Sample records for accelerates central nervous

  1. [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.

  2. 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 ...

  3. 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.

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

    PubMed Central

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

    2016-01-01

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

  5. 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

  6. 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.

  7. 21 CFR 882.5550 - Central nervous system fluid shunt and components.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  8. 21 CFR 882.5550 - Central nervous system fluid shunt and components.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  9. 21 CFR 882.5550 - Central nervous system fluid shunt and components.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  10. 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...

  11. 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...

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Central and peripheral nervous systems: master controllers in cancer metastasis.

    PubMed

    Shi, Ming; Liu, Dan; Yang, Zhengyan; Guo, Ning

    2013-12-01

    Central and sympathetic nervous systems govern functional activities of many organs. Solid tumors like organs are also innervated by sympathetic nerve fibers. Neurotransmitters released from sympathetic nerve fibers can modulate biological behaviors of tumor cells. Multiple physiologic processes of tumor development may be dominated by central and sympathetic nervous systems as well. Recent studies suggest that dysfunction of central and sympathetic nervous systems and disorder of the hormone network induced by psychological stress may influence malignant progression of cancer by inhibiting the functions of immune system, regulating metabolic reprogramming of tumor cells, and inducing interactions between tumor and stromal cells. Over-release of inflammatory cytokines by tumors may aggravate emotional disorder, triggering the vicious cycles in tumor microenvironment and host macroenvironment. It is reasonable to hypothesize that cancer progression may be controlled by central and sympathetic nervous systems. In this review, we will focus on the recent information about the impacts of central and sympathetic nervous systems on tumor invasion and metastasis.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. Improving and Accelerating Drug Development for Nervous System Disorders

    PubMed Central

    Pankevich, Diana E.; Altevogt, Bruce M.; Dunlop, John; Gage, Fred H.; Hyman, Steve E.

    2014-01-01

    Advances in the neurosciences have placed the field in the position where it is poised to significantly reduce the burden of nervous system disorders. However, drug discovery, development and translation for nervous system disorders still pose many unique challenges. The key scientific challenges can be summarized as follows: mechanisms of disease, target identification and validation, predictive models, biomarkers for patient stratification and as endpoints for clinical trials, clear regulatory pathways, reliability and reproducibility of published data, and data sharing and collaboration. To accelerate nervous system drug development the Institute of Medicine’s Forum on Neuroscience and Nervous System Disorders has hosted a series of public workshops that brought together representatives of industry, government (including both research funding and regulatory agencies), academia, and patient groups to discuss these challenges and offer potential strategies to improve the translational neuroscience. PMID:25442933

  5. 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

  6. 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.

  7. 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.

  8. [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.

  9. 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

  10. 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.

  11. 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.

  12. Central nervous system histoplasmosis

    PubMed Central

    Wheat, Joseph; Myint, Thein; Guo, Ying; Kemmer, Phebe; Hage, Chadi; Terry, Colin; Azar, Marwan M.; Riddell, James; Ender, Peter; Chen, Sharon; Shehab, Kareem; Cleveland, Kerry; Esguerra, Eden; Johnson, James; Wright, Patty; Douglas, Vanja; Vergidis, Pascalis; Ooi, Winnie; Baddley, John; Bamberger, David; Khairy, Raed; Vikram, Holenarasipur; Jenny-Avital, Elizabeth; Sivasubramanian, Geetha; Bowlware, Karen; Pahud, Barbara; Sarria, Juan; Tsai, Townson; Assi, Maha; Mocherla, Satish; Prakash, Vidhya; Allen, David; Passaretti, Catherine; Huprikar, Shirish; Anderson, Albert

    2018-01-01

    Abstract Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment. A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment. Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment. While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy. PMID:29595679

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Centralization of the deuterostome nervous system predates chordates.

    PubMed

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

    2009-08-11

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

  7. [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.

  8. Recent Understanding on Diagnosis and Management of Central Nervous System Vasculitis in Children

    PubMed Central

    Iannetti, Ludovico; Zito, Roberta; Bruschi, Simone; Papetti, Laura; Ulgiati, Fiorenza; Nicita, Francesco; Del Balzo, Francesca; Spalice, Alberto

    2012-01-01

    Central nervous system vasculitides in children may develop as a primary condition or secondary to an underlying systemic disease. Many vasculitides affect both adults and children, while some others occur almost exclusively in childhood. Patients usually present with systemic symptoms with single or multiorgan dysfunction. The involvement of central nervous system in childhood is not frequent and it occurs more often as a feature of subtypes like childhood polyarteritis nodosa, Kawasaki disease, Henoch Schönlein purpura, and Bechet disease. Primary angiitis of the central nervous system of childhood is a reversible cause of severe neurological impairment, including acute ischemic stroke, intractable seizures, and cognitive decline. The first line therapy of CNS vasculitides is mainly based on corticosteroids and immunosuppressor drugs. Other strategies include plasmapheresis, immunoglobulins, and biologic drugs. This paper discusses on current understanding of most frequent primary and secondary central nervous system vasculitides in children including a tailored-diagnostic approach and new evidence regarding treatment. PMID:23008735

  9. CENTRAL NERVOUS SYSTEM INFECTION DURING IMMUNOSUPPRESSION

    PubMed Central

    Zunt, Joseph R.

    2009-01-01

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

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

    PubMed

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

    2017-03-15

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

  11. [The Role of Imaging in Central Nervous System Infections].

    PubMed

    Yokota, Hajime; Tazoe, Jun; Yamada, Kei

    2015-07-01

    Many infections invade the central nervous system. Magnetic resonance imaging (MRI) is the main tool that is used to evaluate infectious lesions of the central nervous system. The useful sequences on MRI are dependent on the locations, such as intra-axial, extra-axial, and spinal cord. For intra-axial lesions, besides the fundamental sequences, including T1-weighted images, T2-weighted images, and fluid-attenuated inversion recovery (FLAIR) images, advanced sequences, such as diffusion-weighted imaging, diffusion tensor imaging, susceptibility-weighted imaging, and MR spectroscopy, can be applied. They are occasionally used as determinants for quick and correct diagnosis. For extra-axial lesions, understanding the differences among 2D-conventional T1-weighted images, 2D-fat-saturated T1-weighted images, 3D-Spin echo sequences, and 3D-Gradient echo sequence after the administration of gadolinium is required to avoid wrong interpretations. FLAIR plus gadolinium is a useful tool for revealing abnormal enhancement on the brain surface. For the spinal cord, the sequences are limited. Evaluating the distribution and time course of the spinal cord are essential for correct diagnoses. We summarize the role of imaging in central nervous system infections and show the pitfalls, key points, and latest information in them on clinical practices.

  12. 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.

  13. [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.

  14. Early exposure of rotating magnetic fields promotes central nervous regeneration in planarian Girardia sinensis.

    PubMed

    Chen, Qiang; Lin, Gui-miao; Wu, Nan; Tang, Sheng-wei; Zheng, Zhi-jia; Lin, Marie Chia-mi; Xu, Gai-xia; Liu, Hao; Deng, Yue-yue; Zhang, Xiao-yun; Chen, Si-ping; Wang, Xiao-mei; Niu, Han-ben

    2016-05-01

    Magnetic field exposure is an accepted safe and effective modality for nerve injury. However, it is clinically used only as a supplement or salvage therapy at the later stage of treatment. Here, we used a planarian Girardia sinensis decapitated model to investigate beneficial effects of early rotary non-uniform magnetic fields (RMFs) exposure on central nervous regeneration. Our results clearly indicated that magnetic stimulation induced from early RMFs exposure significantly promoted neural regeneration of planarians. This stimulating effect is frequency and intensity dependent. Optimum effects were obtained when decapitated planarians were cultured at 20 °C, starved for 3 days before head-cutting, and treated with 6 Hz 0.02 T RMFs. At early regeneration stage, RMFs exposure eliminated edema around the wound and facilitated subsequent formation of blastema. It also accelerated cell proliferation and recovery of neuron functionality. Early RMFs exposure up-regulated expression of neural regeneration related proteins, EGR4 and Netrin 2, and mature nerve cell marker proteins, NSE and NPY. These results suggest that RMFs therapy produced early and significant benefit in central nervous regeneration, and should be clinically used at the early stage of neural regeneration, with appropriate optimal frequency and intensity. © 2016 Wiley Periodicals, Inc.

  15. 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

  16. 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.

  17. 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.

  18. An Injectable, Self-Healing Hydrogel to Repair the Central Nervous System.

    PubMed

    Tseng, Ting-Chen; Tao, Lei; Hsieh, Fu-Yu; Wei, Yen; Chiu, Ing-Ming; Hsu, Shan-hui

    2015-06-17

    An injectable, self-healing hydrogel (≈1.5 kPa) is developed for healing nerve-system deficits. Neurosphere-like progenitors proliferate in the hydrogel and differentiate into neuron-like cells. In the zebrafish injury model, the central nervous system function is partially rescued by injection of the hydrogel and significantly rescued by injection of the neurosphere-laden hydrogel. The self-healing hydrogel may thus potentially repair the central nervous system. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Central- and autonomic nervous system coupling in schizophrenia

    PubMed Central

    Schulz, Steffen; Bolz, Mathias; Bär, Karl-Jürgen

    2016-01-01

    The autonomic nervous system (ANS) dysfunction has been well described in schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between the ANS and central brain activity has been not addressed until now in SZ. The interactions between the central nervous system (CNS) and ANS need to be considered as a feedback–feed-forward system that supports flexible and adaptive responses to specific demands. For the first time, to the best of our knowledge, this study investigates central–autonomic couplings (CAC) studying heart rate, blood pressure and electroencephalogram in paranoid schizophrenic patients, comparing them with age–gender-matched healthy subjects (CO). The emphasis is to determine how these couplings are composed by the different regulatory aspects of the CNS–ANS. We found that CAC were bidirectional, and that the causal influence of central activity towards systolic blood pressure was more strongly pronounced than such causal influence towards heart rate in paranoid schizophrenic patients when compared with CO. In paranoid schizophrenic patients, the central activity was a much stronger variable, being more random and having fewer rhythmic oscillatory components. This study provides a more in-depth understanding of the interplay of neuronal and autonomic regulatory processes in SZ and most likely greater insights into the complex relationship between psychotic stages and autonomic activity. PMID:27044986

  20. [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

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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

  10. 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.

  11. [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.

  12. 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.

  13. Neurognathostomiasis, a neglected parasitosis of the central nervous system.

    PubMed

    Katchanov, Juri; Sawanyawisuth, Kittisak; Chotmongkoi, Verajit; Nawa, Yukifumi

    2011-07-01

    Gnathostomiasis is a foodborne zoonotic helminthic infection caused by the third-stage larvae of Gnathostoma spp. nematodes. The most severe manifestation involves infection of the central nervous system, neurognathostomiasis. Although gnathostomiasis is endemic to Asia and Latin America, almost all neurognathostomiasis cases are reported from Thailand. Despite high rates of illness and death, neurognathostomiasis has received less attention than the more common cutaneous form of gnathostomiasis, possibly because of the apparent geographic confinement of the neurologic infection to 1 country. Recently, however, the disease has been reported in returned travelers in Europe. We reviewed the English-language literature on neurognathostomiasis and analyzed epidemiology and geographic distribution, mode of central nervous system invasion, pathophysiology, clinical features, neuroimaging data, and treatment options. On the basis of epidemiologic data, clinical signs, neuroimaging, and laboratory findings, we propose diagnostic criteria for neurognathostomiasis.

  14. [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.

  15. 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.

  16. 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

  17. 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 ...

  18. 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)

  19. 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.

  20. 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.

  1. 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.

  2. Statin Therapy Inhibits Remyelination in the Central Nervous System

    PubMed Central

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

    2009-01-01

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

  3. Gravitational Study of the Central Nervous System

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.

    1983-01-01

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

  4. 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

  5. DNA methylation-based classification of central nervous system tumours.

    PubMed

    Capper, David; Jones, David T W; Sill, Martin; Hovestadt, Volker; Schrimpf, Daniel; Sturm, Dominik; Koelsche, Christian; Sahm, Felix; Chavez, Lukas; Reuss, David E; Kratz, Annekathrin; Wefers, Annika K; Huang, Kristin; Pajtler, Kristian W; Schweizer, Leonille; Stichel, Damian; Olar, Adriana; Engel, Nils W; Lindenberg, Kerstin; Harter, Patrick N; Braczynski, Anne K; Plate, Karl H; Dohmen, Hildegard; Garvalov, Boyan K; Coras, Roland; Hölsken, Annett; Hewer, Ekkehard; Bewerunge-Hudler, Melanie; Schick, Matthias; Fischer, Roger; Beschorner, Rudi; Schittenhelm, Jens; Staszewski, Ori; Wani, Khalida; Varlet, Pascale; Pages, Melanie; Temming, Petra; Lohmann, Dietmar; Selt, Florian; Witt, Hendrik; Milde, Till; Witt, Olaf; Aronica, Eleonora; Giangaspero, Felice; Rushing, Elisabeth; Scheurlen, Wolfram; Geisenberger, Christoph; Rodriguez, Fausto J; Becker, Albert; Preusser, Matthias; Haberler, Christine; Bjerkvig, Rolf; Cryan, Jane; Farrell, Michael; Deckert, Martina; Hench, Jürgen; Frank, Stephan; Serrano, Jonathan; Kannan, Kasthuri; Tsirigos, Aristotelis; Brück, Wolfgang; Hofer, Silvia; Brehmer, Stefanie; Seiz-Rosenhagen, Marcel; Hänggi, Daniel; Hans, Volkmar; Rozsnoki, Stephanie; Hansford, Jordan R; Kohlhof, Patricia; Kristensen, Bjarne W; Lechner, Matt; Lopes, Beatriz; Mawrin, Christian; Ketter, Ralf; Kulozik, Andreas; Khatib, Ziad; Heppner, Frank; Koch, Arend; Jouvet, Anne; Keohane, Catherine; Mühleisen, Helmut; Mueller, Wolf; Pohl, Ute; Prinz, Marco; Benner, Axel; Zapatka, Marc; Gottardo, Nicholas G; Driever, Pablo Hernáiz; Kramm, Christof M; Müller, Hermann L; Rutkowski, Stefan; von Hoff, Katja; Frühwald, Michael C; Gnekow, Astrid; Fleischhack, Gudrun; Tippelt, Stephan; Calaminus, Gabriele; Monoranu, Camelia-Maria; Perry, Arie; Jones, Chris; Jacques, Thomas S; Radlwimmer, Bernhard; Gessi, Marco; Pietsch, Torsten; Schramm, Johannes; Schackert, Gabriele; Westphal, Manfred; Reifenberger, Guido; Wesseling, Pieter; Weller, Michael; Collins, Vincent Peter; Blümcke, Ingmar; Bendszus, Martin; Debus, Jürgen; Huang, Annie; Jabado, Nada; Northcott, Paul A; Paulus, Werner; Gajjar, Amar; Robinson, Giles W; Taylor, Michael D; Jaunmuktane, Zane; Ryzhova, Marina; Platten, Michael; Unterberg, Andreas; Wick, Wolfgang; Karajannis, Matthias A; Mittelbronn, Michel; Acker, Till; Hartmann, Christian; Aldape, Kenneth; Schüller, Ulrich; Buslei, Rolf; Lichter, Peter; Kool, Marcel; Herold-Mende, Christel; Ellison, David W; Hasselblatt, Martin; Snuderl, Matija; Brandner, Sebastian; Korshunov, Andrey; von Deimling, Andreas; Pfister, Stefan M

    2018-03-22

    Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.

  6. Fanconi anemia: correlating central nervous system malformations and genetic complementation groups.

    PubMed

    Johnson-Tesch, Benjamin A; Gawande, Rakhee S; Zhang, Lei; MacMillan, Margaret L; Nascene, David R

    2017-06-01

    Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group. Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations.

  7. [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.

  8. 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.

  9. 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.

  10. 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.…

  11. 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

  12. 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.

  13. Tachykinin-1 in the central nervous system regulates adiposity in rodents.

    PubMed

    Trivedi, Chitrang; Shan, Xiaoye; Tung, Yi-Chun Loraine; Kabra, Dhiraj; Holland, Jenna; Amburgy, Sarah; Heppner, Kristy; Kirchner, Henriette; Yeo, Giles S H; Perez-Tilve, Diego

    2015-05-01

    Ghrelin is a circulating hormone that targets the central nervous system to regulate feeding and adiposity. The best-characterized neural system that mediates the effects of ghrelin on energy balance involves the activation of neuropeptide Y/agouti-related peptide neurons, expressed exclusively in the arcuate nucleus of the hypothalamus. However, ghrelin receptors are expressed in other neuronal populations involved in the control of energy balance. We combined laser capture microdissection of several nuclei of the central nervous system expressing the ghrelin receptor (GH secretagoge receptor) with microarray gene expression analysis to identify additional neuronal systems involved in the control of central nervous system-ghrelin action. We identified tachykinin-1 (Tac1) as a gene negatively regulated by ghrelin in the hypothalamus. Furthermore, we identified neuropeptide k as the TAC1-derived peptide with more prominent activity, inducing negative energy balance when delivered directly into the brain. Conversely, loss of Tac1 expression enhances the effectiveness of ghrelin promoting fat mass gain both in male and in female mice and increases the susceptibility to diet-induced obesity in ovariectomized mice. Taken together, our data demonstrate a role TAC1 in the control energy balance by regulating the levels of adiposity in response to ghrelin administration and to changes in the status of the gonadal function.

  14. 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.

  15. 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 ...

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

    PubMed

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

    2017-10-12

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

  17. 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.

  18. Plants and the central nervous system.

    PubMed

    Carlini, E A

    2003-06-01

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

  19. 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

  20. 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

  1. 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.

  2. 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.

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

    NASA Astrophysics Data System (ADS)

    Harzsch, S.; Dawirs, R. R.

    1993-02-01

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

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

    PubMed

    Murnyák, Balázs; Szepesi, Rita; Hortobágyi, Tibor

    2015-02-01

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

  5. 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.

  6. The Central Nervous Connections Involved in the Vomiting Reflex

    NASA Technical Reports Server (NTRS)

    Brizzee, K. R.; Mehler, W. R.

    1986-01-01

    The vomiting reflex may be elicited by a number of different types or classes of stimuli involving many varieties of receptor structures and considerable diversity in afferent pathways and central connections. Central relay or mediating structures thus may vary widely according to the type of initial emetic stimulus. The emetic circuits which have been most completely delineated to date are probably those in which the Chemoreceptor Trigger Zone (CTZ) in the Area Postrema (AP) functions as a key mediating structure. Even in this system, however, there are large gaps in our knowledge of the nerve tracts and central nervous connections involved. Knowledge of most other emetic circuits subserving the emetic reflex resulting from many diverse types of stimuli such, for example, as emotional stress (e.g. psychogenic vomiting, Wruble et al. 1982), pain (e.g. testicular trauma), and chemical or mechanical irritation of the gastrointestinal tract or urinary tract is quite incomplete at this time, thus precluding any very adequate description of their central connections at present. One physiological system, however, which has received considerable attention recently in relation to the vomiting reflex elicited by motion stimuli is the vestibular system. Due to the paucity of data on central nervous connections of several or the non-vestibular types of emetic stimuli cited above, we will devote most of our attention in this brief review to the central connections of the vestibular system which seem likely to be involved in the vomiting response to motion stimuli. However, the latter part of the review will be concerned with the concept of the reticular vomiting centre in relation to the ParviCellular Reticular Formation (PCRF), and will thus probably pertain to all of the many classes of emetic stimuli since it will address the question of the final common emetic pathway.

  7. 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.

  8. 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…

  9. 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…

  10. 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.

  11. 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.

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

    PubMed

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

    2016-03-01

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

  13. 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)

  14. 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.

  15. 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.

  16. Teleost fish as a model system to study successful regeneration of the central nervous system.

    PubMed

    Zupanc, Günther K H; Sîrbulescu, Ruxandra F

    2013-01-01

    Traumatic brain injury and spinal cord injury are devastating conditions that may result in death or long-term disability. A promising strategy for the development of effective cell replacement therapies involves the study of regeneration-competent organisms. Among this group, teleost fish are distinguished by their excellent potential to regenerate nervous tissue and to regain function after injury to the central nervous system. In this chapter, we summarize our current understanding of the cellular processes that mediate this regenerative potential, and we show that several of these processes are shared with the normal development of the intact central nervous system; we describe how the spontaneous self-repair of the teleostean central nervous system leads to functional recovery, at physiological and behavioral levels; we discuss the possible function of molecular factors associated with the degenerative and regenerative processes after injury; and, finally, we speculate on evolutionary aspects of adult neurogenesis and neuronal regeneration, and on how a better understanding of these aspects could catalyze the development of therapeutic strategies to overcome the regenerative limits of the mammalian CNS.

  17. 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.

  18. Mutations in spalt cause a severe but reversible neurodegenerative phenotype in the embryonic central nervous system of Drosophila melanogaster.

    PubMed

    Cantera, Rafael; Lüer, Karin; Rusten, Tor Erik; Barrio, Rosa; Kafatos, Fotis C; Technau, Gerhard M

    2002-12-01

    The gene spalt is expressed in the embryonic central nervous system of Drosophila melanogaster but its function in this tissue is still unknown. To investigate this question, we used a combination of techniques to analyse spalt mutant embryos. Electron microscopy showed that in the absence of spalt, the central nervous system cells are separated by enlarged extracellular spaces populated by membranous material at 60% of embryonic development. Surprisingly, the central nervous system from slightly older embryos (80% of development) exhibited almost wild-type morphology. An extensive survey by laser confocal microscopy revealed that the spalt mutant central nervous system has abnormal levels of particular cell adhesion and cytoskeletal proteins. Time-lapse analysis of neuronal differentiation in vitro, lineage analysis and transplantation experiments confirmed that the mutation causes cytoskeletal and adhesion defects. The data indicate that in the central nervous system, spalt operates within a regulatory pathway which influences the expression of the beta-catenin Armadillo, its ligand N-Cadherin, Notch, and the cell adhesion molecules Neuroglian, Fasciclin 2 and Fasciclin 3. Effects on the expression of these genes are persistent but many morphological aspects of the phenotype are transient, leading to the concept of sequential redundancy for stable organisation of the central nervous system.

  19. 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.

  20. Longitudinal analysis of hearing loss in a case of hemosiderosis of the central nervous system.

    PubMed

    Weekamp, H H; Huygen, P L M; Merx, J L; Kremer, H P H; Cremers, Cor W R J; Longridge, Neil S

    2003-09-01

    To describe cochleovestibular aspects of superficial hemosiderosis of the central nervous system. Superficial hemosiderosis of the central nervous system is a rare disease in which cochleovestibular impairment, cerebellar ataxia, and myelopathy are the most frequent signs. Chronic recurrent subarachnoidal hemorrhage with bleeding into the cerebrospinal fluid is the cause of deposition of hemosiderin in leptomeningeal and subpial tissue, cranial nerves, and spinal cord. Removing the cause of bleeding can prevent irreversible damage to these structures. Because this is the only effective treatment, an early diagnosis is crucial. Retrospective case review. Tertiary referral center. A 72-year-old woman with superficial hemosiderosis of the central nervous system that developed when she was age 39. Neurologic and imaging diagnostic examinations and longitudinal evaluation of cochleovestibular features were performed. Neurosurgery was not performed. Progressive bilateral sensorineural hearing loss and severe vestibular hyporeflexia developed within 15 years, which can be attributed to lesions in the cochleovestibular system. Additional pathology of the central nervous system developed later. The patient demonstrated cochlear and vestibular findings that are typical of this pathologic condition. It is the first documented case with extensive serial audiometry used to precisely outline the degree of hearing deterioration during the course of the disease.

  1. 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.

  2. 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.

  3. Autoimmune Neurology of the Central Nervous System.

    PubMed

    Tobin, W Oliver; Pittock, Sean J

    2017-06-01

    This article reviews the rapidly evolving spectrum of autoimmune neurologic disorders with a focus on those that involve the central nervous system, providing an understanding of how to approach the diagnostic workup of patients presenting with central nervous system symptoms or signs that could be immune mediated, either paraneoplastic or idiopathic, to guide therapeutic decision making. The past decade has seen a dramatic increase in the discovery of novel neural antibodies and their targets. Many commercial laboratories can now test for these antibodies, which serve as diagnostic markers of diverse neurologic disorders that occur on an autoimmune basis. Some are highly specific for certain cancer types, and the neural antibody profiles may help direct the physician's cancer search. The diagnosis of an autoimmune neurologic disorder is aided by the detection of an objective neurologic deficit (usually subacute in onset with a fluctuating course), the presence of a neural autoantibody, and improvement in the neurologic status after a course of immunotherapy. Neural autoantibodies should raise concern for a paraneoplastic etiology and may inform a targeted oncologic evaluation (eg, N-methyl-D-aspartate [NMDA] receptor antibodies are associated with teratoma, antineuronal nuclear antibody type 1 [ANNA-1, or anti-Hu] are associated with small cell lung cancer). MRI, EEG, functional imaging, videotaped evaluations, and neuropsychological evaluations provide objective evidence of neurologic dysfunction by which the success of immunotherapy may be measured. Most treatment information emanates from retrospective case series and expert opinion. Nonetheless, early intervention may allow reversal of deficits in many patients and prevention of future disability.

  4. 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.

  5. 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.

  6. 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.

  7. [Thyroid hormones and the development of the nervous system].

