 and Th17 lineages. Inspired by a productive AARDA-sponsored colloquium among experts we provide a critical review of the literature on the pathogenesis of different immune-mediated diseases with neurologic manifestations and we discuss the basic immunology of the central nervous system and the interaction between immune cells and the peripheral nervous system.

  6. Psychoneuroimmunology--cross-talk between the immune and nervous systems.

    PubMed

    Ziemssen, Tjalf; Kern, Simone

    2007-05-01

    Psychoneuroimmunology is a relatively new field of study that investigates interactions between behaviour and the immune system, mediated by the endocrine and nervous systems. The immune and central nervous system (CNS) maintain extensive communication. On the one hand, the brain modulates the immune system by hardwiring sympathetic and parasympathetic nerves (autonomic nervous system) to lymphoid organs. On the other hand, neuroendocrine hormones such as corticotrophin-releasing hormone or substance P regulate cytokine balance. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and immune system-mediated disease.

  7. Pharmacology of Cell Adhesion Molecules of the Nervous System

    PubMed Central

    Kiryushko, Darya; Bock, Elisabeth; Berezin, Vladimir

    2007-01-01

    Cell adhesion molecules (CAMs) play a pivotal role in the development and maintenance of the nervous system under normal conditions. They also are involved in numerous pathological processes such as inflammation, degenerative disorders, and cancer, making them attractive targets for drug development. The majority of CAMs are signal transducing receptors. CAM-induced intracellular signalling is triggered via homophilic (CAM-CAM) and heterophilic (CAM - other counter-receptors) interactions, which both can be targeted pharmacologically. We here describe the progress in the CAM pharmacology focusing on cadherins and CAMs of the immunoglobulin (Ig) superfamily, such as NCAM and L1. Structural basis of CAM-mediated cell adhesion and CAM-induced signalling are outlined. Different pharmacological approaches to study functions of CAMs are presented including the use of specific antibodies, recombinant proteins, and synthetic peptides. We also discuss how unravelling of the 3D structure of CAMs provides novel pharmacological tools for dissection of CAM-induced signalling pathways and offers therapeutic opportunities for a range of neurological disorders. PMID:19305742

  8. Pathway analysis of primary central nervous system lymphoma.

    PubMed

    Tun, Han W; Personett, David; Baskerville, Karen A; Menke, David M; Jaeckle, Kurt A; Kreinest, Pamela; Edenfield, Brandy; Zubair, Abba C; O'Neill, Brian P; Lai, Weil R; Park, Peter J; McKinney, Michael

    2008-03-15

    Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL) confined to the CNS. A genome-wide gene expression comparison between PCNSL and non-CNS DLBCL was performed, the latter consisting of both nodal and extranodal DLBCL (nDLBCL and enDLBCL), to identify a "CNS signature." Pathway analysis with the program SigPathway revealed that PCNSL is characterized notably by significant differential expression of multiple extracellular matrix (ECM) and adhesion-related pathways. The most significantly up-regulated gene is the ECM-related osteopontin (SPP1). Expression at the protein level of ECM-related SPP1 and CHI3L1 in PCNSL cells was demonstrated by immunohistochemistry. The alterations in gene expression can be interpreted within several biologic contexts with implications for PCNSL, including CNS tropism (ECM and adhesion-related pathways, SPP1, DDR1), B-cell migration (CXCL13, SPP1), activated B-cell subtype (MUM1), lymphoproliferation (SPP1, TCL1A, CHI3L1), aggressive clinical behavior (SPP1, CHI3L1, MUM1), and aggressive metastatic cancer phenotype (SPP1, CHI3L1). The gene expression signature discovered in our study may represent a true "CNS signature" because we contrasted PCNSL with wide-spectrum non-CNS DLBCL on a genomic scale and performed an in-depth bioinformatic analysis.

  9. [Dementia in Patients with Central Nervous System Mycosis].

    PubMed

    Morita, Akihiko; Ishihara, Masaki; Konno, Michiko

    2016-04-01

    Central nervous system (CNS) mycosis is a potentially life-threatening but treatable neurological emergency. CNS mycoses progress slowly and are sometimes difficult to distinguish from dementia. Though most patients with CNS mycosis have an underlying disease, such as human immunodeficiency virus (HIV) infection, cancer, diabetes mellitus, and/or use of immunosuppressants, cryptococcosis can occur in non-immunosuppressed persons. One of the major difficulties in accurate diagnosis is to detect the pathogen in patients' cerebrospinal fluid (CSF) cultures. Thus, the clinical diagnosis is often made by combining circumstantial evidence, including mononuclear cell-dominant pleocytosis with low glucose and protein elevation in the CSF, as well as positive results from an antigen-based assay and a (1-3)-beta-D-glucan assay using plasma and/or CSF. Polymerase chain reaction (PCR)-based diagnostics, which are not performed as routine examinations and are mostly performed as part of academic research in Japan, are sensitive tools for the early diagnosis of CNS mycosis. Mognetic resonance imaging (MRI) is useful to assess the complications of fungal meningitis, such as abscess, infarction, and hydrocephalus. Clinicians should realize the advantages and disadvantages of these diagnostic tools. Early and accurate diagnosis, including identification of the particular fungal species, enables optimal antifungal treatment that produces good outcomes in patients with CNS mycosis.

  10. Spatiotemporal development of the embryonic nervous system of Saccoglossus kowalevskii.

    PubMed

    Cunningham, Doreen; Casey, Elena Silva

    2014-02-01

    Defining the organization and temporal onset of key steps in neurogenesis in invertebrate deuterostomes is critical to understand the evolution of the bilaterian and deuterostome nervous systems. Although recent studies have revealed the organization of the nervous system in adult hemichordates, little attention has been paid to neurogenesis during embryonic development in this third major phylum of deuterostomes. We examine the early events of neural development in the enteropneust hemichordate Saccoglossus kowalevskii by analyzing the expression of 11 orthologs of key genes associated with neurogenesis in an expansive range of bilaterians. Using in situ hybridization (ISH) and RT-PCR, we follow the course of neural development to track the transition of the early embryonic diffuse nervous system to the more regionalized midline nervous system of the adult. We show that in Saccoglossus, neural progenitor markers are expressed maternally and broadly encircle the developing embryo. An increase in their expression and the onset of pan neural markers, indicate that neural specification occurs in late blastulae - early gastrulae. By mid-gastrulation, punctate expression of markers of differentiating neurons encircling the embryo indicate the presence of immature neurons, and at the end of gastrulation when the embryo begins to elongate, markers of mature neurons are expressed. At this stage, expression of a subset of neuronal markers is concentrated along the trunk ventral and dorsal midlines. These data indicate that the diffuse embryonic nervous system of Saccoglossus is transient and quickly reorganizes before hatching to resemble the adult regionalized, centralized nervous system. This regionalization occurs at a much earlier developmental stage than anticipated indicating that centralization is not linked in S. kowalevskii to a lifestyle change of a swimming larva metamorphosing to a crawling worm-like adult.

  11. [Clinical Importance of Central Nervous System Dysfunction in Myopathy].

    PubMed

    Matsumura, Tsuyoshi

    2016-02-01

    Multidisciplinary treatments including mechanical ventilation and cardioprotective therapy have improved life expectancy in many neuromuscular disorders such as Duchenne muscular dystrophy. For these patients, central nervous system disturbances such as intellectual and/or developmental disability can hinder social activities and communications. In myotonic dystrophy, the personality and/or cognitive dysfunction affects medical consultation behavior and decreases the efficacy of medical treatments. Understanding central nervous system disturbances in myopathies and providing care keeping in mind the patient burden are critical for improving prognosis and quality of life.

  12. Novel RNA modifications in the nervous system: form and function.

    PubMed

    Satterlee, John S; Basanta-Sanchez, Maria; Blanco, Sandra; Li, Jin Billy; Meyer, Kate; Pollock, Jonathan; Sadri-Vakili, Ghazaleh; Rybak-Wolf, Agnieszka

    2014-11-12

    Modified RNA molecules have recently been shown to regulate nervous system functions. This mini-review and associated mini-symposium provide an overview of the types and known functions of novel modified RNAs in the nervous system, including covalently modified RNAs, edited RNAs, and circular RNAs. We discuss basic molecular mechanisms involving RNA modifications as well as the impact of modified RNAs and their regulation on neuronal processes and disorders, including neural fate specification, intellectual disability, neurodegeneration, dopamine neuron function, and substance use disorders.

  13. Benefits and risks of folic acid to the nervous system

    PubMed Central

    Reynolds, E

    2002-01-01

    During three decades of neurological practice I have witnessed a remarkable change in attitudes to the benefits and risks of folic acid therapy in nervous system disorders. In the 1960s all that was known and taught was that folic acid was harmful to the nervous system, especially in precipitating or exacerbating the neurological complications of vitamin B12 deficiency. So deeply held was this view that the possibility of neuropsychological benefits from this vitamin was initially viewed with considerable scepticism.1 PMID:11971038

  14. Novel RNA Modifications in the Nervous System: Form and Function

    PubMed Central

    Basanta-Sanchez, Maria; Blanco, Sandra; Li, Jin Billy; Meyer, Kate; Pollock, Jonathan; Sadri-Vakili, Ghazaleh; Rybak-Wolf, Agnieszka

    2014-01-01

    Modified RNA molecules have recently been shown to regulate nervous system functions. This mini-review and associated mini-symposium provide an overview of the types and known functions of novel modified RNAs in the nervous system, including covalently modified RNAs, edited RNAs, and circular RNAs. We discuss basic molecular mechanisms involving RNA modifications as well as the impact of modified RNAs and their regulation on neuronal processes and disorders, including neural fate specification, intellectual disability, neurodegeneration, dopamine neuron function, and substance use disorders. PMID:25392485

  15. A rare adverse effect of metronidazole: nervous system symptoms.

    PubMed

    Kafadar, Ihsan; Moustafa, Fatma; Yalçın, Koray; Klç, Betül Aydn

    2013-06-01

    Metronidazole, as a 5-nitroimidazole compound, is effective on anaerobic bacteria and protozoon diseases. Mostly, metronidazole is a tolerable drug but rarely presents serious adverse effects on the nervous system. In case of these adverse effects, treatment must be stopped.In this report, a 3-year-old child hospitalized because of diarrhea is presented. During the metronidazole treatment, loss of sight, vertigo, ataxia, and headache occurred as the adverse effects. By this report, we want to express the rare adverse effects of drugs in the differential diagnoses of nervous system diseases.

  16. Inflammation and cutaneous nervous system involvement in hypertrophic scarring

    PubMed Central

    Li, Shao-hua; Yang, Heng-lian; Xiao, Hu; Wang, Yi-bing; Wang, De-chang; Huo, Ran

    2015-01-01

    This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Results of hematoxylin-eosin and immunohistochemical staining demonstrated that inflammation contributed to the formation of a hypertrophic scar and increased the nerve density in scar tissue.Western blot assay verified that interleukin-13 expression was increased in scar tissue. These findings suggest that inflammation and the cutaneous nervous system play a role in hypertrophic scar formation. PMID:26692869

  17. Neuroinflammation of the central and peripheral nervous system: an update.

    PubMed

    Stüve, O; Zettl, U

    2014-03-01

    Inflammatory disorders of the peripheral nervous system (PNS) and central nervous system (CNS) are common, and contribute substantially to physical and emotional disability of affected individuals. Often, the afflicted are young and in their active years. In the past, physicians and scientists often had very little to offer in terms of diagnostic precision and therapeutic effectiveness. During the past two decades, both of these relative shortcomings have clearly improved. Some of the recent developments in clinical neuroimmunology are illustrated in this special edition of Clinical and Experimental Immunology.

  18. Herpes virus infection of the peripheral nervous system.

    PubMed

    Steiner, Israel

    2013-01-01

    Among the human herpes viruses, three are neurotropic and capable of producing severe neurological abnormalities: herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus (VZV). Both the acute, primary infection and the reactivation from the site of latent infection, the dorsal sensory ganglia, are associated with severe human morbidity and mortality. The peripheral nervous system is one of the major loci affected by these viruses. The present review details the virology and molecular biology underlying the human infection. This is followed by detailed description of the symtomatology, clinical presentation, diagnosis, course, therapy, and prognosis of disorders of the peripheral nervous system caused by these viruses.

  19. Brain-computer interface after nervous system injury.

    PubMed

    Burns, Alexis; Adeli, Hojjat; Buford, John A

    2014-12-01

    Brain-computer interface (BCI) has proven to be a useful tool for providing alternative communication and mobility to patients suffering from nervous system injury. BCI has been and will continue to be implemented into rehabilitation practices for more interactive and speedy neurological recovery. The most exciting BCI technology is evolving to provide therapeutic benefits by inducing cortical reorganization via neuronal plasticity. This article presents a state-of-the-art review of BCI technology used after nervous system injuries, specifically: amyotrophic lateral sclerosis, Parkinson's disease, spinal cord injury, stroke, and disorders of consciousness. Also presented is transcending, innovative research involving new treatment of neurological disorders.

  20. Neuroinflammation of the central and peripheral nervous system: an update

    PubMed Central

    Stüve, O; Zettl, U

    2014-01-01

    Inflammatory disorders of the peripheral nervous system (PNS) and central nervous system (CNS) are common, and contribute substantially to physical and emotional disability of affected individuals. Often, the afflicted are young and in their active years. In the past, physicians and scientists often had very little to offer in terms of diagnostic precision and therapeutic effectiveness. During the past two decades, both of these relative shortcomings have clearly improved. Some of the recent developments in clinical neuroimmunology are illustrated in this special edition of Clinical and Experimental Immunology. PMID:24384012

  1. Peroxisome Proliferator-Activated Receptor-γ and Its Ligands in the Treatment of Tumors in the Nervous System.

    PubMed

    Shen, Yun; Lu, Yun; Yu, Fang; Zhu, Chuntie; Wang, Hua; Wang, Jing

    2016-01-01

    The peroxisome proliferator-activated receptor -γ (PPARγ) has been identified in a wide range of cancers, including brain, breast, colon, stomach and lung cancers. It belongs to the thyroid/ steroid hormone receptors superfamily. Binding with their special ligands, PPARγ plays important roles in regulating transcription of their target genes. PPARγ activation suppresses the growth of the tumor cells, implicating the anti-tumor potential of PPARγ ligand. Tumors in the nervous system are among the most devastating cancers. This review highlights key advances in understanding the effects of PPARγ ligands in the treatment of tumors in the nervous system.

  2. Non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases: role of tyrosine kinase inhibitors (TKIs) and evidence in favor or against their use with concurrent cranial radiotherapy

    PubMed Central

    Economopoulou, Panagiota

    2016-01-01

    Central nervous system (CNS) metastases, including brain metastases (BM) and leptomeningeal metastases (LM) represent a frequent complication of non-small cell lung cancer (NSCLC). Patients with BM comprise a heterogeneous group, with a median survival that ranges from 3 to 14 months. However, in the majority of patients, the occurrence of CNS metastases is usually accompanied by severe morbidity and substantial deterioration in quality of life. Local therapies, such as whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) or surgical resection, either alone or as part of a multimodality treatment are available treatment strategies for BM and the choice of therapy varies depending on patient group and prognosis. Meanwhile, introduction of tyrosine kinase inhibitors (TKIs) in clinical practice has led to individualization of therapy based upon the presence of the exact abnormality, resulting in a major therapeutic improvement in patients with NSCLC who harbor epidermal growth factor receptor (EGFR) activating mutations or anaplastic lymphoma kinase (ALK) gene rearrangements, respectively. Based on their clinical activity in systemic disease, such molecular agents could offer the promise of improved BM control without substantial toxicity; however, their role in combination with radiotherapy is controversial. In this review, we discuss the controversy regarding the use of TKIs in combination with radiotherapy and illustrate future perspectives in the treatment of BM in NSCLC. PMID:28149754

  3. Up-to-date monitoring of childhood cancer long-term survival in Europe: tumours of the sympathetic nervous system, retinoblastoma, renal and bone tumours, and soft tissue sarcomas.

    PubMed

    Arndt, V; Lacour, B; Steliarova-Foucher, E; Spix, C; Znaor, A; Pastore, G; Stiller, C; Brenner, H

    2007-10-01

    Prognosis for most types of childhood tumours has improved during the last few decades. In this article we estimate up-to-date period survival for less common, but important childhood malignancies in Europe. Using the database of the Automated Childhood Cancer Information System we calculated period estimates of 10-year survival for the 1995-1999 period for children aged 0-14 years diagnosed during 1985-1999 with tumours of the sympathetic nervous system (NS), retinoblastoma, renal tumours, bone tumours and soft tissue sarcomas in four European regions. Ten-year period survival for 1995-1999 was 66% in children with tumours of the sympathetic NS, 96% for retinoblastoma, 87% for renal tumours, 58% for bone tumours and 61% for soft tissue sarcomas. The higher period estimates, as compared with cohort and complete estimates indicate recent improvement in survival for tumours of the sympathetic NS and to a lesser extent for retinoblastoma and renal tumours. Region-specific period survival estimates were lowest for Eastern Europe for renal, bone and soft tissue tumours, but not for the other two tumour groups. There have been further improvements in the 1990s in long-term survival of children diagnosed with several malignancies, albeit to a different extent in different European regions.

  4. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    SciTech Connect

    Shumilov, V. N. Syryamkin, V. I. Syryamkin, M. V.

    2015-11-17

    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

  5. 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

  6. The renin-angiotensin system and the central nervous system.

    PubMed

    Ganong, W F

    1977-04-01

    One of several factors affecting the secretion of renin by the kidneys is the sympathetic nervous system. The sympathetic input is excitatory and is mediated by beta-adrenergic receptors, which are probably located on the membranes of the juxtaglomerular cells. Stimulation of sympathetic areas in the medulla, midbrain and hypothalamus raises blood pressure and increases renin secretion, whereas stimulation of other parts of the hypothalamus decreases blood pressure and renin output. The centrally active alpha-adrenergic agonist clonidine decreases renin secretion, lowers blood pressure, inhibits ACTH and vasopressin secretion, and increases growth hormone secretion in dogs. The effects on ACTH and growth hormone are abolished by administration of phenoxybenzamine into the third ventricle, whereas the effect on blood pressure is abolished by administration of phenoxybenzamine in the fourth ventricle without any effect on the ACTH and growth hormone responses. Fourth ventricular phenoxybenzamine decreases but does not abolish the inhibitory effect of clonidine on renin secretion. Circulating angiotensin II acts on the brain via the area postrema to raise blood pressure and via the subfornical organ to increase water intake. Its effect on vasopressin secretion is debated. The brain contains a renin-like enzyme, converting enzyme, renin substrate, and angiotensin. There is debate about the nature and physiological significance of the angiotensin II-generating enzyme in the brain, and about the nature of the angiotensin I and angiotensin II that have been reported to be present in the central nervous system. However, injection of angiotensin II into the cerebral ventricles produces drinking, increased secretion of vasopressin and ACTH, and increased blood pressure. The same responses are produced by intraventricular renin. Angiotensin II also facilitates sympathetic discharge in the periphery, and the possibility that it exerts a similar action on the adrenergic neurons

  7. A Role of the Parasympathetic Nervous System in Cognitive Training.

    PubMed

    Lin, Feng; Heffner, Kathi L; Ren, Ping; Tadin, Duje

    2017-01-01

    Vision-based speed of processing (VSOP) training can result in broad cognitive improvements in older adults with amnestic mild cognitive impairment (aMCI). What remains unknown, however, is what neurophysiological mechanisms account for the observed training effect. Much of the work in this area has focused on the central nervous system, neglecting the fact that the peripheral system can contributes to changes of the central nervous system and vice versa. We examined the prospective relationship between an adaptive parasympathetic nervous system response to cognitive stimuli and VSOP training-induced plasticity. Twenty-one participants with aMCI (10 for VSOP training, and 11 for mental leisure activities (MLA) control) were enrolled. We assessed high-frequency heart rate variability (HF-HRV) during training sessions, and striatum-related neural networks and cognition at baseline and post-training. Compared to MLA, the VSOP group showed a significant U-shaped pattern of HF-HRV response during training, as well as decreases in connectivity strength between bilateral striatal and prefrontal regions. These two effects were associated with training-induced improvements in both the trained (attention and processing speed) and transferred (working memory) cognitive domains. This work provides novel support for interactions between the central and the peripheral nervous systems in relation to cognitive training, and motivates further studies to elucidate the causality of the observed link. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Autonomic Nervous System in Viral Myocarditis: Pathophysiology and Therapy.

    PubMed

    Cheng, Zheng; Li-Sha, Ge; Yue-Chun, Li

    2016-01-01

    Myocarditis, which is caused by viral infection, can lead to heart failure, malignant arrhythmias, and even sudden cardiac death in young patients. It is also one of the most important causes of dilated cardiomyopathy worldwide. Although remarkable advances in diagnosis and understanding of pathophysiological mechanisms of viral myocarditis have been gained during recent years, no standard treatment strategies have been defined as yet. Fortunately, recent studies present some evidence that immunomodulating therapy is effective for myocarditis. The immunomodulatory effect of the autonomic nervous system has raised considerable interest over recent decades. Studying the influence on the inflammation and immune system of the sympathetic and parasympathetic nervous systems will not only increase our understanding of the mechanism of disease but could also lead to the identification of potential new therapies for viral myocarditis. Studies have shown that the immunomodulating effect of the sympathetic and parasympathetic nervous system is realized by the release of neurotransmitters to their corresponding receptors (catecholamine for α or β adrenergic receptor, acetylcholine for α7 nicotinic acetylcholinergic receptor). This review will discuss the current knowledge of the roles of both the sympathetic and parasympathetic nervous system in inflammation, with a special focus on their roles in viral myocarditis.

  9. Central nervous system blastomycosis in a dog.

    PubMed

    Gaunt, M Casey; Taylor, Susan M; Kerr, Moira E

    2009-09-01

    An adult golden retriever was presented for progressive neurologic dysfunction. Clinical examination suggested brainstem disease. Blastomycosis was diagnosed based on fine-needle aspiration cytology of a normal sized lymph node and a positive blastomycosis urine antigen test. Systemic blastomycosis with neurologic involvement was confirmed at necropsy.

  10. Central nervous system blastomycosis in a dog

    PubMed Central

    Gaunt, M. Casey; Taylor, Susan M.; Kerr, Moira E.

    2009-01-01

    An adult golden retriever was presented for progressive neurologic dysfunction. Clinical examination suggested brainstem disease. Blastomycosis was diagnosed based on fine-needle aspiration cytology of a normal sized lymph node and a positive blastomycosis urine antigen test. Systemic blastomycosis with neurologic involvement was confirmed at necropsy. PMID:19949557

  11. Immunocytochemical Detection of Acetylcholine in the Rat Central Nervous System

    NASA Astrophysics Data System (ADS)

    Geffard, M.; McRae-Degueurce, A.; Souan, Marie Laure

    1985-07-01

    A specific antibody to acetylcholine was raised and used as a marker for cholinergic neurons in the rat central nervous system. The acetylcholine conjugate was obtained by a two-step immunogen synthesis procedure. An enzyme-linked immunosorbent assay was used to test the specificity and affinity of the antibody in vitro; the results indicated high affinity. A chemical perfusion mixture of allyl alcohol and glutaraldehyde was used to fix the acetylcholine in the nervous tissue. Peroxidase-antiperoxidase immunocytochemistry showed many acetylcholine-immunoreactive cells and fibers in sections from the medial septum region.

  12. Measures of Autonomic Nervous System Regulation

    DTIC Science & Technology

    2011-04-01

    flowing out of the lungs. The optimal level of the individual’s lung function is measured by using three color-coded peak flow zones. The individual...amphetamines, alcohol and monoamine oxidase inhibitors, which may interfere with accurate measurements of catecholamine metabolites. Three tools for...wireless PDA-Based physiological monitoring system for patient transport . IEEE Trans Inf Technol Biomed. 2004;8(4):439. 25. Blank JM, Altman DG

  13. Central nervous system infection during immunosuppression.

    PubMed

    Zunt, Joseph R

    2002-02-01

    Suppression of the immune system by human immunodeficiency virus (HIV) infection or immunosuppressive therapy following transplantation increases susceptibility to CNS infection. Examination of the level and type of immunosuppression, in addition to the clinical and radiologic findings at the time of diagnosis can aid the clinician in determining the most likely etiology of infection. This article discusses how suppression of the host immune status modifies the presentation and diagnosis of selected CNS infections and the recommended treatment for these infections.

  14. Elements of a 'nervous system' in sponges.

    PubMed

    Leys, Sally P

    2015-02-15

    Genomic and transcriptomic analyses show that sponges possess a large repertoire of genes associated with neuronal processes in other animals, but what is the evidence these are used in a coordination or sensory context in sponges? The very different phylogenetic hypotheses under discussion today suggest very different scenarios for the evolution of tissues and coordination systems in early animals. The sponge genomic 'toolkit' either reflects a simple, pre-neural system used to protect the sponge filter or represents the remnants of a more complex signalling system and sponges have lost cell types, tissues and regionalization to suit their current suspension-feeding habit. Comparative transcriptome data can be informative but need to be assessed in the context of knowledge of sponge tissue structure and physiology. Here, I examine the elements of the sponge neural toolkit including sensory cells, conduction pathways, signalling molecules and the ionic basis of signalling. The elements described do not fit the scheme of a loss of sophistication, but seem rather to reflect an early specialization for suspension feeding, which fits with the presumed ecological framework in which the first animals evolved. © 2015. Published by The Company of Biologists Ltd.

