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

Code of Federal Regulations, 2011 CFR

2011-04-01

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

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

Code of Federal Regulations, 2013 CFR

2013-04-01

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

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. © IMechE 2015.

[Late sequelae of central nervous system prophylaxis in children with acute lymphoblastic leukemia: high doses of intravenous methotrexate versus radiotherapy of the central nervous system--review of literature].

PubMed

Zając-Spychała, Olga; Wachowiak, Jacek

2012-01-01

Acute lymphoblastic leukemia is the most common malignancy in children. All current therapy regimens used in the treatment of childhood acute lymphoblastic leukemia include prophylaxis of the central nervous system. Initially it was thought that the best way of central nervous system prophylaxis is radiotherapy. But despite its effectiveness this method, may cause late sequelae and complications. In the programme currently used in Poland to treat acute lymphoblastic leukemia, prophylactic radiotherapy has been reduced by 50% (12 Gy) and is used only in patients stratified into the high risk group and in patients diagnosed as T-cell ALL (T-ALL). Complementary to radiotherapy, intrathecal methotrexate is given alone or in combination with cytarabine and hydrocortisone is given, as well as systemic chemotherapy with intravenous methotrexate is administered in high or medium doses (depending on risk groups and leukemia immunophenotype). Recent studies have shown that high dose irradiation of the central nervous system impairs cognitive development causing memory loss, visuomotor coordination impairment, attention disorders and reduction in the intelligence quotient. It has been proved that the degree of cognitive impairment depends on the radiation dose directed to the medial temporal lobe structures, particularly in the hippocampus and the surrounding cortex. Also, methotrexate used intravenously in high doses, interferes with the metabolism of folic acid which is necessary for normal development and the optimal functioning of neurons in the central nervous system. It has been proved that patients who have been treated with high doses of methotrexate are characterized by reduced memory skills and a lower intelligence quotient. The literature data concerning long term neuroanatomical abnormalities and neuropsychological deficits are ambiguous, and there is still no data concerning current methods of central nervous system prophylaxis with low doses of irradiation in combination with high doses of intravenous methotrexate.

Classification of neural tumors in laboratory rodents, emphasizing the rat.

PubMed

Weber, Klaus; Garman, Robert H; Germann, Paul-Georg; Hardisty, Jerry F; Krinke, Georg; Millar, Peter; Pardo, Ingrid D

2011-01-01

Neoplasms of the nervous system, whether spontaneous or induced, are infrequent in laboratory rodents and very rare in other laboratory animal species. The morphology of neural tumors depends on the intrinsic functions and properties of the cell type, the interactions between the neoplasm and surrounding normal tissue, and regressive changes. The incidence of neural neoplasms varies with sex, location, and age of tumor onset. Although the onset of spontaneous tumor development cannot be established in routine oncogenicity studies, calculations using the time of diagnosis (day of death) have revealed significant differences in tumor biology among different rat strains. In the central nervous system, granular cell tumors (a meningioma variant), followed by glial tumors, are the most common neoplasms in rats, whereas glial cell tumors are observed most frequently in mice. Central nervous system tumors usually affect the brain rather than the spinal cord. Other than adrenal gland pheochromocytomas, the most common neoplasms of the peripheral nervous system are schwannomas. Neural tumors may develop in the central nervous system and peripheral nervous system from other cell lineages (including extraneural elements like adipose tissue and lymphocytes), but such lesions are very rare in laboratory animals.

The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke.

PubMed

Winek, Katarzyna; Dirnagl, Ulrich; Meisel, Andreas

2016-10-01

Research on commensal microbiota and its contribution to health and disease is a new and very dynamically developing field of biology and medicine. Recent experimental and clinical investigations underscore the importance of gut microbiota in the pathogenesis and course of stroke. Importantly, microbiota may influence the outcome of cerebral ischemia by modulating central nervous system antigen-specific immune responses. In this review we summarize studies linking gut microbiota with physiological function and disorders of the central nervous system. Based on these insights we speculate about targeting the gut microbiome in order to treat stroke.

Central Nervous System Vasculitis

MedlinePlus

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

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.

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

PubMed

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

2016-01-12

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

Convection-Enhanced Delivery for the Treatment of Pediatric Neurologic Disorders

PubMed Central

Song, Debbie K.; Lonser, Russell R.

2013-01-01

Direct perfusion of specific regions of the central nervous system by convection-enhanced delivery is becoming more widely used for the delivery of compounds in the research and treatment of various neural disorders. In contrast to other currently available central nervous system delivery techniques, convection-enhanced delivery relies on bulk flow for distribution of solute. This allows for safe, targeted, reliable, and homogeneous delivery of small- and large-molecular-weight substances over clinically relevant volumes in a manner that bypasses the blood-central nervous system barrier. Recent studies have also shown that coinfused imaging surrogate tracers can be used to monitor and control the convective distribution of therapeutic agents in vivo. The unique features of convection-enhanced delivery, including the ability to monitor distribution in real-time, provide an opportunity to develop new research and treatment paradigms for pediatric patients with a variety of intrinsic central nervous system disorders. PMID:18952590

Retinoic acid influences anteroposterior positioning of epidermal sensory neurons and their gene expression in a developing chordate (amphioxus)

PubMed Central

Schubert, Michael; Holland, Nicholas D.; Escriva, Hector; Holland, Linda Z.; Laudet, Vincent

2004-01-01

In developing chordates, retinoic acid (RA) signaling patterns the rostrocaudal body axis globally and affects gene expression locally in some differentiating cell populations. Here we focus on development of epidermal sensory neurons in an invertebrate chordate (amphioxus) to determine how RA signaling influences their rostrocaudal distribution and gene expression (for AmphiCoe, a neural precursor gene; for amphioxus islet and AmphiERR, two neural differentiation genes; and for AmphiHox1, -3, -4, and -6). Treatments with RA or an RA antagonist (BMS009) shift the distribution of developing epidermal neurons anteriorly or posteriorly, respectively. These treatments also affect gene expression patterns in the epidermal neurons, suggesting that RA levels may influence specification of neuronal subtypes. Although colinear expression of Hox genes is well known for the amphioxus central nervous system, we find an unexpected comparable colinearity for AmphiHox1, -3, -4, and -6 in the developing epidermis; moreover, RA levels affect the anteroposterior extent of these Hox expression domains, suggesting that RA signaling controls a colinear Hox code for anteroposterior patterning of the amphioxus epidermis. Thus, in amphioxus, the developing peripheral nervous system appears to be structured by mechanisms parallel to those that structure the central nervous system. One can speculate that, during evolution, an ancestral deuterostome that structured its panepidermal nervous system with an RA-influenced Hox code gave rise to chordates in which this patterning mechanism persisted within the epidermal elements of the peripheral nervous system and was transferred to the neuroectoderm as the central nervous system condensed dorsally. PMID:15226493

Central Nervous System and Vertebrae Development in Horses: a Chronological Study with Differential Temporal Expression of Nestin and GFAP.

PubMed

Rigoglio, Nathia N; Barreto, Rodrigo S N; Favaron, Phelipe O; Jacob, Júlio C F; Smith, Lawrence C; Gastal, Melba O; Gastal, Eduardo L; Miglino, Maria Angélica

2017-01-01

The neural system is one of the earliest systems to develop and the last to be fully developed after birth. This study presents a detailed description of organogenesis of the central nervous system (CNS) at equine embryonic/fetal development between 19 and 115 days of pregnancy. The expression of two important biomarkers in the main structure of the nervous system responsible for neurogenesis in the adult individual, and in the choroid plexus, was demonstrated by Nestin and glial fibrillary acid protein (GFAP) co-labeling. In the 29th day of pregnancy in the undifferentiated lateral ventricle wall, the presence of many cells expressing Nestin and few expressing GFAP was observed. After the differentiation of the lateral ventricle wall zones at 60 days of pregnancy, the subventricular zone, which initially had greater number of Nestin + cells, began to show higher numbers of GFAP + cells at 90 days of pregnancy. A similar pattern was observed for Nestin + and GFAP + cells during development of the choroid plexus. This study demonstrates, for the first time, detailed chronological aspects of the equine central nervous system organogenesis associated with downregulation of Nestin and upregulation of GFAP expression.

A case of primary hypothyroidism causing central nervous system atherosclerosis in a dog.

PubMed

Blois, Shauna L; Poma, Roberto; Stalker, Margaret J; Allen, Dana G

2008-08-01

A 2-year-old, castrated male, Australian shepherd was presented with a history of chronic mild ataxia, obesity, and lethargy. The dog was treated with levothyroxine, but the ataxia worsened. Cranial nerve abnormalities developed and the dog was euthanized. Postmortem examination revealed marked thyroid gland atrophy and widespread, severe central nervous system atherosclerosis.

Video Views and Reviews: Neurulation and the Fashioning of the Vertebrate Central Nervous System

ERIC Educational Resources Information Center

Watters, Christopher

2006-01-01

The central nervous system (CNS) is the first adult organ system to appear during vertebrate development, and the process of its emergence is commonly called neurulation. Such biological "urgency" is perhaps not surprising given the structural and functional complexity of the CNS and the importance of neural function to adaptive behavior and…

CNS Drug Development: Lessons Learned Part 3: Psychiatric and Central Nervous System Drugs Developed Over the Last Decade-Implications for the Field.

PubMed

Preskorn, Sheldon H

2017-09-01

This column reviews the divergence between the approach to drug development in infectious disease, oncology, and immunology versus psychiatry. Between 2009 and 2016, 254 new drugs were approved. Of those, only 9 were for a psychiatric indication; another 5 were labeled to treat central nervous system disorders that are not considered psychiatric per se but are frequently found in individuals with psychiatric illnesses (eg, substantial weight gain). There were 2 additional new products for psychiatric indications that involved either a combination product (Contrave) or a prodrug for the production of aripiprazole (Aristada). The column discusses the reasons behind these different rates of development of psychiatric and/or central nervous system drugs compared with drugs in the areas of infectious disease, oncology, and immunology, and it predicts that this situation will change over the next century as we develop an improved understanding of the neurobiology underlying specific psychiatric illnesses.

A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system

PubMed Central

Bateman, Randall J.; Siemers, Eric R.; Mawuenyega, Kwasi G.; Wen, Guolin; Browning, Karen R.; Sigurdson, Wendy C.; Yarasheski, Kevin E.; Friedrich, Stuart W.; DeMattos, Ronald B.; May, Patrick C.; Paul, Steven M.; Holtzman, David M.

2009-01-01

Objective Accumulation of amyloid-β (Aβ) by over-production or under-clearance in the central nervous system is hypothesized to be a necessary event in the pathogenesis of Alzheimer Disease. However, previously there has not been a method to determine drug effects on Aβ production or clearance in the human central nervous system. The objective of this study was to determine the effects of a gamma-secretase inhibitor on the production of Aβ in the human CNS. Methods We utilized a recently developed method of stable-isotope labeling combined with cerebrospinal fluid sampling to directly measure Aβ production during treatment of a gamma-secretase inhibitor, LY450139. We assessed whether this drug could decrease central nervous system Aβ production in healthy men (age 21–50) at single oral doses of 100mg, 140mg, or 280mg (N=5 per group). Results LY450139 significantly decreased the production of central nervous system Aβ in a dose-dependent fashion, with inhibition of Aβ generation of 47%, 52%, and 84% over a 12 hour period with doses of 100 mg, 140, and 280 mg respectively. There was no difference in Aβ clearance. Interpretation Stable isotope labeling of central nervous system proteins can be utilized to assess the effects of drugs on the production and clearance rates of proteins targeted as potential disease modifying treatments for Alzheimer Disease and other central nervous system disorders. Results from this approach can assist in making decisions about drug dosing and frequency in the design of larger and longer clinical trials for diseases such as Alzheimer Disease, and may accelerate effective drug validation. PMID:19360898

Maximizing functional axon repair in the injured central nervous system: Lessons from neuronal development.

PubMed

Kaplan, Andrew; Bueno, Mardja; Hua, Luyang; Fournier, Alyson E

2018-01-01

The failure of damaged axons to regrow underlies disability in central nervous system injury and disease. Therapies that stimulate axon repair will be critical to restore function. Extensive axon regeneration can be induced by manipulation of oncogenes and tumor suppressors; however, it has been difficult to translate this into functional recovery in models of spinal cord injury. The current challenge is to maximize the functional integration of regenerating axons to recover motor and sensory behaviors. Insights into axonal growth and wiring during nervous system development are helping guide new approaches to boost regeneration and functional connectivity after injury in the mature nervous system. Here we discuss our current understanding of axonal behavior after injury and prospects for the development of drugs to optimize axon regeneration and functional recovery after CNS injury. Developmental Dynamics 247:18-23, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

[Hereditary cerebro-oculo-renal syndromes].

PubMed

Sessa, Galina; Hjortshøj, Tina Duelund; Egfjord, Martin

2014-02-17

Although many congenital diseases present disturbances of the central nervous system, eyes and renal function, only few of these have a defined genetic basis. The first clinical features of cerebro-oculo-renal diseases usually develop in early childhood and deterioration of kidney function and even end-stage kidney disease may occur in a young age. The syndromes should be considered in patients with retarded growth and development, central nervous system abnormalities, impaired vision or blindness and progressive renal failure.

Tuberculous otitis media with mastoiditis and central nervous system involvement.

PubMed

Mongkolrattanothai, Kanokporn; Oram, Ronda; Redleaf, Miriam; Bova, Judy; Englund, Janet A

2003-05-01

Tuberculosis of the middle ear and mastoid is currently a rare disease in developed countries, but this disease still occurs and may cause serious consequences. We report a case of disseminated tuberculosis involving the middle ear, mastoid, lung and central nervous system. Tuberculosis should be considered in the differential diagnosis of chronic ear drainage, especially in young children.

Childhood Central Nervous System Germ Cell Tumors Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood central nervous system (CNS) germ cell tumors form from germ cells (a type of cell that forms as a fetus develops and later becomes sperm in the testicles or eggs in the ovaries). Learn about the signs, tests to diagnose, and treatment of pediatric germ cell tumors in the brain in this expert-reviewed summary.

A case of primary hypothyroidism causing central nervous system atherosclerosis in a dog

PubMed Central

Blois, Shauna L.; Poma, Roberto; Stalker, Margaret J.; Allen, Dana G.

2008-01-01

A 2-year-old, castrated male, Australian shepherd was presented with a history of chronic mild ataxia, obesity, and lethargy. The dog was treated with levothyroxine, but the ataxia worsened. Cranial nerve abnormalities developed and the dog was euthanized. Postmortem examination revealed marked thyroid gland atrophy and widespread, severe central nervous system atherosclerosis. PMID:18978973

Development of primary central nervous system lymphoma in a systemic lupus erythematosus patient after treatment with mycophenolate mofetil and review of the literature.

PubMed

Balci, M A; Pamuk, G E; Unlu, E; Usta, U; Pamuk, O N

2017-10-01

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma and four cases of PCNSL have previously been described in association with mycophenolate mofetil. We report the fifth case of PCNSL in a patient with lupus nephropathy while on mycophenolate mofetil treatment.

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

ClinicalTrials.gov

2013-07-01

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

Spatial sexual dimorphism of X and Y homolog gene expression in the human central nervous system during early male development.

PubMed

Johansson, Martin M; Lundin, Elin; Qian, Xiaoyan; Mirzazadeh, Mohammadreza; Halvardson, Jonatan; Darj, Elisabeth; Feuk, Lars; Nilsson, Mats; Jazin, Elena

2016-01-01

Renewed attention has been directed to the functions of the Y chromosome in the central nervous system during early human male development, due to the recent proposed involvement in neurodevelopmental diseases. PCDH11Y and NLGN4Y are of special interest because they belong to gene families involved in cell fate determination and formation of dendrites and axon. We used RNA sequencing, immunocytochemistry and a padlock probing and rolling circle amplification strategy, to distinguish the expression of X and Y homologs in situ in the human brain for the first time. To minimize influence of androgens on the sex differences in the brain, we focused our investigation to human embryos at 8-11 weeks post-gestation. We found that the X- and Y-encoded genes are expressed in specific and heterogeneous cellular sub-populations of both glial and neuronal origins. More importantly, we found differential distribution patterns of X and Y homologs in the male developing central nervous system. This study has visualized the spatial distribution of PCDH11X/Y and NLGN4X/Y in human developing nervous tissue. The observed spatial distribution patterns suggest the existence of an additional layer of complexity in the development of the male CNS.

The p38α mitogen-activated protein kinase as a central nervous system drug discovery target

PubMed Central

Borders, Aaron S; de Almeida, Lucia; Van Eldik, Linda J; Watterson, D Martin

2008-01-01

Protein kinases are critical modulators of a variety of cellular signal transduction pathways, and abnormal phosphorylation events can be a cause or contributor to disease progression in a variety of disorders. This has led to the emergence of protein kinases as an important new class of drug targets for small molecule therapeutics. A serine/threonine protein kinase, p38α mitogen-activated protein kinase (MAPK), is an established therapeutic target for peripheral inflammatory disorders because of its critical role in regulation of proinflammatory cytokine production. There is increasing evidence that p38α MAPK is also an important regulator of proinflammatory cytokine levels in the central nervous system, raising the possibility that the kinase may be a drug discovery target for central nervous system disorders where cytokine overproduction contributes to disease progression. Development of bioavailable, central nervous system-penetrant p38α MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38α MAPK in neurodegenerative disorders. PMID:19090985

The p38alpha mitogen-activated protein kinase as a central nervous system drug discovery target.

PubMed

Borders, Aaron S; de Almeida, Lucia; Van Eldik, Linda J; Watterson, D Martin

2008-12-03

Protein kinases are critical modulators of a variety of cellular signal transduction pathways, and abnormal phosphorylation events can be a cause or contributor to disease progression in a variety of disorders. This has led to the emergence of protein kinases as an important new class of drug targets for small molecule therapeutics. A serine/threonine protein kinase, p38alpha mitogen-activated protein kinase (MAPK), is an established therapeutic target for peripheral inflammatory disorders because of its critical role in regulation of proinflammatory cytokine production. There is increasing evidence that p38alpha MAPK is also an important regulator of proinflammatory cytokine levels in the central nervous system, raising the possibility that the kinase may be a drug discovery target for central nervous system disorders where cytokine overproduction contributes to disease progression. Development of bioavailable, central nervous system-penetrant p38alpha MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38alpha MAPK in neurodegenerative disorders.

Role of insulin signaling impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice.

PubMed

Anderson, Nicholas J; King, Matthew R; Delbruck, Lina; Jolivalt, Corinne G

2014-06-01

One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ)-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype. © 2014. Published by The Company of Biologists Ltd.

Development of a Physiologically-Based Pharmacokinetic Model of the Rat Central Nervous System

PubMed Central

Badhan, Raj K. Singh; Chenel, Marylore; Penny, Jeffrey I.

2014-01-01

Central nervous system (CNS) drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB), blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF), choroidal epithelial and total cerebrospinal fluid (CSF) compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain) and CSF:plasma ratio (CSF:Plasmau) using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways. PMID:24647103

Next generation of non-mammalian blood-brain barrier models to study parasitic infections of the central nervous system

PubMed Central

Siddiqui, Ruqaiyyah; Edwards-Smallbone, James; Flynn, Robin; Khan, Naveed Ahmed

2012-01-01

Transmigration of neuropathogens across the blood-brain barrier is a key step in the development of central nervous system infections, making it a prime target for drug development. The ability of neuropathogens to traverse the blood-brain barrier continues to inspire researchers to understand the specific strategies and molecular mechanisms that allow them to enter the brain. The availability of models of the blood-brain barrier that closely mimic the situation in vivo offers unprecedented opportunities for the development of novel therapeutics. PMID:21921682

Immunostaining to visualize murine enteric nervous system development.

PubMed

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

2015-04-29

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

High-fat diet feeding differentially affects the development of inflammation in the central nervous system.

PubMed

Guillemot-Legris, Owein; Masquelier, Julien; Everard, Amandine; Cani, Patrice D; Alhouayek, Mireille; Muccioli, Giulio G

2016-08-26

Obesity and its associated disorders are becoming a major health issue in many countries. The resulting low-grade inflammation not only affects the periphery but also the central nervous system. We set out to study, in a time-dependent manner, the effects of a high-fat diet on different regions of the central nervous system with regard to the inflammatory tone. We used a diet-induced obesity model and compared at several time-points (1, 2, 4, 6, 8, and 16 weeks) a group of mice fed a high-fat diet with its respective control group fed a standard diet. We also performed a large-scale analysis of lipids in the central nervous system using HPLC-MS, and we then tested the lipids of interest on a primary co-culture of astrocytes and microglial cells. We measured an increase in the inflammatory tone in the cerebellum at the different time-points. However, at week 16, we evidenced that the inflammatory tone displayed significant differences in two different regions of the central nervous system, specifically an increase in the cerebellum and no modification in the cortex for high-fat diet mice when compared with chow-fed mice. Our results clearly suggest region-dependent as well as time-dependent adaptations of the central nervous system to the high-fat diet. The differences in inflammatory tone between the two regions considered seem to involve astrocytes but not microglial cells. Furthermore, a large-scale lipid screening coupled to ex vivo testing enabled us to identify three classes of lipids-phosphatidylinositols, phosphatidylethanolamines, and lysophosphatidylcholines-as well as palmitoylethanolamide, as potentially responsible for the difference in inflammatory tone. This study demonstrates that the inflammatory tone induced by a high-fat diet does not similarly affect distinct regions of the central nervous system. Moreover, the lipids identified and tested ex vivo showed interesting anti-inflammatory properties and could be further studied to better characterize their activity and their role in controlling inflammation in the central nervous system.

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

PubMed

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

2017-04-04

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

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

PubMed

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

2016-11-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

Gengo, F M; Gabos, C

1988-07-01

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

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

ClinicalTrials.gov

2013-05-01

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

Novel Roles for Immune Molecules in Neural Development: Implications for Neurodevelopmental Disorders

PubMed Central

Garay, Paula A.; McAllister, A. Kimberley

2010-01-01

Although the brain has classically been considered “immune-privileged”, current research suggests an extensive communication between the immune and nervous systems in both health and disease. Recent studies demonstrate that immune molecules are present at the right place and time to modulate the development and function of the healthy and diseased central nervous system (CNS). Indeed, immune molecules play integral roles in the CNS throughout neural development, including affecting neurogenesis, neuronal migration, axon guidance, synapse formation, activity-dependent refinement of circuits, and synaptic plasticity. Moreover, the roles of individual immune molecules in the nervous system may change over development. This review focuses on the effects of immune molecules on neuronal connections in the mammalian central nervous system – specifically the roles for MHCI and its receptors, complement, and cytokines on the function, refinement, and plasticity of geniculate, cortical and hippocampal synapses, and their relationship to neurodevelopmental disorders. These functions for immune molecules during neural development suggest that they could also mediate pathological responses to chronic elevations of cytokines in neurodevelopmental disorders, including autism spectrum disorders (ASD) and schizophrenia. PMID:21423522

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.

An overview of travel-associated central nervous system infectious diseases: risk assessment, general considerations and future directions.

PubMed

Izadi, Morteza; Is'haqi, Arman; Is'haqi, Mohammad Ali; Jonaidi Jafari, Nematollah; Rahamaty, Fatemeh; Banki, Abdolali

2014-08-01

Nervous system infections are among the most important diseases in travellers. Healthy travellers might be exposed to infectious agents of central nervous system, which may require in-patient care. Progressive course is not uncommon in this family of disorders and requires swift diagnosis. An overview of the available evidence in the field is, therefore, urgent to pave the way to increase the awareness of travel-medicine practitioners and highlights dark areas for future research. In November 2013, data were collected from PubMed, Scopus, and Web of Knowledge (1980 to 2013) including books, reviews, and peer-reviewed literature. Works pertained to pre-travel care, interventions, vaccinations related neurological infections were retrieved. Here we provide information on pre-travel care, vaccination, chronic nervous system disorders, and post-travel complications. Recommendations with regard to knowledge gaps, and state-of-the-art research are made. Given an increasing number of international travellers, novel dynamic ways are available for physicians to monitor spread of central nervous system infections. Newer research has made great progresses in developing newer medications, detecting the spread of infections and the public awareness. Despite an ongoing scientific discussion in the field of travel medicine, further research is required for vaccine development, state-of-the-art laboratory tests, and genetic engineering of vectors.

NEURONAL ACTION ON THE DEVELOPING BLOOD VESSEL PATTERN

PubMed Central

James, Jennifer M.; Mukouyama, Yoh-suke

2011-01-01

The nervous system relies on a highly specialized network of blood vessels for development and neuronal survival. Recent evidence suggests that both the central and peripheral nervous systems (CNS and PNS) employ multiple mechanisms to shape the vascular tree to meet its specific metabolic demands, such as promoting nerve-artery alignment in the PNS or the development the blood brain barrier in the CNS. In this article we discuss how the nervous system directly influences blood vessel patterning resulting in neuro-vascular congruence that is maintained throughout development and in the adult. PMID:21978864

Continuing Development of the Vulnerability Model

DTIC Science & Technology

1977-02-01

likely to involve an entirely differ- ent toxic mechanism , brought on by exposure to higher concentrations and affecting the central nervous system... mechanisms with quite dif- ferent syndromes . One is its effect as a depressant of the central ŕ nervous system, in which it acts like many other...other sensory disorder , weakness, muscular incoordination, and epilepsy -- like seizures. All these symptoms have been seen to per- 4 •sist. The

Central Nervous System Symptoms Due to Transient Methemoglobinemia in a Child With G6PD Deficiency.

PubMed

Sharma, Shreya; Srinivasaraghavan, Rangan; Krishnamurthy, Sriram

2017-01-01

The authors herein report a 5-year-old child who presented with massive hemolysis, irritability, and cyanosis. The final diagnosis was glucose-6-phosphate dehydrogenase deficiency with associated central nervous system symptoms probably because of concomitantly acquired methemoglobinemia following oxidant drug exposure. The associated acute-onset anemia would have contributed to the development of cerebral anoxia-related seizures and encephalopathy.

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

PubMed

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

2018-06-07

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

Can pharmaco-electroencephalography help improve survival of central nervous system drugs in early clinical development?

PubMed

Wilson, Frederick J; Leiser, Steven C; Ivarsson, Magnus; Christensen, Søren R; Bastlund, Jesper F

2014-03-01

Pharmaco-electroencephalography has significant yet unrealised promise as a translatable intermediate biomarker of central pharmacodynamic activity that could help reduce Phase 2 attrition in the development of central nervous system drugs. In an effort to understand its true potential, a framework for decision-making was proposed and the utility of pharmaco-electroencephalography was assessed through several case studies. A key finding was that lack of standardisation reduces the value of data pooling and meta-analyses and renders assessment of translatability difficult, limiting utility in all but simple cases. Pre-competitive collaboration is essential both to improving understanding of translation and developing modern signal processing techniques. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Secret Lives of Neurotrophin Receptors | Center for Cancer Research

Cancer.gov

Neurotrophins are a family of growth factors that are critical to the proper development and functioning of the nervous system. Neurotrophins activate a family of tyrosine receptor kinases (Trk), which typically initiate signaling cascades through phosphorylation. This axis is important for central nervous system (CNS) drug development efforts, ranging from pain management to

Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin

NASA Astrophysics Data System (ADS)

Yednock, Ted A.; Cannon, Catherine; Fritz, Lawrence C.; Sanchez-Madrid, Francisco; Steinman, Lawrence; Karin, Nathan

1992-03-01

EXPERIMENTAL autoimmune encephalomyelitis (EAE) is an inflammatory condition of the central nervous system with similarities to multiple sclerosis1,2. In both diseases, circulating leukocytes penetrate the blood-brain barrier and damage myelin, resulting in impaired nerve conduction and paralysis3-5. We sought to identify the adhesion receptors that mediate the attachment of circulating leukocytes to inflamed brain endothelium in EAE, because this interaction is the first step in leukocyte entry into the central nervous system. Using an in vitro adhesion assay on tissue sections, we found that lymphocytes and monocytes bound selectively to inflamed EAE brain vessels. Binding was inhibited by antibodies against the integrin molecule α4βl, but not by antibodies against numerous other adhesion receptors. When tested in vivo, anti-α4 integrin effectively prevented the accumulation of leukocytes in the central nervous system and the development of EAE. Thus, therapies designed to interfere with α4βl integrin may be useful in treating inflammatory diseases of the central nervous system, such as multiple sclerosis.

Boc modifies the spectrum of holoprosencephaly in the absence of Gas1 function

PubMed Central

Seppala, Maisa; Xavier, Guilherme M.; Fan, Chen-Ming; Cobourne, Martyn T.

2014-01-01

ABSTRACT Holoprosencephaly is a heterogeneous developmental malformation of the central nervous system characterized by impaired forebrain cleavage, midline facial anomalies and wide phenotypic variation. Indeed, microforms represent the mildest manifestation, associated with facial anomalies but an intact central nervous system. In many cases, perturbations in sonic hedgehog signaling are responsible for holoprosencephaly. Here, we have elucidated the contribution of Gas1 and an additional hedgehog co-receptor, Boc during early development of the craniofacial midline, by generating single and compound mutant mice. Significantly, we find Boc has an essential role in the etiology of a unique form of lobar holoprosencephaly that only occurs in conjunction with combined loss of Gas1. Whilst Gas1−/− mice have microform holoprosencephaly characterized by a single median maxillary central incisor, cleft palate and pituitary anomalies, Boc−/− mice have a normal facial midline. However, Gas1−/−; Boc−/− mutants have lobar holoprosencephaly associated with clefting of the lip, palate and tongue, secondary to reduced sonic hedgehog transduction in the central nervous system and face. Moreover, maxillary incisor development is severely disrupted in these mice, arresting prior to cellular differentiation as a result of apoptosis in the odontogenic epithelium. Thus, Boc and Gas1 retain an essential function in these tooth germs, independent of their role in midline development of the central nervous system and face. Collectively, this phenotype demonstrates both redundancy and individual requirements for Gas1 and Boc during sonic hedgehog transduction in the craniofacial midline and suggests BOC as a potential digenic locus for lobar holoprosencephaly in human populations. PMID:25063195

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

PubMed

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

2014-03-01

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

Subacute combined degeneration

MedlinePlus

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

[Central nervous system control of energy homeostasis].

PubMed

Machleidt, F; Lehnert, H

2011-03-01

The brain is continuously supplied with information about the distribution and amount of energy stores from the body periphery. Endocrine, autonomic and cognitive-hedonic signals are centrally integrated and exert effects on the whole organism via anabolic and catabolic pathways. The adiposity signals insulin and leptin reflect the amount of body fat and are part of a negative feedback mechanism between the periphery and the central nervous system. The hypothalamic arcuate nucleus is the most important central nervous structure, which integrates this information. Furthermore, the CNS is able to directly measure and to respond to changes in the concentration of certain nutrients. In order to develop effective therapies for the treatment of disorders of energy balance the further elucidation of these neuro-biological processes is of crucial importance. This article provides an overview of the CNS regulation of metabolism and its underlying molecular mechanisms. © Georg Thieme Verlag KG Stuttgart · New York.

Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution.

PubMed

Hejnol, Andreas; Lowe, Christopher J

2015-12-19

Molecular biology has provided a rich dataset to develop hypotheses of nervous system evolution. The startling patterning similarities between distantly related animals during the development of their central nervous system (CNS) have resulted in the hypothesis that a CNS with a single centralized medullary cord and a partitioned brain is homologous across bilaterians. However, the ability to precisely reconstruct ancestral neural architectures from molecular genetic information requires that these gene networks specifically map with particular neural anatomies. A growing body of literature representing the development of a wider range of metazoan neural architectures demonstrates that patterning gene network complexity is maintained in animals with more modest levels of neural complexity. Furthermore, a robust phylogenetic framework that provides the basis for testing the congruence of these homology hypotheses has been lacking since the advent of the field of 'evo-devo'. Recent progress in molecular phylogenetics is refining the necessary framework to test previous homology statements that span large evolutionary distances. In this review, we describe recent advances in animal phylogeny and exemplify for two neural characters-the partitioned brain of arthropods and the ventral centralized nerve cords of annelids-a test for congruence using this framework. The sequential sister taxa at the base of Ecdysozoa and Spiralia comprise small, interstitial groups. This topology is not consistent with the hypothesis of homology of tripartitioned brain of arthropods and vertebrates as well as the ventral arthropod and rope-like ladder nervous system of annelids. There can be exquisite conservation of gene regulatory networks between distantly related groups with contrasting levels of nervous system centralization and complexity. Consequently, the utility of molecular characters to reconstruct ancestral neural organization in deep time is limited. © 2015 The Authors.

Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution

PubMed Central

Hejnol, Andreas; Lowe, Christopher J.

2015-01-01

Molecular biology has provided a rich dataset to develop hypotheses of nervous system evolution. The startling patterning similarities between distantly related animals during the development of their central nervous system (CNS) have resulted in the hypothesis that a CNS with a single centralized medullary cord and a partitioned brain is homologous across bilaterians. However, the ability to precisely reconstruct ancestral neural architectures from molecular genetic information requires that these gene networks specifically map with particular neural anatomies. A growing body of literature representing the development of a wider range of metazoan neural architectures demonstrates that patterning gene network complexity is maintained in animals with more modest levels of neural complexity. Furthermore, a robust phylogenetic framework that provides the basis for testing the congruence of these homology hypotheses has been lacking since the advent of the field of ‘evo-devo’. Recent progress in molecular phylogenetics is refining the necessary framework to test previous homology statements that span large evolutionary distances. In this review, we describe recent advances in animal phylogeny and exemplify for two neural characters—the partitioned brain of arthropods and the ventral centralized nerve cords of annelids—a test for congruence using this framework. The sequential sister taxa at the base of Ecdysozoa and Spiralia comprise small, interstitial groups. This topology is not consistent with the hypothesis of homology of tripartitioned brain of arthropods and vertebrates as well as the ventral arthropod and rope-like ladder nervous system of annelids. There can be exquisite conservation of gene regulatory networks between distantly related groups with contrasting levels of nervous system centralization and complexity. Consequently, the utility of molecular characters to reconstruct ancestral neural organization in deep time is limited. PMID:26554039

AB0 blood types: impact on development of prosthetic mechanical valve thrombosis

PubMed Central

Astarcıoğlu, Mehmet Ali; Kalçık, Macit; Yesin, Mahmut; Gürsoy, Mustafa Ozan; Şen, Taner; Karakoyun, Süleyman; Gündüz, Sabahattin; Özkan, Mehmet

2016-01-01

Objective: The non-O alleles of the ABO genotype have been associated with an increased risk of thrombosis. We aimed to assess the association between blood group status and prosthetic valve thrombosis. Methods: The association between AB0 blood group status and prosthetic valve thrombosis was assessed in this retrospective study. Transesophageal echocardiography was performed in 149 patients with a diagnosis of prosthetic valve thrombosis and in 192 control subjects. Results: Non-0 blood group type (p<0.001), presence of NYHA class III-IV status (p<0.001), and central nervous system (p<0.001) and non-central nervous system (p<0.001) emboli were significantly more prevalent in prosthetic valve thrombosis patients than in the control subjects. The incidence of ineffective anticoagulation was higher in patients with prosthetic valve thrombosis than in controls (p<0.001), as was the presence of moderate to severe left atrial spontaneous echo contrast (p<0.001). The non-0 blood prosthetic valve thrombosis subgroup had a higher incidence of obstructive thrombi and central nervous system thrombotic events than having 0 blood prosthetic valve thrombosis subgroup. Non-0 blood group, ineffective anticoagulation, left atrial spontaneous echo contrast, and a poor NYHA functional capacity were identified to be the predictors of prosthetic valve thrombosis. Conclusion: Our data demonstrate that patients with non-0 compared with 0 blood groups have higher incidence of prosthetic valve thrombosis and central nervous system embolism and similar rates of non-central nervous system embolism at presentation compared with 0 blood group type. Thus, non-O blood group may be a risk factor that may be prone to the development of prosthetic valve thrombosis in patients with prosthetic heart valves. PMID:27488753

Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring

DTIC Science & Technology

2016-10-01

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

Morphogenetic interaction of presumptive neural and mesodermal cells mixed in different ratios.

PubMed

Toivonen, S; Saxen, L

1968-02-02

Cells of the presumptive forebrain region and axial mesoderm of Triturus neurulae were disaggregated and combined in different ratios. The differentiation of the central nervous systen in these explants was dependent on the relative amount of mesodermal cells present: an increase of mesodermal cells resulted in a corresponding increase in the frequency with which caudal structures of the central nervous system developed and a gradual loss of the forebrain formations.

Autonomous requirements of the Menkes disease protein in the nervous system.

PubMed

Hodgkinson, Victoria L; Zhu, Sha; Wang, Yanfang; Ladomersky, Erik; Nickelson, Karen; Weisman, Gary A; Lee, Jaekwon; Gitlin, Jonathan D; Petris, Michael J

2015-11-15

Menkes disease is a fatal neurodegenerative disorder arising from a systemic copper deficiency caused by loss-of-function mutations in a ubiquitously expressed copper transporter, ATP7A. Although this disorder reveals an essential role for copper in the developing human nervous system, the role of ATP7A in the pathogenesis of signs and symptoms in affected patients, including severe mental retardation, ataxia, and excitotoxic seizures, remains unknown. To directly examine the role of ATP7A within the central nervous system, we generated Atp7a(Nes) mice, in which the Atp7a gene was specifically deleted within neural and glial cell precursors without impairing systemic copper homeostasis, and compared these mice with the mottled brindle (mo-br) mutant, a murine model of Menkes disease in which Atp7a is defective in all cells. Whereas mo-br mice displayed neurodegeneration, demyelination, and 100% mortality prior to weaning, the Atp7a(Nes) mice showed none of these phenotypes, exhibiting only mild sensorimotor deficits, increased anxiety, and susceptibility to NMDA-induced seizure. Our results indicate that the pathophysiology of severe neurological signs and symptoms in Menkes disease is the result of copper deficiency within the central nervous system secondary to impaired systemic copper homeostasis and does not arise from an intrinsic lack of ATP7A within the developing brain. Furthermore, the sensorimotor deficits, hypophagia, anxiety, and sensitivity to NMDA-induced seizure in the Atp7a(Nes) mice reveal unique autonomous requirements for ATP7A in the nervous system. Taken together, these data reveal essential roles for copper acquisition in the central nervous system in early development and suggest novel therapeutic approaches in affected patients. Copyright © 2015 the American Physiological Society.