    PubMed

    Mussa, G C; Zaffaroni, M; Mussa, F

    1990-09-01

    The growth and differentiation of the central nervous system are closely related to the presence of iodine and thyroid hormones. During the first trimester of human pregnancy the development of the nervous system depends entirely on the availability of iodine; after 12 week of pregnancy it depends on the initial secretion of iodothyronine by the fetal thyroid gland. During the early stages of the development of the nervous system a thyroid hormone deficit may provoke alterations in the maturation of both noble nervous cells (cortical pyramidal cells, Purkinje cells) and glial cells. Hypothyroidism may lead to cellular hypoplasia and reduced dendritic ramification, gemmules and interneuronal connections. Experimental studies in hypothyroid rats have also shown alterations in the content and organization of neuronal intracytoplasmatic microtubules, the biochemical maturation of synaptosomes and the maturation of nuclear and cytoplasmatic T3 receptors. Excess thyroid hormones during the early stages of development may also cause permanent damage to the central nervous system. Hyperthyroidism may initially induce an acceleration of the maturation processes, including the migration and differentiation of cells, the extension of the dendritic processes and synaptogenesis. An excess of thyroid hormones therefore causes neuronal proliferation to end precociously leading to a reduction of the total number of gemmules. Experimental research and clinical studies have partially clarified the correlation between the maturation of the nervous system and thyroid function during the early stages of development; both a deficit and excess of thyroid hormones may lead to permanent anatomo-functional damage to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. 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.

  9. 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.

  10. Tumor-Like Presentation of Primary Angiitis of the Central Nervous System.

    PubMed

    de Boysson, Hubert; Boulouis, Grégoire; Dequatre, Nelly; Godard, Sophie; Néel, Antoine; Arquizan, Caroline; Detante, Olivier; Bloch-Queyrat, Coralie; Zuber, Mathieu; Touzé, Emmanuel; Bienvenu, Boris; Aouba, Achille; Guillevin, Loïc; Naggara, Olivier; Pagnoux, Christian

    2016-09-01

    We aimed to describe the clinical and imaging features of patients with tumor-like presentation of primary angiitis of the central nervous system. We retrospectively analyzed 10 patients enrolled in the French primary angiitis of the central nervous system cohort, who initially presented tumor-like brain lesions and compared them with other patients within the cohort. The 10 patients with tumor-like presentation in the cohort were younger and had more seizures at diagnosis than the other 75 patients (median of 37 [30-48] years versus 46 [18-79] years; P=0.008; 9 [90%] with seizures versus 22 [29%], P<0.001; respectively). All 10 patients had a biopsy (stereotactic procedure in 7 and open-wedge surgery in 3). Histological findings suggestive of vasculitis were observed in 9 patients in whom conventional cerebral angiography and magnetic resonance angiography were negative. In the remaining patient, vascular imaging demonstrated diffuse bilateral large- and medium-sized vessel involvement (biopsy did not reveal vasculitis). All patients with tumor-like presentation received glucocorticoids, combined with cyclophosphamide in 9 cases. With a median follow-up of 27 (12-130) months, 5 (50%) patients relapsed, but achieved remission again after treatment intensification. Patients with tumor-like presentation of primary angiitis of the central nervous system represent a subgroup characterized with mainly small-sized vessel disease that requires histological confirmation because vascular imaging is often normal. Although relapses are not uncommon, global outcomes are good under treatment with glucocorticoids and cyclophosphamide. © 2016 American Heart Association, Inc.

  11. Programmed cell death acts at different stages of Drosophila neurodevelopment to shape the central nervous system

    PubMed Central

    Desplan, Claude

    2016-01-01

    Nervous system development is a process that integrates cell proliferation, differentiation and programmed cell death (PCD). PCD is an evolutionary conserved mechanism and a fundamental developmental process by which the final cell number in a nervous system is established. In vertebrates and invertebrates, PCD can be determined intrinsically by cell lineage and age, as well as extrinsically by nutritional, metabolic and hormonal states. Drosophila has been an instrumental model for understanding how this mechanism is regulated. We review the role of PCD in Drosophila central nervous system development from neural progenitors to neurons, its molecular mechanism and function, how it is regulated and implemented, and how it ultimately shapes the fly central nervous system from the embryo to the adult. Finally, we discuss ideas that emerge while integrating this information. PMID:27404003

  12. 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...

  13. 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

  14. 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.

  15. 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.

  16. Checkpoints to the Brain: Directing Myeloid Cell Migration to the Central Nervous System

    PubMed Central

    Harrison-Brown, Meredith; Liu, Guo-Jun; Banati, Richard

    2016-01-01

    Myeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding of the unique properties of these cells have inspired interest in their use as delivery vehicles for therapeutic genes, proteins, and drugs, or as “assistants” in the clean-up of aggregated proteins and other molecules when existing drainage systems are no longer adequate. The trafficking of myeloid cells from the periphery to the central nervous system is subject to complex cellular and molecular controls with several ‘checkpoints’ from the blood to their destination in the brain parenchyma. As important components of the neurovascular unit, the functional state changes associated with lineage heterogeneity of myeloid cells are increasingly recognized as important for disease progression. In this review, we discuss some of the cellular elements associated with formation and function of the neurovascular unit, and present an update on the impact of myeloid cells on central nervous system (CNS) diseases in the laboratory and the clinic. We then discuss emerging strategies for harnessing the potential of site-directed myeloid cell homing to the CNS, and identify promising avenues for future research, with particular emphasis on the importance of untangling the functional heterogeneity within existing myeloid subsets. PMID:27918464

  17. [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.

  18. Treatment of HIV in the Central Nervous System.

    PubMed

    Yilmaz, Aylin; Gisslén, Magnus

    2014-02-01

    Central nervous system (CNS) infection is an important part of systemic human immunodeficiency disease (HIV) infection. It is most often asymptomatic, but can sometimes lead to severe neurologic disease, particularly in advanced stages of immunosuppression. CNS HIV infection usually responds well to antiretroviral treatment, but there are concerns that treatment may not always be fully effective in treating or preventing milder CNS disease and that it, under certain circumstances, might be important to consider antiretroviral drug distribution and effects within the CNS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  19. Transcriptome Analysis of the Octopus vulgaris Central Nervous System

    PubMed Central

    Zhang, Xiang; Mao, Yong; Huang, Zixia; Qu, Meng; Chen, Jun; Ding, Shaoxiong; Hong, Jingni; Sun, Tiantian

    2012-01-01

    Background Cephalopoda are a class of Mollusca species found in all the world's oceans. They are an important model organism in neurobiology. Unfortunately, the lack of neuronal molecular sequences, such as ESTs, transcriptomic or genomic information, has limited the development of molecular neurobiology research in this unique model organism. Results With high-throughput Illumina Solexa sequencing technology, we have generated 59,859 high quality sequences from 12,918,391 paired-end reads. Using BLASTx/BLASTn, 12,227 contigs have blast hits in the Swissprot, NR protein database and NT nucleotide database with E-value cutoff 1e−5. The comparison between the Octopus vulgaris central nervous system (CNS) library and the Aplysia californica/Lymnaea stagnalis CNS ESTs library yielded 5.93%/13.45% of O. vulgaris sequences with significant matches (1e−5) using BLASTn/tBLASTx. Meanwhile the hit percentage of the recently published Schistocerca gregaria, Tilapia or Hirudo medicinalis CNS library to the O. vulgaris CNS library is 21.03%–46.19%. We constructed the Phylogenetic tree using two genes related to CNS function, Synaptotagmin-7 and Synaptophysin. Lastly, we demonstrated that O. vulgaris may have a vertebrate-like Blood-Brain Barrier based on bioinformatic analysis. Conclusion This study provides a mass of molecular information that will contribute to further molecular biology research on O. vulgaris. In our presentation of the first CNS transcriptome analysis of O. vulgaris, we hope to accelerate the study of functional molecular neurobiology and comparative evolutionary biology. PMID:22768275

  20. 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…

  1. 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.

  2. Leptin and the central nervous system control of glucose metabolism.

    PubMed

    Morton, Gregory J; Schwartz, Michael W

    2011-04-01

    The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders.

  3. 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

  4. 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.

  5. 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.

  6. Bilastine and the central nervous system.

    PubMed

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

    2011-01-01

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

  7. 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.

  8. MORPHOLOGICAL PATTERN AND FREQUENCY OF CENTRAL NERVOUS SYSTEM TUMOURS IN CHILDREN.

    PubMed

    Bilqees, Fatima; Samina, Khaleeq; Mohammad, Tahir; Khaleeq-uz-Zamaan

    2016-01-01

    Recent studies, including a comprehensive study by National Cancer Institute, have shown that a significant increase in the incidence of childhood brain tumours makes them the most common paediatric tumour. The objectives of this study were to determine the frequency of central nervous system tumours in paediatric age group (0-12 years), and to segregate various morphologic types according to WHO classification. The study included consecutive cases of central nervous system tumours diagnosed in children in the histopathology department at Federal Government Polyclinic, PGMI, Islamabad, during a period of 4.8 years (Jan 2009-Aug 2013). The initial histopathological evaluation of these lesions was performed on H&E stained sections of paraffin embedded tissues. Special stains and immunohistochemistry were performed whenever indicated. Out of 75 cases, 34 (45.3%) were astrocytic tumours, including 16 (47.1%) Pilocytic astrocytomas (WHO Grade-I), 1 (2.9%) diffuse fibrillary astrocytoma (WHO Grade-II), 1 (2.9%) anaplastic astrocytoma (WHO Grade-III) and 16(47.1%) glioblastoma multiforme (WHO Grade-IV); 18 (24%) were embryonal tumours including 17 (94.4%) medulloblastoma (WHO Grade-IV) and 1 (5.6%) neuroblastoma (WHO Grade IV); 10 (13.3%) were craniopharyngiomas (WHO Grade-I) and 5 (6.7%) were ependymal tumours including 1 (20%) myxopapillary ependymoma (WHO Grade-I) and 4 (80%) ependymomas (WHO Grade-II). Miscellaneous entities included 3 (4%) choroid plexus tumours; 1 (2%) anaplastic oligodendroglioma (WHO Grade-III); 1 (2%) atypical meningioma (WHO Grade-II); 1 (2%) schwannoma (WHO Grade-I); 1 (2%) neurofibroma (WHO Grade-I) and 1 (2%) lipoma (WHO Grade-I). Astrocytic tumours are the most common central nervous system tumours in paediatric age group and high grade lesions (WHO Grade-IV) constitute the largest category (45.3%).

  9. [Genetic Syndromes Predisposing to Tumors of Central Nervous System in Children].

    PubMed

    Krutílková, V

    2016-01-01

    The overall incidence of childhood malignancies is rather low. Central nervous system tumours constitute the largest group of solid tumours among children. In contrast to adult population, a genetic predisposition is frequently associated with these malignancies (it is assumed to occur in approximately 15-25% of all childhood tumours) and there is also a number of monogenic hereditary syndromes known to be associated with brain tumours. The purpose of this article is to present an overview of genetic syndromes reported to increase the risk of childhood central nervous system tumours. The outlined tumour predispositions are divided into two groups. Firstly, syndromes with multisystem manifestation, where neoplasia is one of the components, whereas the distinguishing symptom is usually non-oncological. Secondly, there are syndromes that are diagnosed by the associated neoplasm withou any other noticeable phenotypic manifestation. A brief description of particular diseases is provided with a focus on associated central nervous system tumours. Detection of a tumour predisposition in a child is important not only for the child itself, but also for its family relatives. Often, a modification of treatment is necessary in regards to a genetic diagnosis. With the evolution of personalised medicine the possibility of "tailored" therapy will probably be a demanded solution. Last but not least, it is crucial to provide the child with a specialised preventive care owing to the risk of another potential malignancy. The diagnosis of hereditary cancer predisposition has also a big impact on the relatives of the patient. It enables to specify their oncological risk and arrange a specialised preventive care program, if needed. For high-risk parents planning another pregnancy there is a possibility to prevent the transfer of a certain disposition with the aid of preimplantation and prenatal genetic testing.

  10. Bone mineral density in subjects using central nervous system-active medications.

    PubMed

    Kinjo, Mitsuyo; Setoguchi, Soko; Schneeweiss, Sebastian; Solomon, Daniel H

    2005-12-01

    Decreased bone mineral density defines osteoporosis according to the World Health Organization and is an important predictor of future fractures. The use of several types of central nervous system-active drugs, including benzodiazepines, anticonvulsants, antidepressants, and opioids, have all been associated with increased risk of fracture. However, it is unclear whether such an increase in risk is related to an effect of bone mineral density or to other factors, such as increased risk of falls. We sought to examine the relationship between bone mineral density and the use of benzodiazepines, anticonvulsants, antidepressants, and opioids in a representative US population-based sample. We analyzed data on adults aged 17 years and older from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Total femoral bone mineral density of 7114 male and 7532 female participants was measured by dual-energy x-ray absorptiometry. Multivariable linear regression models were used to quantify the relation between central nervous system medication exposure and total femoral bone mineral density. Models controlled for relevant covariates, including age, sex, and body mass index. In linear regression models, significantly reduced bone mineral density was found in subjects taking anticonvulsants (0.92 g/cm2; 95% confidence interval [CI]: 0.89 to 0.94) and opioids (0.92 g/cm2; 95% CI: 0.88 to 0.95) compared with nonusers (0.95 g/cm2; 95% CI: 0.95 to 0.95) after adjusting for several potential confounders. The other central nervous system-active drugs--benzodiazepines or antidepressants--were not associated with significantly reduced bone mineral density. In cross-sectional analysis of NHANES III, anticonvulsants and opioids (but not benzodiazepines or antidepressants) were associated with significantly reduced bone mineral density. These findings have implications for fracture-prevention strategies.

  11. 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

  12. 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.

  13. Central Nervous System Cancers, Version 1.2015.

    PubMed

    Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Baehring, Joachim; Brem, Henry; Brown, Paul; Butowski, Nicholas; Chamberlain, Marc C; Fenstermaker, Robert A; Friedman, Allan; Gilbert, Mark R; Hattangadi-Gluth, Jona; Holdhoff, Matthias; Junck, Larry; Kaley, Thomas; Lawson, Ronald; Loeffler, Jay S; Lovely, Mary P; Moots, Paul L; Mrugala, Maciej M; Newton, Herbert B; Parney, Ian; Raizer, Jeffrey J; Recht, Lawrence; Shonka, Nicole; Shrieve, Dennis C; Sills, Allen K; Swinnen, Lode J; Tran, David; Tran, Nam; Vrionis, Frank D; Weiss, Stephanie; Wen, Patrick Yung; McMillian, Nicole; Engh, Anita M

    2015-10-01

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System (CNS) Cancers provide interdisciplinary recommendations for managing adult CNS cancers. Primary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. These NCCN Guidelines Insights summarize the NCCN CNS Cancers Panel's discussion and highlight notable changes in the 2015 update. This article outlines the data and provides insight into panel decisions regarding adjuvant radiation and chemotherapy treatment options for high-risk newly diagnosed low-grade gliomas and glioblastomas. Additionally, it describes the panel's assessment of new data and the ongoing debate regarding the use of alternating electric field therapy for high-grade gliomas. Copyright © 2015 by the National Comprehensive Cancer Network.

  14. [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.

  15. 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

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

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

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

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

  17. 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…

  18. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.

    PubMed

    Liu, Qiang; Zhang, Juan; Zerbinatti, Celina; Zhan, Yan; Kolber, Benedict J; Herz, Joachim; Muglia, Louis J; Bu, Guojun

    2011-01-11

    Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

  19. 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.

  20. Positional and positioning down-beating nystagmus without central nervous system findings.

    PubMed

    Ogawa, Yasuo; Suzuki, Mamoru; Otsuka, Koji; Shimizu, Shigetaka; Inagaki, Taro; Hayashi, Mami; Hagiwara, Akira; Kitajima, Naoharu

    2009-12-01

    We report the clinical features of 4 cases with positional or positioning down-beating nystagmus in a head-hanging or supine position without any obvious central nervous system disorder. The 4 cases had some findings in common. There were no abnormal findings on neurological tests or brain MRI. They did not have gaze nystagmus. Their nystagmus was observed only in a supine or head-hanging position and it was never observed upon returning to a sitting position and never reversed. The nystagmus had no or little torsional component, had latency and tended to decrease with time. The positional DBN (p-DBN) is known to be indicative of a central nervous system disorder. Recently there were some reports that canalithiasis of the anterior semicircular canal (ASC) causes p-DBN and that patients who have p-DBN without obvious CNS dysfunction are dealt with anterior semicircular canal (ASC) benign paroxysmal positional vertigo (BPPV). There are some doubts as to the validity of making a diagnosis of ASC-BPPV in a case of p-DBN without CNS findings. It is hard to determine the cause of p-DBN in these cases.

  1. Biomaterial Scaffolds in Regenerative Therapy of the Central Nervous System

    PubMed Central

    Tan, Hong

    2018-01-01

    The central nervous system (CNS) is the most important section of the nervous system as it regulates the function of various organs. Injury to the CNS causes impairment of neurological functions in corresponding sites and further leads to long-term patient disability. CNS regeneration is difficult because of its poor response to treatment and, to date, no effective therapies have been found to rectify CNS injuries. Biomaterial scaffolds have been applied with promising results in regeneration medicine. They also show great potential in CNS regeneration for tissue repair and functional recovery. Biomaterial scaffolds are applied in CNS regeneration predominantly as hydrogels and biodegradable scaffolds. They can act as cellular supportive scaffolds to facilitate cell infiltration and proliferation. They can also be combined with cell therapy to repair CNS injury. This review discusses the categories and progression of the biomaterial scaffolds that are applied in CNS regeneration. PMID:29805977

  2. Space radiation risks to the central nervous system

    NASA Astrophysics Data System (ADS)

    Cucinotta, Francis A.; Alp, Murat; Sulzman, Frank M.; Wang, Minli

    2014-07-01

    Central nervous system (CNS) risks which include during space missions and lifetime risks due to space radiation exposure are of concern for long-term exploration missions to Mars or other destinations. Possible CNS risks during a mission are altered cognitive function, including detriments in short-term memory, reduced motor function, and behavioral changes, which may affect performance and human health. The late CNS risks are possible neurological disorders such as premature aging, and Alzheimer's disease (AD) or other dementia. Radiation safety requirements are intended to prevent all clinically significant acute risks. However the definition of clinically significant CNS risks and their dependences on dose, dose-rate and radiation quality is poorly understood at this time. For late CNS effects such as increased risk of AD, the occurrence of the disease is fatal with mean time from diagnosis of early stage AD to death about 8 years. Therefore if AD risk or other late CNS risks from space radiation occur at mission relevant doses, they would naturally be included in the overall acceptable risk of exposure induced death (REID) probability for space missions. Important progress has been made in understanding CNS risks due to space radiation exposure, however in general the doses used in experimental studies have been much higher than the annual galactic cosmic ray (GCR) dose (∼0.1 Gy/y at solar maximum and ∼0.2 Gy/y at solar minimum with less than 50% from HZE particles). In this report we summarize recent space radiobiology studies of CNS effects from particle accelerators simulating space radiation using experimental models, and make a critical assessment of their relevance relative to doses and dose-rates to be incurred on a Mars mission. Prospects for understanding dose, dose-rate and radiation quality dependencies of CNS effects and extrapolation to human risk assessments are described.

  3. Rituximab treatment in primary angiitis of the central nervous system.

    PubMed

    Patel, Shreeya; Ross, Laura; Oon, Shereen; Nikpour, Mandana

    2018-06-01

    Primary angiitis of the central nervous system (PACNS) is a rare autoimmune vasculitis affecting the brain and spinal cord. Treatment with biological agents has revolutionised the treatment of many rheumatic conditions but there is scant literature regarding the use of biological agents in PACNS. We present three cases of PACNS treated with rituximab, including two cases of relapsed disease, and a literature review suggesting a role for rituximab in this condition. © 2018 Royal Australasian College of Physicians.

  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

  5. 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

  6. [Primary lymphoma of the central nervous system: 20 years' experience in a referral hospital].

    PubMed

    Calderón-Garcidueñas, A L; Pacheco-Calleros, J; Castelán-Maldonado, E; Nocedal-Rustrián, F C

    Primary central nervous system lymphomas (PCNSL) are rare neoplasms. AIM. To study the clinical aspects and the immuno-phenotype of all cases of PCNSL in a 20 years lapse in a referral hospital in Northeastern Mexico. From January 1986 to December 2005 all PCNSL histologically confirmed were studied. The primary lymphomas were 1% of malignant central nervous system neoplasms. 21 cases were studied (ages from 9-70 years) with male predominance (2:1). 24% patients had immuno-suppression. The more frequent clinical data were: papilledema (71%), headache (62%), paresis (48%) and seizures (33%). 33% of patients died during the first six months after diagnosis. The T lymphomas were 19% of cases and corresponded to small cell type. PCNSL are still a diagnostic challenge. Multicenter studies are required in order to determine the best treatment protocol.

  7. 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.

  8. 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

  9. Serotonin and central nervous system fatigue: nutritional considerations.

    PubMed

    Davis, J M; Alderson, N L; Welsh, R S

    2000-08-01

    Fatigue from voluntary muscular effort is a complex phenomenon involving the central nervous system (CNS) and muscle. An understanding of the mechanisms within muscle that cause fatigue has led to the development of nutritional strategies to enhance performance. Until recently, little was known about CNS mechanisms of fatigue, even though the inability or unwillingness to generate and maintain central activation of muscle is the most likely explanation of fatigue for most people during normal daily activities. A possible role of nutrition in central fatigue is receiving more attention with the development of theories that provide a clue to its biological mechanisms. The focus is on the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] because of its role in depression, sensory perception, sleepiness, and mood. Nutritional strategies have been designed to alter the metabolism of brain 5-HT by affecting the availability of its amino acid precursor. Increases in brain 5-HT concentration and overall activity have been associated with increased physical and perhaps mental fatigue during endurance exercise. Carbohydrate (CHO) or branched-chain amino acid (BCAA) feedings may attenuate increases in 5-HT and improve performance. However, it is difficult to distinguish between the effects of CHO on the brain and those on the muscles themselves, and most studies involving BCAA show no performance benefits. It appears that important relations exist between brain 5-HT and central fatigue. Good theoretical rationale and data exist to support a beneficial role of CHO and BCAA on brain 5-HT and central fatigue, but the strength of evidence is presently weak.

  10. Central nervous system transplantation benefited by low-level laser irradiation

    NASA Astrophysics Data System (ADS)

    Rochkind, S.; Lubart, Rachel; Wollman, Yoram; Simantov, Rabi; Nissan, Moshe; Barr-Nea, Lilian

    1990-06-01

    Effect of low-level laser irradiation on the central nervous system transplantation is reported. Ernbryonal brain allografts were transplanted into the brain of 20 adult rats and peripheral nerve graft transplanted into the severely injured spinal cord of 16 dogs. The operated wound of 10 rats and 8 dogs were exposed daily for 21 days to lowpower laser irradiation CW HeNe laser (35 mW, 632.8 run, energy density of 30 J/cm2 at each point for rats and 70 J/cm2 at each point for dogs). This study shows that (i) the low-level laser irradiation prevents extensive glial scar formation (a limiting factor in CNS regeneration) between embryonal transplants and host brain; (ii) Dogs made paraplegic by spinal cord injury were able to walk 3-6 months later. Recovery of these dogs was effected by the implantation of a fragment of autologous sciatic nerve at the site of injury and subsequently exposing the dogs to low-level laser irradiation. The effect of laser irradiation on the embryonal nerve cells grown in tissue culture was also observed. We found that low-level laser irradiation induced intensive migration of neurites outward of the aggregates 15-22 The results of the present study and our previous investigations suggest that low-level laser irradiation is a novel tool for treatment of peripheral and central nervous system injuries.

  11. West Nile Virus Infection in the Central Nervous System

    PubMed Central

    Winkelmann, Evandro R.; Luo, Huanle; Wang, Tian

    2016-01-01

    West Nile virus (WNV), a neurotropic single-stranded flavivirus has been the leading cause of arboviral encephalitis worldwide.  Up to 50% of WNV convalescent patients in the United States were reported to have long-term neurological sequelae.  Neither antiviral drugs nor vaccines are available for humans.  Animal models have been used to investigate WNV pathogenesis and host immune response in humans.  In this review, we will discuss recent findings from studies in animal models of WNV infection, and provide new insights on WNV pathogenesis and WNV-induced host immunity in the central nervous system. PMID:26918172

  12. 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.

  13. 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.

  14. Similar chemokine receptor profiles in lymphomas with central nervous system involvement - possible biomarkers for patient selection for central nervous system prophylaxis, a retrospective study.

    PubMed

    Lemma, Siria A; Pasanen, Anna Kaisa; Haapasaari, Kirsi-Maria; Sippola, Antti; Sormunen, Raija; Soini, Ylermi; Jantunen, Esa; Koivunen, Petri; Salokorpi, Niina; Bloigu, Risto; Turpeenniemi-Hujanen, Taina; Kuittinen, Outi

    2016-05-01

    Central nervous system (CNS) relapse occurs in around 5% of diffuse large B-cell lymphoma (DLBCL) cases. No biomarkers to identify high-risk patients have been discovered. We evaluated the expression of lymphocyte-guiding chemokine receptors in systemic and CNS lymphomas. Immunohistochemical staining for CXCR4, CXCR5, CCR7, CXCL12, and CXCL13 was performed on 89 tissue samples, including cases of primary central nervous system lymphoma (PCNSL), secondary CNS lymphoma (sCNSL), and systemic DLBCL. Also, 10 reactive lymph node samples were included. Immunoelectron microscopy was performed on two PCNSLs, one sCNSL, one systemic DLBCL, and one reactive lymph node samples, and staining was performed for CXCR4, CXCR5, CXCL12, and CXCL13. Chi-square test was used to determine correlations between clinical parameters, diagnostic groups, and chemokine receptor expression. Strong nuclear CXCR4 positivity correlated with systemic DLBCL, whereas strong cytoplasmic CXCR5 positivity correlated with CNS involvement (P = 0.003 and P = 0.039). Immunoelectron microscopy revealed a nuclear CXCR4 staining in reactive lymph node, compared with cytoplasmic and membranous localization seen in CNS lymphomas. We found that CNS lymphoma presented a chemokine receptor profile different from systemic disease. Our findings give new information on the CNS tropism of DLBCL and, if confirmed, may contribute to more effective targeting of CNS prophylaxis among patients with DLBCL. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Cannabinoid/opioid crosstalk in the central nervous system.