  15. Neuroscience. Stout guards of the central nervous system.

    PubMed

    Mechoulam, R; Lichtman, A H

    2003-10-03

    Endocannabinoids have paradoxical effects on the mammalian nervous system: Sometimes they block neuronal excitability and other times they augment it. In their Perspective, Mechoulam and Lichtman discuss new work (Marsicano et al.) showing that activation of the cannabinoid receptor CB1 by the endocannabinoid anandamide protects against excitotoxic damage in a mouse model of kainic acid-induced epilepsy.

  16. Pediatric central nervous system infections and inflammatory white matter disease.

    PubMed

    Silvia, Mary T; Licht, Daniel J

    2005-08-01

    This article reviews the immunology of the central nervous system and the clinical presentation, diagnosis, and treatment of children with viral or parainfectious encephalitis. The emphasis is on the early recognition of treatable causes of viral encephalitis (herpes simplex virus), and the diagnosis and treatment of acute disseminated encephalomyelitis are described in detail. Laboratory and imaging findings in the two conditions also are described.

  17. Thiophene Scaffold as Prospective Central Nervous System Agent: A Review.

    PubMed

    Deep, Aakash; Narasimhan, Balasubramanian; Aggarwal, Swati; Kaushik, Dhirender; Sharma, Arun K

    2016-01-01

    Heterocyclic compounds are extensively dispersed in nature and are vital for life. Various investigational approaches towards Structural Activity Relationship that focus upon the exploration of optimized candidates have become vastly important. Literature studies tell that for a series of compounds that are imperative in industrial and medicinal chemistry, thiophene acts as parent. Among various classes of heterocyclic compounds that have potential central nervous system activity, thiophene is the most important one. In the largely escalating chemical world of heterocyclic compounds showing potential pharmacological character, thiophene nucleus has been recognized as the budding entity. Seventeen Papers were included in this review article to define the central nervous system potential of thiophene. This review article enlightens the rationalized use and scope of thiophene scaffold as novel central nervous system activity such as anticonvulsant, acetylcholinesterase inhibitor, cyclin-dependent kinase 5 (cdk5/p25) inhibitors, CNS depressant, capability to block norepinephrine, serotonin and dopamine reuptake by their respective transporters etc. The Finding of this review confirm the importance of thiophene scaffold as potential central nervous system agents. From this outcome, ideas for future molecular modifications leading to the novel derivatives with better constructive pharmacological potential may be derived.

  18. The Nervous System, Science (Experimental): 5363.02.

    ERIC Educational Resources Information Center

    Weiss, Alan; And Others

    This unit of instruction was designed as an intensive in-depth study of the nervous impulse, neurons, brain, spinal cord, and sensory organs. Also included is a study of the endocrine system in its role of maintaining homeostasis. The booklet lists the relevant state-adopted texts and states the performance objectives for the unit. It provides an…

  19. THE SYMPATHETIC NERVOUS SYSTEM ALTERATIONS IN HUMAN HYPERTENSION

    PubMed Central

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-01-01

    A number of articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as “promoters” and “amplifiers” of human hypertension. We expand on the role of the sympathetic nervous system in two increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves. PMID:25767284

  20. Aberrant nerve fibres within the central nervous system.

    PubMed

    Moffie, D

    1992-01-01

    Three cases of aberrant nerve fibres in the spinal cord and medulla oblongata are described. The literature on these fibres is discussed and their possible role in regeneration. Different views on the possibility of regeneration or functional recovery of the central nervous system are mentioned in the light of recent publications, which are more optimistic than before.

  1. The Role of Central Nervous System Plasticity in Tinnitus

    ERIC Educational Resources Information Center

    Saunders, James C.

    2007-01-01

    Tinnitus is a vexing disorder of hearing characterized by sound sensations originating in the head without any external stimulation. The specific etiology of these sensations is uncertain but frequently associated with hearing loss. The "neurophysiogical" model of tinnitus has enhanced appreciation of central nervous system (CNS) contributions.…

  2. School Reentry for Children with Acquired Central Nervous Systems Injuries

    ERIC Educational Resources Information Center

    Carney, Joan; Porter, Patricia

    2009-01-01

    Onset of acquired central nervous system (CNS) injury during the normal developmental process of childhood can have impact on cognitive, behavioral, and motor function. This alteration of function often necessitates special education programming, modifications, and accommodations in the education setting for successful school reentry. Special…

  3. Central nervous system depressant effect of Hoslundia opposita vahl.

    PubMed

    Olajide, O A; Awe, S O; Makinde, J M

    1999-08-01

    The chloroform extract of the dried root of Hoslundia opposita has been evaluated for effects on the central nervous system (CNS). The extract significantly potentiated the phenobarbitone sleeping time in mice and produced a 60% protection against leptazol-induced convulsion. Neuropharmacological screening revealed CNS depression. Copyright 1999 John Wiley & Sons, Ltd.

  4. [Association between low blood lead exposure and nervous system symptoms].

    PubMed

    Dou, Qianru; Wang, Yan; Cai, Chang; Li, Jimeng; Tan, Hongzhuan

    2015-05-01

    To explore the association between low blood lead exposure and nervous system symptoms among the workers exposed to oil paint. Through cluster sampling, workers with occupational oil paint exposure in 2 factories were selected to conduct a questionnaire survey, biochemical detection and health examination. χ2 test and unconditional logistic regression analysis were performed for the determinants analysis. A total of 525 oil paint workers completed the survey, in whom, 55 (10.5%) were blood lead positive, the mean of blood lead concentration was (0.0884±0.0539) mg/L, 278 (52.95%) had nervous system like symptoms and 69 (13.14%) had peripheral neuropathy symptoms. Multinomial logistic regression analysis showed that working age (OR=1.827), drinking (OR=1.607), health status (OR=3.862), blood lead (OR=1.983) were risk factors for nervous system like symptoms. Working age (OR=2.282), and drinking (OR=2.704) were risk factors for peripheral neuropathy. Low blood lead exposure might be associated with nervous system like symptoms.

  5. Nervous System Development and Pattern Preference in Infants.

    ERIC Educational Resources Information Center

    Woodruff, Diana S.; Gerrity, Kathleen M.

    This study examined behavioral correlates of the rapid central nervous system changes occurring in the first 4 months of life. It was hypothesized that during the early months of infancy, visual preference would occur as a function of quantitative dimensions of the stimuli (size) which could be mediated at a subcortical level. It was further…

  6. Central Auditory Nervous System Dysfunction in Echolalic Autistic Individuals.

    ERIC Educational Resources Information Center

    Wetherby, Amy Miller; And Others

    1981-01-01

    The results showed that all the Ss had normal hearing on the monaural speech tests; however, there was indication of central auditory nervous system dysfunction in the language dominant hemisphere, inferred from the dichotic tests, for those Ss displaying echolalia. (Author)

  7. Axon guidance in the vertebrate central nervous system.

    PubMed

    Lumsden, A; Cohen, J

    1991-08-01

    The development of connections in the central nervous system depends on the ability of the tips of growing axons to find their appropriate, often distant, target field. Factors that regulate axon outgrowth may be distinct from those that influence direction finding. Tissue culture methods have helped to distinguish between possible in vivo mechanisms and, in some cases, have identified candidate molecules.

  8. The Role of Central Nervous System Plasticity in Tinnitus

    ERIC Educational Resources Information Center

    Saunders, James C.

    2007-01-01

    Tinnitus is a vexing disorder of hearing characterized by sound sensations originating in the head without any external stimulation. The specific etiology of these sensations is uncertain but frequently associated with hearing loss. The "neurophysiogical" model of tinnitus has enhanced appreciation of central nervous system (CNS) contributions.…

  9. The nervous and the immune systems: conspicuous physiological analogies.

    PubMed

    Sotelo, Julio

    2015-02-01

    From all biological constituents of complex organisms, two are highly sophisticated: the nervous and the immune systems. Interestingly, their goals and processes appear to be distant from each other; however, their physiological mechanisms keep notorious similarities. Both construct intelligence, learn from experience, and keep memory. Their precise responses to innumerable stimuli are delicately modulated, and the exposure of the individual to thousands of potential challenges integrates their functionality; they use a large part of their constituents not in excitatory activities but in the maintenance of inhibitory mechanisms to keep silent vast intrinsic potentialities. The nervous and immune systems are integrated by a basic cell lineage (neurons and lymphocytes, respectively) but each embodies countless cell subgroups with different and specialized deeds which, in contrast with cells from other organs, labyrinthine molecular arrangements conduct to "one cell, one function". Also, nervous and immune actions confer identity that differentiates every individual from countless others in the same species. Both systems regulate and potentiate their responses aided by countless biological resources of variable intensity: hormones, peptides, cytokines, pro-inflammatory molecules, etc. How the immune and the nervous systems buildup memory, learning capability, and exquisite control of excitatory/inhibitory mechanisms constitute major intellectual challenges for contemporary research.

  10. Brain Facts: A Primer on the Brain and Nervous System.

    ERIC Educational Resources Information Center

    Carey, Joseph, Ed.

    This booklet describes only a glimpse of what is known about the nervous system, brain disorders, and the exciting avenues of research that promise new therapies for many of the most devastating neurological and psychiatric diseases. The neuron, brain development, sensation and perception, learning and memory, movement, advances and challenges in…

  11. School Reentry for Children with Acquired Central Nervous Systems Injuries

    ERIC Educational Resources Information Center

    Carney, Joan; Porter, Patricia

    2009-01-01

    Onset of acquired central nervous system (CNS) injury during the normal developmental process of childhood can have impact on cognitive, behavioral, and motor function. This alteration of function often necessitates special education programming, modifications, and accommodations in the education setting for successful school reentry. Special…

  12. Parasitic central nervous system infections in immunocompromised hosts.

    PubMed

    Walker, Melanie; Zunt, Joseph R

    2005-04-01

    Immunosuppression due to therapy after transplantation or associated with HIV infection increases susceptibility to various central nervous system (CNS) infections. This article discusses how immunosuppression modifies the presentation, diagnosis, and treatment of selected parasitic CNS infections, with a focus on toxoplasmosis, Chagas disease, neurocysticercosis, schistosomiasis, and strongyloidiasis.

  13. Parasitic Central Nervous System Infections in Immunocompromised Hosts

    PubMed Central

    Walker, Melanie; Zunt, Joseph R.

    2009-01-01

    Immunosuppression due to therapy after transplantation or associated with HIV infection increases susceptibility to various central nervous system (CNS) infections. This article discusses how immunosuppression modifies the presentation, diagnosis, and treatment of selected parasitic CNS infections, with a focus on toxoplasmosis, Chagas disease, neurocysticercosis, schistosomiasis, and strongyloidiasis. PMID:15824993

  14. Nodal signalling and asymmetry of the nervous system.

    PubMed

    Signore, Iskra A; Palma, Karina; Concha, Miguel L

    2016-12-19

    The role of Nodal signalling in nervous system asymmetry is still poorly understood. Here, we review and discuss how asymmetric Nodal signalling controls the ontogeny of nervous system asymmetry using a comparative developmental perspective. A detailed analysis of asymmetry in ascidians and fishes reveals a critical context-dependency of Nodal function and emphasizes that bilaterally paired and midline-unpaired structures/organs behave as different entities. We propose a conceptual framework to dissect the developmental function of Nodal as asymmetry inducer and laterality modulator in the nervous system, which can be used to study other types of body and visceral organ asymmetries. Using insights from developmental biology, we also present novel evolutionary hypotheses on how Nodal led the evolution of directional asymmetry in the brain, with a particular focus on the epithalamus. We intend this paper to provide a synthesis on how Nodal signalling controls left-right asymmetry of the nervous system.This article is part of the themed issue 'Provocative questions in left-right asymmetry'.

  15. An emerging role for voltage-gated Na+ channels in cellular migration: regulation of central nervous system development and potentiation of invasive cancers.

    PubMed

    Brackenbury, William J; Djamgoz, Mustafa B A; Isom, Lori L

    2008-12-01

    Voltage-gated Na(+) channels (VGSCs) exist as macromolecular complexes containing a pore-forming alpha subunit and one or more beta subunits. The VGSC alpha subunit gene family consists of 10 members, which have distinct tissue-specific and developmental expression profiles. So far, four beta subunits (beta1-beta4) and one splice variant of beta1 (beta1A, also called beta1B) have been identified. VGSC beta subunits are multifunctional, serving as modulators of channel activity, regulators of channel cell surface expression, and as members of the immunoglobulin superfamily, cell adhesion molecules (CAMs). beta subunits are substrates of beta-amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase, yielding intracellular domains (ICDs) that may further modulate cellular activity via transcription. Recent evidence shows that beta1 regulates migration and pathfinding in the developing postnatal CNS in vivo. The alpha and beta subunits, together with other components of the VGSC signaling complex, may have dynamic interactive roles depending on cell/tissue type, developmental stage, and pathophysiology. In addition to excitable cells like nerve and muscle, VGSC alpha and beta subunits are functionally expressed in cells that are traditionally considered nonexcitable, including glia, vascular endothelial cells, and cancer cells. In particular, the alpha subunits are up-regulated in line with metastatic potential and are proposed to enhance cellular migration and invasion. In contrast to the alpha subunits, beta1 is more highly expressed in weakly metastatic cancer cells, and evidence suggests that its expression enhances cellular adhesion. Thus, novel roles are emerging for VGSC alpha and beta subunits in regulating migration during normal postnatal development of the CNS as well as during cancer metastasis.

  16. Heterotopic ossification after central nervous system trauma

    PubMed Central

    Sullivan, M. P.; Torres, S. J.; Mehta, S.; Ahn, J.

    2013-01-01

    Neurogenic heterotopic ossification (NHO) is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury. Ectopic bone forms around joints in characteristic patterns, causing pain and limiting movement especially around the hip and elbow. Clinical sequelae of neurogenic heterotopic ossification include urinary tract infection, pressure injuries, pneumonia and poor hygiene, making early diagnosis and treatment clinically compelling. However, diagnosis remains difficult with more investigation needed. Our pathophysiological understanding stems from mechanisms of basic bone formation enhanced by evidence of systemic influences from circulating humor factors and perhaps neurological ones. This increasing understanding guides our implementation of current prophylaxis and treatment including the use of non-steroidal anti-inflammatory drugs, bisphosphonates, radiation therapy and surgery and, importantly, should direct future, more effective ones. PMID:23610702

  17. The Nervous Systems of Basally Branching Nemertea (Palaeonemertea)

    PubMed Central

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas

    2013-01-01

    In recent years, a lot of studies have been published dealing with the anatomy of the nervous system in different spiralian species. The only nemertean species investigated in this context probably shows derived characters and thus the conditions found there are not useful in inferring the relationship between nemerteans and other spiralian taxa. Ingroup relationships within Nemertea are still unclear, but there is some agreement that the palaeonemerteans form a basal, paraphyletic grade. Thus, palaeonemertean species are likely the most informative when comparing with other invertebrate groups. We therefore analyzed the nervous system of several palaeonemertean species by combining histology and immunostaining. 3D reconstructions based on the aligned slices were performed to get an overall impression of the central nervous system, and immunohistochemistry was chosen to reveal fine structures and to be able to compare the data with recently published results. The insights presented here permit a first attempt to reconstruct the primary organization of the nemertean nervous system. This comparative analysis allows substantiating homology hypotheses for nerves of the peripheral nervous system. This study also provides evidence that the nemertean brain primarily consists of two lobes connected by a strong ventral commissure and one to several dorsal commissures. During nemertean evolution, the brain underwent continuous compartmentalization into a pair of dorsal and ventral lobes interconnected by commissures and lateral tracts. Given that this conclusion can be corroborated by cladistic analyses, nemerteans should share a common ancestor with spiralians that primarily have a simple brain consisting of paired medullary, frontally commissurized and reinforced cords. Such an organization resembles the situation found in presumably basally branching annelids or mollusks. PMID:23785478

  18. The nervous systems of basally branching nemertea (palaeonemertea).

    PubMed

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas

    2013-01-01

    In recent years, a lot of studies have been published dealing with the anatomy of the nervous system in different spiralian species. The only nemertean species investigated in this context probably shows derived characters and thus the conditions found there are not useful in inferring the relationship between nemerteans and other spiralian taxa. Ingroup relationships within Nemertea are still unclear, but there is some agreement that the palaeonemerteans form a basal, paraphyletic grade. Thus, palaeonemertean species are likely the most informative when comparing with other invertebrate groups. We therefore analyzed the nervous system of several palaeonemertean species by combining histology and immunostaining. 3D reconstructions based on the aligned slices were performed to get an overall impression of the central nervous system, and immunohistochemistry was chosen to reveal fine structures and to be able to compare the data with recently published results. The insights presented here permit a first attempt to reconstruct the primary organization of the nemertean nervous system. This comparative analysis allows substantiating homology hypotheses for nerves of the peripheral nervous system. This study also provides evidence that the nemertean brain primarily consists of two lobes connected by a strong ventral commissure and one to several dorsal commissures. During nemertean evolution, the brain underwent continuous compartmentalization into a pair of dorsal and ventral lobes interconnected by commissures and lateral tracts. Given that this conclusion can be corroborated by cladistic analyses, nemerteans should share a common ancestor with spiralians that primarily have a simple brain consisting of paired medullary, frontally commissurized and reinforced cords. Such an organization resembles the situation found in presumably basally branching annelids or mollusks.

  19. The application of real-time PCR technique to detect rare cell clones with primary T790M Substitution of EGFR gene in metastases of non-small cell lung cancer to central nervous system in chemotherapy naive patients.

    PubMed

    Powrózek, Tomasz; Krawczyk, Paweł; Jarosz, Bożena; Mlak, Radosław; Wojas-Krawczyk, Kamila; Sawicki, Marek; Stencel, Dariusz; Trojanowski, Tomasz; Milanowski, Janusz

    2014-10-01

    The time-limited efficacy of reversible EGFR-TKIs in patients with advanced non-small cell lung cancer (NSCLC) with EGFR gene activating mutations is associated with development of treatment resistance after some period of therapy. This resistance predominantly results from secondary mutations located in EGFR gene, especially T790M substitution. There is limited information available concerning the prevalence of primary T790M mutations in patients with metastatic NSCLC tumors before treatment with EGFR-TKIs. The aim of work was to assess the prevalence of de novo T790M mutations in EGFR gene in tissue samples from NSCLC metastatases in central nervous system (CNS) in both chemotherapy and EGFR-TKI naive NSCLC patients. We analyzed DNA samples isolated from paraffin-embedded tissue from CNS metastases for T790M mutations using real-time PCR and TaqMan probe against the T790M mutant sequence. The tissue samples were taken during palliative neurosurgery in 143 NSCLC patients. Amplification of the T790M-specific sequence was detected in 25 patients (17.5 %). The quantity of mutated DNA was less than 1 % in all samples with amplification, and in vast majority (20 patients, 14 % of all samples) it was even less that 0.1 %. In 5 patients (3.5 %) quantity of mutated DNA ranged from 0.1 to 1 % and true positive results of T790M mutation presence in these patients were most possible. Amplification of this sequence was not concurrent with common EGFR mutations and was not associated with sex, smoking status and pathological type of cancer. There is a possibility to detect the primary T790M mutation in brain metastases of NSCLC in EGFR-TKIs naïve patients.

  20. Sensitive methods for detection of the S768R substitution in exon 18 of the DDR2 gene in patients with central nervous system metastases of non-small cell lung cancer.

    PubMed

    Nicoś, Marcin; Powrózek, Tomasz; Krawczyk, Paweł; Jarosz, Bożena; Pająk, Beata; Sawicki, Marek; Kucharczyk, Krzysztof; Trojanowski, Tomasz; Milanowski, Janusz

    2014-10-01

    Discoidin death receptor 2 (DDR2) receptor belongs to a DDR family that shows a tyrosine kinase activity. The somatic mutations in DDR2 gene, reported in non-small cell lung cancer (NSCLC), are involved in up-regulation of cells' migration, proliferation and survival. A S768R substitution in DDR2 gene was commonly reported in squamous cell lung carcinoma. Clinical data of patients carrying the DDR2 gene mutation suggest that its presence can be independent of gender and age. The effectiveness of an oral dual-specific (Src and Abl) multikinase inhibitors-dasatinib-was observed in different cell lines and in some NSCLC patients with identified DDR2 mutation. In the present study, we have used three molecular methods (ASP-real-time PCR, ASP-DNA-FLA PCR and direct sequencing) to detect the DDR2 gene mutation in 143 patients with NSCLC metastases to the central nervous system (CNS). The prevalence of the DDR2 gene mutation was correlated with the occurrence of mutations in the EGFR, KRAS, HER2 and BRAF genes. We identified three patients (2.1% of studied group) with DDR2 mutation. The mutation was observed in two patients with low differentiated squamous cell lung cancer and in one patient with adeno-squamous cell carcinoma (ADSCC). In ADSCC patients, DDR2 mutation coexisted with G12C substitution in KRAS gene. According to the current knowledge, examination of the presence of the DDR2 gene mutation in metastatic lesion is the first such report worldwide. The information, that these driver mutations are present in CNS metastases of NSCLC, could broaden therapeutic choices in such group of patients.

  1. A Brief Report of the Status of Central Nervous System Metastasis Enrollment Criteria for Advanced Non-Small Cell Lung Cancer Clinical Trials: A Review of the ClinicalTrials.gov Trial Registry.

    PubMed

    McCoach, Caroline E; Berge, Eamon M; Lu, Xian; Barón, Anna E; Camidge, D Ross

    2016-03-01

    Central nervous system (CNS) metastases are common in non-small cell lung cancer (NSCLC), yet clinical trials of new drugs in advanced NSCLC have varying inclusion and exclusion criteria for CNS disease. The true extent of variation in CNS-related enrollment criteria in NSCLC clinical trials has not been documented. We performed a systematic search of the ClinicalTrials.gov website to characterize interventional drug trials enrolling adult patients with advanced NSCLC. Of 413 open trials, 78 (19%) strictly excluded patients with leptomeningeal disease (LMD). Separate from LMD, patients with any history of CNS metastases were strictly excluded in 59 trials (14%), allowed after local treatment in 169 (41%), and allowed with no prior treatment in 106 (26%). No explicit mention of CNS disease was made in 79 trials (19%). In multivariate analysis looking at trial phase, location, sponsor, and treatment type, only sponsor was statistically significant, with pharmaceutical industry-sponsored trials having higher odds of excluding patients with brain metastases than did university or investigator-initiated trials (OR = 2.262, 95% confidence interval: 1.063-4.808, p = 0.0342) CONCLUSIONS: With 14% to 19% of trials excluding any history of LMD or CNS parenchymal metastatic disease and 41% of trials permitting CNS disease only after prior CNS-directed treatment, direct evidence of activity of a treatment on CNS disease cannot be reliably generated in most NSCLC trials. Given the high frequency of CNS disease in NSCLC and only sponsor being associated with specific CNS exclusion criteria, sponsors should consider tailoring trial designs to explore CNS benefit more explicitly. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  2. Effect of hyperthermia on the central nervous system: a review.

    PubMed

    Sminia, P; van der Zee, J; Wondergem, J; Haveman, J

    1994-01-01

    Experimental data show that nervous tissue is sensitive to heat. Animal data indicate that the maximum tolerated heat dose after local hyperthermia of the central nervous system (CNS) lies in the range of 40-60 min at 42-42 x 5 degrees C or 10-30 min at 43 degrees C. No conclusions concerning the heat sensitivity of nervous tissue can be derived from clinical studies using localized hyperthermia. The choice whether or not to exceed the critical heat dose, as derived from laboratory studies, in clinical practice is very much dependent on the clinical situation such as the anatomical site and volume of the tissue involved, and prior therapy. Data on clinical application of whole body hyperthermia (WBH) show that nervous tissue can withstand a slightly higher heat dose than after localized heating, which might be the result of developing thermal resistance during treatment. Expression of thermotolerance was observed in the spinal cord of laboratory animals. After WBH in man at a maximum between 40 and 43 degrees C for 6 h-30 min CNS complications were reported, but other complications seemed to be more life-threatening. Most studies indicate that impairment of the CNS after WBH was not due to direct heat injury to the brain or spinal cord, but was secondary as a result of physiological changes. Heat, at least if applied shortly after X-rays, enhances the response of nervous tissue to radiation. Neurotoxicity of chemotherapeutic drugs does not seem to be a limiting complication in hyperthermia if combined with chemotherapy, but only few data are available. The limited clinical experience shows that safe hyperthermic treatment of CNS malignancies or tumours located close to the CNS seems feasible under appropriate technical conditions with adequate thermometry and taking the sensitivity of the surrounding normal nervous tissue into account.

  3. Molecular clocks and the early evolution of metazoan nervous systems.

    PubMed

    Wray, Gregory A

    2015-12-19

    The timing of early animal evolution remains poorly resolved, yet remains critical for understanding nervous system evolution. Methods for estimating divergence times from sequence data have improved considerably, providing a more refined understanding of key divergences. The best molecular estimates point to the origin of metazoans and bilaterians tens to hundreds of millions of years earlier than their first appearances in the fossil record. Both the molecular and fossil records are compatible, however, with the possibility of tiny, unskeletonized, low energy budget animals during the Proterozoic that had planktonic, benthic, or meiofaunal lifestyles. Such animals would likely have had relatively simple nervous systems equipped primarily to detect food, avoid inhospitable environments and locate mates. The appearance of the first macropredators during the Cambrian would have changed the selective landscape dramatically, likely driving the evolution of complex sense organs, sophisticated sensory processing systems, and diverse effector systems involved in capturing prey and avoiding predation.