40 CFR 721.72 - Hazard communication program.

Code of Federal Regulations, 2011 CFR

2011-07-01

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

40 CFR 721.72 - Hazard communication program.

Code of Federal Regulations, 2010 CFR

2010-07-01

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

40 CFR 721.72 - Hazard communication program.

Code of Federal Regulations, 2012 CFR

2012-07-01

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

40 CFR 721.72 - Hazard communication program.

Code of Federal Regulations, 2014 CFR

2014-07-01

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

40 CFR 721.72 - Hazard communication program.

Code of Federal Regulations, 2013 CFR

2013-07-01

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

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

ClinicalTrials.gov

2017-08-30

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

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

NASA Technical Reports Server (NTRS)

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

2003-01-01

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

4H Syndrome

MedlinePlus

... syndrome? 4H syndrome is short for hypomyelination, hypogonadotropic hypogonadism and hypodontia. Hypomyelination means that there is lack ... myelin in the central nervous system. In hypogonadotropic hypogonadism, normal puberty development is absent because the central ...

Axonal sprouting and laminin appearance after destruction of glial sheaths.

PubMed Central

Masuda-Nakagawa, L M; Muller, K J; Nicholls, J G

1993-01-01

Laminin, a large extracellular matrix molecule, is associated with axonal outgrowth during development and regeneration of the nervous system in a variety of animals. In the leech central nervous system, laminin immunoreactivity appears after axon injury in advance of the regenerating axons. Although studies of vertebrate nervous system in culture have implicated glial and Schwann cells as possible sources, the cells that deposit laminin at sites crucial for regeneration in the living animal are not known. We have made a direct test to determine whether, in the central nervous system of the leech, cells other than ensheathing glial cells can produce laminin. Ensheathing glial cells of adult leeches were ablated selectively by intracellular injection of a protease. As a result, leech laminin accumulated within 10 days in regions of the central nervous system where it is not normally found, and undamaged, intact axons began to sprout extensively. In normal leeches laminin immunoreactivity is situated only in the basement membrane that surrounds the central nervous system, whereas after ablation of ensheathing glia it appeared in spaces through which neurons grew. Within days of ablation of the glial cell, small mobile phagocytes, or microglia, accumulated in the spaces formerly occupied by the glial cell. Microglia were concentrated at precisely the sites of new laminin appearance and axon sprouting. These results suggest that in the animal, as in culture, leech laminin promotes sprouting and that microglia may be responsible for its appearance. Images Fig. 1 Fig. 2 Fig. 3 PMID:8506343

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

MedlinePlus

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

Strategies for Enhanced Drug Delivery to the Central Nervous System

PubMed Central

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

2008-01-01

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

APOPTOSIS DURING DEVELOPMENT AND AGING AND IN RESPONSE TO MERCURY EXPOSURE.

EPA Science Inventory

In the central nervous system from embryogenesis through senescence, cell number is regulated, in part, by apoptosis. Each region of the nervous system has a characteristic temporal pattern of programmed cell death, which includes far greater numbers of cells undergoing apop...

Expression of the Hsp23 chaperone during Drosophila embryogenesis: association to distinct neural and glial lineages

PubMed Central

Michaud, Sébastien; Tanguay, Robert M

2003-01-01

Background In addition to their strong induction following stress, small heat shock proteins (Hsp) are also expressed during development in a wide variety of organisms. However, the precise identity of cell(s) expressing these proteins and the functional contribution of small heat shock proteins in such developmental context remain to be determined. The present study provides a detailed description of the Drosophila small heat shock protein Hsp23 expression pattern during embryogenesis and evaluates its functional contribution to central nervous system development. Results Throughout embryogenesis, Hsp23 is expressed in a stage-specific manner by a restricted number of neuronal and glial lineages of the central nervous system. Hsp23 is also detected in the amnioserosa and within a single lateral chordotonal organ. Its expression within the MP2 lineage does not require the presence of a functional midline nor the activity of the Notch signaling pathway. Transactivation assays demonstrate that transcription factors implicated in the differentiation of the midline also regulate hsp23 promoter activity. Phenotypic analysis of a transgenic line exhibiting loss of Hsp23 expression in the central nervous system suggests that Hsp23 is not required for development and function of this tissue. Likewise, its overexpression does not cause deleterious effects, as development remains unaffected. Conclusions Based on the presented data, we suggest that the tightly regulated developmental expression of Hsp23 is not actively involved in cell differentiation and central nervous system development per se but rather reflects a putative role in preventive "pre-stress" neuroprotection or in non-vital process(es) common to the identified cell lineages. PMID:14617383

Carbon nanotubes and graphene as emerging candidates in neuroregeneration and neurodrug delivery

PubMed Central

John, Agnes Aruna; Subramanian, Aruna Priyadharshni; Vellayappan, Muthu Vignesh; Balaji, Arunpandian; Mohandas, Hemanth; Jaganathan, Saravana Kumar

2015-01-01

Neuroregeneration is the regrowth or repair of nervous tissues, cells, or cell products involved in neurodegeneration and inflammatory diseases of the nervous system like Alzheimer’s disease and Parkinson’s disease. Nowadays, application of nanotechnology is commonly used in developing nanomedicines to advance pharmacokinetics and drug delivery exclusively for central nervous system pathologies. In addition, nanomedical advances are leading to therapies that disrupt disarranged protein aggregation in the central nervous system, deliver functional neuroprotective growth factors, and change the oxidative stress and excitotoxicity of affected neural tissues to regenerate the damaged neurons. Carbon nanotubes and graphene are allotropes of carbon that have been exploited by researchers because of their excellent physical properties and their ability to interface with neurons and neuronal circuits. This review describes the role of carbon nanotubes and graphene in neuroregeneration. In the future, it is hoped that the benefits of nanotechnologies will outweigh their risks, and that the next decade will present huge scope for developing and delivering technologies in the field of neuroscience. PMID:26170663

Carbon nanotubes and graphene as emerging candidates in neuroregeneration and neurodrug delivery.

PubMed

John, Agnes Aruna; Subramanian, Aruna Priyadharshni; Vellayappan, Muthu Vignesh; Balaji, Arunpandian; Mohandas, Hemanth; Jaganathan, Saravana Kumar

2015-01-01

Neuroregeneration is the regrowth or repair of nervous tissues, cells, or cell products involved in neurodegeneration and inflammatory diseases of the nervous system like Alzheimer's disease and Parkinson's disease. Nowadays, application of nanotechnology is commonly used in developing nanomedicines to advance pharmacokinetics and drug delivery exclusively for central nervous system pathologies. In addition, nanomedical advances are leading to therapies that disrupt disarranged protein aggregation in the central nervous system, deliver functional neuroprotective growth factors, and change the oxidative stress and excitotoxicity of affected neural tissues to regenerate the damaged neurons. Carbon nanotubes and graphene are allotropes of carbon that have been exploited by researchers because of their excellent physical properties and their ability to interface with neurons and neuronal circuits. This review describes the role of carbon nanotubes and graphene in neuroregeneration. In the future, it is hoped that the benefits of nanotechnologies will outweigh their risks, and that the next decade will present huge scope for developing and delivering technologies in the field of neuroscience.

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

Code of Federal Regulations, 2012 CFR

2012-10-01

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

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

Code of Federal Regulations, 2013 CFR

2013-10-01

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

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

Code of Federal Regulations, 2011 CFR

2011-10-01

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

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

Code of Federal Regulations, 2014 CFR

2014-10-01

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

[Correlates between Munich Functional Development Diagnostics and postural reactivity findings based on seven provovoked postural reactions modus Vojta during the first period of child's life].

PubMed

Gajewska, Ewa; Sobieska, Magdalena; Samborski, Włodzimierz

2006-01-01

This work presents two diagnostic methods which were used to examine 57 children during their first three months of life. By classifying abnormalities of central nervous coordination we compared seven postural reactions according to Vojta with spontaneous behaviour of the child according to Munich Functional Development Diagnostics. It was demonstrated that both methods for the detection of early lesions in the central nervous system are sensitive. Good coherence of the results suggests that both methods may be used interchangeably.

[Guillain-Barré syndrome in a patient with primary sicca syndrome].

PubMed

Pryszmont, M; Sierakowski, S; Popławska, T; Domysławska, I; Pryszmont, J; Pawlak-Tumiel, B

2000-01-01

At the age of 23 the patient showed the first signs of dryness syndrome. Those symptoms developed progressively and during a few years primary Sjögren syndrome was noted. In the 37th year of life suddenly the patient developed very severe Gullian-Barré syndrome with involvement of the peripheral and central nervous system and with a considerable autonomic component. After treatment the patient improved, however mild symptoms of central and peripheral nervous system destruction remained. Those symptoms are still present and the patient is under the care of the Neurology and Rheumatology Clinic.

[Micro/nano-engineering to control growth of neuronal cells and tissue engineering applied to the central nervous system].

PubMed

Béduer, Amélie; Vaysse, Laurence; Loubinoux, Isabelle; Vieu, Christophe

2013-01-01

Central nervous system pathologies are often characterized by the loss of cell populations. A promising therapy now being developed consists in using bioactive materials, associating grafted cells to biopolymers which provide a scaffold for the in vitro building of new tissues, to be implanted in vivo. In the present article, the state of the art of this field, at crossroads between microtechnology and neuroscience, is described in detail; thereafter our own approach and results about interactions between adult human neural stem cells and microstructured polymers are summarized and discussed. In a second part, some central nervous system repair strategies, based on cerebral tissue engineering, are presented. We will report the main results of our studies to work out and characterize in vivo a cerebral bioprosthesis. © Société de Biologie, 2014.

Central nervous system complications and neuroradiological findings in children with chronic active Epstein-Barr virus infection.

PubMed

Ishikawa, Nobutsune; Kawaguchi, Hiroshi; Nakamura, Kazuhiro; Kobayashi, Masao

2013-02-01

Although many neurological complications have been described in acute Epstein-Barr virus infection, few reports have discussed the central nervous system complications in chronic active Epstein-Barr virus (CAEBV) infection. We retrospectively surveyed the medical records of 14 patients with CAEBV infection in our institute. Neuroradiological studies were performed in 10 of these patients. Five had no neurological symptoms, whereas two presented with posterior reversible encephalopathy syndrome, one presented with basal ganglia calcification, and one presented with falx cerebri hemorrhage. Although both of the posterior reversible encephalopathy syndrome cases developed epilepsy several years after recovering from prolonged neurological deterioration, the others had no neurological sequelae. This study revealed that various central nervous system complications may occur during the clinical course in pediatric CAEBV patients. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

Imaging the fetal central nervous system

PubMed Central

De Keersmaecker, B.; Claus, F.; De Catte, L.

2011-01-01

The low prevalence of fetal central nervous system anomalies results in a restricted level of exposure and limited experience for most of the obstetricians involved in prenatal ultrasound. Sonographic guidelines for screening the fetal brain in a systematic way will probably increase the detection rate and enhance a correct referral to a tertiary care center, offering the patient a multidisciplinary approach of the condition. This paper aims to elaborate on prenatal sonographic and magnetic resonance imaging (MRI) diagnosis and outcome of various central nervous system malformations. Detailed neurosonographic investigation has become available through high resolution vaginal ultrasound probes and the development of a variety of 3D ultrasound modalities e.g. ultrasound tomographic imaging. In addition, fetal MRI is particularly helpful in the detection of gyration and neurulation anomalies and disorders of the gray and white matter. PMID:24753859

[New concepts on the role of cytokines in the central nervous system].

PubMed

Jacque, C; Tchélingérian, J L

1994-11-01

Initially described as modulatory molecules in the peripheral immune system and during haematopoiesis, several cytokines also play a role in the brain. Their synthesis in the central nervous system (CNS) is not due solely to glial cell activation or invading immune cells. On the one hand, several functions of central neurons are modulated by cytokines such as IL-1, TNF alpha, IL-2 and IL-6. Thus, IL-1 and TNF alpha modulate the synthesis of several neuromediators and modify ion influxes. IL-2 regulates the effects of central dopaminergic neurons on cholinergic, noradrenergic, serotoninergic and glutamatergic functions. On the other hand, neurons have recently been shown to be able to synthesize some of these cytokines under specific traumatic conditions. For example, a lesion to the hippocampus induces neuronal synthesis of IL-1 alpha and TNF alpha. This induction through neuronal circuits may operate at a distance in contrast to the glial reaction operating only locally. The recent demonstration of the expression by central neurons of receptors specific for these cytokines support a potentially crucial role for these molecules in brain function. Some data emerge in the literature demonstrating a potent expression of cytokines in the central nervous system in numerous pathological situations. Then, it appears that, at the interface between nervous and immune systems, cytokines may bear a pivotal role in the development of specific symptoms in neuroimmune diseases.

From Central Pattern Generator to Sensory Template in the Evolution of Birdsong

ERIC Educational Resources Information Center

Konishi, Masakazu

2010-01-01

Central nervous networks, be they a part of the human brain or a group of neurons in a snail, may be designed to produce distinct patterns of movement. Central pattern generators can account for the development and production of normal vocal signals without auditory feedback in non-songbirds. Songbirds need auditory feedback to develop and…

Glossary

MedlinePlus

... effective, directed treatments. Central Nervous System The "central command system" of the body, it includes the brain, ... The central nervous system (CNS) is the "central command system" of the body, and includes the brain, ...

KCC3 axonopathy: neuropathological features in the central and peripheral nervous system.

PubMed

Auer, Roland N; Laganière, Janet L; Robitaille, Yves O; Richardson, John; Dion, Patrick A; Rouleau, Guy A; Shekarabi, Masoud

2016-09-01

Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC) is an autosomal recessive disease of the central and peripheral nervous system that presents as early-onset polyneuropathy. Patients are hypotonic and areflexic from birth, with abnormal facial features and atrophic muscles. Progressive peripheral neuropathy eventually confines them to a wheelchair in the second decade of life, and death occurs by the fourth decade. We here define the neuropathologic features of the disease in autopsy tissues from eight cases. Both developmental and neurodegenerative features were found. Hypoplasia or absence of the major telencephalic commissures and a hypoplasia of corticospinal tracts to half the normal size, were the major neurodevelopmental defects we observed. Despite being a neurodegenerative disease, preservation of brain weight and a conspicuous absence of neuronal or glial cell death were signal features of this disease. Small tumor-like overgrowths of axons, termed axonomas, were found in the central and peripheral nervous system, indicating attempted axonal regeneration. We conclude that the neurodegenerative deficits in HMSN/ACC are primarily caused by an axonopathy superimposed upon abnormal development, affecting peripheral but also central nervous system axons, all ultimately because of a genetic defect in the axonal cotransporter KCC3.

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.

The blood-brain barrier: an engineering perspective

PubMed Central

Wong, Andrew D.; Ye, Mao; Levy, Amanda F.; Rothstein, Jeffrey D.; Bergles, Dwight E.; Searson, Peter C.

2013-01-01

It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Since Ehrlich's first experiments, only a small number of molecules, such as alcohol and caffeine have been found to cross the blood-brain barrier, and this selective permeability remains the major roadblock to treatment of many central nervous system diseases. At the same time, many central nervous system diseases are associated with disruption of the blood-brain barrier that can lead to changes in permeability, modulation of immune cell transport, and trafficking of pathogens into the brain. Therefore, advances in our understanding of the structure and function of the blood-brain barrier are key to developing effective treatments for a wide range of central nervous system diseases. Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective. New insight into the physics of the blood-brain barrier could ultimately lead to clinical advances in the treatment of central nervous system diseases. PMID:24009582

78 FR 9311 - Hazard Communication; Corrections and Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-08

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

From CNS stem cells to neurons and glia: Sox for everyone.

PubMed

Reiprich, Simone; Wegner, Michael

2015-01-01

Neuroepithelial precursor cells of the vertebrate central nervous system either self-renew or differentiate into neurons, oligodendrocytes or astrocytes under the influence of a gene regulatory network that consists in transcription factors, epigenetic modifiers and microRNAs. Sox transcription factors are central to this regulatory network, especially members of the SoxB, SoxC, SoxD, SoxE and SoxF groups. These Sox proteins are widely expressed in neuroepithelial precursor cells and in newly specified, differentiating and mature neurons, oligodendrocytes and astrocytes and influence their identity, survival and development. They exert their effect predominantly at the transcriptional level but also have substantial impact on expression at the epigenetic and posttranscriptional levels with some Sox proteins acting as pioneer factors, recruiting chromatin-modifying and -remodelling complexes or influencing microRNA expression. They interact with a large variety of other transcription factors and influence the expression of regulatory molecules and effector genes in a cell-type-specific and temporally controlled manner. As versatile regulators with context-dependent functions, they are not only indispensable for central nervous system development but might also be instrumental for the development of reprogramming and cell conversion strategies for replacement therapies and for assisted regeneration after injury or degeneration-induced cell loss in the central nervous system.

75 FR 37301 - Exempt Chemical Mixtures Containing Gamma-Butyrolactone

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-29

... their central nervous system (CNS) depressant effect. An overdose from GBL or GHB may result in... the central nervous system that is substantially similar to or greater than the stimulant, depressant, or hallucinogenic effect on the central nervous system of a controlled substance in schedule I or II...

76 FR 44595 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug... Committee: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee...

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.

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.

The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

PubMed

Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

2017-02-01

Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central nervous system positivity in T-cell acute lymphoblastic leukemia (odds ratio=11.00, 95% confidence interval, 2.00-60.62). We propose zeta-chain-associated protein kinase 70, CCR7 and CXCR4 as markers of central nervous system infiltration in acute lymphoblastic leukemia warranting prospective investigation. Copyright© Ferrata Storti Foundation.

[Protocadherin α gene cluster is required for myelination and oligodendrocyte development].

PubMed

Yu, Yu; Suo, Lun; Wu, Qiang

2012-08-01

This work used Immunohistochemistry to examine the expression of myelin basic protein and accumulation of oligodendrocytes in Pchdα knockout and control littermate mice. Data showed that in Pchdα knockout mice, Myelin proteins decrease in the central nervous system and mature oligodendrocytes in the cerebellum also decrease. Furthermore, deletion of the Pcdhα cluster does not cause any change to the axons and astrocytes in quantification of relative marker proteins. These findings suggest that the Pcdhα cluster may be required for myelination and oligodendrite development of the brain in mice, and that Pcdhα cluster may play a key role in the development of the central nervous system.

75 FR 17417 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

78 FR 63478 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

75 FR 36428 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

77 FR 20037 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

78 FR 63481 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

76 FR 3912 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

75 FR 12768 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy.

PubMed

Hoffmann, Christine; Ziegler, Ute; Buschmann, Anne; Weber, Artur; Kupfer, Leila; Oelschlegel, Anja; Hammerschmidt, Baerbel; Groschup, Martin H

2007-03-01

To elucidate the still-unknown pathogenesis of bovine spongiform encephalopathy (BSE), an oral BSE challenge and sequential kill study was carried out on 56 calves. Relevant tissues belonging to the peripheral and central nervous system, as well as to the lymphoreticular tract, from necropsied animals were analysed by highly sensitive immunohistochemistry and immunoblotting techniques to reveal the presence of BSE-associated pathological prion protein (PrPSc) depositions. Our results demonstrate two routes involving the autonomic nervous system through which BSE prions spread by anterograde pathways from the gastrointestinal tract (GIT) to the central nervous system (CNS): (i) via the coeliac and mesenteric ganglion complex, splanchnic nerves and the lumbal/caudal thoracic spinal cord (representing the sympathetic GIT innervation); and (ii) via the Nervus vagus (parasympathetic GIT innervation). The dorsal root ganglia seem to be subsequently affected, so it is likely that BSE prion invasion of the non-autonomic peripheral nervous system (e.g. sciatic nerve) is a secondary retrograde event following prion replication in the CNS. Moreover, BSE-associated PrPSc was already detected in the brainstem of an animal 24 months post-infection, which is 8 months earlier than reported previously. These findings are important for the understanding of BSE pathogenesis and for the development of new diagnostic strategies for this infectious disease.

Tumors of the central nervous system: clinical aspects, molecular mechanisms, unanswered questions, and future research directions.

PubMed

Babcock, Michael A; Kostova, Felina V; Guha, Abhijit; Packer, Roger J; Pollack, Ian F; Maria, Bernard L

2008-10-01

Central nervous system tumors are the most common solid tumors in children. Many histological subtypes and biological variants exist. The 2007 Neurobiology of Disease in Children Symposium, held in conjunction with the 36th annual meeting of the Child Neurology Society, aimed to define current knowledge in the field and to develop specific aims for future clinical, translational, and fundamental science. Because of advances in structural and metabolic imaging, surgical technique, and combination therapies, the life expectancy of children with some of the most common tumors, such as cerebellar astrocytomas and medulloblastomas, has improved. Other common tumor types, including diffuse pontine gliomas and malignant embryonal tumors, still have a dismal prognosis. As novel therapies are identified for pediatric central nervous system tumors, long-term survival may be associated with considerable disability. A cooperative effort is crucial to early diagnosis and to translating basic research findings into safe, effective new treatments.

Neuroimaging of Pain: Human Evidence and Clinical Relevance of Central Nervous System Processes and Modulation.

PubMed

Martucci, Katherine T; Mackey, Sean C

2018-06-01

Neuroimaging research has demonstrated definitive involvement of the central nervous system in the development, maintenance, and experience of chronic pain. Structural and functional neuroimaging has helped elucidate central nervous system contributors to chronic pain in humans. Neuroimaging of pain has provided a tool for increasing our understanding of how pharmacologic and psychologic therapies improve chronic pain. To date, findings from neuroimaging pain research have benefitted clinical practice by providing clinicians with an educational framework to discuss the biopsychosocial nature of pain with patients. Future advances in neuroimaging-based therapeutics (e.g., transcranial magnetic stimulation, real-time functional magnetic resonance imaging neurofeedback) may provide additional benefits for clinical practice. In the future, with standardization and validation, brain imaging could provide objective biomarkers of chronic pain, and guide treatment for personalized pain management. Similarly, brain-based biomarkers may provide an additional predictor of perioperative prognoses.

Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring

DTIC Science & Technology

2016-10-01

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

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

PubMed

Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

2016-04-01

Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic leukemia are due to other etiologies in approximately 80% of cases. Analysis of the cerebrospinal fluid has high sensitivity but limited specificity to distinguish clinically significant chronic lymphocytic leukemia involvement from other etiologies. Copyright© Ferrata Storti Foundation.

[Prevalence of central nervous system tumours and histological identification in the operated patient: 20 years of experience].

PubMed

Anaya-Delgadillo, Gustavo; de Juambelz-Cisneros, Pedro Pablo; Fernández-Alvarado, Basilio; Pazos-Gómez, Fernando; Velasco-Torre, Andrea; Revuelta-Gutiérrez, Rogelio

Central nervous system tumours comprise a heterogeneous group of neoplasms with great histological diversity. Despite the rising prevalence of these tumours in developing countries, some places like Mexico and Latin America have no representative studies that show the real impact of these tumours in our population. To describe the characteristics of the primary and secondary tumours of the central nervous system in the last 20 years in a Mexican institution. Patients with histopathological diagnosis from 1993 to 2013 in our institution, grouping them according to WHO classification 2007, characterising them by age group, gender, and anatomical location. There were a total of 511 tumours of the central nervous system. Of those, 292 were women and 219 men, with a ratio 1.3: 1, and a mean age of 49.3 years. Tumours with higher prevalence were: Meningeal tumours, 171 (33%), followed by neuroepithelial, 121 (24%). Astrocytoma had the highest prevalence in paediatric patients, whereas in those older than 20 years it was the meningioma. The supratentorial location was the most involved. This is the first study of a series of cases in Mexico that is performed by taking into account benign and malignant tumours of the central nervous system, with patients of all age groups with a range of 20 years. While this work only represents a retrospective analysis of an institution, it can be a strong indication of the epidemiology of these tumours in our environment. Copyright © 2016. Publicado por Masson Doyma México S.A.

Protein profiles of Taenia solium cysts obtained from skeletal muscles and the central nervous system of pigs: Search for tissue-specific proteins.

PubMed

Navarrete-Perea, José; Moguel, Bárbara; Bobes, Raúl José; Villalobos, Nelly; Carrero, Julio César; Sciutto, Edda; Soberón, Xavier; Laclette, Juan Pedro

2017-01-01

Taeniasis/cysticercosis caused by the tapeworm Taenia solium is a parasite disease transmitted among humans and pigs, the main intermediate host. The larvae/cysts can lodge in several tissues of the pig, i.e. skeletal muscles and different locations of the central nervous system. The molecular mechanisms associated to tissue preferences of the cysts remain poorly understood. The major public health concern about this zoonosis is due to the human infections by the larval form in the central nervous system, causing a highly pleomorphic and debilitating disease known as neurocysticercosis. This study was aimed to explore the 2DE protein maps of T. solium cysts obtained from skeletal muscles and central nervous system of naturally infected pigs. The gel images were analyzed through a combination of PDQuest™ and multivariate analysis. Results showed that differences in the protein patterns of cysts obtained from both tissues were remarkably discrete. Only 7 protein spots were found specifically associated to the skeletal muscle localization of the cysts; none was found significantly associated to the central nervous system. The use of distinct protein fractions of cysts allowed preliminary identification of several tissue-specific antigenic bands. The implications of these findings are discussed, as well as several strategies directed to achieve the complete characterization of this parasite's proteome, in order to extend our understanding of the molecular mechanisms underlying tissue localization of the cysts and to open avenues for the development of immunological tissue-specific diagnosis of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Combined central diabetes insipidus and cerebral salt wasting syndrome in children.

PubMed

Lin, Jainn-Jim; Lin, Kuang-Lin; Hsia, Shao-Hsuan; Wu, Chang-Teng; Wang, Huei-Shyong

2009-02-01

Central diabetes insipidus, a common consequence of acute central nervous system injury, causes hypernatremia; cerebral salt wasting syndrome can cause hyponatremia. The two conditions occurring simultaneous are rarely described in pediatric patients. Pediatric cases of combined diabetes insipidus and cerebral salt wasting after acute central nervous system injury between January 2000 and December 2007 were retrospectively reviewed, and clinical characteristics were systemically assessed. Sixteen patients, aged 3 months to 18 years, met study criteria: 11 girls and 5 boys. The most common etiologies were severe central nervous system infection (n = 7, 44%) and hypoxic-ischemic event (n = 4, 25%). In 15 patients, diabetes insipidus was diagnosed during the first 3 days after acute central nervous system injury. Onset of cerebral salt wasting syndrome occurred 2-8 days after the onset of diabetes insipidus. In terms of outcome, 13 patients died (81%) and 3 survived under vegetative status (19%). Central diabetes insipidus and cerebral salt wasting syndrome may occur after acute central nervous system injury. A combination of both may impede accurate diagnosis. Proper differential diagnoses are critical, because the treatment strategy for each entity is different.

Optical coherence tomography of the preterm eye: from retinopathy of prematurity to brain development

PubMed Central

Rothman, Adam L; Mangalesh, Shwetha; Chen, Xi; Toth, Cynthia A

2016-01-01

Preterm infants with retinopathy of prematurity are at increased risk of poor neurodevelopmental outcomes. Because the neurosensory retina is an extension of the central nervous system, anatomic abnormalities in the anterior visual pathway often relate to system and central nervous system health. We describe optical coherence tomography as a powerful imaging modality that has recently been adapted to the infant population and provides noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside. Optical coherence tomography has increased understanding of normal eye development and has identified several potential biomarkers of brain abnormalities and poorer neurodevelopment. PMID:28539807

Chondroitin sulfates and their binding molecules in the central nervous system.

PubMed

Djerbal, L; Lortat-Jacob, H; Kwok, Jcf

2017-06-01

Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases.

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.

Vitamin D and the central nervous system.

PubMed

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

2013-01-01

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

Pío del Río-Hortega: A Visionary in the Pathology of Central Nervous System Tumors

PubMed Central

Ramon y Cajal Agüeras, Santiago

2016-01-01

The last 140 years have seen considerable advances in knowledge of central nervous system tumors. However, the main tumor types had already been described during the early years of the twentieth century. The studies of Dr. Pío del Río Hortega have been ones of the most exhaustive histology and cytology-based studies of nervous system tumors. Río Hortega's work was performed using silver staining methods, which require a high level of practical skill and were therefore difficult to standardize. His technical aptitude and interest in nervous system tumors played a key role in the establishment of his classification, which was based on cell lineage and embryonic development. Río Hortega's approach was controversial when he proposed it. Current classifications are not only based on cell type and embryonic lineage, as well as on clinical characteristics, anatomical site, and age. PMID:26973470

Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

PubMed

Hur, Eun-Mi; Lee, Byoung Dae

2014-12-01

Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

Applications of CRISPR/Cas9 in the Mammalian Central Nervous System



PubMed Central

Savell, Katherine E.; Day, Jeremy J.

2017-01-01

Within the central nervous system, gene regulatory mechanisms are crucial regulators of cellular development and function, and dysregulation of these systems is commonly observed in major neuropsychiatric and neurological disorders. However, due to a lack of tools to specifically modulate the genome and epigenome in the central nervous system, many molecular and genetic mechanisms underlying cognitive function and behavior are still unknown. Although genome editing tools have been around for decades, the recent emergence of inexpensive, straightforward, and widely accessible CRISPR/Cas9 systems has led to a revolution in gene editing. The development of the catalytically dead Cas9 (dCas9) expanded this flexibility even further by acting as an anchoring system for fused effector proteins, structural scaffolds, and RNAs. Together, these advances have enabled robust, modular approaches for specific targeting and modification of the local chromatin environment at a single gene. This review highlights these advancements and how the combination of powerful modulatory tools paired with the versatility of CRISPR-Cas9-based systems offer great potential for understanding the underlying genetic and epigenetic contributions of neuronal function, behavior, and neurobiological diseases. PMID:29259522

Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma

ClinicalTrials.gov

2017-08-28

B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Central Nervous System Lymphoma; Intraocular Lymphoma; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Recurrent Adult Diffuse Large Cell Lymphoma; Retinal Lymphoma

75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug Safety... and Central Nervous System Drugs Advisory Committee and the Drug Safety and Risk Management Advisory...

Physiology of motion sickness symptoms

NASA Technical Reports Server (NTRS)

Harm, Deborah L.

1990-01-01

Motion sickness research is reviewed with the emphasis placed on theories developed to explain its symptomatology. A general review of central nervous system, autonomic nervous system, and neuroendocrine system involvement in the syndrome. Particular attention is given to signs, symptoms, and physiological correlates, methodological issues, and directions for future research based on a dynamic interactive systems model.

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

The Gut Microbiota and Autism Spectrum Disorders

PubMed Central

Li, Qinrui; Han, Ying; Dy, Angel Belle C.; Hagerman, Randi J.

2017-01-01

Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies have shown alterations in the composition of the fecal flora and metabolic products of the gut microbiome in patients with ASD. The gut microbiota influences brain development and behaviors through the neuroendocrine, neuroimmune and autonomic nervous systems. In addition, an abnormal gut microbiota is associated with several diseases, such as inflammatory bowel disease (IBD), ASD and mood disorders. Here, we review the bidirectional interactions between the central nervous system and the gastrointestinal tract (brain-gut axis) and the role of the gut microbiota in the central nervous system (CNS) and ASD. Microbiome-mediated therapies might be a safe and effective treatment for ASD. PMID:28503135

Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

PubMed Central

Cancela, Camila Silva Peres; Murao, Mitiko; Viana, Marcos Borato; de Oliveira, Benigna Maria

2012-01-01

Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count < 50 x 109/L (p-value = 0.0008). There was no difference in cumulative central nervous system relapse (isolated or combined) for the other analyzed variables: immunophenotype, traumatic lumbar puncture, interval between diagnosis and first lumbar puncture and place where the procedure was performed. Conclusions These results suggest that a leukocyte count > 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

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

PubMed

Maduna, Tando; Lelievre, Vincent

2016-12-01

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

Central sympathoexcitatory actions of angiotensin II: role of type 1 angiotensin II receptors.

PubMed

DiBona, G F

1999-01-01

The role of the renin-angiotensin system in the control of sympathetic nerve activity is reviewed. Two general mechanisms are considered, one that involves the effects of circulating angiotensin II (AngII) on the central nervous system and a second that involves the central nervous system effects of AngII that originates within the central nervous system. The role of type 1 AngII receptors in discrete brain sites that mediate the sympathoexcitatory actions of AngII of either circulating or central nervous system origin is examined. AngII of circulating origin has ready access to the subfornical organ and area postrema, where it can bind to type 1 AngII receptors on neurons whose connections to the nucleus tractus solitarius and rostral ventrolateral medulla result in sympathoexcitation. In the rostral ventrolateral medulla, angiotensin peptides of central nervous system origin, likely involving angiotensin species in addition to AngII and binding to receptors other than type 1 or 2 AngII receptors, tonically support sympathetic nerve activity.

Femoral-facial syndrome with malformations in the central nervous system.

PubMed

Leal, Evelia; Macías-Gómez, Nelly; Rodríguez, Lisa; Mercado, F Miguel; Barros-Núñez, Patricio

2003-01-01

The femoral hypoplasia-unusual facies syndrome (FFS) is a very rare association of femoral and facial abnormalities. Maternal diabetes mellitus has been mainly involved as the causal agent. We report the second case of FFS with anomalies in the central nervous system (CNS) including corticosubcortical atrophy, colpocephaly, partial agenesis of corpus callosum, hypoplasia of the falx cerebri and absent septum pellucidum. The psychomotor development has been normal. We propose that the CNS defects observed in these patients are part of the spectrum of abnormalities in the FFS.

Virus signaling and apoptosis in the central nervous system infection.

PubMed

Perkins, Dana

2005-09-01

Viruses target the central nervous system (CNS) incidentally, due to complications of systemic infection, or specifically, by ascending via the axons of peripheral and cranial nerves. In the CNS, viruses cause acute disease (viz. encephalitis), latent infections or neurodegenerative pathology. Causation of acute disease or immune-mediated pathology, and virus involvement in the etiology of chronic neurodegenerative diseases depends, at least in part, on the ability to commander signaling pathways. Better understanding of these virus-host cell interactions will help identify molecular targets for the development of improved therapeutic strategies.

A Case of the Cauda Equina Syndrome Associated With the Intrathecal Chemotherapy in a Patient With Primary Central Nervous System Lymphoma

PubMed Central

Park, Seunglee; Kang, Jung-Il; Bang, Hyun; Kim, Bo-Ram

2013-01-01

The intrathecal chemotherapy with methotrexate and cytarabine arabinoside is used for the treatment and prophylaxis of the primary central nervous system lymphoma. The therapy may induce neurotoxicity including the cauda equina syndrome. We report a case of a 58-year-old man with the diffuse large B-cell lymphoma, who developed the cauda equina syndrome after the administration of intrathecal methotrexate and cytarabine arabinoside, as diagnosed by the electrodiagnostic, urodynamic, and radiologic approaches. PMID:23869341

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

PubMed

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

2006-11-01

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

Primary central nervous system B-cell lymphoma in a young dog

PubMed Central

Kim, Na-Hyun; Ciesielski, Thomas; Kim, Jung H.; Yhee, Ji-Young; Im, Keum-Soon; Nam, Hae-Mi; Kim, Il-Hwan; Kim, Jong-Hyuk; Sur, Jung-Hyang

2012-01-01

This report describes a primary central nervous system B-cell lymphoma in a 3-year-old intact female Maltese dog. Canine primary central nervous system lymphomas constitute about 4% of all intracranial primary neoplasms, but comprehensive histopathologic classifications have rarely been carried out. This is the first report of this disease in a young adult dog. PMID:23115372

ADDME – Avoiding Drug Development Mistakes Early: central nervous system drug discovery perspective

PubMed Central

Tsaioun, Katya; Bottlaender, Michel; Mabondzo, Aloise

2009-01-01

The advent of early absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening has increased the attrition rate of weak drug candidates early in the drug-discovery process, and decreased the proportion of compounds failing in clinical trials for ADMET reasons. This paper reviews the history of ADMET screening and its place in pharmaceutical development, and central nervous system drug discovery in particular. Assays that have been developed in response to specific needs and improvements in technology that result in higher throughput and greater accuracy of prediction of human mechanisms of absorption and toxicity are discussed. The paper concludes with the authors' forecast of new models that will better predict human efficacy and toxicity. PMID:19534730

Natural History Study of Children With Metachromatic Leukodystrophy

ClinicalTrials.gov

2016-04-19

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

[Process in menstrual blood-derived mesenchymal stem cells for treatment of central nervous system diseases].