    PubMed

    Corchero, Javier; Manzanares, Jorge; Fuentes, José A

    2004-01-01

    Promising therapeutic uses and a great variety of pharmacological effects are the leading forces that focus actual cannabinoid research. Cannabinoid and opioid systems share neuroanatomical, neurochemical, and paharmacological features. This fact supports the notion that actions induced by each one of these types of drugs involved an interaction between the endogenous opioid and endocannabinoid neuronal systems. Over the last decade our group and others have investigated cannabinoid/opioid crosstalk in the central nervous system by studying the mechanisms underlying pharmacological and biochemical interactions between the two systems in experimental paradigms of antinociception, drug reinforcement, and anxiety. The goal of this review is to revise the latest work done on this subject, with special emphasis on the research done with genetically modified animals. Whereas clinical progress is going ahead slowly, basic research in this area is progressing rapidly. Clinical applications derived from the cannabinoid/opioid crosstalk and based tightly on medical evidence are yet to come, but it is hoped that knowledge of this central messenger interaction will help to develop new alternatives for the treatment of some pathological states.

  16. 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.

  17. 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.

  18. [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.

  19. 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.

  20. Innate immune responses in central nervous system inflammation.

    PubMed

    Finsen, Bente; Owens, Trevor

    2011-12-01

    In autoimmune diseases of the central nervous system (CNS), innate glial cell responses play a key role in determining the outcome of leukocyte infiltration. Access of leukocytes is controlled via complex interactions with glial components of the blood-brain barrier that include angiotensin II receptors on astrocytes and immunoregulatory mediators such as Type I interferons which regulate cellular traffic. Myeloid cells at the blood-brain barrier present antigen to T cells and influence cytokine effector function. Myelin-specific T cells interact with microglia and promote differentiation of oligodendrocyte precursor cells in response to axonal injury. These innate responses offer potential targets for immunomodulatory therapy. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  1. Localization of rem2 in the central nervous system of the adult rainbow trout (Oncorhynchus mykiss).

    PubMed

    Downs, Anna G; Scholles, Katie R; Hollis, David M

    2016-12-01

    Rem2 is member of the RGK (Rem, Rad, and Gem/Kir) subfamily of the Ras superfamily of GTP binding proteins known to influence Ca 2+ entry into the cell. In addition, Rem2, which is found at high levels in the vertebrate brain, is also implicated in cell proliferation and synapse formation. Though the specific, regional localization of Rem2 in the adult mammalian central nervous system has been well-described, such information is lacking in other vertebrates. Rem2 is involved in neuronal processes where the capacities between adults of different vertebrate classes vary. Thus, we sought to localize the rem2 gene in the central nervous system of an adult anamniotic vertebrate, the rainbow trout (Oncorhynchus mykiss). In situ hybridization using a digoxigenin (DIG)-labeled RNA probe was used to identify the regional distribution of rem2 expression throughout the trout central nervous system, while real-time polymerase chain reaction (rtPCR) further supported these findings. Based on in situ hybridization, the regional distribution of rem2 occurred within each major subdivision of the brain and included large populations of rem2 expressing cells in the dorsal telencephalon of the cerebrum, the internal cellular layer of the olfactory bulb, and the optic tectum of the midbrain. In contrast, no rem2 expressing cells were resolved within the cerebellum. These results were corroborated by rtPCR, where differential rem2 expression occurred between the major subdivisions assayed with the highest levels being found in the cerebrum, while it was nearly absent in the cerebellum. These data indicate that rem2 gene expression is broadly distributed and likely influences diverse functions in the adult fish central nervous system. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. [Primary central nervous system lymphoma mimicking ventriculitis].

    PubMed

    Yamamoto, Shiro; Nagano, Seiji; Shibata, Sumiya; Kunieda, Takeharu; Imai, Yukihiro; Kohara, Nobuo

    2013-01-01

    A 66-year-old man presented with deteriorated bradykinesia, gait disturbance, disorientation, and urinary incontinence for three weeks. Magnetic resonance imaging (MRI) showed dilatation of the ventricles. Cerebrospinal fluid (CSF) examination demonstrated lymphocytic pleocytosis, elevation of protein levels, and decreased of glucose levels. A gadolinium-enhanced MRI revealed lesions in the ventricular wall and choroid plexus, mimicking ventriculitis. No evidence of bacterial, fungal, mycobacterial, or viral infections were observed in the CSF. Flow cytometry of CSF showed predominance of CD20+, λ+ cells. PCR examination of CSF revealed positive IgH gene rearrangement, suggesting B cell lymphoma. Endoscopic brain biopsy showed diffuse large B cell lymphoma. As the patient had no evidence of lymphoma in the other organs, we made a diagnosed of primary central nervous system lymphoma (PCNSL). A limited intraventricular spread of PCNSL is rare but important as one of differential diagnosis of ventriculitis.

  3. [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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.

    PubMed

    Maggi, Pietro; Absinta, Martina; Grammatico, Matteo; Vuolo, Luisa; Emmi, Giacomo; Carlucci, Giovanna; Spagni, Gregorio; Barilaro, Alessandro; Repice, Anna Maria; Emmi, Lorenzo; Prisco, Domenico; Martinelli, Vittorio; Scotti, Roberta; Sadeghi, Niloufar; Perrotta, Gaetano; Sati, Pascal; Dachy, Bernard; Reich, Daniel S; Filippi, Massimo; Massacesi, Luca

    2018-02-01

    In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294. © 2018 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on

  9. 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

  10. Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system.

    PubMed

    Segura-Uribe, Julia J; Pinto-Almazán, Rodolfo; Coyoy-Salgado, Angélica; Fuentes-Venado, Claudia E; Guerra-Araiza, Christian

    2017-08-01

    Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1 (MAP1), MAP2, neurofilament 38 (NF38) by different mechanisms of action and at different levels: neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.

  11. Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system

    PubMed Central

    Segura-Uribe, Julia J.; Pinto-Almazán, Rodolfo; Coyoy-Salgado, Angélica; Fuentes-Venado, Claudia E.; Guerra-Araiza, Christian

    2017-01-01

    Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1 (MAP1), MAP2, neurofilament 38 (NF38) by different mechanisms of action and at different levels: neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects. PMID:28966632

  12. 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.

  13. Magnetic resonance imaging of the central nervous system

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

    Not Available

    1988-02-26

    This report reviews the current applications of magnetic resonance imaging of the central nervous system. Since its introduction into the clinical environment in the early 1980's, this technology has had a major impact on the practice of neurology. It has proved to be superior to computed tomography for imaging many diseases of the brain and spine. In some instances it has clearly replaced computed tomography. It is likely that it will replace myelography for the assessment of cervicomedullary junction and spinal regions. The magnetic field strengths currently used appear to be entirely safe for clinical application in neurology except inmore » patients with cardiac pacemakers or vascular metallic clips. Some shortcomings of magnetic resonance imaging include its expense, the time required for scanning, and poor visualization of cortical bone.« less

  14. Central nervous system toxicity of metallic nanoparticles

    PubMed Central

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

    2015-01-01

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

  15. Advances in Primary Central Nervous System Lymphoma.

    PubMed

    Patrick, Lauren B; Mohile, Nimish A

    2015-12-01

    Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that is limited to the CNS. Although novel imaging techniques aid in discriminating lymphoma from other brain tumors, definitive diagnosis requires brain biopsy, vitreoretinal biopsy, or cerebrospinal fluid analysis. Survival rates in clinical studies have improved over the past 20 years due to the addition of high-dose methotrexate-based chemotherapy regimens to whole-brain radiotherapy. Long-term survival, however, is complicated by clinically devastating delayed neurotoxicity. Newer regimens are attempting to reduce or eliminate radiotherapy from first-line treatment with chemotherapy dose intensification. Significant advances have also been made in the fields of pathobiology and treatment, with more targeted treatments on the horizon. The rarity of the disease makes conducting of prospective clinical trials challenging, requiring collaborative efforts between institutions. This review highlights recent advances in the biology, detection, and treatment of PCNSL in immunocompetent patients.

  16. Primary Central Nervous System Fibrosarcoma.

    PubMed

    Vinodh, V P; Harun, Rahmat; Sellamuthu, Pulivendhan; Kandasamy, Regunath

    2017-08-01

    We report a rare case of a young female with primary brain fibrosarcoma, and to the best of our knowledge, we believe that only <50 cases have been reported or described worldwide so far. Fibrosarcoma is a malignant neoplasm, in which histologically the predominant cells are fibroblasts that divide excessively without cellular control and they can invade local tissues or metastasize. Primary central nervous system fibrosarcomas are very aggressive neoplasms and generally have a poor prognosis. This tumor is either from sarcomatous transformation of a meningioma or arises de novo within the brain parenchyma. Our patient, a 48-year-old woman, who presented with progressive speech disorder over the period of 4 months, showed a left temporoparietal lesion with surrounding edema and local mass effect. Total surgical resection was achieved. Histopathology revealed classical fibrosarcoma features and secondary screening revealed no other distant lesion as diagnosis of primary brain fibrosarcoma was established. This case is deemed to be extremely rare because most reports claim that recurrence is within 6 months with poor prognosis; however, this patient is currently recurrence-free at 3 years. This would suggest of the possibility for a relook into this disease's course and recurrence rate when complete excision is achieved. Due to extreme rarity of these tumors, more comparative studies will be needed to improve the disease outcome.

  17. Rejuvenation of antioxidant system in central nervous system of aged rats by grape seed extract.

    PubMed

    Balu, Muthaiya; Sangeetha, Purushotham; Haripriya, Dayalan; Panneerselvam, Chinnakannu

    2005-08-05

    Oxidative stress is considered as a major risk factor that contributes to age-related increase in lipid peroxidation and declined antioxidants in the central nervous system during aging. Grape seed extract, one of the bioflavonoid, is widely used for its medicinal properties. In the present study, we evaluated the role of grape seed extract on lipid peroxidation and antioxidant status in discrete regions of the central nervous system of young and aged rats. Male albino rats of Wistar strain were divided into four groups: Group I-control young rats, Group II-young rats treated with grape seed extract (100 mg/kg body weight) for 30 days, Group III-aged control rats and Group IV-aged rats supplemented with grape seed extract (100 mg/kg body weight) for 30 days. Age-associated increase in lipid peroxidation was observed in the spinal cord, cerebral cortex, striatum and the hippocampus regions of aged rats (Group III). Activities of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and levels of non-enzymic antioxidants like reduced glutathione, Vitamin C and Vitamin E were found to be significantly decreased in all the brain regions studied in aged rats when compared to young rats. However, normalized lipid peroxidation and antioxidant defenses were reported in the grape seed extract-supplemented aged rats. These findings demonstrated that grape seed extract enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation in the central nervous system of aged rats.

  18. Evaluation of central nervous system in patients with glycogen storage disease type 1a.

    PubMed

    Aydemir, Yusuf; Gürakan, Figen; Saltık Temizel, İnci Nur; Demir, Hülya; Oğuz, Kader Karlı; Yalnızoğlu, Dilek; Topçu, Meral; Özen, Hasan; Yüce, Aysel

    2016-01-01

    We aimed to evaluate structure and functions of central nervous system (CNS) in children with glycogen storage disease (GSD) type 1a. Neurological examination, psychometric tests, electroencephalography (EEG), magnetic resonance imaging (MRI), visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) were performed. The results were compared between patients with good and poor metabolic control and healthy children. Twenty-three patients with GSD type 1a were studied. Twelve patients were in poor metabolic control group and 11 patients in good metabolic control group. Five patients had intellectual disability, 10 had EEG abnormalities, seven had abnormal VEP and two had abnormal BAEP results. MRI was abnormal in five patients. There was significant correlation between the number of hypoglycemic attacks and MRI abnormalities. Central nervous system may be affected in GSD type 1a even in patients with normal neurologic examination. Accumulation of abnormal results in patients with poor metabolic control supports the importance of metabolic control in GSD type 1a.

  19. Metronidazole-induced central nervous system toxicity: a systematic review.

    PubMed

    Kuriyama, Akira; Jackson, Jeffrey L; Doi, Asako; Kamiya, Toru

    2011-01-01

    To assess patient and medication factors that contribute to metronidazole toxicity. We searched PUBMED from 1965 through April 7, 2011, and performed a hand search of bibliographies. Case reports or case series reporting metronidazole-induced central nervous toxicity. Two authors independently abstracted demographics, metronidazole indication, dose and duration, neurological manifestations, and outcomes as well as brain imaging findings. Among 64 patients, 48 (77%) had cerebellar dysfunction, 21 (33%) had altered mental status, and 8 (15%) had seizures. Patients' ages averaged 53.3 years (range, 12-87 years), and 64% were male. The median duration of metronidazole was 54 days, although 26% had taken it less than a week and 11% had taken it less than 72 hours. Among cases with outcome data, most patients either improved (n = 18 [29%]) or had complete resolution of their symptoms with discontinuation of metronidazole (n = 41 [65%]). There was no difference in resolution of symptom by age (P = 0.71) or sex (P = 0.34). The patients with cerebellar dysfunction were less likely to experience complete resolution than those with mental status changes or seizures (relative risk, 0.67; 95% confidence interval (CI), 0.49-0.92). Nearly all patients (n = 55 [86%]) underwent imaging of the brain: 44 (69%) underwent magnetic resonance imaging (MRI) and 12 (19%) underwent computed tomographic studies. All patients with cerebellar dysfunction had abnormalities on imaging: 93% (n = 39) had a cerebellar lesion, although numerous areas in the brain were affected. On follow-up MRIs, 25 patients (83%) had complete resolution of abnormalities. Metronidazole can rarely cause central nervous system toxicity; it does not seem to be a dose- or duration-related phenomenon. Most patients will have MRI abnormalities. Prognosis is excellent with metronidazole cessation.

  20. 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.

  1. 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

  2. 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

  3. Central nervous system filariasis masquerading as a glioma: case report.

    PubMed

    Shrivastava, Adesh; Arora, Prateek; Khare, Akriti; Goel, Garima; Kapoor, Neelkamal

    2017-09-01

    Filariasis, an endemic zoonosis in the Southeast Asia region, has been reported to affect various organs as well as the central nervous system (CNS). Inflammatory reactions mimicking those from neoplastic lesions clinically and radiologically have been reported in the breast and urinary bladder. To date, a CNS manifestation of filarial infestation has been reported in the form of meningoencephalitis. The authors here present an interesting case of a young man presenting in status epilepticus, which on radiological evaluation appeared to be a glioma. However, postoperative histopathological examination changed the provisional diagnosis to a filarial infection of the CNS mimicking a primary CNS neoplasm.

  4. Concordance of Time-of-Flight MRA and Digital Subtraction Angiography in Adult Primary Central Nervous System Vasculitis.

    PubMed

    de Boysson, H; Boulouis, G; Parienti, J-J; Touzé, E; Zuber, M; Arquizan, C; Dequatre, N; Detante, O; Bienvenu, B; Aouba, A; Guillevin, L; Pagnoux, C; Naggara, O

    2017-10-01

    3D-TOF-MRA and DSA are 2 available tools to demonstrate neurovascular involvement in primary central nervous system vasculitis. We aimed to compare the diagnostic concordance of vessel imaging using 3D-TOF-MRA and DSA in patients with primary central nervous system vasculitis. We retrospectively identified all patients included in the French primary central nervous system vasculitis cohort of 85 patients who underwent, at baseline, both intracranial 3D-TOF-MRA and DSA in an interval of no more than 2 weeks and before treatment initiation. Two neuroradiologists independently reviewed all 3D-TOF-MRA and DSA imaging. Brain vasculature was divided into 25 arterial segments. Concordance between 3D-TOF-MRA and DSA for the identification of arterial stenosis was assessed by the Cohen κ Index. Thirty-one patients met the inclusion criteria, including 20 imaged with a 1.5T MR unit and 11 with a 3T MR unit. Among the 25 patients (81%) with abnormal DSA findings, 24 demonstrated abnormal 3D-TOF-MRA findings, whereas all 6 remaining patients with normal DSA findings had normal 3D-TOF-MRA findings. In the per-segment analysis, concordance between 1.5T 3D-TOF-MRA and DSA was 0.82 (95% CI, 0.75-0.93), and between 3T 3D-TOF-MRA and DSA, it was 0.87 (95% CI, 0.78-0.91). 3D-TOF-MRA shows a high concordance with DSA in diagnostic performance when analyzing brain vasculature in patients with primary central nervous system vasculitis. In patients with negative 3T 3D-TOF-MRA findings, the added diagnostic value of DSA is limited. © 2017 by American Journal of Neuroradiology.

  5. 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.

  6. Responses to increasing exercise upon reaching the anaerobic threshold, and their control by the central nervous system.

    PubMed

    Peinado, Ana B; Rojo, Jesús J; Calderón, Francisco J; Maffulli, Nicola

    2014-01-01

    The anaerobic threshold (AT) has been one of the most studied of all physiological variables. Many authors have proposed the use of several markers to determine the moment at with the AT is reached. The present work discusses the physiological responses made to exercise - the measurement of which indicates the point at which the AT is reached - and how these responses might be controlled by the central nervous system. The detection of the AT having been reached is a sign for the central nervous system (CNS) to respond via an increase in efferent activity via the peripheral nervous system (PNS). An increase in CNS and PNS activities are related to changes in ventilation, cardiovascular function, and gland and muscle function. The directing action of the central command (CC) allows for the coordination of the autonomous and motor systems, suggesting that the AT can be identified in the many ways: changes in lactate, ventilation, plasma catecholamines, heart rate (HR), salivary amylase and muscular electrical activity. This change in response could be indicative that the organism would face failure if the exercise load continued to increase. To avoid this, the CC manages the efferent signals that show the organism that it is running out of homeostatic potential.

  7. Responses to increasing exercise upon reaching the anaerobic threshold, and their control by the central nervous system

    PubMed Central

    2014-01-01

    The anaerobic threshold (AT) has been one of the most studied of all physiological variables. Many authors have proposed the use of several markers to determine the moment at with the AT is reached. The present work discusses the physiological responses made to exercise - the measurement of which indicates the point at which the AT is reached - and how these responses might be controlled by the central nervous system. The detection of the AT having been reached is a sign for the central nervous system (CNS) to respond via an increase in efferent activity via the peripheral nervous system (PNS). An increase in CNS and PNS activities are related to changes in ventilation, cardiovascular function, and gland and muscle function. The directing action of the central command (CC) allows for the coordination of the autonomous and motor systems, suggesting that the AT can be identified in the many ways: changes in lactate, ventilation, plasma catecholamines, heart rate (HR), salivary amylase and muscular electrical activity. This change in response could be indicative that the organism would face failure if the exercise load continued to increase. To avoid this, the CC manages the efferent signals that show the organism that it is running out of homeostatic potential. PMID:24818009

  8. 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.

  9. Acid-$beta$-glycerophosphatase reaction products in the central nervous system mitochondria following x-ray irradiation

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

    Roizin, L.; Orlovskaja, D.; Liu, J.C.

    A survey of the literature to date on the enzyme histochemistry of intracellular organelles has not yielded any reference to the presence of acid phosphatase reaction products in the mammalian mitochondria of the central nervous system. A combination of Gomori's acid phosphatase method, however, with standard electron microscopy has disclosed the presence of enzyme reaction products in the mitochondria of the central nervous system of rats from 2 hr to 22 weeks after x-ray irradiation, as well as in a cerebral biopsy performed on a patient affected by Huntington's chorea. No enzyme reaction products, on the other hand, were observedmore » in serial sections that had been incubated in substrates either containing sodium fluoride or lacking in $beta$- glycerophosphate. The abnormal mitochondrial enzyme reaction (chemical lesion) is considered to be the consequence of the pathologic process affecting the ultrastructural-chemical organization of the organelle. (auth)« less

  10. 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.

  11. 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

  12. 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.

  13. 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…

  14. Hemangiopericytoma in the central nervous system. A study of eight cases.

    PubMed

    Mekni, A; Kourda, J; Chelly, I; Ferchichi, L; Bellil, K; Hammouda, K B; Kchir, N; Zitouna, M; Khaldi, M; Haouet, S

    2008-02-01

    Most hemangiopericytomas (HPC) are located in the musculoskeletal system and the skin, while the location in the central nervous system (CNS) is rare. The latter represents 2 to 4% in large series of meningeal tumors, thus accounting for less than 1% of all CNS tumors. In the central nervous system, tumors with a hemangiopericytomatous histolopathological pattern can be either hemangiopericytomas or solitary fibrous tumors. CNS-HPCs have a relentless tendency for local recurrence and metastases outside the CNS. Metastasis can also appear many years after adequate treatment of the primary tumor. We present a pathological study of eight patients with CNS-HPC and compare our results with corresponding published data. The CNS-HPC group consisted of three males and five females with a mean age of 36.75 years. The tumors were supratentorial in four cases, infratentorial in two cases, tentorial in one case and located in the spinal cord in the last one. Histologically, CNS-HPCs were similar to their soft tissue counterparts. One case demonstrated increased cellularity, marked nuclear hyperchromasia and marked cellular pleomorphism with infiltration of the cerebellum. All patients underwent surgery with gross-total resection in all cases. No patients received postoperative radiation therapy. Only four patients recurred locally after six, seven and eight months, and five years. Our study presents the pathological features of CNS-HPC as a distinct entity from both meningioma and solitary fibrous tumors. A comparative review of literature with our results is discussed.

  15. Misdiagnosis of acute peripheral vestibulopathy in central nervous ischemic infarction.

    PubMed

    Braun, Eva Maria; Tomazic, Peter Valentin; Ropposch, Thorsten; Nemetz, Ulrike; Lackner, Andreas; Walch, Christian

    2011-12-01

    Vertigo is a very common symptom at otorhinolaryngology (ENT), neurological, and emergency units, but often, it is difficult to distinguish between vertigo of peripheral and central origin. We conducted a retrospective analysis of a hospital database, including all patients admitted to the ENT University Hospital Graz after neurological examination, with a diagnosis of peripheral vestibular vertigo and subsequent diagnosis of central nervous infarction as the actual cause for the vertigo. Twelve patients were included in this study. All patients with acute spinning vertigo after a thorough neurological examination and with uneventful computed tomographic scans were referred to our ENT department. Nine of them presented with horizontal nystagmus. Only 1 woman experienced additional hearing loss. The mean diagnostic delay to the definite diagnosis of a central infarction through magnetic resonance imaging was 4 days (SD, 2.3 d). A careful otologic and neurological examination, including the head impulse test and caloric testing, is mandatory. Because ischemic events cannot be diagnosed in computed tomographic scans at an early stage, we strongly recommend to perform cranial magnetic resonance imaging within 48 hours from admission if vertigo has not improved under conservative treatment.

  16. 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.

  17. 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.

  18. Toxocariasis of the central nervous system: With report of two cases.

    PubMed

    Abir, Bouthouri; Malek, Mansour; Ridha, Mrissa

    2017-03-01

    Toxocariasis is a parasitic infection caused by the roundworms Toxocara canis or Toxocara cati, mostly due to accidental ingestion of embryonated eggs. Clinical manifestations vary and are classified according to the organs affected. Central nervous system involvement is an unusual complication. Here, we report two cases with neurological manifestations, in which there was cerebrospinal fluid (CSF) eosinophilia with marked blood eosinophilia and a positive serology for Toxocara both in serum and CSF. Improvement of signs and symptoms after specific treatment was observed in the two cases. Copyright © 2017. Published by Elsevier B.V.

  19. Strychnine Binding Associated with Glycine Receptors of the Central Nervous System

    PubMed Central

    Young, Anne B.; Snyder, Solomon H.

    1973-01-01

    [3H]Strychnine binds to synaptic-membrane fractions of the spinal cord in a selective fashion, indicating an interaction with postsynaptic glycine receptors. Displacement of strychnine by glycine and other amino acids parallels their glycine-like neurophysiologic activity. The regional localization of strychnine binding in the central nervous system correlates closely with endogenous glycine concentrations. In subcellular fractionation experiments, strychnine binding is most enhanced in synaptic-membrane fractions. Strychnine binding is saturable, with affinity constants for glycine and strychnine of 10 and 0.03 μM, respectively. PMID:4200724

  20. Evaluation of small molecule tuberculostats for targeting tuberculosis infections of the central nervous system.

    PubMed

    Bartzatt, Ronald

    2012-03-01

    Tuberculosis infection of the central nervous system is a serious and frequently fatal disease. Four drugs have been found to very efficiently inhibit the growth of Mycobacterium tuberculosis and are examined for molecular properties that enable penetration of the blood-brain barrier. Drugs 1, 2, and 3 are aromatic compounds having a single bromine atom in ortho, meta, and para-position, respectively, relative to the hydrazide group (-C(O)NHNH2). A paraposition for bromine enabled the strongest inhibition of Mycobacterium tuberculosis. Drug 4 is a hydrazide derivative of ciprofloxacin. All drugs showed molecular properties suitable for targeting tuberculosis infections of the central nervous system. Drugs 1, 2, 3, 4, and isoniazid showed zero violations of the Rule of 5 and potential capability for oral administration. Values of BB (Cbrain/Cblood) suggested that drugs 1, 2, and 3 will be able to penetrate the brain approximately three times greater than isoniazid. Similarly, the calculated value of BB for drug 4 is comparable to that of isoniazid. Calculated values of polar surface area for drugs 1, 2, 3, and isoniazid indicated a potential rate of intestinal absorption of greater than 75% of drug amount present. The intestinal absorption of drug 4 is predicted to be greater than 50% of total amount present. Drug concentrations necessary for achieving MIC50 for 1, 2, 3, 4, and isoniazid are determined to be 65.9 μg/mL, 29.5 μg/mL, 21.5 μg/mL, 36.4 μg/mL, and 16.7 μg/mL, respectively. The position of the bromine atom within drugs 1, 2, and 3 appears to substantially influence the effectiveness of growth inhibition. These compounds show substantial potential for targeting tuberculosis infections within the central nervous system.