  4. Molecular clocks and the early evolution of metazoan nervous systems

    PubMed Central

    Wray, Gregory A.

    2015-01-01

    The timing of early animal evolution remains poorly resolved, yet remains critical for understanding nervous system evolution. Methods for estimating divergence times from sequence data have improved considerably, providing a more refined understanding of key divergences. The best molecular estimates point to the origin of metazoans and bilaterians tens to hundreds of millions of years earlier than their first appearances in the fossil record. Both the molecular and fossil records are compatible, however, with the possibility of tiny, unskeletonized, low energy budget animals during the Proterozoic that had planktonic, benthic, or meiofaunal lifestyles. Such animals would likely have had relatively simple nervous systems equipped primarily to detect food, avoid inhospitable environments and locate mates. The appearance of the first macropredators during the Cambrian would have changed the selective landscape dramatically, likely driving the evolution of complex sense organs, sophisticated sensory processing systems, and diverse effector systems involved in capturing prey and avoiding predation. PMID:26554040

  5. Quest for the basic plan of nervous system circuitry

    PubMed Central

    Swanson, Larry W.

    2007-01-01

    The basic plan of nervous system organization has been investigated since classical antiquity. The first model centered on pneumas pumped from sensory nerves through the ventricular system and out motor nerves to muscles. It was popular well into the seventeenth century and diverted attention from the organization of brain parenchyma itself. Willis focused on gray matter production and white matter conduction of pneumas in 1664, and by the late nineteenth century a clear cellular model of nervous system organization based on sensory, motor, and association neuron classes transmitting nerve impulses was elaborated by Cajal and his contemporaries. Today, revolutionary advances in experimental pathway tracing methods, molecular genetics, and computer science inspire systems neuroscience. Seven minimal requirements are outlined for knowledge management systems capable of describing, analyzing, and modeling the basic plan of nervous system circuitry in general, and the plan evolved for vertebrates, for mammals, and ultimately for humans in particular. The goal remains a relatively simple, easy to understand model analogous to the one Harvey elaborated in 1628 for circulation in the cardiovascular system. As Cajal wrote in 1909, “To extend our understanding of neural function to the most complex human physiological and psychological activities, it is essential that we first generate a clear and accurate view of the structure of the relevant centers, and of the human brain itself, so that the basic plan—the overview—can be grasped in the blink of an eye.” PMID:17267046

  6. Quest for the basic plan of nervous system circuitry.

    PubMed

    Swanson, Larry W

    2007-10-01

    The basic plan of nervous system organization has been investigated since classical antiquity. The first model centered on pneumas pumped from sensory nerves through the ventricular system and out motor nerves to muscles. It was popular well into the 17th century and diverted attention from the organization of brain parenchyma itself. Willis focused on gray matter production and white matter conduction of pneumas in 1664, and by the late 19th century a clear cellular model of nervous system organization based on sensory, motor, and association neuron classes transmitting nerve impulses was elaborated by Cajal and his contemporaries. Today, revolutionary advances in experimental pathway tracing methods, molecular genetics, and computer science inspire systems neuroscience. Seven minimal requirements are outlined for knowledge management systems capable of describing, analyzing, and modeling the basic plan of nervous system circuitry in general, and the plan evolved for vertebrates, for mammals, and ultimately for humans in particular. The goal remains a relatively simple, easy to understand model analogous to the one Harvey elaborated in 1628 for blood circulation in the cardiovascular system. As Cajal wrote in 1909, "To extend our understanding of neural function to the most complex human physiological and psychological activities, it is essential that we first generate a clear and accurate view of the structure of the relevant centers, and of the human brain itself, so that the basic plan--the overview--can be grasped in the blink of an eye."

  7. Craniospinal irradiation using helical tomotherapy for central nervous system tumors.

    PubMed

    Schiopu, Sanziana R I; Habl, Gregor; Häfner, Matthias; Katayama, Sonja; Herfarth, Klaus; Debus, Juergen; Sterzing, Florian

    2017-01-17

    The aim of this study was to describe early and late toxicity, survival and local control in 45 patients with primary brain tumors treated with helical tomotherapy craniospinal irradiation (HT-CSI). From 2006 to 2014, 45 patients with central nervous system malignancies were treated with HT-CSI. The most common tumors were medulloblastoma in 20 patients, ependymoma in 10 patients, intracranial germinoma (ICG) in 7 patients, and primitive neuroectodermal tumor in 4 patients. Hematological toxicity during treatment included leukopenia Grades 1-4 (6.7%, 33.3%, 37.8% and 17.8%, respectively), anemia Grades 1-4 (44.4%, 22.2%, 22.2% and 0%, respectively) and thrombocytopenia Grades 1-4 (51.1%, 15.6%, 15.6% and 6.7%, respectively). The most common acute toxicities were nausea, vomiting, fatigue, loss of appetite, alopecia and neurotoxicity. No Grade 3 or higher late toxicity occurred. The overall 3- and 5-year survival rates were 80% and 70%, respectively. Survival for the main tumor entities included 3- and 5-year survival rates of 80% and 70%, respectively, for patients with medulloblastoma, 70% for both in patients with ependymoma, and 100% for both in patients with ICG. Relapse occurred in 11 patients (24.4%): 10 with local and 1 with multifocal relapse. One patient experienced a secondary cancer. M-status and the results of the re-evaluation at the end of treatment were significantly related to survival. Survival after HT-CSI was in line with the existing literature, and acute treatment-induced toxicity resolved quickly. Compared with conventional radiotherapy, HT offers benefits such as avoiding gaps and junctions, sparing organs, and better and more homogeneous dose distribution and coverage of the target volume.

  8. Functional structure and dynamics of the human nervous system

    NASA Technical Reports Server (NTRS)

    Lawrence, J. A.

    1981-01-01

    The status of an effort to define the directions needed to take in extending pilot models is reported. These models are needed to perform closed-loop (man-in-the-loop) feedback flight control system designs and to develop cockpit display requirements. The approach taken is to develop a hypothetical working model of the human nervous system by reviewing the current literature in neurology and psychology and to develop a computer model of this hypothetical working model.

  9. Central nervous system involvement of polyarteritis nodosa: a case report.

    PubMed

    Altinok, D; Yildiz, Y T; Ruşen, E; Eryilmaz, M; Tacal, T

    2001-01-01

    Polyarteritis nodosa (PAN) is a necrotizing vasculitis involving small and medium-sized arteries and it affects multiple organ systems in the body Central nervous system (CNS) involvement appears less frequently, and usually develops after the disease is established. Although aneurysms are common in visceral arteries in PAN, intracranial aneurysms are uncommon and have been documented rarely. This case is reported to raise awareness among radiologists as it has characteristic and rare, if not specific, imaging findings of CNS involvement of PAN.

  10. [VARICELLA ZOSTER VIRUS AND DISEASES OF CENTRAL NERVOUS SYSTEM VESSELS].

    PubMed

    Kazanova, A S; Lavrov, V F; Zverev, V V

    2015-01-01

    Systemized data on epidemiology, pathogenesis, clinical manifestation, diagnostics and therapy of VZV-vasculopathy--a disease, occurring due to damage of arteries of the central nervous system by Varicella Zoster virus, are presented in the review. A special attention in the paper is given to the effect of vaccine prophylaxis of chicken pox and herpes zoster on the frequency of development and course of VZV-vasculopathy.

  11. Regulation of Neurotransmitter Responses in the Central Nervous System

    DTIC Science & Technology

    1990-02-05

    neurotransmitter systems was of general physiological relevance to mammalian central nervous system function and (2) that multiple CABA receptors may exist...pharmacologically distinct CABA receptors in mammalian tissues. Furthermore, the results predict it may be possible to develop more potent compounds which...present. Project co-ordination and scientific direction. E. Coupling Activities. S.J. Enna, Ph.D., invited speaker, First International CABA Receptor

  12. Regulation of sympathetic nervous system function after cardiovascular deconditioning

    NASA Technical Reports Server (NTRS)

    Hasser, E. M.; Moffitt, J. A.

    2001-01-01

    Humans subjected to prolonged periods of bed rest or microgravity undergo deconditioning of the cardiovascular system, characterized by resting tachycardia, reduced exercise capability, and a predisposition for orthostatic intolerance. These changes in cardiovascular function are likely due to a combination of factors, including changes in control of body fluid balance or cardiac alterations resulting in inadequate maintenance of stroke volume, altered arterial or venous vascular function, reduced activation of cardiovascular hormones, and diminished autonomic reflex function. There is evidence indicating a role for each of these mechanisms. Diminished reflex activation of the sympathetic nervous system and subsequent vasoconstriction appear to play an important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model of deconditioning, evaluated the potential role of altered arterial baroreflex control of the sympathetic nervous system. These studies indicate that HU results in blunted baroreflex-mediated activation of both renal and lumbar sympathetic nerve activity in response to a hypotensive stimulus. HU rats are less able to maintain arterial pressure during hemorrhage, suggesting that diminished ability to increase sympathetic activity has functional consequences for the animal. Reflex control of vasopressin secretion appears to be enhanced following HU. Blunted baroreflex-mediated sympathoexcitation appears to involve altered central nervous system function. Baroreceptor afferent activity in response to changes in arterial pressure is unaltered in HU rats. However, increases in efferent sympathetic nerve activity for a given decrease in afferent input are blunted after HU. This altered central nervous system processing of baroreceptor inputs appears to involve an effect at the rostral ventrolateral medulla (RVLM). Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is enhanced after HU. Augmented inhibition apparently

  13. Regulation of sympathetic nervous system function after cardiovascular deconditioning

    NASA Technical Reports Server (NTRS)

    Hasser, E. M.; Moffitt, J. A.

    2001-01-01

    Humans subjected to prolonged periods of bed rest or microgravity undergo deconditioning of the cardiovascular system, characterized by resting tachycardia, reduced exercise capability, and a predisposition for orthostatic intolerance. These changes in cardiovascular function are likely due to a combination of factors, including changes in control of body fluid balance or cardiac alterations resulting in inadequate maintenance of stroke volume, altered arterial or venous vascular function, reduced activation of cardiovascular hormones, and diminished autonomic reflex function. There is evidence indicating a role for each of these mechanisms. Diminished reflex activation of the sympathetic nervous system and subsequent vasoconstriction appear to play an important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model of deconditioning, evaluated the potential role of altered arterial baroreflex control of the sympathetic nervous system. These studies indicate that HU results in blunted baroreflex-mediated activation of both renal and lumbar sympathetic nerve activity in response to a hypotensive stimulus. HU rats are less able to maintain arterial pressure during hemorrhage, suggesting that diminished ability to increase sympathetic activity has functional consequences for the animal. Reflex control of vasopressin secretion appears to be enhanced following HU. Blunted baroreflex-mediated sympathoexcitation appears to involve altered central nervous system function. Baroreceptor afferent activity in response to changes in arterial pressure is unaltered in HU rats. However, increases in efferent sympathetic nerve activity for a given decrease in afferent input are blunted after HU. This altered central nervous system processing of baroreceptor inputs appears to involve an effect at the rostral ventrolateral medulla (RVLM). Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is enhanced after HU. Augmented inhibition apparently

  14. Role of Exosomes/Microvesicles in the Nervous System and Use in Emerging Therapies

    PubMed Central

    Lai, Charles Pin-Kuang; Breakefield, Xandra Owen

    2012-01-01

    Extracellular membrane vesicles (EMVs) are nanometer sized vesicles, including exosomes and microvesicles capable of transferring DNAs, mRNAs, microRNAs, non-coding RNAs, proteins, and lipids among cells without direct cell-to-cell contact, thereby representing a novel form of intercellular communication. Many cells in the nervous system have been shown to release EMVs, implicating their active roles in development, function, and pathologies of this system. While substantial progress has been made in understanding the biogenesis, biophysical properties, and involvement of EMVs in diseases, relatively less information is known about their biological function in the normal nervous system. In addition, since EMVs are endogenous vehicles with low immunogenicity, they have also been actively investigated for the delivery of therapeutic genes/molecules in treatment of cancer and neurological diseases. The present review summarizes current knowledge about EMV functions in the nervous system under both physiological and pathological conditions, as well as emerging EMV-based therapies that could be applied to the nervous system in the foreseeable future. PMID:22754538

  15. 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

  16. [Pleasure, pain and affectivity in the nervous system].

    PubMed

    Houdart, R

    1999-01-01

    Affectivity plays an essential role in human life. It gives life its quality, and is responsible for what human beings have always considered to be main endeavor happiness. Still, looking for its description or organisation, in physiology or neurology, treatises is fruitless; there only one of its components is described pain, with no mention of pleasure. We wish to show, here, first, that pain and pleasure, depend of a same function, of which they are, of sorts, both extremities, and which in nothing but the most primitive function of the nervous system, and secondly, that this function in one of the components of an "affectivity center", which has its organisation in the limbic system. This center, integrating all the informations that arrives to the nervous system, triggers to each of them neuro-vegetative and neuro-hormonal informations that are "felt" by the organism, and thus transforms the information in a subjective feeling.

  17. [Neurogenesis as a therapeutic strategy to regenerate central nervous system].

    PubMed

    Arias-Carrión, O; Drucker-Colín, R

    In the past few years, it has been demonstrated that the adult mammalian brain maintains the capacity to generate new neurons from neural stem/progenitor cells. These new neurons integrate into pre-existing systems through a process referred to as 'neurogenesis in the adult brain'. This discovery has modified our understanding of how the central nervous system functions in health and disease. Until today, a great effort has been made attempting to decipher the mechanisms regulating adult neurogenesis, which might help to induce neuronal endogenous cell replacement in various neurological diseases. In this revision, we will attempt to shed some light on the neurogenesis process with respect to diseases of the central nervous system and we will describe some therapeutic potentials in relation to neurodegenerative diseases.

  18. Vulnerable periods and processes during central nervous system development.

    PubMed Central

    Rodier, P M

    1994-01-01

    The developing central nervous system (CNS) is the organ system most frequently observed to exhibit congenital abnormalities. While the developing CNS lacks a blood brain barrier, the characteristics of known teratogens indicate that differential doses to the developing vs mature brain are not the major factor in differential sensitivity. Instead, most agents seem to act on processes that occur only during development. Thus, it appears that the susceptibility of the developing brain compared to the mature one depends to a great extent on the presence of processes sensitive to disruption. Yet cell proliferation, migration, and differentiation characterize many other developing organs, so the difference between CNS and other organs must depend on other properties of the developing CNS. The most important of these is probably the fact that nervous system development takes much longer than development of other organs, making it subject to injury over a longer period. PMID:7925182

  19. Multigenic control of thyroid hormone functions in the nervous system

    PubMed Central

    Nunez, Jacques; Celi, Francesco S.; Ng, Lily; Forrest, Douglas

    2008-01-01

    Summary Thyroid hormone (TH) has a remarkable range of actions in the development and function of the nervous system. A multigenic picture is emerging of the mechanisms that specify these diverse functions in target tissues. Distinct responses are mediated by α and β isoforms of TH receptor which act as ligand-regulated transcription factors. Receptor activity can be regulated at several levels including that of uptake of TH ligand and the activation or inactivation of ligand by deiodinase enzymes in target tissues. Processes under the control of TH range from learning and anxiety-like behaviour to sensory function. At the cellular level, TH controls events as diverse as axonal outgrowth, hippocampal synaptic activity and the patterning of opsin photopigments necessary for colour vision. Overall, TH coordinates this variety of events in both central and sensory systems to promote the function of the nervous system as a complete entity. PMID:18448240

  20. Pharmacologic action of oseltamivir on the nervous system.

    PubMed

    Ishii, K; Hamamoto, H; Sasaki, T; Ikegaya, Y; Yamatsugu, K; Kanai, M; Shibasaki, M; Sekimizu, K

    2008-02-01

    Oseltamivir, an antiviral drug used for the treatment of influenza, contains the L-glutamic acid motif in its chemical structure. We focused on this structural characteristic of oseltamivir and examined the pharmacologic effects of the drug on the nervous system in invertebrate and vertebrate animal models. Injection of oseltamivir or L-glutamic acid into silkworm (Bombyx mori) larvae induced muscle relaxation. Oseltamivir and L-glutamic acid inhibited kainate-induced rapid muscle contraction, but neither drug affected insect cytokine paralytic peptide-induced slow muscle contraction. In the mammalian system, mice (Mus musculus) treated intracerebrally with oseltamivir developed convulsive seizures. Hydrolyzed oseltamivir, the active form containing a carboxylic acid, evoked epileptiform firing of hippocampal neurons in rat (Rattus norvegicus) organotypic hippocampal slice cultures. These results are the first to demonstrate that oseltamivir exerts pharmacologic effects on the nervous system in insects and mammals.

  1. D-Amino Acids in the Nervous and Endocrine Systems

    PubMed Central

    Kiriyama, Yoshimitsu

    2016-01-01

    Amino acids are important components for peptides and proteins and act as signal transmitters. Only L-amino acids have been considered necessary in mammals, including humans. However, diverse D-amino acids, such as D-serine, D-aspartate, D-alanine, and D-cysteine, are found in mammals. Physiological roles of these D-amino acids not only in the nervous system but also in the endocrine system are being gradually revealed. N-Methyl-D-aspartate (NMDA) receptors are associated with learning and memory. D-Serine, D-aspartate, and D-alanine can all bind to NMDA receptors. H2S generated from D-cysteine reduces disulfide bonds in receptors and potentiates their activity. Aberrant receptor activity is related to diseases of the central nervous system (CNS), such as Alzheimer's disease, amyotrophic lateral sclerosis, and schizophrenia. Furthermore, D-amino acids are detected in parts of the endocrine system, such as the pineal gland, hypothalamus, pituitary gland, pancreas, adrenal gland, and testis. D-Aspartate is being investigated for the regulation of hormone release from various endocrine organs. Here we focused on recent findings regarding the synthesis and physiological functions of D-amino acids in the nervous and endocrine systems. PMID:28053803

  2. [The interleukin-10 in the central nervous system].

    PubMed

    Kurowska, Ewelina; Majkutewicz, Irena

    2015-07-27

    Cytokines, including interleukin-10 (IL-10), are cell signaling molecules taking part in cell‑to‑cell communication, cell proliferation, differentiation, migration and apoptosis. Cytokines also have the ability to induce, regulate, and inhibit inflammation. Cytokines are produced mainly by activated peripheral immune cells, but due to dissemination of the concept of the central nervous system as an immunologically specialized zone, it is considered that cytokine signaling is one of the components of the immune system which can modulate brain functioning. IL-10 shows immunosuppressive properties, and since expression of this cytokine has been shown in the central nervous system, researchers have started to investigate the therapeutic possibilities of IL-10 action in the context of neurodegenerative diseases, which may involve neuroinflammation in their pathogenesis. Recent studies using cell cultures or animal models of neurodegenerative disorders have shown that the importance of IL-10 in the central nervous system goes beyond the anti-inflammatory activity of this cytokine. Involvement of IL-10 in neuroprotection, neurogenesis, regulation of the stress response and hippocampal synaptic plasticity connected with learning and memory is suggested.

  3. Genome integrity and disease prevention in the nervous system.

    PubMed

    McKinnon, Peter J

    2017-06-15

    Multiple DNA repair pathways maintain genome stability and ensure that DNA remains essentially unchanged over the life of a cell. Various human diseases occur if DNA repair is compromised, and most of these impact the nervous system, in some cases exclusively. However, it is often unclear what specific endogenous damage underpins disease pathology. Generally, the types of causative DNA damage are associated with replication, transcription, or oxidative metabolism; other direct sources of endogenous lesions may arise from aberrant topoisomerase activity or ribonucleotide incorporation into DNA. This review focuses on the etiology of DNA damage in the nervous system and the genome stability pathways that prevent human neurologic disease. © 2017 McKinnon; Published by Cold Spring Harbor Laboratory Press.

  4. Neurotropic Enterovirus Infections in the Central Nervous System.

    PubMed

    Huang, Hsing-I; Shih, Shin-Ru

    2015-11-24

    Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS) and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells.

  5. Neurotropic Enterovirus Infections in the Central Nervous System

    PubMed Central

    Huang, Hsing-I; Shih, Shin-Ru

    2015-01-01

    Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS) and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells. PMID:26610549

  6. Neuroimmune interactions: dendritic cell modulation by the sympathetic nervous system.

    PubMed

    Takenaka, Maisa C; Guereschi, Marcia G; Basso, Alexandre S

    2017-02-01

    Dendritic cells are of paramount importance bridging innate and adaptive immune responses. Depending on the context, after sensing environmental antigens, commensal microorganisms, pathogenic agents, or antigens from the diet, dendritic cells may drive either different effector adaptive immune responses or tolerance, avoiding tissue damage. Although the plasticity of the immune response and the capacity to regulate itself are considered essential to orchestrate appropriate physiological responses, it is known that the nervous system plays a relevant role controlling immune cell function. Dendritic cells present in the skin, the intestine, and lymphoid organs, besides expressing adrenergic receptors, can be reached by neurotransmitters released by sympathetic fibers innervating these tissues. These review focus on how neurotransmitters from the sympathetic nervous system can modulate dendritic cell function and how this may impact the immune response and immune-mediated disorders.

  7. Is Ghrelin Synthesized in the Central Nervous System?

    PubMed Central

    Cabral, Agustina; López Soto, Eduardo J.; Epelbaum, Jacques; Perelló, Mario

    2017-01-01

    Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a), and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals. PMID:28294994

  8. Nanoneuromedicines for Degenerative, Inflammatory, and Infectious Nervous System Diseases

    PubMed Central

    Gendelman, Howard E.; Anantharam, Vellareddy; Bronich, Tatiana; Ghaisas, Shivani; Jin, Huajun; Kanthasamy, Anumantha G.; Liu, Xinming; McMillan, JoEllyn; Mosley, R. Lee; Narasimhan, Balaji; Mallapragada, Surya K.

    2015-01-01

    Interest in nanoneuromedicine has grown rapidly due to the immediate need for improved biomarkers and therapies for psychiatric, developmental, traumatic, inflammatory, infectious and degenerative nervous system disorders. These, in whole or in part, are a significant societal burden due to growth in numbers of affected people and in disease severity. Lost productivity of the patient and his or her caregiver, and the emotional and financial burden cannot be overstated. The need for improved health care, treatment and diagnostics are immediate. A means to such an end is nanotechnology. Indeed, recent developments of health-care enabling nanotechnologies and nanomedicines range from biomarker discovery including neuroimaging to therapeutic applications for degenerative, inflammatory and infectious disorders of the nervous system. This review focuses on the current and future potential of the field to positively affect clinical outcomes. PMID:25645958

  9. ROLE OF SYMPATHETIC NERVOUS SYSTEM IN OBESITY RELATED HYPERTENSION

    PubMed Central

    da Silva, Alexandre; doCarmo, Jussara; Dubinion, John; Hall, John E.

    2010-01-01

    Obesity is recognized as a major, worldwide, health problem. Excess weight is a major cause of increased blood pressure in most patients with essential hypertension, and greatly increases the risk for diabetes, cardiovascular diseases, and end stage renal disease. Although the mechanisms by which obesity raises blood pressure are not completely understood, increased renal sodium reabsorption, impaired pressure natriuresis, and volume expansion appear to play important roles. Several potential mechanisms have been suggested to contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), and physical compression of the kidneys, especially when visceral obesity is present. Activation of the SNS in obesity may be due, in part, to hyperleptinemia and other factors secreted by adipocytes and the gastrointestinal tract, activation of the central nervous melanocortin pathway, and baroreceptor dysfunction. PMID:19442330

  10. [LIM kinases and their roles in the nervous system].

    PubMed

    Zhang, Ru-yi; Ding, Yue-min; Zhang, Li-huang

    2014-01-01

    LIM kinase-1 (LIMK1) and LIM kinase-2 (LIMK2) are kinases that have serine/threonine and tyrosine dual specificity. Although they show significant structural similarity, LIMK1 and LIMK2 have different expression patterns, subcellular localization, and functions. Activation of LIM kinases regulates the downstream of Rho GTPases, and influences the architecture of the actin cytoskeleton by regulating the activity of cofilin. Recent studies have shown that LIM kinases play important roles in the nervous system. For example, development of the central nervous system is reliant upon the presence of LIMK1, and deletion of Limk1 gene is involved in the development of the human genetic disorder Williams syndrome. Therefore, it is of vital physiological significance to investigate the neuronal function of LIM kinases. In this review, we outline the structure, phosphorylation regulation and neuronal function of LIM kinases, so as to provide new ideas for the treatment of these neurological diseases.

  11. High-throughput screening in the C. elegans nervous system.

    PubMed

    Kinser, Holly E; Pincus, Zachary

    2016-06-03

    The nematode Caenorhabditis elegans is widely used as a model organism in the field of neurobiology. The wiring of the C. elegans nervous system has been entirely mapped, and the animal's optical transparency allows for in vivo observation of neuronal activity. The nematode is also small in size, self-fertilizing, and inexpensive to cultivate and maintain, greatly lending to its utility as a whole-animal model for high-throughput screening (HTS) in the nervous system. However, the use of this organism in large-scale screens presents unique technical challenges, including reversible immobilization of the animal, parallel single-animal culture and containment, automation of laser surgery, and high-throughput image acquisition and phenotyping. These obstacles require significant modification of existing techniques and the creation of new C. elegans-based HTS platforms. In this review, we outline these challenges in detail and survey the novel technologies and methods that have been developed to address them.