PubMed

Liu, Mengmeng; Cheng, Xinran; Li, Kaikai; Xu, Mingrui; Wu, Yongji; Wang, Mengli; Zhang, Qianru; Yan, Wenyong; Luo, Chang; Zhao, Shanting

2018-05-25

Stem cell research has become a frontier in the field of life sciences, and provides an ideal model for exploring developmental biology problems such as embryogenesis, histiocytosis, and gene expression regulation, as well as opens up new doors for clinical tissue defective and inheritance diseases. Among them, menstrual blood-derived stem cells (MenSCs) are characterized by wide source, multi-directional differentiation potential, low immune rejection characteristics. Thus, MenSCs can achieve individual treatment and have the most advantage of the clinical application. The central nervous system, including brain and spinal cord, is susceptible to injury. And lethality and morbidity of them tops the list of all types of trauma. Compared to peripheral nervous system, recovery of central nervous system after damage remains extremely hard. However, the treatment of stem cells, especially MenSCs, is expected to solve this problem. Therefore, biological characteristics of MenSCs and their treatment in the respect of central nervous system diseases have been reviewed at home and abroad in recent years, so as to provide reference for the treatment of central nervous system diseases.

The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system.

PubMed

Mihm, Bernhard; Bergmann, Markus; Brück, Wolfgang; Probst-Cousin, Stefan

2014-06-01

To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14-positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8-positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process. © 2013 Japanese Society of Neuropathology.

Magnetic resonance imaging characteristics in four dogs with central nervous system neosporosis.

PubMed

Parzefall, Birgit; Driver, Colin J; Benigni, Livia; Davies, Emma

2014-01-01

Neosporosis is a polysystemic disease that can affect dogs of any age and can cause inflammation of the central nervous system. Antemortem diagnosis can be challenging, as clinical and conventional laboratory test findings are often nonspecific. A previous report described cerebellar lesions in brain MRI studies of seven dogs and proposed that these may be characteristic for central nervous system Neosporosis. The purpose of this retrospective study was to describe MRI characteristics in another group of dogs with confirmed central nervous system neosporosis and compare them with the previous report. The hospital's database was searched for dogs with confirmed central nervous system neosporosis and four observers recorded findings from each dog's MRI studies. A total of four dogs met inclusion criteria. Neurologic examination was indicative of a forebrain and cerebellar lesion in dog 2 and multifocal central nervous system disease in dogs 1, 3, and 4. Magnetic resonance imaging showed mild bilateral and symmetrical cerebellar atrophy in three of four dogs (dogs 2, 3, 4), intramedullary spinal cord changes in two dogs (dogs 3, 4) and a mesencephalic and metencephalic lesion in one dog (dog 2). Multifocal brain lesions were recognized in two dogs (dogs 1, 4) and were present in the thalamus, lentiform nucleus, centrum semiovale, internal capsule, brainstem and cortical gray matter of the frontal, parietal or temporal lobe. Findings indicated that central nervous system neosporosis may be characterized by multifocal MRI lesions as well as cerebellar involvement in dogs. © 2014 American College of Veterinary Radiology.

Postnatal testosterone may be an important mediator of the association between prematurity and male neurodevelopmental disorders: a hypothesis.

PubMed

Rice, Timothy R

2017-04-01

Children born premature are at risk for neurodevelopmental disorders, including autism and schizophrenia. This piece advances the hypothesis that altered androgen exposure observed in premature infants is an important mediator of the neurodevelopmental risk in males associated with prematurity. Specifically, the alterations of normative physiologic postnatal activations of the hypothalamic-pituitary-gonadal axis that occur in preterm males are hypothesized to contribute to the risk of neuropsychiatric pathology of prematurity through altered androgen-mediated organizational effects on the developing brain. The physiology of testosterone and male central nervous system development in full-term births is reviewed and compared to the developmental processes of prematurity. The effects of the altered testosterone physiology observed within prematurity outside of the central nervous system are reviewed as a segue into a discussion of the effects within the nervous system, with a special focus on autism spectrum disorders and attention deficit hyperactivity disorder. The explanatory power of this model is reviewed as a supplement to the preexisting models of prematurity and neurodevelopmental risk, including infection and other perinatal central nervous system insults. The emphasis is placed on altered androgen exposure as serving as just one among many mediators of neurodevelopmental risk that may be of interest for further research and evidence-based investigation. Implications for diagnosis, management and preventative treatments conclude the piece.

This Neural Implant is designed to be implanted in the Human Central and Nervous System

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

None

A new class of neural implants being developed at the Livermore Lab are the first clinical quality devices capable of two-way conversations with the human nervous systems. Unlike existing interfaces that only sense or only stimulate, these devices are capable of stimulating and sensing using both electric and chemical signals.

This Neural Implant is designed to be implanted in the Human Central and Nervous System

ScienceCinema

None

2018-06-12

A new class of neural implants being developed at the Livermore Lab are the first clinical quality devices capable of two-way conversations with the human nervous systems. Unlike existing interfaces that only sense or only stimulate, these devices are capable of stimulating and sensing using both electric and chemical signals.

Potential Side Effect of Inadvertent Intravascular Administration of Liposomal Bupivacaine

DTIC Science & Technology

2017-06-01

treat and is potentially fatal. LAST can impair function of the central nervous system and cause cardiovascular collapse, with potentially...in the reversal of cardiovascular and central nervous system symptoms of local anesthetic and other lipophilic drug overdoses. ILE is gaining...to the sites of toxic action in the central nervous system and the heart. However, liposomal formulations of local anesthetics (EXPAREL in

Nervous system development in lecithotrophic larval and juvenile stages of the annelid Capitella teleta.

PubMed

Meyer, Néva P; Carrillo-Baltodano, Allan; Moore, Richard E; Seaver, Elaine C

2015-01-01

Reconstructing the evolutionary history of nervous systems requires an understanding of their architecture and development across diverse taxa. The spiralians encompass diverse body plans and organ systems, and within the spiralians, annelids exhibit a variety of morphologies, life histories, feeding modes and associated nervous systems, making them an ideal group for studying evolution of nervous systems. We describe nervous system development in the annelid Capitella teleta (Blake JA, Grassle JP, Eckelbarger KJ. Capitella teleta, a new species designation for the opportunistic and experimental Capitella sp. I, with a review of the literature for confirmed records. Zoosymposia. 2009;2:25-53) using whole-mount in situ hybridization for a synaptotagmin 1 homolog, nuclear stains, and cross-reactive antibodies against acetylated α-tubulin, 5-HT and FMRFamide. Capitella teleta is member of the Sedentaria (Struck TH, Paul C, Hill N, Hartmann S, Hosel C, Kube M, et al. Phylogenomic analyses unravel annelid evolution. Nature. 2011;471:95-8) and has an indirectly-developing, lecithotrophic larva. The nervous system of C. teleta shares many features with other annelids, including a brain and a ladder-like ventral nerve cord with five connectives, reiterated commissures, and pairs of peripheral nerves. Development of the nervous system begins with the first neurons differentiating in the brain, and follows a temporal order from central to peripheral and from anterior to posterior. Similar to other annelids, neurons with serotonin-like-immunoreactivity (5HT-LIR) and FMRFamide-like-immunoreactivity (FMRF-LIR) are found throughout the brain and ventral nerve cord. A small number of larval-specific neurons and neurites are present, but are visible only after the central nervous system begins to form. These larval neurons are not visible after metamorphosis while the rest of the nervous system is largely unchanged in juveniles. Most of the nervous system that forms during larvogenesis in C. teleta persists into the juvenile stage. The first neurons differentiate in the brain, which contrasts with the early formation of peripheral, larval-specific neurons found in some spiralian taxa with planktotrophic larvae. Our study provides a clear indication that certain shared features among annelids - e.g., five connectives in the ventral nerve cord - are only visible during larval stages in particular species, emphasizing the need to include developmental data in ancestral character state reconstructions. The data provided in this paper will serve as an important comparative reference for understanding evolution of nervous systems, and as a framework for future molecular studies of development.

Differential expression of neuroligin genes in the nervous system of zebrafish.

PubMed

Davey, Crystal; Tallafuss, Alexandra; Washbourne, Philip

2010-02-01

The establishment and maturation of appropriate synaptic connections is crucial in the development of neuronal circuits. Cellular adhesion is believed to play a central role in this process. Neuroligins are neuronal cell adhesion molecules that are hypothesized to act in the initial formation and maturation of synaptic connections. In order to establish the zebrafish as a model to investigate the in vivo role of Neuroligin proteins in nervous system development, we identified the zebrafish orthologs of neuroligin family members and characterized their expression. Zebrafish possess seven neuroligin genes. Synteny analysis and sequence comparisons show that NLGN2, NLGN3, and NLGN4X are duplicated in zebrafish, but NLGN1 has a single zebrafish ortholog. All seven zebrafish neuroligins are expressed in complex patterns in the developing nervous system and in the adult brain. The spatial and temporal expression patterns of these genes suggest that they occupy a role in nervous system development and maintenance.

Central voice production and pathophysiology of spasmodic dysphonia.

PubMed

Mor, Niv; Simonyan, Kristina; Blitzer, Andrew

2018-01-01

Our ability to speak is complex, and the role of the central nervous system in controlling speech production is often overlooked in the field of otolaryngology. In this brief review, we present an integrated overview of speech production with a focus on the role of central nervous system. The role of central control of voice production is then further discussed in relation to the potential pathophysiology of spasmodic dysphonia (SD). Peer-review articles on central laryngeal control and SD were identified from PUBMED search. Selected articles were augmented with designated relevant publications. Publications that discussed central and peripheral nervous system control of voice production and the central pathophysiology of laryngeal dystonia were chosen. Our ability to speak is regulated by specialized complex mechanisms coordinated by high-level cortical signaling, brainstem reflexes, peripheral nerves, muscles, and mucosal actions. Recent studies suggest that SD results from a primary central disturbance associated with dysfunction at our highest levels of central voice control. The efficacy of botulinum toxin in treating SD may not be limited solely to its local effect on laryngeal muscles and also may modulate the disorder at the level of the central nervous system. Future therapeutic options that target the central nervous system may help modulate the underlying disorder in SD and allow clinicians to better understand the principal pathophysiology. NA.Laryngoscope, 128:177-183, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Central Nervous System Infections in Denmark

ClinicalTrials.gov

2018-02-04

Central Nervous System Infections; Bacterial Meningitis; Viral Meningitis; Aseptic Meningitis; Encephalitis; Brain Abscess; Neuroborreliosis; Neurosyphilis; Lyme Disease; Tertiary Syphilis; Cerebral Abscess; Meningitis

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

PubMed

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

2018-02-22

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

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…

Major diagnostic and pathological features of iniencephaly based on twenty-four cases.

PubMed

Joó, József Gábor; Beke, Artúr; Papp, Csaba; Szigeti, Zsanett; Csaba, Akos; Papp, Zoltán

2008-01-01

Iniencephaly is quite a rare malformation the etiology of which is still not fully understood. In the majority of cases it is a grave and lethal condition. It is often complicated by other abnormalities affecting the central nervous system (spina bifida, anencephaly), but malformations involving other organs and systems may also be observed. Based on 24 cases the authors have surveyed the diagnostics of iniencephaly with special regard to the disorders affecting the central and non-central nervous systems. In addition, they have compared the results of prenatal diagnostics and pathological investigations. In the sample, maternal age ranged between 17 and 42 (median 24) years. Positive obstetrical-gynecological and genetic findings in the patients' history have been reported in 4 and 2 cases, respectively. In these cases, the maternal serum alpha-fetoprotein (AFP) values ranged between 0.7 and 3.9 (median 2.0) MoM, while the amniotic fluid AFP values were between 0.9 and 2.7 (median 1.4) MoM. Spina bifida (50%) and anencephaly (42%) were the most commonly occurring complications affecting the central nervous system. Among the non-central nervous system disorders, malformations of the abdominal (omphalocele) and thoracic walls (diaphragmatic hernia) were found most frequently and the tendency to develop associated polyhydramnios was also very high (75%). Pathological investigations revealed developmental disorders such as cleft lip and palate, ventricular septal defect and facial dysmorphism, which are difficult to detect using ultrasonography. Copyright 2008 S. Karger AG, Basel.

Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects

PubMed Central

Darwazeh, Rami; Yan, Yi

2013-01-01

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study. PMID:25206579

Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects.

PubMed

Darwazeh, Rami; Yan, Yi

2013-10-05

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study.

46 CFR Appendix C to Subpart C of... - Medical Surveillance Guidelines for Benzene

Code of Federal Regulations, 2014 CFR

2014-10-01

... depression of the hematopoietic system, pancytopenia, aplastic anemia, and leukemia. Inhalation of high concentrations may affect the functioning of the central nervous system. Aspiration of small amounts of liquid... an initial stimulatory effect on the central nervous system characterized by exhilaration, nervous...

46 CFR Appendix C to Subpart C to... - Medical Surveillance Guidelines for Benzene

Code of Federal Regulations, 2011 CFR

2011-10-01

... depression of the hematopoietic system, pancytopenia, aplastic anemia, and leukemia. Inhalation of high concentrations may affect the functioning of the central nervous system. Aspiration of small amounts of liquid... an initial stimulatory effect on the central nervous system characterized by exhilaration, nervous...

46 CFR Appendix C to Subpart C of... - Medical Surveillance Guidelines for Benzene

Code of Federal Regulations, 2013 CFR

2013-10-01

... depression of the hematopoietic system, pancytopenia, aplastic anemia, and leukemia. Inhalation of high concentrations may affect the functioning of the central nervous system. Aspiration of small amounts of liquid... an initial stimulatory effect on the central nervous system characterized by exhilaration, nervous...

46 CFR Appendix C to Subpart C of... - Medical Surveillance Guidelines for Benzene

Code of Federal Regulations, 2012 CFR

2012-10-01

... depression of the hematopoietic system, pancytopenia, aplastic anemia, and leukemia. Inhalation of high concentrations may affect the functioning of the central nervous system. Aspiration of small amounts of liquid... an initial stimulatory effect on the central nervous system characterized by exhilaration, nervous...

Plasticity and Activation of Spared Intraspinal Respiratory Circuits Following Spinal Cord Injury

DTIC Science & Technology

2016-10-01

fluorescent immunohistochemistry (IHC) procedures. Accordingly, we performed IHC with two markers commonly used in the central nervous system (GFAP and...immunohistochemistry (IHC) procedures. Accordingly, we performed IHC with two 365 markers commonly used in the central nervous system (GFAP and NeuN) either...905 mammalian central nervous system . J Neurosci Methods 1: 107-132, 1979. 906 Kirkwood PA, Munson JB, Sears TA, and Westgaard RH. Respiratory

Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

ClinicalTrials.gov

2014-11-04

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

Enriched Environment Increases PCNA and PARP1 Levels in Octopus vulgaris Central Nervous System: First Evidence of Adult Neurogenesis in Lophotrochozoa.

PubMed

Bertapelle, Carla; Polese, Gianluca; Di Cosmo, Anna

2017-06-01

Organisms showing a complex and centralized nervous system, such as teleosts, amphibians, reptiles, birds and mammals, and among invertebrates, crustaceans and insects, can adjust their behavior according to the environmental challenges. Proliferation, differentiation, migration, and axonal and dendritic development of newborn neurons take place in brain areas where structural plasticity, involved in learning, memory, and sensory stimuli integration, occurs. Octopus vulgaris has a complex and centralized nervous system, located between the eyes, with a hierarchical organization. It is considered the most "intelligent" invertebrate for its advanced cognitive capabilities, as learning and memory, and its sophisticated behaviors. The experimental data obtained by immunohistochemistry and western blot assay using proliferating cell nuclear antigen and poli (ADP-ribose) polymerase 1 as marker of cell proliferation and synaptogenesis, respectively, reviled cell proliferation in areas of brain involved in learning, memory, and sensory stimuli integration. Furthermore, we showed how enriched environmental conditions affect adult neurogenesis. © 2017 Wiley Periodicals, Inc.

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.

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.

[Central Nervous Involvement in Patients with Fukuyama Congenital Muscular Dystrophy].

PubMed

Ishigaki, Keiko

2016-02-01

Fukuyama congenital muscular dystrophy (FCMD), the second most common muscular dystrophy in the Japanese population, is an autosomal recessive disorder caused by mutations in the fukutin (FKTN) gene. The main features of FCMD are a combination of infantile-onset hypotonia, generalized muscle weakness, eye abnormalities and central nervous system involvement with mental retardation and seizures associated with cortical migration defects. The FKTN gene product is thought to be necessary for maintaining migrating neurons in an immature state during migration, and for supporting migration via α-dystroglycan in the central nervous system. Typical magnetic resonance imaging findings in FCMD patients are cobblestone lissencephaly and cerebellar cystic lesions. White matter abnormalities with hyperintensity on T(2)-weighted images are seen especially in younger patients and those with severe phenotypes. Most FCMD patients are mentally retarded and the level is moderate to severe, with IQs ranging from 30 to 50. In our recent study, 62% of patients developed seizures. Among them, 71% had only febrile seizures, 6% had afebrile seizures from the onset, and 22% developed afebrile seizures following febrile seizures. Most patients had seizures that were controllable with just 1 type of antiepileptic drug, but 18% had intractable seizures that must be treated with 3 medications.

Successful Treatment of Combined Aspergillus and Cytomegalovirus Abscess in Brain and Lung After Liver Transplant for Toxic Fulminant Hepatitis.

PubMed

Kim, Tae-Seok; Ahn, Keun Soo; Kim, Yong Hoon; Kim, Hyoung Tae; Jang, Byoung Kuk; Hwang, Jae Seok; Kim, Il-Man; Kang, Yu Na; Kang, Koo Jeong

2017-02-01

Invasive aspergillosis is one of the most important and fatal complications after liver transplant, especially in patients with involvement of the central nervous system. We present a case of a patient who developed cerebral and pulmonary aspergillosis, coinfected with cytomegalovirus, after liver transplant for toxic fulminant hepatitis. The patient was treated successfully with neurosurgical intervention and voriconazole. Voriconazole is considered more effective in cerebral aspergillosis than other anti-fungal agents due to the greater penetration into central nervous system and higher cerebrospinal fluid and brain tissue levels.

Do Helminths cause Epilepsy?

PubMed Central

Wagner, Ryan G; Newton, Charles R

2012-01-01

Both helminthiases and epilepsy occur globally, and are particularly prevalent in developing regions of the world. Studies have suggested an association between epilepsy and helminth infection, but a causal relationship is not established in many helminths, except perhaps with neurocysticercosis. We review the available literature on the global burden of helminths, and the epidemiological evidence linking helminths to epilepsy. We discuss possible routes that helminths affect the central nervous system of humans and the immunological response to helminth infection in the central nervous system, looking at possible mechanisms of epileptogenesis. Finally, we discuss the current gaps in knowledge about the interaction between helminths and epilepsy. PMID:19825109

[Analysis of changes in peripheral and central nervous system in irregularly treated adult patients with primary congenital hypothyroidism].

PubMed

Łacka, Katarzyna; Florczak, Jolanta; Gradecka-Kubik, Ilona; Rajewska, Justyna; Junik, Roman

2010-03-01

Lack of thyroid hormones in the womb and the first years of life causes changes in the nervous system and mental retardation. The aim of the study was to assess changes in peripheral and central nervous system in 29 adult patients with primary congenital hypothyroidism (PCH) depending on the cause of the disease and systematic treatment of L-thyroxine. The analysis was performed in 29 adult patients with PCH (16 women, 13 men) on the basis of the results of neurological examination, EEG, SPECT (Computer tomography single photon emission) of the brain. Changes in the nervous system were found in 72% of respondents. Patients who had implemented replacement therapy L-thyroxine after completing 12 months of age showed the most neurological disorders. There were variations in the cranial nerves III, IX, IV and VI. In 34% of respondents revealed paraneoplastic cerebellar symptoms, while the pyramid, and extrapyramidal symptoms in 10% and 3% of the people. EEG showed changes in brain bioelectrical activity in the entire study group. In the 83% found a significant asymmetry in regional cerebral blood flow (rCBF). Hypoperfusion outbreak occurred mainly in the stands and leading occipital. The relationship between time of initiation of treatment, and the presence of a systematic change in the nervous system was inversely proportional. In turn, analyzing the causes of most PCH deviations were found in the nervous system in patients with athyreosis. Brain SPECT study in these patients confirmed the organic changes in brain development. CONCLUSIONS. The presence and extent of changes in peripheral and central nervous system depends on the cause PCH, pending the implementation of L-thyroxine treatment and systematic. Studies of brain SPECT and EEG confirmed the existence of developmental changes of the brain in patients with PCH.

The Serine Protease Inhibitor Neuroserpin Is Required for Normal Synaptic Plasticity and Regulates Learning and Social Behavior

ERIC Educational Resources Information Center

Reumann, Rebecca; Vierk, Ricardo; Zhou, Lepu; Gries, Frederice; Kraus, Vanessa; Mienert, Julia; Romswinkel, Eva; Morellini, Fabio; Ferrer, Isidre; Nicolini, Chiara; Fahnestock, Margaret; Rune, Gabriele; Glatzel, Markus; Galliciotti, Giovanna

2017-01-01

The serine protease inhibitor neuroserpin regulates the activity of tissue-type plasminogen activator (tPA) in the nervous system. Neuroserpin expression is particularly prominent at late stages of neuronal development in most regions of the central nervous system (CNS), whereas it is restricted to regions related to learning and memory in the…

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

PubMed

Ibáñez, Carlos F; Andressoo, Jaan-Olle

2017-01-01

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

Imaging in Central Nervous System Drug Discovery.

PubMed

Gunn, Roger N; Rabiner, Eugenii A

2017-01-01

The discovery and development of central nervous system (CNS) drugs is an extremely challenging process requiring large resources, timelines, and associated costs. The high risk of failure leads to high levels of risk. Over the past couple of decades PET imaging has become a central component of the CNS drug-development process, enabling decision-making in phase I studies, where early discharge of risk provides increased confidence to progress a candidate to more costly later phase testing at the right dose level or alternatively to kill a compound through failure to meet key criteria. The so called "3 pillars" of drug survival, namely; tissue exposure, target engagement, and pharmacologic activity, are particularly well suited for evaluation by PET imaging. This review introduces the process of CNS drug development before considering how PET imaging of the "3 pillars" has advanced to provide valuable tools for decision-making on the critical path of CNS drug development. Finally, we review the advances in PET science of biomarker development and analysis that enable sophisticated drug-development studies in man. Copyright © 2017 Elsevier Inc. All rights reserved.

Radiation-Induced Central Nervous System Death - A study of the Pathologic Findings in Monkeys Irradiated with Massive Doses of Cobalt-60 (Gamma) Radiation

DTIC Science & Technology

1959-04-01

U.S. DEPARTMENT OF COMMERCE National Technical Information Service AD-AO36 168 RADIATION-INDUCED CENTRAL NERVOUS SYSTEM DEATH - A STUDY OF THE...ý." - ý " . :..’ýý.ý-. .. , . ý 4 ý .. -- ’ý.- -!:;:ý’,. 1,ý,-: WJiAUOK4KOUED CENTRAL NERVOUS SYSTEM NT A Study of the Pathologic Findings in...University SCHOOL OF AVIATION MEDICINE, USAF Randolph AFB, Texas April 1959 7757-. AdIAIONH-INDUCED CENTRAL NEVOUS $Y$194 DUTH A Study of the Pathologic

Stages of AIDS-Related Lymphoma

MedlinePlus

... trials is also available. AIDS-Related Primary Central Nervous System Lymphoma Treatment of AIDS-related primary central nervous system lymphoma may include the following: External radiation therapy . ...

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

PubMed

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

2017-11-01

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

Treatment Options for AIDS-Related Lymphoma

MedlinePlus

... trials is also available. AIDS-Related Primary Central Nervous System Lymphoma Treatment of AIDS-related primary central nervous system lymphoma may include the following: External radiation therapy . ...

21 CFR 520.600 - Dichlorvos.

Code of Federal Regulations, 2014 CFR

2014-04-01

... administration of muscle relaxant drugs, phenothiazine derived tranquilizers or central nervous system depressant..., phenothiazine derived tranquilizers, or central nervous system depressants. (4) Do not use in horses which are...

21 CFR 520.600 - Dichlorvos.

Code of Federal Regulations, 2012 CFR

2012-04-01

... administration of muscle relaxant drugs, phenothiazine derived tranquilizers or central nervous system depressant..., phenothiazine derived tranquilizers, or central nervous system depressants. (4) Do not use in horses which are...

21 CFR 520.600 - Dichlorvos.

Code of Federal Regulations, 2013 CFR

2013-04-01

... administration of muscle relaxant drugs, phenothiazine derived tranquilizers or central nervous system depressant..., phenothiazine derived tranquilizers, or central nervous system depressants. (4) Do not use in horses which are...

21 CFR 520.600 - Dichlorvos.

Code of Federal Regulations, 2011 CFR

2011-04-01

... administration of muscle relaxant drugs, phenothiazine derived tranquilizers or central nervous system depressant..., phenothiazine derived tranquilizers, or central nervous system depressants. (4) Do not use in horses which are...

21 CFR 520.600 - Dichlorvos.

Code of Federal Regulations, 2010 CFR

2010-04-01

... administration of muscle relaxant drugs, phenothiazine derived tranquilizers or central nervous system depressant..., phenothiazine derived tranquilizers, or central nervous system depressants. (4) Do not use in horses which are...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

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

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

Code of Federal Regulations, 2013 CFR

2013-07-01

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

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

Code of Federal Regulations, 2010 CFR

2010-07-01

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

76 FR 77895 - Schedules of Controlled Substances: Placement of Ezogabine Into Schedule V

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-15

... ester, is a new chemical substance with central nervous system depressant properties and is classified... nervous system as an anticonvulsant and the potential side effects of the drug therein, warrant closer... the central nervous system is alone not enough to merit its inclusion into Schedule IV of the CSA, nor...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

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

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

Code of Federal Regulations, 2012 CFR

2012-07-01

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

Central Nervous System Oxygen Toxicity in Closed-Circuit Scuba Divers

DTIC Science & Technology

1986-03-01

CENTRAL NERVOUS SYSTEM OXYGEN TOXICITY IN CLOSED -CIRCUIT SCUBA DIVERS III By F. K. Butler, Jr., LCDR, MC, USN NAVY EXPERIMENTAL DIVING UNIT DTIC...PANAMA CITY. FLORIDA 321407 IN. aLV OMW Vol NAVY EXPERIMENTAL DIVING UNIT REPORT NO. 5-86 CENTRAL NERVOUS SYSTEM OXYGEN TOXICITY IN CLOSED -CIRCUIT SCUBA...BUTLER, Jr. J . .d.M. HAMILTON LCDR, MC, USK CDR, MC, USK CDR, USKN Medical Research Officer Senior Medical Officer Comanding Officer UNCLASSIFIED 4

IκB kinase 2 determines oligodendrocyte loss by non-cell-autonomous activation of NF-κB in the central nervous system

PubMed Central

Raasch, Jenni; Zeller, Nicolas; van Loo, Geert; Merkler, Doron; Mildner, Alexander; Erny, Daniel; Knobeloch, Klaus-Peter; Bethea, John R.; Waisman, Ari; Knust, Markus; Del Turco, Domenico; Deller, Thomas; Blank, Thomas; Priller, Josef; Brück, Wolfgang

2011-01-01

The IκB kinase complex induces nuclear factor kappa B activation and has recently been recognized as a key player of autoimmunity in the central nervous system. Notably, IκB kinase/nuclear factor kappa B signalling regulates peripheral myelin formation by Schwann cells, however, its role in myelin formation in the central nervous system during health and disease is largely unknown. Surprisingly, we found that brain-specific IκB kinase 2 expression is dispensable for proper myelin assembly and repair in the central nervous system, but instead plays a fundamental role for the loss of myelin in the cuprizone model. During toxic demyelination, inhibition of nuclear factor kappa B activation by conditional ablation of IκB kinase 2 resulted in strong preservation of central nervous system myelin, reduced expression of proinflammatory mediators and a significantly attenuated glial response. Importantly, IκB kinase 2 depletion in astrocytes, but not in oligodendrocytes, was sufficient to protect mice from myelin loss. Our results reveal a crucial role of glial cell-specific IκB kinase 2/nuclear factor kappa B signalling for oligodendrocyte damage during toxic demyelination. Thus, therapies targeting IκB kinase 2 function in non-neuronal cells may represent a promising strategy for the treatment of distinct demyelinating central nervous system diseases. PMID:21310728

Review of dextromethorphan administration in 18 patients with subacute methotrexate central nervous system toxicity.

PubMed

Afshar, Maryam; Birnbaum, Daniel; Golden, Carla

2014-06-01

The pathogenesis of methotrexate central nervous system toxicity is multifactorial, but it is likely related to central nervous system folate homeostasis. The use of folinate rescue has been described to decrease toxicity in patients who had received intrathecal methotrexate. It has also been described in previous studies that there is an elevated level of homocysteine in plasma and cerebrospinal fluid of patients who had received intrathecal methotrexate. Homocysteine is an N-methyl-D-aspartate receptor agonist. The use of dextromethorphan, noncompetitive N-methyl-D-aspartate receptor receptor antagonist, has been used in the treatment of sudden onset of neurological dysfunction associated with methotrexate toxicity. It remains unclear whether the dextromethorphan impacted the speed of recovery, and its use remains controversial. This study reviews the use of dextromethorphan in the setting of subacute methotrexate central nervous system toxicity. Charts of 18 patients who had sudden onset of neurological impairments after receiving methotrexate and were treated with dextromethorphan were reviewed. The use of dextromethorphan in most of our patients resulted in symptomatic improvement. In this patient population, earlier administration of dextromethorphan resulted in faster improvement of impairments and led to prevention of recurrence of seizure activity induced by methotrexate central nervous system toxicity. Our study provides support for the use of dextromethorphan in patients with subacute methotrexate central nervous system toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

[The role of recombinant activated factor VII in neuro- surgical and neurocritical patients].

PubMed

Rama-Maceiras, P; Ingelmo-Ingelmo, I; Fábregas-Juliá, N; Hernández-Palazón, J

2011-06-01

Central nervous system haemorrhage is a severe pathology, as a small amount of bleeding inside the brain can result in devastating consequences. Haemostatic agents might decrease the consequences of intra- cranial bleeding, whichever spontaneous, traumatic, or anticoagulation treatment etiology. Proacogulant recombinant activated factor VII (rFVIIa) has been given after central nervous system bleeding, with an off-label indication. In this update, we go over the drug mechanism of action, its role in the treatment of central nervous system haemorrhage and the published evidences regarding this subject. We carried out a literature review concerning the treatment with rFVIIa in central nervous system haemorrhage, neurocritical pathologies and neurosurgical procedures, searching in MEDLINE and in clinical trials registry: http://clinicaltrials.gov (last review September 2010), as well as performing a manual analysis of collected articles, looking for aditional references. The results of randomized clinical trials do not support the systematic administration of rFVIIa for spontaneous intracranial cerebral haemorrhage. In other central nervous system related haemorrhages, the current available data consist on retrospective studies, expert opinion or isolated case reports.

Biological restoration of central nervous system architecture and function: part 3-stem cell- and cell-based applications and realities in the biological management of central nervous system disorders: traumatic, vascular, and epilepsy disorders.

PubMed

Farin, Azadeh; Liu, Charles Y; Langmoen, Iver A; Apuzzo, Michael L J

2009-11-01

STEM CELL THERAPY has emerged as a promising novel therapeutic endeavor for traumatic brain injury, spinal cord injury, stroke, and epilepsy in experimental studies. A few preliminary clinical trials have further supported its safety and early efficacy after transplantation into humans. Although not yet clinically available for central nervous system disorders, stem cell technology is expected to evolve into one of the most powerful tools in the biological management of complex central nervous system disorders, many of which currently have limited treatment modalities. The identification of stem cells, discovery of neurogenesis, and application of stem cells to treat central nervous system disorders represent a dramatic evolution and expansion of the neurosurgeon's capabilities into the neurorestoration and neuroregeneration realms. In Part 3 of a 5-part series on stem cells, we discuss the theory, experimental evidence, and clinical data pertaining to the use of stem cells for the treatment of traumatic, vascular, and epileptic disorders.

Apoptotic cell death in the central nervous system of Bufo arenarum tadpoles induced by cypermethrin.

PubMed

Casco, V H; Izaguirre, M F; Marín, L; Vergara, M N; Lajmanovich, R C; Peltzer, P; Soler, A Peralta

2006-05-01

Tadpoles of the toad Bufo arenarum treated with cypermethrin (CY) at concentrations above 39 mug CY/L showed dose-dependent apoptotic cell death in immature cells of the central nervous system as demonstrated by morphometric analysis, the TUNEL method, and DNA fragmentation assay. Light-and electron-microscopic studies showed structural alterations in the intermediate and marginal layers of the brain. Immature cerebral tissue showed cellular shrinkage, nuclear fragmentation and increase of intercellular spaces. In this study we demonstrated high toxicity of CY to larval stages of Bufo arenarum. Our results show that doses lower than those used in routine insecticide applications can cause massive apoptosis in the immature cells of the central nervous system. These results coincide with our previous studies in Physalaemus biligonigerus, confirming the severe toxic effects of CY to the central nervous system of anuran species from Argentina. This may increase the mortality index in wild animals and contribute to the loss of biodiversity in our agroecosystems. We postulate that CY induces apoptosis in central nervous system cells of Bufo arenarum tadpoles by specific neurotoxic mechanisms.

Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

PubMed

Nijs, Jo; Loggia, Marco L; Polli, Andrea; Moens, Maarten; Huysmans, Eva; Goudman, Lisa; Meeus, Mira; Vanderweeën, Luc; Ickmans, Kelly; Clauw, Daniel

2017-08-01

The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization. Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development. Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.

Capability of Virtual Environments to Meet Military Requirements

DTIC Science & Technology

2000-11-01

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

21 CFR 1308.13 - Schedule III.

Code of Federal Regulations, 2011 CFR

2011-04-01

... any quantity of the following substances having a depressant effect on the central nervous system: (1... a stimulant effect on the central nervous sxstem, including its salts, isomers (whether optical...

21 CFR 1308.13 - Schedule III.

Code of Federal Regulations, 2014 CFR

2014-04-01

... a stimulant effect on the central nervous system, including its salts, isomers (whether optical... any quantity of the following substances having a depressant effect on the central nervous system: (1...

21 CFR 1308.13 - Schedule III.

Code of Federal Regulations, 2012 CFR

2012-04-01

... a stimulant effect on the central nervous system, including its salts, isomers (whether optical... any quantity of the following substances having a depressant effect on the central nervous system: (1...

21 CFR 1308.13 - Schedule III.

Code of Federal Regulations, 2010 CFR

2010-04-01

... any quantity of the following substances having a depressant effect on the central nervous system: (1... a stimulant effect on the central nervous sxstem, including its salts, isomers (whether optical...

21 CFR 1308.13 - Schedule III.

Code of Federal Regulations, 2013 CFR

2013-04-01

... a stimulant effect on the central nervous system, including its salts, isomers (whether optical... any quantity of the following substances having a depressant effect on the central nervous system: (1...

Farber's Disease

MedlinePlus

... of these disorders. Additional studies will emphasize the quantitative analysis of the central nervous system structure and ... of these disorders. Additional studies will emphasize the quantitative analysis of the central nervous system structure and ...

Central nervous system tissue heterotopia of the nose: case report and review of the literature

PubMed Central

Altissimi, G; Ascani, S; Falcetti, S; Cazzato, C; Bravi, I

2009-01-01

Summary The Authors present a case of heterotopic central nervous system tissue observed in an 81-year-old male in the form of an ethmoidal polyp. A review of the literature indicates that this is a rare condition characterised by a connective tissue lesion with astrocytic and oligodendrocytic glial cells, which may be located outside the nasal pyramid in some cases and inside the nasal cavity in others. The most important diagnostic aspect involves differentiating these from meningoencephalocele, which maintains an anatomical connection with central nervous system tissue. Contrast-enhanced imaging is essential for diagnosis, as in cases of heterotopic central nervous system tissue, it will demonstrate that there are no connections with intra-cranial tissue. Endoscopic excision is the treatment of choice. PMID:20161881

[The role of neurotrophic factors in regeneration of the nervous system].

PubMed

Machaliński, Bogusław; Lażewski-Banaszak, Piotr; Dąbkowska, Elżbieta; Paczkowska, Edyta; Gołąb-Janowska, Monika; Nowacki, Przemysław

2012-01-01

Neurotrophic factors regulate survival, development, and function of nervous tissue. They act via two different classes of receptors and activation of various signaling pathways in the target cells. Illumination of their physiological role in the maintenance of central nervous system homeostasis as well as regeneration of damaged tissue have ignited expectations to heal neurodegenerative diseases, including amyotrophic late-ral sclerosis and Parkinson disease. Advances in pharmaco-therapy, gene therapy, and stem cell biology have enabled development of novel therapies with application of regenerating cell transplantation. In the foreseeable future, it may lead to the establishment of safe and effective ways of treatment of these severe and currently incurable diseases.

21 CFR 1308.11 - Schedule I.

Code of Federal Regulations, 2010 CFR

2010-04-01

... substances having a depressant effect on the central nervous system, including its salts, isomers, and salts... following substances having a stimulant effect on the central nervous system, including its salts, isomers...

21 CFR 1308.11 - Schedule I.

Code of Federal Regulations, 2012 CFR

2012-04-01

... substances having a depressant effect on the central nervous system, including its salts, isomers, and salts... following substances having a stimulant effect on the central nervous system, including its salts, isomers...

21 CFR 1308.11 - Schedule I.

Code of Federal Regulations, 2013 CFR

2013-04-01

... substances having a depressant effect on the central nervous system, including its salts, isomers, and salts... following substances having a stimulant effect on the central nervous system, including its salts, isomers...