  1. Leishmania amastigotes in the central nervous system of a naturally infected dog.

    PubMed

    Márquez, Merce; Pedregosa, José Raúl; López, Jesús; Marco-Salazar, Paola; Fondevila, Dolors; Pumarola, Martí

    2013-01-01

    A 4-year-old male Labrador Retriever dog was presented with a 10-day history of tetraplegia, depression, and absent postural reflexes. The cerebrospinal fluid was positive for Leishmania spp. DNA. At necropsy, a 2-cm long mass was observed adhered to C(7) and C(8) left spinal nerves. Microscopically, nerve fiber destruction together with mixed inflammatory infiltration was observed in the spinal nerves. Cervical spinal cord sections showed multifocal, diffuse granulomatous inflammation in the white matter. In the brain, perivascular infiltrates were observed in some areas together with subtle pallor of the parenchyma. Immunohistochemistry for Leishmania infantum confirmed the presence of amastigotes in the spinal nerves, spinal cord, brain parenchyma, and choroid plexuses. The current study describes the presence of Leishmania amastigotes in nervous tissue inciting radiculoneuritis, myelitis, and mild meningoencephalitis, suggesting a likely route by which L. infantum amastigotes reach and affect the central nervous system parenchyma.

  2. 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.

  3. Predicting Adaptive Behavior in the Environment from Central Nervous System Dynamics

    PubMed Central

    Proekt, Alex; Wong, Jane; Zhurov, Yuriy; Kozlova, Nataliya; Weiss, Klaudiusz R.; Brezina, Vladimir

    2008-01-01

    To generate adaptive behavior, the nervous system is coupled to the environment. The coupling constrains the dynamical properties that the nervous system and the environment must have relative to each other if adaptive behavior is to be produced. In previous computational studies, such constraints have been used to evolve controllers or artificial agents to perform a behavioral task in a given environment. Often, however, we already know the controller, the real nervous system, and its dynamics. Here we propose that the constraints can also be used to solve the inverse problem—to predict from the dynamics of the nervous system the environment to which they are adapted, and so reconstruct the production of the adaptive behavior by the entire coupled system. We illustrate how this can be done in the feeding system of the sea slug Aplysia. At the core of this system is a central pattern generator (CPG) that, with dynamics on both fast and slow time scales, integrates incoming sensory stimuli to produce ingestive and egestive motor programs. We run models embodying these CPG dynamics—in effect, autonomous Aplysia agents—in various feeding environments and analyze the performance of the entire system in a realistic feeding task. We find that the dynamics of the system are tuned for optimal performance in a narrow range of environments that correspond well to those that Aplysia encounter in the wild. In these environments, the slow CPG dynamics implement efficient ingestion of edible seaweed strips with minimal sensory information about them. The fast dynamics then implement a switch to a different behavioral mode in which the system ignores the sensory information completely and follows an internal “goal,” emergent from the dynamics, to egest again a strip that proves to be inedible. Key predictions of this reconstruction are confirmed in real feeding animals. PMID:18989362

  4. [Effect of angiotensin II depot administration on bioelectric functional processes of the central nervous system].

    PubMed

    Martin, G; Baumann, H; Grieger, F

    1976-01-01

    Using the average evoked potential technique, angiotensin-II depot effects (1 mg implantate = 3--4 mg/kg body weight angiotensin-II) were studied neuroelectrophysiologically in reticular, hippocampal and neocrotical structures of albino rats. A multivariate variance and discriminance analysis program revealed differentiated changes of the bioelectrical processing data of the CNS. Evidence was obtained for a varying structural sensitivity of central-nervous substructures under depot administration of angiotensin-II. In later phases of angiotensin-II action, the hippocampus was characterized by an electrographic synchronization phenomenon with high-amplitude average evoked potentials. The reticular formation, and to a lesser extent the visual cortex, showed an angiotensin-induced diminution of bioelectrical excitation. However, the intensity of the change in functional CNS patterns did not always correlate with maximal blood pressure rises. The described changes of afference processing to standardized sensory stimuli, especially in hippocampal and reticular structures of the CNS foll owing angiotensin depot action, point to a central-nervous action mechanism of angiotensin-II.

  5. Pericyte function in the physiological central nervous system.

    PubMed

    Muramatsu, Rieko; Yamashita, Toshihide

    2014-01-01

    Damage to the central nervous system (CNS) leads to disruption of the vascular network, causing vascular dysfunction. Vascular dysfunction is the major event in the pathogenesis of CNS diseases and is closely associated with the severity of neuronal dysfunction. The suppression of vascular dysfunction has been considered a promising avenue to limit damage to the CNS, leading to efforts to clarify the cellular and molecular basis of vascular homeostasis maintenance. A reduction of trophic support and oxygen delivery due to circulatory insufficiency has long been regarded as a major cause of vascular damage. Moreover, recent studies provide a new perspective on the importance of the structural stability of blood vessels in CNS diseases. This updated article discusses emerging information on the key role of vascular integrity in CNS diseases, specially focusing on pericyte function. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  6. [The blood-brain barrier and drug delivery in the central nervous system].

    PubMed

    Loch-Neckel, Gecioni; Koepp, Janice

    2010-08-01

    To provide an updated view of the difficulties due to barriers and strategies used to allow the release of drugs in the central nervous system. The difficulty for the treatment of many diseases of the central nervous system, through the use of intra-venous drugs, is due to the presence of barriers that prevent the release of the same: the blood-brain barrier, blood-cerebro-spinal fluid barrier and the blood-arachnoid barrier. The blood-brain barrier is the main barrier for the transport of drugs in the brain that also acts as a immunologic and metabolic barrier. The endothelial cells of the blood-brain barrier are connected to a junction complex through the interaction of transmembrane proteins that protrude from de inside to the outside, forming a connection between the endothelial cells. The transport of substances to the brain depends on the mechanisms of transport present in the barrier and the diffusion of these compounds also depends on the physicochemical characteristics of the molecule. Some diseases alter the permeability of the blood-brain barrier and thus the passage of drugs. Strategies such as the use of methods for drug delivery in the brain have been investigated. Further details regarding the mechanisms of transport across the blood-brain barrier and the changes in neuropathology would provide important information about the etiology of diseases and lead to better therapeutic strategies.

  7. 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

  8. Aldosterone acting through the central nervous system sensitizes angiotensin II-induced hypertension.

    PubMed

    Xue, Baojian; Zhang, Zhongming; Roncari, Camila F; Guo, Fang; Johnson, Alan Kim

    2012-10-01

    Previous studies have shown that preconditioning rats with a nonpressor dose of angiotensin II (Ang II) sensitizes the pressor response produced by later treatment with a higher dose of Ang II and that Ang II and aldosterone (Aldo) can modulate each other's pressor effects through actions involving the central nervous system. The current studies tested whether Aldo can cross-sensitize the pressor actions of Ang II to enhance hypertension by employing an induction-delay-expression experimental design. Male rats were implanted for telemetered blood pressure recording. During induction, subpressor doses of either subcutaneous or intracerebroventricular Aldo were delivered for 1 week. Rats were then rested for 1 week (delay) to assure that any exogenous Aldo was metabolized. After this, Ang II was given subcutaneously for 2 weeks (expression). During induction and delay, Aldo had no sustained effect on blood pressure. However, during expression, Ang II-induced hypertension was greater in the groups receiving subcutaneous or intracerebroventricular Aldo during induction in comparison with those groups receiving vehicle. Central administration of mineralocorticoid receptor antagonist blocked sensitization. Brain tissue collected at the end of delay and expression showed increased mRNA expression of several renin-angiotensin-aldosterone system components in cardiovascular-related forebrain regions of cross-sensitized rats. Cultured subfornical organ neurons preincubated with Aldo displayed greater increases in [Ca2+]i after Ang II treatment, and there was a greater Fra-like immunoreactivity present at the end of expression in cardiovascular-related forebrain structures. Taken together, these results indicate that Aldo pretreatment cross-sensitizes the development of Ang II-induced hypertension probably by mechanisms that involve the central nervous system.

  9. Spatiotemporal processing of linear acceleration: primary afferent and central vestibular neuron responses

    NASA Technical Reports Server (NTRS)

    Angelaki, D. E.; Dickman, J. D.

    2000-01-01

    Spatiotemporal convergence and two-dimensional (2-D) neural tuning have been proposed as a major neural mechanism in the signal processing of linear acceleration. To examine this hypothesis, we studied the firing properties of primary otolith afferents and central otolith neurons that respond exclusively to horizontal linear accelerations of the head (0.16-10 Hz) in alert rhesus monkeys. Unlike primary afferents, the majority of central otolith neurons exhibited 2-D spatial tuning to linear acceleration. As a result, central otolith dynamics vary as a function of movement direction. During movement along the maximum sensitivity direction, the dynamics of all central otolith neurons differed significantly from those observed for the primary afferent population. Specifically at low frequencies (central otolith neurons peaked in phase with linear velocity, in contrast to primary afferents that peaked in phase with linear acceleration. At least three different groups of central response dynamics were described according to the properties observed for motion along the maximum sensitivity direction. "High-pass" neurons exhibited increasing gains and phase values as a function of frequency. "Flat" neurons were characterized by relatively flat gains and constant phase lags (approximately 20-55 degrees ). A few neurons ("low-pass") were characterized by decreasing gain and phase as a function of frequency. The response dynamics of central otolith neurons suggest that the approximately 90 degrees phase lags observed at low frequencies are not the result of a neural integration but rather the effect of nonminimum phase behavior, which could arise at least partly through spatiotemporal convergence. Neither afferent nor central otolith neurons discriminated between gravitational and inertial components of linear acceleration. Thus response sensitivity was indistinguishable during 0.5-Hz pitch oscillations and fore-aft movements

  10. Central nervous system leukemia in a patient with concurrent nasopharyngeal carcinoma and acute myeloid leukaemia: A case report.

    PubMed

    Liu, Jun-Qing; Mai, Wen-Yuan; Wang, Si-Ben; Lou, Yin-Jun; Yan, Sen-Xiang; Jin, Jie; Xu, Wei-Lai

    2017-12-01

    Concurrent case of nasopharyngeal carcinoma (NPC) and acute myeloid leukemia (AML) has not been reported. Here, we report a case of NPC, who was concurrently suffered from AML one mother after the NPC diagnosis. The patient was a 45-year-old male who presented with a mass on his right side neck. The patient was diagnosed with Epstein-Barr virus negative type-2 non-keratinizing carcinoma with clivus involvement and unilateral metastasis to the cervical lymph node. He was treated with one cycle of cisplatin and 69.76 Gy of concurrent external-beam radiation. Three months after completion of chemo-radiotherapy, the patient was diagnosed as acute myeloid leukemia, which achieved complete remission after one course induction chemotherapy. Two months later, however, the patient was diagnosed as central nervous system leukemia. He ultimately died of relapsed leukemia. The overall survival of the patient was 10 months. The co-occurrence of NPC and AML is rare and prognosis is poor. Radiotherapy in NPC can disrupt the blood-brain barrier, which may contribute to the pathogenesis of central nervous system leukemia. Early alert and prevention of central nervous system leukemia following radiotherapy in NPC patient is recommended. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  11. Mosaic serine proteases in the mammalian central nervous system.

    PubMed

    Mitsui, Shinichi; Watanabe, Yoshihisa; Yamaguchi, Tatsuyuki; Yamaguchi, Nozomi

    2008-01-01

    We review the structure and function of three kinds of mosaic serine proteases expressed in the mammalian central nervous system (CNS). Mosaic serine proteases have several domains in the proenzyme fragment, which modulate proteolytic function, and a protease domain at the C-terminus. Spinesin/TMPRSS5 is a transmembrane serine protease whose presynaptic distribution on motor neurons in the spinal cord suggests that it is significant for neuronal plasticity. Cell type-specific alternative splicing gives this protease diverse functions by modulating its intracellular localization. Motopsin/PRSS12 is a mosaic protease, and loss of its function causes mental retardation. Recent reports indicate the significance of this protease for cognitive function. We mention the fibrinolytic protease, tissue plasminogen activator (tPA), which has physiological and pathological functions in the CNS.

  12. 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.

  13. Focused Ultrasound Immunotherapy for Central Nervous System Pathologies: Challenges and Opportunities

    PubMed Central

    Curley, Colleen T.; Sheybani, Natasha D.; Bullock, Timothy N.; Price, Richard J.

    2017-01-01

    Immunotherapy is rapidly emerging as the cornerstone for the treatment of several forms of metastatic cancer, as well as for a host of other pathologies. Meanwhile, several new high-profile studies have uncovered remarkable linkages between the central nervous and immune systems. With these recent developments, harnessing the immune system for the treatment of brain pathologies is a promising strategy. Here, we contend that MR image-guided focused ultrasound (FUS) represents a noninvasive approach that will allow for favorable therapeutic immunomodulation in the setting of the central nervous system. One obstacle to effective immunotherapeutic drug delivery to the brain is the blood brain barrier (BBB), which refers to the specialized structure of brain capillaries that prevents transport of most therapeutics from the blood into brain tissue. When applied in the presence of circulating microbubbles, FUS can safely and transiently open the BBB to facilitate the delivery of immunotherapeutic agents into the brain parenchyma. Furthermore, it has been demonstrated that physical perturbations of the tissue microenvironment via FUS can modulate immune response in both normal and diseased tissue. In this review article, we provide an overview of FUS energy regimens and corresponding tissue bioeffects, followed by a review of the literature pertaining to FUS for therapeutic antibody delivery in normal brain and preclinical models of brain disease. We provide an overview of studies that demonstrate FUS-mediated immune modulation in both the brain and peripheral settings. Finally, we provide remarks on challenges facing FUS immunotherapy and opportunities for future expansion in this area. PMID:29109764

  14. 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)…

  15. 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.

  16. [Neural pathway of Powassan virus spread in the central nervous system of white mice].

    PubMed

    Sobolev, S G; Shestopalova, N M

    1978-01-01

    Electron microscopic investigation of the brains and lumbar spinal cords of adult albino mice infected with Powassan virus was carried out. Virus particles were found within all parts of neurons (perikarya, dendrites, axon), as well as within synaptic apparatus and intercellular gaps of the central nervous tissue. The possibility of the virus spread both throughout the cytoplasm of nerve cells and their processes and the extracellular spaces of the brain was confirmed. Localization of virions within neurons, synapses and myelinated fibers of the spinal cord after intracerebral inoculation suggests that virus spread in the CNS can occur through the CNS parenchyma and also through the nervous conduction pathways. The possible mechanisms of virus dissemination in the CNS of albino mice with experimental Powassan virus encephalomyelitis are discussed.

  17. Beneficial Effects of X-Irradiation on Recovery of lesioned Mammalian Central Nervous Tissue

    NASA Astrophysics Data System (ADS)

    Kalderon, Nurit; Alfieri, Alan A.; Fuks, Zvi

    1990-12-01

    We examined the potential of x-irradiation, at clinical dose levels, to manipulate the cellular constituents and thereby change the consequences of transection injury to adult mammalian central nervous tissue (rat olfactory bulb). Irradiation resulted in reduction or elimination of reactive astrocytes at the site of incision provided that it was delivered within a defined time window postinjury. Under conditions optimal for the elimination of gliosis (15-18 days postinjury), irradiation of severed olfactory bulbs averted some of the degenerative consequences of lesion. We observed that irradiation was accompanied by prevention of tissue degeneration around the site of lesion, structural healing with maintenance of the typical cell lamination, and rescue of some axotomized mitral cells (principal bulb neurons). Thus radiation resulted in partial preservation of normal tissue morphology. It is postulated that intrusive cell populations are generated in response to injury and reactive astrocytes are one such group. Our results suggest that selective elimination of these cells by irradiation enabled some of the regenerative processes that are necessary for full recovery to maintain their courses. The cellular targets of these cells, their modes of intervention in recovery, and the potential role of irradiation as a therapeutic modality for injured central nervous system are discussed.

  18. Mosaic expression of Atrx in the mouse central nervous system causes memory deficits

    PubMed Central

    Tamming, Renee J.; Siu, Jennifer R.; Jiang, Yan; Prado, Marco A. M.; Beier, Frank

    2017-01-01

    ABSTRACT The rapid modulation of chromatin organization is thought to play a crucial role in cognitive processes such as memory consolidation. This is supported in part by the dysregulation of many chromatin-remodelling proteins in neurodevelopmental and psychiatric disorders. A key example is ATRX, an X-linked gene commonly mutated in individuals with syndromic and nonsyndromic intellectual disability. The consequences of Atrx inactivation for learning and memory have been difficult to evaluate because of the early lethality of hemizygous-null animals. In this study, we evaluated the outcome of brain-specific Atrx deletion in heterozygous female mice. These mice exhibit a mosaic pattern of ATRX protein expression in the central nervous system attributable to the location of the gene on the X chromosome. Although the hemizygous male mice die soon after birth, heterozygous females survive to adulthood. Body growth is stunted in these animals, and they have low circulating concentrations of insulin growth factor 1. In addition, they are impaired in spatial, contextual fear and novel object recognition memory. Our findings demonstrate that mosaic loss of ATRX expression in the central nervous system leads to endocrine defects and decreased body size and has a negative impact on learning and memory. PMID:28093507

  19. Mosaic expression of Atrx in the mouse central nervous system causes memory deficits.

    PubMed

    Tamming, Renee J; Siu, Jennifer R; Jiang, Yan; Prado, Marco A M; Beier, Frank; Bérubé, Nathalie G

    2017-02-01

    The rapid modulation of chromatin organization is thought to play a crucial role in cognitive processes such as memory consolidation. This is supported in part by the dysregulation of many chromatin-remodelling proteins in neurodevelopmental and psychiatric disorders. A key example is ATRX, an X-linked gene commonly mutated in individuals with syndromic and nonsyndromic intellectual disability. The consequences of Atrx inactivation for learning and memory have been difficult to evaluate because of the early lethality of hemizygous-null animals. In this study, we evaluated the outcome of brain-specific Atrx deletion in heterozygous female mice. These mice exhibit a mosaic pattern of ATRX protein expression in the central nervous system attributable to the location of the gene on the X chromosome. Although the hemizygous male mice die soon after birth, heterozygous females survive to adulthood. Body growth is stunted in these animals, and they have low circulating concentrations of insulin growth factor 1. In addition, they are impaired in spatial, contextual fear and novel object recognition memory. Our findings demonstrate that mosaic loss of ATRX expression in the central nervous system leads to endocrine defects and decreased body size and has a negative impact on learning and memory. © 2017. Published by The Company of Biologists Ltd.

  20. Localization of PPARdelta in murine central nervous system: expression in oligodendrocytes and neurons.

    PubMed

    Woods, John W; Tanen, Michael; Figueroa, David J; Biswas, Chhabi; Zycband, Emanuel; Moller, David E; Austin, Christopher P; Berger, Joel P

    2003-06-13

    The peroxisome proliferator-activated receptors (PPARs), PPARdelta, PPARgamma and PPARalpha, comprise a subclass of the supergene family of nuclear receptors. As such they are ligand-regulated transcription factors whose major effects are mediated by altering expression of target genes. PPARdelta has been shown to be ubiquitously expressed in mammals. However, its primary biological role(s) has yet to be defined. Several recent studies have demonstrated that PPARdelta is the most highly expressed PPAR isoform in the central nervous system, but ambiguity still exists as to the specific brain sub-regions and cells in which it is expressed. Here, utilizing novel, isoform-selective PPARdelta riboprobes and an anti-peptide antibody, we performed a series of in situ hybridization and immunolocalization studies to determine the distribution of PPARdelta in the central nervous system (CNS) of mice. We found that PPARdelta mRNA and protein is expressed throughout the brain, with particularly high levels in the entorhinal cortex, hypothalamus and hippocampus, and lower levels in the corpus callosum and caudate putamen. At the cellular level, PPARdelta mRNA and protein were found to be expressed in oligodendrocytes and neurons but not astrocytes. Such results suggest a role for PPARdelta in both myelination and neuronal functioning within the CNS.

  1. Central nervous system Aspergillus infection after epidural analgesia: diagnosis, therapeutic challenges, and literature review

    PubMed Central

    Genzen, Jonathan R.; Kenney, Barton

    2009-01-01

    Aspergillus terreus was identified in an intra-dural spinal biopsy specimen from an African female with recurrent headache and hydrocephalus. Prior laboratory testing of cerebrospinal fluid (CSF) was non-diagnostic, despite extensive central nervous system (CNS) involvement. CNS Aspergillus infection presents a diagnostic and therapeutic challenge and is reviewed in the context of this particularly instructive and difficult case. PMID:19717262

  2. Cnidarian Neurotoxic Peptides Affecting Central Nervous System Targets.

    PubMed

    Lazcano-Pérez, Fernando; Hernández-Guzmán, Ulises; Sánchez-Rodríguez, Judith; Arreguín-Espinosa, Roberto

    2016-01-01

    Natural products from animal venoms have been used widely in the discovery of novel molecules with particular biological activities that enable their use as potential drug candidates. The phylum Cnidaria (jellyfish, sea anemones, corals zoanthids, hydrozoans, etc.) is the most ancient venomous phylum on earth. Its venoms are composed of a complex mixture of peptidic compounds with neurotoxic and cytolitic properties that have shown activity on mammalian systems despite the fact that they are naturally targeted against fish and invertebrate preys, mainly crustaceans. For this reason, cnidarian venoms are an interesting and vast source of molecules with a remarkable activity on central nervous system, targeting mainly voltage-gated ion channels, ASIC channels, and TRPV1 receptors. In this brief review, we list the amino acid sequences of most cnidarian neurotoxic peptides reported to date. Additionally, we propose the inclusion of a new type of voltage-gated sea anemone sodium channel toxins based on the most recent reports.

  3. Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems

    PubMed Central

    Chan, Ken Y; Jang, Min J; Yoo, Bryan B; Greenbaum, Alon; Ravi, Namita; Wu, Wei-Li; Sánchez-Guardado, Luis; Lois, Carlos; Mazmanian, Sarkis K; Deverman, Benjamin E; Gradinaru, Viviana

    2017-01-01

    Adeno-associated viruses (AAVs) are commonly used for in vivo gene transfer. Nevertheless, AAVs that provide efficient transduction across specific organs or cell populations are needed. Here, we describe AAV-PHP.eB and AAV-PHP.S, capsids that efficiently transduce the central and peripheral nervous systems, respectively. In the adult mouse, intravenous administration of 1×1011 vector genomes (vg) of AAV-PHP.eB transduced 69% of cortical and 55% of striatal neurons, while 1×1012 vg AAV-PHP.S transduced 82% of dorsal root ganglion neurons, as well as cardiac and enteric neurons. The efficiency of these vectors facilitates robust co-transduction and stochastic, multicolor labeling for individual cell morphology studies. To support such efforts, we provide methods for labeling a tunable fraction of cells without compromising color diversity. Furthermore, when used with cell type-specific promoters, these AAVs provide targeted gene expression across the nervous system and enable efficient and versatile gene manipulation throughout the nervous system of transgenic and non-transgenic animals. PMID:28671695

  4. The Role of Neuropeptides in Persistent Virus Infections of the Central Nervous System

    DTIC Science & Technology

    1990-05-10

    5000 61153N RR04108 441f722 11. TITLE (include Security Classification) (U) The role of neuropeptides in persistent virus infections of the central...identify by block number) FIELD GROUP SUB-GROUP opioids, lymphocytes, infections , nervous system, virus, immunity, neuropeptides 19 ABSTRACT (Continue on...endorphin, 24 h after reconstitution of nude mice with splenocytes and 24 h prior to infection with virus, re- sulted in 74% survival; and 39% of the

  5. No support for premature central nervous system aging in HIV-1 when measured by cerebrospinal fluid phosphorylated tau (p-tau).

    PubMed

    Krut, Jan J; Price, Richard W; Zetterberg, Henrik; Fuchs, Dietmar; Hagberg, Lars; Yilmaz, Aylin; Cinque, Paola; Nilsson, Staffan; Gisslén, Magnus

    2017-07-04

    The prevalence of neurocognitive deficits are reported to be high in HIV-1 positive patients, even with suppressive antiretroviral treatment, and it has been suggested that HIV can cause accelerated aging of the brain. In this study we measured phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) as a potential marker for premature central nervous system (CNS) aging. P-tau increases with normal aging but is not affected by HIV-associated neurocognitive disorders. With a cross-sectional retrospective design, p-tau, total tau (t-tau), neopterin and HIV-RNA were measured in CSF together with plasma HIV-RNA and blood CD4 + T-cells of 225 HIV-infected patients <50 y of age, subdivided into 3 groups: untreated neuroasymptomatic (NA) (n = 145), on suppressive antiretroviral treatment (cART) (n = 49), and HIV-associated dementia (HAD) (n = 31). HIV-negative healthy subjects served as controls (n = 79). P-tau was not significantly higher in any HIV-infected group compared to HIV-negative controls. Significant increases in t-tau were found as expected in patients with HAD compared to NA, cART, and control groups (p < 0.001 ). P-tau was not higher in HIV-infected patients compared to uninfected controls, thus failing to support a role for premature or accelerated brain aging in HIV infection.

  6. [Antibiotic diffusion to central nervous system].

    PubMed

    Cabrera-Maqueda, J M; Fuentes Rumí, L; Valero López, G; Baidez Guerrero, A E; García Molina, E; Díaz Pérez, J; García-Vázquez, E

    2018-02-01

    Central nervous system (CNS) infections caused by pathogens with a reduced sensitivity to drugs are a therapeutic challenge. Transport of fluid and solutes is tightly controlled within CNS, where vasculature exhibits a blood-brain barrier (BBB).The entry of drugs, including antibiotics, into the cerebro-spinal fluid (CSF) is governed by molecular size, lipophilicity, plasma protein binding and their affinity to transport systems at the BBB. The ratio of the AUCCSF (Area under the curve in CSF)/AUCS (Area under the curve in serum) is the most accurate parameter to characterize drug penetration into the CSF. Linezolid, some fluoroquinolones and metronidazole get high CSF concentrations and are useful for treating susceptible pathogens. Some highly active antibiotic compounds with low BBB permeability can be directly administered into the ventricles together with concomitant intravenous therapy. The ideal antibiotic to treat CNS infections should be that with a small moderately lipophilic molecule, low plasma protein binding and low affinity to efflux pumps at BBB. Knowledge of the pharmacokinetics and pharmacodynamics of antibiotics at the BBB will assist to optimize antibiotic treatment in CNS infections. This article reviews the physicochemical properties of the main groups of antibiotics to assess which compounds are most promising for the treatment of CNS infections and how to use them in the daily clinical practice. © The Author 2018. Published by Sociedad Española de Quimioterapia.