  12. Pathophysiological mechanisms of Flavivirus infection of the central nervous system.

    PubMed

    Pardigon, N

    2017-09-01

    Flaviviruses are important human pathogens. Transmitted by the bite of infected mosquitoes, Flaviviruses such as West Nile and Japanese encephalitis may reach the central nervous system where they can elicit severe diseases. Their ability to cross the blood-brain-barrier is still poorly understood. The newly emerging Zika Flavivirus on the other hand very rarely reaches the brain of adults, but can infect neural progenitors in the developing central nervous system of fetuses, eliciting devastating congenital malformations including microcephaly. This short review focuses on selected aspects of West Nile, Japanese encephalitis and Zika virus pathophysiological features such as neuroinvasion and neurovirulence, and highlights what we know about some possible mechanisms involved in Flaviviral neuropathogenesis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Central nervous system histoplasmosis in an immunocompetent pediatric patient.

    PubMed

    Esteban, Ignacio; Minces, Pablo; De Cristofano, Analía M; Negroni, Ricardo

    2016-06-01

    Neurohistoplasmosis is a rare disease, most prevalent in immunosuppressed patients, secondary to disseminated disease with a high mortality rate when diagnosis and treatment are delayed. We report a previously healthy 12 year old girl, from a bat infested region of Tucuman Province, Argentine Republic, who developed meningoencephalitis due to Histoplasma capsulatum. Eighteen months prior to admission the patient started with headaches and intermittent fever. The images of the central nervous system showed meningoencephalitis suggestive of tuberculosis. She received antibiotics and tuberculostatic medications without improvement. Liposomal amphotericin B was administered for six weeks. The patient's clinical status improved remarkably. Finally the culture of cerebral spinal fluid was positive for micelial form of Histoplasma capsulatum. The difficulties surrounding the diagnosis and treatment of neurohistoplasmosis in immunocompetent patients are discussed in this manuscript, as it also intends to alert to the presence of a strain of Histoplasma capsulatum with affinity for the central nervous system.

  14. Enrico Sereni: research on the nervous system of cephalopods.

    PubMed

    De Leo, A

    2008-01-01

    This essay focuses on a paradigmatic moment in neurobiological studies of invertebrates: the research on the nervous system of cephalopods carried out by Enrico Sereni at the Naples Zoological Station between 1925 and 1931. Although he remained unknown on the historiographic scenario, probably due to his early death, he contributed to Italian science of the first half of the twentieth century. In my paper particular attention will be given to Sereni's study on the pigmentary-effector, neurohumoral, and peripheral nervous systems, since they also accounted for the historical foundation of the experimental vein that, through the years, would lead John Zachary Young, Sereni's follower, to the most well-known discovery of the giant nerve fibers.

  15. Fiber optic in vivo imaging in the mammalian nervous system

    PubMed Central

    Mehta, Amit D; Jung, Juergen C; Flusberg, Benjamin A; Schnitzer, Mark J

    2010-01-01

    The compact size, mechanical flexibility, and growing functionality of optical fiber and fiber optic devices are enabling several new modalities for imaging the mammalian nervous system in vivo. Fluorescence microendoscopy is a minimally invasive fiber modality that provides cellular resolution in deep brain areas. Diffuse optical tomography is a non-invasive modality that uses assemblies of fiber optic emitters and detectors on the cranium for volumetric imaging of brain activation. Optical coherence tomography is a sensitive interferometric imaging technique that can be implemented in a variety of fiber based formats and that might allow intrinsic optical detection of brain activity at a high resolution. Miniaturized fiber optic microscopy permits cellular level imaging in the brains of behaving animals. Together, these modalities will enable new uses of imaging in the intact nervous system for both research and clinical applications. PMID:15464896

  16. Neurogenesis during development of the vertebrate central nervous system

    PubMed Central

    Paridaen, Judith TML; Huttner, Wieland B

    2014-01-01

    During vertebrate development, a wide variety of cell types and tissues emerge from a single fertilized oocyte. One of these tissues, the central nervous system, contains many types of neurons and glial cells that were born during the period of embryonic and post-natal neuro- and gliogenesis. As to neurogenesis, neural progenitors initially divide symmetrically to expand their pool and switch to asymmetric neurogenic divisions at the onset of neurogenesis. This process involves various mechanisms involving intrinsic as well as extrinsic factors. Here, we discuss the recent advances and insights into regulation of neurogenesis in the developing vertebrate central nervous system. Topics include mechanisms of (a)symmetric cell division, transcriptional and epigenetic regulation, and signaling pathways, using mostly examples from the developing mammalian neocortex. PMID:24639559

  17. Measurement of autophagy flux in the nervous system in vivo

    PubMed Central

    Castillo, K; Valenzuela, V; Matus, S; Nassif, M; Oñate, M; Fuentealba, Y; Encina, G; Irrazabal, T; Parsons, G; Court, F A; Schneider, B L; Armentano, D; Hetz, C

    2013-01-01

    Accurate methods to measure autophagic activity in vivo in neurons are not available, and most of the studies are based on correlative and static measurements of autophagy markers, leading to conflicting interpretations. Autophagy is an essential homeostatic process involved in the degradation of diverse cellular components including organelles and protein aggregates. Autophagy impairment is emerging as a relevant factor driving neurodegeneration in many diseases. Moreover, strategies to modulate autophagy have been shown to provide protection against neurodegeneration. Here we describe a novel and simple strategy to express an autophagy flux reporter in the nervous system of adult animals by the intraventricular delivery of adeno-associated viruses (AAV) into newborn mice. Using this approach we efficiently expressed a monomeric tandem mCherry-GFP-LC3 construct in neurons of the peripheral and central nervous system, allowing the measurement of autophagy activity in pharmacological and disease settings. PMID:24232093

  18. Music and Autonomic Nervous System (Dys)function

    PubMed Central

    Ellis, Robert J.; Thayer, Julian F.

    2010-01-01

    Despite a wealth of evidence for the involvement of the autonomic nervous system (ANS) in health and disease and the ability of music to affect ANS activity, few studies have systematically explored the therapeutic effects of music on ANS dysfunction. Furthermore, when ANS activity is quantified and analyzed, it is usually from a point of convenience rather than from an understanding of its physiological basis. After a review of the experimental and therapeutic literatures exploring music and the ANS, a “Neurovisceral Integration” perspective on the interplay between the central and autonomic nervous systems is introduced, and the associated implications for physiological, emotional, and cognitive health are explored. The construct of heart rate variability is discussed both as an example of this complex interplay and as a useful metric for exploring the sometimes subtle effect of music on autonomic response. Suggestions for future investigations using musical interventions are offered based on this integrative account. PMID:21197136

  19. [Functions and mechanisms of dehydroepiandrosterone in nervous system].

    PubMed

    Xie, Li; Sun, Hui-Ying; Gao, Jing; Liao, Hong

    2006-10-01

    Dehydroepiandrosterone is the precursor of sex hormone, and can be synthesized in the brain de novo, which means it is a kind of neurosteroid. Animal experiments and clinical researches have proved that DHEA exhibits a variety of functional activities in the nervous system, including neurotrophic, neuroprotective effects and enhancement' of learning and memory, which suggests that it may be useful in preventing and treating some neural diseases such as neurodegenerative diseases, cerebral ischemia, trauma, psychosis and so on. The mechanisms of the effect of DHEA on protection against oxidative stress, excitotoxicity, apoptosis etc. were found to be through both genomic and nongenomic way. These effects and mechanisms in nervous system were summarized in the present paper.

  20. Is Ghrelin Synthesized in the Central Nervous System?

    PubMed

    Cabral, Agustina; López Soto, Eduardo J; Epelbaum, Jacques; Perelló, Mario

    2017-03-15

    Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a), and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals.

  1. Molecular Targets for Organophosphates in the Central Nervous System

    DTIC Science & Technology

    2006-04-01

    interest is the report that at the neuromuscular junction VX increases acetylcholine (ACh) release by a mechanism unrelated to cholinesterase...neurons of the central nervous system (CNS) are different from those modulating the release of ACh at the neuromuscular junction. Not only do the...solution, and when miniature postsynaptic currents (MPSCs) were recorded, the muscarinic blocker atropine (1 µM) was also added to the external

  2. Isolated central nervous system Whipple's disease: Two cases.

    PubMed

    Vural, Atay; Acar, Nazire Pinar; Soylemezoglu, Figen; Oguz, Kader K; Dericioğlu, Neşe; Saka, Esen

    2015-12-01

    Although it is an orphan disease, isolated central nervous system Whipple's disease is one of the "must be known" conditions in neurology because it belongs to the list of "treatable disorders". Here, we present two cases which highlight the importance of early diagnosis. Additionally, we provide a discussion on up to date diagnostic approach to this life-threatening disorder. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Atypical presentation of pheochromocytoma: Central nervous system pseudovasculitis

    PubMed Central

    Rupala, Ketankumar; Mittal, Varun; Gupta, Rajiv; Yadav, Rajiv

    2017-01-01

    Pheochromocytoma has atypical presentation in 9%–10% of patients. Atypical presentations include myocardial infarction, renal failure, and rarely cerebrovascular events. Various etiologies for central nervous system (CNS) involvement in pheochromocytoma have been described in the literature. A rare association of CNS vasculitis-like features has been described with pheochromocytoma. We report a rare case of pheochromocytoma detected on evaluation for CNS vasculitis-like symptoms. PMID:28197038

  4. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

    PubMed

    Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

    2015-10-01

    The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Autoimmune disorders affecting both the central and peripheral nervous system.

    PubMed

    Kamm, Christoph; Zettl, Uwe K

    2012-01-01

    Various case series of patients with autoimmune demyelinating disease affecting both the central and peripheral nervous system (CNS and PNS), either sequentially or simultaneously, have been reported for decades, but their frequency is considerably lower than that of the "classical" neurological autoimmune diseases affecting only either CNS or PNS, such as multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP) or Guillain-Barré-Syndrome (GBS), and attempts to define or even recognize the former as a clinical entity have remained elusive. Frequently, demyelination started with CNS involvement with subsequent PNS pathology, in some cases with a relapsing-remitting course. Three potential mechanisms for the autoimmune etiology of these conditions can be discussed: (I) They could be caused by a common autoimmunological reactivity against myelin antigens or epitopes present in both the central and peripheral nervous system; (II) They could be due to a higher general susceptibility to autoimmune disease, which in some cases may have been caused or exacerbated by immunomodulatory treatment, e.g. b-interferon; (III) Their co-occurrence might be coincidental. Another example of an autoimmune disease variably involving the central or peripheral nervous system or both is the overlapping and continuous clinical spectrum of Fisher syndrome (FS), as a variant of GBS, and Bickerstaff brainstem encephalitis (BBE). Recent data from larger patient cohorts with demonstration of common autoantibodies, antecedent infections, and results of detailed clinical, neuroimaging and neurophysiological investigations suggest that these three conditions are not separate disorders, but rather form a continuous spectrum with variable central and peripheral nervous system involvement. We herein review clinical and paraclinical data and therapeutic options of these disorders and discuss potential underlying common vs. divergent immunopathogenic mechanisms.

  6. Effects of snake venom polypeptides on central nervous system.

    PubMed

    Osipov, Alexey; Utkin, Yuri

    2012-12-01

    The nervous system is a primary target for animal venoms as the impairment of its function results in the fast and efficient immobilization or death of a prey. There are numerous evidences about effects of crude snake venoms or isolated toxins on peripheral nervous system. However, the data on their interactions with the central nervous system (CNS) are not abundant, as the blood-brain barrier (BBB) impedes penetration of these compounds into brain. This updated review presents the data about interaction of snake venom polypeptides with CNS. Such data will be described according to three main modes of interactions: - Direct in vivo interaction of CNS with venom polypeptides either capable to penetrate BBB or injected into the brain. - In vitro interactions of cell or sub-cellular fractions of CNS with crude venoms or purified toxins. - Indirect effects of snake venoms or their components on functioning of CNS under different conditions. Although the venom components penetrating BBB are not numerous, they seem to be the most suitable candidates for the leads in drug design. The compounds with other modes of action are more abundant and better studied, but the lack of the data about their ability to penetrate BBB may substantially aggravate the potentials for their medical perspectives. Nevertheless, many such compounds are used for research of CNS in vitro. These investigations may give invaluable information for understanding the molecular basis of CNS diseases and thus lay the basis for targeted drug design. This aspect also will be outlined in the review.

  7. Gangliosides in the Nervous System: Biosynthesis and Degradation

    NASA Astrophysics Data System (ADS)

    Yu, Robert K.; Ariga, Toshio; Yanagisawa, Makoto; Zeng, Guichao

    Gangliosides, abundant in the nervous system, are known to play crucial modulatory roles in cellular recognition, interaction, adhesion, and signal transduction, particularly during early developmental stages. The expression of gangliosides in the nervous system is developmentally regulated and is closely related to the differentiation state of the cell. Ganglioside biosynthesis occurs in intracellular organelles, from which gangliosides are transported to the plasma membrane. During brain development, the ganglioside composition of the nervous system undergoes remarkable changes and is strictly regulated by the activities of glycosyltransferases, which can occur at different levels of control, including glycosyltransferase gene transcription and posttranslational modification. Genes for glycosyltransferase involved in ganglioside biosynthesis have been cloned and classified into families of glycosyltransferases based on their amino acid sequence similarities. The donor and acceptor substrate specificities are determined by enzymatic analysis of the glycosyltransferase gene products. Cell-type specific regulation of these genes has also been studied. Gangliosides are degraded by lysosomal exoglycosidases. The action of these enzymes occurs frequently in cooperation with activator proteins. Several human diseases are caused by defects of degradative enzymes, resulting in massive accumulation of certain glycolipids, including gangliosides in the lysosomal compartment and other organelles in the brain and visceral organs. Some of the representative lysosomal storage diseases (LSDs) caused by the accumulation of lipids in late endosomes and lysosomes will be discussed.

  8. Heterogeneity of nervous system mitochondria: location, location, location!

    PubMed

    Dubinsky, Janet M

    2009-08-01

    Mitochondrial impairments have been associated with many neurological disorders, from inborn errors of metabolism or genetic disorders to age and environmentally linked diseases of aging (DiMauro S., Schon E.A. 2008. Mitochondrial disorders in the nervous system. Annu. Rev., Neurosci. 31, 91-123.). In these disorders, specific nervous system components or brain regions appear to be initially more susceptible to the triggering event or pathological process. Such regional variation in susceptibility to multiple types of stressors raises the possibility that inherent differences in mitochondrial function may mediate some aspect of pathogenesis. Regional differences in the distribution or number of mitochondria, mitochondrial enzyme activities, enzyme expression levels, mitochondrial genes or availability of necessary metabolites become attractive explanations for selective vulnerability of a nervous system structure. While regionally selective mitochondrial vulnerability has been documented, regional variations in other cellular and tissue characteristics may also contribute to metabolic impairment. Such environmental variables include high tonic firing rates, neurotransmitter phenotype, location of mitochondria within a neuron, or the varied tissue perfusion pressure of different cerebral arterial branches. These contextual variables exert regionally distinct regulatory influences on mitochondria to tune their energy production to local demands. Thus to understand variations in mitochondrial functioning and consequent selective vulnerability to injury, the organelle must be placed within the context of its cellular, functional, developmental and neuroanatomical environment.

  9. Centralization of the deuterostome nervous system predates chordates.

    PubMed

    Nomaksteinsky, Marc; Röttinger, Eric; Dufour, Héloïse D; Chettouh, Zoubida; Lowe, Chris J; Martindale, Mark Q; Brunet, Jean-François

    2009-08-11

    The origin of the chordate central nervous system (CNS) is unknown. One theory is that a CNS was present in the first bilaterian and that it gave rise to both the ventral cord of protostomes and the dorsal cord of deuterostomes. Another theory proposes that the chordate CNS arose by a dramatic process of dorsalization and internalization from a diffuse nerve net coextensive with the skin of the animal, such as enteropneust worms (Hemichordata, Ambulacraria) are supposed to have. We show here that juvenile and adult enteropneust worms in fact have a bona fide CNS, i.e., dense agglomerations of neurons associated with a neuropil, forming two cords, ventral and dorsal. The latter is internalized in the collar as a chordate-like neural tube. Contrary to previous assumptions, the greater part of the adult enteropneust skin is nonneural, although elements of the peripheral nervous system (PNS) are found there. We use molecular markers to show that several neuronal types are anatomically segregated in the CNS and PNS. These neuroanatomical features, whatever their homologies with the chordate CNS, imply that nervous system centralization predates the evolutionary separation of chordate and hemichordate lineages.

  10. Radon exposure and tumors of the central nervous system.

    PubMed

    Ruano-Ravina, Alberto; Dacosta-Urbieta, Ana; Barros-Dios, Juan Miguel; Kelsey, Karl T

    2017-03-15

    To review the published evidence of links between radon exposure and central nervous system tumors through a systematic review of the scientific literature. We performed a thorough bibliographic search in Medline (PubMed) and EMBASE. We combined MeSH (Medical Subject Heading) terms and free text. We developed a purpose-designed scale to assess the quality of the included manuscripts. We have included 18 studies, 8 performed on miners, 3 on the general population and 7 on children, and the results have been structured using this classification. The results are inconclusive. An association between radon exposure and central nervous system tumors has been observed in some studies on miners, but not in others. The results observed in the general adult population and in children are also mixed, with some research evincing a statistically significant association and others showing no effect. We cannot conclude that there is a relationship between radon exposure and central nervous system tumors. The available studies are extremely heterogeneous in terms of design and populations studied. Further research is needed in this topic, particularly in the general population residing in areas with high levels of radon. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. FoxO Proteins in the Nervous System

    PubMed Central

    Maiese, Kenneth

    2015-01-01

    Acute as well as chronic disorders of the nervous system lead to significant morbidity and mortality for millions of individuals globally. Given the ability to govern stem cell proliferation and differentiated cell survival, mammalian forkhead transcription factors of the forkhead box class O (FoxO) are increasingly being identified as potential targets for disorders of the nervous system, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and auditory neuronal disease. FoxO proteins are present throughout the body, but they are selectively expressed in the nervous system and have diverse biological functions. The forkhead O class transcription factors interface with an array of signal transduction pathways that include protein kinase B (Akt), serum- and glucocorticoid-inducible protein kinase (SgK), IκB kinase (IKK), silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), growth factors, and Wnt signaling that can determine the activity and integrity of FoxO proteins. Ultimately, there exists a complex interplay between FoxO proteins and their signal transduction pathways that can significantly impact programmed cell death pathways of apoptosis and autophagy as well as the development of clinical strategies for the treatment of neurodegenerative disorders. PMID:26171319

  12. Gross anatomy and development of the peripheral nervous system.

    PubMed

    Catala, Martin; Kubis, Nathalie

    2013-01-01

    The nervous system is divided into the central nervous system (CNS) composed of the brain, the brainstem, the cerebellum, and the spinal cord and the peripheral nervous system (PNS) made up of the different nerves arising from the CNS. The PNS is divided into the cranial nerves III to XII supplying the head and the spinal nerves that supply the upper and lower limbs. The general anatomy of the PNS is organized according to the arrangement of the fibers along the rostro-caudal axis. The control of the development of the PNS has been unravelled during the last 30 years. Motor nerves arise from the ventral neural tube. This ventralization is induced by morphogenetic molecules such as sonic hedgehog. In contrast, the sensory elements of the PNS arise from a specific population of cells originating from the roof of the neural tube, namely the neural crest. These cells give rise to the neurons of the dorsal root ganglia, the autonomic ganglia and the paraganglia including the adrenergic neurons of the adrenals. Furthermore, the supportive glial Schwann cells of the PNS originate from the neural crest cells. Growth factors as well as myelinating proteins are involved in the development of the PNS.

  13. Functional roles of neuropeptides in the insect central nervous system

    NASA Astrophysics Data System (ADS)

    Nässel, D. R.

    With the completion of the Drosophila genome sequencing project we can begin to appreciate the extent of the complexity in the components involved in signal transfer and modulation in the nervous system of an animal with reasonably complex behavior. Of all the different classes of signaling substances utilized by the nervous system, the neuropeptides are the most diverse structurally and functionally. Thus peptidergic mechanisms of action in the central nervous system need to be analyzed in the context of the neuronal circuits in which they act and generalized traits cannot be established. By taking advantage of Drosophila molecular genetics and the presence of identifiable neurons, it has been possible to interfere with peptidergic signaling in small populations of central neurons and monitor the consequences on behavior. These studies and experiments on other insects with large identifiable neurons, permitting cellular analysis of signaling mechanisms, have outlined important principles for temporal and spatial action of neuropeptides in outputs of the circadian clock and in orchestrating molting behavior. Considering the large number of neuropeptides available in each insect species and their diverse distribution patterns, it is to be expected that different neuropeptides play roles in most aspects of insect physiology and behavior.

  14. Efficacy of alectinib in central nervous system metastases in crizotinib-resistant ALK-positive non-small-cell lung cancer: Comparison of RECIST 1.1 and RANO-HGG criteria.

    PubMed

    Gandhi, Leena; Ou, Sai-Hong Ignatius; Shaw, Alice T; Barlesi, Fabrice; Dingemans, Anne-Marie C; Kim, Dong-Wan; Camidge, D Ross; Hughes, Brett G M; Yang, James C-H; de Castro, Javier; Crino, Lucio; Léna, Hervé; Do, Pascal; Golding, Sophie; Bordogna, Walter; Zeaiter, Ali; Kotb, Ahmed; Gadgeel, Shirish

    2017-09-01

    Central nervous system (CNS) progression is common in patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) receiving crizotinib. Next-generation ALK inhibitors have shown activity against CNS metastases, but accurate assessment of response and progression is vital. Data from two phase II studies in crizotinib-refractory ALK+ NSCLC were pooled to examine the CNS efficacy of alectinib, a CNS-active ALK inhibitor, using Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) and Response Assessment in Neuro-Oncology high-grade glioma (RANO-HGG) criteria. Both studies enrolled patients aged ≥18 years who had previously received crizotinib. NP28761 was conducted in North America and NP28673 was a global study. All patients received 600 mg oral alectinib twice daily and had baseline CNS imaging. CNS response for those with baseline CNS metastases was determined by an independent review committee. Baseline measurable CNS disease was identified in 50 patients by RECIST and 43 by RANO-HGG. CNS objective response rate was 64.0% by RECIST (95% confidence interval [CI]: 49.2-77.1; 11 CNS complete responses [CCRs]) and 53.5% by RANO-HGG (95% CI: 37.7-68.8; eight CCRs). CNS responses were durable, with consistent estimates of median duration of 10.8 months with RECIST and 11.1 months with RANO-HGG. Of the 39 patients with measurable CNS disease by both RECIST and RANO-HGG, only three (8%) had CNS progression according to one criteria but not the other (92% concordance rate). Alectinib demonstrated promising efficacy in the CNS for ALK+ NSCLC patients pretreated with crizotinib, regardless of the assessment criteria used. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Whole-brain radiotherapy and high-dose methylprednisolone for elderly patients with primary central nervous system lymphoma: Results of North Central Cancer Treatment Group (NCCTG) 96-73-51

    SciTech Connect

    Laack, Nadia N.; Ballman, Karla V.; Brown, Paul B.; O'Neill, Brian Patrick . E-mail: boneill@mayo.edu

    2006-08-01

    Purpose: The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radiotherapy-treated (WBRT) and high-dose methylprednisolone (HDMP)-treated in elderly patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients with PCNSL who were 70 years and older received 1 g of methylprednisolone daily for 5 days, 30 days after WBRT. Patients then received 1 g of methylprednisolone every 28 days until progression. The primary endpoint was overall survival (OS) at 6 months. Results were compared with those in patients on the previous North Central Cancer Treatment Group (NCCTG) trial who received pre-WBRT cytoxan, adriamycin, vincristine, prednisone (CHOP) and high-dose cytarabine (CHOP-WBRT). A planned interim analysis was performed. The current regimen would be considered inactive if survival was not improved from patients treated with CHOP-WBRT. Results: Nineteen patients were accrued between 1998 and 2003. Median age was 76 years. Interim analysis revealed a 6-month survival of 33%, resulting in closure of the trial. Toxicity, OS, and event-free survival (EFS) were similar to those in patients more than 70 years of age who received CHOP-WBRT. The subgroup of patients who received HDMP had longer OS (12.1 vs. 7.0 months, p = 0.76) and EFS (11.7 vs. 4.0 months, p = 0.04) compared with the CHOP-WBRT patients alive 60 days after the start of treatment. Conclusions: Patients on-study long enough to receive HDMP had prolongation of OS and EFS compared to patients receiving CHOP-WBRT. Although the numbers of patients are too small for statistical conclusions, the HDMP regimen deserves further study.

  16. Fourier domain OCT imaging of American cockroach nervous system

    NASA Astrophysics Data System (ADS)

    Wyszkowska, Joanna; Gorczynska, Iwona; Ruminski, Daniel; Karnowski, Karol; Kowalczyk, Andrzej; Stankiewicz, Maria; Wojtkowski, Maciej

    2012-01-01

    In this pilot study we demonstrate results of structural Fourier domain OCT imaging of the nervous system of Periplaneta americana L. (American cockroach). The purpose of this research is to develop an OCT apparatus enabling structural imaging of insect neural system. Secondary purpose of the presented research is to develop methods of the sample preparation and handling during the OCT imaging experiments. We have performed imaging in the abdominal nerve cord excised from the American cockroach. For this purpose we have developed a Fourier domain / spectral OCT system operating at 820 nm wavelength range.