21 CFR 1308.11 - Schedule I.

Code of Federal Regulations, 2011 CFR

2011-04-01

... substances having a depressant effect on the central nervous system, including its salts, isomers, and salts... following substances having a stimulant effect on the central nervous system, including its salts, isomers...

Rare Primary Central Nervous System Tumors

PubMed Central

Kubicky, Charlotte Dai; Sahgal, Arjun; Chang, Eric L.; Lo, Simon S.

2014-01-01

There are close to 70,000 new cases of primary central nervous system tumors diagnosed annually in the United States. Meningiomas, gliomas, nerve sheath tumors and pituitary tumors account for 85% of them. There is abundant literature on these commonly occurring tumors but data from the literature on infrequently encountered tumors such as atypical teratoid/rhabdoid tumor, choroid plexus carcinoma, ganglioglioma, hemangiopericytoma, and pleomorphic xanthoastrocytoma are limited. This review provides an overview of the clinicopathologic and therapeutic aspects of these rare primary central nervous system tumors. PMID:25276324

A pediatric renal lymphoma case presenting with central nervous system findings.

PubMed

Baran, Ahmet; Küpeli, Serhan; Doğru, Omer

2013-06-01

In pediatric patients renal lymphoma frequently presents in the form of multiple, bilateral mass lesions, infrequently as a single or retroperitoneal mass, and rarely as diffuse infiltrative lesions. In patients with apparent central nervous system involvement close attention to other physical and laboratory findings are essential for preventing a delay in the final diagnosis. Herein we present a pediatric patient with renal lymphoma that presented with central nervous system findings that caused a delay in diagnosis. None declared.

Ontogeny of the collar cord: neurulation in the hemichordate Saccoglossus kowalevskii.

PubMed

Kaul, Sabrina; Stach, Thomas

2010-10-01

The chordate body plan is characterized by a central notochord, a pharynx perforated by gill pores, and a dorsal central nervous system. Despite progress in recent years, the evolutionary origin of each of theses characters remains controversial. In the case of the nervous system, two contradictory hypotheses exist. In the first, the chordate nervous system is derived directly from a diffuse nerve net; whereas, the second proposes that a centralized nervous system is found in hemichordates and, therefore, predates chordate evolution. Here, we document the ontogeny of the collar cord of the enteropneust Saccoglossus kowalevskii using transmission electron microscopy and 3D-reconstruction based on completely serially sectioned stages. We demonstrate that the collar cord develops from a middorsal neural plate that is closed in a posterior to anterior direction. Transversely oriented ependymal cells possessing myofilaments mediate this morphogenetic process and surround the remnants of the neural canal in juveniles. A mid-dorsal glandular complex is present in the collar. The collar cord in juveniles is clearly separated into a dorsal saddle-like region of somata and a ventral neuropil. We characterize two cell types in the somata region, giant neurons and ependymal cells. Giant neurons connect via a peculiar cell junction that seems to function in intercellular communication. Synaptic junctions containing different vesicle types are present in the neuropil. These findings support the hypotheses that the collar cord constitutes a centralized element of the nervous system and that the morphogenetic process in the ontogeny of the collar cord is homologous to neurulation in chordates. Moreover, we suggest that these similarities are indicative of a close phylogenetic relationship between enteropneusts and chordates. ©2010 Wiley-Liss, Inc.

Childhood Astrocytomas Treatment

MedlinePlus

... symptoms and almost all need treatment. The central nervous system controls many important body functions. Astrocytomas are most common in these parts of the central nervous system (CNS): Cerebrum : The largest part of the brain, ...

Central nervous system medication use in older adults with intellectual disability: Results from the successful ageing in intellectual disability study.

PubMed

Chitty, Kate M; Evans, Elizabeth; Torr, Jennifer J; Iacono, Teresa; Brodaty, Henry; Sachdev, Perminder; Trollor, Julian N

2016-04-01

Information on the rates and predictors of polypharmacy of central nervous system medication in older people with intellectual disability is limited, despite the increased life expectancy of this group. This study examined central nervous system medication use in an older sample of people with intellectual disability. Data regarding demographics, psychiatric diagnoses and current medications were collected as part of a larger survey completed by carers of people with intellectual disability over the age of 40 years. Recruitment occurred predominantly via disability services across different urban and rural locations in New South Wales and Victoria. Medications were coded according to the Monthly Index of Medical Specialties central nervous system medication categories, including sedatives/hypnotics, anti-anxiety agents, antipsychotics, antidepressants, central nervous system stimulants, movement disorder medications and anticonvulsants. The Developmental Behaviour Checklist for Adults was used to assess behaviour. Data were available for 114 people with intellectual disability. In all, 62.3% of the sample was prescribed a central nervous system medication, with 47.4% taking more than one. Of those who were medicated, 46.5% had a neurological diagnosis (a seizure disorder or Parkinson's disease) and 45.1% had a psychiatric diagnosis (an affective or psychotic disorder). Linear regression revealed that polypharmacy was predicted by the presence of neurological and psychiatric diagnosis, higher Developmental Behaviour Checklist for Adults scores and male gender. This study is the first to focus on central nervous system medication in an older sample with intellectual disability. The findings are in line with the wider literature in younger people, showing a high degree of prescription and polypharmacy. Within the sample, there seems to be adequate rationale for central nervous system medication prescription. Although these data do not indicate non-adherence to guidelines for prescribing in intellectual disability, the high rate of polypharmacy and its relationship to Developmental Behaviour Checklist for Adults scores reiterate the importance of continued medication review in older people with intellectual disability. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Organic brain syndrome in rheumatoid arthritis following corticosteroid withdrawal.

PubMed

Gupta, V P; Ehrlich, G E

1976-01-01

Six patients with seropositive nodule-forming rheumatoid arthritis developed severe central nervous system manifestations consistent with a diagnosis of organic brain syndrome. Organic brain syndrome occurred while 5 of these patients were undergoing corticosteroid withdrawal after prolonged administration. Neuropsychiatric symptoms rapidly cleared, responding to reinstitution of oral or parenteral corticosteroids in large doses in 4 patients, to increase in dosage in 1 patient, and to no drug therapy in the remaining 1. Marked reduction in rheumatoid factor in sera and demonstration of IgM deposits in the choroid plexus in 1 of the patients raised the possibility of immune complex-mediated central nervous system vasculitis.

Neurotoxicity Associated With Dimethyl Sulfoxide Used in Allogeneic Stem Cell Transplantation.

PubMed

Ataseven, Eda; Tüfekçi, Özlem; Yilmaz, Şebnem; Güleryüz, Handan; Ören, Hale

2017-07-01

Dimethyl sulfoxide (DMSO) is a cryoprotective agent used in storage of frozen stem cells in stem cell transplantation. Central nervous system side effects of DMSO such as epileptic seizures, stroke, transient global amnesia, and temporary leucoencephalopathy are rarely seen. Here, we report a pediatric patient who developed seizures after DMSO-cryopreserved stem cell infusion and whose magnetic resonance imaging of the brain demonstrated parietal and occipital focal cortical T2-signal intensity increase. DMSO toxicity should be kept in mind in patients who received cryopreserved stem cell infusion and magnetic resonance imaging may be helpful in differential diagnosis of central nervous system involvement.

Clinical applications of penetrating neural interfaces and Utah Electrode Array technologies

NASA Astrophysics Data System (ADS)

Normann, Richard A.; Fernandez, Eduardo

2016-12-01

This paper briefly describes some of the recent progress in the development of penetrating microelectrode arrays and highlights the use of two of these devices, Utah electrode arrays and Utah slanted electrode arrays, in two therapeutic interventions: recording volitional skeletal motor commands from the central nervous system, and recording motor commands and evoking somatosensory percepts in the peripheral nervous system (PNS). The paper also briefly explores other potential sites for microelectrode array interventions that could be profitably pursued and that could have important consequences in enhancing the quality of life of patients that has been compromised by disorders of the central and PNSs.

[Case of acute ophthalmoparesis with gaze nystagmus].

PubMed

Ikuta, Naomi; Tada, Yukiko; Koga, Michiaki

2012-01-01

A 61-year-old man developed double vision subsequent to diarrheal illness. Mixed horizontal-vertical gaze palsy in both eyes, diminution of tendon reflexes, and gaze nystagmus were noted. His horizontal gaze palsy was accompanied by gaze nystagmus in the abducent direction, indicative of the disturbance in central nervous system. Neither limb weakness nor ataxia was noted. Serum anti-GQ1b antibody was detected. Brain magnetic resonance imaging (MRI) findings were normal. The patient was diagnosed as having acute ophthalmoparesis. The ophthalmoparesis and nystagmus gradually disappeared in 3 months. The accompanying nystagmus suggests that central nervous system disturbance may also be present with acute ophthalmoparesis.

Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors

ClinicalTrials.gov

2018-05-23

Childhood Brain Stem Neoplasm; Childhood Lymphoma; Childhood Solid Neoplasm; Pineal Region Neoplasm; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Visual Pathway Glioma; Refractory Central Nervous System Neoplasm

Sex differences in the effects of androgens acting in the central nervous system on metabolism

PubMed Central

Morford, Jamie; Mauvais-Jarvis, Franck

2016-01-01

One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose and energy homeostasis by testosterone in males and females. Testosterone deficiency predisposes men to metabolic dysfunction, with excess adiposity, insulin resistance, and type 2 diabetes, whereas androgen excess predisposes women to insulin resistance, adiposity, and type 2 diabetes. This review discusses how testosterone acts in the central nervous system, and especially the hypothalamus, to promote metabolic homeostasis or dysfunction in a sexually dimorphic manner. We compare the organizational actions of testosterone, which program the hypothalamic control of metabolic homeostasis during development, and the activational actions of testosterone, which affect metabolic function after puberty. We also discuss how the metabolic effect of testosterone is centrally mediated via the androgen receptor. PMID:28179813

Sex and Stress Hormone Influences on the Expression and Activity of Brain-Derived Neurotrophic Factor

PubMed Central

Carbone, David L.; Handa, Robert J.

2012-01-01

The neurotrophin, brain-derived neurotrophic factor (BDNF), is recognized as a key component in the regulation of central nervous system ontogeny, homeostasis and adult neuroplasticity. The importance of BDNF in central nervous system development and function is well documented by numerous reports from animal studies linking abnormal BDNF signaling to metabolic disturbances and anxiety or depressive-like behavior. Despite the diverse roles for BDNF in nearly all aspects of central nervous system physiology, the regulation of BDNF expression, as well as our understanding of the signaling mechanisms associated with this neurotrophin, remains incomplete. However, links between sex hormones such as estradiol and testosterone, as well as endogenous and synthetic glucocorticoids, have emerged as important mediators of BDNF expression and function. Examples of such regulation include brain region-specific induction of Bdnf mRNA in response to estradiol. Additional studies have also documented regulation of the expression of the high-affinity BDNF receptor TrkB by estradiol, thus implicating sex steroids not only in the regulation of BDNF expression, but on mechanisms of signaling associated with it. In addition to gonadal steroids, further evidence also suggests functional interaction between BDNF and glucocorticoids, such as in the regulation of corticotrophin-releasing hormone and other important neuropeptides. In this review, we provide an overview of the roles played by selected sex or stress hormones in the regulation of BDNF expression and signaling in the central nervous system PMID:23211562

[Pharmacological correction of central nervous system function in exposure to Coriolis acceleration].

PubMed

Karkishchenko, N N; Dimitriadi, N A; Molchanovskiĭ, V V

1986-01-01

Healthy volunteers with a low vestibular tolerance were exposed to Coriolis acceleration. Potassium orotate, pyracetame and riboxine were used as prophylactic measures against disorders in the function of the vestibular apparatus and higher compartments of the higher nervous system. The central nervous function was assessed with respect to the spectral power of electroencephalograms, short-term memory and mental performance. Potassium orotate given at a dose of 40 mg/kg body weight/day during 12-14 days as well as pyracetame given at a dose of 30 mg/kg body weight/day during 3 or 7 days increased significantly statokinetic tolerance and produced a protective effect on the central nervous function against Coriolis acceleration.

Tools for studying drug transport and metabolism in the brain.

PubMed

Pitcher, Meagan R; Quevedo, João

2016-01-01

Development of xenobiotics that cross the blood-brain barrier in therapeutically-relevant quantities is an expensive and time-consuming undertaking. However, central nervous system diseases are an under-addressed cause of high mortality and morbidity, and drug development in this field is a worthwhile venture. We aim to familiarize the reader with available methodologies for studying drug transport into the brain. Current understanding of the blood-brain barrier structure has been well-described in other manuscripts, and first we briefly review the path that xenobiotics take through the brain - from bloodstream, to endothelial cells of the blood-brain barrier, to interstitial space, to brain parenchymal cells, and then to an exit point from the central nervous system. The second half of the review discusses research tools available to determine if xenobiotics are making the journey through the brain successfully and offers commentary on the translational utility of each methodology. Theoretically, non-human mammalian and human blood-brain barriers are similar in composition; however, some findings demonstrate important differences across species. Translational methodologies may provide more reliable information about how a drug may act across species. The recent finding of lymphatic vessels within the central nervous system may provide new tools and strategies for drug delivery to the brain.

[A case of primary central nervous system anaplastic lymphoma kinase positive anaplastic large cell lymphoma manifested as a unilateral pachymeningits].

PubMed

Fujisawa, Etsuco; Shibayama, Hidehiro; Mitobe, Fumi; Katada, Fumiaki; Sato, Susumu; Fukutake, Toshio

2017-11-25

There have been 23 reports of primary central nervous system anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma in the literature. Here we report the 24th case of a 40-year-old man who presented with occipital headache for one month. His contrast-enhanced brain MRI showed enhancement around the right temporal lobe, which suggested a diagnosis of hypertrophic pachymeningitis. He improved with steroid therapy. After discharge, however, he was readmitted with generalized convulsive seizures. Finally, he was diagnosed as primary central nervous system ALK-positive anaplastic large cell lymphoma by brain biopsy. Primary central nervous system lymphoma invading dura matter can rarely manifests as a unilateral pachymeningitis. Therefore, in case of pachymeningitis, we should pay attention to the possibility of infiltration of lymophoma with meticulous clinical follow-up.

The Central Nervous System Sites Mediating the Orexigenic Actions of Ghrelin

PubMed Central

Mason, B.L.; Wang, Q.; Zigman, J.M.

2014-01-01

The peptide hormone ghrelin is important for both homeostatic and hedonic eating behaviors, and its orexigenic actions occur mainly via binding to the only known ghrelin receptor, the growth hormone secretagogue receptor (GHSR). GHSRs are located in several distinct regions of the central nervous system. This review discusses those central nervous system sites that have been found to play critical roles in the orexigenic actions of ghrelin, including hypothalamic nuclei, the hippocampus, the amygdala, the caudal brain stem, and midbrain dopaminergic neurons. Hopefully, this review can be used as a stepping stone for the reader wanting to gain a clearer understanding of the central nervous system sites of direct ghrelin action on feeding behavior, and as inspiration for future studies to provide an even-more-detailed map of the neurocircuitry controlling eating and body weight. PMID:24111557

Neuropsychiatric lupus erythematosus, cerebral infarctions, and anticardiolipin antibodies.

PubMed Central

Fields, R A; Sibbitt, W L; Toubbeh, H; Bankhurst, A D

1990-01-01

Anticardiolipin antibody (aCL) has been associated with thromboembolic phenomena, including stroke, in certain patients with systemic lupus erythematosus (SLE); however, the relation between this antibody and the central nervous system manifestations of SLE is unknown. Serum samples and cerebrospinal fluid from five patients with SLE and acute central nervous system manifestations were assayed for the presence of aCL. Anticardiolipin antibody was identified in sera from four of the five patients but in none of the cerebrospinal fluid samples. Nuclear magnetic resonance imaging showed 'infarct-like' lesions in these four patients. This preliminary study suggests that a correlation between serum aCL and cerebral infarcts in central nervous system lupus may potentially exist. From this limited study it seems unlikely that aCL has a direct pathogenic role in the diffuse encephalopathy of acute central nervous system lupus. Images PMID:2317112

Effects of Brazilian scorpion venoms on the central nervous system.

PubMed

Nencioni, Ana Leonor Abrahão; Neto, Emidio Beraldo; de Freitas, Lucas Alves; Dorce, Valquiria Abrão Coronado

2018-01-01

In Brazil, the scorpion species responsible for most severe incidents belong to the Tityus genus and, among this group, T. serrulatus , T. bahiensis , T. stigmurus and T. obscurus are the most dangerous ones. Other species such as T. metuendus , T. silvestres, T. brazilae , T. confluens , T. costatus , T. fasciolatus and T. neglectus are also found in the country, but the incidence and severity of accidents caused by them are lower. The main effects caused by scorpion venoms - such as myocardial damage, cardiac arrhythmias, pulmonary edema and shock - are mainly due to the release of mediators from the autonomic nervous system. On the other hand, some evidence show the participation of the central nervous system and inflammatory response in the process. The participation of the central nervous system in envenoming has always been questioned. Some authors claim that the central effects would be a consequence of peripheral stimulation and would be the result, not the cause, of the envenoming process. Because, they say, at least in adult individuals, the venom would be unable to cross the blood-brain barrier. In contrast, there is some evidence showing the direct participation of the central nervous system in the envenoming process. This review summarizes the major findings on the effects of Brazilian scorpion venoms on the central nervous system, both clinically and experimentally. Most of the studies have been performed with T. serrulatus and T. bahiensis . Little information is available regarding the other Brazilian Tityus species.

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lactate overrides central nervous but not beta-cell glucose sensing in humans.

PubMed

Schmid, Sebastian M; Jauch-Chara, Kamila; Hallschmid, Manfred; Oltmanns, Kerstin M; Peters, Achim; Born, Jan; Schultes, Bernd

2008-12-01

Lactate has been shown to serve as an alternative energy substrate in the central nervous system and to interact with hypothalamic glucose sensors. On the background of marked similarities between central nervous and beta-cell glucose sensing, we examined whether lactate also interacts with pancreatic glucose-sensing mechanisms in vivo. The effects of intravenously infused lactate vs placebo (saline) on central nervous and pancreatic glucose sensing were assessed during euglycemic and hypoglycemic clamp experiments in 10 healthy men. The release of neuroendocrine counterregulatory hormones during hypoglycemia was considered to reflect central nervous glucose sensing, whereas endogenous insulin secretion as assessed by serum C-peptide levels served as an indicator of pancreatic beta-cell glucose sensing. Lactate infusion blunted the counterregulatory hormonal responses to hypoglycemia, in particular, the release of epinephrine (P = .007) and growth hormone (P = .004), so that higher glucose infusion rates (P = .012) were required to maintain the target blood glucose levels. In contrast, the decrease in C-peptide concentrations during the hypoglycemic clamp remained completely unaffected by lactate (P = .60). During euglycemic clamp conditions, lactate infusion did not affect the concentrations of C-peptide and of counterregulatory hormones, with the exception of norepinephrine levels that were lower during lactate than saline infusion (P = .049) independently of the glycemic condition. Data indicate that glucose sensing of beta-cells is specific to glucose, whereas glucose sensing at the central nervous level can be overridden by lactate, reflecting the brain's ability to rely on lactate as an alternative major energy source.

Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

PubMed

Hallschmid, M; Schultes, B

2009-11-01

Research on functions and signalling pathways of insulin has traditionally focused on peripheral tissues such as muscle, fat and liver, while the brain was commonly believed to be insensitive to the effects of this hormone secreted by pancreatic beta cells. However, since the discovery some 30 years ago that insulin receptors are ubiquitously found in the central nervous system, an ever-growing research effort has conclusively shown that circulating insulin accesses the brain, which itself does not synthesise insulin, and exerts pivotal functions in central nervous networks. As an adiposity signal reflecting the amount of body fat, insulin provides direct negative feedback to hypothalamic nuclei that control whole-body energy and glucose homeostasis. Moreover, insulin affects distinct cognitive processes, e.g. by triggering the formation of psychological memory contents. Accordingly, metabolic and cognitive disorders such as obesity, type 2 diabetes mellitus and Alzheimer's disease are associated with resistance of central nervous structures to the effects of insulin, which may derive from genetic polymorphisms as well as from long-term exposure to excess amounts of circulating insulin due to peripheral insulin resistance. Thus, overcoming central nervous insulin resistance, e.g. by pharmacological interventions, appears to be an attractive strategy in the treatment and prevention of these disorders. Enhancement of central nervous insulin signalling by administration of intranasal insulin, insulin analogues and insulin sensitisers in basic research approaches has yielded encouraging results that bode well for the successful translation of these effects into future clinical practice.

An optimised procedure for prenatal ethanol exposure with determination of its effects on central nervous system connections.

PubMed

Sbriccoli, A; Carretta, D; Santarelli, M; Granato, A; Minciacchi, D

1999-01-01

We describe the protocol set-up to investigate an experimental model of foetal alcohol syndrome in the rat. The protocol has been devised to expose specific cell populations of the central nervous system to ethanol during their neurogenesis and has been applied to the study of diencephalo-telencephalic connections. We were able to demonstrate specific permanent changes of the adult thalamo-cortical circuitry. Our protocol can be applied to study other aspects of central nervous system-ethanol interactions, such as neurotransmitter and receptor patterns. It can also represent a useful tool to test the effects of different diets to prevent nutritional deficiencies and the efficacy of drug treatments to prevent foetal alcohol syndrome. We have shown in fact that ethanol-induced thalamo-cortical alterations are partially prevented by concurrent administration of acetyl-L-carnitine. Finally, the present protocol can be used to investigate the effects of ethanol exposure on the development of different brain structures. To this purpose, the gestational period for ethanol exposure must be chosen according to the peak of neurogenesis for the investigated structure.

Evaluation of central and peripheral neuropathy in patients with chronic obstructive pulmonary disease.

PubMed

Aras, Yeşim Güzey; Aydemir, Yusuf; Güngen, Belma Doğan; Güngen, Adil Can

2018-01-01

The aim of the study was to investigate the frequency and characteristics of peripheral nervous system (PNS) and central nervous system (CNS) involvement in COPD. The study included 41 COPD patients and 41 healthy volunteers. Electrophysiological studies were carried out: electromyography (EMG) and visual evoked potentials (VEPs). The median nerve, ulnar nerve, common peroneal nerve, and tibial nerve were evaluated for latency, amplitude, and conduction velocity. The mean age of patients with COPD was 61.8 years and disease duration 10.3 years. There was no difference between patient and control groups in terms of age, BMI, smoking status, or biochemical parameters. Upon VEP examination, latencies were significantly prolonged and amplitudes shortened in the patient group compared to the control group. In EMG measurements, conduction velocity and amplitudes in all nerves were low in the patient group. Similarly, latencies in all nerves were higher in patients with COPD. Central and peripheral nervous system involvement could develop in patients with moderate-severe COPD, and these patients should be monitored for neuropathic changes in combination with neurological examination.

Central nervous system side effects associated with zolpidem treatment.

PubMed

Toner, L C; Tsambiras, B M; Catalano, G; Catalano, M C; Cooper, D S

2000-01-01

Zolpidem is one of the newer medications developed for the treatment of insomnia. It is an imidazopyridine agent that is an alternative to the typical sedative-hypnotic agents. Zolpidem use is gaining favor because of its efficacy and its side effect profile, which is milder and less problematic than that of the benzodiazepines and barbiturates used to treat insomnia. Still, side effects are not uncommon with zolpidem use. We report a series of cases in which the patients developed delirium, nightmares and hallucinations during treatment with zolpidem. We will review its pharmacology, discuss previous reports of central nervous system side effects, examine the impact of drug interactions with concurrent use of antidepressants, examine gender differences in susceptibility to side effects, and explore the significance of protein binding in producing side effects.

The neurobiology of climate change

NASA Astrophysics Data System (ADS)

O'Donnell, Sean

2018-02-01

Directional climate change (global warming) is causing rapid alterations in animals' environments. Because the nervous system is at the forefront of animals' interactions with the environment, the neurobiological implications of climate change are central to understanding how individuals, and ultimately populations, will respond to global warming. Evidence is accumulating for individual level, mechanistic effects of climate change on nervous system development and performance. Climate change can also alter sensory stimuli, changing the effectiveness of sensory and cognitive systems for achieving biological fitness. At the population level, natural selection forces stemming from directional climate change may drive rapid evolutionary change in nervous system structure and function.

The neurobiology of climate change.

PubMed

O'Donnell, Sean

2018-01-06

Directional climate change (global warming) is causing rapid alterations in animals' environments. Because the nervous system is at the forefront of animals' interactions with the environment, the neurobiological implications of climate change are central to understanding how individuals, and ultimately populations, will respond to global warming. Evidence is accumulating for individual level, mechanistic effects of climate change on nervous system development and performance. Climate change can also alter sensory stimuli, changing the effectiveness of sensory and cognitive systems for achieving biological fitness. At the population level, natural selection forces stemming from directional climate change may drive rapid evolutionary change in nervous system structure and function.

Dependence of palmar sweating response and central nervous system activity on the frequency of whole-body vibration.

PubMed

Ando, Hideo; Noguchi, Ryo

2003-06-01

This study was carried out to determine the effects of the frequency of whole-body vibration on palmar sweating response and the activity of the central sympathetic nervous system. Palmar sweating volume was measured on the right palm of six healthy men before and during 3 minutes of exposure to sinusoidal whole-body vibration at three different frequencies (16, 31.5, and 63 Hz). The whole-body vibration had a frequency-weighted, root mean square (rms) acceleration magnitude of 2.0 m/s2. As the index of the activated central sympathetic nervous system, saliva level of 3-methoxy-4-hydroxyphenylglycol (MHPG) was analyzed before and immediately after each vibration exposure. Each vibration frequency induced a palmar sweating response, that of 31.5 Hz being the largest. However, no significant difference was found between the three vibration conditions. Saliva MHPG increased in all the vibration exposures, and the largest change was observed at 31.5 Hz, the difference being significant. Acute exposure to whole-body vibration induced a palmar sweating response and activated the central sympathetic nervous system. The effects on the central nervous system were found to be dependent on the frequency of the vibration.

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases.

PubMed

Yarandi, Shadi S; Peterson, Daniel A; Treisman, Glen J; Moran, Timothy H; Pasricha, Pankaj J

2016-04-30

Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.

Maternal adiposity negatively influences infant brain white matter development

USDA-ARS?s Scientific Manuscript database

Objective: To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants. Methods: Diffusion tensor imaging was used to evaluate brain white matter development in 2-week-old, full-term, appropriate for gestational age infants from uncomplicat...

Melanoma central nervous system metastases: current approaches, challenges, and opportunities

PubMed Central

Cohen, Justine V.; Tawbi, Hussain; Margolin, Kim A.; Amravadi, Ravi; Bosenberg, Marcus; Brastianos, Priscilla K.; Chiang, Veronica L.; de Groot, John; Glitza, Isabella C.; Herlyn, Meenhard; Holmen, Sheri L.; Jilaveanu, Lucia B.; Lassman, Andrew; Moschos, Stergios; Postow, Michael A.; Thomas, Reena; Tsiouris, John A.; Wen, Patrick; White, Richard M.; Turnham, Timothy; Davies, Michael A.; Kluger, Harriet M.

2017-01-01

Summary Melanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here, we provide a review of the current status of the field of melanoma brain metastasis research; identify key challenges and opportunities for improving the outcomes in patients with melanoma brain metastases; and set a framework to optimize future research in this critical area. PMID:27615400

Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System Following Neural Injury

DTIC Science & Technology

2017-08-01

AWARD NUMBER: W81XWH-12-1-0051 TITLE: Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System ...Central Nervous System Following Neural Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0051 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Robert...induces re- growth of dopaminergic axons at 3 to 6 weeks after destruction by a neurotoxin. However, this approach cannot be used in humans because

Structural characterization of a novel neuropeptide from the central nervous system of the leech Erpobdella octoculata. The leech osmoregulator factor.

PubMed

Salzet, M; Bulet, P; Weber, W M; Clauss, W; Verger-Bocquet, M; Malecha, J

1996-03-22

Purification of a material immunoreactive to an antiserum against the C-terminal part of the oxytocin (Pro-Leu-Gly-amide) and present in the central nervous system of the Pharyngobdellid leech Erpobdella octoculata was performed by reversed-phase high performance liquid chromatography combined with both enzyme-linked immunosorbent and dot immunobinding assays for oxytocin. The amino acid sequence of the purified peptide (Ile-Pro-Glu-Pro-Tyr-Val-Trp-Asp) was established by Edman degradation and confirmed by electrospray mass spectrometry measurement. When injected in leeches, purified or synthetic peptides exert an anti-diuretic effect, the most effective ranged between 10 pmol and 1 nmol. They provoked an uptake of water 1-2 h post-injection. Furthermore, electrophysiological experiments conducted in the leech Hirudo medicinalis revealed an inhibition of the potency of Na+ conductances of leech skin by this peptide. Immunocytochemical studies with an antiserum against synthetic oxytocin-like molecule provided the cytological basis for existence of a neuropeptide, since large amounts of immunoreactive neurons were detected in the central nervous systems of E. octoculata. The purified molecule is both different to peptides of the oxytocin/vasopressin family and is a novel neuropeptide in the animal kingdom. It was named the leech osmoregulator factor (LORF). An identification of the proteins immunoreactive to an antiserum against oxytocin performed at the level of both central nervous systems extracts and in vitro central nervous system-translated RNA products indicated that in the two cases, a single protein was detected. These proteins with a molecular masses of, respectively, approximately 34 kDa (homodimer of 17 kDa) for the central nervous systems extracts and approximately 19 kDa for in vitro central nervous system-translated RNA products were not recognized by the antiserum against MSEL- and VLDV-neurophysin (proteins associated to oxytocin and vasopressin), confirming that LORF did not belong to the oxytocin/vasopressin family.

Analytical and Biological Methods for Probing the Blood-Brain Barrier

PubMed Central

Sloan, Courtney D. Kuhnline; Nandi, Pradyot; Linz, Thomas H.; Aldrich, Jane V.; Audus, Kenneth L.; Lunte, Susan M.

2013-01-01

The blood-brain barrier (BBB) is an important interface between the peripheral and central nervous systems. It protects the brain against the infiltration of harmful substances and regulates the permeation of beneficial endogenous substances from the blood into the extracellular fluid of the brain. It can also present a major obstacle in the development of drugs that are targeted for the central nervous system. Several methods have been developed to investigate the transport and metabolism of drugs, peptides, and endogenous compounds at the BBB. In vivo methods include intravenous injection, brain perfusion, positron emission tomography, and microdialysis sampling. Researchers have also developed in vitro cell-culture models that can be employed to investigate transport and metabolism at the BBB without the complication of systemic involvement. All these methods require sensitive and selective analytical methods to monitor the transport and metabolism of the compounds of interest at the BBB. PMID:22708905

21 CFR 866.3870 - Trypanosoma spp. serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... by fever, chills, headache, and vomiting. Central nervous system involvement produces typical.... Chagas disease, an acute form of trypanosomiasis in children, most seriously affects the central nervous system and heart muscle. (b) Classification. Class I (general controls). ...

21 CFR 866.3870 - Trypanosoma spp. serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... by fever, chills, headache, and vomiting. Central nervous system involvement produces typical.... Chagas disease, an acute form of trypanosomiasis in children, most seriously affects the central nervous system and heart muscle. (b) Classification. Class I (general controls). ...

21 CFR 866.3870 - Trypanosoma spp. serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... by fever, chills, headache, and vomiting. Central nervous system involvement produces typical.... Chagas disease, an acute form of trypanosomiasis in children, most seriously affects the central nervous system and heart muscle. (b) Classification. Class I (general controls). ...

21 CFR 866.3870 - Trypanosoma spp. serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... by fever, chills, headache, and vomiting. Central nervous system involvement produces typical.... Chagas disease, an acute form of trypanosomiasis in children, most seriously affects the central nervous system and heart muscle. (b) Classification. Class I (general controls). ...

21 CFR 866.3870 - Trypanosoma spp. serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... by fever, chills, headache, and vomiting. Central nervous system involvement produces typical.... Chagas disease, an acute form of trypanosomiasis in children, most seriously affects the central nervous system and heart muscle. (b) Classification. Class I (general controls). ...

Childhood Central Nervous System Embryonal Tumors Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood central nervous system embryonal tumors and pineal tumors are treated with surgery, radiation therapy, chemotherapy, high-dose chemotherapy with stem cell rescue and targeted therapy. Learn more in this expert-reviewed summary.

American Society of Neuroradiology

MedlinePlus

... Tumors of the Central Nervous System: A Practical Approach for Gliomas, Part 1. Basic Tumor Genetics The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Practical Approach for Gliomas, Part 2. Isocitrate Dehydrogenase Status—Imaging ...

The Effects of Psychotropic Drugs.

ERIC Educational Resources Information Center

Bonnardeaux, Jef-Louis

1984-01-01

Presents information on psychotropic drugs for individuals who are not specialists in pharmacology. Discusses: alcohol and barbituates; dependence and withdrawal; central nervous system depressors (anaesthetics, narcotic analgesics, sedatives and hypnotic drugs, tranquilizers), central nervous stimulants (amphetamines, cocaine, tobacco, caffeine),…

Local Nitric Oxide Production in Viral and Autoimmune Diseases of the Central Nervous System

NASA Astrophysics Data System (ADS)

Hooper, D. Craig; Tsuyoshi Ohnishi, S.; Kean, Rhonda; Numagami, Yoshihiro; Dietzschold, Bernhard; Koprowski, Hilary

1995-06-01

Because of the short half-life of NO, previous studies implicating NO in central nervous system pathology during infection had to rely on the demonstration of elevated levels of NO synthase mRNA or enzyme expression or NO metabolites such as nitrate and nitrite in the infected brain. To more definitively investigate the potential causative role of NO in lesions of the central nervous system in animals infected with neurotropic viruses or suffering from experimental allergic encephalitis, we have determined directly the levels of NO present in the central nervous system of such animals. Using spin trapping of NO and electron paramagnetic resonance spectroscopy, we confirm here that copious amounts of NO (up to 30-fold more than control) are elaborated in the brains of rats infected with rabies virus or borna disease virus, as well as in the spinal cords of rats that had received myelin basic protein-specific T cells.

[Primary malignant melanoma of the central nervous system: A diagnostic challenge].

PubMed

Quillo-Olvera, Javier; Uribe-Olalde, Juan Salvador; Alcántara-Gómez, Leopoldo Alberto; Rejón-Pérez, Jorge Dax; Palomera-Gómez, Héctor Guillermo

2015-01-01

The rare incidence of primary malignant melanoma of the central nervous system and its ability to mimic other melanocytic tumors on images makes it a diagnostic challenge for the neurosurgeon. A 51-year-old patient, with a tumor located in the right forniceal callosum area. Total surgical excision was performed. Histopathological result was consistent with the diagnosis of primary malignant melanoma of the central nervous system, after ruling out extra cranial and extra spinal melanocytic lesions. The primary malignant melanoma of the central nervous system is extremely rare. There are features in magnetic resonance imaging that increase the diagnostic suspicion; nevertheless there are other tumors with more prevalence that share some of these features through image. Since there is not an established therapeutic standard its prognosis is discouraging. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

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.

Transport across the choroid plexus epithelium.

PubMed

Praetorius, Jeppe; Damkier, Helle Hasager

2017-06-01

The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1 ) the choroid plexus epithelium as the source of mediators necessary for central nervous system development, 2 ) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and 3 ) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy. Copyright © 2017 the American Physiological Society.

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

Planar induction of anteroposterior pattern in the developing central nervous system of Xenopus laevis

NASA Technical Reports Server (NTRS)

Doniach, T.; Phillips, C. R.; Gerhart, J. C.

1992-01-01

It has long been thought that anteroposterior (A-P) pattern in the vertebrate central nervous system is induced in the embryo's dorsal ectoderm exclusively by signals passing vertically from underlying, patterned dorsal mesoderm. Explants from early gastrulae of the frog Xenopus laevis were prepared in which vertical contact between dorsal ectoderm and mesoderm was prevented but planar contact was maintained. In these, four position-specific neural markers (engrailed-2, Krox-20, XlHbox 1, and XlHbox 6) were expressed in the ectoderm in the same A-P order as in the embryo. Thus, planar signals alone, following a path available in the normal embryo, can induce A-P neural pattern.

Evoked potentials in multiple sclerosis.

PubMed

Kraft, George H

2013-11-01

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

Adult Central Nervous System Tumors Treatment (PDQ®)—Patient Version

Cancer.gov

Adult central nervous system tumor treatment may include surgery, radiosurgery, radiation therapy, chemotherapy, surveillance, and targeted therapy. Treatment depends on the tumor type. Learn more about brain and spinal tumor treatment in this expert-reviewed summary.

Contraindications to Athletic Participation. Cardiac, Respiratory, and Central Nervous System Conditions.

ERIC Educational Resources Information Center

Moeller, James L.

1996-01-01

Discusses contraindications to athletic participation, examining the cardiac, respiratory, and central nervous system conditions that warrant activity disqualification. Provides guidelines about when it is safe for individuals to participate, and discusses the physician's responsibility. (SM)

An Integrated Model of the Cardiovascular and Central Nervous Systems for Analysis of Microgravity Induced Fluid Redistribution

NASA Technical Reports Server (NTRS)

Price, R.; Gady, S.; Heinemann, K.; Nelson, E. S.; Mulugeta, L.; Ethier, C. R.; Samuels, B. C.; Feola, A.; Vera, J.; Myers, J. G.