  7. Time Perception Mechanisms at Central Nervous System.

    PubMed

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

    2016-04-01

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

  8. 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...

  9. Serum VEGF-A concentrations in patients with central nervous system (CNS) tumors

    PubMed Central

    2018-01-01

    Angiogenesis plays an essential role in tumors development. In case of central nervous system tumors, the most important role in this process plays VEGF-A. The purpose of this study was to determine the plasma concentration of this agent in patients treated surgically because of intracranial tumors. The study involved 48 adult patients, both sexes, treated surgically because of a brain tumor. The control group consisted of 50 adult volunteers of both sexes, without cancer diagnosis. Based on the studies, it was found that serum VEGF-A levels before surgery are higher in patients with central nervous system tumors (10.39–150.57 pg/ml, median 41.70 pg/ml) than in non-cancer patients (0.00–130.77 pg/ml, median 22.56 pg/ml). The association between serum VEGF-A level and malignancy and histological type of intracranial tumor has not beed confirmed. The highest average preoperative serum VEGF-A level was found in patients with low grade gliomas, slightly lower (close to each other) in those with high grade gliomas and meningiomas, while the lowest level was characteristic for metastatic tumors. High variation in results was observed in patients with low grade gliomas (52.56 pg/ml)—higher than those reported in patients with high grade gliomas (32.38 pg/ml). In the rest types of tumors the differentiation was similar and oscillated within 23.08–27.50 pg/ml. PMID:29590109

  10. Central Nervous System Effects of Intrauterine Zika Virus Infection: A Pictorial Review.

    PubMed

    Ribeiro, Bianca Guedes; Werner, Heron; Lopes, Flávia P P L; Hygino da Cruz, L Celso; Fazecas, Tatiana M; Daltro, Pedro A N; Nogueira, Renata A

    2017-10-01

    Relatively few agents have been associated with congenital infections involving the brain. One such agent is the Zika virus, which has caused several outbreaks worldwide and has spread in the Americas since 2015. The Zika virus is an arbovirus transmitted by infected female mosquito vectors, such as the Aedes aegypti mosquito. This virus has been commonly associated with congenital infections of the central nervous system and has greatly increased the rates of microcephaly. Ultrasonography (US) remains the method of choice for fetal evaluation of congenital Zika virus infection. For improved assessment of the extent of the lesions, US should be complemented by magnetic resonance (MR) imaging. Postnatal computed tomography and MR imaging can also unveil additional findings of central nervous system involvement, such as microcephaly with malformation of cortical development, ventriculomegaly, and multifocal calcifications in the cortical-subcortical junction, along with associated cortical atrophy. The calcifications may be punctate, dystrophic, linear, or coarse and may follow a predominantly bandlike distribution. A small anterior fontanelle with prematurely closed sutures is also observed with Zika virus infection. In this review, the prenatal and postnatal neurologic imaging findings of congenital Zika virus infection are covered. Radiologists must be aware of this challenging entity and have knowledge of the various patterns that may be depicted with each imaging modality and the main differential diagnosis of the disease. As in other neurologic infections, serial imaging is able to help demonstrate the progression of the findings. © RSNA, 2017.

  11. [BCL-2 in primary central nervous system lymphomas. Immunohistochemistry and molecular biology].

    PubMed

    Buccoliero, A M; Castiglione, F; Caldarella, A; Rossi Degl'Innocenti, D; Taddei, A; Ammannati, F; Mennonna, P; Taddei, G L

    2004-10-01

    BCL-2 is a membrane protein known to be an apoptosis inhibitor. It is the product of the bcl-2 gene located on chromosome 18. Several different tumors show BCL-2 over-expression as result of a translocation or independently from it. More than 85% of follicular lymphomas and a smaller number of diffuse large cell B lymphomas contain t(14;18) (q32;q21). The aim of this study was to investigate the immunohistochemical expression of the BCL-2 protein and to ascertain, by means of traditional PCR (Polimerase Chain Reaction), its possible dependence from t(14;18) (q32;q21) in 9 primary central nervous system lymphomas. Six cases (67%) shoved immunohistochemical BCL-2 over-expression and 3 cases (33%) had t(14;18). Precisely: 2 cases (22%) had immunohistochemical BCL-2 over-expression and t(14;18) (q32;q21); 4 cases (44%) had BCL-2 over-expression without translocation; 1 case (11%) did not show diffuse BCL-2 over-expression in presence of the traslocation; the remaining 2 cases (22%) did not demonstrate BCL-2 over-expression or t(14;18) (q32;q21). In conclusion, our results indicate primary central nervous system lymphomas frequently show BCL-2 over-expression that in some case may be related to t(14;18) (q32;q21). Nevertheless, t(14;18) (q32;q21), as evaluated by traditional PCR, may not correspond to diffuse immunohistochemical BCL-2 positivity.

  12. Methods for Gene Transfer to the Central Nervous System

    PubMed Central

    Kantor, Boris; Bailey, Rachel M.; Wimberly, Keon; Kalburgi, Sahana N.; Gray, Steven J.

    2015-01-01

    Gene transfer is an increasingly utilized approach for research and clinical applications involving the central nervous system (CNS). Vectors for gene transfer can be as simple as an unmodified plasmid, but more commonly involve complex modifications to viruses to make them suitable gene delivery vehicles. This chapter will explain how tools for CNS gene transfer have been derived from naturally occurring viruses. The current capabilities of plasmid, retroviral, adeno-associated virus, adenovirus, and herpes simplex virus vectors for CNS gene delivery will be described. These include both focal and global CNS gene transfer strategies, with short- or long-term gene expression. As is described in this chapter, an important aspect of any vector is the cis-acting regulatory elements incorporated into the vector genome that control when, where, and how the transgene is expressed. PMID:25311922

  13. Protective and Pathological Immunity during Central Nervous System Infections.

    PubMed

    Klein, Robyn S; Hunter, Christopher A

    2017-06-20

    The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted that innate pathways limit pathogen invasion of the CNS and adaptive immunity mediates control of many neural infections. As protective responses can result in bystander damage, there are regulatory mechanisms that balance protective and pathological inflammation, but these mechanisms might also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in our understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection. Advances in these areas have broadened our comprehension of how the immune system functions in the brain and can readily overcome immune privilege. Copyright © 2017. Published by Elsevier Inc.

  14. Anticholinergics and Central Nervous System Effects: Are We Confused?

    PubMed Central

    Staskin, David R; Zoltan, Edward

    2007-01-01

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

  15. 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

  16. [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.

  17. Immune responses to West Nile virus infection in the central nervous system.

    PubMed

    Cho, Hyelim; Diamond, Michael S

    2012-12-17

    West Nile virus (WNV) continues to cause outbreaks of severe neuroinvasive disease in humans and other vertebrate animals in the United States, Europe, and other regions of the world. This review discusses our understanding of the interactions between virus and host that occur in the central nervous system (CNS), the outcome of which can be protection, viral pathogenesis, or immunopathogenesis. We will focus on defining the current state of knowledge of WNV entry, tropism, and host immune response in the CNS, all of which affect the balance between injury and successful clearance.

  18. [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.

  19. Characteristics of Rosai-Dorfman Disease Primarily Involved in the Central Nervous System: 3 Case Reports and Review of Literature.

    PubMed

    Luo, Zhengxiang; Zhang, Yansong; Zhao, Penglai; Lu, Hucheng; Yang, Kun; Zhang, Yuhai; Zeng, Yanjun

    2017-01-01

    This study aimed to summarize the clinical characteristics of Rosai-Dorfman disease primarily involving the central nervous system and to explore diagnosis and treatment. We analyzed the clinical, imaging, and pathologic characteristics; treatment; and prognosis in 3 cases of Rosai-Dorfman disease primarily involving the central nervous system. We also performed a literature review. The largest of multiple intracranial lesions was totally resected, and steroid administration and radiotherapy were performed in phases for the remaining lesions. During the 1-year follow-up period, the excised lesion did not recur, and no obvious variations were observed in the other lesions. Subtotal resection was performed of the largest of another group of multiple intracranial lesions, and the residual did not show any obvious variations during the 1-year follow-up period. The isolated lesion was totally resected and did not recur during a 2-year follow-up period. Rosai-Dorfman disease with multiple lesions primarily involving the central nervous system is rare. Imaging characteristics are similar to meningiomas, and the pathological features include lymphocytes and plasma cells reaching tissue cells with large volume and abundant cytoplasm. Surgery is the preferred treatment, as the effects of steroid administration and radiotherapy are not apparent. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Immunocytochemical distribution of glial fibrillary acidic protein in the central nervous system of the Japanese quail (Coturnix coturnix japonica).

    PubMed

    Cameron-Curry, P; Aste, N; Viglietti-Panzica, C; Panzica, G C

    1991-01-01

    In the present study we detailed the distribution of GFAP-immunopositive structures within the central nervous system of the Japanese quail. Different fixation and embedding procedures were applied. The best results were obtained on frozen cryostatic sections from freshly dissected brains subsequently fixed by a short immersion in cold acetone. Immunopositive structures were observed both with immunofluorescence, and with immunoperoxidase methods. Immunoreactive cell bodies and processes were observed within the whole central nervous system, and different cell types can be identified on the basis of their topographical location and morphology. A first class of astrocytes is composed of intensely stained unipolar cells lining the inner surface of the pia mater and the large blood vessels. A second type is represented by multipolar astrocytes of variable size, provided with an irregular cell body. The last type is represented by similar elements, showing an immunonegative cell body, that can be identified only by the presence of converging processes. These three types of cells, and several isolated processes, show a differential distribution within the quail central nervous system, both in the grey and in the white matter. Present results suggest that GFAP may represent a good marker for at least part of the astroglial population in quail.

  1. Effect of high fat diets on the NTPDase, 5'-nucleotidase and acetylcholinesterase activities in the central nervous system.

    PubMed

    Kaizer, Rosilene Rodrigues; Spanevello, Rosélia Maria; Costa, Eduarda; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

    2018-02-01

    High fat diets are associated with the promotion of neurological diseases, such as Alzheimer disease (AD). This study aim investigate the high fat diets role to promotion of AD using as biochemistry parameter of status of central nervous system through the NTPDase, 5'-nucleotidase and acetylcholinesterase (AChE) activities in brain of young rats. The intake of high fat diets promotes an inhibition of purinergic and cholinergic functions, mainly in the long-term exposure to saturated and saturated/unsaturated diets. The AChE activity was decreased to supernatant and synaptosomes tissues preparations obtained from cerebral cortex in average of 20%, to both groups exposed to saturated and saturated/unsaturated diets, when compared to the control group. Very similar results were found in hippocampus and cerebellum brain areas. At same time, the adenine nucleotides hydrolysis in synaptosomes of cerebral cortex were decreased to ATP, ADP and AMP after the long-term exposure to high fat diets, as saturated and saturated/unsaturated. The inhibition of ATP hydrolysis was of 26% and 39% to saturated and saturated/unsaturated diets, respectively. ADP hydrolysis was decreased in 20% to saturated diet, and AMP hydrolysis was decreased in 25% and 33% to saturated and saturated/unsaturated diets, respectively, all in comparison to the control. Thus, we can suggest that the effects of high diets on the purinergic and cholinergic nervous system may contribute to accelerate the progressive memory loss, to decline in language and other cognitive disruptions, such as AD patients presents. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  2. 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.

  3. 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,…

  4. Comparative morphology of serotonergic-like immunoreactive elements in the central nervous system of kinorhynchs (Kinorhyncha, Cyclorhagida).

    PubMed

    Herranz, María; Pardos, Fernando; Boyle, Michael J

    2013-03-01

    Cycloneuralian taxa exhibit similar organ system architectures, providing informative characters of metazoan evolution, yet very few modern comparative descriptions of cellular and molecular homologies within and among those taxa are available. We immunolabeled and characterized elements of the serotonergic nervous system in the kinorhynchs Echinoderes spinifurca, Antygomonas paulae, and Zelinkaderes brightae using confocal laser scanning microscopy. Fluorescent markers targeting DNA were combined with observations of auto-fluorescent structures to guide interpretations of the internal and external anatomy in each species. Results show a common pattern of the central nervous system with a circumenteric brain divided into ring-shaped anterior and posterior neuronal somata and a central neuropil connected to a multi-stringed, longitudinal ventral nerve cord. Structural similarities and differences in the nervous systems of these species were observed and described, stressing the incomplete ring nature of the anterior region of the kinorhynch brain, the functional relationship between the brain and the movable introvert, and the number and arrangement of nerve strings and somata of the ventral nerve cord. The ventral cord ends in two ventrolateral cell bodies in E. spinifurca, and forms a terminal loop associated with a midterminal spine in A. paulae and Z. brightae. The possible functional and phylogenetic significance of these features and arrangements are discussed. Copyright © 2012 Wiley Periodicals, Inc.

  5. 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

  6. [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.

  7. Preoperative assessment and preparation of patients with diseases affecting the central nervous system.

    PubMed

    Milaković, Branko; Dimitrijević, Ivan; Malenković, Vesna; Marković, Dejan; Pantić-Palibrk, Vesna; Gvozdenović, Ljiljana

    2011-01-01

    This review will examine the most important issues of preoperative evaluation and preparation in relation to patients with deseases affecting the central nervous system. Those patients may undergo various forms of surgery unrelated to the central nervous system disease. We discuss the effect of physiologic and pharmacological factors on cerebral autoregulation and control of intracranial pressure alongside its clinical relevance with the help of new evidence. Regardless of the reason for surgery, coexisting diseases of brain often have important implications when selecting anesthetic drugs, procedures and monitoring techniques. Suppression of cerebral metabolic rate is not the sole mechanism for the neuroprotective effect of anaesthetic agents. There are certain general principles, but also some specific circumstances, when we are talking about optimal anesthetic procedure for a patient with coexisting brain disease. Intravenous anesthesia, such as combination of propofol and remifentanil, provides best preservation of autoregulation. Among inhaled agents isoflurane and sevoflurane appear to preserve autoregulation at all doses, whereas with other agents autoregulation is impaired in a dose-related manner. During maintenance of anesthesia the patient is ventilated by intermittent positive pressure ventilation, at intermediate hyperventilation (PaCO2 25-30 mmHg). Intraoperative cerebral autoregulation monitoring is an important consideration for the patients with coexisting neurological disease. Transcranial Doppler based static autoregulation measurements appears to be the most robust bedside method for this purpose.

  8. 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

  9. 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...

  10. 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.

  11. Evolving Character of Chronic Central Nervous System HIV Infection

    PubMed Central

    Price, Richard W.; Spudich, Serena S.; Peterson, Julia; Joseph, Sarah; Fuchs, Dietmar; Zetterberg, Henrik; Gisslén, Magnus; Swanstrom, Ronald

    2014-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) begins early in systemic infection and continues throughout its untreated course. Despite a common cerebrospinal fluid inflammatory response, it is usually neurologically asymptomatic for much of this course, but can evolve in some individuals to HIV-associated dementia (HAD), a severe encephalopathy with characteristic cognitive and motor dysfunction. While widespread use of combination antiretroviral therapy (ART) has led to a marked decline in both the CNS infection and its neurologic severe consequence, HAD continues to afflict individuals presenting with advanced systemic infection in the developed world and a larger number in resource-poor settings where ART is more restricted. Additionally, milder CNS injury and dysfunction have broader prevalence, including in those treated with ART. Here we review the history and evolving nomenclature of HAD, its viral pathogenesis, clinical presentation and diagnosis, and treatment. PMID:24715483

  12. Neuroinvasion and Inflammation in Viral Central Nervous System Infections

    PubMed Central

    Schroten, Horst

    2016-01-01

    Neurotropic viruses can cause devastating central nervous system (CNS) infections, especially in young children and the elderly. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) have been described as relevant sites of entry for specific viruses as well as for leukocytes, which are recruited during the proinflammatory response in the course of CNS infection. In this review, we illustrate examples of established brain barrier models, in which the specific reaction patterns of different viral families can be analyzed. Furthermore, we highlight the pathogen specific array of cytokines and chemokines involved in immunological responses in viral CNS infections. We discuss in detail the link between specific cytokines and chemokines and leukocyte migration profiles. The thorough understanding of the complex and interrelated inflammatory mechanisms as well as identifying universal mediators promoting CNS inflammation is essential for the development of new diagnostic and treatment strategies. PMID:27313404

  13. 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.

  14. Calcium signal communication in the central nervous system.

    PubMed

    Braet, Katleen; Cabooter, Liesbet; Paemeleire, Koen; Leybaert, Luc

    2004-02-01

    The communication of calcium signals between cells is known to be operative between neurons where these signals integrate intimately with electrical and chemical signal communication at synapses. Recently, it has become clear that glial cells also exchange calcium signals between each other in cultures and in brain slices. This communication pathway has received utmost attention since it is known that astrocytic calcium signals can be induced by neuronal stimulation and can be communicated back to the neurons to modulate synaptic transmission. In addition to this, cells that are generally not considered as brain cells become progressively incorporated in the picture, as astrocytic calcium signals are reported to be communicated to endothelial cells of the vessel wall and can affect smooth muscle cell tone to influence the vessel diameter and thus blood flow. We review the available evidence for calcium signal communication in the central nervous system, taking into account a basic functional unit -the brain cell tripartite- consisting of neurons, glial cells and vascular cells and with emphasis on glial-vascular calcium signaling aspects.

  15. Central nervous system infection due to Mycobacterium haemophilum in a patient with acquired immunodeficiency syndrome.

    PubMed

    Buppajarntham, Aubonphan; Apisarnthanarak, Anucha; Rutjanawech, Sasinuj; Khawcharoenporn, Thana

    2015-03-01

    Mycobacterium haemophilum is an environmental organism that rarely causes infections in humans. We report a patient with acquired immunodeficiency syndrome who had central nervous system infection due to M. haemophilum. The diagnosis required brain tissue procurement and molecular identification method while the treatment outcome was unfavourable. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  16. Beyond the Joint: The Role of Central Nervous System Reorganizations in Chronic Musculoskeletal Disorders.

    PubMed

    Roy, Jean-Sébastien; Bouyer, Laurent J; Langevin, Pierre; Mercier, Catherine

    2017-11-01

    To a large extent, management of musculoskeletal disorders has traditionally focused on structural dysfunctions found within the musculoskeletal system, mainly around the affected joint. While a structural-dysfunction approach may be effective for musculoskeletal conditions in some populations, especially in acute presentations, its effectiveness remains limited in patients with recurrent or chronic musculoskeletal pain. Numerous studies have shown that the human central nervous system can undergo plastic reorganizations following musculoskeletal disorders; however, they can be maladaptive and contribute to altered joint control and chronic pain. In this Viewpoint, the authors argue that to improve rehabilitation outcomes in patients with chronic musculoskeletal pain, a global view of the disorder that incorporates both central (neural) and peripheral (joint-level) changes is needed. The authors also discuss the challenge of evaluating and rehabilitating central changes and the need for large, high-level studies to evaluate approaches incorporating central and peripheral changes and emerging therapies. J Orthop Sports Phys Ther 2017;47(11):817-821. doi:10.2519/jospt.2017.0608.

  17. Central nervous system regulation of intestinal lipid and lipoprotein metabolism.

    PubMed

    Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

    2016-02-01

    In response to nutrient availability, the small intestine and brain closely communicate to modulate energy homeostasis and metabolism. The gut-brain axis involves complex nutrient sensing mechanisms and an integration of neuronal and hormonal signaling. This review summarizes recent evidence implicating the gut-brain axis in regulating lipoprotein metabolism, with potential implications for the dyslipidemia of insulin resistant states. The intestine and brain possess distinct mechanisms for sensing lipid availability, which triggers subsequent regulation of feeding, glucose homeostasis, and adipose tissue metabolism. More recently, central receptors, neuropeptides, and gut hormones that communicate with the brain have been shown to modulate hepatic and intestinal lipoprotein metabolism via parasympathetic and sympathetic signaling. Gut-derived glucagon-like peptides appear to be particularly important in modulating the intestinal secretion of chylomicron particles via a novel brain-gut axis. Dysregulation of these pathways may contribute to postprandial diabetic dyslipidemia. Emerging evidence implicates the central and enteric nervous systems in controlling many aspects of lipid and lipoprotein metabolism. Bidirectional communication between the gut and brain involving neuronal pathways and gut peptides is critical for regulating feeding and metabolism, and forms a neuroendocrine circuit to modulate dietary fat absorption and intestinal production of atherogenic chylomicron particles.

  18. 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.

  19. 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.

  20. 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.

  1. Comparative mapping of GABA-immunoreactive neurons in the central nervous systems of nudibranch molluscs.

    PubMed

    Gunaratne, Charuni A; Sakurai, Akira; Katz, Paul S

    2014-03-01

    The relative simplicity of certain invertebrate nervous systems, such as those of gastropod molluscs, allows behaviors to be dissected at the level of small neural circuits composed of individually identifiable neurons. Elucidating the neurotransmitter phenotype of neurons in neural circuits is important for understanding how those neural circuits function. In this study, we examined the distribution of γ-aminobutyric-acid;-immunoreactive (GABA-ir) neurons in four species of sea slugs (Mollusca, Gastropoda, Opisthobranchia, Nudibranchia): Tritonia diomedea, Melibe leonina, Dendronotus iris, and Hermissenda crassicornis. We found consistent patterns of GABA immunoreactivity in the pedal and cerebral-pleural ganglia across species. In particular, there were bilateral clusters in the lateral and medial regions of the dorsal surface of the cerebral ganglia as well as a cluster on the ventral surface of the pedal ganglia. There were also individual GABA-ir neurons that were recognizable across species. The invariant presence of these individual neurons and clusters suggests that they are homologous, although there were interspecies differences in the numbers of neurons in the clusters. The GABAergic system was largely restricted to the central nervous system, with the majority of axons confined to ganglionic connectives and commissures, suggesting a central, integrative role for GABA. GABA was a candidate inhibitory neurotransmitter for neurons in central pattern generator (CPG) circuits underlying swimming behaviors in these species, however none of the known swim CPG neurons were GABA-ir. Although the functions of these GABA-ir neurons are not known, it is clear that their presence has been strongly conserved across nudibranchs. Copyright © 2013 Wiley Periodicals, Inc.

  2. Innate immune interactions within the central nervous system modulate pathogenesis of viral infections

    PubMed Central

    Nair, Sharmila; Diamond, Michael S.

    2015-01-01

    The innate immune system mediates protection against neurotropic viruses that replicate in the central nervous system (CNS). Virus infection within specific cells of the CNS triggers activation of several families of pattern recognition receptors including Toll-like receptors, retinoic acid-inducible gene 1 like receptors, nucleotide-binding oligomerization domain-like receptors, and cytosolic DNA sensors. In this review, we highlight recent advances in our understanding of how cell-intrinsic host defenses within the CNS modulate infection of different DNA and RNA viruses. PMID:26163762

  3. Central nervous system correlates of behavioral deficits following simian immunodeficiency virus infection.

    PubMed

    Weed, Michael R; Hienz, Robert D; Brady, Joseph V; Adams, Robert J; Mankowski, Joseph L; Clements, Janice E; Zink, M Christine

    2003-08-01

    Despite the high incidence of cognitive and motor impairment in acquired immunodeficiency syndrome (AIDS) patients, the mechanisms of AIDS-related central nervous system (CNS) pathology are not completely understood. Infection with simian immunodeficiency virus (SIV) in macaques provides an excellent model of AIDS, including human immunodeficiency virus (HIV)-induced CNS pathology and cognitive/behavioral impairment. Co-inoculation with two SIV strains, SIV/17E-Fr and SIV/DeltaB670, accelerates SIV CNS disease, producing SIV encephalitis in over 90% of pig-tailed macaques within 3 months. In the present study, this SIV model was employed to identify cellular and viral correlates of behavioral impairment following SIV infection. Measures of psychomotor speed (simple reaction time), fine motor control (bimanual motor task), and general motor activity (home cage movement) were all adversely affected by SIV disease. Prior to euthanasia, performance was significantly impaired in both a simple reaction time task in 6 of 12 monkeys and a bimanual motor task in 5 of 6 monkeys. All monkeys evaluated (11 of 11) showed significant reductions in spontaneous motor activity. Significant correlations were found between impaired performance on the bimanual motor test and axonal damage (accumulation of beta-amyloid precursor protein in the corpus callosum) as well as increased microglial activation and macrophage infiltration (levels of CD68 and Ham56 immunostaining). These results suggest that axonal damage is related to the behavioral impairment induced by infection with SIV. The axonal damage may result from neuroimmune responses, including microglial and macrophage activation. Therefore, axonal damage may be a morphologic manifestation of neuronal dysfunction that underlies development of behavioral impairment in HIV/SIV CNS infection.

  4. 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.

  5. Gut-central nervous system axis is a target for nutritional therapies.

    PubMed

    Pimentel, Gustavo D; Micheletti, Thayana O; Pace, Fernanda; Rosa, José C; Santos, Ronaldo V T; Lira, Fabio S

    2012-04-10

    Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies.

  6. The role of microbiome in central nervous system disorders

    PubMed Central

    Wang, Yan; Kasper, Lloyd H.