  17. Patterning the nervous system through development and evolution.

    PubMed

    Ghysen, Alain; Dambly-Chaudière, Christine; Raible, David W

    2010-01-01

    We report presentations and discussions at a meeting held in May 2010 in the small village of Minerve, in the south of France. The meeting was devoted mostly but not exclusively to patterning in the nervous system, with an emphasis on two model organisms, Drosophila Melanogaster and Danio rerio. Among the major issues presented were fear and its neuroanatomy, life in darkness, patterning of sensory systems, as well as fundamental issues of neural connectivity, including the role of lineage in neural development. Talks on large-scale patterning and re-patterning, and on the mouse as a third model system, concluded the meeting.

  18. Images of the nervous system in Cajal's scientific thought.

    PubMed

    Barona, J L

    1999-01-01

    Since his death in 1934, a wide range of publications have outlined Santiago Ramon y Cajal's (1852-1934) scientific personality as well as his contribution to the acceptance of the neuron theory. Trying to go beyond the traditional biographical approach, the present paper aims to set up the historical origins and the development of his scientific conributions. His global image of the nervous system, the neuron theory and other aspects of his scientific views are also related to his intellectual background. Not only his scientific papers, but also his own remembrances, biographical texts and general reflections are taken into account to describe the historical context of Cajal's scientific work, his discovery of the dynamic polarization of neuron cells and his contributions to the knowledge of the texture of the nervous centers and cells, the regeneration and degeneration of nerves, as well as Cajal's scientific bibliogaphy.

  19. Lysophosphatidic acid (LPA) signaling in the nervous system

    PubMed Central

    Yung, Yun C.; Stoddard, Nicole C.; Mirendil, Hope; Chun, Jerold

    2015-01-01

    Summary The brain is composed of many lipids with varied forms that serve not only as structural components but also as essential signaling molecules. Lysophosphatidic acid (LPA) is an important bioactive lipid species that is part of the lysophospholipid (LP) family. LPA is primarily derived from membrane phospholipids and signals through six cognate G protein-coupled receptors (GPCRs), LPA1-6. These receptors are expressed on most cell types within central and peripheral nervous tissues and have been functionally linked to many neural processes and pathways. This review covers a current understanding of LPA signaling in the nervous system, with particular focus on the relevance of LPA to both physiological and diseased states. PMID:25695267

  20. Central nervous system dysfunction in obesity-induced hypertension.

    PubMed

    Head, Geoffrey A; Lim, Kyungjoon; Barzel, Benjamin; Burke, Sandra L; Davern, Pamela J

    2014-09-01

    The activation of the sympathetic nervous system is a major mechanism underlying both human and experimental models of obesity-related hypertension. While insulin and the adipokine leptin have long been thought to contribute to obesity-related neurogenic mechanisms, the evidence is now very strong that they play a major role, shown particularly in animal studies using selective receptor antagonists. There is not just maintenance of leptin's sympatho-excitatory actions as previously suggested but considerable amplification particularly in renal sympathetic nervous activity. Importantly, these changes are not dependent on short-term elevation or reduction in plasma leptin or insulin, but require some weeks to develop indicating a slow "neural adaptivity" within hypothalamic signalling. These effects can be carried across generations even when offspring are raised on a normal diet. A better understanding of the underlying mechanism should be a high research priority given the prevalence of obesity not just in the current population but also for future generations.

  1. [Electroencephalography and the general physiology of the nervous system].

    PubMed

    Wyss, O A

    1974-01-01

    The contributions of electro-encephalography to the general physiology of the nervous system - studies based on 50 years of experimental and clinical research on the EEG of animals and man - have established irrefutable facts underlying present-day concepts in neurophysiology. This conclusion holds true, even if allowance must be made with regard to the alpha-rhythm, reasons having been given to suppose that this phenomenon is in reality, partially or entirely, an ocular tremor phenomenon (Lippold). The fundamental principles of neuronal activity such as (1) the electrogenesis of gray matter, i.e., the electric current and membrane potential aspects of the existence and the functioning of nerve cells and neuronal aggregates, (2) the rhythmicity and periodicity of nervous activity in single cells or networks of neurones, (3) the synchronization of such nervous activity due, at the site of its source, to electric interaction between neurones belonging together and 'beating in unison', and (4) the autonomous automaticity of nerve cells and nerve centres as being the basic feature of neuronal activity, are among the prominent topics dealt with in this report. Particular attention is paid to the autonomy-concept of nervous activity, a concept ofter forgotten, neglected or discarded from physiological thinking, although life of any kind, in any type of living system, can only be understood if spontaneous existence and activity are accepted for living matter. In this respect the EEG has contributed in a large measure to save the physiology of our period from the materialism which prevailed at the beginning of the century and which threatens once more to emerge towards its end.

  2. [Frontiers in Live Bone Imaging Researches. Functional cross talk between bone and nervous system].

    PubMed

    Fukuda, Toru; Takeda, Shu

    2015-06-01

    Bone homeostasis is maintained by bone formation and bone resorption. The traditional view of bone metabolism as a primarily endocrine regulation has been expanded in recent years following the identification of nervous system controlling bone metabolism. Especially, sympathetic and parasympathetic nervous system regulates bone formation and bone resorption. In addition, sensory nervous system also has been shown to be involved in the regulation of bone homeostasis. These studies demonstrated that nervous system is closely related to bone remodeling.

  3. Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA.

    PubMed

    Krop, I E; Lin, N U; Blackwell, K; Guardino, E; Huober, J; Lu, M; Miles, D; Samant, M; Welslau, M; Diéras, V

    2015-01-01

    We characterized the incidence of central nervous system (CNS) metastases after treatment with trastuzumab emtansine (T-DM1) versus capecitabine-lapatinib (XL), and treatment efficacy among patients with pre-existing CNS metastases in the phase III EMILIA study. In EMILIA, patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer previously treated with trastuzumab and a taxane were randomized to T-DM1 or XL until disease progression. Patients with treated, asymptomatic CNS metastases at baseline and patients developing postbaseline CNS metastases were identified retrospectively by independent review; exploratory analyses were carried out. Among 991 randomized patients (T-DM1 = 495; XL = 496), 95 (T-DM1 = 45; XL = 50) had CNS metastases at baseline. CNS progression occurred in 9 of 450 (2.0%) and 3 of 446 (0.7%) patients without CNS metastases at baseline in the T-DM1 and XL arms, respectively, and in 10 of 45 (22.2%) and 8 of 50 (16.0%) patients with CNS metastases at baseline. Among patients with CNS metastases at baseline, a significant improvement in overall survival (OS) was observed in the T-DM1 arm compared with the XL arm [hazard ratio (HR) = 0.38; P = 0.008; median, 26.8 versus 12.9 months]. Progression-free survival by independent review was similar in the two treatment arms (HR = 1.00; P = 1.000; median, 5.9 versus 5.7 months). Multivariate analyses demonstrated similar results. Grade ≥3 adverse events were reported in 48.8% and 63.3% of patients with CNS metastases at baseline administered T-DM1 and XL, respectively; no new safety signals were observed. In this retrospective, exploratory analysis, the rate of CNS progression in patients with HER2-positive advanced breast cancer was similar for T-DM1 and for XL, and higher overall in patients with CNS metastases at baseline compared with those without CNS metastases at baseline. In patients with treated, asymptomatic CNS metastases at baseline, T-DM1 was associated

  4. Eag1 K+ Channel: Endogenous Regulation and Functions in Nervous System

    PubMed Central

    Tokay, Tursonjan; Zhang, Guangming; Sun, Peng

    2017-01-01

    Ether-à-go-go1 (Eag1, Kv10.1, KCNH1) K+ channel is a member of the voltage-gated K+ channel family mainly distributed in the central nervous system and cancer cells. Like other types of voltage-gated K+ channels, the EAG1 channels are regulated by a variety of endogenous signals including reactive oxygen species, rendering the EAG1 to be in the redox-regulated ion channel family. The role of EAG1 channels in tumor development and its therapeutic significance have been well established. Meanwhile, the importance of hEAG1 channels in the nervous system is now increasingly appreciated. The present review will focus on the recent progress on the channel regulation by endogenous signals and the potential functions of EAG1 channels in normal neuronal signaling as well as neurological diseases. PMID:28367272

  5. Eag1 K(+) Channel: Endogenous Regulation and Functions in Nervous System.

    PubMed

    Han, Bo; Tokay, Tursonjan; Zhang, Guangming; Sun, Peng; Hou, Shangwei

    2017-01-01

    Ether-à-go-go1 (Eag1, Kv10.1, KCNH1) K(+) channel is a member of the voltage-gated K(+) channel family mainly distributed in the central nervous system and cancer cells. Like other types of voltage-gated K(+) channels, the EAG1 channels are regulated by a variety of endogenous signals including reactive oxygen species, rendering the EAG1 to be in the redox-regulated ion channel family. The role of EAG1 channels in tumor development and its therapeutic significance have been well established. Meanwhile, the importance of hEAG1 channels in the nervous system is now increasingly appreciated. The present review will focus on the recent progress on the channel regulation by endogenous signals and the potential functions of EAG1 channels in normal neuronal signaling as well as neurological diseases.

  6. Molecular mechanisms underlying the effects of statins in the central nervous system.

    PubMed

    McFarland, Amelia J; Anoopkumar-Dukie, Shailendra; Arora, Devinder S; Grant, Gary D; McDermott, Catherine M; Perkins, Anthony V; Davey, Andrew K

    2014-11-10

    3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins' effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins' effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system. This review aims to provide an updated discussion on the molecular mechanisms contributing to statins' possible effects on cognitive function, neurodegenerative disease, and various neurological disorders such as stroke, epilepsy, depression and CNS cancers. Additionally, the pharmacokinetic differences between statins and how these may result in statin-specific neurological effects are also discussed.

  7. Molecular Mechanisms Underlying the Effects of Statins in the Central Nervous System

    PubMed Central

    McFarland, Amelia J.; Anoopkumar-Dukie, Shailendra; Arora, Devinder S.; Grant, Gary D.; McDermott, Catherine M.; Perkins, Anthony V.; Davey, Andrew K.

    2014-01-01

    3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins’ effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins’ effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system. This review aims to provide an updated discussion on the molecular mechanisms contributing to statins’ possible effects on cognitive function, neurodegenerative disease, and various neurological disorders such as stroke, epilepsy, depression and CNS cancers. Additionally, the pharmacokinetic differences between statins and how these may result in statin-specific neurological effects are also discussed. PMID:25391045

  8. 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.

  9. Hepatic Control of Energy Metabolism via the Autonomic Nervous System

    PubMed Central

    2017-01-01

    Although the human liver comprises approximately 2.8% of the body weight, it plays a central role in the control of energy metabolism. While the biochemistry of energy substrates such as glucose, fatty acids, and ketone bodies in the liver is well understood, many aspects of the overall control system for hepatic metabolism remain largely unknown. These include mechanisms underlying the ascertainment of its energy metabolism status by the liver, and the way in which this information is used to communicate and function together with adipose tissues and other organs involved in energy metabolism. This review article summarizes hepatic control of energy metabolism via the autonomic nervous system. PMID:27592630

  10. Insulin-like growth factors in the peripheral nervous system.

    PubMed

    Sakowski, Stacey A; Feldman, Eva L

    2012-06-01

    Insulin-like growth factors (IGFs) play an integral role in development, growth, and survival. This article details the current understanding of the effects of IGFs in the peripheral nervous system (PNS) during health and disease, and introduces how the IGF system regulates PNS development and impacts growth and survival of PNS cells. Also discussed are implications of IGF signaling in neurodegeneration and the status and prospects of IGF therapies for PNS conditions. There is substantial support for the application of IGF therapies in the treatment of PNS injury and disease.

  11. Vestigial expression in the Drosophila embryonic central nervous system.

    PubMed

    Guss, Kirsten A; Mistry, Hemlata; Skeath, James B

    2008-09-01

    The Drosophila central nervous system is an excellent model system in which to resolve the genetic and molecular control of neuronal differentiation. Here we show that the wing selector vestigial is expressed in discrete sets of neurons. We track the axonal trajectories of VESTIGIAL-expressing cells in the ventral nerve cord and show that these cells descend from neuroblasts 1-2, 5-1, and 5-6. In addition, along the midline, VESTIGIAL is expressed in ventral unpaired median motorneurons and cells that may descend from the median neuroblast. These studies form the requisite descriptive foundation for functional studies addressing the role of vestigial during interneuron differentiation.

  12. Inflammatory diseases of the central nervous system in dogs.

    PubMed

    Thomas, W B

    1998-08-01

    Inflammatory diseases of the central nervous system (CNS) are important causes of seizures in dogs. Specific diseases include canine distemper, rabies, cryptococcosis, coccidioidomycosis, toxoplasmosis, neosporosis, Rocky Mountain spotted fever, ehrlichiosis, granulomatous meningoencephalomyelitis, and pug dog encephalitis. Inflammatory disorders should be considered when a dog with seizures has persistent neurological deficits, suffers an onset of seizures at less than 1 or greater than 5 years of age, or exhibits signs of systemic illness. A thorough history, examination, and analysis of cerebrospinal fluid are important in the diagnosis of inflammatory diseases. However, even with extensive diagnostic testing, a specific etiology is identified in less than two thirds of dogs with inflammatory diseases of the CNS.

  13. Hepatic Control of Energy Metabolism via the Autonomic Nervous System.

    PubMed

    Yahagi, Naoya

    2017-01-01

    Although the human liver comprises approximately 2.8% of the body weight, it plays a central role in the control of energy metabolism. While the biochemistry of energy substrates such as glucose, fatty acids, and ketone bodies in the liver is well understood, many aspects of the overall control system for hepatic metabolism remain largely unknown. These include mechanisms underlying the ascertainment of its energy metabolism status by the liver, and the way in which this information is used to communicate and function together with adipose tissues and other organs involved in energy metabolism.This review article summarizes hepatic control of energy metabolism via the autonomic nervous system.

  14. Cancer in Patients With Gabapentin (GPRD)

    ClinicalTrials.gov

    2012-02-02

    Pain, Neuropathic; Epilepsy; Renal Pelvis Cancer; Pancreatic Cancer; Breast Cancer; Nervous System Cancer; Chronic Pancreatitis; Stomach Cancer; Renal Cell Carcinoma; Diabetes; Bladder Cancer; Bone and Joint Cancer; Penis Cancer; Anal Cancer; Cancer; Renal Cancer

  15. Effect of Artificial Gravity: Central Nervous System Neurochemical Studies

    NASA Technical Reports Server (NTRS)

    Fox, Robert A.; D'Amelio, Fernando; Eng, Lawrence F.

    1997-01-01

    The major objective of this project was to assess chemical and morphological modifications occurring in muscle receptors and the central nervous system of animals subjected to altered gravity (2 x Earth gravity produced by centrifugation and simulated micro gravity produced by hindlimb suspension). The underlying hypothesis for the studies was that afferent (sensory) information sent to the central nervous system by muscle receptors would be changed in conditions of altered gravity and that these changes, in turn, would instigate a process of adaptation involving altered chemical activity of neurons and glial cells of the projection areas of the cerebral cortex that are related to inputs from those muscle receptors (e.g., cells in the limb projection areas). The central objective of this research was to expand understanding of how chronic exposure to altered gravity, through effects on the vestibular system, influences neuromuscular systems that control posture and gait. The project used an approach in which molecular changes in the neuromuscular system were related to the development of effective motor control by characterizing neurochemical changes in sensory and motor systems and relating those changes to motor behavior as animals adapted to altered gravity. Thus, the objective was to identify changes in central and peripheral neuromuscular mechanisms that are associated with the re-establishment of motor control which is disrupted by chronic exposure to altered gravity.

  16. Measuring cardiac autonomic nervous system (ANS) activity in children.

    PubMed

    van Dijk, Aimée E; van Lien, René; van Eijsden, Manon; Gemke, Reinoud J B J; Vrijkotte, Tanja G M; de Geus, Eco J

    2013-04-29

    The autonomic nervous system (ANS) controls mainly automatic bodily functions that are engaged in homeostasis, like heart rate, digestion, respiratory rate, salivation, perspiration and renal function. The ANS has two main branches: the sympathetic nervous system, preparing the human body for action in times of danger and stress, and the parasympathetic nervous system, which regulates the resting state of the body. ANS activity can be measured invasively, for instance by radiotracer techniques or microelectrode recording from superficial nerves, or it can be measured non-invasively by using changes in an organ's response as a proxy for changes in ANS activity, for instance of the sweat glands or the heart. Invasive measurements have the highest validity but are very poorly feasible in large scale samples where non-invasive measures are the preferred approach. Autonomic effects on the heart can be reliably quantified by the recording of the electrocardiogram (ECG) in combination with the impedance cardiogram (ICG), which reflects the changes in thorax impedance in response to respiration and the ejection of blood from the ventricle into the aorta. From the respiration and ECG signals, respiratory sinus arrhythmia can be extracted as a measure of cardiac parasympathetic control. From the ECG and the left ventricular ejection signals, the preejection period can be extracted as a measure of cardiac sympathetic control. ECG and ICG recording is mostly done in laboratory settings. However, having the subjects report to a laboratory greatly reduces ecological validity, is not always doable in large scale epidemiological studies, and can be intimidating for young children. An ambulatory device for ECG and ICG simultaneously resolves these three problems. Here, we present a study design for a minimally invasive and rapid assessment of cardiac autonomic control in children, using a validated ambulatory device (1-5), the VU University Ambulatory Monitoring System (VU

  17. Regulation of autonomic nervous system in space and magnetic storms

    NASA Astrophysics Data System (ADS)

    Baevsky, R. M.; Petrov, V. M.; Chernikova, A. G.

    Variations in the earth's magnetic field and magnetic storms are known to be a risk factor for the development of cardiovascular disorders. The main ``targets'' for geomagnetic perturbations are the central nervous system and the neural regulation of vascular tone and heart rate variability. This paper presents the data about effect of geomagnetic fluctuations on human body in space. As a method for research the analysis of heart rate variability was used, which allows evaluating the state of the sympathetic and parasympathetic parts of the autonomic nervous system, vasomotor center and subcortical neural centers activity. Heart rate variability data were analyzed for 30 cosmonauts at the 2-nd day of space flight on transport spaceship Soyuz (32nd orbit). There were formed three groups of cosmonauts: without magnetic storm (n=9), on a day with magnetic storm (n=12) and 1-2 days after magnetic storm (n=9). The present study was the first to demonstrate a specific impact of geomagnetic perturbations on the system of autonomic circulatory control in cosmonauts during space flight. The increasing of highest nervous centers activity was shown for group with magnetic storms, which was more significant on 1-2 days after magnetic storm. The use of discriminate analysis allowed to classify indicated three groups with 88 % precision. Canonical variables are suggested to be used as criterions for evaluation of specific and non-specific components of cardiovascular reactions to geomagnetic perturbations. The applied aspect of the findings from the present study should be emphasized. They show, in particular, the need to supplement the medical monitoring of cosmonauts with predictions of probable geomagnetic perturbations in view of the prevention of unfavorable states appearances if the adverse reactions to geomagnetic perturbations are added to the tension experienced by regulatory systems during various stresses situations (such as work in the open space).

  18. Regulation of autonomic nervous system in space and magnetic storms.

    PubMed

    Baevsky, R M; Petrov, V M; Chernikova, A G

    1998-01-01

    Variations in the earth's magnetic field and magnetic storms are known to be a risk factor for the development of cardiovascular disorders. The main "targets" for geomagnetic perturbations are the central nervous system and the neural regulation of vascular tone and heart rate variability. This paper presents the data about effect of geomagnetic fluctuations on human body in space. As a method for research the analysis of heart rate variability was used, which allows evaluating the state of the sympathetic and parasympathetic parts of the autonomic nervous system, vasomotor center and subcortical neural centers activity. Heart rate variability data were analyzed for 30 cosmonauts at the 2nd day of space flight on transport spaceship Soyuz (32nd orbit). There were formed three groups of cosmonauts: without magnetic storm (n=9), on a day with magnetic storm (n=12) and 1-2 days after magnetic storm (n=9). The present study was the first to demonstrate a specific impact of geomagnetic perturbations on the system of autonomic circulatory control in cosmonauts during space flight. The increasing of highest nervous centers activity was shown for group with magnetic storms, which was more significant on 1-2 days after magnetic storm. The use of discriminate analysis allowed to classify indicated three groups with 88% precision. Canonical variables are suggested to be used as criterions for evaluation of specific and non-specific components of cardiovascular reactions to geomagnetic perturbations. The applied aspect of the findings from the present study should be emphasized. They show, in particular, the need to supplement the medical monitoring of cosmonauts with predictions of probable geomagnetic perturbations in view of the prevention of unfavorable states appearances if the adverse reactions to geomagnetic perturbations are added to the tension experienced by regulatory systems during various stresses situations (such as work in the open space).

  19. The Adverse Effects of Air Pollution on the Nervous System

    PubMed Central

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  20. [When prions use the systems of communication between the immune system and the peripheral nervous system].

    PubMed

    Dorban, Gauthier; Antoine, Nadine; Defaweux, Valérie

    2010-01-01

    Prion disease pathogenesis has been largely studied since the inter-species transmissibility of the infectious protein (PrPSc), the oral uptake as natural route of infection and the exceptional implication in a problem of public health were highlighted. Two sequential preclinical stages are observed before the development of irreversible and fatal lesions in the central nervous system: the lymphoinvasion and the neuroinvasion. The first is characterized by the accumulation of PrPSc within lymphoid tissues and the second by PrPSc scattering the peripheral nervous system towards the central nervous system. The mechanisms involved in the communication between the immune and the peripheral nervous system are still debated. Recent studies even suggest that neuroinvasion can occur through the hematogenous route, independently of the peripheral nervous system. This review analyses (i) the role of immune cells, implicated in prion pathogenesis: dendritic cells as PrPSc vehicle, follicular dendritic cells as PrPSc accumulator and nerve fibres as PrPSc driver and (ii) the respective relations they maintain with peripheral nerve fibres to migrate to the brain.

  1. Zeb2: A multifunctional regulator of nervous system development.

    PubMed

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

    2015-09-01

    Zinc finger E-box binding homeobox (Zeb) 2 is a transcription factor, identified due its ability to bind Smad proteins, and consists of multiple functional domains which interact with a variety of transcriptional co-effectors. The complex nature of the Zeb2, both at its genetic and protein levels, underlie its multifunctional properties, with Zeb2 capable of acting individually or as part of a transcriptional complex to repress, and occasionally activate, target gene expression. This review introduces Zeb2 as an essential regulator of nervous system development. Zeb2 is expressed in the nervous system throughout its development, indicating its importance in neurogenic and gliogenic processes. Indeed, mutation of Zeb2 has dramatic neurological consequences both in animal models, and in humans with Mowat-Wilson syndrome, which results from heterozygous ZEB2 mutations. The mechanisms by which Zeb2 regulates the induction of the neuroectoderm (CNS primordium) and the neural crest (PNS primordium) are reviewed herein. We then describe how Zeb2 acts to direct the formation, delamination, migration and specification of neural crest cells. Zeb2 regulation of the development of a number of cerebral regions, including the neocortex and hippocampus, are then described. The diverse molecular mechanisms mediating Zeb2-directed development of various neuronal and glial populations are reviewed. The role of Zeb2 in spinal cord and enteric nervous system development is outlined, while its essential function in CNS myelination is also described. Finally, this review discusses how the neurodevelopmental defects of Zeb2 mutant mice delineate the developmental dysfunctions underpinning the multiple neurological defects observed in Mowat-Wilson syndrome patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Applications of Nanotechnology to the Central Nervous System

    NASA Astrophysics Data System (ADS)

    Blumling, James P., II

    Nanotechnology and nanomaterials, in general, have become prominent areas of academic research. The ability to engineer at the nano scale is critical to the advancement of the physical and medical sciences. In the realm of physical sciences, the applications are clear: smaller circuitry, more powerful computers, higher resolution intruments. However, the potential impact in the fields of biology and medicine are perhaps even grander. The implementation of novel nanodevices is of paramount importance to the advancement of drug delivery, molecular detection, and cellular manipulation. The work presented in this thesis focuses on the development of nanotechnology for applications in neuroscience. The nervous system provides unique challenges and opportunities for nanoscale research. This thesis discusses some background in nanotechnological applications to the central nervous system and details: (1) The development of a novel calcium nanosenser for use in neurons and astrocytes. We implemented the calcium responsive component of Dr. Roger Tsien's Cameleon sensor, a calmodulin-M13 fusion, in the first quantum dot-based calcium sensor. (2) The exploration of cell-penetrating peptides as a delivery mechanism for nanoparticles to cells of the nervous system. We investigated the application of polyarginine sequences to rat primary cortical astrocytes in order to assess their efficacy in a terminally differentiated neural cell line. (3) The development of a cheap, biocompatible alternative to quantum dots for nanosensor and imaging applications. We utilized a positively charged co-matrix to promote the encapsulation of free sulforhodamine B in silica nanoparticles, a departure from conventional reactive dye coupling to silica matrices. While other methods have been invoked to trap dye not directly coupled to silica, they rely on positively charged dyes that typically have a low quantum yield and are not extensively tested biologically, or they implement reactive dyes bound

  3. Enteric nervous system development: migration, differentiation, and disease

    PubMed Central

    Lake, Jonathan I.