2015-01-01

A recognized side effect of prolonged microgravity exposure is visual impairment and intracranial pressure (VIIP) syndrome. The medical understanding of this phenomenon is at present preliminary, although it is hypothesized that the headward shift of bodily fluids in microgravity may be a contributor. Computational models can be used to provide insight into the origins of VIIP. In order to further investigate this phenomenon, NASAs Digital Astronaut Project (DAP) is developing an integrated computational model of the human body which is divided into the eye, the cerebrovascular system, and the cardiovascular system. This presentation will focus on the development and testing of the computational model of an integrated model of the cardiovascular system (CVS) and central nervous system (CNS) that simulates the behavior of pressures, volumes, and flows within these two physiological systems.

Strategies for drug delivery to the central nervous system by systemic route.

PubMed

Kasinathan, Narayanan; Jagani, Hitesh V; Alex, Angel Treasa; Volety, Subrahmanyam M; Rao, J Venkata

2015-05-01

Delivery of a drug into the central nervous system (CNS) is considered difficult. Most of the drugs discovered over the past decade are biological, which are high in molecular weight and polar in nature. The delivery of such drugs across the blood-brain barrier presents problems. This review discusses some of the options available to reach the CNS by systemic route. The focus is mainly on the recent developments in systemic delivery of a drug to the CNS. Databases such as Scopus, Google scholar, Science Direct, SciFinder and online journals were referred for preparing this article including 89 references. There are at least nine strategies that could be adopted to achieve the required drug concentration in the CNS. The recent developments in drug delivery are very promising to deliver biologicals into the CNS.

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

PubMed

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

2005-01-01

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

Adult Central Nervous System Tumors Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult central nervous system tumor treatment options include surgery, radiosurgery, radiation therapy, chemotherapy, surveillance, and supportive care. Get detailed information about the types and treatment of newly diagnosed and recurrent brain and spinal tumors in this clinician summary.

Diagnostics and Discovery in Viral Central Nervous System Infections.

PubMed

Lipkin, Walter Ian; Hornig, Mady

2015-09-01

The range of viruses implicated in central nervous system disease continues to grow with globalization of travel and trade, emergence and reemergence of zoonoses and investments in discovery science. Diagnosis of viral central nervous system infections is challenging in that brain tissue, where the pathogen concentration is likely to be highest, is not readily obtained and sensitive methods for molecular and serological detection of infection are not available in most clinical microbiology laboratories. Here we review these challenges and discuss how they may be addressed using advances in molecular, proteomic and immunological methods. © 2015 International Society of Neuropathology.

Common multifractality in the heart rate variability and brain activity of healthy humans

NASA Astrophysics Data System (ADS)

Lin, D. C.; Sharif, A.

2010-06-01

The influence from the central nervous system on the human multifractal heart rate variability (HRV) is examined under the autonomic nervous system perturbation induced by the head-up-tilt body maneuver. We conducted the multifractal factorization analysis to factor out the common multifractal factor in the joint fluctuation of the beat-to-beat heart rate and electroencephalography data. Evidence of a central link in the multifractal HRV was found, where the transition towards increased (decreased) HRV multifractal complexity is associated with a stronger (weaker) multifractal correlation between the central and autonomic nervous systems.

Central Nervous System Cancers, Version 2.2014

PubMed Central

Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Brem, Henry; Brown, Paul; Butowski, Nicholas; Chamberlain, Marc C.; DeAngelis, Lisa M.; Fenstermaker, Robert A.; Friedman, Allan; Gilbert, Mark R.; Hattangadi-Gluth, Jona; Hesser, Deneen; Holdhoff, Matthias; Junck, Larry; Lawson, Ronald; Loeffler, Jay S.; Moots, Paul L.; Mrugala, Maciej M.; Newton, Herbert B.; Raizer, Jeffrey J.; Recht, Lawrence; Shonka, Nicole; Shrieve, Dennis C.; Sills, Allen K.; Swinnen, Lode J.; Tran, David; Tran, Nam; Vrionis, Frank D.; Wen, Patrick Yung; McMillian, Nicole R.; Ho, Maria

2015-01-01

The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases. PMID:25361798

Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

ClinicalTrials.gov

2018-05-02

Adult Central Nervous System Germ Cell Tumor; Adult Embryonal Tumor With Multilayered Rosettes, C19MC-Altered; Adult Medulloblastoma; Adult Pineoblastoma; Adult Supratentorial Embryonal Tumor, Not Otherwise Specified; Atypical Teratoid/Rhabdoid Tumor; Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Embryonal Tumor With Multilayered Rosettes, C19MC-Altered; Medulloepithelioma; Ototoxicity; Recurrent Adult Brain Neoplasm; Recurrent Childhood Central Nervous System Embryonal Neoplasm; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified

Central nervous system magnesium deficiency.

PubMed

Langley, W F; Mann, D

1991-03-01

The central nervous system concentration of magnesium (Mg++) appears to have a critical level below which neurologic dysfunction occurs. Observations presented suggest that the interchange of the Mg++ ion between the cerebrospinal fluid, extracellular fluid, and bone is more rapid and dynamic than is usually believed. This is especially so when the hypertrophied parathyroid gland is associated with significant skeletal depletion of Mg++ as judged by history rather than serum level. Magnesium, much like calcium, has a large presence in bone and has a negative feedback relationship with the parathyroid gland. A decline in central nervous system Mg++ may occur when the skeletal buffer system orchestrated largely by the parathyroid glands is activated by an increase in serum calcium. Observations in veterinary medicine and obstetrics suggest that the transfer of Mg++ from the extracellular fluid into bone during mineralization processes may be extensive. If the inhibition of the hypertrophied parathyroid gland is prolonged and the skeletal depletion of Mg++ extreme, serious neurologic symptoms, including seizures, coma, and death, may occur. Noise, excitement, and bodily contact appear to precipitate neurologic symptoms in Mg+(+)-deficient human subjects as it has been documented to occur in Mg+(+)-deficient experimental animals. The similarity of the acute central nervous system demyelinating syndromes with reactive central nervous system Mg++ deficiency is reviewed.

Integrated genomic classification of melanocytic tumors of the central nervous system using mutation analysis, copy number alterations and DNA methylation profiling.

PubMed

Griewank, Klaus; Koelsche, Christian; van de Nes, Johannes A P; Schrimpf, Daniel; Gessi, Marco; Möller, Inga; Sucker, Antje; Scolyer, Richard A; Buckland, Michael E; Murali, Rajmohan; Pietsch, Torsten; von Deimling, Andreas; Schadendorf, Dirk

2018-06-11

In the central nervous system, distinguishing primary leptomeningeal melanocytic tumors from melanoma metastases and predicting their biological behavior solely using histopathologic criteria can be challenging. We aimed to assess the diagnostic and prognostic value of integrated molecular analysis. Targeted next-generation-sequencing, array-based genome-wide methylation analysis and BAP1 immunohistochemistry was performed on the largest cohort of central nervous system melanocytic tumors analyzed to date, incl. 47 primary tumors of the central nervous system, 16 uveal melanomas. 13 cutaneous melanoma metastasis and 2 blue nevus-like melanomas. Gene mutation, DNA-methylation and copy-number profiles were correlated with clinicopathological features. Combining mutation, copy-number and DNA-methylation profiles clearly distinguished cutaneous melanoma metastases from other melanocytic tumors. Primary leptomeningeal melanocytic tumors, uveal melanomas and blue nevus-like melanoma showed common DNA-methylation, copy-number alteration and gene mutation signatures. Notably, tumors demonstrating chromosome 3 monosomy and BAP1 alterations formed a homogeneous subset within this group. Integrated molecular profiling aids in distinguishing primary from metastatic melanocytic tumors of the central nervous system. Primary leptomeningeal melanocytic tumors, uveal melanoma and blue nevus-like melanoma share molecular similarity with chromosome 3 and BAP1 alterations markers of poor prognosis. Copyright ©2018, American Association for Cancer Research.

The familial dysautonomia disease gene IKBKAP is required in the developing and adult mouse central nervous system

PubMed Central

Chaverra, Marta; George, Lynn; Thorne, Julian; Grindeland, Andrea; Ueki, Yumi; Eiger, Steven; Cusick, Cassie; Babcock, A. Michael; Carlson, George A.

2017-01-01

ABSTRACT Hereditary sensory and autonomic neuropathies (HSANs) are a genetically and clinically diverse group of disorders defined by peripheral nervous system (PNS) dysfunction. HSAN type III, known as familial dysautonomia (FD), results from a single base mutation in the gene IKBKAP that encodes a scaffolding unit (ELP1) for a multi-subunit complex known as Elongator. Since mutations in other Elongator subunits (ELP2 to ELP4) are associated with central nervous system (CNS) disorders, the goal of this study was to investigate a potential requirement for Ikbkap in the CNS of mice. The sensory and autonomic pathophysiology of FD is fatal, with the majority of patients dying by age 40. While signs and pathology of FD have been noted in the CNS, the clinical and research focus has been on the sensory and autonomic dysfunction, and no genetic model studies have investigated the requirement for Ikbkap in the CNS. Here, we report, using a novel mouse line in which Ikbkap is deleted solely in the nervous system, that not only is Ikbkap widely expressed in the embryonic and adult CNS, but its deletion perturbs both the development of cortical neurons and their survival in adulthood. Primary cilia in embryonic cortical apical progenitors and motile cilia in adult ependymal cells are reduced in number and disorganized. Furthermore, we report that, in the adult CNS, both autonomic and non-autonomic neuronal populations require Ikbkap for survival, including spinal motor and cortical neurons. In addition, the mice developed kyphoscoliosis, an FD hallmark, indicating its neuropathic etiology. Ultimately, these perturbations manifest in a developmental and progressive neurodegenerative condition that includes impairments in learning and memory. Collectively, these data reveal an essential function for Ikbkap that extends beyond the peripheral nervous system to CNS development and function. With the identification of discrete CNS cell types and structures that depend on Ikbkap, novel strategies to thwart the progressive demise of CNS neurons in FD can be developed. PMID:28167615

Genetic autonomic disorders.

PubMed

Axelrod, Felicia B

2013-03-01

Genetic disorders affecting the autonomic nervous system can result in abnormal development of the nervous system or they can be caused by neurotransmitter imbalance, an ion-channel disturbance or by storage of deleterious material. The symptoms indicating autonomic dysfunction, however, will depend upon whether the genetic lesion has disrupted peripheral or central autonomic centers or both. Because the autonomic nervous system is pervasive and affects every organ system in the body, autonomic dysfunction will result in impaired homeostasis and symptoms will vary. The possibility of genetic confirmation by molecular testing for specific diagnosis is increasing but treatments tend to remain only supportive and directed toward particular symptoms. Copyright © 2013 Elsevier Inc. All rights reserved.

Unimpaired Autoreactive T-Cell Traffic Within the Central Nervous System During Tumor Necrosis Factor Receptor-Mediated inhibition of Experimental Autoimmune Encephalomyelitis

NASA Astrophysics Data System (ADS)

Korner, Heinrich; Goodsall, Anna L.; Lemckert, Frances A.; Scallon, Bernard J.; Ghrayeb, John; Ford, Andrew L.; Sedgwick, Jonathon D.

1995-11-01

The critical role of tumor necrosis factor (TNF) as a mediator in autoimmune inflammatory processes is evident from in vivo studies with TNF-blocking agents. However, the mechanisms by which TNF, and possibly also its homologue lymphotoxin α, contributes to development of pathology in rheumatoid arthritis and Crohn disease and in animal models like experimental autoimmune encephalomyelitis is unclear. Possibilities include regulation of vascular adhesion molecules enabling leukocyte movement into tissues or direct cytokine-mediated effector functions such as mediation of tissue damage. Here we show that administration of a TNF receptor (55 kDa)-IgG fusion protein prevented clinical signs of actively induced experimental autoimmune encephalomyelitis. Significantly, the total number of CD4^+ T lymphocytes isolated from the central nervous system of clinically healthy treated versus diseased control animals was comparable. By using a CD45 congenic model of passively transferred experimental autoimmune encephalomyelitis to enable tracking of myelin basic protein-specific effector T lymphocytes, prevention of clinical signs of disease was again demonstrated in treated animals but without quantitative or qualitative impediment to the movement of autoreactive T lymphocytes to and within the central nervous system. Thus, despite the uninterrupted movement of specific T lymphocytes into the target tissue, subsequent disease development was blocked. This provides compelling evidence for a direct effector role of TNF/lymphotoxin α in autoimmune tissue damage.

Angubindin-1 opens the blood-brain barrier in vivo for delivery of antisense oligonucleotide to the central nervous system.

PubMed

Zeniya, Satoshi; Kuwahara, Hiroya; Daizo, Kaiichi; Watari, Akihiro; Kondoh, Masuo; Yoshida-Tanaka, Kie; Kaburagi, Hidetoshi; Asada, Ken; Nagata, Tetsuya; Nagahama, Masahiro; Yagi, Kiyohito; Yokota, Takanori

2018-05-17

Within the field of RNA therapeutics, antisense oligonucleotide-based therapeutics are a potentially powerful means of treating intractable diseases. However, if these therapeutics are used for the treatment of neurological disorders, safe yet efficient methods of delivering antisense oligonucleotides across the blood-brain barrier to the central nervous system must be developed. Here, we examined the use of angubindin-1, a binder to the tricellular tight junction, to modulate paracellular transport between brain microvascular endothelial cells in the blood-brain barrier for the delivery of antisense oligonucleotides to the central nervous system. This proof-of-concept study demonstrated that intravenously injected angubindin-1 increased the permeability of the blood-brain barrier and enabled transient delivery of subsequently administered antisense oligonucleotides into the mouse brain and spinal cord, leading to silencing of a target RNA without any overt adverse effects. We also found that two bicellular tight junction modulators did not produce such a silencing effect, suggesting that the tricellular tight junction is likely a better target for the delivery of antisense oligonucleotides than the bicellular tight junction. Our delivery strategy of modulating the tricellular tight junction in the blood-brain barrier via angubindin-1 provides a novel avenue of research for the development of antisense oligonucleotide-based therapeutics for the treatment of neurological disorders. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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,…

Environmental Complexity and Central Nervous System Development and Function

ERIC Educational Resources Information Center

Lewis, Mark H.

2004-01-01

Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching,…

9 CFR 55.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of any signs of central nervous system disease in herd animals; maintaining records of the... State or APHIS representative of any clinical signs of a central nervous system disease or chronic... identification number (AIN). A numbering system for the official identification of individual animals in the...

9 CFR 55.1 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... of any signs of central nervous system disease in herd animals; maintaining records of the... State or APHIS representative of any clinical signs of a central nervous system disease or chronic... identification number (AIN). A numbering system for the official identification of individual animals in the...

9 CFR 55.1 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... of any signs of central nervous system disease in herd animals; maintaining records of the... State or APHIS representative of any clinical signs of a central nervous system disease or chronic... identification number (AIN). A numbering system for the official identification of individual animals in the...

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)

Talazoparib and Temozolomide in Treating Younger Patients With Refractory or Recurrent Malignancies

ClinicalTrials.gov

2018-03-02

Adult Solid Neoplasm; Childhood Solid Neoplasm; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Malignant Solid Neoplasm; Refractory Central Nervous System Neoplasm

Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor Treatment

MedlinePlus

... information about the treatment of childhood central nervous system atypical teratoid and rhabdoid tumor. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care. Reviewers and ...

Testosterone Plus Finasteride Treatment After Spinal Cord Injury

ClinicalTrials.gov

2018-05-16

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

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

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

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

PubMed

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

2017-08-01

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

Mechanisms of insulin action on sympathetic nerve activity

NASA Technical Reports Server (NTRS)

Muntzel, Martin S.; Anderson, Erling A.; Johnson, Alan Kim; Mark, Allyn L.

1996-01-01

Insulin resistance and hyperinsulinemia may contribute to the development of arterial hypertension. Although insulin may elevate arterial pressure, in part, through activation of the sympathetic nervous system, the sites and mechanisms of insulin-induced sympathetic excitation remain uncertain. While sympathoexcitation during insulin may be mediated by the baroreflex, or by modulation of norepinephrine release from sympathetic nerve endings, it has been shown repeatedly that insulin increases sympathetic outflow by actions on the central nervous system. Previous studies employing norepinephrine turnover have suggested that insulin causes sympathoexcitation by acting in the hypothalamus. Recent experiments from our laboratory involving direct measurements of regional sympathetic nerve activity have provided further evidence that insulin acts in the central nervous system. For example, administration of insulin into the third cerebralventricle increased lumbar but not renal or adrenal sympathetic nerve activity in normotensive rats. Interestingly, this pattern of regional sympathetic nerve responses to central neural administration of insulin is similar to that seen with systemic administration of insulin. Further, lesions of the anteroventral third ventricle hypothalamic (AV3V) region abolished increases in sympathetic activity to systemic administration of insulin with euglycemic clamp, suggesting that AV3V-related structures are critical for insulin-induced elevations in sympathetic outflow.

Primary Angiitis of the Central Nervous System: Magnetic Resonance Imaging Spectrum of Parenchymal, Meningeal, and Vascular Lesions at Baseline.

PubMed

Boulouis, Grégoire; de Boysson, Hubert; Zuber, Mathieu; Guillevin, Loïc; Meary, Eric; Costalat, Vincent; Pagnoux, Christian; Naggara, Olivier

2017-05-01

Primary angiitis of the central nervous system remains challenging. To report an overview and pictorial review of brain magnetic resonance imaging findings in adult primary angiitis of the central nervous system and to determine the distribution of parenchymal, meningeal, and vascular lesions in a large multicentric cohort. Adult patients from the French COVAC cohort (Cohort of Patients With Primary Vasculitis of the Central Nervous System), with biopsy or angiographically proven primary angiitis of the central nervous system and brain magnetic resonance imaging available at the time of diagnosis were included. A systematic imaging review was performed blinded to clinical data. Sixty patients met inclusion criteria. Mean age was 45 years (±12.9). Patients initially presented focal deficit(s) (83%), headaches (53%), cognitive disorder (40%), and seizures (38.3%). The most common magnetic resonance imaging finding observed in 42% of patients was multiterritorial, bilateral, distal acute stroke lesions after small to medium artery distribution, with a predominant carotid circulation distribution. Hemorrhagic infarctions and parenchymal hemorrhages were also frequently found in the cohort (55%). Acute convexity subarachnoid hemorrhage was found in 26% of patients and 42% demonstrated pre-eminent leptomeningeal enhancement, which is found to be significantly more prevalent in biopsy-proven patients (60% versus 28%; P =0.04). Seven patients had tumor-like presentations. Seventy-seven percent of magnetic resonance angiographic studies were abnormal, revealing proximal/distal stenoses in 57% and 61% of patients, respectively. Adult primary angiitis of the central nervous system is a heterogenous disease, with multiterritorial, distal, and bilateral acute stroke being the most common pattern of parenchymal lesions found on magnetic resonance imaging. Our findings suggest a higher than previously thought prevalence of hemorrhagic transformation and other hemorrhagic manifestations. © 2017 American Heart Association, Inc.

Serotonin 1A receptor (5-HT1A) of the sea lamprey: cDNA cloning and expression in the central nervous system.

PubMed

Cornide-Petronio, María Eugenia; Anadón, Ramón; Barreiro-Iglesias, Antón; Rodicio, María Celina

2013-09-01

Serotonergic cells are among the earliest neurons to be born in the developing central nervous system and serotonin is known to regulate the development of the nervous system. One of the major targets of the activity of serotonergic cells is the serotonin 1A receptor (5-HT1A), an ancestral archetypical serotonin receptor. In this study, we cloned and characterized the 3D structure of the sea lamprey 5-HT1A, and studied the expression of its transcript in the central nervous system by means of in situ hybridization. In phylogenetic analyses, the sea lamprey 5-HT1A sequence clustered together with 5-HT1A sequences of vertebrates and emerged as an outgroup to all gnathostome sequences. In situ hybridization analysis during prolarval, larval and adult stages showed a widespread expression of the lamprey 5-ht1a transcript. In P1 prolarvae 5-ht1a mRNA expression was observed in diencephalic nuclei, the rhombencephalon and rostral spinal cord. At P2 prolarval stage the 5-ht1a expression extended to other brain areas including telencephalic regions. 5-ht1a expression in larvae was observed throughout almost all the main brain regions with the strongest expression in the olfactory bulbs, lateral pallium, striatum, preoptic region, habenula, prethalamus, thalamus, pretectum, hypothalamus, rhombencephalic reticular area, dorsal column nucleus and rostral spinal cord. In adults, the 5-ht1a transcript was also observed in cells of the subcommissural organ. Comparison of the expression of 5-ht1a between the sea lamprey and other vertebrates reveals a conserved pattern in most of the brain regions, likely reflecting the ancestral vertebrate condition.

The intestinal microbiome, probiotics and prebiotics in neurogastroenterology

PubMed Central

Saulnier, Delphine M.; Ringel, Yehuda; Heyman, Melvin B.; Foster, Jane A.; Bercik, Premysl; Shulman, Robert J.; Versalovic, James; Verdu, Elena F.; Dinan, Ted G.; Hecht, Gail; Guarner, Francisco

2013-01-01

The brain-gut axis allows bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent experimental work suggests that the gut microbiota have an impact on the brain-gut axis. A group of experts convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) discussed the role of gut bacteria on brain functions and the implications for probiotic and prebiotic science. The experts reviewed and discussed current available data on the role of gut microbiota on epithelial cell function, gastrointestinal motility, visceral sensitivity, perception and behavior. Data, mostly gathered from animal studies, suggest interactions of gut microbiota not only with the enteric nervous system but also with the central nervous system via neural, neuroendocrine, neuroimmune and humoral links. Microbial colonization impacts mammalian brain development in early life and subsequent adult behavior. These findings provide novel insights for improved understanding of the potential role of gut microbial communities on psychological disorders, most particularly in the field of psychological comorbidities associated with functional bowel disorders like irritable bowel syndrome (IBS) and should present new opportunity for interventions with pro- and prebiotics. PMID:23202796

The Postnatal Development of Spinal Sensory Processing

NASA Astrophysics Data System (ADS)

Fitzgerald, Maria; Jennings, Ernest

1999-07-01

The mechanisms by which infants and children process pain should be viewed within the context of a developing sensory nervous system. The study of the neurophysiological properties and connectivity of sensory neurons in the developing spinal cord dorsal horn of the intact postnatal rat has shed light on the way in which the newborn central nervous system analyzes cutaneous innocuous and noxious stimuli. The receptive field properties and evoked activity of newborn dorsal horn cells to single repetitive and persistent innocuous and noxious inputs are developmentally regulated and reflect the maturation of excitatory transmission within the spinal cord. These changes will have an important influence on pain processing in the postnatal period.

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

PubMed

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

2017-10-27

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

A review of Heinrich Obersteiner's 1888 textbook on the central nervous system by the neurologist Sigmund Freud.

PubMed

Hatzigiannakoglou, Paul D; Triarhou, Lazaros C

2011-06-01

In 1888, the Austrian neuroanatomist Heinrich Obersteiner, founder of Vienna's Neurological Institute, published his "Introduction to the Study of the Structure of the Central Nervous Organs in Health and Disease", a fundamental textbook in which he summarised the state-of-the-art knowledge available then on the normal and pathological anatomy of the human nervous system, incorporating many of his original research findings. The book became "the Bible for generations of budding neurologists" worldwide and was crucial for the eventual development of neurology as an independent medical discipline. In his early career as a neuroanatomist, Sigmund Freud wrote a review of Obersteiner's book for the Wiener Medizinische Wochenschrift. That review was not included in the "Standard Edition of the Complete Psychological Works". The present article provides an English translation of Freud's review and further discusses its historical context, especially regarding the influence of Theodor Meynert on his two illustrious students, Freud and Obersteiner.

Regulation of lipid metabolism by energy availability: a role for the central nervous system.

PubMed

Nogueiras, R; López, M; Diéguez, C

2010-03-01

The central nervous system (CNS) is crucial in the regulation of energy homeostasis. Many neuroanatomical studies have shown that the white adipose tissue (WAT) is innervated by the sympathetic nervous system, which plays a critical role in adipocyte lipid metabolism. Therefore, there are currently numerous reports indicating that signals from the CNS control the amount of fat by modulating the storage or oxidation of fatty acids. Importantly, some CNS pathways regulate adipocyte metabolism independently of food intake, suggesting that some signals possess alternative mechanisms to regulate energy homeostasis. In this review, we mainly focus on how neuronal circuits within the hypothalamus, such as leptin- ghrelin-and resistin-responsive neurons, as well as melanocortins, neuropeptide Y, and the cannabinoid system exert their actions on lipid metabolism in peripheral tissues such as WAT, liver or muscle. Dissecting the complicated interactions between peripheral signals and neuronal circuits regulating lipid metabolism might open new avenues for the development of new therapies preventing and treating obesity and its associated cardiometabolic sequelae.

21 CFR 1308.15 - Schedule V.

Code of Federal Regulations, 2010 CFR

2010-04-01

... depressant effect on the central nervous system, including its salts: (1) Lacosamide [(R)-2-acetoamido-N... which contains any quantity of the following substances having a stimulant effect on the central nervous system, including its salts, isomers and salts of isomers: (1) Pyrovalerone 1485. (2) [Reserved] (e...

21 CFR 1308.15 - Schedule V.

Code of Federal Regulations, 2011 CFR

2011-04-01

... depressant effect on the central nervous system, including its salts: (1) Lacosamide [(R)-2-acetoamido-N... which contains any quantity of the following substances having a stimulant effect on the central nervous system, including its salts, isomers and salts of isomers: (1) Pyrovalerone 1485. (2) [Reserved] (e...

Childhood Central Nervous System Germ Cell Tumors Treatment (PDQ®)—Health Professional Version

Cancer.gov

Treatment for children with central nervous system germ cell tumors (GCT) depend upon the specific tumor type. Options include radiation therapy, chemotherapy, surgery (in various combinations) and stem cell rescue. Get detailed information about GCTs in this clinician summary.

Axonal Regeneration in Mammals with Spinal Cord Injury

DTIC Science & Technology

1983-09-14

Cajal, S. 1905. Notas preventivas sobre la degeneracion y regeneracion las vias nerviosos centrales . Trab. Lab. Invest. Biol. Univ. Madrid, 4: 295-301...S. 1914. Degeneracion y Regeneration del Sistema Nervioso , Vol. 1, 2. (Nicolas Moya, Madrid), Ramon y Cajal, S. 1928. Degeneration and Regeneration...field of central nervous system (CNS) regeneration research. These developments have revealed important aspects regarding the histology and

The Intrinsic Electrophysiological Properties of Mammalian Neurons: Insights into Central Nervous System Function

NASA Astrophysics Data System (ADS)

Llinas, Rodolfo R.

1988-12-01

This article reviews the electroresponsive properties of single neurons in the mammalian central nervous system (CNS). In some of these cells the ionic conductances responsible for their excitability also endow them with autorhythmic electrical oscillatory properties. Chemical or electrical synaptic contacts between these neurons often result in network oscillations. In such networks, autorhytmic neurons may act as true oscillators (as pacemakers) or as resonators (responding preferentially to certain firing frequencies). Oscillations and resonance in the CNS are proposed to have diverse functional roles, such as (i) determining global functional states (for example, sleep-wakefulness or attention), (ii) timing in motor coordination, and (iii) specifying connectivity during development. Also, oscillation, especially in the thalamo-cortical circuits, may be related to certain neurological and psychiatric disorders. This review proposes that the autorhythmic electrical properties of central neurons and their connectivity form the basis for an intrinsic functional coordinate system that provides internal context to sensory input.

Epigenetic Mistakes in Neurodevelopmental Disorders.

PubMed

Mastrototaro, Giuseppina; Zaghi, Mattia; Sessa, Alessandro

2017-04-01

Epigenetics is the array of the chromatin modifications that customize in cell-, stage-, or condition-specific manner the information encloses in plain DNA molecules. Increasing evidences suggest the importance of epigenetic mechanisms for development and maintenance of central nervous system. In fact, a large number of newly discovered genetic causes of neurodevelopmental disorders such as intellectual disability, autism spectrum disorders, and many other syndromes are mutations within genes encoding for chromatin remodeling enzymes. Here, we review recent findings on the epigenetic origin of human diseases, with emphasis on disorders that affect development of the nervous system, and discuss novel therapeutic avenues that target epigenetic mechanisms.

Noncongenital central nervous system infections in children: radiology review.

PubMed

Acosta, Jorge Humberto Davila; Rantes, Claudia Isabel Lazarte; Arbelaez, Andres; Restrepo, Feliza; Castillo, Mauricio

2014-06-01

Infections of the central nervous system (CNS) are a very common worldwide health problem in childhood with significant morbidity and mortality. In children, viruses are the most common cause of CNS infections, followed by bacterial etiology, and less frequent due to mycosis and other causes. Noncomplicated meningitis is easier to recognize clinically; however, complications of meningitis such as abscesses, infarcts, venous thrombosis, or extra-axial empyemas are difficult to recognize clinically, and imaging plays a very important role on this setting. In addition, it is important to keep in mind that infectious process adjacent to the CNS such as mastoiditis can develop by contiguity in an infectious process within the CNS. We display the most common causes of meningitis and their complications.

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

PubMed

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

2003-04-01

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

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

PubMed

Hanson, Kimberly E; Couturier, Marc Roger

2016-11-15

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

Neuritogenesis: A model for space radiation effects on the central nervous system

NASA Technical Reports Server (NTRS)

Vazquez, M. E.; Broglio, T. M.; Worgul, B. V.; Benton, E. V.

1994-01-01

Pivotal to the astronauts' functional integrity and survival during long space flights are the strategies to deal with space radiations. The majority of the cellular studies in this area emphasize simple endpoints such as growth related events which, although useful to understand the nature of primary cell injury, have poor predictive value for extrapolation to more complex tissues such as the central nervous system (CNS). In order to assess the radiation damage on neural cell populations, we developed an in vitro model in which neuronal differentiation, neurite extension, and synaptogenesis occur under controlled conditions. The model exploits chick embryo neural explants to study the effects of radiations on neuritogenesis. In addition, neurobiological problems associated with long-term space flights are discussed.

Pleiotropic function of TRPV4 ion channels in the central nervous system

PubMed Central

Kanju, Patrick; Liedtke, Wolfgang

2016-01-01

TRPV4 ion channels are osmo-mechano-TRP channels with pleiotropic function and expression in many different types of tissues and cells. They have also been found involved in pain and inflammation. Studies have focused on the role of TRPV4 in peripheral sensory neurons, but its expression and function in central nervous glial cells and neurons has also been documented. In this overview, based on the senior author’s lecture at the recent physiology meeting in Dublin, we concisely review evidence of TRPV4 expression and function in the CNS, and how TRPV4 function can be modulated for therapeutic benefit of neuro-psychiatric disorders. Novel TRPV4-inhibitory compounds developed recently in the authors’ lab will also be discussed PMID:27701788

Central nervous system manifestations of Angiostrongylus cantonensis infection.

PubMed

Martins, Yuri C; Tanowitz, Herbert B; Kazacos, Kevin R

2015-01-01

Over 20 species of Angiostrongylus have been described from around the world, but only Angiostrongylus cantonensis has been confirmed to cause central nervous system disease in humans. A neurotropic parasite that matures in the pulmonary arteries of rats, A. cantonensis is the most common cause of eosinophilic meningitis in southern Asia and the Pacific and Caribbean islands. The parasite can also cause encephalitis/encephalomyelitis and rarely ocular angiostrongyliasis. The present paper reviews the life cycle, epidemiology, pathogenesis, clinical features, diagnosis, treatment, prevention and prognosis of A. cantonesis infection. Emphasis is given on the spectrum of central nervous system manifestations and disease pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines.

PubMed

Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Brem, Henry; Brown, Paul; Butowski, Nicholas; Chamberlain, Marc C; DeAngelis, Lisa M; Fenstermaker, Robert A; Friedman, Allan; Gilbert, Mark R; Hattangadi-Gluth, Jona; Hesser, Deneen; Holdhoff, Matthias; Junck, Larry; Lawson, Ronald; Loeffler, Jay S; Moots, Paul L; Mrugala, Maciej M; Newton, Herbert B; Raizer, Jeffrey J; Recht, Lawrence; Shonka, Nicole; Shrieve, Dennis C; Sills, Allen K; Swinnen, Lode J; Tran, David; Tran, Nam; Vrionis, Frank D; Wen, Patrick Yung; McMillian, Nicole R; Ho, Maria

2014-11-01

The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases. Copyright © 2014 by the National Comprehensive Cancer Network.

Wnt and lithium: a common destiny in the therapy of nervous system pathologies?

PubMed

Meffre, Delphine; Grenier, Julien; Bernard, Sophie; Courtin, Françoise; Dudev, Todor; Shackleford, Ghjuvan'Ghjacumu; Jafarian-Tehrani, Mehrnaz; Massaad, Charbel

2014-04-01

Wnt signaling is required for neurogenesis, the fate of neural progenitors, the formation of neuronal circuits during development, neuron positioning and polarization, axon and dendrite development and finally for synaptogenesis. This signaling pathway is also implicated in the generation and differentiation of glial cells. In this review, we describe the mechanisms of action of Wnt signaling pathways and their implication in the development and correct functioning of the nervous system. We also illustrate how a dysregulated Wnt pathway could lead to psychiatric, neurodegenerative and demyelinating pathologies. Lithium, used for the treatment of bipolar disease, inhibits GSK3β, a central enzyme of the Wnt/β-catenin pathway. Thus, lithium could, to some extent, mimic Wnt pathway. We highlight the possible dialogue between lithium therapy and modulation of Wnt pathway in the treatment of the diseases of the nervous system.

Research advances on potential neurotoxicity of quantum dots.

PubMed

Wu, Tianshu; Zhang, Ting; Chen, Yilu; Tang, Meng

2016-03-01

With rapid development of nanotechnology, quantum dots (QDs) as advanced nanotechnology products have been widely used in biological and biomedical studies, including neuroscience, due to their superior optical properties. In recent years, there has been intense concern regarding the toxicity of QDs with a growing number of studies. However, the knowledge of neurotoxic consequences of QDs applied in living organisms is lagging behind their development, while a potential risk of neurotoxicity arises if mass production of QDs leads to increased exposure and distribution in the nervous system. Owing to the quantum size effect of QDs, they are capable of crossing the blood-brain barrier or moving along neural pathways and entering the brain. Nevertheless, the interactions of QDs with cells and tissues in the central nervous system are not well understood. This review highlighted research advances on the neurotoxicity of QDs in the central nervous system, including oxidative stress injury, elevated cytoplasmic Ca(2+) levels and autophagy to damage in vitro neural cells, and impairments of synaptic transmission and plasticity as well as brain functions in tested animals, with the hope of throwing light on future research directions of QD neurotoxicity, which is a demanding topic that requires further exploration. Copyright © 2015 John Wiley & Sons, Ltd.

Hypotonia

MedlinePlus

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

A 3-year-old boy with Guillain-Barré syndrome and encephalitis associated with Mycoplasma pneumoniae infection.

PubMed

Hanzawa, Fumie; Fuchigami, Tatsuo; Ishii, Wakako; Nakajima, Sonoko; Kawamura, Yuki; Endo, Ayumi; Arakawa, Chikako; Kohira, Ryutaro; Fujita, Yukihiko; Takahashi, Shori

2014-02-01

Mycoplasma pneumoniae is a common cause of respiratory tract illness in children. Among the most common extrapulmonary manifestations are disorders of the central nervous system, including meningitis, meningoencephalitis, cerebellitis, polyneuropathy, acute disseminated encephalomyelitis, and Guillain-Barré syndrome. Guillain-Barré syndrome, also known as acute inflammatory demyelinating polyradiculoneuropathy, is an acute-onset, immune-mediated disorder of the peripheral nervous system. The central nervous system is usually intact in patients with Guillain-Barré syndrome. However, there have been some reports of an association of Guillain-Barré syndrome with central nervous system involvement in children. We report a 3-year-old boy with M. pneumoniae infection associated with Guillain-Barré syndrome and encephalitis. Both serum anti-GM1 ganglioside (IgG and IgM) and anti-galactocerebroside IgG antibodies were detected in our patient: the former in the earlier stage of the disease, and the latter in the later stage. We speculate that anti-GM1 ganglioside was associated more with encephalitis, and anti-galactocerebroside antibody was associated more with GBS in our case. Our patient is the youngest report of Guillain-Barré syndrome with central nervous system involvement, and the first report of a pediatric patient with associated M. pneumoniae infection. Such cases are rarely reported, but highlight the need for awareness of the association of the infection with Guillain-Barré syndrome with central nervous system involvement. Copyright © 2013 Japanese Society of Chemotherapy and The Japanese Association for Infectious Disease. Published by Elsevier Ltd. All rights reserved.

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…

21 CFR 1308.15 - Schedule V.

Code of Federal Regulations, 2014 CFR

2014-04-01

... depressant effect on the central nervous system, including its salts: (1) Ezogabine [N-[2-amino-4-(4... which contains any quantity of the following substances having a stimulant effect on the central nervous system, including its salts, isomers and salts of isomers: (1) Pyrovalerone 1485. (2) [Reserved] (e...

21 CFR 1308.15 - Schedule V.

Code of Federal Regulations, 2012 CFR

2012-04-01

... depressant effect on the central nervous system, including its salts: (1) Ezogabine [N-[2-amino-4-(4... which contains any quantity of the following substances having a stimulant effect on the central nervous system, including its salts, isomers and salts of isomers: (1) Pyrovalerone 1485. (2) [Reserved] (e...