    2014-01-01

    Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome-gut-brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome-CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders. PMID:24370461

  7. 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

  8. Phase I Trial Using Patupilone (Epothilone B) and Concurrent Radiotherapy for Central Nervous System Malignancies

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

    Fogh, Shannon; Machtay, Mitchell; Werner-Wasik, Maria

    Purpose: Based on preclinical data indicating the radiosensitizing potential of epothilone B, the present study was designed to evaluate the toxicity and response rate of patupilone, an epothilone B, with concurrent radiotherapy (RT) for the treatment of central nervous system malignancies. Methods and Materials: The present Phase I study evaluated the toxicities associated with patupilone combined with RT to establish the maximal tolerated dose. Eligible patients had recurrent gliomas (n = 10) primary (n = 5) or metastatic (n = 17) brain tumors. Dose escalation occurred if no dose-limiting toxicities, defined as any Grade 4-5 toxicity or Grade 3 toxicitymore » requiring hospitalization, occurred during treatment. Results: Of 14 patients, 5 were treated with weekly patupilone at 1.5 mg/m{sup 2}, 4 at 2.0 mg/m{sup 2}, 4 at 2.5 mg/m{sup 2}, and 1 at 4 mg/m{sup 2}. Of 18 patients, 7 were treated in the 6-mg/m{sup 2} group, 6 in the 8-mg/m{sup 2} group, and 5 in the 10-mg/m{sup 2} group. Primary central nervous system malignancies received RT to a median dose of 60 Gy. Central nervous system metastases received whole brain RT to a median dose of 37.4 Gy, and patients with recurrent gliomas underwent stereotactic RT to a median dose of 37.5 Gy. One dose-limiting toxicity (pneumonia) was observed in group receiving 8-mg/m{sup 2} every 3 weeks. At the subsequent dose level (10 mg/m{sup 2}), two Grade 4 dose-limiting toxicities occurred (renal failure and pulmonary hemorrhage); thus, 8 mg/m{sup 2} every 3 weeks was the maximal tolerated dose and the recommended Phase II dose. Conclusion: Combined with a variety of radiation doses and fractionation schedules, concurrent patupilone was well tolerated and safe, with a maximal tolerated dose of 8 mg/m{sup 2} every 3 weeks.« less

  9. Whole-central nervous system functional imaging in larval Drosophila

    PubMed Central

    Lemon, William C.; Pulver, Stefan R.; Höckendorf, Burkhard; McDole, Katie; Branson, Kristin; Freeman, Jeremy; Keller, Philipp J.

    2015-01-01

    Understanding how the brain works in tight concert with the rest of the central nervous system (CNS) hinges upon knowledge of coordinated activity patterns across the whole CNS. We present a method for measuring activity in an entire, non-transparent CNS with high spatiotemporal resolution. We combine a light-sheet microscope capable of simultaneous multi-view imaging at volumetric speeds 25-fold faster than the state-of-the-art, a whole-CNS imaging assay for the isolated Drosophila larval CNS and a computational framework for analysing multi-view, whole-CNS calcium imaging data. We image both brain and ventral nerve cord, covering the entire CNS at 2 or 5 Hz with two- or one-photon excitation, respectively. By mapping network activity during fictive behaviours and quantitatively comparing high-resolution whole-CNS activity maps across individuals, we predict functional connections between CNS regions and reveal neurons in the brain that identify type and temporal state of motor programs executed in the ventral nerve cord. PMID:26263051

  10. 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

  11. Evolving character of chronic central nervous system HIV infection.

    PubMed

    Price, Richard W; Spudich, Serena S; Peterson, Julia; Joseph, Sarah; Fuchs, Dietmar; Zetterberg, Henrik; Gisslén, Magnus; Swanstrom, Ronald

    2014-02-01

    Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) begins early in systemic infection and continues throughout its untreated course. Despite a common cerebrospinal fluid inflammatory response, it is usually neurologically asymptomatic for much of this course, but can evolve in some individuals to HIV-associated dementia (HAD), a severe encephalopathy with characteristic cognitive and motor dysfunction. While widespread use of combination antiretroviral therapy (ART) has led to a marked decline in both the CNS infection and its neurologic severe consequence, HAD continues to afflict individuals presenting with advanced systemic infection in the developed world and a larger number in resource-poor settings where ART is more restricted. Additionally, milder CNS injury and dysfunction have broader prevalence, including in those treated with ART. Here we review the history and evolving nomenclature of HAD, its viral pathogenesis, clinical presentation and diagnosis, and treatment. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Connexin32 expression in central and peripheral nervous systems

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

    Deschenes, S.M.; Scherer, S.S.; Fischbeck, K.H.

    1994-09-01

    Mutations have been identified in the gap junction gene, connexin32 (Cx32), in patients affected with the X-linked form of the demyelinating neuropathy, Charcot-Marie-Tooth disease (CMTX). Gap junctions composed of Cx32 are present and developmentally regulated in a wide variety of tissues. In peripheral nerve, our immunohistochemical analysis localized Cx32 to the noncompacted myelin of the paranodal regions and the Schmidt-Lantermann incisures, where previous studies describe gap junctions. In contrast to the location of Cx32 in peripheral nerve and the usual restriction of clinical manifestations to the peripheral nervous system (PNS) (abstract by Paulson describes an exception), preliminary studies show thatmore » Cx32 is present in the compacted myelin of the central nervous system (CNS), as demonstrated by radial staining through the myelin sheath of oligodendrocytes in rat spinal cord. Analysis of Cx32 expression in various regions of rat CNS during development shows that the amount of Cx32 mRNA and protein increases as myelination increases, a pattern observed for other myelin genes. Studies in the PNS provide additional evidence that Cx32 and myelin genes are coordinately regulated at the transcriptional level; Cx32 and peripheral myelin gene PMP-22 mRNAs are expressed in parallel following transient or permanent nerve injury. Differences in post-translational regulation of Cx32 in the CNS and PNS may be indicated by the presence of a faster migrating form of Cs32 in cerebrum versus peripheral nerve. Studies are currently underway to determine the unique role of Cx32 in peripheral nerve.« less

  13. 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.

  14. [Epidemiology of parechovirus infections of the central nervous system in a French pediatric unit].

    PubMed

    Escuret, A; Mirand, A; Dommergues, M-A; Couzon, B; Foucaud, P; Peigue-Lafeuille, H; Marque-Juillet, S

    2013-05-01

    Human parechoviruses (HPeV), like their counterpart enteroviruses (EV), are associated with clinical manifestations ranging from asymptomatic disease to infections of the central nervous system. Newborn and young infants are particularly at risk for severe infection. In the last 5 years, the molecular diagnosis of HPeV infection in cerebrospinal fluid (CSF) and the identification of the associated HPeV type revealed the specific association between HPeV3 and meningitis or sepsis-like illness in neonates and infants. HPeV infection is not yet routinely diagnosed in clinical virology laboratories. To determine the clinical, biological, and epidemiological characteristics of HPeV infections of patients hospitalized at the Centre Hospitalier de Versailles, France. A total of 380 CSF samples originally referred to our laboratory for enterovirus testing between January 1st, 2007 and August 31st, 2011, were selected and retrospectively screened for the genome detection of HPeV. All HPeV detected were identified by amplification and sequencing of the complete 1D sequence encoding the VP1 protein. The HPeV genome was detected in CSF samples from nine (2.8%) patients. All were young infants under 18 months of age (median, 30 days; age range, 8 days to 18 months). Fever was observed for all children and eight out of nine (89%) presented with irritability. No pleiocytosis and normal glucose and protein levels were observed. The mean duration of the hospital stay was 4 days (range, 2-7 days) and antibiotics were administered to five patients (55.6%). Yearly frequency of genome detection varied remarkably: 1.1% in 2007, 0% in 2008 and 2011, 2.9% in 2009 and 7.1% in 2010. All genotyped viruses were HPeV3. This study confirmed the importance of the HPeV genome detection in CSF samples from patients presenting with sepsis-like illness or suspected infection of the central nervous system, particularly in children under 2 years of age. The introduction of the molecular diagnosis of

  15. [Multicenter investigation of bufavirus in the etiology of viral central nervous system infections of adults and children].

    PubMed

    Altay Koçak, Aylin; Öcal, Murat; Polat, Meltem; Kanık Yüksek, Saliha; Aktaş Tapısız, Anıl; Tezer, Hasan; Özkul, Aykut; Ergünay, Koray; Bozdayı, Gülendam; Ahmed, Kamruddin

    2017-04-01

    Bufavirus (BuV) is a newly-identified parvovirus in the family of Parvoviridae. Metagenomic analysis of fecal samples from children in Burkina Faso with acute diarrhea showed a highly divergent parvovirus, which was named bufavirus (BuV). The global distribution, epidemiology and genetic characteristics of BuVs infections are obscure. It was first discovered as an agent causing gastroenteritis but the association of BuV infections with various clinical presentations mostly remain to be explored. The aims of this study were to investigate probable impact of BuV in central nervous system infections in a region where it was previously reported to cause human infections and to detect enteroviruses (EV) which are reported as a cause of central nervous system infections in our country. The study was undertaken in three institutions in Ankara province, Central Anatolia, Turkey. Patients, clinically diagnosed with febrile disease and/or central nervous system infections of presumed viral etiology, were enrolled in the study with informed consent. Cerebrospinal fluid specimens were collected from 93 children attended to Gazi University Hospital and Dışkapı Yıldırım Beyazıt Hospital from October 2011-April 2015 and 33 adult patients, attended to Hacettepe University Hospital from June 2012 to March 2013. Clinical history and follow-up, physical examination and standard laboratory findings of the patients were recorded. Nucleic acid extraction was performed via commercially available spin-column assays and complementery DNA (cDNA) synthesis was performed by using commercially available cDNA synthesis kit with randomised hexamer primers. BuV detection was carried out by in house nested-polymerase chain reaction (PCR) utilized with previously-described primers. EV detection was carried out by in house PCR with pan-enterovirus primers. Seventy-four percent (93/126) and 26% (33/126) of the patients were children (0-18) and adults (19-86), respectively. In all patients

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. Evolution of bilaterian central nervous systems: a single origin?

    PubMed Central

    2013-01-01

    The question of whether the ancestral bilaterian had a central nervous system (CNS) or a diffuse ectodermal nervous system has been hotly debated. Considerable evidence supports the theory that a CNS evolved just once. However, an alternative view proposes that the chordate CNS evolved from the ectodermal nerve net of a hemichordate-like ancestral deuterostome, implying independent evolution of the CNS in chordates and protostomes. To specify morphological divisions along the anterior/posterior axis, this ancestor used gene networks homologous to those patterning three organizing centers in the vertebrate brain: the anterior neural ridge, the zona limitans intrathalamica and the isthmic organizer, and subsequent evolution of the vertebrate brain involved elaboration of these ancestral signaling centers; however, all or part of these signaling centers were lost from the CNS of invertebrate chordates. The present review analyzes the evidence for and against these theories. The bulk of the evidence indicates that a CNS evolved just once – in the ancestral bilaterian. Importantly, in both protostomes and deuterostomes, the CNS represents a portion of a generally neurogenic ectoderm that is internalized and receives and integrates inputs from sensory cells in the remainder of the ectoderm. The expression patterns of genes involved in medio/lateral (dorso/ventral) patterning of the CNS are similar in protostomes and chordates; however, these genes are not similarly expressed in the ectoderm outside the CNS. Thus, their expression is a better criterion for CNS homologs than the expression of anterior/posterior patterning genes, many of which (for example, Hox genes) are similarly expressed both in the CNS and in the remainder of the ectoderm in many bilaterians. The evidence leaves hemichordates in an ambiguous position – either CNS centralization was lost to some extent at the base of the hemichordates, or even earlier, at the base of the hemichordates

  3. Peripheral Nervous System Genes Expressed in Central Neurons Induce Growth on Inhibitory Substrates

    PubMed Central

    Buchser, William J.; Smith, Robin P.; Pardinas, Jose R.; Haddox, Candace L.; Hutson, Thomas; Moon, Lawrence; Hoffman, Stanley R.; Bixby, John L.; Lemmon, Vance P.

    2012-01-01

    Trauma to the spinal cord and brain can result in irreparable loss of function. This failure of recovery is in part due to inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared to central nervous system neurons, even in the presence of inhibitory environments. Previously, we identified over a thousand genes differentially expressed in PNS neurons relative to CNS neurons. These genes represent intrinsic differences that may account for the PNS’s enhanced regenerative ability. Cerebellar neurons were transfected with cDNAs for each of these PNS genes to assess their ability to enhance neurite growth on inhibitory (CSPG) or permissive (laminin) substrates. Using high content analysis, we evaluated the phenotypic profile of each neuron to extract meaningful data for over 1100 genes. Several known growth associated proteins potentiated neurite growth on laminin. Most interestingly, novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX). Bioinformatic approaches also uncovered a number of novel gene families that altered neurite growth of CNS neurons. PMID:22701605

  4. Yeast central nervous system infection in a critically ill patient: a case report.

    PubMed

    Frantzeskaki, Frantzeska; Diakaki, Chryssi; Rizos, Michalis; Theodorakopoulou, Maria; Papadopoulos, Panagiotis; Antonopoulou, Anastasia; Nikitas, Nikitas; Lignos, Michail; Brountzos, Elias; Velegraki, Aristea; Paramythiotou, Elisabeth; Panagyotides, John; Armaganidis, Apostolos; Dimopoulos, George

    2014-07-15

    Invasive fungal infections are alarmingly common in intensive care unit patients; invasive fungal infections are associated with increased morbidity and mortality. Risk factors are the increased use of indwelling central venous catheters, the use of broad spectrum antibiotics, parenteral nutrition, renal replacement therapy and immunosuppression. Diagnosis of these infections might be complicated, requiring tissue cultures. In addition, therapy of invasive fungal infections might be difficult, given the rising resistance of fungi to antifungal agents. We describe the case of a 28-year-old Greek man with yeast central nervous system infection. Difficult-to-treat fungal infections may complicate the clinical course of critically ill patients and render their prognosis unfavorable. This report presents a case that was rare and difficult to treat, along with a thorough review of the investigation and treatment of these kinds of fungal infections in critically ill patients.

  5. The pharmacological effects of Salvia species on the central nervous system.

    PubMed

    Imanshahidi, Mohsen; Hosseinzadeh, Hossein

    2006-06-01

    Salvia is an important genus consisting of about 900 species in the family Lamiaceae. Some species of Salvia have been cultivated world wide for use in folk medicine and for culinary purposes. The dried root of Salvia miltiorrhiza, for example, has been used extensively for the treatment of coronary and cerebrovascular disease, sleep disorders, hepatitis, hepatocirrhosis, chronic renal failure, dysmenorrhea, amenorrhea, carbuncles and ulcers. S. officinalis, S. leriifolia, S. haematodes, S. triloba and S. divinorum are other species with important pharmacological effects. In this review, the pharmacological effects of Salvia species on the central nervous system will be reviewed. These include sedative and hypnotic, hallucinogenic, skeletal muscle relaxant, analgesic, memory enhancing, anticonvulsant, neuroprotective and antiparkinsonian activity, as well as the inhibition of ethanol and morphine withdrawal syndrome.

  6. Central nervous system lymphoma presenting as trigeminal neuralgia: A diagnostic challenge

    PubMed Central

    Ang, Jensen W. J.; Khanna, Arjun; Walcott, Brian P.; Kahle, Kristopher T.; Eskandar, Emad N.

    2015-01-01

    We describe an atypical man with diffuse large B cell lymphoma localized to the sphenoid wing and adjacent cavernous sinus, initially presenting with isolated ipsilateral facial pain mimicking trigeminal neuralgia due to invasion of Meckel’s cave but subsequently progressing to intra-axial extension and having synchronous features of systemic lymphoma. Primary central nervous system lymphoma is uncommon, accounting for approximately 2% of all primary intra-cranial tumors, but its incidence has been steadily increasing in some groups [1]. It usually arises in periventricular cerebral white matter, reports of lymphoma in extra-axial regions are rare [2]. This man highlights the importance of maintaining lymphoma in the differential diagnosis of tumors of the skull base presenting with trigeminal neuralgia-like symptoms. PMID:25865026

  7. 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.

  8. Central nervous system regulation of hepatic lipid and lipoprotein metabolism.

    PubMed

    Taher, Jennifer; Farr, Sarah; Adeli, Khosrow

    2017-02-01

    Hepatic lipid and lipoprotein metabolism is an important determinant of fasting dyslipidemia and the development of fatty liver disease. Although endocrine factors like insulin have known effects on hepatic lipid homeostasis, emerging evidence also supports a regulatory role for the central nervous system (CNS) and neuronal networks. This review summarizes evidence implicating a bidirectional liver-brain axis in maintaining metabolic lipid homeostasis, and discusses clinical implications in insulin-resistant states. The liver utilizes sympathetic and parasympathetic afferent and efferent fibers to communicate with key regulatory centers in the brain including the hypothalamus. Hypothalamic anorexigenic and orexigenic peptides signal to the liver via neuronal networks to modulate lipid content and VLDL production. In addition, peripheral hormones such as insulin, leptin, and glucagon-like-peptide-1 exert control over hepatic lipid by acting directly within the CNS or via peripheral nerves. Central regulation of lipid metabolism in other organs including white and brown adipose tissue may also contribute to hepatic lipid content indirectly via free fatty acid release and changes in lipoprotein clearance. The CNS communicates with the liver in a bidirectional manner to regulate hepatic lipid metabolism and lipoprotein production. Impairments in these pathways may contribute to dyslipidemia and hepatic steatosis in insulin-resistant states.

  9. 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.

  10. 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.

  11. Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review

    PubMed Central

    Wang, Huiying; Lee, In-Seon; Braun, Christoph; Enck, Paul

    2016-01-01

    To systematically review the effects of probiotics on central nervous system function in animals and humans, to summarize effective interventions (species of probiotic, dose, duration), and to analyze the possibility of translating preclinical studies. Literature searches were conducted in Pubmed, Medline, Embase, and the Cochrane Library. Only randomized controlled trials were included. In total, 38 studies were included: 25 in animals and 15 in humans (2 studies were conducted in both). Most studies used Bifidobacterium (eg, B. longum, B. breve, and B. infantis) and Lactobacillus (eg, L. helveticus, and L. rhamnosus), with doses between 109 and 1010 colony-forming units for 2 weeks in animals and 4 weeks in humans. These probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder (ASD), obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. Because many of the basic science studies showed some efficacy of probiotics on central nervous system function, this background may guide and promote further preclinical and clinical studies. Translating animal studies to human studies has obvious limitations but also suggests possibilities. Here, we provide several suggestions for the translation of animal studies. More experimental designs with both behavioral and neuroimaging measures in healthy volunteers and patients are needed in the future. PMID:27413138

  12. Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review.

    PubMed

    Wang, Huiying; Lee, In-Seon; Braun, Christoph; Enck, Paul

    2016-10-30

    To systematically review the effects of probiotics on central nervous system function in animals and humans, to summarize effective interventions (species of probiotic, dose, duration), and to analyze the possibility of translating preclinical studies. Literature searches were conducted in Pubmed, Medline, Embase, and the Cochrane Library. Only randomized controlled trials were included. In total, 38 studies were included: 25 in animals and 15 in humans (2 studies were conducted in both). Most studies used Bifidobacterium (eg, B. longum , B. breve , and B. infantis ) and Lactobacillus (eg, L. helveticus , and L. rhamnosus ), with doses between 10⁸ and 10¹⁰ colony-forming units for 2 weeks in animals and 4 weeks in humans. These probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder (ASD), obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. Because many of the basic science studies showed some efficacy of probiotics on central nervous system function, this background may guide and promote further preclinical and clinical studies. Translating animal studies to human studies has obvious limitations but also suggests possibilities. Here, we provide several suggestions for the translation of animal studies. More experimental designs with both behavioral and neuroimaging measures in healthy volunteers and patients are needed in the future.

  13. Evaluation system for minor nervous dysfunction by pronation and supination of forearm using wireless acceleration and angular velocity sensors.

    PubMed

    Iramina, Keiji; Kamei, Yuuichiro; Katayama, Yoshinori

    2011-01-01

    We developed a simple, portable and easy system to the motion of pronation and supination of the forearm. This motion was measured by wireless acceleration and angular velocity sensor. The aim of this system is evaluation of minor nervous dysfunction. It is for the screening of the developmental disorder child. In this study, in order to confirm the effectiveness of this system, the reference curve of the neuromotor development was experimentally obtained. We studied 212 participants (108 males, 104 females) aged 7 to 12 years attending the kindergarten school. We could obtain the reference curve of the neuromotor development using this system. We also investigated the difference of neuromotor function between normally developed children and a ADHD child. There is a possibility that abnormality of the minor nervous dysfunction can be detected by using this system.

  14. Pharmacological MRI (phMRI) of the Human Central Nervous System.

    PubMed

    Lanfermann, H; Schindler, C; Jordan, J; Krug, N; Raab, P

    2015-10-01

    Pharmacological magnetic resonance imaging (phMRI) of the central nervous system (CNS) addresses the increasing demands in the biopharma industry for new methods that can accurately predict, as early as possible, whether novel CNS agents will be effective and safe. Imaging of physiological and molecular-level function can provide a more direct measure of a drug mechanism of action, enabling more predictive measures of drug activity. The availability of phMRI of the nervous system within the professional infrastructure of the Clinical Research Center (CRC) Hannover as proof of concept center ensures that advances in basic science progress swiftly into benefits for patients. Advanced standardized MRI techniques including quantitative MRI, kurtosis determination, functional MRI, and spectroscopic imaging of the entire brain are necessary for phMRI. As a result, MR scanners will evolve into high-precision measuring instruments for assessment of desirable and undesirable effects of drugs as the basic precondition for individually tailored therapy. The CRC's Imaging Unit with high-end large-scale equipment will allow the following unique opportunities: for example, identification of MR-based biomarkers to assess the effect of drugs (surrogate parameters), establishment of normal levels and reference ranges for MRI-based biomarkers, evaluation of the most relevant MRI sequences for drug monitoring in outpatient care. Another very important prerequisite for phMRI is the MHH Core Facility as the scientific and operational study unit of the CRC partner Hannover Medical School. This unit is responsible for the study coordination, conduction, complete study logistics, administration, and application of the quality assurance system based on required industry standards.

  15. Central nervous system.

    PubMed

    Adamson, D Cory; Rasheed, B Ahmed K; McLendon, Roger E; Bigner, Darell D

    2010-01-01

    Several different types of tumors, benign and malignant, have been identified in the central nervous system (CNS). The prognoses for these tumors are related to several factors, such as the age of the patient and the location and histology of the tumor. In adults, about half of all CNS tumors are malignant, whereas in pediatric patients, more than 75% are malignant. For most benign CNS tumors that require treatment, neurosurgeons can offer curative resections or at least provide significant relief from mass effect. Unfortunately, we still lack effective treatments for most primary and secondary malignant CNS tumors. However, the past decade has witnessed an explosion in the understanding of the early molecular events in malignant primary CNS tumors, and for the first time in history, oncologists are seeing that a plethora of new therapies targeting these molecular events are being tested in clinical trials. There is hope on the horizon for the fight against these deadly tumors. The distribution of CNS tumors by location has remained constant for numerous years. The majority of primary CNS tumors arise in the major cortical lobes. Twenty nine percent of primary CNS tumors arise from the dural meninges that encase the CNS structures. The vast majority of these are meningiomas, of which over 90% are benign. About 10% of primary CNS tumors are found in the sella turcica region, where the pituitary gland resides. Other much less common sites of primary CNS tumors include the pineal region, ventricular system, cerebellum, brain stem, cranial nerves, and spinal cord. The distribution of CNS tumors by histology has seen a slight increase in more malignant tumors over the past decade, possibly due to increased neuroimaging practices or environmental exposures. Arising from glial cells, gliomas represent over 36% of all primary CNS tumors and consist of astrocytomas, oligodendrogliomas, ependymomas, mixed gliomas, and neuroepithelial tumors. The benign meningiomas make up 32

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Planarian homologs of netrin and netrin receptor are required for proper regeneration of the central nervous system and the maintenance of nervous system architecture.

    PubMed

    Cebrià, Francesc; Newmark, Phillip A

    2005-08-01

    Conserved axon guidance mechanisms are essential for proper wiring of the nervous system during embryogenesis; however, the functions of these cues in adults and during regeneration remain poorly understood. Because freshwater planarians can regenerate a functional central nervous system (CNS) from almost any portion of their body, they are useful models in which to study the roles of guidance cues during neural regeneration. Here, we characterize two netrin homologs and one netrin receptor family member from Schmidtea mediterranea. RNAi analyses indicate that Smed-netR (netrin receptor) and Smed-netrin2 are required for proper CNS regeneration and that Smed-netR may mediate the response to Smed-netrin2. Remarkably, Smed-netR and Smed-netrin2 are also required in intact planarians to maintain the proper patterning of the CNS. These results suggest a crucial role for guidance cues, not only in CNS regeneration but also in maintenance of neural architecture.

  1. 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…

  2. Potential Clinical Impact of The Filmarray Meningitis Encephalitis Panel In Children With Suspected Central Nervous System Infections

    PubMed Central

    Messacar, Kevin; Breazeale, Garrett; Robinson, Christine C.; Dominguez, Samuel R.