    2013-01-01

    The enteric nervous system (ENS) provides the intrinsic innervation of the bowel and is the most neurochemically diverse branch of the peripheral nervous system, consisting of two layers of ganglia and fibers encircling the gastrointestinal tract. The ENS is vital for life and is capable of autonomous regulation of motility and secretion. Developmental studies in model organisms and genetic studies of the most common congenital disease of the ENS, Hirschsprung disease, have provided a detailed understanding of ENS development. The ENS originates in the neural crest, mostly from the vagal levels of the neuraxis, which invades, proliferates, and migrates within the intestinal wall until the entire bowel is colonized with enteric neural crest-derived cells (ENCDCs). After initial migration, the ENS develops further by responding to guidance factors and morphogens that pattern the bowel concentrically, differentiating into glia and neuronal subtypes and wiring together to form a functional nervous system. Molecules controlling this process, including glial cell line-derived neurotrophic factor and its receptor RET, endothelin (ET)-3 and its receptor endothelin receptor type B, and transcription factors such as SOX10 and PHOX2B, are required for ENS development in humans. Important areas of active investigation include mechanisms that guide ENCDC migration, the role and signals downstream of endothelin receptor type B, and control of differentiation, neurochemical coding, and axonal targeting. Recent work also focuses on disease treatment by exploring the natural role of ENS stem cells and investigating potential therapeutic uses. Disease prevention may also be possible by modifying the fetal microenvironment to reduce the penetrance of Hirschsprung disease-causing mutations. PMID:23639815

  4. Enteric nervous system development: migration, differentiation, and disease.

    PubMed

    Lake, Jonathan I; Heuckeroth, Robert O

    2013-07-01

    The enteric nervous system (ENS) provides the intrinsic innervation of the bowel and is the most neurochemically diverse branch of the peripheral nervous system, consisting of two layers of ganglia and fibers encircling the gastrointestinal tract. The ENS is vital for life and is capable of autonomous regulation of motility and secretion. Developmental studies in model organisms and genetic studies of the most common congenital disease of the ENS, Hirschsprung disease, have provided a detailed understanding of ENS development. The ENS originates in the neural crest, mostly from the vagal levels of the neuraxis, which invades, proliferates, and migrates within the intestinal wall until the entire bowel is colonized with enteric neural crest-derived cells (ENCDCs). After initial migration, the ENS develops further by responding to guidance factors and morphogens that pattern the bowel concentrically, differentiating into glia and neuronal subtypes and wiring together to form a functional nervous system. Molecules controlling this process, including glial cell line-derived neurotrophic factor and its receptor RET, endothelin (ET)-3 and its receptor endothelin receptor type B, and transcription factors such as SOX10 and PHOX2B, are required for ENS development in humans. Important areas of active investigation include mechanisms that guide ENCDC migration, the role and signals downstream of endothelin receptor type B, and control of differentiation, neurochemical coding, and axonal targeting. Recent work also focuses on disease treatment by exploring the natural role of ENS stem cells and investigating potential therapeutic uses. Disease prevention may also be possible by modifying the fetal microenvironment to reduce the penetrance of Hirschsprung disease-causing mutations.

  5. Local microwave ablation with continued EGFR tyrosine kinase inhibitor as a treatment strategy in advanced non-small cell lung cancers that developed extra-central nervous system oligoprogressive disease during EGFR tyrosine kinase inhibitor treatment

    PubMed Central

    Ni, Yang; Bi, Jingwang; Ye, Xin; Fan, Weijun; Yu, Guohua; Yang, Xia; Huang, Guanghui; Li, Wenhong; Wang, Jiao; Han, Xiaoying; Ni, Xiang; Wei, Zhigang; Han, Mingyong; Zheng, Aimin; Meng, Min; Xue, Guoliang; Zhang, Liang; Wan, Chao

    2016-01-01

    Abstract The non-small cell lung cancer (NSCLC) patients that experienced good clinical response to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) will ultimately develop acquired resistance. This retrospective study was performed to explore the potential survival benefit of microwave ablation (MWA) therapy in epidermal growth factor receptor (EGFR)-mutant NSCLC that developed extra-central nervous system (CNS) oligoprogressive disease during TKI treatment. We retrospectively analyzed 54 NSCLC patients with EGFR mutations who showed a clinical benefit from initial EGFR-TKI therapy and developed extra-CNS oligoprogressive disease at our institutions. Twenty eight patients received MWA as a local therapy for the metastatic sites and continued on the same TKIs (MWA group). The following 26 patients received systemic chemotherapy after progression (chemotherapy group). The progression-free survival (PFS1) was calculated from initiation of targeted therapy to first progression. Progression-free survival (PFS2) was defined from first progression to second progression after MWA or chemotherapy. Overall survival (OS) was calculated from the time of diagnosis to the date of last follow-up or death. The median PFS1 for both groups was similar (median 12.6 vs. 12.9 months, HR 0.63). However, the MWA group patients had a significantly longer PFS2 (median 8.8 vs. 5.8 months, hazards ratio [HR] 0.357) and better OS (median 27.7 vs. 20.0, HR 0.238) in comparison with chemotherapy group. Multivariate analysis and the internal validation identified MWA as the main favorable prognostic factor for PFS2 and OS. In the MWA group, the median PFS2 for complete ablation was significantly longer than that for incomplete ablation (11 vs. 4.2 months, HR 0.29, P < 0.05). MWA with continued EGFR inhibition might be associated with favorable progression-free survival (PFS) and OS in patients with extra-CNS oligometastatic disease. MWA as a local therapy for extra

  6. Configuring a robust nervous system with Fat cadherins.

    PubMed

    Avilés, Evelyn C; Goodrich, Lisa V

    2017-09-01

    Atypical Fat cadherins represent a small but versatile group of signaling molecules that influence proliferation and tissue polarity. With huge extracellular domains and intracellular domains harboring many independent protein interaction sites, Fat cadherins are poised to translate local cell adhesion events into a variety of cell behaviors. The need for such global coordination is particularly prominent in the nervous system, where millions of morphologically diverse neurons are organized into functional networks. As we learn more about their biological functions and molecular properties, increasing evidence suggests that Fat cadherins mediate contact-induced changes that ultimately impose a structure to developing neuronal circuits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. [Extranuclear functions of protein sumoylation in the central nervous system].

    PubMed

    Martin, Stéphane

    2009-01-01

    Post-translational protein modifications play essential roles in many aspects of cellular functions and therefore in the maintenance of cell integrity. These protein modifications are involved at all stages of neuronal communication within the central nervous system. Sumoylation is a reversible post-translational protein modification that consists in the covalent labelling of a small protein called SUMO to lysine residues of selected target proteins. Sumoylation is a well characterized regulator of nuclear functions and has recently emerged as a key factor for numerous extranuclear processes. Furthermore, sumoylation has recently been shown to modulate synaptic transmission and is also implicated in a wide range of neurodegenerative diseases.

  8. [Primary central nervous system lymphoma: pathogenesis and histomorphology].

    PubMed

    Méhes, Gábor

    2017-03-08

    Lymphoproliferative diseases of the central nervous system are rare, diagnostics and treatment are accordingly challenging. Since the introduction of the 2008 WHO lymphoma classification, primary CNS DLBCL - also covering the associated primary ocular (vitreoretinal) lymphoma - is a separate entity. The special localization is related with a series of newly recognized genetic, genomic and immunologic features directing to the strong interaction between transformed lymphoma cells, neural tissue components and the local immune response. Histological differentiation is frequently disabled by the limited sampling opportunities and requires the application of all available hematopathologic technologies including immunohistochemistry, cytology, liquor serology, flow cytometry, fluorescence in situ hybridization and polymerase chain reaction with sequencing.

  9. [Congenital anomalies of the central nervous system in autopsy specimens].

    PubMed

    Sobaniec-Lotowska, M; Ostapiuk, H; Sulkowski, S; Sobaniec, W; Sulik, M; Famulski, W

    1989-02-01

    On the basis of an analysis of 2398 autopsies of infants aged up to 1 year in 194 cases congenital anomalies of the central nervous system were found (8.1%). Most cases of these anomalies were noted in the group of newborns (85%) and the most frequent anomalies were: myelomeningocele (35.6%), multiple anomalies (20.1%), congenital hydrocephalus (17%), anencephaly (14.4%) and corpus callosum malformations (3.6%). Myelomeningocele, congenital hydrocephalus, anencephaly and true microcephaly were more frequent in girls, while multiple anomalies and corpus callosum malformations were more frequent in boys.

  10. Clinical implications of thyroid hormones effects on nervous system development.

    PubMed

    Carreón-Rodríguez, Alfonso; Pérez-Martínez, Leonor

    2012-03-01

    Thyroid hormones have an important role throughout prenatal and postnatal nervous system development. They are involved in several processes such as neurogenesis, gliogenesis, myelination, synaptogenesis, etc., as shown in many cases of deficiency like congenital hypothyroidism or hypothyroxinemia. Those pathologies if untreated could lead to severe damages in cognitive, motor, neudoendocrine functions among other effects. Some could be reversed after adequate supplementation of thyroid hormones at birth, however there are other cellular processes highly sensitive to low levels of thyroid hormones and lasting a limited period of time during which if thyroid hormone action is lacking or deficient, the functional and structural damages would produce permanent defects.

  11. Herpesvirus Transport to the Nervous System and Back Again

    PubMed Central

    Smith, Gregory

    2013-01-01

    Herpes simplex virus, varicella zoster virus, and pseudorabies virus are neurotropic pathogens of the Alphaherpesvirinae subfamily of the Herpesviridae. These viruses efficiently invade the peripheral nervous system and establish lifelong latency in neurons resident in peripheral ganglia. Primary and recurrent infections cycle virus particles between neurons and the peripheral tissues they innervate. This remarkable cycle of infection is the topic of this review. In addition, some of the distinguishing hallmarks of the infections caused by these viruses are evaluated in terms of their underlying similarities. PMID:22726218

  12. Area 51: How do Acanthamoeba invade the central nervous system?

    PubMed

    Siddiqui, Ruqaiyyah; Emes, Richard; Elsheikha, Hany; Khan, Naveed Ahmed

    2011-05-01

    Acanthamoeba granulomatous encephalitis generally develops as a result of haematogenous spread, but it is unclear how circulating amoebae enter the central nervous system (CNS) and cause inflammation. At present, the mechanisms which Acanthamoeba use to invade this incredibly well-protected area of the CNS and produce infection are not well understood. In this paper, we propose two key virulence factors: mannose-binding protein and extracellular serine proteases as key players in Acanthamoeba traversal of the blood-brain barrier leading to neuronal injury. Both molecules should provide excellent opportunities as potential targets in the rational development of therapeutic interventions against Acanthamoeba encephalitis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Magnetic resonance imaging of the central nervous system

    SciTech Connect

    Brant-Zawadzki, M.; Norman, D.

    1987-01-01

    This text provides an introduction to magnetic resonance imaging (MRI) of disorders of the central nervous system, spine, neck, and nasopharynx. The book offers guidance in performing and interpreting MRI studies for specific clinical problems. Included are more than 800 images showing pathologic findings for various disorders and demonstrating how abnormalities detected in MRI scans can aid both in differential diagnosis and in clinical staging. The book summarizes the basic principles of MRI and describes the major equipment components and contrast agents. A review of the principles and potential applications of magnetic resonance spectroscopy is also included.

  14. Neuroactive steroids and the peripheral nervous system: An update.

    PubMed

    Giatti, Silvia; Romano, Simone; Pesaresi, Marzia; Cermenati, Gaia; Mitro, Nico; Caruso, Donatella; Tetel, Marc J; Garcia-Segura, Luis Miguel; Melcangi, Roberto C

    2015-11-01

    In the present review we summarize observations to date supporting the concept that neuroactive steroids are synthesized in the peripheral nervous system, regulate the physiology of peripheral nerves and exert notable neuroprotective actions. Indeed, neuroactive steroids have been recently proposed as therapies for different types of peripheral neuropathy, like for instance those occurring during aging, chemotherapy, physical injury and diabetes. Moreover, pharmacological tools able to increase the synthesis of neuroactive steroids might represent new interesting therapeutic strategy to be applied in case of peripheral neuropathy.

  15. Current and future imaging of the peripheral nervous system.

    PubMed

    Ohana, M; Moser, T; Moussaouï, A; Kremer, S; Carlier, R Y; Liverneaux, P; Dietemann, J-L

    2014-01-01

    Peripheral nervous system (PNS) imaging is usually carried out by ultrasound and MRI. Thanks to its wide availability and excellent spatial resolution, ultrasound is a mature investigation with clearly established indications, particularly in entrapment syndromes and tumors. MRI is generally a second-line examination, which provides decisive additional information thanks to its excellent contrast resolution and its multiplanar abilities. This review describes the current methods for imaging the PNS, concentrating on acquisition techniques, normal results and basic pathological semiology. Ongoing and future developments are described in order to underline the forthcoming changes in this very dynamic field of musculoskeletal radiology.

  16. Electricity in the treatment of nervous system disease.

    PubMed

    Fodstad, H; Hariz, M

    2007-01-01

    Electricity has been used in medicine for almost two millenniums beginning with electrical chocks from the torpedo fish and ending with the implantation of neuromodulators and neuroprostheses. These implantable stimulators aim to improve functional independence and quality of life in various groups of disabled people. New indications for neuromodulation are still evolving and the field is rapidly advancing. Thanks to modern science and computer technology, electrotherapy has reached a degree of sophistication where it can be applied relatively safely and effectively in a variety of nervous system diseases, including pain, movement disorders, epilepsy, Tourette syndrome, psychiatric disease, addiction, coma, urinary incontinence, impotence, infertility, respiratory paralysis, tinnitus and blindness.

  17. 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.

  18. Neurofeedback: an emerging technology for treating central nervous system dysregulation.

    PubMed

    Larsen, Stephen; Sherlin, Leslie

    2013-03-01

    Neurofeedback is a machine-mediated noninvasive treatment modality based on the analysis and "feeding back" of electroencephalogram brainwaves, which has shown efficacy with a variety of central nervous system-based problems. It has special application where patients have adverse reaction to psychopharmacologic treatments and psychotherapy, cognitive behavioral therapy, and dialectical behavior therapy have proved ineffective. Treatment modalities include active forms based on operant conditioning, involving a subject's response to stimuli. Neurofeedback is strong in clinical confirmations of efficacy (case studies) and has thus far limited controlled studies in the peer-reviewed journals. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Language disorders in children with central nervous system injury

    PubMed Central

    Dennis, Maureen

    2011-01-01

    Children with injury to the central nervous system (CNS) exhibit a variety of language disorders that have been described by members of different disciplines, in different journals, using different descriptors and taxonomies. This paper is an overview of language deficits in children with CNS injury, whether congenital or acquired after a period of normal development. It first reviews the principal CNS conditions associated with language disorders in childhood. It then describes a functional taxonomy of language, with examples of the phenomenology and neurobiology of clinical deficits in children with CNS insults. Finally, it attempts to situate language in the broader realm of cognition and in current theoretical accounts of embodied cognition. PMID:20397297

  20. Central Nervous System Complications of Hemorrhagic and Coagulation Disorders.

    PubMed

    Filatova, Irina; Stratchko, Lindsay L; Kanekar, Sangam

    2016-08-01

    Hematologic disorders affect the central nervous system in a variety of ways, producing a wide range of neurologic disturbances. Early identification of these complications allows for early intervention and better outcome. Cross-sectional imaging plays an important role in identifying brain abnormalities and helps the clinician in deciding appropriate course of action and treatment. This article discuss in short the basics of hemostasis including the coagulation cascade and the application of basic laboratory tests in evaluation of hematologic function. Imaging features of various neurologic disorders associated with these clotting and bleeding diatheses are discussed in detail with illustrations. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. [Metastasis tumors of the central nervous system: molecular biology].

    PubMed

    Bello, M Josefa; González-Gómez, P; Rey, J A

    2004-12-01

    Metastases in the nervous system represent an important and growing problem in the clinical practice, being the cause of a great mortality in the developed countries. This article reviews the few data available on the molecular mechanisms involved in the pathogenesis of these tumours, leading to oncogene activation, inactivation of tumour suppressor genes, not only by the classical mechanisms, but also by the tumour cell epigenetic balance alteration. We conclude that all this knowledge will lead in the future to a better diagnosis, treatment and clinic evolution of these patients.

  2. Central nervous system tuberculosis: pathophysiology and imaging findings.

    PubMed

    Patkar, Deepak; Narang, Jayant; Yanamandala, Rama; Lawande, Malini; Shah, Gaurang V

    2012-11-01

    With the onset of the human immunodeficiency virus pandemic, the incidence of tuberculosis, including central nervous system (CNS) tuberculosis, has increased in developed countries. It is no longer a disease confined to underdeveloped and developing countries. The imaging appearance has become more complex with the onset of multidrug-resistant tuberculosis. Imaging plays an important role in the early diagnosis of CNS tuberculosis and may prevent unnecessary morbidity and mortality. This article presents an extensive review of typical and atypical imaging appearances of intracranial tuberculosis, and discusses pathogenesis, patterns of involvement, and advances in imaging of intracranial tuberculosis.

  3. 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.

  4. Central- and autonomic nervous system coupling in schizophrenia

    PubMed Central

    Schulz, Steffen; Bolz, Mathias; Bär, Karl-Jürgen

    2016-01-01

    The autonomic nervous system (ANS) dysfunction has been well described in schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between the ANS and central brain activity has been not addressed until now in SZ. The interactions between the central nervous system (CNS) and ANS need to be considered as a feedback–feed-forward system that supports flexible and adaptive responses to specific demands. For the first time, to the best of our knowledge, this study investigates central–autonomic couplings (CAC) studying heart rate, blood pressure and electroencephalogram in paranoid schizophrenic patients, comparing them with age–gender-matched healthy subjects (CO). The emphasis is to determine how these couplings are composed by the different regulatory aspects of the CNS–ANS. We found that CAC were bidirectional, and that the causal influence of central activity towards systolic blood pressure was more strongly pronounced than such causal influence towards heart rate in paranoid schizophrenic patients when compared with CO. In paranoid schizophrenic patients, the central activity was a much stronger variable, being more random and having fewer rhythmic oscillatory components. This study provides a more in-depth understanding of the interplay of neuronal and autonomic regulatory processes in SZ and most likely greater insights into the complex relationship between psychotic stages and autonomic activity. PMID:27044986

  5. Heart failure as an autonomic nervous system dysfunction.

    PubMed

    Kishi, Takuya

    2012-03-01

    In heart failure, it has been recognized that the sympathetic nervous system (SNS) is activated and the imbalance of the activity of the SNS and vagal activity interaction occurs. The abnormal activation of the SNS leads to further worsening of heart failure. Many previous clinical and basic studies have demonstrated that the abnormal activation of the SNS is caused by the enhancement of excitatory inputs including changes in: (1) peripheral baroreceptor and chemoreceptor reflexes; (2) chemical mediators that control sympathetic outflow; and (3) central sites that integrate sympathetic outflow. In particular, the abnormalities in central SNS regulation due to the renin angiotensin system-oxidative stress axis have recently been in focus. In the treatment of heart failure, the inhibition of the activated SNS, such as with beta-blockers and/or exercise training, is important. Furthermore, many experimental studies have demonstrated that vagal stimulation has beneficial effects on heart failure, and recently several clinical studies have also demonstrated that vagal stimulation is a possible novel therapy for heart failure. In conclusion, we must recognize that heart failure is a complex syndrome with an autonomic nervous system dysfunction, and that the autonomic imbalance with the activation of the SNS and the reduction of vagal activity should be treated. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  6. Effects of melatonin on nervous system aging: neurogenesis and neurodegeneration.

    PubMed

    Sarlak, Golmaryam; Jenwitheesuk, Anorut; Chetsawang, Banthit; Govitrapong, Piyarat

    2013-09-20

    Neural aging as a progressive loss of function involves central and peripheral post-mitotic neurons and neural stem cells (NSCs). It promotes neurodegeneration, impairs neurogenesis, and can be considered a cause of cognitive impairment and sensory and motor deficits in the elderly. Age-related morphological atrophic changes and cellular alterations are addressed by neural aging mechanisms. Neurogenesis declines during aging through several mechanisms such as an increase in quiescence state, changes in lineage fate, telomerase dysfunction, the failure of the DNA repair system, increased apoptosis, and the impairment of self-renewal. The self-renewal transcriptional factor Sox2 has been correlated with retrotransposon L1 and certain cell-cycle- and epigenetic-related factors, which are sometimes considered age-related factors in NSC aging. As neurogenesis decreases, non-mitotic neurons undergo neurodegeneration by oxidative stress, sirtuin, insulin signaling and mTOR alteration, mitochondrial dysfunction, and protein misfolding and aggregation. As neurodegeneration and impaired neurogenesis promote the nervous system aging process, the identification of neuronal anti-aging is required to raise life expectancy. The role of melatonin in increasing neurogenesis and protecting against neurodegeneration has been investigated. Here, we review nervous system aging that is correlated with mechanisms of neurodegeneration and the impairment of neurogenesis and evaluate the effects of melatonin on these processes.

  7. Ion Channels as Drug Targets in Central Nervous System Disorders

    PubMed Central

    Waszkielewicz, A.M; Gunia, A; Szkaradek, N; Słoczyńska, K; Krupińska, S; Marona, H

    2013-01-01

    Ion channel targeted drugs have always been related with either the central nervous system (CNS), the peripheral nervous system, or the cardiovascular system. Within the CNS, basic indications of drugs are: sleep disorders, anxiety, epilepsy, pain, etc. However, traditional channel blockers have multiple adverse events, mainly due to low specificity of mechanism of action. Lately, novel ion channel subtypes have been discovered, which gives premises to drug discovery process led towards specific channel subtypes. An example is Na+ channels, whose subtypes 1.3 and 1.7-1.9 are responsible for pain, and 1.1 and 1.2 – for epilepsy. Moreover, new drug candidates have been recognized. This review is focusing on ion channels subtypes, which play a significant role in current drug discovery and development process. The knowledge on channel subtypes has developed rapidly, giving new nomenclatures of ion channels. For example, Ca2+ channels are not any more divided to T, L, N, P/Q, and R, but they are described as Cav1.1-Cav3.3, with even newer nomenclature α1A-α1I and α1S. Moreover, new channels such as P2X1-P2X7, as well as TRPA1-TRPV1 have been discovered, giving premises for new types of analgesic drugs. PMID:23409712

  8. Interactions between taurine and ethanol in the central nervous system.

    PubMed

    Olive, M F

    2002-01-01

    This purpose of this review will be to summarize the interactions between the endogenous amino acid taurine and ethyl alcohol (ethanol) in the central nervous system (CNS). Taurine is one of the most abundant amino acids in the CNS and plays an integral role in physiological processes such as osmoregulation, neuroprotection and neuromodulation. Both taurine and ethanol exert positive allosteric modulatory effects on neuronal ligand-gated chloride channels (i.e., GABA(A) and glycine receptors) as well as inhibitory effects on other ligand- and voltage-gated cation channels (i.e., NMDA and Ca(2+) channels). Behavioral evidence suggests that taurine can alter the locomotor stimulatory, sedating, and motivational effects of ethanol in a strongly dose-dependent manner. Microdialysis studies have revealed that ethanol elevates extracellular levels of taurine in numerous brain regions, although the functional consequences of this phenomenon are currently unknown. Finally, taurine and several related molecules including the homotaurine derivative acamprosate (calcium acetylhomotaurinate) can reduce ethanol self-administration and relapse to drinking in both animals and humans. Taken together, these data suggest that the endogenous taurine system may be an important modulator of effects of ethanol on the nervous system, and may represent a novel therapeutic avenue for the development of medications to treat alcohol abuse and alcoholism.

  9. The effect of octopamine on the locust stomatogastric nervous system.

    PubMed

    Rand, David; Knebel, Daniel; Ayali, Amir

    2012-01-01

    Octopamine (OA) is a prominent neuromodulator of invertebrate nervous systems, influencing multiple physiological processes. Among its many roles in insects are the initiation and maintenance of various rhythmic behaviors. Here, the neuromodulatory effects of OA on the components of the locust stomatogastric nervous system were studied, and one putative source of OA modulation of the system was identified. Bath application of OA was found to abolish the endogenous rhythmic output of the fully isolated frontal ganglion (FG), while stimulating motor activity of the fully isolated hypocerebral ganglion (HG). OA also induced rhythmic movements in a foregut preparation with intact HG innervation. Complex dose-dependent effects of OA on interconnected FG-HG preparations were seen: 10(-5) M OA accelerated the rhythmic activity of both the HG and FG in a synchronized manner, while 10(-4) M OA decreased both rhythms. Intracellular stimulation of an identified octopaminergic dorsal unpaired median neuron in the subesophageal ganglion was found to exert a similar effect on the FG motor output as that of OA application. Our findings suggest a mechanism of regulation of insect gut patterns and feeding-related behavior during stress and times of high energy demand.

  10. Gut Commensalism, Cytokines, and Central Nervous System Demyelination

    PubMed Central

    Ochoa-Repáraz, Javier; Kasper, Lloyd H.

    2014-01-01

    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. PMID:25084177

  11. GABA-ergic neurons in the leach central nervous system

    SciTech Connect

    Cline, H.T.