21 CFR 1308.15 - Schedule V.

Code of Federal Regulations, 2013 CFR

2013-04-01

... depressant effect on the central nervous system, including its salts: (1) Ezogabine [N-[2-amino-4-(4... which contains any quantity of the following substances having a stimulant effect on the central nervous system, including its salts, isomers and salts of isomers: (1) Pyrovalerone 1485. (2) [Reserved] (e...

Transplanting Conductive Education: Practice Development and Professional Training in a Cross-European Initiative.

ERIC Educational Resources Information Center

Read, Janet

1994-01-01

Describes the development of a British-Hungarian project focused on training specialist teachers (conductors) in Great Britain in conductive education, a system of special education developed at the Peto Institute in Hungary for children and adults with central nervous system disorders affecting motor control. Conductors enable the physical,…

Neurovascular patterning cues and implications for central and peripheral neurological disease

PubMed Central

Gamboa, Nicholas T.; Taussky, Philipp; Park, Min S.; Couldwell, William T.; Mahan, Mark A.; Kalani, M. Yashar S.

2017-01-01

The highly branched nervous and vascular systems run along parallel trajectories throughout the human body. This stereotyped pattern of branching shared by the nervous and vascular systems stems from a common reliance on specific cues critical to both neurogenesis and angiogenesis. Continually emerging evidence supports the notion of later-evolving vascular networks co-opting neural molecular mechanisms to ensure close proximity and adequate delivery of oxygen and nutrients to nervous tissue. As our understanding of these biologic pathways and their phenotypic manifestations continues to advance, identification of where pathways go awry will provide critical insight into central and peripheral nervous system pathology. PMID:28966815

Scientific Study of Malnutrition as a Limiting Factor in the Development of Education.

ERIC Educational Resources Information Center

Picasso de Oyague, Alfredo

This study on malnutrition as a limiting factor in the development of education (and, hence, in socioeconomic development generally) was presented to the UNESCO Seminar on Education, Nutrition, Agriculture and Man. The paper reports on recent research showing that the development of the central nervous system in very young children (including the…

Incidence and Predictive Factors of Central Nervous System Dysfunction in Patients Consulting for Dengue Fever in Cayenne Hospital, French Guiana.

PubMed

Djossou, Félix; Vesin, Guillaume; Bidaud, Bastien; Mosnier, Emilie; Simonnet, Christine; Matheus, Séverine; Prince, Christelle; Balcaen, John; Donutil, Gerd; Egmann, Gérald; Okandze, Antoine; Malvy, Denis; Nacher, Mathieu

2016-01-01

The frequency, the clinical characteristics, and the prognosis of dengue is highly variable. Dengue fever is associated with a range of neurological manifestations. The objective of the present study was to determine the incidence of neurological signs and their predictive factors using data from cases of dengue seen and followed in Cayenne Hospital during the Dengue 2 epidemic in 2013. In 2013, a longitudinal study using data from all cases of dengue seen in Cayenne hospital was collected. Medical records used a standardized form to collect demographic information, clinical signs and biological results and the date at which they were present. The analysis used Cox proportional modeling to obtain adjusted Hazard ratios. A total of 1574 patients were included 221 of whom developed central nervous system signs. These signs were spontaneously resolutive. There were 9298person days of follow-up and the overall incidence rate for central nervous system signs was 2.37 per 100 person-days. The variables independently associated with central nervous system anomalies were headache, Adjusted Hazard ratio (AHR) = 1.9(95%CI = 1.4-2.6), bleeding AHR = 2 ((95%CI = 1.3-3.1), P = 0.001, abdominal pain AHR = 1.9 ((95%CI = 1.4-2.6), P<0.001, aches AHR = 2.1 ((95%CI = 1.5-2.9), P<0.001, and fatigue AHR = 1.5 ((95%CI = 1.3-1.7), P<0.001. Overall, the present study suggests that neurological signs of dengue are not exceptional even in patients without the most severe features of dengue. These manifestations were spontaneously resolutive. Here it was not possible to distinguish between encephalitis or encephalopathy. Further studies would require more in depth exploration of the patients.

Plasticity in the Developing Brain: Implications for Rehabilitation

ERIC Educational Resources Information Center

Johnston, Michael V.

2009-01-01

Neuronal plasticity allows the central nervous system to learn skills and remember information, to reorganize neuronal networks in response to environmental stimulation, and to recover from brain and spinal cord injuries. Neuronal plasticity is enhanced in the developing brain and it is usually adaptive and beneficial but can also be maladaptive…

Early Malnutrition and Central Nervous System Function

ERIC Educational Resources Information Center

Scrimshaw, Nevin S.

1969-01-01

Discusses the consequences of severe malnutrition in young experimental animals. Development of the brain is permanently impaired. Studies of the effects of malnutrition on children are included. (This paper was presented at the Eighth Annual Lecture of the Merrill-Palmer Historical Library in Child Development and Family Life, October 25, 1968.)…

Developmental Exposure to Perfluorohexane Sulfonate (PFHxS) Induces Hypothyroxinemia in Rat Dams and Offspring: Examination of Thyroid Gland and Behavior

EPA Science Inventory

The developing mammalian central nervous system is dependent on thyroid hormones (TH) to control neurogenesis, differentiation and migration. In humans, low maternal serum thyroxine (T4) levels have been correlated to impaired child brain development. Perfluorinated chemicals are...

Learning Disabilities: A Neurobiological Perspective in Humans.

ERIC Educational Resources Information Center

Bonnet, Kenneth A.

1989-01-01

The mechanisms of both language-based and non-language-based learning disabilities are presented within the framework of central nervous system development and the compromises to that development that arise from genetic, hormonal, antibody, medication, and postnatal compromises. Also reviewed is the need for a taxonomy of learning disabilities.…

[Systemic paracoccidioidomycosis with central nervous system involvement].

PubMed

Duarte, A L; Baruffa, G; Terra, H B; Renck, D V; de Moura, D; Petrucci, C

1999-01-01

A clinical case of a patient bearing systemic paracoccidioidomycosis with regional ganglionic and oral exposure and later pulmonary involvement is presented. The patient was treated with specific drugs (amphotericin B, itraconazole, sulfamethoxazole-trimethoprim) and followed throughout a 6-year period and eventually died showing an extensive involvement of the central nervous system.

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.…

Complex Cognitive Performance and Antihistamine Use

DTIC Science & Technology

1990-04-01

22 Antihistamine Use and Sedation ...........................................24 Antihistamine Use and Physiological Measures...Reactivity and Sedation in Healthy Volunteers after Administration of Hismanal, Alone or in Combination with Central Nervous System Depressants...cross the blood-brain barrier easily, resulting in central nervous system effects such as sedation , drowsiness, and altered psychomotor performance

Borrelia miyamotoi-Associated Neuroborreliosis in Immunocompromised Person.

PubMed

Boden, Katharina; Lobenstein, Sabine; Hermann, Beate; Margos, Gabriele; Fingerle, Volker

2016-09-01

Borrelia miyamotoi is a newly recognized human pathogen in the relapsing fever group of spirochetes. We investigated a case of B. miyamotoi infection of the central nervous system resembling B. burgdorferi-induced Lyme neuroborreliosis and determined that this emergent agent of central nervous system infection can be diagnosed with existing methods.

In vitro Alternative Methodologies for Central Nervous System Assessment: A Critique using Nanoscale Materials as an Example.

EPA Science Inventory

Identifying the potential health hazards to the central nervous system of a new family of materials presents many challenges. Whole-animal toxicity testing has been the tradition, but in vitro methods have been steadily gaining popularity. There are numerous challenges in testing...

The mechanisms of neurotoxicity and the selective vulnerability of nervous system sites.

PubMed

Maurer, Laura L; Philbert, Martin A

2015-01-01

The spatial heterogeneity of the structure, function, and cellular composition of the nervous system confers extraordinary complexity and a multiplicity of mechanisms of chemical neurotoxicity. Because of its relatively high metabolic demands and functional dependence on postmitotic neurons, the nervous system is vulnerable to a variety of xenobiotics that affect essential homeostatic mechanisms that support function. Despite protection from the neuroglia and blood-brain barrier, the central nervous system is prone to attack from lipophilic toxicants and those that hijack endogenous transport, receptor, metabolic, and other biochemical systems. The inherent predilection of chemicals for highly conserved biochemical systems confers selective vulnerability of the nervous system to neurotoxicants. This chapter discusses selective vulnerability of the nervous system in the context of neuron-specific decrements (axonopathy, myelinopathy, disruption of neurotransmission), and the degree to which neuronal damage is facilitated or ameliorated by surrounding nonneural cells in both the central and peripheral nervous systems. © 2015 Elsevier B.V. All rights reserved.

SoxNeuro orchestrates central nervous system specification and differentiation in Drosophila and is only partially redundant with Dichaete

PubMed Central

2014-01-01

Background Sox proteins encompass an evolutionarily conserved family of transcription factors with critical roles in animal development and stem cell biology. In common with vertebrates, the Drosophila group B proteins SoxNeuro and Dichaete are involved in central nervous system development, where they play both similar and unique roles in gene regulation. Sox genes show extensive functional redundancy across metazoans, but the molecular basis underpinning functional compensation mechanisms at the genomic level are currently unknown. Results Using a combination of genome-wide binding analysis and gene expression profiling, we show that SoxNeuro directs embryonic neural development from the early specification of neuroblasts through to the terminal differentiation of neurons and glia. To address the issue of functional redundancy and compensation at a genomic level, we compare SoxNeuro and Dichaete binding, identifying common and independent binding events in wild-type conditions, as well as instances of compensation and loss of binding in mutant backgrounds. Conclusions We find that early aspects of group B Sox functions in the central nervous system, such as stem cell maintenance and dorsoventral patterning, are highly conserved. However, in contrast to vertebrates, we find that Drosophila group B1 proteins also play prominent roles during later aspects of neural morphogenesis. Our analysis of the functional relationship between SoxNeuro and Dichaete uncovers evidence for redundant and independent functions for each protein, along with unexpected examples of compensation and interdependency, thus providing new insights into the general issue of transcription factor functional redundancy. PMID:24886562

KSC-98pc270

NASA Image and Video Library

1998-02-05

KENNEDY SPACE CENTER, FLA. -- The STS-90 Neurolab payload is lowered into its payload canister in KSC's Operations and Checkout Building. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90, slated for launch in April, will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-98pc292

NASA Image and Video Library

1998-02-12

The STS-90 Neurolab payload is positioned into the cargo bay of Space Shuttle Columbia today in Orbiter Processing Facility bay 3. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90, slated for launch in April, will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-98pc269

NASA Image and Video Library

1998-02-05

KENNEDY SPACE CENTER, FLA. -- The STS-90 Neurolab payload is lowered into its payload canister in KSC's Operations and Checkout Building. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90, slated for launch in April, will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa.

PubMed

Dantzer, Robert

2018-01-01

Because of the compartmentalization of disciplines that shaped the academic landscape of biology and biomedical sciences in the past, physiological systems have long been studied in isolation from each other. This has particularly been the case for the immune system. As a consequence of its ties with pathology and microbiology, immunology as a discipline has largely grown independently of physiology. Accordingly, it has taken a long time for immunologists to accept the concept that the immune system is not self-regulated but functions in close association with the nervous system. These associations are present at different levels of organization. At the local level, there is clear evidence for the production and use of immune factors by the central nervous system and for the production and use of neuroendocrine mediators by the immune system. Short-range interactions between immune cells and peripheral nerve endings innervating immune organs allow the immune system to recruit local neuronal elements for fine tuning of the immune response. Reciprocally, immune cells and mediators play a regulatory role in the nervous system and participate in the elimination and plasticity of synapses during development as well as in synaptic plasticity at adulthood. At the whole organism level, long-range interactions between immune cells and the central nervous system allow the immune system to engage the rest of the body in the fight against infection from pathogenic microorganisms and permit the nervous system to regulate immune functioning. Alterations in communication pathways between the immune system and the nervous system can account for many pathological conditions that were initially attributed to strict organ dysfunction. This applies in particular to psychiatric disorders and several immune-mediated diseases. This review will show how our understanding of this balance between long-range and short-range interactions between the immune system and the central nervous system has evolved over time, since the first demonstrations of immune influences on brain functions. The necessary complementarity of these two modes of communication will then be discussed. Finally, a few examples will illustrate how dysfunction in these communication pathways results in what was formerly considered in psychiatry and immunology to be strict organ pathologies.

Fifth Symposium on the Role of the Vestibular Organs in Space Exploration

NASA Technical Reports Server (NTRS)

1973-01-01

Vestibular problems of manned space flight are investigated for weightlessness and reduced gravity conditions with emphasis on space station development. Intensive morphological studies on the vestibular system and its central nervous system connections are included.

Are Pesticides Taking Away the Ability of Our Children to Learn?

ERIC Educational Resources Information Center

O'Brien, Mary

1991-01-01

The effects of neurotoxins on the development of the central and peripheral nervous systems are discussed. Organophosphates, carbamates, organic solvents, and dioxin are highlighted. The effects of long- and short-term exposure are described. (CW)

Talking back: Development of the olivocochlear efferent system.

PubMed

Frank, Michelle M; Goodrich, Lisa V

2018-06-26

Developing sensory systems must coordinate the growth of neural circuitry spanning from receptors in the peripheral nervous system (PNS) to multilayered networks within the central nervous system (CNS). This breadth presents particular challenges, as nascent processes must navigate across the CNS-PNS boundary and coalesce into a tightly intermingled wiring pattern, thereby enabling reliable integration from the PNS to the CNS and back. In the auditory system, feedforward spiral ganglion neurons (SGNs) from the periphery collect sound information via tonotopically organized connections in the cochlea and transmit this information to the brainstem for processing via the VIII cranial nerve. In turn, feedback olivocochlear neurons (OCNs) housed in the auditory brainstem send projections into the periphery, also through the VIII nerve. OCNs are motor neuron-like efferent cells that influence auditory processing within the cochlea and protect against noise damage in adult animals. These aligned feedforward and feedback systems develop in parallel, with SGN central axons reaching the developing auditory brainstem around the same time that the OCN axons extend out toward the developing inner ear. Recent findings have begun to unravel the genetic and molecular mechanisms that guide OCN development, from their origins in a generic pool of motor neuron precursors to their specialized roles as modulators of cochlear activity. One recurrent theme is the importance of efferent-afferent interactions, as afferent SGNs guide OCNs to their final locations within the sensory epithelium, and efferent OCNs shape the activity of the developing auditory system. This article is categorized under: Nervous System Development > Vertebrates: Regional Development. © 2018 Wiley Periodicals, Inc.

Neuromuscular development of Aeolidiella stephanieae Valdéz, 2005 (Mollusca, Gastropoda, Nudibranchia)

PubMed Central

2010-01-01

Background Studies on the development of the nervous system and the musculature of invertebrates have become more sophisticated and numerous within the last decade and have proven to provide new insights into the evolutionary history of organisms. In order to provide new morphogenetic data on opisthobranch gastropods we investigated the neuromuscular development in the nudibranch Aeolidiella stephanieae Valdéz, 2005 using immunocytochemistry as well as F-actin labelling in conjunction with confocal laser scanning microscopy (cLSM). Results The ontogenetic development of Aeolidiella stephanieae can be subdivided into 8 stages, each recognisable by characteristic morphological and behavioural features as well as specific characters of the nervous system and the muscular system, respectively. The larval nervous system of A. stephanieae includes an apical organ, developing central ganglia, and peripheral neurons associated with the velum, foot and posterior, visceral part of the larva. The first serotonergic and FMRFamidergic neural structures appear in the apical organ that exhibits an array of three sensory, flask-shaped and two non-sensory, round neurons, which altogether disappear prior to metamorphosis. The postmetamorphic central nervous system (CNS) becomes concentrated, and the rhinophoral ganglia develop together with the anlage of the future rhinophores whereas oral tentacle ganglia are not found. The myogenesis in A. stephanieae begins with the larval retractor muscle followed by the accessory larval retractor muscle, the velar or prototroch muscles and the pedal retractors that all together degenerate during metamorphosis, and the adult muscle complex forms de novo. Conclusions Aeolidiella stephanieae comprises features of the larval and postmetamorphic nervous as well as muscular system that represent the ground plan of the Mollusca or even the Trochozoa (e. g. presence of the prototrochal or velar muscle ring). On the one hand, A. stephanieae shows some features shared by all nudibranchs like the postmetamorphic condensation of the CNS, the possession of rhinophoral ganglia and the lack of oral tentacle ganglia as well as the de novo formation of the adult muscle complex. On the other hand, the structure and arrangement of the serotonergic apical organ is similar to other caenogastropod and opisthobranch gastropods supporting their sister group relationship. PMID:20205753

Central nervous system granulomastous phlebitis with limited extracranial involvement of the heart and lungs: An autopsy case.

PubMed

Mlakar, Jernej; Zorman, Jerneja Videčnik; Matičič, Mojca; Vrabec, Matej; Alibegović, Armin; Popović, Mara

2016-02-01

Primary angiitis of the central nervous system is a rare condition, usually with an insidious onset. There is a wide variety of histological types (granulomatous, lymphocytic or necrotizing vasculitis) and types of vessel involved (arteries, veins or both). Most cases are idiopathic. We describe a first case of idiopathic granulomatous central nervous system phlebitis with additional limited involvement of the heart and lung, exclusively affecting small and medium sized veins in a 22-year-old woman, presenting as a sub acute headache. The reasons for this peculiar limitation of inflammation to the veins and the involvement of the heart and lungs are unknown. © 2015 Japanese Society of Neuropathology.

Hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus in the central nervous system.

PubMed

Magaki, Shino; Ostrzega, Nora; Ho, Elliot; Yim, Catherine; Wu, Phillis; Vinters, Harry V

2017-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare immune hyperactivation syndrome which may be primary (genetic) or secondary to various immune-related conditions including infection, immunodeficiency, and malignancies. Rapid diagnosis and treatment are essential because it can be associated with significant morbidity and mortality. Epstein-Barr virus (EBV) is a known infectious cause of acquired HLH, but EBV-associated HLH involving the central nervous system is rare and not well characterized neuropathologically. We report a case of fatal EBV-associated HLH with severe involvement of the central nervous system showing florid hemophagocytosis in the choroid plexus, with extensive neuron loss and gliosis in the cerebrum, cerebellum, and brainstem. Copyright © 2016 Elsevier Inc. All rights reserved.

Gross anatomy of central nervous system in firefly, Pteroptyx tener (Coleoptera: Lampyridae)

NASA Astrophysics Data System (ADS)

Hudawiyah, Nur; Wahida, O. Nurul; Norela, S.

2015-09-01

This paper describes for the first time the organization and fine structure of the central nervous system (CNS) in the fireflies, Pteroptyx tener (Coleoptera: Lampyridae). The morphology of the CNS was examined by using Carl Zeiss AxioScope A1 photomicroscope with iSolution Lite software. Some specific structural features such as the localization of protocerebrum, deutocerebrum and tritocerebrum in the brain region were analyzed. Other than that, the nerve cord and its peripheral structure were also analyzed. This study suggests that, there is a very obvious difference between male and female central nervous system which illustrates that they may differ in function in controlling physiological and behavioral activities.

Does gravity influence the early stages of the development of the nervous system in an amphibian?

PubMed

Duprat, A M; Husson, D; Gualandris-Parisot, L

1998-11-01

As a result of previous studies using hypergravity (centrifuge) or virtual microgravity (clinostat), it was proposed that gravity was involved in embryonic development, i.e., in the establishment of the embryonic polarities and the body plan pattern which subsequently direct morphogenesis and organogenesis of the central nervous system and of sensory organs. Recent experiments were performed in space using sounding rockets and orbiting space-modules to ascertain whether gravity is indeed required for embryogenesis in Invertebrates and Vertebrates. Eggs fertilised in vivo or in vitro in microgravity showed some abnormalities during embryonic development but were able to regulate and produce nearly normal larvae. Copyright 1998 Elsevier Science B.V.

Perceptions of Young Adult Central Nervous System Cancer Survivors and Their Parents Regarding Career Development and Employment

ERIC Educational Resources Information Center

Strauser, David R.; Wagner, Stacia; Chan, Fong; Wong, Alex W. K.

2014-01-01

Purpose: Identify barriers to career development and employment from both the survivor and parent perspective. Method: Young adult survivors (N = 43) and their parents participated in focus groups to elicit information regarding perceptions regarding career development and employment. Results: Perceptions of both the young adults and parents…

Annual Research Review: Epigenetic Mechanisms and Environmental Shaping of the Brain during Sensitive Periods of Development

ERIC Educational Resources Information Center

Roth, Tania L.; Sweatt, J. David

2011-01-01

Experiences during early development profoundly affect development of the central nervous system (CNS) to impart either risk for or resilience to later psychopathology. Work in the developmental neuroscience field is providing compelling data that epigenetic marking of the genome may underlie aspects of this process. Experiments in rodents…

Space, Time, and Dyslexia: Central Nervous System Factors in Reading Disability.

ERIC Educational Resources Information Center

Krippner, Stanley

Developmental and post-traumatic dyslexia are discussed in terms of a dysfunction of the central nervous system resulting in reading disabilities. The relationship of reading to other language functions is considered, with emphasis on the temporal aspects of speech and reading. An interdisciplinary approach is held necessary for the diagnosis of…

A Comparative Study of Successful Central Nervous System Drugs Using Molecular Modeling

ERIC Educational Resources Information Center

Kim, Hyosub; Sulaimon, Segun; Menezes, Sandra; Son, Anne; Menezes, Warren J. C.

2011-01-01

Molecular modeling is a powerful tool used for three-dimensional visualization and for exploring electrostatic forces involved in drug transport. This tool enhances student understanding of structure-property relationships, as well as actively engaging them in class. Molecular modeling of several central nervous system (CNS) drugs is used to…

Borrelia miyamotoi–Associated Neuroborreliosis in Immunocompromised Person

PubMed Central

Lobenstein, Sabine; Hermann, Beate; Margos, Gabriele; Fingerle, Volker

2016-01-01

Borrelia miyamotoi is a newly recognized human pathogen in the relapsing fever group of spirochetes. We investigated a case of B. miyamotoi infection of the central nervous system resembling B. burgdorferi–induced Lyme neuroborreliosis and determined that this emergent agent of central nervous system infection can be diagnosed with existing methods. PMID:27533748

A Comparison of the Anorexic Effects of Chicken, Porcine, Human and Bovine Insulin on the Central Nervous System of Chicks

USDA-ARS?s Scientific Manuscript database

The aim of the present study was to determine if some naturally-occurring substitutions of amino acid residues of insulin could act differentially within the central nervous system (CNS) of neonatal chicks to control ingestive behavior. Intracerebroventricular (ICV) administration of chicken insuli...

Diagnostic Challenges of Central Nervous System Tuberculosis

PubMed Central

Loeffler, Ann M.; Honarmand, Somayeh; Flood, Jennifer M.; Baxter, Roger; Jacobson, Susan; Alexander, Rick; Glaser, Carol A.

2008-01-01

Central nervous system tuberculosis (TB) was identified in 20 cases of unexplained encephalitis referred to the California Encephalitis Project. Atypical features (encephalitic symptoms, rapid onset, age) and diagnostic challenges (insensitive cerebrospinal fluid [CSF] TB PCR result, elevated CSF glucose levels in patients with diabetes, negative result for tuberculin skin test) complicated diagnosis. PMID:18760024

Pazopanib efficacy in recurrent central nervous system hemangiopericytomas.

PubMed

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

2018-04-26

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

Neonatal hypoglycemia.

PubMed

Straussman, Sharon; Levitsky, Lynne L

2010-02-01

Hypoglycemia in the newborn may be associated with both acute decompensation and long-term neuronal loss. Studies of the cause of hypoglycemic brain damage and the relationship of hypoglycemia to disorders associated with hyperinsulinism have aided in our understanding of this common clinical finding. A recent consensus workshop concluded that there has been little progress toward a precise numerical definition of neonatal hypoglycemia. Nonetheless, newer brain imaging modalities have provided insight into the relationship between neuronal energy deficiency and central nervous system damage. Laboratory studies have begun to reveal the mechanism of hypoglycemic damage. In addition, there is new information about hyperinsulinemic hypoglycemia of genetic, environmental, and iatrogenic origin. The quantitative definition of hypoglycemia in the newborn remains elusive because it is a surrogate marker for central nervous system energy deficiency. Nonetheless, the recognition that hyperinsulinemic hypoglycemia, which produces profound central nervous system energy deficiency, is most likely to lead to long-term central nervous system damage, has altered management of children with hypoglycemia. In addition, imaging studies on neonates and laboratory evaluation in animal models have provided insight into the mechanism of neuronal damage.

76 FR 5711 - Bispyribac-sodium; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-02

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

The presumed central nervous system effects of rocuronium in a neonate and its reversal with sugammadex.

PubMed

Langley, Ross J; McFadzean, Jillian; McCormack, Jon

2016-01-01

We describe a 2-day-old male infant who received rocuronium as part of general anesthesia for a tracheal esophageal fistula repair. Postoperatively, he had prolonged central and peripheral neuromuscular blockade despite cessation of the rocuronium infusion several hours previously. This case discusses the presumed central nervous system effects of rocuronium in a neonate and its effective reversal with sugammadex. © 2015 John Wiley & Sons Ltd.

Determining Optimal Post-Stroke Exercise (DOSE)

ClinicalTrials.gov

2018-02-13

Cerebrovascular Accident; Stroke; Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Evolving gene regulation networks into cellular networks guiding adaptive behavior: an outline how single cells could have evolved into a centralized neurosensory system

PubMed Central

Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L.

2014-01-01

Understanding the evolution of the neurosensory system of man, able to reflect on its own origin, is one of the major goals of comparative neurobiology. Details of the origin of neurosensory cells, their aggregation into central nervous systems and associated sensory organs, their localized patterning into remarkably different cell types aggregated into variably sized parts of the central nervous system begin to emerge. Insights at the cellular and molecular level begin to shed some light on the evolution of neurosensory cells, partially covered in this review. Molecular evidence suggests that high mobility group (HMG) proteins of pre-metazoans evolved into the definitive Sox [SRY (sex determining region Y)-box] genes used for neurosensory precursor specification in metazoans. Likewise, pre-metazoan basic helix-loop-helix (bHLH) genes evolved in metazoans into the group A bHLH genes dedicated to neurosensory differentiation in bilaterians. Available evidence suggests that the Sox and bHLH genes evolved a cross-regulatory network able to synchronize expansion of precursor populations and their subsequent differentiation into novel parts of the brain or sensory organs. Molecular evidence suggests metazoans evolved patterning gene networks early and not dedicated to neuronal development. Only later in evolution were these patterning gene networks tied into the increasing complexity of diffusible factors, many of which were already present in pre-metazoans, to drive local patterning events. It appears that the evolving molecular basis of neurosensory cell development may have led, in interaction with differentially expressed patterning genes, to local network modifications guiding unique specializations of neurosensory cells into sensory organs and various areas of the central nervous system. PMID:25416504

Evolving gene regulatory networks into cellular networks guiding adaptive behavior: an outline how single cells could have evolved into a centralized neurosensory system.

PubMed

Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L

2015-01-01

Understanding the evolution of the neurosensory system of man, able to reflect on its own origin, is one of the major goals of comparative neurobiology. Details of the origin of neurosensory cells, their aggregation into central nervous systems and associated sensory organs and their localized patterning leading to remarkably different cell types aggregated into variably sized parts of the central nervous system have begun to emerge. Insights at the cellular and molecular level have begun to shed some light on the evolution of neurosensory cells, partially covered in this review. Molecular evidence suggests that high mobility group (HMG) proteins of pre-metazoans evolved into the definitive Sox [SRY (sex determining region Y)-box] genes used for neurosensory precursor specification in metazoans. Likewise, pre-metazoan basic helix-loop-helix (bHLH) genes evolved in metazoans into the group A bHLH genes dedicated to neurosensory differentiation in bilaterians. Available evidence suggests that the Sox and bHLH genes evolved a cross-regulatory network able to synchronize expansion of precursor populations and their subsequent differentiation into novel parts of the brain or sensory organs. Molecular evidence suggests metazoans evolved patterning gene networks early, which were not dedicated to neuronal development. Only later in evolution were these patterning gene networks tied into the increasing complexity of diffusible factors, many of which were already present in pre-metazoans, to drive local patterning events. It appears that the evolving molecular basis of neurosensory cell development may have led, in interaction with differentially expressed patterning genes, to local network modifications guiding unique specializations of neurosensory cells into sensory organs and various areas of the central nervous system.

Microbiota-gut-brain axis and the central nervous system.

PubMed

Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

2017-08-08

The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseases.

Alpha-7 Nicotinic Receptors in Nervous System Disorders: From Function to Therapeutic Perspectives.

PubMed

De Jaco, Antonella; Bernardini, Laura; Rosati, Jessica; Tata, Ada Maria

2017-01-01

The α7 nicotinic receptor consists of identical subunits and is one of the most abundant acetylcholine receptors in the mammalian central nervous system. However its expression is also found in the peripheral nervous system as well as in the immune system and various peripheral tissues. Nicotinic Receptors: They are involved in the regulation of several activities ranging from excitatory neurotransmission, the modulation of the release of several neurotransmitters, regulation of neurite outgrowth, and even neuronal survival/death. Its expression is found in brain areas that underlie learning and memory, suggesting their involvement in regulating cognitive functions. The α7-nicotinic receptor has a strategic role during development in regulating molecular pathways activated during neurogenesis. Because of its pleiotropic effects, receptor dysfunction or dysregulated expression is found in pathophysiological conditions of the nervous system including neurodegenerative diseases and neurodevelopmental disorders. Here we review the physiological and pathological roles of alpha-7 nicotinic receptor in different nervous system disorders and the current therapeutic strategies developed to target selectively this receptor for potentiating or reducing its functions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Intellectual Deficits After Transient Tyrosinemia in the Term Neonate

ERIC Educational Resources Information Center

Mamunes, Peter; And Others

1976-01-01

In order to determine if prolonged significant transient neonatal tyrosinemia is injurious to the developing central nervous system, 15 term infants who had suffered from this disorder (involving high blood levels of the amino acid tyrosine) were evaluated. (Author/DB)

Development of Strategies to Increase Enrollment in Clinical Trials for Children With Cancer

ClinicalTrials.gov

2014-02-12

Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Leukemia; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Psychosocial Effects of Cancer and Its Treatment; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Case of Primary Central Nervous System Lymphoma Arising at Site of Remote Herpes Encephalitis.

PubMed

Li, Victor; Levine, Adrian B; Gooderham, Peter A; Yip, Stephen; Chew, Jason

2018-05-01

Primary central nervous system lymphoma (PCNSL) is a rare malignancy that usually arises in the context of severe immunosuppression but has incompletely understood etiology, limiting effective treatments. We present the case of an 81-year-old immunocompetent man who developed a PCNSL in the right temporal lobe, at the site of a remote episode of herpes simplex virus (HSV) encephalitis 8 years prior. There are numerous viruses with known oncogenic associations; however, to our knowledge, this is the first reported case of PCNSL with an antecedent HSV infection. We discuss this case in the context of our current understandings of the pathogenesis of HSV encephalitis and PCNSL and postulate mechanisms through which the 2 could be associated. Copyright © 2018 Elsevier Inc. All rights reserved.

Optimized optical clearing method for imaging central nervous system

NASA Astrophysics Data System (ADS)

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

2015-03-01

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

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

Experimental evidence of a dual endocrine control of biosynthesis in the main nidamental glands of Sepia officinalis L. by factors from the central nervous system and the ovary.

PubMed

Henry, J; Boucaud-Camou, E

1993-12-01

1. A rapid, reliable and quantitative in vitro bioassay was developed to study the endocrine control of the biosynthesis of the egg capsule: incorporation of 14C-labelled D-glucose in polysaccharides and glycoproteins increased in dispersed-cell suspensions of main nidamental glands from maturing females. 2. Brain, optic lobes (OL) and ovary extracts from mature and maturing females stimulated the incorporation of 14C-labelled D-glucose in polysaccharidic and glycoproteic fractions of a nidamental cell suspension, whereas optic gland (OG) had no effect. 3. These results bring the first experimental evidence that one of the spawning events (egg-capsule edification) is controlled by the central nervous system and the ovary in a cephalopod.

Adams-Oliver Syndrome with Unusual Central Nervous System Findings and an Extrahepatic Portosystemic Shunt

PubMed Central

Pérez-García, Carlos; Martín, Yolanda Ruíz; del Hoyo, Alejandra Aguado; Rodríguez, Carlos Marín; Domínguez, Minia Campos

2017-01-01

We report a case of a premature neonate girl with scalp and skull defects and brachydactyly of the feet consistent with an Adams-Oliver syndrome (AOS). The patient had central nervous system abnormalities, such as periventricular calcifications, hypoplastic corpus callosum, and bilateral hemispheric corticosubcortical hemorrhagic lesions. A muscular ventricular septal defect and a portosystemic shunt were diagnosed. To our knowledge, this is the first report of congenital supratentorial grey-white matter junction lesions without dural sinus thrombosis in association with AOS. Some of these lesions may be secondary to birth trauma (given the skull defect) whilst others have a watershed location, perhaps as further evidence of vascular disruption and decreased perfusion during critical periods of fetal brain development as the previously proposed pathogenesis of this syndrome. PMID:28706620

New laser technologies in the clinic of neurosurgery

NASA Astrophysics Data System (ADS)

Stupak, V. V.; Fomichev, N. G.; Tsvetovsky, S. B.; Dmitriev, A. B.; Kobosev, V. V.; Bagaev, S. N.; Mayorov, A. P.; Struts, S. G.

2005-08-01

In report summarized more then 10 experience of authors in Novosibirsk Traumatology and orthopedics research institute Neurosurgery clinic on usage of laser technologies in treatment of central nervous system tumors. On the basis of ND-YAG laser application original technologies have been developed and used in surgical treatment of patients with various neurosurgical pathology and protected by 8 Patents of the Russian Federation. 427 patients were operated on with the use of YAG:Nd3+ laser. Out of them 152 patients had extracerebral tumors of various volume and localization, 135 patients - spinal cord tumors, 74 patients - a pathology of cerebrospinal transition (Amold-Chiari syndrome of 1-2 types), and 66 patients - intramedullary tumors of deep localization. Results showed good results of laser technologies usage for central nervous system tumors removal.

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

PubMed

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

2017-09-15

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

[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.

Descriptive epidemiology of childhood central nervous system tumours in Tunisia. experience of a single institution over a 15-year period (1990-2004).

PubMed

Bellil, Salma; Limaiem, Faten; Mahfoudhi, Houaïda; Bellil, Khadija; Chelly, Inès; Mekni, Amina; Jemel, Hafedh; Khaldi, Moncef; Haouet, Slim; Zitouna, Moncef; Kchir, Nidhameddine

2008-01-01

Central nervous system tumours represent 20% of all childhood cancers, and are the second most common group of neoplasms after leukaemias. To describe epidemiological characteristics of central nervous system tumours in a paediatric Tunisian population. A retrospective study of 492 childhood central nervous system tumours operated between 1990 and 2004 was undertaken. We investigated the age-related location, gender distribution and the histology of all tumours, and adopted the latest WHO classification (2007) in grouping all the tumours. There were 488 primary and 4 secondary tumours; 426 (86.6%) were intracranial and 66 (13.4%) were intraspinal. Of the 426 intracranial tumours, 214 (50.24%) were supratentorial and 212 (49.76%) were infratentorial. The median age at diagnosis was 8 years, with a male:female ratio of 1.14:1. Low-grade tumours (WHO I/II) constituted 67.3% of all lesions and the rest (32.7%) were high-grade tumours (WHO III/IV). The most common tumour found in our series was astrocytoma (38%), followed by medulloblastoma (16.2%), then ependymoma (6.9%), cystic tumours (6.3%) and craniopharyngioma (5.3%). The overall 5-year survival rate was 45% with a mean follow-up period of 36 months. In our patient population, the incidence and distribution of central nervous system tumours were similar to those reported in literature. Overall survival rates varied according to tumour location and histopathology. (c) 2008 S. Karger AG, Basel.

A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies

PubMed Central

Drusco, Alessandra; Bottoni, Arianna; Laganà, Alessandro; Acunzo, Mario; Fassan, Matteo; Cascione, Luciano; Antenucci, Anna; Kumchala, Prasanthi; Vicentini, Caterina; Gardiman, Marina P.; Alder, Hansjuerg; Carosi, Mariantonia A.; Ammirati, Mario; Gherardi, Stefano; Luscrì, Marilena; Carapella, Carmine; Zanesi, Nicola; Croce, Carlo M.

2015-01-01

Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application. The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies. CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization. Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies. This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications. PMID:26246487

A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies.

PubMed

Drusco, Alessandra; Bottoni, Arianna; Laganà, Alessandro; Acunzo, Mario; Fassan, Matteo; Cascione, Luciano; Antenucci, Anna; Kumchala, Prasanthi; Vicentini, Caterina; Gardiman, Marina P; Alder, Hansjuerg; Carosi, Mariantonia A; Ammirati, Mario; Gherardi, Stefano; Luscrì, Marilena; Carapella, Carmine; Zanesi, Nicola; Croce, Carlo M

2015-08-28

Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application.The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies.CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization.Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies.This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications.

Neurologic complications of electrolyte disturbances and acid-base balance.