    2016-01-01

    The FilmArray Meningitis Encephalitis Panel, a multiplex PCR for testing of cerebrospinal fluid, was compared to conventional diagnostic methods in children with suspected central nervous system infections. The panel had comparable diagnostic yield (96% agreement) and improved time-to-diagnosis by 10.3 hours with potential for more judicious antimicrobial use, particularly acyclovir. PMID:27342782

  3. Antiretroviral Therapy and Central Nervous System HIV-1 Infection

    PubMed Central

    Price, Richard W.; Spudich, Serena

    2008-01-01

    Central nervous system (CNS) HIV-1 infection begins during primary viremia and continues throughout the course of untreated systemic infection. While frequently accompanied by local inflammatory reactions detectable in cerebrospinal fluid (CSF), CNS HIV-1 infection is not usually clinically apparent. In a minority of patients, CNS HIV-1 infection evolves late in the course of systemic infection into encephalitis, which compromises brain function and presents clinically as AIDS dementia complex (ADC). Combination highly active antiretroviral therapy (HAART) has had a major impact on all aspects of HIV-1 CNS infection and disease. In those with asymptomatic infection, HAART usually effectively suppresses CSF HIV-1 and markedly reduces the incidence of symptomatic ADC. In those presenting with ADC, HAART characteristically prevents neurological progression and leads to variable, and at times substantial, recovery. Treatment has similarly reduced CNS opportunistic infections. With better control of these severe disorders, attention has turned to the possible consequences of chronic silent infection, and the issue of whether indolent, low-grade brain injury might require earlier treatment intervention. PMID:18447615

  4. Changing central nervous system control following intercostal nerve transfer.

    PubMed

    Malessy, M J; Thomeer, R T; van Dijk, J G

    1998-10-01

    The goal of this study was to find which central nervous system (CNS) pathways are involved in volitional control over reinnervated biceps or pectoral muscles. Intercostal nerves (ICNs) were coapted to the musculocutaneous nerve (MCN) or the medial pectoral nerve (MPN) in 23 patients with root avulsions of the brachial plexus to restore biceps or pectoral muscle function. The facilitatory effects of respiration and voluntary contraction on cortical motor-evoked potentials of biceps or pectoral muscles were used to study CNS control over the reinnervated muscles. The time course of the facilitatory effect of respiration and voluntary contraction differed significantly. In the end stage of nerve regeneration, the facilitatory effect of voluntary contraction was significantly larger than that of respiration, indicating that the CNS control network over the muscle comes to resemble that of the recipient nerve (MCN or MPN) rather than that of the donor nerve (ICN). The strengthening of previously subthreshold synaptic connections in a CNS network connecting ICN to MCN or MPN neurons may underlie changing excitability.

  5. A Review on Central Nervous System Effects of Gastrodin

    PubMed Central

    Liu, Yuan; Gao, Jialiang; Peng, Min; Meng, Hongyan; Ma, Hongbo; Cai, Pingping; Xu, Yuan; Zhao, Qiong; Si, Guomin

    2018-01-01

    Rhizoma Gastrodiae (also known as Tian ma), the dried rhizome of Gastrodia elata Blume, is a famous Chinese herb that has been traditionally used for the treatment of headache, dizziness, spasm, epilepsy, stoke, amnesia and other disorders for centuries. Gastrodin, a phenolic glycoside, is the main bioactive constituent of Rhizoma Gastrodiae. Since identified in 1978, gastrodin has been extensively investigated on its pharmacological properties. In this article, we reviewed the central nervous system (CNS) effects of gastrodin in preclinical models of CNS disorders including epilepsy, Alzheimer's disease, Parkinson's disease, affective disorders, cerebral ischemia/reperfusion, cognitive impairment as well as the underlying mechanisms involved and, where possible, clinical data that support the pharmacological activities. The sources and pharmacokinetics of gastrodin were also reviewed here. As a result, gastrodin possesses a broad range of beneficial effects on the above-mentioned CNS diseases, and the mechanisms of actions include modulating neurotransmitters, antioxidative, anti-inflammatory, suppressing microglial activation, regulating mitochondrial cascades, up-regulating neurotrophins, etc. However, more detailed clinical trials are still in need for positioning it in the treatment of neurological disorders. PMID:29456504

  6. Peptidomics of prolyl endopeptidase in the central nervous system

    PubMed Central

    Nolte, Whitney M.; Tagore, Debarati M.; Lane, William S.; Saghatelian, Alan

    2009-01-01

    Prolyl endopeptidase (Prep) is a member of the prolyl peptidase family and is of interest due to its unique biochemistry and connections to cognitive function. Using an unbiased mass spectrometry (MS)-based peptidomics platform, we identified Prep regulated peptides in the central nervous system (CNS) of mice by measuring changes in the peptidome as a function of Prep activity. This approach was validated by the identification of known Prep substrates, such as the neuropeptide substance P and thymosin-β4, the precursor to the bioactive peptide Ac-SDKP. In addition to these known substrates, we also discovered that Prep regulates many additional peptides, including additional bioactive peptides and proline rich peptides (PRPs). Biochemical experiments confirmed that some of these Prep regulated peptides are indeed substrates of the enzyme. Moreover, these experiments also supported the known preference of Prep for shorter peptides, while revealing a previously unknown cleavage site specificity of Prep when processing certain multi-proline containing peptides, including PRPs. The discovery of Prep regulated peptides implicates Prep in new biological pathways and provides insights into the biochemistry of this enzyme. PMID:19911840

  7. 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.

  8. [Central nervous system involvement in systemic diseases: Spectrum of MRI findings].

    PubMed

    Drier, A; Bonneville, F; Haroche, J; Amoura, Z; Dormont, D; Chiras, J

    2010-12-01

    Central nervous system (CNS) involvement in systemic disease (SD) is unusual. MRI features of such lesions are unfamiliar to most radiologists. The diagnosis of SD is still based on clinical features and laboratory findings but some characteristic MRI findings exist for each SD: micronodular leptomeningeal enhancement in sarcoidosis, diffuse or focal pachymeningeal involvement in Wegener disease, dentate nuclei and brain stem lesions in Langerhans cell histiocytosis, meningeal masses, dentate nuclei lesions and periarterial infiltration in Erdheim-Chester disease, meningeal masses in Rosai-Dorfman disease, veinular pontic lesions and cerebral vein thrombosis in Behçet, supratentorial microvascular lesions in lupus and antiphospholipid and Gougerot-Sjögren syndrome. In this work, we explain, describe and illustrate the most characteristic MRI findings for each disease. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  9. Coexposure to toluene and p-xylene in man: central nervous functions.

    PubMed Central

    Olson, B A; Gamberale, F; Iregren, A

    1985-01-01

    Sixteen men were studied in an exposure chamber to assess the effect of four hours' exposure to toluene (3.25 mmol/m3), xylene (2.84 mmol/m3), a mixture of toluene and xylene (2.20 + 0.94 mmol/m3), and a control condition. With the aid of microcomputers, subjects performed tests of simple reaction time, short term memory, and choice reaction time immediately after entering the chamber, after two, and after four hours' exposure. The results indicate that the performance on the tests was unaffected by exposure. In the light of this result the risk of an acute effect on central nervous functions after exposure for four hours at concentrations that do not exceed the Swedish threshold limit values was considered to be minimal. PMID:3970870

  10. Central nervous system lymphoma presenting as trigeminal neuralgia: A diagnostic challenge.

    PubMed

    Ang, Jensen W J; Khanna, Arjun; Walcott, Brian P; Kahle, Kristopher T; Eskandar, Emad N

    2015-07-01

    We describe an atypical man with diffuse large B cell lymphoma localized to the sphenoid wing and adjacent cavernous sinus, initially presenting with isolated ipsilateral facial pain mimicking trigeminal neuralgia due to invasion of Meckel's cave but subsequently progressing to intra-axial extension and having synchronous features of systemic lymphoma. Primary central nervous system lymphoma is uncommon, accounting for approximately 2% of all primary intracranial tumors, but its incidence has been steadily increasing in some groups [1]. It usually arises in the periventricular cerebral white matter, and reports of lymphoma in extra-axial regions are rare [2]. This man highlights the importance of maintaining lymphoma in the differential diagnosis of tumors of the skull base presenting with trigeminal neuralgia-like symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Glia-derived signals induce synapse formation in neurones of the rat central nervous system

    PubMed Central

    Nägler, Karl; Mauch, Daniela H; Pfrieger, Frank W

    2001-01-01

    To study the effects of glial cells on synapse formation, we established microcultures of purified rat retinal ganglion cells (RGCs) and monitored synapse (autapse) development in single neurones using electrophysiological recordings, FM1-43 labelling and immunocytochemistry.Solitary neurones grew ramifying neurites, but formed only very few and inefficient excitatory autapses, when cultured for up to 2 weeks in defined medium and in the absence of glial cells.Treatment of glia-free microcultures of RGCs with glia-conditioned medium (GCM) increased the number of autapses per neurone by up to 10-fold. This was indicated by a similar increase in the frequency of spontaneous events and the number of FM1-43-labelled functional release sites and of puncta, where pre- and postsynaptic markers colocalized.In addition, GCM treatment enhanced the efficacy of presynaptic transmitter release as indicated by lower failure rates of stimulation-induced excitatory autaptic currents, a 200-fold increase in the frequency of asynchronous release and an accelerated stimulation-induced FM1-43 destaining. Furthermore, GCM induced an increase in the quantal size.GCM affected autaptic activity not immediately, but with a delay of 24 h, and the effects on stimulation-induced autaptic currents occurred before changes in the frequency of spontaneous events indicating an early strengthening of existing autapses followed by a later increase in autapse number.The observed effects were mediated by proteinase K-sensitive factors in GCM and occurred independently of electrical activity.These results suggest that soluble glia-derived signals induce synapse formation and maturation in neurones of the central nervous system (CNS). PMID:11410625

  12. Primary central nervous system diffuse large B-cell lymphoma in the immunocompetent: Immunophenotypic subtypes and Epstein-Barr virus association.

    PubMed

    Mahadevan, Anita; Rao, Clementina Rama; Shanmugham, M; Shankar, Susarla Krishna

    2015-01-01

    Primary central nervous system diffuse large B-cell lymphoma (PCNSL DLBCL) in the immunocompetent is an uncommon tumor that has an activated B-cell immunophenotype resembling germinal center exit B cells. They also differ from primary central nervous diffuse large B-cell lymphomas in the immunocompromised as they show no association with the Epstein-Barr virus. To determine if immunophenotypic subtyping of PCNS DLBCL from Asian subcontinent are also different similar to its systemic counterpart is unclear, as there are only limited studies from Asia, and none from India. The immunohistochemical profile of 24 South Indian patients with primary central nervous system diffuse large B-cell lymphoma was studied using germinal center markers - CD10 and Bcl-6, and activation markers - MUM1 and CD138, which are markers for late/post germinal centre B cells. Insitu hybridization for EBV genome and LMP1 by immunohistochemistry was carried out in all cases to determine association with EBV. Centroblastic morphology and uniform activated B-cell phenotype with positivity for MUM1 was seen in 91.6% of tumors. Co-expression of Bcl-6 and MUM1 was evident in 50%, which is more frequent than in systemic diffuse large B-cell lymphomas. All cases were negative for Epstein-Barr virus using EBER in-situ hybridization and LMP1 immunohistochemistry. Primary diffuse large B-cell lymphoma in the immunocompetent is a distinct clinicopathological entity with centroblastic morphology, a uniform activated B-cell immunophenotype that is not associated with the Epstein-Barr virus regardless of geographic origin.

  13. Central nervous system stimulants and sport practice

    PubMed Central

    Avois, L; Robinson, N; Saudan, C; Baume, N; Mangin, P; Saugy, M

    2006-01-01

    Background and objectives Central nervous system (CNS) stimulants may be used to reduce tiredness and increase alertness, competitiveness, and aggression. They are more likely to be used in competition but may be used during training to increase the intensity of the training session. There are several potential dangers involving their misuse in contact sports. This paper reviews the three main CNS stimulants, ephedrine, amfetamine, and cocaine, in relation to misuse in sport. Methods Description of the pharmacology, actions, and side effects of amfetamine, cocaine, and ephedrine. Results CNS stimulants have psychotropic effects that may be perceived to be ergogenic. Some are prescription drugs, such as Ephedra alkaloids, and there are issues regarding their appropriate therapeutic use. Recently attention has been given to their widespread use by athletes, despite the lack of evidence regarding any ergogenic or real performance benefit, and their potentially serious side effects. Recreational drugs, some of which are illegal (cocaine, amfetamines), are commonly used by athletes and cause potential ergolytic effects. Overall, these drugs are important for their frequent use and mention in anti‐doping laboratories statistics and the media, and their potentially serious adverse effects. Conclusions Doping with CNS stimulants is a real public health problem and all sports authorities should participate in its prevention. Dissemination of information is essential to prevent doping in sport and to provide alternatives. Adequate training and education in this domain should be introduced. PMID:16799095

  14. Isolated central nervous system progression on Crizotinib

    PubMed Central

    Chun, Stephen G.; Choe, Kevin S.; Iyengar, Puneeth; Yordy, John S.; Timmerman, Robert D.

    2012-01-01

    Advanced non-small lung cancer (NSCLC) remains almost uniformly lethal with marginal long-term survival despite efforts to target specific oncogenic addiction pathways that may drive these tumors with small molecularly targeted agents and biologics. The EML4-ALK fusion gene encodes a chimeric tyrosine kinase that activates the Ras signaling pathway, and this fusion protein is found in approximately 5% of NSCLC. Targeting EML4-ALK with Crizotinib in this subset of NSCLC has documented therapeutic efficacy, but the vast majority of patients eventually develop recurrent disease that is often refractory to further treatments. We present the clinicopathologic features of three patients with metastatic NSCLC harboring the EML4-ALK translocation that developed isolated central nervous system (CNS) metastases in the presence of good disease control elsewhere in the body. These cases suggest a differential response of NSCLC to Crizotinib in the brain in comparison to other sites of disease, and are consistent with a previous report of poor CNS penetration of Crizotinib. Results of ongoing clinical trials will clarify whether the CNS is a major sanctuary site for EML4-ALK positive NSCLC being treated with Crizotinib. While understanding molecular mechanisms of resistance is critical to overcome therapeutic resistance, understanding physiologic mechanisms of resistance through analyzing anatomic patterns of failure may be equally crucial to improve long-term survival for patients with EML4-ALK translocation positive NSCLC. PMID:22986231

  15. The physiological functions of central nervous system pericytes and a potential role in pain

    PubMed Central

    Beazley-Long, Nicholas; Durrant, Alexandra M; Swift, Matthew N; Donaldson, Lucy F

    2018-01-01

    Central nervous system (CNS) pericytes regulate critical functions of the neurovascular unit in health and disease. CNS pericytes are an attractive pharmacological target for their position within the neurovasculature and for their role in neuroinflammation. Whether the function of CNS pericytes also affects pain states and nociceptive mechanisms is currently not understood. Could it be that pericytes hold the key to pain associated with CNS blood vessel dysfunction? This article reviews recent findings on the important physiological functions of CNS pericytes and highlights how these neurovascular functions could be linked to pain states. PMID:29623199

  16. Central nervous system infection with Staphylococcus intermedius secondary to retrobulbar abscessation in a dog.

    PubMed

    Oliver, James A C; Llabrés-Diaz, Francisco J; Gould, David J; Powell, Roger M

    2009-01-01

    In this report, we describe a case of retrobulbar abscessation in a dog that was initially diagnosed as masticatory myositis and treated with immunosuppressive doses of corticosteroids. Secondary bacterial infection of the central nervous system (CNS) occurred and was definitively diagnosed by the analysis and culture of the cerebrospinal fluid. This is the first time that retrobulbar infection has been definitively shown to result in secondary bacterial infection of the CNS in the dog and highlights the importance of ruling out infectious causes of retrobulbar disease before assuming and treating for an immune-mediated etiology.

  17. Central Nervous System Control of Voice and Swallowing

    PubMed Central

    Ludlow, Christy L.

    2015-01-01

    This review of the central nervous control systems for voice and swallowing has suggested that the traditional concepts of a separation between cortical and limbic and brain stem control should be refined and more integrative. For voice production, a separation of the non-human vocalization system from the human learned voice production system has been posited based primarily on studies of non-human primates. However, recent humans studies of emotionally based vocalizations and human volitional voice production has shown more integration between these two systems than previously proposed. Recent human studies have shown that reflexive vocalization as well as learned voice production not involving speech, involve a common integrative system. On the other hand, recent studies of non-human primates have provided evidence of some cortical activity during vocalization and cortical changes with training during vocal behavior. For swallowing, evidence from the macaque and functional brain imaging in humans indicates that the control for the pharyngeal phase of swallowing is not primarily under brain stem mechanisms as previously proposed. Studies suggest that the initiation and patterning of swallowing for the pharyngeal phase is also under active cortical control for both spontaneous as well as volitional swallowing in awake humans and non-human primates. PMID:26241238

  18. Central Nervous System Histoplasmosis in Acquired Immunodeficiency Syndrome.

    PubMed

    Nyalakonda, Harita; Albuerne, Marisol; Suazo Hernandez, Lia Patricia; Sarria, Juan C

    2016-02-01

    Involvement of the central nervous system (CNS) by Histoplasma capsulatum in AIDS is uncommon and not easily recognized. CNS histoplasmosis cases from our institution were identified by a retrospective chart review from 2004-2014. A thorough literature search was performed for additional cases and their characteristics were compared. Clinical findings, treatment and outcomes are discussed. A total of 5 cases from our institution were identified. They had a clinical presentation that included classic signs of meningitis, often with evidence of disseminated involvement, and was typically severe with important neurological impairment. These cases were treated with antifungal agents, including a lipid amphotericin B formulation and azole drugs, but eventually 3 experienced nonresolution of their disease likely because of lack of adherence to therapy and died from their infection. The clinical presentation, treatment and outcome of these cases did not significantly differ from cases found in the review of the literature. Clinicians practicing in endemic areas should be aware of this rare but serious form of histoplasmosis. The recognition of 5 cases of CNS histoplasmosis in AIDS patients from a single institution suggests that histoplasmosis should be included in the differential diagnosis of the CNS complications of AIDS. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    Morita, Akihiko; Ishihara, Masaki; Konno, Michiko

    2016-04-01

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

  20. Primary central nervous system lymphoma masquerading as bilateral vitreous floaters.

    PubMed

    Tsanaktsidis, G; McNeill, O; Katelaris, C

    2012-04-01

    A 72-year-old female presented with a 6-month history of bilateral floaters and visual blurring. Clinically, the posterior vitreous was cellular bilaterally, with no signs of subretinal infiltrates, retinal vasculitis, disc oedema or macula oedema. A vitreous biopsy and vitrectomy were scheduled following left cataract surgery because of the presence of a dense cataract. One month after cataract surgery, the patient developed signs of florid left arteritis involving the first-order branches of the central retinal artery. A 23-gauge vitreous biopsy and vitrectomy were performed, and preservative-free triamcinolone was injected. Cytology of the biopsy demonstrated benign T-lymphocytes and histiocytes suggestive of mild chronic inflammation only. Magnetic resonance imaging (MRI) of the brain was normal as was lumbar puncture. Subsequently, the patient developed right upper motor neuron facial nerve palsy. MRI imaging on this occasion demonstrated multiple hyper-intense white matter lesions. A third MRI was subsequently obtained due to new neurological deficits and demonstrated enlargement of the pre-existing lesions. Brain biopsy confirmed the presence of primary cerebral lymphoma. The present case highlights the role of various tissue biopsies, including vitreous, cerebrospinal fluid and brain tissue, to establish an elusive diagnosis of primary central nervous system lymphoma presenting as benign vitreous floaters. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

  1. Patients with primary diffuse large B-cell lymphoma of female genital tract have high risk of central nervous system relapse.

    PubMed

    Cao, Xin-xin; Li, Jian; Zhang, Wei; Duan, Ming-hui; Shen, Ti; Zhou, Dao-bin

    2014-06-01

    The objective of this study was to evaluate retrospectively the clinical characteristics, treatments, and outcomes of patients with primary diffuse large B-cell lymphoma (DLBCL) of the female genital tract. The basic characteristics, treatments, and outcomes of six patients diagnosed with primary DLBCL of the female genital tract, including the ovary, uterine cervix, and vagina, treated in our hospital between 2000 and 2012, were analyzed retrospectively. Seven of 323 (2.2 %) newly diagnosed DLBCLs were diagnosed as primary female genital tract DLBCL. Six patients with complete medical data were included in the analysis. The median age at diagnosis was 52.5 years (range 20-65). The presenting symptoms included abnormal vaginal bleeding, increased vaginal discharge, abdominal fullness, and abdominal pain. Two patients had stage IE disease and four patients had stage IIE disease. Treatment included chemotherapy only in five patients, and combined chemotherapy and localized radiation in one patient. After a median follow-up of 58 months, four patients showed relapse in the central nervous system and two had died from progressive disease. The median progression-free survival was 27 months and the median overall survival for this group has not been reached. Patients with primary female genital tract DLBCL may have poor outcomes and a high risk of central nervous system relapse. Central nervous system prophylaxis might be considered in addition to systemic chemotherapy for DLBCL of the female genital tract.

  2. Inhalation of Hydrocarbon Jet Fuel Suppress Central Auditory Nervous System Function.

    PubMed

    Guthrie, O'neil W; Wong, Brian A; McInturf, Shawn M; Reboulet, James E; Ortiz, Pedro A; Mattie, David R

    2015-01-01

    More than 800 million L/d of hydrocarbon fuels is used to power cars, boats, and jet airplanes. The weekly consumption of these fuels necessarily puts the public at risk for repeated inhalation exposure. Recent studies showed that exposure to hydrocarbon jet fuel produces lethality in presynaptic sensory cells, leading to hearing loss, especially in the presence of noise. However, the effects of hydrocarbon jet fuel on the central auditory nervous system (CANS) have not received much attention. It is important to investigate the effects of hydrocarbons on the CANS in order to complete current knowledge regarding the ototoxic profile of such exposures. The objective of the current study was to determine whether inhalation exposure to hydrocarbon jet fuel might affect the functions of the CANS. Male Fischer 344 rats were randomly divided into four groups (control, noise, fuel, and fuel + noise). The structural and functional integrity of presynaptic sensory cells was determined in each group. Neurotransmission in both peripheral and central auditory pathways was simultaneously evaluated in order to identify and differentiate between peripheral and central dysfunctions. There were no detectable effects on pre- and postsynaptic peripheral functions. However, the responsiveness of the brain was significantly depressed and neural transmission time was markedly delayed. The development of CANS dysfunctions in the general public and the military due to cumulative exposure to hydrocarbon fuels may represent a significant but currently unrecognized public health issue.

  3. Biopsy-proven case of Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system.

    PubMed

    Kano, Kohei; Katayama, Takayuki; Takeguchi, Shiori; Asanome, Asuka; Takahashi, Kae; Saito, Tsukasa; Sawada, Jun; Saito, Masato; Anei, Ryogo; Kamada, Kyousuke; Miyokawa, Naoyuki; Nishihara, Hiroshi; Hasebe, Naoyuki

    2017-06-01

    A 75-year-old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7-year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2-weighted MRI showed diffuse high-intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein-Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV-encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system. High-dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy-proven EBV-positive/HIV-negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV-associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis. © 2016 Japanese Society of Neuropathology.

  4. Regenerative Therapies for Central Nervous System Diseases: a Biomaterials Approach

    PubMed Central

    Tam, Roger Y; Fuehrmann, Tobias; Mitrousis, Nikolaos; Shoichet, Molly S

    2014-01-01

    The central nervous system (CNS) has a limited capacity to spontaneously regenerate following traumatic injury or disease, requiring innovative strategies to promote tissue and functional repair. Tissue regeneration strategies, such as cell and/or drug delivery, have demonstrated promising results in experimental animal models, but have been difficult to translate clinically. The efficacy of cell therapy, which involves stem cell transplantation into the CNS to replace damaged tissue, has been limited due to low cell survival and integration upon transplantation, while delivery of therapeutic molecules to the CNS using conventional methods, such as oral and intravenous administration, have been limited by diffusion across the blood–brain/spinal cord-barrier. The use of biomaterials to promote graft survival and integration as well as localized and sustained delivery of biologics to CNS injury sites is actively being pursued. This review will highlight recent advances using biomaterials as cell- and drug-delivery vehicles for CNS repair. PMID:24002187

  5. Tau Kinetics in Neurons and the Human Central Nervous System.

    PubMed

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

    2018-03-21

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

  6. Altered central nervous system processing of baroreceptor input following hindlimb unloading in rats

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    The effect of cardiovascular deconditioning on central nervous system processing of baroreceptor afferent activity was evaluated following 14 days of hindlimb unloading (HU). Inactin-anesthetized rats were instrumented with catheters, renal sympathetic nerve electrodes, and aortic depressor nerve electrodes for measurement of mean arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and aortic depressor nerve activity (ADNA). Baroreceptor and baroreflex functions were assessed during infusion of phenylephrine and sodium nitroprusside. Central processing of baroreceptor afferent input was evaluated by linear regression relating RSNA to ADNA. The maximum baroreflex-elicited increase in RSNA was significantly reduced in HU rats (122 +/- 3.8 vs. 144 +/- 4.9% of baseline RSNA), whereas ADNA was not altered. The slope (-0.18 +/- 0.04 vs. -0.40 +/- 0.04) and y-intercept (121 +/- 3.2 vs. 146 +/- 4.3) of the linear regression relating increases in efferent RSNA to decreases in afferent ADNA during hypotension were significantly reduced in HU rats. There were no differences during increases in arterial pressure. Results demonstrate that the attenuation in baroreflex-mediated increases in RSNA following HU is due to changes in central processing of baroreceptor afferent information rather than aortic baroreceptor function.

  7. Implementation of Intraoperative Neurophysiological Monitoring during Endovascular Procedures in the Central Nervous System.

    PubMed

    Martinez Piñeiro, Alicia; Cubells, Carles; Garcia, Pablo; Castaño, Carlos; Dávalos, Antonio; Coll-Canti, Jaume

    2015-03-01

    Intraoperative monitoring (IOM) has been used in different surgical disciplines since the 1980s. Nonetheless, regular routine use of IOM in interventional neuroradiology units has only been reported in a few centers. The aim of this study is to report our experience, 1 year after deciding to implement standardized IOM during endovascular treatment of vascular abnormalities of the central nervous system. Basic recordings included somatosensory-evoked potentials (SEPs) and motor-evoked potentials (MEPs). Corticobulbar motor-evoked potentials and flash-visual-evoked potentials were also recorded depending on the topography of the lesion. Intra-arterial provocative tests (PTs) with amobarbital and lidocaine were also performed. All patients except 1 were under total intravenous anesthesia. Clinical outcome was assessed prospectively and correlated with IOM events. Twelve patients and 15 procedures were monitored during the inclusion period. Significant IOM events were detected during 3 of the 15 procedures (20%). We observed temporary MEP changes in 2 cases which resolved after interruption of the embolization or application of corrective measures, leaving no postoperative neurological deficits. In 1 case, persistent SEP and MEP deterioration was detected secondary to a frontal hematoma, resulting in mild sensory-motor deficit in the right upper extremity after the procedure. Overall, 12 PTs (4 spinal cord and 8 brain abnormalities) were performed using lidocaine and sodium amytal injections. One positive result occurred after the injection of lidocaine. No false negatives were detected. IOM may provide continuous real-time data about the functional status of eloquent areas and pathways of the central nervous system in patients under general anesthesia. It therefore allows us to detect early neurological damage in time to perform specific actions that may prevent irreversible neurological deficits.