    1985-01-01

    GABA is a candidate for an inhibitory neurotransmitter in the leech central nervous system because of the well-documented inhibitory action of GABA in other invertebrates. To demonstrate that GABA meets the criteria used to identify a substance as a neurotransmitter, the author examined GABA metabolism and synaptic interactions of inhibitory motor neurons in two leech species, Hirudo medicinalis and Haementeria ghilianii. Segmental ganglia of the leech ventral nerve cord and identified inhibitors have the capacity to synthesize GABA when incubated in the presence of the precursor glutamate. Application of GABA to cell bodies of excitatory motor neurons or muscle fibers innervated by the inhibitors hyperpolarizes the membrane potential of the target cell and activates a chloride ion conductance channel, similar to the inhibitory membrane response following intracellular stimulation of the inhibitor. Bicuculline methiodide (5 x 10/sup -5/M), GABA receptor antagonist, blocks reversibly the response to applied GABA and the inhibitory synaptic inputs onto the postsynaptic neurons or muscle fibers without interfering with their excitatory inputs. Furthermore, the inhibitors are included among approximately 25 neurons per segmental ganglion that take up GABA by a high affinity uptake system, as revealed by /sup 3/H-GABA-autoradiography. The development of the capacities to synthesize and to take up GABA were examined in leech embryos. The embryos are able to synthesize GABA at early stages of the development of the nervous system, before any neurons have extended neutrites.

  12. Mechanisms of immunological tolerance in central nervous system inflammatory demyelination.

    PubMed

    Mari, Elisabeth R; Moore, Jason N; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2015-08-01

    Multiple sclerosis is a complex autoimmune disease of the central nervous system that results in a disruption of the balance between pro-inflammatory and anti-inflammatory signals in the immune system. Given that central nervous system inflammation can be suppressed by various immunological tolerance mechanisms, immune tolerance has become a focus of research in the attempt to induce long-lasting immune suppression of pathogenic T cells. Mechanisms underlying this tolerance induction include induction of regulatory T cell populations, anergy and the induction of tolerogenic antigen-presenting cells. The intravenous administration of encephalitogenic peptides has been shown to suppress experimental autoimmune encephalomyelitis and induce tolerance by promoting the generation of regulatory T cells and inducing apoptosis of pathogenic T cells. Safe and effective methods of inducing long-lasting immune tolerance are essential for the treatment of multiple sclerosis. By exploring tolerogenic mechanisms, new strategies can be devised to strengthen the regulatory, anti-inflammatory cell populations thereby weakening the pathogenic, pro-inflammatory cell populations.

  13. Chemokines and their receptors in central nervous system disease.

    PubMed

    Biber, Knut; de Jong, Eiko K; van Weering, Hilmar R J; Boddeke, Hendrikus W G M

    2006-01-01

    Almost a decade ago, it was discovered that the human deficiency virus (HIV) makes use of chemokine receptors to infect blood cells. This appreciation of the clinical relevance of specific chemokine receptors has initiated a considerable boost in the field of chemokine research. It is clear today that chemokine signaling orchestrates the immune system and is widely involved in both physiological and pathophysiological processes. Since the chemokine system offers various targets through which pathology could be influenced, most pharmaceutical companies have chosen this system as a therapeutic target for a variety of diseases. Here recent developments concerning the role of chemokines in diseases of the central nervous system (CNS) as well as their possible therapeutic relevance are discussed.

  14. 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.

  15. Saturable Active Efflux by P-Glycoprotein and Breast Cancer Resistance Protein at the Blood-Brain Barrier Leads to Nonlinear Distribution of Elacridar to the Central Nervous System

    PubMed Central

    Sane, Ramola; Agarwal, Sagar; Mittapalli, Rajendar K.

    2013-01-01

    The study objective was to investigate factors that affect the central nervous system (CNS) distribution of elacridar. Elacridar inhibits transport mediated by P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) and has been used to study the influence of transporters on brain distribution of chemotherapeutics. Adequate distribution of elacridar across the blood-brain barrier (BBB) and into the brain parenchyma is necessary to target tumor cells in the brain that overexpress transporters and reside behind an intact BBB. We examined the role of P-gp and Bcrp on brain penetration of elacridar using Friend leukemia virus strain B wild-type, Mdr1a/b(−/−), Bcrp1(−/−), and Mdr1a/b(−/−)Bcrp1(−/−) mice. Initially, the mice were administered 2.5 mg/kg of elacridar intravenously, and the plasma and brain concentrations were determined. The brain-to-plasma partition coefficient of elacridar in the wild-type mice was 0.82, as compared with 3.5 in Mdr1a/b(−/−) mice, 6.6 in Bcrp1(−/−) mice, and 15 in Mdr1a/b(−/−)Bcrp1(−/−) mice, indicating that both P-gp and Bcrp limit the brain distribution of elacridar. The four genotypes were then administered increasing doses of elacridar, and the CNS distribution of elacridar was determined. The observed and model predicted maximum brain-to-plasma ratios (Emax) at the highest dose were not significantly different in all genotypes. However, the ED50 was lower for Mdr1a/b(−/−) mice compared with Bcrp1(−/−) mice. These findings correlate with the relative expression of P-gp and Bcrp at the BBB in these mice and demonstrate the quantitative enhancement in elacridar CNS distribution as a function of its dose. Overall, this study provides useful concepts for future applications of elacridar as an adjuvant therapy to improve targeting of chemotherapeutic agents to tumor cells in the brain parenchyma. PMID:23397054

  16. 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…

  17. 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…

  18. The origin and evolution of chordate nervous systems.

    PubMed

    Holland, Linda Z

    2015-12-19

    In the past 40 years, comparisons of developmental gene expression and mechanisms of development (evodevo) joined comparative morphology as tools for reconstructing long-extinct ancestral forms. Unfortunately, both approaches typically give congruent answers only with closely related organisms. Chordate nervous systems are good examples. Classical studies alone left open whether the vertebrate brain was a new structure or evolved from the anterior end of an ancestral nerve cord like that of modern amphioxus. Evodevo plus electron microscopy showed that the amphioxus brain has a diencephalic forebrain, small midbrain, hindbrain and spinal cord with parts of the genetic mechanisms for the midbrain/hindbrain boundary, zona limitans intrathalamica and neural crest. Evodevo also showed how extra genes resulting from whole-genome duplications in vertebrates facilitated evolution of new structures like neural crest. Understanding how the chordate central nervous system (CNS) evolved from that of the ancestral deuterostome has been truly challenging. The majority view is that this ancestor had a CNS with a brain that gave rise to the chordate CNS and, with loss of a discrete brain, to one of the two hemichordate nerve cords. The minority view is that this ancestor had no nerve cord; those in chordates and hemichordates evolved independently. New techniques such as phylostratigraphy may help resolve this conundrum.

  19. Skin biopsies in the assessment of the autonomic nervous system.

    PubMed

    Wang, Ningshan; Gibbons, Christopher H

    2013-01-01

    Cutaneous punch biopsies are widely used to evaluate nociceptive C fibers in patients with suspected small-fiber neuropathy. Recent advances in immunohistochemical techniques and interest in cutaneous autonomic innervation has expanded the role of skin biopsy in the evaluation of the peripheral nervous system. The dermal layers of the skin provide a unique window into the structural evaluation of the autonomic nervous system. Peripheral adrenergic and cholinergic fibers innervate a number of cutaneous structures, such as sweat glands and arrector pili muscles, and can easily be seen with punch skin biopsies. Skin biopsies allow for both regional sampling, in diseases with patchy distribution, and the opportunity for repeated sampling in progressive disorders. The structural evaluation of cutaneous autonomic innervation is still in its scientific infancy, with a number of different methodologies and techniques that will require standardization and widespread acceptance before becoming a standard of care. Future studies of autonomic innervation in acquired, hereditary, neurodegenerative, or autoimmune disorders will be necessary to determine the clinical utility of skin biopsy in these disease states.

  20. Signaling Mechanisms Regulating Myelination in the Central Nervous System

    PubMed Central

    AHRENDSEN, Jared T.; MACKLIN, Wendy B.

    2014-01-01

    The precise and coordinated production of myelin is essential for proper development and function of the nervous system. Diseases that disrupt myelin, including multiple sclerosis (MS), cause significant functional disability. Current treatment aims to reduce the inflammatory component of the disease, thereby preventing damage resulting from demyelination. However, therapies are not yet available to improve natural repair processes after damage has already occurred. A thorough understanding of the signaling mechanisms that regulate myelin generation will improve our ability to enhance repair. In this review, we summarize the positive and negative regulators of myelination, focusing primarily on central nervous system myelination. Axon-derived signals, extracellular signals from both diffusible factors and the extracellular matrix, and intracellular signaling pathways within myelinating oligodendrocytes are discussed. Much more is known about the positive regulators that drive myelination, while less is known about the negative regulators that shift active myelination to myelin maintenance at the appropriate time. Therefore, we also provide new data on potential negative regulators of CNS myelination. PMID:23558589

  1. Detection of BMAA in the human central nervous system.

    PubMed

    Berntzon, L; Ronnevi, L O; Bergman, B; Eriksson, J

    2015-04-30

    Amyotrophic lateral sclerosis (ALS) is an extremely devastating neurodegenerative disease with an obscure etiology. The amino acid β-N-methylamino-l-alanine (BMAA) produced by globally widespread phytoplankton has been implicated in the etiology of human motor neuron diseases [corrected]. BMAA was recently proven to be present in Baltic Sea food webs, ranging from plankton to larger Baltic Sea organisms, some serving as important food items (fish) for humans. To test whether exposure to BMAA in a Baltic Sea setting is reflected in humans, blood and cerebrospinal fluid (CSF) from individuals suffering from ALS were analyzed, together with sex- and age-matched individuals not inflicted with ALS. Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and multiple reaction monitoring (MRM), in conjunction with diagnostic transitions revealed BMAA in three (12%) of the totally 25 Swedish individuals tested, with no preference for those suffering from ALS. The three BMAA-positive samples were all retrieved from the CSF, while BMAA was not detected in the blood. The data show that BMAA, potentially originating from Baltic Sea phytoplankton, may reach the human central nervous system, but does not lend support to the notion that BMAA is resident specifically in ALS-patients. However, while dietary exposure to BMAA may be intermittent and, if so, difficult to detect, our data provide the first demonstration of BMAA in the central nervous system of human individuals ante mortem quantified with UHPLC-MS/MS, and therefore calls for extended research efforts.

  2. Role of the autonomic nervous system in modulating cardiac arrhythmias.

    PubMed

    Shen, Mark J; Zipes, Douglas P

    2014-03-14

    The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.

  3. The origin and evolution of chordate nervous systems

    PubMed Central

    Holland, Linda Z.

    2015-01-01

    In the past 40 years, comparisons of developmental gene expression and mechanisms of development (evodevo) joined comparative morphology as tools for reconstructing long-extinct ancestral forms. Unfortunately, both approaches typically give congruent answers only with closely related organisms. Chordate nervous systems are good examples. Classical studies alone left open whether the vertebrate brain was a new structure or evolved from the anterior end of an ancestral nerve cord like that of modern amphioxus. Evodevo plus electron microscopy showed that the amphioxus brain has a diencephalic forebrain, small midbrain, hindbrain and spinal cord with parts of the genetic mechanisms for the midbrain/hindbrain boundary, zona limitans intrathalamica and neural crest. Evodevo also showed how extra genes resulting from whole-genome duplications in vertebrates facilitated evolution of new structures like neural crest. Understanding how the chordate central nervous system (CNS) evolved from that of the ancestral deuterostome has been truly challenging. The majority view is that this ancestor had a CNS with a brain that gave rise to the chordate CNS and, with loss of a discrete brain, to one of the two hemichordate nerve cords. The minority view is that this ancestor had no nerve cord; those in chordates and hemichordates evolved independently. New techniques such as phylostratigraphy may help resolve this conundrum. PMID:26554041

  4. Extracellular vesicles and intercellular communication within the nervous system

    PubMed Central

    Fitzpatrick, Zachary; Maguire, Casey A.; Breakefield, Xandra O.

    2016-01-01

    Extracellular vesicles (EVs, including exosomes) are implicated in many aspects of nervous system development and function, including regulation of synaptic communication, synaptic strength, and nerve regeneration. They mediate the transfer of packets of information in the form of nonsecreted proteins and DNA/RNA protected within a membrane compartment. EVs are essential for the packaging and transport of many cell-fate proteins during development as well as many neurotoxic misfolded proteins during pathogenesis. This form of communication provides another dimension of cellular crosstalk, with the ability to assemble a “kit” of directional instructions made up of different molecular entities and address it to specific recipient cells. This multidimensional form of communication has special significance in the nervous system. How EVs help to orchestrate the wiring of the brain while allowing for plasticity associated with learning and memory and contribute to regeneration and degeneration are all under investigation. Because they carry specific disease-related RNAs and proteins, practical applications of EVs include potential uses as biomarkers and therapeutics. This Review describes our current understanding of EVs and serves as a springboard for future advances, which may reveal new important mechanisms by which EVs in coordinate brain and body function and dysfunction. PMID:27035811

  5. TrkB/BDNF signalling patterns the sympathetic nervous system

    PubMed Central

    Kasemeier-Kulesa, Jennifer C.; Morrison, Jason A.; Lefcort, Frances; Kulesa, Paul M.

    2015-01-01

    The sympathetic nervous system is essential for maintaining mammalian homeostasis. How this intricately connected network, composed of preganglionic neurons that reside in the spinal cord and post-ganglionic neurons that comprise a chain of vertebral sympathetic ganglia, arises developmentally is incompletely understood. This problem is especially complex given the vertebral chain of sympathetic ganglia derive secondarily from the dorsal migration of ‘primary' sympathetic ganglia that are initially located several hundred microns ventrally from their future pre-synaptic partners. Here we report that the dorsal migration of discrete ganglia is not a simple migration of individual cells but a much more carefully choreographed process that is mediated by extensive interactions of pre-and post-ganglionic neurons. Dorsal migration does not occur in the absence of contact with preganglionic axons, and this is mediated by BDNF/TrkB signalling. Thus BDNF released by preganglionic axons acts chemotactically on TrkB-positive sympathetic neurons, to pattern the developing peripheral nervous system. PMID:26404565

  6. Spectral Mixing in Nervous Systems: Experimental Evidenceand Biologically Plausible Circuits

    NASA Astrophysics Data System (ADS)

    Kleinfeld, D.; Mehta, S. B.

    The ability to compute the difference frequency for two periodic signals depends on a nonlinear operation that mixes those signals. Behavioral and psychophysical evidence suggest that such mixing is likely to occur in the vertebrate nervous system as a means to compare rhythmic sensory signals, such as occurs in human audition, and as a means to lock an intrinsic rhythm to a sensory input. Electrophysiological data from electroreceptors in the immobilized electric fish and somatosensory cortex in the anesthetized rat yield direct evidence for such mixing, providing a neurological substrate for the modulation and demodulation of rhythmic neuronal signals. We consider an analytical model of spectral mixing that makes use of the threshold characteristics of neuronal firing and which has features consistent with the experimental observations. This model serves as a guide for constructing circuits that isolate given mixture components. In particular, such circuits can generate nearly pure difference tones from sinusoidal inputs without the use of band-pass filters, in analogy to an image-reject mixer in communications engineering. We speculate that such computations may play a role in coding of sensory input and feedback stabilization of motor output in nervous systems.

  7. Pediatric Hashimoto's encephalopathy with peripheral nervous system involvement.

    PubMed

    Salpietro, Vincenzo; Mankad, Kshitij; Polizzi, Agata; Sugawara, Yuji; Granata, Francesca; David, Emanuele; Ferraù, Valeria; Gallizzi, Romina; Tortorella, Gaetano; Ruggieri, Martino

    2014-06-01

    Hashimoto encephalopathy is a syndrome of encephalopathy associated with elevated concentration of circulating serum anti-thyroid antibodies usually responsive to steroid therapy. We report a 13-year-old girl with Hashimoto encephalopathy and peripheral nervous system involvement. The child had experienced high-grade pyrexia, global headache and sleeplessness. After admission she had an ileus with a distended urinary bladder, hallucinations and cognitive impairment. She had reduced deep tendon reflexes and distal sensory deficiency. Anti-thyroglobulin antibodies were raised at 2121 IU/mL (normal, 0-40) and the anti-thyroperoxidase was high at 886 IU/mL (normal, 0-50). Progressive neurological and psychiatric remission was noted after i.v. methylprednisolone. Follow-up magnetic resonance imaging showed complete resolution of the foci of signal abnormality previously yielded. This case report is the first, to the best of our knowledge, to describe peripheral nervous system involvement in a child with a diagnosis of Hashimoto's encephalopathy.

  8. Sexual dysfunction in patients with peripheral nervous system lesions.

    PubMed

    Podnar, Simon; Vodušek, David B

    2015-01-01

    Peripheral nervous system (PNS) disorders may cause sexual dysfunction (SD) in patients of both genders. These disorders include mainly polyneuropathies (particularly those affecting the autonomic nervous system (ANS)) and localized lesions affecting the innervation of genital organs. Impaired neural control may produce a malfunction of the genital response consisting of loss of genital sensitivity, erectile dysfunction, loss of vaginal lubrication, ejaculation disorder, and orgasmic disorder. In addition, there is often a loss of desire which actually has a complex pathogenesis, which goes beyond the mere loss of relevant nerve function. In patients who have no manifest health problems - particularly men with erectile dysfunction - one should always consider the possibility of an underlying polyneuropathy; in patients with SD after suspected denervation lesions of the innervation of genital organs within the lumbosacral spinal canal and in the pelvis, clinical neurophysiologic testing may clarify the PNS involvement. SD can alter self-esteem and lower patients' quality of life; opening up a discussion on sexual issues should be a part of the management of patients with PNS disorders. They may greatly benefit from counseling, education on coping strategies, and specific treatments.

  9. Engineering Biomaterial Properties for Central Nervous System Applications

    NASA Astrophysics Data System (ADS)

    Rivet, Christopher John

    Biomaterials offer unique properties that are intrinsic to the chemistry of the material itself or occur as a result of the fabrication process; iron oxide nanoparticles are superparamagnetic, which enables controlled heating in the presence of an alternating magnetic field, and a hydrogel and electrospun fiber hybrid material provides minimally invasive placement of a fibrous, artificial extracellular matrix for tissue regeneration. Utilization of these unique properties towards central nervous system disease and dysfunction requires a thorough definition of the properties in concert with full biological assessment. This enables development of material-specific features to elicit unique cellular responses. Iron oxide nanoparticles are first investigated for material-dependent, cortical neuron cytotoxicity in vitro and subsequently evaluated for alternating magnetic field stimulation induced hyperthermia, emulating the clinical application for enhanced chemotherapy efficacy in glioblastoma treatment. A hydrogel and electrospun fiber hybrid material is first applied to a rat brain to evaluate biomaterial interface astrocyte accumulation as a function of hybrid material composition. The hybrid material is then utilized towards increasing functional engraftment of dopaminergic progenitor neural stem cells in a mouse model of Parkinson's disease. Taken together, these two scenarios display the role of material property characterization in development of biomaterial strategies for central nervous system repair and regeneration.

  10. Evaluating the autonomic nervous system in patients with laryngopharyngeal reflux.

    PubMed

    Huang, Wan-Ju; Shu, Chih-Hung; Chou, Kun-Ta; Wang, Yi-Fen; Hsu, Yen-Bin; Ho, Ching-Yin; Lan, Ming-Ying

    2013-06-01

    The pathogenesis of laryngopharyngeal reflux (LPR) remains unclear. It is linked to but distinct from gastroesophageal reflux disease (GERD), which has been shown to be related to disturbed autonomic regulation. The aim of this study is to investigate whether autonomic dysfunction also plays a role in the pathogenesis of LPR. Case-control study. Tertiary care center. Seventeen patients with LPR and 19 healthy controls, aged between 19 and 50 years, were enrolled in the study. The patients were diagnosed with LPR if they had a reflux symptom index (RSI) ≥ 13 and a reflux finding score (RFS) ≥ 7. Spectral analysis of heart rate variability (HRV) analysis was used to assess autonomic function. Anxiety and depression levels measured by the Beck Anxiety Inventory (BAI) and Beck Depression Inventory II (BDI-II) were also conducted. In HRV analysis, high frequency (HF) represents the parasympathetic activity of the autonomic nervous system, whereas low frequency (LF) represents the total autonomic activity. There were no significant differences in the LF power and HF power between the 2 groups. However, significantly lower HF% (P = .003) and a higher LF/HF ratio (P = .012) were found in patients with LPR, who demonstrated poor autonomic modulation and higher sympathetic activity. Anxiety was also frequently observed in the patient group. The study suggests that autonomic dysfunction seems to be involved in the pathogenesis of LPR. The potential beneficial effect of autonomic nervous system modulation as a therapeutic modality for LPR merits further investigation.

  11. 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

  12. Dietary Glutamate: Interactions With the Enteric Nervous System

    PubMed Central

    Wang, Guo-Du; Wang, Xi-Yu; Xia, Yun

    2014-01-01

    Background/Aims Digestion of dietary protein elevates intraluminal concentrations of glutamate in the small intestine, some of which gain access to the enteric nervous system (ENS). Glutamate, in the central nervous system (CNS), is an excitatory neurotransmitter. A dogma that glutamatergic neurophysiology in the ENS recapitulates CNS glutamatergic function persists. We reassessed the premise that glutamatergic signaling in the ENS recapitulates its neurotransmitter role in the CNS. Methods Pharmacological analysis of actions of receptor agonists and antagonists in concert with immunohistochemical localization of glutamate transporters and receptors was used. Analysis focused on intracellularly-recorded electrical and synaptic behavior of ENS neurons, on stimulation of mucosal secretion by secretomotor neurons in the submucosal plexus and on muscle contractile behavior mediated by musculomotor neurons in the myenteric plexus. Results Immunoreactivity for glutamate was expressed in ENS neurons. ENS neurons expressed immunoreactivity for the EAAC-1 glutamate transporter. Neither L-glutamate nor glutamatergic receptor agonists had excitatory actions on ENS neurons. Metabotropic glutamatergic receptor agonists did not directly stimulate neurogenic mucosal chloride secretion. Neither L-glutamate nor the metabotropic glutamatergic receptor agonist, aminocyclopentane-1,3-dicarboxylic acid (ACPD), changed the mean amplitude of spontaneously occurring contractions in circular or longitudinal strips of intestinal wall from either guinea pig or human small intestinal preparations. Conclusions Early discoveries, for excitatory glutamatergic neurotransmission in the CNS, inspired enthusiasm that investigation in the ENS would yield discoveries recapitulating the CNS glutamatergic story. We found this not to be the case. PMID:24466444

  13. Golgi, Cajal, and the Fine Structure of the Nervous System

    PubMed Central

    Peters, Alan

    2012-01-01

    Towards the middle of the twentieth century, neuroanatomy was on the decline. It was revived by the development of two new methods. One was the Nauta-Gygax method, which selectively stained nerve fibers that had been caused to degenerate by experimental lesions. This allowed connections between various parts of the nervous system to be better determined. The second was electron microscopy, which allowed the structure of neurons and the synapses between them to be examined in detail, and eventually this led to a revival of the Golgi impregnation methods. This occurred in the 1970s because of the desire of electron microscopists to determine the origins of the neuronal profiles they encountered in electron micrographs of various parts of the central nervous system. Eventually this led to the development of Golgi/EM techniques, whereby individual impregnated neurons could first be characterized by light microscopy and then thin sectioned for detailed analyses. Examining the axon terminals of such impregnated neurons, especially those in the cerebral cortex, for the first time revealed details of intercellular connections and allowed neuronal circuits to be postulated. However, Golgi/EM had only a brief, but fruitful existence. It was soon superceded by intracellular filling techniques, which allowed the added dimension that the physiological properties of identified neurons could also be determined. PMID:17270274

  14. Glycobiology of ion transport in the nervous system.

    PubMed

    Nowycky, Martha C; Wu, Gusheng; Ledeen, Robert W

    2014-01-01

    The nervous system is richly endowed with large transmembrane proteins that mediate ion transport, including gated ion channels as well as energy-consuming pumps and transporters. Transport proteins undergo N-linked glycosylation which can affect expression, location, stability, and function. The N-linked glycans of ion channels are large, contributing between 5 and 50 % of their molecular weight. Many contain a high density of negatively charged sialic acid residues which modulate voltage-dependent gating of ion channels. Changes in the size and chemical composition of glycans are responsible for developmental and cell-specific variability in the biophysical and functional properties of many ion channels. Glycolipids, principally gangliosides, exert considerable influence on some forms of ion transport, either through direct association with ion transport proteins or indirectly through association with proteins that activate transport through appropriate signaling. Examples of both pumps and ion channels have been revealed which depend on ganglioside regulation. While some of these processes are localized in the plasma membrane, ganglioside-regulated ion transport can also occur at various loci within the cell including the nucleus. This chapter will describe ion channel and ion pump structures with a focus on the functional effects of glycosylation on ion channel availability and function, and effects of alterations in glycosylation on nervous system function. It will also summarize highlights of the research on glycolipid/ganglioside-mediated regulation of ion transport.

  15. Probing disorders of the nervous system using reprogramming approaches

    PubMed Central

    Ichida, Justin K; Kiskinis, Evangelos

    2015-01-01

    The groundbreaking technologies of induced pluripotency and lineage conversion have generated a genuine opportunity to address fundamental aspects of the diseases that affect the nervous system. These approaches have granted us unrestricted access to the brain and spinal cord of patients and have allowed for the study of disease in the context of human cells, expressing physiological levels of proteins and under each patient's unique genetic constellation. Along with this unprecedented opportunity have come significant challenges, particularly in relation to patient variability, experimental design and data interpretation. Nevertheless, significant progress has been achieved over the past few years both in our ability to create the various neural subtypes that comprise the nervous system and in our efforts to develop cellular models of disease that recapitulate clinical findings identified in patients. In this Review, we present tables listing the various human neural cell types that can be generated and the neurological disease modeling studies that have been reported, describe the current state of the field, highlight important breakthroughs and discuss the next steps and future challenges. PMID:25925386

  16. Interleukin-1β in Central Nervous System Injury and Repair

    PubMed Central

    Hewett, Sandra J.