PubMed

Espay, Alberto J

2014-01-01

Electrolyte and acid-base disturbances are common occurrences in daily clinical practice. Although these abnormalities can be readily ascertained from routine laboratory findings, only specific clinical correlates may attest as to their significance. Among a wide phenotypic spectrum, acute electrolyte and acid-base disturbances may affect the peripheral nervous system as arreflexic weakness (hypermagnesemia, hyperkalemia, and hypophosphatemia), the central nervous system as epileptic encephalopathies (hypomagnesemia, dysnatremias, and hypocalcemia), or both as a mixture of encephalopathy and weakness or paresthesias (hypocalcemia, alkalosis). Disabling complications may develop not only when these derangements are overlooked and left untreated (e.g., visual loss from intracranial hypertension in respiratory or metabolic acidosis; quadriplegia with respiratory insufficiency in hypermagnesemia) but also when they are inappropriately managed (e.g., central pontine myelinolisis when rapidly correcting hyponatremia; cardiac arrhythmias when aggressively correcting hypo- or hyperkalemia). Therefore prompt identification of the specific neurometabolic syndromes is critical to correct the causative electrolyte or acid-base disturbances and prevent permanent central or peripheral nervous system injury. This chapter reviews the pathophysiology, clinical investigations, clinical phenotypes, and current management strategies in disorders resulting from alterations in the plasma concentration of sodium, potassium, calcium, magnesium, and phosphorus as well as from acidemia and alkalemia. © 2014 Elsevier B.V. All rights reserved.

Rare association between cystic fibrosis, Chiari I malformation, and hydrocephalus in a baby: a case report and review of the literature

PubMed Central

2011-01-01

Introduction Cystic fibrosis, an epithelial cell transport disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator gene, is not generally associated with malformations of the central nervous system. We review eight previously published reports detailing an infrequent association between cystic fibrosis and Chiari I malformation. Case presentation To the best of our knowledge, our report describes only the ninth case of a baby presenting with a new diagnosis of cystic fibrosis and Chiari I malformation, in this case in a 10-month-old, full-term Caucasian baby boy from the United States of America. Neurosurgical consultation was obtained for associated developmental delay, macrocephaly, bulging anterior fontanel, and papilledema. An MRI scan demonstrated an extensive Chiari I malformation with effacement of the fourth ventricle, obliteration of the outlets of the fourth ventricle and triventricular hydrocephalus without aqueductal stenosis. Our patient was taken to the operating room for ventriculoperitoneal shunt placement. Conclusions It is possible that the cystic fibrosis transmembrane conductance regulator gene may play a previously unrecognized role in central nervous system development; alternatively, this central nervous system abnormality may have been acquired due to constant valsalva from recurrent coughing or wheezing or metabolic and electrolyte imbalances that occur characteristically in cystic fibrosis. PMID:21838874

Differentiation of Enhancing Glioma and Primary Central Nervous System Lymphoma by Texture-Based Machine Learning.

PubMed

Alcaide-Leon, P; Dufort, P; Geraldo, A F; Alshafai, L; Maralani, P J; Spears, J; Bharatha, A

2017-06-01

Accurate preoperative differentiation of primary central nervous system lymphoma and enhancing glioma is essential to avoid unnecessary neurosurgical resection in patients with primary central nervous system lymphoma. The purpose of the study was to evaluate the diagnostic performance of a machine-learning algorithm by using texture analysis of contrast-enhanced T1-weighted images for differentiation of primary central nervous system lymphoma and enhancing glioma. Seventy-one adult patients with enhancing gliomas and 35 adult patients with primary central nervous system lymphomas were included. The tumors were manually contoured on contrast-enhanced T1WI, and the resulting volumes of interest were mined for textural features and subjected to a support vector machine-based machine-learning protocol. Three readers classified the tumors independently on contrast-enhanced T1WI. Areas under the receiver operating characteristic curves were estimated for each reader and for the support vector machine classifier. A noninferiority test for diagnostic accuracy based on paired areas under the receiver operating characteristic curve was performed with a noninferiority margin of 0.15. The mean areas under the receiver operating characteristic curve were 0.877 (95% CI, 0.798-0.955) for the support vector machine classifier; 0.878 (95% CI, 0.807-0.949) for reader 1; 0.899 (95% CI, 0.833-0.966) for reader 2; and 0.845 (95% CI, 0.757-0.933) for reader 3. The mean area under the receiver operating characteristic curve of the support vector machine classifier was significantly noninferior to the mean area under the curve of reader 1 ( P = .021), reader 2 ( P = .035), and reader 3 ( P = .007). Support vector machine classification based on textural features of contrast-enhanced T1WI is noninferior to expert human evaluation in the differentiation of primary central nervous system lymphoma and enhancing glioma. © 2017 by American Journal of Neuroradiology.

Primary central nervous system diffuse large B-cell lymphoma shows an activated B-cell-like phenotype with co-expression of C-MYC, BCL-2, and BCL-6.

PubMed

Li, Xiaomei; Huang, Ying; Bi, Chengfeng; Yuan, Ji; He, Hong; Zhang, Hong; Yu, QiuBo; Fu, Kai; Li, Dan

2017-06-01

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, whose main prognostic factor is closely related to germinal center B-cell-like subtype (GCB- DLBCL) or activated B-cell-like type (non-GCB-DLBCL). The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear. This study aims to stratify primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) according to the cell-of-origin (COO) and to investigate the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53, further to elucidate the reason why primary central nervous system diffuse large B-cell lymphoma possesses a poor clinical outcome as well. Nineteen cases of primary central nervous system DLBCL were stratified according to immunostaining algorithms of Hans, Choi and Meyer (Tally) and we investigated the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53. The Epstein-Barr virus and Borna disease virus infection were also detected. Among nineteen cases, most (15-17 cases) were assigned to the activated B-cell-like subtype, highly expression of C-MYC (15 cases, 78.9%), BCL-2 (10 cases, 52.6%), BCL-6 (15 cases, 78.9%). Unfortunately, two cases were positive for PD-L1 while PD-L2 was not expressed in any case. Two cases infected with BDV but no one infected with EBV. In conclusion, most primary central nervous system DLBCLs show an activated B-cell-like subtype characteristic and have multiple expressions of C-MYC, BCL-2, BCL-6 protein, these features might be significant factor to predict the outcome and guide treatment of PCNS-DLBCLs. Copyright © 2017 Elsevier GmbH. All rights reserved.

Essential tremor

MedlinePlus

... Tremor - familial; Benign essential tremor; Shaking - essential tremor Images Central nervous system and peripheral nervous system References Jankovic J. Parkinson disease and other movement disorders. In: Daroff ...

Olivopontocerebellar atrophy

MedlinePlus

... degeneration; Multiple system atrophy cerebellar predominance; MSA-C Images Central nervous system and peripheral nervous system References Jankovic J, Lang AE. Diagnosis and assessment of Parkinson disease ...

Movement - uncontrollable

MedlinePlus

... movements; Body movements - uncontrollable; Dyskinesia; Athetosis; Myoclonus; Ballismus Images Central nervous system and peripheral nervous system References Jankovic J, Lang AE. Diagnosis and assessment of Parkinson disease ...

Basic Concepts of CNS Development.

ERIC Educational Resources Information Center

Nowakowski, R. S.

1987-01-01

The goals of this review are to: (1) provide a set of concepts to aid in the understanding of complex processes which occur during central nervous system (CNS) development; (2) illustrate how they contribute to our knowlege of adult brain anatomy; and (3) delineate how modifications of normal developmental processes may affect the structure and…

A Case of Systemic Lupus Erythematosus developing Two years after Remission of Thrombotic Thrombocytopenic Purpura

PubMed Central

Myung, Seung-Jae; Yoo, Bin; Lee, Kyoo-Hyung; Yoo, Mi-Ran; Choi, Seung-Won; Yoo, Eun-Sil; Chi, Hyun-Sook; Moon, Hee-Bom

1996-01-01

We describe a 17-year-old male who presented with thrombotic thrombocytopenic purpura (TTP) and 2 years thereafter developed central nervous system lupus and nephritis. The association of TTP and systemic lupus erythematosus has been described, but the unusual sequence and chronological separation is very rare. PMID:8854658

[Update on congenital and neonatal herpes infections: infection due to cytomegalovirus and herpes simplex].

PubMed

Baquero-Artigao, F

2017-05-17

Newborn infants are a population which is especially susceptible to viral infections that frequently affect the central nervous system. Herpes infections can be transmitted to the foetus and to the newborn infant, and give rise to severe clinical conditions with long-term sensory and cognitive deficits. Two thirds of newborn infants with encephalitis due to herpes simplex virus and half of the children with symptomatic congenital infection by cytomegalovirus develop sequelae, which results in high community health costs in the long term. Fortunately, the better knowledge about these infections gained in recent years together with the development of effective antiviral treatments have improved the patients' prognosis. Valganciclovir (32 mg/kg/day in two doses for six months) prevents the development of hypoacusis and improves the neurological prognosis in symptomatic congenital infection due to cytomegalovirus. Acyclovir (60 mg/kg/day in three doses for 2-3 weeks) prevents the development of severe forms in skin-eyes-mouth herpes disease, and lowers the rate of mortality and sequelae when the disease has disseminated and is located in the central nervous system.

Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature.

PubMed

Verheij, Johanna B G M; Sival, Deborah A; van der Hoeven, Johannes H; Vos, Yvonne J; Meiners, Linda C; Brouwer, Oebele F; van Essen, Anthonie J

2006-01-01

Shah-Waardenburg syndrome is a rare congenital disorder with variable clinical expression, characterised by aganglionosis of the rectosigmoïd (Hirschsprung disease), and abnormal melanocyte migration, resulting in pigmentary abnormalities and sensorineural deafness (Waardenburg syndrome). Mutations in the EDN, EDNRB and SOX10 genes can be found in patients with this syndrome. SOX10 mutations are specifically associated with a more severe phenotype called PCWH: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease. Neuronal expression of SOX10 occurs in neural crest cells during early embryonic development and in glial cells of the peripheral and central nervous systems during late embryonic development and in adults. We present a 4-year-old girl with the PCWH phenotype associated with a de novo nonsense mutation (S384X) in SOX10. Main clinical features were mental retardation, peripheral neuropathy, deafness, Hirschsprung disease, distal arthrogryposis, white hairlock, and growth retardation. She presented with hypotonia, developmental delay, reduced peripheral nerve conduction velocities, and radiologically assessed central hypomyelination. Subsequently, the formation of abnormal myelin within the central and peripheral nervous system was functionally and radiologically assessed. Children presenting with features of Waardenburg syndrome and neurological dysfunction should be tested for mutations in the SOX10 gene to enable diagnosis and counselling.

Development of the auditory system

PubMed Central

Litovsky, Ruth

2015-01-01

Auditory development involves changes in the peripheral and central nervous system along the auditory pathways, and these occur naturally, and in response to stimulation. Human development occurs along a trajectory that can last decades, and is studied using behavioral psychophysics, as well as physiologic measurements with neural imaging. The auditory system constructs a perceptual space that takes information from objects and groups, segregates sounds, and provides meaning and access to communication tools such as language. Auditory signals are processed in a series of analysis stages, from peripheral to central. Coding of information has been studied for features of sound, including frequency, intensity, loudness, and location, in quiet and in the presence of maskers. In the latter case, the ability of the auditory system to perform an analysis of the scene becomes highly relevant. While some basic abilities are well developed at birth, there is a clear prolonged maturation of auditory development well into the teenage years. Maturation involves auditory pathways. However, non-auditory changes (attention, memory, cognition) play an important role in auditory development. The ability of the auditory system to adapt in response to novel stimuli is a key feature of development throughout the nervous system, known as neural plasticity. PMID:25726262

The development of biomarkers to reduce attrition rate in drug discovery focused on oncology and central nervous system.

PubMed

Safavi, Maliheh; Sabourian, Reyhaneh; Abdollahi, Mohammad

2016-10-01

The task of discovery and development of novel therapeutic agents remains an expensive, uncertain, time-consuming, competitive, and inefficient enterprise. Due to a steady increase in the cost and time of drug development and the considerable amount of resources required, a predictive tool is needed for assessing the safety and efficacy of a new chemical entity. This study is focused on the high attrition rate in discovery and development of oncology and central nervous system (CNS) medicines, because the failure rate of these medicines is higher than others. Some approaches valuable in reducing attrition rates are proposed and the judicious use of biomarkers is discussed. Unlike the significant progress made in identifying and characterizing novel mechanisms of disease processes and targeted therapies, the process of novel drug development is associated with an unacceptably high attrition rate. The application of clinically qualified predictive biomarkers holds great promise for further development of therapeutic targets, improved survival, and ultimately personalized medicine sets for patients. Decisions such as candidate selection, development risks, dose ranging, early proof of concept/principle, and patient stratification are based on the measurements of biologically and/or clinically validated biomarkers.

Progressive supranuclear palsy

MedlinePlus

... dystonia; Richardson-Steele-Olszewski syndrome; Palsy - progressive supranuclear Images Central nervous system and peripheral nervous system References Jankovic J. Parkinson disease and other movement disorders. In: Daroff ...

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.

Novel Dissection of the Central Nervous System to Bridge Gross Anatomy and Neuroscience for an Integrated Medical Curriculum

ERIC Educational Resources Information Center

Hlavac, Rebecca J.; Klaus, Rachel; Betts, Kourtney; Smith, Shilo M.; Stabio, Maureen E.

2018-01-01

Medical schools in the United States continue to undergo curricular change, reorganization, and reformation as more schools transition to an integrated curriculum. Anatomy educators must find novel approaches to teach in a way that will bridge multiple disciplines. The cadaveric extraction of the central nervous system (CNS) provides an…

Conventional external beam radiotherapy for central nervous system malignancies

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

Halperin, E.C.; Burger, P.C.

1985-11-01

Fractionated external beam photon radiotherapy is an important component of the clinical management of malignant disease of the central nervous system. The practicing neurologist or neurosurgeon frequently relies on the consultative and treatment skills of a radiotherapist. This article provides a review for the nonradiotherapist of the place of conventional external beam radiotherapy in neuro-oncology. 23 references.

National Training Course. Emergency Medical Technician. Paramedic. Instructor's Lesson Plans. Module VII. Central Nervous System.

ERIC Educational Resources Information Center

National Highway Traffic Safety Administration (DOT), Washington, DC.

This instructor's lesson plan guide on the central nervous system is one of fifteen modules designed for use in the training of emergency medical technicians. Four units of study are presented: (1) anatomy and physiology; (2) assessment of patients with neurological problems; (3) pathophysiology and management of neurological problems; (4)…

Disseminated Cryptococcosis With Brain Involvement in Patients With Chronic Lymphoid Malignancies on Ibrutinib.

PubMed

Messina, Julia A; Maziarz, Eileen K; Spec, Andrej; Kontoyiannis, Dimitrios P; Perfect, John R

2017-01-01

We report 2 cases of disseminated cryptococcosis with central nervous system involvement in patients with chronic lymphoid malignancies occurring within 1 month of starting on ibrutinib. Characteristically, in both cases, no inflammation was seen in the cerebrospinal fluid. Central nervous system mycoses should be considered as a potential complication of ibrutinib.

Effects of Gentiana lutea ssp. symphyandra on the central nervous system in mice.

PubMed

Oztürk, Nilgün; Başer, K Hüsnü Can; Aydin, Süleyman; Oztürk, Yusuf; Caliş, Ihsan

2002-11-01

A methanolic extact of Gentiana lutea ssp. symphyandra roots has been investigated for its possible effects on the central nervous system of mice. At doses of 250 and 500 mg/kg (i.p.), the methanol extract of Gentiana roots caused a significant increase in the swimming endurance test and exhibited slight analgesic activity, but no lethality in mice suggesting some activity on the central nervous system. However, there was no indication of sedation or muscular fatigue at the doses employed. HPLC analysis showed that three secoiridoid compounds, gentiopicroside, swertiamarine and sweroside were present and may have been responsible for the CNS effects of the methanol extract of Gentiana lutea ssp. symphyandra roots. Copyright 2002 John Wiley & Sons, Ltd.

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

PubMed

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

2003-01-01

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

[Central nervous system dysgerminoma: a clinicopathological study of 3 cases].

PubMed

Bellil, Selma; Braham, Emna; Limaiem, Faten; Bellil, Khadija; Chelly, Ines; Mekni, Amina; Haouet, Slim; Zitouna, Moncef; Jemel, Hafedh; Khaldi, Moncef; Kchir, Nidhameddine

2009-03-01

Intracranial germ cell tumors are rarely seen and typically localize in the pineal or suprasellar region. The largest category of germ cell tumors is dysgerminoma. to describe clinicopathological features and immunohistochemical profile of dysgerminomas. We report three cases of central nervous system dysgerminomas. There were two young women and a man who were 6, 11 and 23-year-old. They presented with symptoms of insipidus diabetes (n=3) with association to visual field defects in the third case. Radiological findings showed a supra seller lesion in two cases. Double localization in the pineal and suprasellar regions was seen in the third case. Histologic examination and immunohistochemical study of surgical specimen were consistent with primary central nervous system dysgerminoma.

Primary central nervous system lymphoma can be histologically diagnosed after previous corticosteroid use: a pilot study to determine whether corticosteroids prevent the diagnosis of primary central nervous system lymphoma.

PubMed

Porter, Alyx B; Giannini, Caterina; Kaufmann, Timothy; Lucchinetti, Claudia F; Wu, Wenting; Decker, Paul A; Atkinson, John L D; O'Neill, Brian Patrick

2008-05-01

The objective is to determine whether corticosteroid administration before biopsy prevents histopathological diagnosis of primary central nervous system lymphoma (PCNSL). A retrospective review was performed of immunocompetent PCNSL patients from 1985 to 2005. A total of 109 patients was identified. Sixty-eight (63.6%) patients received corticosteroids before diagnosis. Thirteen patients (of 109; 12%) had undergone repeat brain biopsy to confirm PCNSL. These included 8 (of 68) patients who had received corticosteroids (12%), and 5 (of 39) who had not (13%) (p = 1.0). The majority of PCNSL patients who received corticosteroids before diagnosis did not experience significant radiographic change or require second biopsy for diagnosis.

Co-culture of oligodendrocytes and neurons can be used to assess drugs for axon regeneration in the central nervous system

PubMed Central

Gang, Lin; Yao, Yu-chen; Liu, Ying-fu; Li, Yi-peng; Yang, Kai; Lu, Lei; Cheng, Yuan-chi; Chen, Xu-yi; Tu, Yue

2015-01-01

We present a novel in vitro model in which to investigate the efficacy of experimental drugs for the promotion of axon regeneration in the central nervous system. We co-cultured rat hippocampal neurons and cerebral cortical oligodendrocytes, and tested the co-culture system using a Nogo-66 receptor antagonist peptide (NEP1–40), which promotes axonal growth. Primary cultured oligodendrocytes suppressed axonal growth in the rat hippocampus, but NEP1–40 stimulated axonal growth in the co-culture system. Our results confirm the validity of the neuron-oligodendrocyte co-culture system as an assay for the evaluation of drugs for axon regeneration in the central nervous system. PMID:26692858

[Pressure distribution measurements during use of wheelchairs].

PubMed

Meiners, T; Friedrich, G; Krüger, A; Böhm, V

2001-04-01

There is a growing number of mobility-impaired and wheelchair-dependent patients caused by diseases and injuries of the central nervous system. The risk is high for pressure sores to develop due to disturbances of the motor, sensory, and autonomic nervous system. Numerous seating systems for prophylaxis and treatment of decubitus ulcer are available. To identify risk parameters, the literature on animal experiments regarding pressure ulcers was reviewed. A study on the reproducibility of the analysis method with capacitive sensors tested in ten paraplegics with 470 measurements is presented. It shows the reliability of the procedure.

[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.

Neuropsychological Functioning in Survivors of Childhood Leukemia.

ERIC Educational Resources Information Center

Reeb, Roger N.; Regan, Judith M.

1998-01-01

Examined neuropsychological functioning of survivors of acute lymphoblastic leukemia who underwent central-nervous-system prophylactic treatment. Findings replicated past research in showing survivors perform poorly on visual-motor integration tasks and develop a Nonverbal Learning Disability. Findings offer recommendations for future research and…

Psychology in Action: Psychology in China

ERIC Educational Resources Information Center

Hsiao, Sigmund

1977-01-01

"Psychologists in the People's Republic of China are engaged in research concerning theory, Chinese language, child development, vision, audition, and areas of physiological psychology including acupuncture, pain, memory, and central nervous system functioning. The Institute of Psychology within the Chinese Academy of Sciences represents the…

KSC-98pc146

NASA Image and Video Library

1998-01-09

STS-90 Mission Specialist Dafydd "Dave" Rhys Williams, M.D., with the Canadian Space Agency, and back-up Payload Specialist Chiaki Mukai, M.D., Ph.D., with the National Space Development Agency of Japan, examine items to be used during the Crew Equipment Interface Test (CEIT) in Kennedy Space Center's (KSC's) Operations and Checkout Building, where the Neurolab payload is undergoing processing. The CEIT gives astronauts an opportunity to get a hands-on look at the payloads with which they will be working on-orbit. STS-90 is scheduled to launch aboard the Shuttle Columbia from KSC on April 2. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system

KSC-97PC1813

NASA Image and Video Library

1997-12-12

The Neurolab payload for STS-90, scheduled to launch aboard the Shuttle Columbia from Kennedy Space Center (KSC) on April 2, 1998, undergoes further processing in the Operations and Checkout Building at KSC. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90 will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-97PC1815

NASA Image and Video Library

1997-12-12

The Neurolab payload for STS-90, scheduled to launch aboard the Shuttle Columbia from Kennedy Space Center (KSC) on April 2, 1998, undergoes further processing in the Operations and Checkout Building at KSC. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90 will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-98pc290

NASA Image and Video Library

1998-02-12

The STS-90 Neurolab payload is lowered into position into the cargo bay of Space Shuttle Columbia today in Orbiter Processing Facility bay 3. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90, slated for launch in April, will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-97PC1812

NASA Image and Video Library

1997-12-12

The Neurolab payload for STS-90, scheduled to launch aboard the Shuttle Columbia from Kennedy Space Center (KSC) on April 2, 1998, undergoes further processing in the Operations and Checkout Building at KSC. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90 will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-98pc343

NASA Image and Video Library

1998-03-09

KENNEDY SPACE CENTER, FLA. -- The STS-90 Neurolab payload and four Getaway Specials (GAS) await payload bay door closure in the orbiter Columbia today in Orbiter Processing Facility bay 3. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90, slated for launch in April, will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-97PC1714

NASA Image and Video Library

1997-11-11

The Neurolab payload for STS-90, scheduled to launch aboard the Shuttle Columbia from Kennedy Space Center (KSC) on April 2, 1998, is moved to its workstand in the Operations and Checkout Building at KSC. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90 will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-98pc267

NASA Image and Video Library

1998-02-05

KENNEDY SPACE CENTER, FLA. -- A technician looks at the STS-90 Neurolab payload as it is moved from its test stand in KSC's Operations and Checkout Building. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90, slated for launch in April, will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-98pc291

NASA Image and Video Library

1998-02-12

The STS-90 Neurolab payload is lowered into position into the cargo bay of Space Shuttle Columbia today in Orbiter Processing Facility bay 3. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90, slated for launch in April, will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-97PC1814

NASA Image and Video Library

1997-12-12

The Neurolab payload for STS-90, scheduled to launch aboard the Shuttle Columbia from Kennedy Space Center (KSC) on April 2, 1998, undergoes further processing in the Operations and Checkout Building at KSC. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90 will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-98pc289

NASA Image and Video Library

1998-02-12

The STS-90 Neurolab payload is prepared to be positioned into the cargo bay of Space Shuttle Columbia today in Orbiter Processing Facility bay 3. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90, slated for launch in April, will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-98pc149

NASA Image and Video Library

1998-01-09

STS-90 crew members study manuals and drawings for the mission's Neurolab payload during the Crew Equipment Interface Test (CEIT) in Kennedy Space Center's (KSC's) Operations and Checkout Building, where the payload is undergoing processing. The CEIT gives astronauts an opportunity to get a hands-on look at the payloads with which they will be working on-orbit. STS-90 is scheduled to launch aboard the Shuttle Columbia from KSC on April 2. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system

KSC-98pc268

NASA Image and Video Library

1998-02-05

KENNEDY SPACE CENTER, FLA. -- Technicians gather around the STS-90 Neurolab payload during weight and center-of-gravity measurements in KSC's Operations and Checkout Building. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90, slated for launch in April, will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-97PC1713

NASA Image and Video Library

1997-11-11

The Neurolab payload for STS-90, scheduled to launch aboard the Shuttle Columbia from Kennedy Space Center (KSC) on April 2, 1998, is moved to its workstand in the Operations and Checkout Building at KSC. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90 will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-97PC1715

NASA Image and Video Library

1997-11-11

The Neurolab payload for STS-90, scheduled to launch aboard the Shuttle Columbia from Kennedy Space Center (KSC) on April 2, 1998, is moved to its workstand in the Operations and Checkout Building at KSC. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90 will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

Fluoxetine Opens Window to Improve Motor Recovery After Stroke

ClinicalTrials.gov

2018-05-01

Stroke; Cerebrovascular Accident; Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Pick disease

MedlinePlus

... Frontotemporal dementia; FTD; Arnold Pick disease; 3R tauopathy Images Central nervous system and peripheral nervous system References Bang J, Spina S, Miller BL. Frontotemporal dementia. Lancet . 2015;386( ...

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

PubMed

Dimitri, Paul; Rosen, Cliff

2017-05-01

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

Growth of adult spinal cord in knifefish: Development and parametrization of a distributed model.

PubMed

Ilieş, Iulian; Sipahi, Rifat; Zupanc, Günther K H

2018-01-21

The study of indeterminate-growing organisms such as teleost fish presents a unique opportunity for improving our understanding of central nervous tissue growth during adulthood. Integrating the existing experimental data associated with this process into a theoretical framework through mathematical or computational modeling provides further research avenues through sensitivity analysis and optimization. While this type of approach has been used extensively in investigations of tumor growth, wound healing, and bone regeneration, the development of nervous tissue has been rarely studied within a modeling framework. To address this gap, the present work introduces a distributed model of spinal cord growth in the knifefish Apteronotus leptorhynchus, an established teleostean model of adult growth in the central nervous system. The proposed model incorporates two mechanisms, cell proliferation by active stem/progenitor cells and cell drift due to population pressure, both of which are subject to global constraints. A coupled reaction-diffusion equation approach was adopted to represent the densities of actively-proliferating and non-proliferating cells along the longitudinal axis of the spinal cord. Computer simulations using this model yielded biologically-feasible growth trajectories. Subsequent comparisons with whole-organism growth curves allowed the estimation of previously-unknown parameters, such as relative growth rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Drug Development and Conservation of Biodiversity in West and Central Africa: Performance of Neurochemical and Radio Receptor Assays of Plant Extracts Drug Discovery for the Central Nervous System

DTIC Science & Technology

2004-09-01

7) Hui, D.; Sao-Xing, C. J. Nat. Prod. 1998, 61, 142-144. (8) Aldrich Libray of 13C and 1H FT NMR spectra 1992, 2, 326A. (9) Kadota, S .; Hui, D...Biodiversity in West and Central Africa: Performance of Neurochemical and Radio Receptor Assays of Plant Extracts Drug Discovery for the Central... s ) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation

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

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.

Altered development of the brain after focal herpesvirus infection of the central nervous system.

PubMed

Koontz, Thad; Bralic, Marina; Tomac, Jelena; Pernjak-Pugel, Ester; Bantug, Glen; Jonjic, Stipan; Britt, William J

2008-02-18

Human cytomegalovirus infection of the developing central nervous system (CNS) is a major cause of neurological damage in newborn infants and children. To investigate the pathogenesis of this human infection, we developed a mouse model of infection in the developing CNS. Intraperitoneal inoculation of newborn animals with murine cytomegalovirus resulted in virus replication in the liver followed by virus spread to the brain. Virus infection of the CNS was associated with the induction of inflammatory responses, including the induction of a large number of interferon-stimulated genes and histological evidence of focal encephalitis with recruitment of mononuclear cells to foci containing virus-infected cells. The morphogenesis of the cerebellum was delayed in infected animals. The defects in cerebellar development in infected animals were generalized and, although correlated temporally with virus replication and CNS inflammation, spatially unrelated to foci of virus-infected cells. Specific defects included decreased granular neuron proliferation and migration, expression of differentiation markers, and activation of neurotrophin receptors. These findings suggested that in the developing CNS, focal virus infection and induction of inflammatory responses in resident and infiltrating mononuclear cells resulted in delayed cerebellar morphogenesis.

Altered development of the brain after focal herpesvirus infection of the central nervous system

PubMed Central

Koontz, Thad; Bralic, Marina; Tomac, Jelena; Pernjak-Pugel, Ester; Bantug, Glen; Jonjic, Stipan; Britt, William J.

2008-01-01

Human cytomegalovirus infection of the developing central nervous system (CNS) is a major cause of neurological damage in newborn infants and children. To investigate the pathogenesis of this human infection, we developed a mouse model of infection in the developing CNS. Intraperitoneal inoculation of newborn animals with murine cytomegalovirus resulted in virus replication in the liver followed by virus spread to the brain. Virus infection of the CNS was associated with the induction of inflammatory responses, including the induction of a large number of interferon-stimulated genes and histological evidence of focal encephalitis with recruitment of mononuclear cells to foci containing virus-infected cells. The morphogenesis of the cerebellum was delayed in infected animals. The defects in cerebellar development in infected animals were generalized and, although correlated temporally with virus replication and CNS inflammation, spatially unrelated to foci of virus-infected cells. Specific defects included decreased granular neuron proliferation and migration, expression of differentiation markers, and activation of neurotrophin receptors. These findings suggested that in the developing CNS, focal virus infection and induction of inflammatory responses in resident and infiltrating mononuclear cells resulted in delayed cerebellar morphogenesis. PMID:18268036

AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)

ClinicalTrials.gov

2018-05-21

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Nervous System Diseases; Central Nervous System Diseases

Developmental expression of VGF mRNA in the prenatal and postnatal rat.

PubMed

Snyder, S E; Pintar, J E; Salton, S R

1998-04-27

VGF is a developmentally regulated, secretory peptide precursor that is expressed by neurons and neuroendocrine cells and that has its transcription and secretion induced rapidly by neurotrophins and by depolarization. To gain insight into the possible functions and regulation of VGF in vivo, we have characterized the distribution of VGF mRNA in the developing rat nervous system. VGF expression was first detectable at embryonic day 11.5 in the primordia of cranial, sympathetic, and dorsal root ganglia, and its distribution expanded throughout development to include significant expression throughout the brain, spinal cord, and retina of the adult rat. The earliest expression of VGF, therefore, appeared in the peripheral nervous system as developing neurons settled in their designated ganglia. In many regions of the brain, VGF mRNA levels were found to be highest during periods when axonal outgrowth and synaptogenesis predominate. Areas of the central nervous system that contain predominantly dividing cells never displayed any VGF mRNA expression, nor did the vast majority of nonneural tissues.

Interoceptive inference: From computational neuroscience to clinic.

PubMed

Owens, Andrew P; Allen, Micah; Ondobaka, Sasha; Friston, Karl J

2018-04-22

The central and autonomic nervous systems can be defined by their anatomical, functional and neurochemical characteristics, but neither functions in isolation. For example, fundamental components of autonomically mediated homeostatic processes are afferent interoceptive signals reporting the internal state of the body and efferent signals acting on interoceptive feedback assimilated by the brain. Recent predictive coding (interoceptive inference) models formulate interoception in terms of embodied predictive processes that support emotion and selfhood. We propose interoception may serve as a way to investigate holistic nervous system function and dysfunction in disorders of brain, body and behaviour. We appeal to predictive coding and (active) interoceptive inference, to describe the homeostatic functions of the central and autonomic nervous systems. We do so by (i) reviewing the active inference formulation of interoceptive and autonomic function, (ii) survey clinical applications of this formulation and (iii) describe how it offers an integrative approach to human physiology; particularly, interactions between the central and peripheral nervous systems in health and disease. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Nociceptive transmission and modulation via P2X receptors in central pain syndrome.

PubMed

Kuan, Yung-Hui; Shyu, Bai-Chuang

2016-05-26

Painful sensations are some of the most frequent complaints of patients who are admitted to local medical clinics. Persistent pain varies according to its causes, often resulting from local tissue damage or inflammation. Central somatosensory pathway lesions that are not adequately relieved can consequently cause central pain syndrome or central neuropathic pain. Research on the molecular mechanisms that underlie this pathogenesis is important for treating such pain. To date, evidence suggests the involvement of ion channels, including adenosine triphosphate (ATP)-gated cation channel P2X receptors, in central nervous system pain transmission and persistent modulation upon and following the occurrence of neuropathic pain. Several P2X receptor subtypes, including P2X2, P2X3, P2X4, and P2X7, have been shown to play diverse roles in the pathogenesis of central pain including the mediation of fast transmission in the peripheral nervous system and modulation of neuronal activity in the central nervous system. This review article highlights the role of the P2X family of ATP receptors in the pathogenesis of central neuropathic pain and pain transmission. We discuss basic research that may be translated to clinical application, suggesting that P2X receptors may be treatment targets for central pain syndrome.

Hierarchy of evidence referring to the central nervous system in a high-impact radiation oncology journal: a 10-year assessment. Descriptive critical appraisal study.

PubMed

Moraes, Fabio Ynoe; Bonifacio, Lorine Arias; Marta, Gustavo Nader; Hanna, Samir Abdallah; Atallah, Álvaro Nagib; Moraes, Vinícius Ynoe; Silva, João Luis Fernandes; Carvalho, Heloísa Andrade

2015-01-01

To the best of our knowledge, there has been no systematic assessment of the classification of scientific production within the scope of radiation oncology relating to central nervous system tumors. The aim of this study was to systematically assess the status of evidence relating to the central nervous system and to evaluate the geographic origins and major content of these published data. Descriptive critical appraisal study conducted at a private hospital in São Paulo, Brazil. We evaluated all of the central nervous system studies published in the journal Radiotherapy & Oncology between 2003 and 2012. The studies identified were classified according to their methodological design and level of evidence. Information regarding the geographical location of the study, the institutions and authors involved in the publication, main condition or disease investigated and time of publication was also obtained. We identified 3,004 studies published over the 10-year period. Of these, 125 (4.2%) were considered eligible, and 66% of them were case series. Systematic reviews and randomized clinical trials accounted for approximately 10% of all the published papers. We observed an increase in high-quality evidence and a decrease in low-quality published papers over this period (P = 0.036). The inter-rater reliability demonstrated significant agreement between observers in terms of the level of evidence. Increases in high-level evidence and in the total number of central nervous system papers were clearly demonstrated, although the overall number of such studies remained relatively small.

Cancer Seeding Risk from an Epidural Blood Patch in Patients with Leukemia or Lymphoma.

PubMed

Demaree, Christopher J; Soliz, Jose M; Gebhardt, Rodolfo

2017-04-01

Lumber punctures are a common procedure in patients with cancer. However, a potential complication of a lumbar puncture is a postdural puncture headache. The risk of neoplastic seeding to the central nervous system has led to concern over performing epidural blood patches (EBPs) for the treatment of postdural puncture headaches in patients with cancer. The goal of this retrospective study was to evaluate cancer seeding in the central nervous system in patients diagnosed with leukemia or lymphoma. Institutional electronic records were queried over a 13-year period from 2000 to 2013 for patients with leukemia and/or lymphoma and who received at least one EBP. Demographic and procedural data, cancer treatments, and mortality were all examined. Patient records were reviewed for evidence of new-onset neoplastic central nervous system seeding after an epidural blood patch. A total of 80 patients were identified for review. Eighteen patients had a diagnosis of leukemia, and 62 had lymphoma. Following an EBP, none of the patients experienced new cancer or cancer seeding in the central nervous system following an epidural blood patch at a median follow-up of 3.74 years. Though the risks of EBP in the cancer patient population have been hypothesized, no previous studies have assessed the risk of seeding cancer to the central nervous system. Based on our results, an epidural blood patch bears low risk of cancer seeding when used to treat postdural puncture headache that is unresponsive to conservative treatments. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

A Multi-Axial Scheme for Assessment and Intervention.

ERIC Educational Resources Information Center

Kirkland, John; Morgan, Griffith

1984-01-01

Describes a scheme consisting of nine elements or "themes" ordered in terms of their more probable links developed from clinical work with crying infants. Theme categories are genetic/hereditary, psychiatric disorder, central nervous system, medical health (chronic), medical health (acute), nutrition/allergy, form, psychosocial…

Hemorrhage and Hemorrhagic Shock in Swine: A Review

DTIC Science & Technology

1989-11-01

17 Temperature Regulation ....................... 18 Blood Gas and Acid- Base Status ....................... 18 Electrolyte...22 Renal Function .................................. 23 Hepatic Function ................................ 24 Central Nervous System Function...MODELS Most porcine hemorrhage models are based on concepts and procedures previously developed in other species, especially the dog. As a consequence

[Polymethyleneamine alkaloids of animal origin: II. Polyamine neurotoxins].

PubMed

Rogoza, L N; Salakhutdinov, N F; Tolstikov, G A

2006-01-01

Information on the structure and biological activity of animal alkaloids, polymethyleneamine components of spider and wasp venoms, is considered and systematized. These natural compounds are used for the development and modification of medicines for treating the functional disturbances in the central nervous system of humans.

Electrical Interactions between Mammalian Cortical Neutons

DTIC Science & Technology

1990-05-24

direct responses to acetyl- the entire mammalian central nervous sys- choline and nicotine. Deadvyler and col- teni (19, 32).’The development of...BERT J. (1985) Neurotoxic lesion ; of the athmic neurons recorded near the par-anterior hypothalamus disrupt the JoSentricular in vitro. Brain Res. Bull

Learning Disability: An Educational Adventure. The 1967 Kappa Delta Pi Lecture.

ERIC Educational Resources Information Center

Kephart, Newell C.

Educational implications and symptoms are described for learning disorders, the disruption in the processing of information within the central nervous system caused by brain damage, emotional disturbance, or inadequate presentation of learning experiences. Developmental sequences, developmental progression, and restoration of development are…

Neuronopathic lysosomal storage disorders: Approaches to treat the central nervous system.

PubMed

Scarpa, Maurizio; Bellettato, Cinzia Maria; Lampe, Christina; Begley, David J

2015-03-01

Pharmacological research has always focused on developing new therapeutic strategies capable of modifying a disease's natural history and improving patients' quality of life. Despite recent advances within the fields of medicine and biology, some diseases still represent a major challenge for successful therapy. Neuronopathic lysosomal storage disorders, in particular, have high rates of morbidity and mortality and a devastating socio-economic effect. Many of the available therapies, such as enzyme replacement therapy, can reverse the natural history of the disease in peripheral organs but, unfortunately, are still unable to reach the central nervous system effectively because they cannot cross the blood-brain barrier that surrounds and protects the brain. Moreover, many lysosomal storage disorders are characterized by a number of blood-brain barrier dysfunctions, which may further contribute to disease neuropathology and accelerate neuronal cell death. These issues, and their context in the development of new therapeutic strategies, will be discussed in detail in this chapter. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cell fate control in the developing central nervous system

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

Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie, E-mail: Fanie.Barnabe-Heider@ki.se

The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatmentsmore » of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals.« less

The “window of susceptibility” for inflammation in the immature central nervous system is characterized by a leaky blood brain barrier and the local expression of inflammatory chemokines

PubMed Central

Schoderboeck, Lucia; Adzemovic, Milena; Nicolussi, Eva-Maria; Crupinschi, Claudia; Hochmeister, Sonja; Fischer, Marie-Therese; Lassmann, Hans; Bradl, Monika

2013-01-01

Early in postnatal development, the immature central nervous system (CNS) is more susceptible to inflammation than its adult counterpart. We show here that this “window of susceptibility” is characterized by the presence of leaky vessels in the CNS, and by a global chemokine expression profile which is clearly distinct from the one observed in the adult CNS and has three important characteristics. First, it contains chemokines with known roles in the differentiation and maturation of glia and neurons. Secondly, these chemokines have been described before in inflammatory lesions of the CNS, where they are important for the recruitment of monocytes and T cells. And last, the chemokine profile is shaped by pathological changes like oligodendrocyte stress and attempts of myelin repair. Changes in the chemokine expression profile along with a leaky blood brain barrier pave the ground for an accelerated development of CNS inflammation. PMID:19520164

Synaptogenesis in the CNS: An Odyssey from Wiring Together to Firing Together

PubMed Central

Munno, David W; Syed, Naweed I

2003-01-01

To acquire a better comprehension of nervous system function, it is imperative to understand how synapses are assembled during development and subsequently altered throughout life. Despite recent advances in the fields of neurodevelopment and synaptic plasticity, relatively little is known about the mechanisms that guide synapse formation in the central nervous system (CNS). Although many structural components of the synaptic machinery are pre-assembled prior to the arrival of growth cones at the site of their potential targets, innumerable changes, central to the proper wiring of the brain, must subsequently take place through contact-mediated cell-cell communications. Identification of such signalling molecules and a characterization of various events underlying synaptogenesis are pivotal to our understanding of how a brain cell completes its odyssey from ‘wiring together to firing together’. Here we attempt to provide a comprehensive overview that pertains directly to the cellular and molecular mechanisms of selection, formation and refinement of synapses during the development of the CNS in both vertebrates and invertebrates. PMID:12897180

CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion of the Central Nervous System

PubMed Central

Swamydas, Muthulekha; Rodriguez, Carlos A.; Lim, Jean K.; Mendez, Laura M.; Fink, Danielle L.; Hsu, Amy P.; Zhai, Bing; Karauzum, Hatice; Mikelis, Constantinos M.; Rose, Stacey R.; Ferre, Elise M. N.; Yockey, Lynne; Lemberg, Kimberly; Kuehn, Hye Sun; Rosenzweig, Sergio D.; Lin, Xin; Chittiboina, Prashant; Datta, Sandip K.; Belhorn, Thomas H.; Weimer, Eric T.; Hernandez, Michelle L.; Hohl, Tobias M.; Kuhns, Douglas B.; Lionakis, Michail S.

2015-01-01

Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9 -/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9 -/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans. PMID:26679537

The ALK receptor in sympathetic neuron development and neuroblastoma.

PubMed

Janoueix-Lerosey, Isabelle; Lopez-Delisle, Lucille; Delattre, Olivier; Rohrer, Hermann

2018-05-01

The ALK gene encodes a tyrosine kinase receptor characterized by an expression pattern mainly restricted to the developing central and peripheral nervous systems. In 2008, the discovery of ALK activating mutations in neuroblastoma, a tumor of the sympathetic nervous system, represented a breakthrough in the understanding of the pathogenesis of this pediatric cancer and established mutated ALK as a tractable therapeutic target for precision medicine. Subsequent studies addressed the identity of ALK ligands, as well as its physiological function in the sympathoadrenal lineage, its role in neuroblastoma development and the signaling pathways triggered by mutated ALK. This review focuses on these different aspects of the ALK biology and summarizes the various therapeutic strategies relying on ALK inhibition in neuroblastoma, either as monotherapies or combinatory treatments.

Microgliomatosis in a Schnauzer dog.

PubMed

Willard, M D; Delahunta, A

1982-04-01

Microgliomatosis was found in the central nervous system of a 7-year-old male Standard Schnauzer. History, neurologic examination, laboratory tests and electrodiagnostics could not localize the disease process in the central nervous system. The animal was not treated, continued to deteriorate, and was euthanatized approximately 8 weeks after clinical signs were first detected. Diagnosis was made upon histologic examination of the brain.

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...

Electromagnetic Fields for the Regulation of Neural Stem Cells

PubMed Central

Cui, Mengchu; Ge, Hongfei; Zhao, Hengli; Zou, Yongjie

2017-01-01

Localized magnetic fields (MFs) could easily penetrate the scalp, skull, and meninges, thus inducing an electrical current in both the central and peripheral nervous systems, which is primarily used in transcranial magnetic stimulation (TMS) for inducing specific effects on different regions or cells that play roles in various brain activities. Studies of repetitive transcranial magnetic stimulation (rTMS) have led to novel attractive therapeutic approaches. Neural stem cells (NSCs) in adult human brain are able to self-renew and possess multidifferential ability to maintain homeostasis and repair damage after acute central nervous system. In the present review, we summarized the electrical activity of NSCs and the fundamental mechanism of electromagnetic fields and their effects on regulating NSC proliferation, differentiation, migration, and maturation. Although it was authorized for the rTMS use in resistant depression patients by US FDA, there are still unveiling mechanism and limitations for rTMS in clinical applications of acute central nervous system injury, especially on NSC regulation as a rehabilitation strategy. More in-depth studies should be performed to provide detailed parameters and mechanisms of rTMS in further studies, making it a powerful tool to treat people who are surviving with acute central nervous system injuries. PMID:28932245

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

PubMed

Bartzatt, Ronald

2013-06-01

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

[Neurological disorders and the blood-brain barrier. Strategies and limitations for drug delivery to the brain].

PubMed

Domínguez, Alazne; Álvarez, Antonia; Suárez-Merino, Blanca; Goñi-de-Cerio, Felipe

2014-03-01

The incidence in the central nervous system diseases has increased with a growing elderly population. Unfortunately, conventional treatments used to treat the mentioned diseases are frequently ineffective due to the presence of the blood brain barrier. To illustrate the blood-brain barrier properties that limit drug transport into the brain and the main strategies employed to treat neurologic disorders. The blood-brain barrier is mainly composed of a specialized microvascular endothelium and of glial cells. It constitutes a valuable tool to separate the central nervous system from the rest of the body. Nevertheless, it also represents an obstacle to the delivery of therapeutic drugs to the brain. To be effective, drugs must reach their target in the brain. On one hand, therapeutic agents could be designed to be able to cross the blood brain barrier. On the other hand, drug delivery systems could be employed to facilitate the therapeutic agents' entry into the central nervous system. In vivo models of neurological diseases, in addition to in vitro models of the blood brain barrier, have been widely employed for the evaluation of drugs utilized to treat central nervous system diseases.

Graded Positive Feedback in Elasmobranch Ampullae of Lorenzini

NASA Astrophysics Data System (ADS)

Kalmijn, Ad. J.

2003-05-01

The acute electrical sensitivity of marine sharks and rays is the greatest known in the Animal Kingdom. I investigate the possibility that the underlying biophysical principles are the very same as those encountered in the central nervous system of animal and man. The elasmobranch ampullae of Lorenzini detect the weak electric fields originating from the oceanic environment, whereas the nerve cells of the brain detect the electric fields arising, well, from the central nervous system. In responding to electrical signals, the cell membranes of excitable cells behave in different regions of the cell as negative or positive conductors. The negative and positive conductances in series, loaded by the cell's electrolytic environment, constitute a positive feedback circuit. The result may be of an all-or-none nature, as in peripheral nerve conduction, or of a graded nature, as in central processing. In this respect, the operation of the elasmobranch ampullae of Lorenzini is more akin to the graded, integrative processes of higher brain centers than to the conduction of nerve action potentials. Hence, the positive-feedback ampullary circuit promises to help elucidate the functioning of the central nervous system as profoundly as the squid giant axon has served to reveal the process of nervous conduction.

Comparison of intermediate-dose methotrexate with cranial irradiation for the post-induction treatment of acute lymphocytic leukemia in children

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

Freeman, A.I.; Weinberg, V.; Brecher, M.L.

1983-03-03

The authors compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other sanctuary areas. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation. Among patients with standard risk, hematologic relapses occurred in 9 of 117 given methotrexate and 24 ofmore » 120 given irradiation. The rate of central-nervous-system relapse was higher in the methotrexate group (23 of 117) than in the irradiation group. Among patients with increased risk, radiation offered greater protection to the central nervous system than methotrexate; there was no difference in the rate of hematologic relapse. Methotrexate offered better protection against systemic relapse in standard-risk patients and better protection against testicular relapse overall, but it offered less protection against relapses in the central nervous system than cranial irradiation.« less

Evidence of Early Childhood Defects Due to Prenatal Over-Exposure to Vitamin A: A Case Study

ERIC Educational Resources Information Center

Naude, H.; Marx, J.; Pretorius, E.; Hislop-Esterhuyzen, N.

2007-01-01

One of the important nutrients during pregnancy is vitamin A or related compounds called retinoids. Although it is well-known that vitamin A deficiency may be detrimental to foetal development, overdosage of retinoids might cause developmental defects, particularly affecting the central nervous system development of the foetus, causing hindbrain…

Stab wound injury of the zebrafish adult telencephalon: a method to investigate vertebrate brain neurogenesis and regeneration.

PubMed

Schmidt, Rebecca; Beil, Tanja; Strähle, Uwe; Rastegar, Sepand

2014-08-04

Adult zebrafish have an amazing capacity to regenerate their central nervous system after injury. To investigate the cellular response and the molecular mechanisms involved in zebrafish adult central nervous system (CNS) regeneration and repair, we developed a zebrafish model of adult telencephalic injury. In this approach, we manually generate an injury by pushing an insulin syringe needle into the zebrafish adult telencephalon. At different post injury days, fish are sacrificed, their brains are dissected out and stained by immunohistochemistry and/or in situ hybridization (ISH) with appropriate markers to observe cell proliferation, gliogenesis, and neurogenesis. The contralateral unlesioned hemisphere serves as an internal control. This method combined for example with RNA deep sequencing can help to screen for new genes with a role in zebrafish adult telencephalon neurogenesis, regeneration, and repair.

Effects of low-dose prenatal irradiation on the central nervous system

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

Not Available

1992-04-01

Scientists are in general agreement about the effects of prenatal irradiation, including those affecting the central nervous system (CNS). Differing concepts and research approaches have resulted in some uncertainties about some quantitative relationships, underlying interpretations, and conclusions. Examples of uncertainties include the existence of a threshold, the quantitative relationships between prenatal radiation doses and resulting physical and functional lesions, and processes by which lesions originate and develop. A workshop was convened in which scientists with varying backgrounds and viewpoints discussed these relationships and explored ways in which various disciplines could coordinate concepts and methodologies to suggest research directions for resolvingmore » uncertainties. This Workshop Report summarizes, in an extended fashion, salient features of the presentations on the current status of our knowledge about the radiobiology and neuroscience of prenatal irradiation and the relationships between them.« less

Prophylactic central nervous system therapy in childhood acute lymphatic leukemia. Effect of poor-risk patients on the results.

PubMed

Virag, I; Kende, G; Agahai, E; Ramot, B

1976-11-01

The results of treatment in a group of 50 children with acute lymphatic leukemia are summarized. A comparison was made between those who received prophylactic central nervous systen (CNS) therapy on attaining complete remission and those who did not. Although none of the prophylactically treated children developed CNS leukemia, the expected prolongation of median complete remission time was not achieved. It was found that there was a high percentage of poor-risk patients in the CNS-treated group, and these patients relapsed early in the course of the disease. The prevention of CNS leukemia, a late complication of the disease, did not change the natural course of the disease in poor-risk patients. A need exists for new treatment protocols aimed at better control of the disease in these poor-risk cases.

Dendrimer advances for the central nervous system delivery of therapeutics.

PubMed

Xu, Leyuan; Zhang, Hao; Wu, Yue

2014-01-15

The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included.

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.

Leptin sustains spontaneous remyelination in the adult central nervous system

PubMed Central

Matoba, Ken; Muramatsu, Rieko; Yamashita, Toshihide

2017-01-01

Demyelination is a common feature of many central nervous system (CNS) diseases and is associated with neurological impairment. Demyelinated axons are spontaneously remyelinated depending on oligodendrocyte development, which mainly involves molecules expressed in the CNS environment. In this study, we found that leptin, a peripheral hormone secreted from adipocytes, promoted the proliferation of oligodendrocyte precursor cells (OPCs). Leptin increased the OPC proliferation via in vitro phosphorylation of extracellular signal regulated kinase (ERK); whereas leptin neutralization inhibited OPC proliferation and remyelination in a mouse model of toxin-induced demyelination. The OPC-specific leptin receptor long isoform (LepRb) deletion in mice inhibited both OPC proliferation and remyelination in the response to demyelination. Intrathecal leptin administration increased OPC proliferation. These results demonstrated a novel molecular mechanism by which leptin sustained OPC proliferation and remyelination in a pathological CNS. PMID:28091609

In Vivo Imaging of Histone Deacetylases (HDACs) in the Central Nervous System and Major Peripheral Organs

PubMed Central

2015-01-01

Epigenetic enzymes are now targeted to treat the underlying gene expression dysregulation that contribute to disease pathogenesis. Histone deacetylases (HDACs) have shown broad potential in treatments against cancer and emerging data supports their targeting in the context of cardiovascular disease and central nervous system dysfunction. Development of a molecular agent for non-invasive imaging to elucidate the distribution and functional roles of HDACs in humans will accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and validation of an HDAC imaging agent, [11C]6. Our imaging results demonstrate that this probe has high specificity, good selectivity, and appropriate kinetics and distribution for imaging HDACs in the brain, heart, kidney, pancreas, and spleen. Our findings support the translational potential for [11C]6 for human epigenetic imaging. PMID:25203558

Laboratory models for central nervous system tumor stem cell research.

PubMed

Khan, Imad Saeed; Ehtesham, Moneeb

2015-01-01

Central nervous system (CNS) tumors are complex organ systems comprising of a neoplastic component with associated vasculature, inflammatory cells, and reactive cellular and extracellular components. Research has identified a subset of cells in CNS tumors that portray defining properties of neural stem cells, namely, that of self-renewal and multi-potency. Growing evidence suggests that these tumor stem cells (TSC) play an important role in the maintenance and growth of the tumor. Furthermore, these cells have also been shown to be refractory to conventional therapy and may be crucial for tumor recurrence and metastasis. Current investigations are focusing on isolating these TSC from CNS tumors to investigate their unique biological processes. This understanding will help identify and develop more effective and comprehensive treatment strategies. This chapter provides an overview of some of the most commonly used laboratory models for CNSTSC research.

The logistics of myelin biogenesis in the central nervous system.

PubMed

Snaidero, Nicolas; Simons, Mikael

2017-07-01

Rapid nerve conduction depends on myelin, but not all axons in the central nervous system (CNS) are myelinated to the same extent. Here, we review our current understanding of the biology of myelin biogenesis in the CNS. We focus on how the different steps of myelination are interconnected and how distinct patterns of myelin are generated. Possibly, a "basal" mode of myelination is laying the groundwork in areas devoted to basic homeostasis early in development, whereas a "targeted" mode generates myelin in regions controlling more complex tasks throughout adulthood. Such mechanisms may explain why myelination progresses in some areas according to a typical chronological and topographic sequence, while in other regions it is regulated by environmental stimuli contributing to interindividual variability of myelin structure. GLIA 2017;65:1021-1031. © 2017 Wiley Periodicals, Inc.

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

PubMed Central

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

2016-01-01

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

Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

PubMed Central

2013-01-01

The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included. PMID:24274162

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

PubMed Central

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

2017-01-01

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

Effects of low-dose prenatal irradiation on the central nervous system

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

Not Available

Scientists are in general agreement about the effects of prenatal irradiation, including those affecting the central nervous system (CNS). Differing concepts and research approaches have resulted in some uncertainties about some quantitative relationships, underlying interpretations, and conclusions. Examples of uncertainties include the existence of a threshold, the quantitative relationships between prenatal radiation doses and resulting physical and functional lesions, and processes by which lesions originate and develop. A workshop was convened in which scientists with varying backgrounds and viewpoints discussed these relationships and explored ways in which various disciplines could coordinate concepts and methodologies to suggest research directions for resolvingmore » uncertainties. This Workshop Report summarizes, in an extended fashion, salient features of the presentations on the current status of our knowledge about the radiobiology and neuroscience of prenatal irradiation and the relationships between them.« less

Potential of glyburide to reduce intracerebral edema in brain metastases.

PubMed

Boggs, Drexell Hunter; Simard, J Marc; Steven, Andrew; Mehta, Minesh P

2014-04-01

Metastatic disease to the brain results in significant morbidity because of edema in the central nervous system. Current anti-edema therapies are either expensive or result in unwanted long-term side effects. Sulfonylurea receptor 1 (Sur1) is a transmembrane protein that, when activated in the central nervous system, allows for unregulated sodium influx into cells, a process that has been linked to cytotoxic edema formation in ischemic stroke, subarachnoid hemorrhage, spinal cord injury, traumatic brain injury, and, most recently, brain metastases. In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema.

75 FR 10867 - Determinations Concerning Illnesses Discussed in the Institute of Medicine Report on Gulf War and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-09

... cancer; nervous system disease; reproductive or developmental dysfunction; non-malignant respiratory... nervous system cancers, stomach cancer, prostatic cancer and testicular cancer. The non-malignant diseases... and bladder cancer exists. G. Brain and Other Central Nervous System Cancers Of the 20 published...

SOX2 expression levels distinguish between neural progenitor populations of the developing dorsal telencephalon.

PubMed

Hutton, Scott R; Pevny, Larysa H

2011-04-01

The HMG-Box transcription factor SOX2 is expressed in neural progenitor populations throughout the developing and adult central nervous system and is necessary to maintain their progenitor identity. However, it is unclear whether SOX2 levels are uniformly expressed across all neural progenitor populations. In the developing dorsal telencephalon, two distinct populations of neural progenitors, radial glia and intermediate progenitor cells, are responsible for generating a majority of excitatory neurons found in the adult neocortex. Here we demonstrate, using both cellular and molecular analyses, that SOX2 is differentially expressed between radial glial and intermediate progenitor populations. Moreover, utilizing a SOX2(EGFP) mouse line, we show that this differential expression can be used to prospectively isolate distinct, viable populations of radial glia and intermediate cells for in vitro analysis. Given the limited repertoire of cell-surface markers currently available for neural progenitor cells, this provides an invaluable tool for prospectively identifying and isolating distinct classes of neural progenitor cells from the central nervous system. Copyright © 2011 Elsevier Inc. All rights reserved.

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

PubMed

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

2011-07-01

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

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

PubMed Central

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

2011-01-01

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

The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision.

PubMed

Yu, R T; Chiang, M Y; Tanabe, T; Kobayashi, M; Yasuda, K; Evans, R M; Umesono, K

2000-03-14

Although the development of the vertebrate eye is well described, the number of transcription factors known to be key to this process is still limited. The localized expression of the orphan nuclear receptor Tlx in the optic cup and discrete parts of the central nervous system suggested the possible role of Tlx in the formation or function of these structures. Analyses of Tlx targeted mice revealed that, in addition to the central nervous system cortical defects, lack of Tlx function results in progressive retinal and optic nerve degeneration with associated blindness. An extensive screen of Tlx-positive and Tlx-negative P19 neural precursors identified Pax2 as a candidate target gene. This identification is significant, because Pax2 is known to be involved in retinal development in both the human and the mouse eye. We find that Pax2 is a direct target and that the Tlx binding site in its promoter is conserved between mouse and human. These studies show that Tlx is a key component of retinal development and vision and an upstream regulator of the Pax2 signaling cascade.

The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision

PubMed Central

Yu, Ruth T.; Chiang, Ming-Yi; Tanabe, Teruyo; Kobayashi, Mime; Yasuda, Kunio; Evans, Ronald M.; Umesono, Kazuhiko

2000-01-01

Although the development of the vertebrate eye is well described, the number of transcription factors known to be key to this process is still limited. The localized expression of the orphan nuclear receptor Tlx in the optic cup and discrete parts of the central nervous system suggested the possible role of Tlx in the formation or function of these structures. Analyses of Tlx targeted mice revealed that, in addition to the central nervous system cortical defects, lack of Tlx function results in progressive retinal and optic nerve degeneration with associated blindness. An extensive screen of Tlx-positive and Tlx-negative P19 neural precursors identified Pax2 as a candidate target gene. This identification is significant, because Pax2 is known to be involved in retinal development in both the human and the mouse eye. We find that Pax2 is a direct target and that the Tlx binding site in its promoter is conserved between mouse and human. These studies show that Tlx is a key component of retinal development and vision and an upstream regulator of the Pax2 signaling cascade. PMID:10706625

Interfacing with the nervous system: a review of current bioelectric technologies.

PubMed

Sahyouni, Ronald; Mahmoodi, Amin; Chen, Jefferson W; Chang, David T; Moshtaghi, Omid; Djalilian, Hamid R; Lin, Harrison W

2017-10-23

The aim of this study is to discuss the state of the art with regard to established or promising bioelectric therapies meant to alter or control neurologic function. We present recent reports on bioelectric technologies that interface with the nervous system at three potential sites-(1) the end organ, (2) the peripheral nervous system, and (3) the central nervous system-while exploring practical and clinical considerations. A literature search was executed on PubMed, IEEE, and Web of Science databases. A review of the current literature was conducted to examine functional and histomorphological effects of neuroprosthetic interfaces with a focus on end-organ, peripheral, and central nervous system interfaces. Innovations in bioelectric technologies are providing increasing selectivity in stimulating distinct nerve fiber populations in order to activate discrete muscles. Significant advances in electrode array design focus on increasing selectivity, stability, and functionality of implantable neuroprosthetics. The application of neuroprosthetics to paretic nerves or even directly stimulating or recording from the central nervous system holds great potential in advancing the field of nerve and tissue bioelectric engineering and contributing to clinical care. Although current physiotherapeutic and surgical treatments seek to restore function, structure, or comfort, they bear significant limitations in enabling cosmetic or functional recovery. Instead, the introduction of bioelectric technology may play a role in the restoration of function in patients with neurologic deficits.

[Electromagnetic radiation of non-thermal intensity and short exposition as a sub-threshold irritant for the central nervous system].

PubMed

Luk'ianova, S N

2013-01-01

This work represents generalization and the analysis of the long-term own materials characterizing reaction of the brain on electromagnetic radiation of low intensity (energy flow density in the continuous regime or in the impulse approximately 500 microW/sm2) and a short exposition (approximately 30 min). A set of the experimental results received on separate neurons, formations and brain as a whole give an idea about the reaction of the central nervous system to the studied influence. Comparison of these data with the corresponding responses to the known incentives (light, sound, electric current) testifies to the electromagnetic radiation of low energy flow density and a short exposition as a sub-threshold irritant for the central nervous system.

Applications of fluorescence spectroscopy to problems of food safety: detection of fecal contamination and of the presence of central nervous system tissue and diagnosis of neurological disease

NASA Astrophysics Data System (ADS)

Adhikary, Ramkrishna; Bose, Sayantan; Casey, Thomas A.; Gapsch, Al; Rasmussen, Mark A.; Petrich, Jacob W.

2010-02-01

Applications of fluorescence spectroscopy that enable the real-time or rapid detection of fecal contamination on beef carcasses and the presence of central nervous system tissue in meat products are discussed. The former is achieved by employing spectroscopic signatures of chlorophyll metabolites; the latter, by exploiting the characteristic structure and intensity of lipofuscin in central nervous system tissue. The success of these techniques has led us to investigate the possibility of diagnosing scrapie in sheep by obtaining fluorescence spectra of the retina. Crucial to this diagnosis is the ability to obtain baseline correlations of lipofuscin fluorescence with age. A murine model was employed as a proof of principle of this correlation.

Protective Actions of 17β-Estradiol and Progesterone on Oxidative Neuronal Injury Induced by Organometallic Compounds

PubMed Central

Ishihara, Yasuhiro; Takemoto, Takuya; Yamazaki, Takeshi

2015-01-01

Steroid hormones synthesized in and secreted from peripheral endocrine glands pass through the blood-brain barrier and play a role in the central nervous system. In addition, the brain possesses an inherent endocrine system and synthesizes steroid hormones known as neurosteroids. Increasing evidence shows that neuroactive steroids protect the central nervous system from various harmful stimuli. Reports show that the neuroprotective actions of steroid hormones attenuate oxidative stress. In this review, we summarize the antioxidative effects of neuroactive steroids, especially 17β-estradiol and progesterone, on neuronal injury in the central nervous system under various pathological conditions, and then describe our recent findings concerning the neuroprotective actions of 17β-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds, tributyltin, and methylmercury. PMID:25815107

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.

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

Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson's Disease

ClinicalTrials.gov

2018-02-27

Idiopathic Parkinson's Disease; Parkinson's Disease; Basal Ganglia Disease; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Nervous System Diseases; Neurodegenerative Diseases; Parkinsonian Disorders

The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia

PubMed Central

2011-01-01

Pain is a key component of most rheumatologic diseases. In fibromyalgia, the importance of central nervous system pain mechanisms (for example, loss of descending analgesic activity and central sensitization) is well documented. A few studies have also noted alterations in central pain processing in osteoarthritis, and some data, including the observation of widespread pain sensitivity, suggest that central pain-processing defects may alter the pain response in rheumatoid arthritis patients. When central pain is identified, different classes of analgesics (for example, serotonin-norepinephrine reuptake inhibitors, α2δ ligands) may be more effective than drugs that treat peripheral or nociceptive pain (for example, nonsteroidal anti-inflammatory drugs and opioids). PMID:21542893

Adult Onset-hypothyroidism has Minimal Effects on Synaptic Transmission in the Hippocampus of Rats Independent of Hypothermia

EPA Science Inventory

Introduction: Thyroid hormones (TH) influence central nervous system (CNS) function during development and in adulthood. The hippocampus, a brain area critical for learning and memory is sensitive to TH insufficiency. Synaptic transmission in the hippocampus is impaired following...

Adult onset-hypothyroidism increases response latency and long-term potentiation (LTP) in rat hippocampus

EPA Science Inventory

Thyroid hormones (TH) influence central nervous system (CNS) function during both development and in adulthood. The hippocampus is critical for some types of learning and memory and is particularly sensitive to thyroid hormone deficiency. Hypothyroidism in adulthood has been ass...

Assessment of Gestational Age and Neuromaturation

ERIC Educational Resources Information Center

Allen, Marilee C.

2005-01-01

Neuromaturation is the functional development of the central nervous system (CNS). It is by its very nature a dynamic process, a continuous interaction between the genome and first the intrauterine environment, then the extrauterine environment. Understanding neuromaturation and being able to measure it is fundamental to infant neurodevelopmental…

Pathogenesis and Transmission of Feral Swine Pseudorabies Virus Isolates in Domestic Pigs

USDA-ARS?s Scientific Manuscript database

Pseudorabies is one of the oldest described swine diseases recognized as reproductive failure, and respiratory and central nervous system disease. It is caused by pseudorabies virus (PRV). The development of vaccines and serologic tests that allow the differentiation of vaccinated pigs from naturall...

Acute Neuroactive Drug Exposures alter Locomotor Activity in Larval Zebrafish

EPA Science Inventory

As part of the development of a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae by assessing the acute effects of prototypic drugs that act on the central nervous system. Initially,...

Pediatric HIV Infection: A Neuropsychological and Educational Challenge.

ERIC Educational Resources Information Center

Armstrong, F. Daniel; And Others

1993-01-01

This article reviews the effects of human immunodeficiency virus (HIV) on the central nervous system and the educational implications of increasing numbers of students with perinatal HIV infection and pediatric acquired immunodeficiency syndrome (AIDS). Studies on the relationship between HIV and child development are urged. (Author/DB)

Development of micro-electrode array based tests for neurotoxicity: assessment of interlaboratory reproducibility with neuroactive chemicals

EPA Science Inventory

Neuronal assemblies within the Central Nervous System (CNS) produce spontaneous or stimulus-evoked electrophysiological activity that can be monitored and quantified in terms of action potential patterns. Such patterns provide a sensitive endpoint to detect effects of chemicals, ...

Prader-Willi Disease: A Case Study.

ERIC Educational Resources Information Center

Forbus, William R., III

A case study focuses on the characteristics and physical management of a 15-year-old with Prader-Willi Syndrome, a birth defect associated with hypotonia, insatiable appetite, hypogonadism, central nervous system dysfunction, and abnormal growth and development . A literature review addresses studies dealing with behavior modification of obesity…

[Neural control of somatic muscle function in the earthworm, Allobophora longa, and in the leech, Hirudo medicinalis].

PubMed

David, O F

1978-01-01

Studies have been made on the electrical activity of the segmentary nerves and connectives of the abdominal nervous chain in the earthworm and leech. It was shown that the electrical activity of the isolated piece of the abdominal chain of the leech is manifested of periodic outbursts of impulsation. Presumably this central periodicity accounts for the discharge-like pattern of muscle rhythmic activity which was revealed in our earlier investigations. The electrical activity in the central nervous system of the earthworm depends on afferent influences which pass to the ganglia from the peripheral sensory nervous cells. Stimulation of the abdominal nervous chain did not result in extra discharges of muscle activity, but only affected some of the parameters of the latter.

The Secret Lives of Neurotrophin Receptors | Center for Cancer Research

Cancer.gov

Neurotrophins are a family of growth factors that are critical to the proper development and functioning of the nervous system. Neurotrophins activate a family of tyrosine receptor kinases (Trk), which typically initiate signaling cascades through phosphorylation. This axis is important for central nervous system (CNS) drug development efforts, ranging from pain management to neurodegeneration. However, neurotrophin-activated pathways are important for a variety of cancers and their metastatic properties. Indeed, TrkA, the prototype of the neurotrophin receptor family, was first identified at NCI as part of a fusion oncogene. Moreover, Trks are widely expressed in many different organs where their misactivation has been associated with tumor formation. Trks are also present as truncated receptor isoforms, lacking kinase activity, and these forms are particularly prominent in adult tissues. Little is known about the role of neurotrophins and Trk receptors outside the nervous system. Lino Tessarollo, Ph.D., Director of CCR’s Mouse Cancer Genetics Program, uses his expertise in developing genetically modified mouse models to dissect the functions of these receptors, with the goal of developing insights that will guide the successful targeting of therapeutic interventions.

Cost Effectiveness of Alectinib vs. Crizotinib in First-Line Anaplastic Lymphoma Kinase-Positive Advanced Non-Small-Cell Lung Cancer.

PubMed

Carlson, Josh J; Suh, Kangho; Orfanos, Panos; Wong, William

2018-04-01

The recently completed ALEX trial demonstrated that alectinib improved progression-free survival, and delayed time to central nervous system progression compared with crizotinib in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer. However, the long-term clinical and economic impact of using alectinib vs. crizotinib has not been evaluated. The objective of this study was to determine the potential cost utility of alectinib vs. crizotinib from a US payer perspective. A cost-utility model was developed using partition survival methods and three health states: progression-free, post-progression, and death. ALEX trial data informed the progression-free and overall survival estimates. Costs included drug treatments and supportive care (central nervous system and non-central nervous system). Utility values were obtained from trial data and literature. Sensitivity analyses included one-way and probabilistic sensitivity analyses. Treatment with alectinib vs. crizotinib resulted in a gain of 0.91 life-years, 0.87 quality-adjusted life-years, and incremental costs of US$34,151, resulting in an incremental cost-effectiveness ratio of US$39,312/quality-adjusted life-year. Drug costs and utilities in the progression-free health state were the main drivers of the model in the one-way sensitivity analysis. From the probabilistic sensitivity analysis, alectinib had a 64% probability of being cost effective at a willingness-to-pay threshold of US$100,000/quality adjusted life-year. Alectinib increased time in the progression-free state and quality-adjusted life-years vs. crizotinib. The marginal cost increase was reflective of longer treatment durations in the progression-free state. Central nervous system-related costs were considerably lower with alectinib. Our results suggest that compared with crizotinib, alectinib may be a cost-effective therapy for treatment-naïve patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer.

Manipulating central nervous mechanisms of food intake and body weight regulation by intranasal administration of neuropeptides in man.

PubMed

Hallschmid, Manfred; Benedict, Christian; Born, Jan; Fehm, Horst-Lorenz; Kern, Werner

2004-10-30

Maintaining a stable body weight set-point is assumed to rely on a homeostatic central nervous system (CNS) regulation of body fat with the particular involvement of hypothalamic pathways. The peripheral adiposity signals insulin and leptin convey information on the amount of energy stored as body fat to the arcuate nucleus of the hypothalamus, where anabolic/orexigenic and catabolic/anorexigenic pathways interact to regulate food intake and energy expenditure. One of the most prominent orexigenic messengers is neuropeptide Y (NPY), whereas melanocortins, including alpha-melanocyte-stimulating hormone (alpha-MSH), are essential for inducing anorexigenic effects. The melanocortin receptor 4 (MC4-R) plays the most important role in mediating catabolic effects of alpha-MSH. In this review, we present a series of own studies on NPY, insulin and MSH/ACTH4-10, an MC4-R agonist. The studies were all based on the intranasal route of administration which enables a direct access of the peptides to hypothalamic functions. NPY acutely attenuated electrocortical signs of meal-related satiety. Prolonged intranasal administration of insulin as well as of MSH induced weight loss in healthy human subjects. However, overweight subjects did not lose body fat after MSH administration. The results corroborate in humans the significance of all three messengers for the central nervous regulation of adiposity and might contribute to the future development of medical strategies against body-weight-related disorders.

Increase in peripheral oxidative stress during hypercholesterolemia is not reflected in the central nervous system: evidence from two mouse models.

PubMed

Ding, Tao; Yao, Yeumang; Praticò, Domenico

2005-05-01

In recent years oxidative stress has been widely implicated as a pathogenetic mechanism of several diseases, and a variety of indices and assays have been developed to assess this phenomenon in complex biological systems. Most of these biomarkers can be measured virtually in every biological fluid and tissue, providing us with the opportunity to assess their formation at local site of oxidative injury. However, despite their widespread use, it is still not completely clear how their peripheral formation correlates with the levels measured in the central nervous system. For this reason, we utilized two well-characterized animal models of chronic peripheral oxidative stress, low-density lipoprotein receptor (LDLR)-deficient and C57BL/6 mice on a high fat diet. After 8 weeks on the diet, we assessed isoprostane, marker of lipid peroxidation, and carbonyls, marker of protein oxidation, in several organs of these animals. Compared with animals on chow, mice on the high fat diet showed a significant increase in both biomarkers in plasma, heart, aorta and liver but not in brain tissues. This observation was confirmed by the selective accumulation of radioactivity in the peripheral organs but not in the brains of mice injected with tritiated isoprostane. Our findings indicate that in hypercholesterolemia the peripheral formation of oxidative products does not contribute to their levels found in the central nervous system.

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

PubMed

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

2010-09-01

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

KSC-97PC1716

NASA Image and Video Library

1997-11-11

The Neurolab payload for STS-90, scheduled to launch aboard the Shuttle Columbia from Kennedy Space Center (KSC) on April 2, 1998, is ready for processing after being placed in its workstand in the Operations and Checkout Building at KSC. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90 will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D

KSC-97PC1720

NASA Image and Video Library

1997-11-12

The Neurolab payload for STS-90, scheduled to launch aboard the Shuttle Columbia from Kennedy Space Center (KSC) on April 2, 1998, is installed in the Spacelab module by Boeing technicians in the Operations and Checkout Building at KSC. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Specifically, experiments will study the adaptation of the vestibular system, the central nervous system, and the pathways that control the ability to sense location in the absence of gravity, as well as the effect of microgravity on a developing nervous system. The crew of STS-90 will include Commander Richard Searfoss, Pilot Scott Altman, Mission Specialists Richard Linnehan, Dafydd (Dave) Williams, M.D., and Kathryn (Kay) Hire, and Payload Specialists Jay Buckey, M.D., and James Pawelczyk, Ph.D