    2015-01-01

    Summary Acute inflammation is a self-limiting, complex biological response mounted to combat pathogen invasion, to protect against tissue damage, and to promote tissue repair should it occur. However, unabated inflammation can be deleterious and contribute to injury and pathology. Interleukin-1β (IL-1β), a prototypical “pro-inflammatory” cytokine, is essential to cellular defense and tissue repair in nearly all tissues. With respect to brain, however, studies suggest that IL-1β has pleiotrophic effects. It acts as a neuromodulator in the healthy central nervous system (CNS), has been implicated in the pathogenic processes associated with a number of CNS maladies, but may also provide protection to the injured CNS. Here, we will review the physiological and pathophysiological functions of IL-1β in the central nervous system with regard to synaptic plasticity. With respect to disease, emphasis will be placed on stroke, epilepsy, Parkinson’s disease and Alzheimer’s disease where the ultimate injurious or reparative effects of IL-1β appear to depend on time, concentration and environmental milieu. PMID:26082912

  17. [Components of plastic disrupt the function of the nervous system].

    PubMed

    Szychowski, Konrad Andrzej; Wójtowicz, Anna Katarzyna

    2013-05-27

    Development of the chemical industry leads to the development of new chemical compounds, which naturally do not exist in the environment. These chemicals are used to reduce flammability, increase plasticity, or improve solubility of other substances. Many of these compounds, which are components of plastic, the new generation of cosmetics, medical devices, food packaging and other everyday products, are easily released into the environment. Many studies have shown that a major lipophilicity characterizes substances such as phthalates, BPA, TBBPA and PCBs. This feature allows them to easily penetrate into living cells, accumulate in the tissues and the organs, and affect human and animal health. Due to the chemical structures, these compounds are able to mimic some endogenous hormones such as estradiol and to disrupt the hormone homeostasis. They can also easily pass the placental barrier and the blood-brain barrier. As numerous studies have shown, these chemicals disturb the proper functions of the nervous system from the earliest moments of life. It has been proven that these compounds affect neurogenesis as well as the synaptic transmission process. As a consequence, they interfere with the formation of the sex of the brain, as well as with the learning processes, memory and behavior. Additionally, the cytotoxic and pro-apoptotic effect may cause neurodegenerative diseases. This article presents the current state of knowledge about the effects of phthalates, BPA, TBBPA, and PCBs on the nervous system.

  18. Role of metallothionein-III following central nervous system damage.

    PubMed

    Carrasco, Javier; Penkowa, Milena; Giralt, Mercedes; Camats, Jordi; Molinero, Amalia; Campbell, Iain L; Palmiter, Richard D; Hidalgo, Juan

    2003-06-01

    We evaluated the physiological relevance of metallothionein-III (MT-III) in the central nervous system following damage caused by a focal cryolesion onto the cortex by studying Mt3-null mice. In normal mice, dramatic astrogliosis and microgliosis and T-cell infiltration were observed in the area surrounding the lesioned tissue, along with signs of increased oxidative stress and apoptosis. There was also significant upregulation of cytokines/growth factors such as tumor necrosis factor-alpha, interleukin (IL)-1 alpha/beta, and IL-6 as measured by ribonuclease protection assay. Mt3-null mice did not differ from control mice in these responses, in sharp contrast to results obtained in Mt1- Mt2-null mice. In contrast, Mt3-null mice showed increased expression of several neurotrophins as well as of the neuronal sprouting factor GAP-43. Thus, unlike MT-I and MT-II, MT-III does not affect the inflammatory response elicited in the central nervous system by a cryoinjury, nor does it serve an important antioxidant role, but it may influence neuronal regeneration during the recovery process.

  19. ATR maintains select progenitors during nervous system development

    PubMed Central

    Lee, Youngsoo; Shull, Erin RP; Frappart, Pierre-Olivier; Katyal, Sachin; Enriquez-Rios, Vanessa; Zhao, Jingfeng; Russell, Helen R; Brown, Eric J; McKinnon, Peter J

    2012-01-01

    The ATR (ATM (ataxia telangiectasia mutated) and rad3-related) checkpoint kinase is considered critical for signalling DNA replication stress and its dysfunction can lead to the neurodevelopmental disorder, ATR-Seckel syndrome. To understand how ATR functions during neurogenesis, we conditionally deleted Atr broadly throughout the murine nervous system, or in a restricted manner in the dorsal telencephalon. Unexpectedly, in both scenarios, Atr loss impacted neurogenesis relatively late during neural development involving only certain progenitor populations. Whereas the Atr-deficient embryonic cerebellar external germinal layer underwent p53- (and p16Ink4a/Arf)-independent proliferation arrest, other brain regions suffered apoptosis that was partially p53 dependent. In contrast to other organs, in the nervous system, p53 loss did not worsen the outcome of Atr inactivation. Coincident inactivation of Atm also did not affect the phenotype after Atr deletion, supporting non-overlapping physiological roles for these related DNA damage-response kinases in the brain. Rather than an essential general role in preventing replication stress, our data indicate that ATR functions to monitor genomic integrity in a selective spatiotemporal manner during neurogenesis. PMID:22266795

  20. HIV Immune Recovery Inflammatory Syndrome and Central Nervous System Paracoccidioidomycosis.

    PubMed

    de Almeida, Sérgio Monteiro; Roza, Thiago Henrique

    2017-04-01

    The immune reconstitution inflammatory syndrome (IRIS) is a deregulated inflammatory response to invading microorganisms. It is manifested when there is an abrupt change in host immunity from an anti-inflammatory and immunosuppressive state to a pro-inflammatory state as a result of rapid depletion or removal of factors that promote immune suppression or inhibition of inflammation. The aim of this paper is to discuss and re-interpret the possibility of association of paracoccidioidomycosis (PCM) with IRIS in the central nervous system (CNS) in a case from Brazil published by Silva-Vergara ML. et al. (Mycopathologia 177:137-141, 6). An AIDS patient who was not receiving medical care developed pulmonary PCM successfully treated with itraconazole. The patient developed central nervous system PCM (NPCM) after starting the ARV therapy with recovery of immunity and control of HIV viral load, although it was not interpreted as IRIS by the authors, it fulfills the criteria for CNS IRIS. This could be the first case of NPCM associated with IRIS described. Although not frequent, IRIS must be considered in PCM patients and HIV, from endemic areas or patients that traveled to endemic areas, receiving ARV treatment and with worsening symptoms.

  1. Targeted Temperature Management in Pediatric Central Nervous System Disease

    PubMed Central

    Newmyer, Robert; Mendelson, Jenny; Pang, Diana; Fink, Ericka L.

    2015-01-01

    Opinion Statement Acute central nervous system conditions due to hypoxic-ischemic encephalopathy, traumatic brain injury (TBI), status epilepticus, and central nervous system infection/inflammation, are a leading cause of death and disability in childhood. There is a critical need for effective neuroprotective therapies to improve outcome targeting distinct disease pathology. Fever, defined as patient temperature > 38°C, has been clearly shown to exacerbate brain injury. Therapeutic hypothermia (HT) is an intervention using targeted temperature management that has multiple mechanisms of action and robust evidence of efficacy in multiple experimental models of brain injury. Prospective clinical evidence for its neuroprotective efficacy exists in narrowly-defined populations with hypoxic-ischemic injury outside of the pediatric age range while trials comparing hypothermia to normothermia after TBI have failed to demonstrate a benefit on outcome but consistently demonstrate potential use in decreasing refractory intracranial pressure. Data in children from prospective, randomized controlled trials using different strategies of targeted temperature management for various outcomes are few but a large study examining HT versus controlled normothermia to improve neurological outcome in cardiac arrest is underway. PMID:26042193

  2. Detrimental impact of hyperlipidemia on the peripheral nervous system

    PubMed Central

    Wu, Song; Cao, Xu; He, Rongzhen; Xiong, Kun

    2012-01-01

    Recently, epidemiological studies on the etiology of peripheral neuropathies have revealed that hyperlipidemia is a novel risk factor. Plasma lipid levels were confirmed to be associated with the incidence of many peripheral neuropathies including axonal distal polyneuropathy, vision and hearing loss, motor nerve system lesions and sympathetic nerve system dysfunction. Moreover, different lipid components such as cholesterol, triacylglycerols and lipoprotein are involved in the pathogenesis of these neuropathies. This review aimed to discuss the effect of hyperlipidemia on the peripheral nervous system and its association with peripheral neuropathies. Furthermore, a detailed discussion focusing on the explicit mechanisms related to hyperlipidemia-induced peripheral neuropathies is presented here. These mechanisms, including intracellular oxidative stress, inflammatory lesions, ischemia and dysregulation of local lipid metabolism, share pathways and interact mutually. In addition, we examined current information on clinical trials to prevent and treat peripheral neuropathies caused by hyperlipidemia, with a predictive discussion regarding the orientation of future investigations. PMID:25774180

  3. Choroid plexus in the central nervous system: biology and physiopathology.

    PubMed

    Strazielle, N; Ghersi-Egea, J F

    2000-07-01

    Choroid plexuses (CPs) are localized in the ventricular system of the brain and form one of the interfaces between the blood and the central nervous system (CNS). They are composed of a tight epithelium responsible for cerebrospinal fluid secretion, which encloses a loose connective core containing permeable capillaries and cells of the lymphoid lineage. In accordance with its peculiar localization between 2 circulating fluid compartments, the CP epithelium is involved in numerous exchange processes that either supply the brain with nutrients and hormones, or clear deleterious compounds and metabolites from the brain. Choroid plexuses also participate in neurohumoral brain modulation and neuroimmune interactions, thereby contributing greatly in maintaining brain homeostasis. Besides these physiological functions, the implication of choroid plexuses in pathological processes is increasingly documented. In this review, we focus on some of the novel aspects of CP functions in relation to brain development, transfer of neuro-humoral information, brain/immune system interactions, brain aging, and cerebral pharmaco-toxicology.

  4. [Histoplasmosis of the central nervous system in an immunocompetent patient].

    PubMed

    Osorio, Natalia; López, Yúrika; Jaramillo, Juan Camilo

    2014-01-01

    Histoplasmosis is a multifaceted condition caused by the dimorphic fungi Histoplasma capsulatum whose infective spores are inhaled and reach the lungs, the primary organ of infection. The meningeal form, considered one of the most serious manifestations of this mycosis, is usually seen in individuals with impaired cellular immunity such as patients with acquired immunodeficiency syndrome, systemic lupus erythematous or solid organ transplantation, and infants given their immunological immaturity. The most common presentation is self-limited and occurs in immunocompetent individuals who have been exposed to high concentrations of conidia and mycelia fragments of the fungi. In those people, the condition is manifested by pulmonary disorders and late dissemination to other organs and systems. We report a case of central nervous system histoplasmosis in an immunocompetent child.

  5. Career readiness, developmental work personality and age of onset in young adult central nervous system survivors.

    PubMed

    Strauser, David; Wagner, Stacia; Wong, Alex W K; O'Sullivan, Deidre

    2013-04-01

    The primary purpose of this paper is to undertake foundational research in the area of career readiness, work personality and age of onset with young adult central nervous system (CNS) survivors. Participants for this study consisted of 43 individuals whose age range from 18 to 30 (M = 21.64, SD = 3.46), an average age of brain tumor onset of 9.50 years (SD = 4.73) and average years off of treatment of 7.25 years (SD = 5.80). Packets were distributed to survivors who were participating in a psychosocial cancer treatment program. Participants completed multiple career instruments and a demographic form. Differences between groups and among the variables were examined and size effect sizes were analyzed. Young adult CNS survivors had significantly lower levels of work personality and career readiness when compared to young adult non-cancer survivors with CNS cancer with those between the ages of 6 and 12 reported significantly lower levels when compared to individuals diagnosed before age 6 and after the age of 13. Young adult CNS survivors at an increased risk for having lower levels of work personality and career readiness then a norm group comparison. Age of onset (between 6 and 12) may be at significant risk factor for developing poor or dysfunctional work and career behaviors. • Young adults with central nervous system (CNS) cancer are at particular risk for experiencing difficulties related to career and employment. • Work personality and career readiness are two constructs that have been found to be related to one's ability to meet the demands of work. • Young adult CNS cancer survivors have lower levels of work personality and career readiness. • Individuals diagnosed between the ages of 6 and 12 may be at particular risk and may need specific vocational rehabilitation interventions. • The results of this study point to the need for comprehensive career and vocational services for young adult CNS cancer survivors.

  6. International study on low-grade primary central nervous system lymphoma.

    PubMed

    Jahnke, Kristoph; Korfel, Agnieszka; O'Neill, Brian Patrick; Blay, Jean-Yves; Abrey, Lauren E; Martus, Peter; Poortmans, Philip M P; Shenkier, Tamara N; Batchelor, Tracy T; Neuwelt, Edward A; Raizer, Jeffrey J; Schiff, David; Pels, Hendrik; Herrlinger, Ulrich; Stein, Harald; Thiel, Eckhard

    2006-05-01

    The aim of this study was to characterize the clinical presentation, course, and outcome of low-grade primary central nervous system lymphoma. Cases were assessed in a retrospective series collected from 18 cancer centers in 5 countries. Forty patients (18 men, 22 women; median age, 60 years [range, 19-78]) were identified. Involvement of a cerebral hemisphere or deeper brain structures was seen in 37 patients, only leptomeningeal involvement in 2 patients, and spinal cord disease in 1 patient. Chemotherapy/radiotherapy was conducted in 15 patients, radiotherapy alone in 12, chemotherapy alone in 10, and tumor resection alone in 2, whereas 1 patient received no treatment. The median progression-free, disease-specific, and overall survival were 61.5 (range, 0-204), 130 (range, 1-204), and 79 (range, 1-204) months, respectively. Only age 60 years or older was associated with shorter progression-free (p = 0.009), disease-specific (p = 0.015), and overall survival (p = 0.001) in multivariate analysis. Low-grade primary central nervous system lymphoma differs from the high-grade subtype in its pathological, clinical, and radiological features. It has a better long-term outcome than primary central nervous system lymphoma in general with age 60 years or older adversely affecting survival.

  7. Central Nervous System Vasculitis: Still More Questions than Answers

    PubMed Central

    Alba, Marco A; Espígol-Frigolé, Georgina; Prieto-González, Sergio; Tavera-Bahillo, Itziar; García-Martínez, Ana; Butjosa, Montserrat; Hernández-Rodríguez, José; Cid, Maria C

    2011-01-01

    The central nervous system (CNS) may be involved by a variety of inflammatory diseases of blood vessels. These include primary angiitis of the central nervous system (PACNS), a rare disorder specifically targeting the CNS vasculature, and the systemic vasculitides which may affect the CNS among other organs and systems. Both situations are severe and convey a guarded prognosis. PACNS usually presents with headache and cognitive impairment. Focal symptoms are infrequent at disease onset but are common in more advanced stages. The diagnosis of PACNS is difficult because, although magnetic resonance imaging is almost invariably abnormal, findings are non specific. Angiography has limited sensitivity and specificity. Brain and leptomeningeal biopsy may provide a definitive diagnosis when disclosing blood vessel inflammation and are also useful to exclude other conditions presenting with similar findings. However, since lesions are segmental, a normal biopsy does not completely exclude PACNS. Secondary CNS involvement by systemic vasculitis occurs in less than one fifth of patients but may be devastating. A prompt recognition and aggressive treatment is crucial to avoid permanent damage and dysfunction. Glucocorticoids and cyclophosphamide are recommended for patients with PACNS and for patients with secondary CNS involvement by small-medium-sized systemic vasculitis. CNS involvement in large-vessel vasculitis is usually managed with high-dose glucocorticoids (giant-cell arteritis) or glucocorticoids and immunosuppressive agents (Takayasu’s disease). However, in large vessel vasculitis, where CNS symptoms are usually due to involvement of extracranial arteries (Takayasu’s disease) or proximal portions of intracranial arteries (giant-cell arteritis), revascularization procedures may also have an important role. PMID:22379458

  8. The function of NOD-like receptors in central nervous system diseases.

    PubMed

    Kong, Xiangxi; Yuan, Zengqiang; Cheng, Jinbo

    2016-12-28

    NOD-like receptors (NLRs) are critical cytoplasmic pattern-recognition receptors (PRRs) that play an important role in the host innate immune response and immunity homeostasis. There is a growing body of evidence that NLRs are involved in a wide range of inflammatory diseases, including cancer, metabolic diseases, and autoimmune disorders. Recent studies have indicated that the proteins of the NLR family are linked with the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), and psychological diseases. In this review, we mainly focus on the role of NLRs and the underlying signaling pathways in central nervous system (CNS) diseases. © 2016 Wiley Periodicals, Inc.

  9. Xenopus laevis neuronal cell adhesion molecule (nrcam): plasticity of a CAM in the developing nervous system.

    PubMed

    Lokapally, Ashwin; Metikala, Sanjeeva; Hollemann, Thomas

    2017-01-01

    Neuron-glial-related cell adhesion molecule (NRCAM) is a neuronal cell adhesion molecule of the L1 immunoglobulin superfamily, which plays diverse roles during nervous system development including axon growth and guidance, synapse formation, and formation of the myelinated nerve. Perturbations in NRCAM function cause a wide variety of disorders, which can affect wiring and targeting of neurons, or cause psychiatric disorders as well as cancers through abnormal modulation of signaling events. In the present study, we characterize the Xenopus laevis homolog of nrcam. Expression of Xenopus nrcam is most abundant along the dorsal midline throughout the developing brain and in the outer nuclear layer of the retina.

  10. [Stem cell-based therapy in central nervous system diseases].

    PubMed

    Paczkowska, Edyta; Dabkowska, Elzbieta; Nowacki, Przemysław; Machaliński, Bogusław

    2009-01-01

    Much of the current research into stem cell biology is focused on its potential for regeneration of various tissues and organs. Stem cell-based therapy with autologous bone marrow stem cells could provide an attractive alternative to the classical therapeutic approach in the foreseeable future. The possibility of nervous tissue regeneration in neurodegenerative disorders of the central nervous system generates a special challenge for researchers and clinicians involved in that field of medicine. Very small embryonic-like stem cells (VSEL SCs), recently discovered in murine bone marrow and human umbilical cord blood, arouse great hope. VSEL SCs display several features typical for embryonic stem cells, such as a large nucleus surrounded by a narrow rim of cytoplasm, euchromatin, and expression of pluripotent markers (Oct-4, Nanog, SSEA-4). Application of these cells in regenerative medicine could have considerable advantages over strategies using embryonic stem cells, since ethical concerns might be naturally solved. Thus, these cells can become a recommended source of stem cells for cell therapy as compared to those isolated from developing embryos.

  11. Evolution and regeneration of the planarian central nervous system.

    PubMed

    Umesono, Yoshihiko; Agata, Kiyokazu

    2009-04-01

    More than 100 years ago, early workers realized that planarians offer an excellent system for regeneration studies. Another unique aspect of planarians is that they occupy an interesting phylogenetic position with respect to the nervous system in that they possess an evolutionarily primitive brain structure and can regenerate a functional brain from almost any tiny body fragment. Recent molecular studies have revisited planarian regeneration and revealed key information about the cellular and molecular mechanisms underlying brain regeneration in planarians. One of our great advances was identification of a gene, nou-darake, which directs the formation of a proper extrinsic environment for pluripotent stem cells to differentiate into brain cells in the planarian Dugesia japonica. Our recent findings have provided mechanistic insights into stem cell biology and also evolutionary biology.

  12. Control of Prosthetic Hands via the Peripheral Nervous System

    PubMed Central

    Ciancio, Anna Lisa; Cordella, Francesca; Barone, Roberto; Romeo, Rocco Antonio; Bellingegni, Alberto Dellacasa; Sacchetti, Rinaldo; Davalli, Angelo; Di Pino, Giovanni; Ranieri, Federico; Di Lazzaro, Vincenzo; Guglielmelli, Eugenio; Zollo, Loredana

    2016-01-01

    This paper intends to provide a critical review of the literature on the technological issues on control and sensorization of hand prostheses interfacing with the Peripheral Nervous System (i.e., PNS), and their experimental validation on amputees. The study opens with an in-depth analysis of control solutions and sensorization features of research and commercially available prosthetic hands. Pros and cons of adopted technologies, signal processing techniques and motion control solutions are investigated. Special emphasis is then dedicated to the recent studies on the restoration of tactile perception in amputees through neural interfaces. The paper finally proposes a number of suggestions for designing the prosthetic system able to re-establish a bidirectional communication with the PNS and foster the prosthesis natural control. PMID:27092041

  13. Convection-enhanced delivery to the central nervous system.

    PubMed

    Lonser, Russell R; Sarntinoranont, Malisa; Morrison, Paul F; Oldfield, Edward H

    2015-03-01

    Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

  14. Development-Inspired Reprogramming of the Mammalian Central Nervous System

    PubMed Central

    Amamoto, Ryoji; Arlotta, Paola

    2014-01-01

    In 2012, John Gurdon and Shinya Yamanaka shared the Nobel Prize for the exciting demonstration that the identity of differentiated cells is not irreversibly determined but can be changed back to a pluripotent state under appropriate instructive signals. The principle that differentiated cells can revert to an embryonic state and even be converted directly from one cell-type into another not only turns fundamental principles of development on their head but also has profound implications for regenerative medicine. Replacement of diseased tissue with newly reprogrammed cells and modeling of human disease are concrete opportunities. Here, we focus on the central nervous system to consider whether and how reprogramming of cell identity may impact regeneration and modeling of a system historically considered immutable and hardwired. PMID:24482482

  15. Protective and Pathological Immunity during Central Nervous System Infections.

    PubMed

    Klein, Robyn S; Hunter, Christopher A

    2017-06-20

    The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted that innate pathways limit pathogen invasion of the CNS and adaptive immunity mediates control of many neural infections. As protective responses can result in bystander damage, there are regulatory mechanisms that balance protective and pathological inflammation, but these mechanisms might also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in our understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection. Advances in these areas have broadened our comprehension of how the immune system functions in the brain and can readily overcome immune privilege. Copyright © 2017. Published by Elsevier Inc.

  16. Development-inspired reprogramming of the mammalian central nervous system.

    PubMed

    Amamoto, Ryoji; Arlotta, Paola

    2014-01-31

    In 2012, John Gurdon and Shinya Yamanaka shared the Nobel Prize for the demonstration that the identity of differentiated cells is not irreversibly determined but can be changed back to a pluripotent state under appropriate instructive signals. The principle that differentiated cells can revert to an embryonic state and even be converted directly from one cell type into another not only turns fundamental principles of development on their heads but also has profound implications for regenerative medicine. Replacement of diseased tissue with newly reprogrammed cells and modeling of human disease are concrete opportunities. Here, we focus on the central nervous system to consider whether and how reprogramming of cell identity may affect regeneration and modeling of a system historically considered immutable and hardwired.

  17. Interferons, Signal Transduction Pathways, and the Central Nervous System

    PubMed Central

    Nallar, Shreeram C.

    2014-01-01

    The interferon (IFN) family of cytokines participates in the development of innate and acquired immune defenses against various pathogens and pathogenic stimuli. Discovered originally as a proteinaceous substance secreted from virus-infected cells that afforded immunity to neighboring cells from virus infection, these cytokines are now implicated in various human pathologies, including control of tumor development, cell differentiation, and autoimmunity. It is now believed that the IFN system (IFN genes and the genes induced by them, and the factors that regulate these processes) is a generalized alarm of cellular stress, including DNA damage. IFNs exert both beneficial and deleterious effects on the central nervous system (CNS). Our knowledge of the IFN-regulated processes in the CNS is far from being clear. In this article, we reviewed the current understanding of IFN signal transduction pathways and gene products that might have potential relevance to diseases of the CNS. PMID:25084173

  18. 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.

  19. R1 autonomic nervous system in acute kidney injury.

    PubMed

    Hering, Dagmara; Winklewski, Pawel J

    2017-02-01

    Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented. © 2016 John Wiley & Sons Australia, Ltd.

  20. Autonomic nervous system correlates in movement observation and motor imagery

    PubMed Central

    Collet, C.; Di Rienzo, F.; El Hoyek, N.; Guillot, A.

    2013-01-01

    The purpose of the current article is to provide a comprehensive overview of the literature offering a better understanding of the autonomic nervous system (ANS) correlates in motor imagery (MI) and movement observation. These are two high brain functions involving sensori-motor coupling, mediated by memory systems. How observing or mentally rehearsing a movement affect ANS activity has not been extensively investigated. The links between cognitive functions and ANS responses are not so obvious. We will first describe the organization of the ANS whose main purposes are controlling vital functions by maintaining the homeostasis of the organism and providing adaptive responses when changes occur either in the external or internal milieu. We will then review how scientific knowledge evolved, thus integrating recent findings related to ANS functioning, and show how these are linked to mental functions. In turn, we will describe how movement observation or MI may elicit physiological responses at the peripheral level of the autonomic effectors, thus eliciting autonomic correlates to cognitive activity. Key features of this paper are to draw a step-by step progression from the understanding of ANS physiology to its relationships with high mental processes such as movement observation or MI. We will further provide evidence that mental processes are co-programmed both at the somatic and autonomic levels of the central nervous system (CNS). We will thus detail how peripheral physiological responses may be analyzed to provide objective evidence that MI is actually performed. The main perspective is thus to consider that, during movement observation and MI, ANS activity is an objective witness of mental processes. PMID:23908623