  8. 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

  9. A virtual tissue bank for primary central nervous system lymphomas in immunocompetent individuals.

    PubMed

    Ponzoni, Maurilio; Kwee, Ivo; Mazzucchelli, Luca; Ferreri, Andrés J M; Zucca, Emanuele; Doglioni, Claudio; Cavalli, Franco; Bertoni, Francesco

    2007-01-01

    Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma with continuously increasing incidence in both immunosuppressed and immunocompetent individuals. PCNSL is a very aggressive tumor with a poor outcome, and its clinical outcome is much worse than for nodal lymphomas. Differently from lymphomas arising in lymph nodes or in other extranodal sites, the treatment of PCNSL remains very unsatisfactory. Current biologic knowledge of PCNSL is still limited and several fundamental questions remain to be answered. This is mainly due to the paucity of PCNSL material for adequate translational research. With the aim of providing biologic material to investigators interested in PCNSL, we have implemented a virtual tissue bank (VTB) for PCNSL in immunocompetent patients. After registration, the VTB is accessible via any web browser at www.ielsg.org. Only anonymous data are centralized at the website of the International Extranodal Lymphoma Study Group, whilst the pathologic material is maintained at the local pathology institutes. (c) 2007 S. Karger AG, Basel.

  10. 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.

  11. Disrupted in schizophrenia 1 and synaptic function in the mammalian central nervous system

    PubMed Central

    Randall, Andrew D; Kurihara, Mai; Brandon, Nicholas J; Brown, Jon T

    2014-01-01

    The disrupted in schizophrenia 1 (DISC1) gene is found at the breakpoint of an inherited chromosomal translocation, and segregates with major mental illnesses. Its potential role in central nervous system (CNS) malfunction has triggered intensive investigation of the biological roles played by DISC1, with the hope that this may shed new light on the pathobiology of psychiatric disease. Such work has ranged from investigations of animal behavior to detailed molecular-level analysis of the assemblies that DISC1 forms with other proteins. Here, we discuss the evidence for a role of DISC1 in synaptic function in the mammalian CNS. PMID:24712987

  12. Proposal for research and education: joint lectures and practicals on central nervous system anatomy and physiology.

    PubMed

    Kageyama, Ikuo; Yoshimura, Ken; Satoh, Yoshihide; Nanayakkara, Chinthani D; Pallegama, Ranjith W; Iwasaki, Shin-Ichi

    2016-07-01

    We coordinated anatomy and physiology lectures and practicals to facilitate an integrated understanding of morphology and function in a basic medical science program for dental students and to reduce the time spent on basic science education. This method is a means to provide the essential information and skills in less time. The overall impression was that the practice of joint central nervous system lectures and practicals was an efficient method for students, which suggests that joint lectures might also be useful for clinical subjects. About two-thirds of students felt that the joint anatomy and physiology lecture on the central nervous system was useful and necessary in understanding the relationship between morphology and function, at least for this subject. One-third of students were neutral on the effectiveness of this method. However, the survey results suggest that improvements are needed in the method and timing of joint lectures and practicals. The present teaching approach can be further improved by conducting combined lectures in which the form and function of anatomic structures are presented by the relevant departments during the same lecture. Finally, joint lecturers and practicals offer an opportunity to increase student understanding of the importance of new research findings by the present authors and other researchers.

  13. A Role for Central Nervous Growth Hormone-Releasing Hormone Signaling in the Consolidation of Declarative Memories

    PubMed Central

    Michel, Christian; Perras, Boris; Born, Jan

    2011-01-01

    Contributions of somatotropic hormonal activity to memory functions in humans, which are suggested by clinical observations, have not been systematically examined. With previous experiments precluding a direct effect of systemic growth hormone (GH) on acute memory formation, we assessed the role of central nervous somatotropic signaling in declarative memory consolidation. We examined the effect of intranasally administered growth hormone releasing-hormone (GHRH; 600 µg) that has direct access to the brain and suppresses endogenous GHRH via an ultra-short negative feedback loop. Twelve healthy young men learned word-pair associates at 2030 h and were administered GHRH and placebo, respectively, at 2100 h. Retrieval was tested after 11 hours of wakefulness. Compared to placebo, intranasal GHRH blunted GH release within 3 hours after substance administration and reduced the number of correctly recalled word-pairs by ∼12% (both P<0.05). The impairment of declarative memory consolidation was directly correlated to diminished GH concentrations (P<0.05). Procedural memory consolidation as examined by the parallel assessment of finger sequence tapping performance was not affected by GHRH administration. Our findings indicate that intranasal GHRH, by counteracting endogenous GHRH release, impairs hippocampal memory processing. They provide first evidence for a critical contribution of central nervous somatotropic activity to hippocampus-dependent memory consolidation. PMID:21850272

  14. 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

  15. 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

  16. Identification of Genes from the Fungal Pathogen Cryptococcus neoformans Related to Transmigration into the Central Nervous System

    PubMed Central

    Tseng, Hsiang-Kuang; Liu, Chang-Pan; Price, Michael S.; Jong, Ambrose Y.; Chang, Jui-Chih; Toffaletti, Dena L.; Betancourt-Quiroz, Marisol; Frazzitta, Aubrey E.; Cho, Wen-Long; Perfect, John R.

    2012-01-01

    Background A mouse brain transmigration assessment (MBTA) was created to investigate the central nervous system (CNS) pathogenesis of cryptococcal meningoencephalitis. Methodology/Principal Findings Two cryptococcal mutants were identified from a pool of 109 pre-selected mutants that were signature-tagged with the nourseothricin acetyltransferase (NAT) resistance cassette. These two mutants displayed abnormal transmigration into the central nervous system. One mutant displaying decreased transmigration contains a null mutation in the putative FNX1 gene, whereas the other mutant possessing a null mutation in the putative RUB1 gene exhibited increased transmigration into the brain. Two macrophage adhesion-defective mutants in the pool, 12F1 and 3C9, showed reduced phagocytosis by macrophages, but displayed no defects in CNS entry suggesting that transit within macrophages (the “Trojan horse” model of CNS entry) is not the primary mechanism for C. neoformans migration into the CNS in this MBTA. Conclusions/Significance This research design provides a new strategy for genetic impact studies on how Cryptococcus passes through the blood-brain barrier (BBB), and the specific isolated mutants in this assay support a transcellular mechanism of CNS entry. PMID:23028773

  17. 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.

  18. 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

  19. A deletion in the alpha2B-adrenergic receptor gene and autonomic nervous function in central obesity.

    PubMed

    Sivenius, Katariina; Niskanen, Leo; Laakso, Markku; Uusitupa, Matti

    2003-08-01

    We investigated the impact of a three-amino acid deletion (12Glu9) polymorphism in the alpha(2B)-adrenergic receptor gene on autonomic nervous function. The short form (Glu(9)/Glu(9)) of the polymorphism has previously been associated with a reduced basal metabolic rate in obese subjects. Because autonomic nervous function participates in the regulation of energy metabolism, there could be a link between this polymorphism and autonomic nervous function. Data of a 10-year follow-up study with 126 nondiabetic control subjects and 84 type 2 diabetic patients were used to determine the effects of the 12Glu9 polymorphism on autonomic nervous function. A deep breathing test and an orthostatic test were used to investigate parasympathetic and sympathetic autonomic nervous function. In addition, cardiovascular autonomic function was studied using power spectral analysis of heart rate variability. No significant differences were found in the frequency of the 12Glu9 deletion polymorphism between nondiabetic and diabetic subjects. The nondiabetic men with the Glu(9)/Glu(9) genotype, especially those with abdominal obesity, had significantly lower total and low-frequency power values in the power spectral analysis when compared with other men. Furthermore, in a longitudinal analysis of 10 years, the decrease in parasympathetic function was greater in nondiabetic men with the Glu(9)/Glu(9) genotype than in the men with the Glu(9)/Glu(12) or Glu(12)/Glu(12) genotypes. The results of the present study suggest that the 12Glu9 polymorphism of the alpha(2B)-adrenergic receptor gene modulates autonomic nervous function in Finnish nondiabetic men. In the nondiabetic men with the Glu(9)/Glu(9) genotype, the general autonomic tone is depressed, and vagal activity especially becomes impaired with time. Furthermore, this association is accentuated by central obesity.

  20. Unexperienced mechanical effects of muscular fatigue can be predicted by the Central Nervous System as revealed by anticipatory postural adjustments.

    PubMed

    Monjo, Florian; Forestier, Nicolas

    2014-09-01

    Muscular fatigue effects have been shown to be compensated by the implementation of adaptive compensatory neuromuscular strategies, resulting in modifications of the initial motion coordination. However, no studies have focused on the efficiency of the feedforward motor commands when muscular fatigue occurs for the first time during a particular movement. This study included 18 healthy subjects who had to perform arm-raising movements in a standing posture at a maximal velocity before and after a fatiguing procedure involving focal muscles. The arm-raising task implies the generation of predictive processes of control, namely Anticipatory Postural Adjustments (APAs), whose temporal and quantitative features have been shown to be dependent on the kinematics of the upcoming arm-raising movement. By altering significantly the kinematic profile of the focal movement with a fatiguing procedure, we sought to find out whether APAs scaled to the lower mechanical disturbance. APAs were measured using surface electromyography. Following the fatiguing procedure, acceleration peaks of the arm movement decreased by ~27%. APAs scaled to this lower fatigue-related disturbance during the very first trial post-fatigue, suggesting that the Central Nervous System can predict unexperienced mechanical effects of muscle fatigue. It is suggested that these results are accounted for by prediction processes in which the central integration of the groups III and IV afferents leads to an update of the internal model by remapping the relationship between focal motor command magnitude and the actual mechanical output.

  1. 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...

  2. 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.

  3. Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

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

    Levin, Victor A., E-mail: vlevin49@comcast.ne; Bidaut, Luc; Hou, Ping

    Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeksmore » after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients-and none of the placebo-treated patients-showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with

  4. 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.

  5. Various drug delivery approaches to the central nervous system.

    PubMed

    Pasha, Santosh; Gupta, Kshitij

    2010-01-01

    The presence of the blood-brain barrier (BBB), an insurmountable obstacle, in particular, and other barriers in brain and periphery contribute to hindrance of the successful diagnosis and treatment of a myriad of central nervous system pathologies. This review discusses several strategies adopted to define a rational drug delivery approach to the CNS along with a short description of the strategies implemented by the authors' group to enhance the analgesic activity, a CNS property, of chimeric peptide of Met-enkephalin and FMRFa (YGGFMKKKFMRFa-YFa). Various approaches for drug delivery to the CNS with their beneficial and non-beneficial aspects, supported by an extensive literature survey published recently, up to August 2009. The reader will have the privilege of gaining an understanding of previous as well as recent approaches to breaching the CNS barriers. Among the various strategies discussed, the potential for efficacious CNS drug targeting in future lies either with the non-invasively administered multifunctional nanosystems or these nanosystems without characterstics such as long systemic circulating capability and avoiding reticuloendothelial system scavenging system of the body, endogenous transporters and efflux inhibitors administered by convection-enhanced delivery.

  6. Clinical Proton MR Spectroscopy in Central Nervous System Disorders

    PubMed Central

    Alger, Jeffry R.; Barker, Peter B.; Bartha, Robert; Bizzi, Alberto; Boesch, Chris; Bolan, Patrick J.; Brindle, Kevin M.; Cudalbu, Cristina; Dinçer, Alp; Dydak, Ulrike; Emir, Uzay E.; Frahm, Jens; González, Ramón Gilberto; Gruber, Stephan; Gruetter, Rolf; Gupta, Rakesh K.; Heerschap, Arend; Henning, Anke; Hetherington, Hoby P.; Howe, Franklyn A.; Hüppi, Petra S.; Hurd, Ralph E.; Kantarci, Kejal; Klomp, Dennis W. J.; Kreis, Roland; Kruiskamp, Marijn J.; Leach, Martin O.; Lin, Alexander P.; Luijten, Peter R.; Marjańska, Małgorzata; Maudsley, Andrew A.; Meyerhoff, Dieter J.; Mountford, Carolyn E.; Nelson, Sarah J.; Pamir, M. Necmettin; Pan, Jullie W.; Peet, Andrew C.; Poptani, Harish; Posse, Stefan; Pouwels, Petra J. W.; Ratai, Eva-Maria; Ross, Brian D.; Scheenen, Tom W. J.; Schuster, Christian; Smith, Ian C. P.; Soher, Brian J.; Tkáč, Ivan; Vigneron, Daniel B.; Kauppinen, Risto A.

    2014-01-01

    A large body of published work shows that proton (hydrogen 1 [1H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of 1H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of 1H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which 1H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units. © RSNA, 2014 Online supplemental material is available for this article. PMID:24568703

  7. Behavioural conditioning of immune functions: how the central nervous system controls peripheral immune responses by evoking associative learning processes.

    PubMed

    Riether, Carsten; Doenlen, Raphaël; Pacheco-López, Gustavo; Niemi, Maj-Britt; Engler, Andrea; Engler, Harald; Schedlowski, Manfred

    2008-01-01

    During the last 30 years of psychoneuroimmunology research the intense bi-directional communication between the central nervous system (CNS) and the immune system has been demonstrated in studies on the interaction between the nervous-endocrine-immune systems. One of the most intriguing examples of such interaction is the capability of the CNS to associate an immune status with specific environmental stimuli. In this review, we systematically summarize experimental evidence demonstrating the behavioural conditioning of peripheral immune functions. In particular, we focus on the mechanisms underlying the behavioural conditioning process and provide a theoretical framework that indicates the potential feasibility of behaviourally conditioned immune changes in clinical situations.

  8. 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.

  9. Acute effects of an organic solvent mixture on the human central nervous system.

    PubMed

    Muttray, Axel; Martus, P; Schachtrup, S; Müller, E; Mayer-Popken, O; Konietzko, J

    2005-09-12

    At workplaces, organic solvents are often used as mixtures. Nevertheless, there is limited knowledge of their acute effects on human central nervous system. Here we report the effects of a toluene-acetone mixture. In a parallel design, subgroups of 12 healthy men each were exposed to a mixture containing 25 ppm acetone and 250 ppm toluene or to air (control) in an exposure chamber for 4.5 hours. Concentrations corresponded to the German TLV (TRGS 403). Concentrations of toluene and acetone in venous blood were measured by headspace gas chromatography. Subjects were sedentary. The following tests were performed before and at the end of exposure: Questionnaires, simple reaction time, vigilance, quantitative analysis of EEG with open and closed eyes and during the Color Word Stress test, and visual evoked potentials (VEP). Blood levels were 0.14 (+/- 0.04 SD) mg toluene/l and 5.43 (+/- 1.37 SD) mg acetone/l at the end of solvent exposure. Scores of neurotoxic and irritating symptoms were not elevated during solvent exposure. Exposed subjects performed as well as control subjects on the simple reaction time test and on the vigilance test, neither reaction time nor number of hits differed significantly. A general linear model on log transformed spectral power values showed insignificant changes in EEG. In the alpha subset2-band an average reduction to 86 % was observed in exposed as compared to non exposed subjects with closed eyes, a reduction to 88 % in the theta-band with open eyes, and a reduction to 92 % in the theta-band during the Color Word Stress test. VEP P 100 latencies and amplitudes did not change. The mixture consisting of toluene and acetone did not cause any adverse acute effect. With respect to EEG data, possible subclinical effects on central nervous system cannot be excluded.

  10. Hydrogels Derived from Central Nervous System Extracellular Matrix

    PubMed Central

    Medberry, Christopher J.; Crapo, Peter M.; Siu, Bernard F.; Carruthers, Christopher A.; Wolf, Matthew T.; Nagarkar, Shailesh P.; Agrawal, Vineet; Jones, Kristen E.; Kelly, Jeremy; Johnson, Scott A.; Velankar, Sachin S.; Watkins, Simon C.; Modo, Michel

    2012-01-01

    Biologic scaffolds composed of extracellular matrix (ECM) are commonly used repair devices in preclinical and clinical settings; however the use of these scaffolds for peripheral and central nervous system (CNS) repair has been limited. Biologic scaffolds developed from brain and spinal cord tissue have recently been described, yet the conformation of the harvested ECM limits therapeutic utility. An injectable CNS-ECM derived hydrogel capable of in vivo polymerization and conformation to irregular lesion geometries may aid in tissue reconstruction efforts following complex neurologic trauma. The objectives of the present study were to develop hydrogel forms of brain and spinal cord ECM and compare the resulting biochemical composition, mechanical properties, and neurotrophic potential of a brain derived cell line to a non-CNS-ECM hydrogel, urinary bladder matrix. Results showed distinct differences between compositions of brain ECM, spinal cord ECM, and urinary bladder matrix. The rheologic modulus of spinal cord ECM hydrogel was greater than that of brain ECM and urinary bladder matrix. All ECMs increased the number of cells expressing neurites, but only brain ECM increased neurite length, suggesting a possible tissue-specific effect. All hydrogels promoted three-dimensional uni- or bi-polar neurite outgrowth following 7 days in culture. These results suggest that CNS-ECM hydrogels may provide supportive scaffolding to promote in vivo axonal repair. PMID:23158935

  11. A case of disseminated central nervous system sparganosis.

    PubMed

    Noiphithak, Raywat; Doungprasert, Gahn

    2016-01-01

    Sparganosis is a very rare parasitic infection in various organs caused by the larvae of tapeworms called spargana. The larva usually lodges in the central nervous system (CNS) and the orbit. However, lumbar spinal canal involvement, as noted in the present case, is extremely rare. We report a rare case of disseminated CNS sparganosis involving the brain and spinal canal and review the literature. A 54-year-old man presented with progressive low back pain and neurological deficit at the lumbosacral level for 2 months. Imaging indicated arachnoiditis and an abnormal lesion at the L4-5 vertebral level. The patient underwent laminectomy of the L4-5 with lesionectomy and lysis of adhesions between the nerve roots. Microscopic examination indicated sparganum infection. Further brain imaging revealed evidence of chronic inflammation in the left parieto-occipital area without evidence of live parasites. In addition, an ophthalmologist reported a nonactive lesion in the right conjunctiva. The patient recovered well after surgery, although he had residual back pain and bladder dysfunction probably due to severe adhesion of the lumbosacral nerve roots. CNS sparganosis can cause various neurological symptoms similar to those of other CNS infections. A preoperative enzyme-linked immunosorbent assay is helpful for diagnosis, especially in endemic areas. Surgical removal of the worm remains the treatment of choice.

  12. 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

  13. Squash preparation: A reliable diagnostic tool in the intraoperative diagnosis of central nervous system tumors

    PubMed Central

    Mitra, Sumit; Kumar, Mohan; Sharma, Vivek; Mukhopadhyay, Debasis

    2010-01-01

    Background: Intraoperative cytology is an important diagnostic modality improving on the accuracy of the frozen sections. It has shown to play an important role especially in the intraoperative diagnosis of central nervous system tumors. Aim: To study the diagnostic accuracy of squash preparation and frozen section (FS) in the intraoperative diagnosis of central nervous system (CNS) tumors. Materials and Methods: This prospective study of 114 patients with CNS tumors was conducted over a period of 18 months (September 2004 to February 2006). The cytological preparations were stained by the quick Papanicolaou method. The squash interpretation and FS diagnosis were later compared with the paraffin section diagnosis. Results: Of the 114 patients, cytological diagnosis was offered in 96 cases. Eighteen nonneoplastic or noncontributory cases were excluded. Using hematoxylin and eosin-stained histopathology sections as the gold standard, the diagnostic accuracy of cytology was 88.5% (85/96) and the accuracy on FS diagnosis was 90.6% (87/96). Among these cases, gliomas formed the largest category of tumors (55.2%). The cytological accuracy in this group was 84.9% (45/53) and the comparative FS figure was 86.8% (46/53). In cases where the smear and the FS diagnosis did not match, the latter opinion was offered. Conclusions: Squash preparation is a reliable, rapid and easy method and can be used as a complement to FS in the intraoperative diagnosis of CNS tumors. PMID:21187881

  14. Central nervous systen alpha-adrenergic mechanisms and cardiovascular regulation in rats.

    PubMed

    Boudier, H S; Smeets, G; Brouwer, G; Van Rossum, J M

    1975-02-01

    Noradrenaline (NA) induced a decrease in blood pressure and heart rate when injected into specific areas in either the medulla oblongata or the hypothalamus. In the medulla the area of the nucleus tractus solitarius was specifically sensitive to NA; in the hypothalamus depressor effects were obtained only after NA injections into the anterior hypothalamic/preoptic region. The cardiovascular effects induced by NA (3-40 nmol) in these areas consisted of an immediate decrease in both arterial pressure and heart rate. Size and duration of these effects depended upon the dose of NA injected. Alpha-methylNA (5-15 nmol) induced a long lasting decrease in blood pressure and heart rate when injected into the anterior hypothalamic/preoptic region. These data are discussed in view of the existence of at least two sites within the central nervous system (CNS) from which interference with noradrenergic mechanisms can cause changes in the cardiovascular system.

  15. Primary Central Nervous System Lymphoma of Optic Chiasma: Endoscopic Endonasal Treatment.

    PubMed

    Ozdemir, Evin Singar; Yildirim, Ali Erdem; Can, Aslihan Yavas

    2018-01-01

    Isolated primary central nervous system lymphoma arising from anterior visual pathway is very rare. A 76-year-old immunocompetent previously healthy man presented bilateral decreased visual acuity in 1 month. Pituitary magnetic resonans imaging (MRI) showed a lobulated mass with homogeneous enhancement after gadolinium administration that arising from optic chiasm suggested that inflammatory disease or an optic glioma. The patient underwent an extended endoscopic endonasal transsphenoidal surgery. Postoperative course and outcomes were wonderful. Histopathological diagnosis was diffuse large B-cell lymphoma. The patient underwent investigations for systemic lymphomatous involvement, did not detect any evidence of systemic disease. In this case, we claimed that differential diagnoses of anterior visual pathway lesions are difficult because of similarity of lesions on clinical and radiological examinations. Biopsy is essential for these lesions. As a biopsy technique, endoscopic endonasal transsphenoidal approach is safer and more effective than open procedures.

  16. Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems

    PubMed Central

    Fernandes Azevedo, Bruna; Barros Furieri, Lorena; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra; Frizera Vassallo, Paula; Ronacher Simões, Maylla; Fiorim, Jonaina; Rossi de Batista, Priscila; Fioresi, Mirian; Rossoni, Luciana; Stefanon, Ivanita; Alonso, María Jesus; Salaices, Mercedes; Valentim Vassallo, Dalton

    2012-01-01

    Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced. PMID:22811600

  17. 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

  18. Parasitic diseases of the central nervous system: lessons for clinicians and policy makers

    PubMed Central

    Carpio, Arturo; Romo, Matthew L.; Parkhouse, R. M. E.; Short, Brooke; Dua, Tarun

    2016-01-01

    ABSTRACT Parasitic diseases of the central nervous system are associated with high mortality and morbidity, especially in resource-limited settings. The burden of these diseases is amplified as survivors are often left with neurologic sequelae affecting mobility, sensory organs, and cognitive functions, as well as seizures/epilepsy. These diseases inflict suffering by causing lifelong disabilities, reducing economic productivity, and causing social stigma. The complexity of parasitic life cycles and geographic specificities, as well as overlapping clinical manifestations in the host reflecting the diverse pathogenesis of parasites, can present diagnostic challenges. We herein provide an overview of these parasitic diseases and summarize clinical aspects, diagnosis, therapeutic strategies and recent milestones, and aspects related to prevention and control. PMID:26894629

  19. [Confirmation of West Nile virus seroreactivity in central nervous system infections of unknown etiology from Ankara Province, Central Anatolia, Turkey].

    PubMed

    Ergünay, Koray; Özkul, Aykut

    2011-04-01

    West Nile virus (WNV) infections may trigger febrile conditions and/or neuroinvasive disease in a portion of the exposed individuals. Serosurveillance data from various regions of Turkey indicate WNV activity. The aim of this study was to confirm the antibody specificity of the serum samples via virus neutralization assay, previously reported to be reactive for WNV IgM. The samples originated from two individuals with the preliminary diagnosis of aseptic meningitis/encephalitis of unknown etiology in 2009 and had been classified as probable WNV infections. Cerebrospinal fluid and sera samples of these patients had been evaluated as negative for WNV RNA and IgG antibodies. Only one serum sample could be included in the neutralization assay due to the limited amounts in the current investigation. The sample was observed as positive in dilutions of 1/20 and 1/40, thus confirming the diagnosis of WNV-related central nervous system infection in a 62 year-old female patient from Ankara, Central Anatolia, Turkey.

  20. 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.

  1. The Role of Gap Junction Channels During Physiologic and Pathologic Conditions of the Human Central Nervous System

    PubMed Central

    Basilio, Daniel; Sáez, Juan C.; Orellana, Juan A.; Raine, Cedric S.; Bukauskas, Feliksas; Bennett, Michael V. L.; Berman, Joan W.

    2013-01-01

    Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP3, and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system. PMID:22438035

  2. [Comparative study of the central nervous system effect of the beta receptor blockaders pindolol and bisoprolol].

    PubMed

    Görtelmeyer, R; Klingmann, I

    1985-01-01

    In a total of 36 volunteers with cardiac hyperreaction, investigations were carried out on the effect of bisoprolol (designated tradename: Concor), pindolol and placebo on central nervous functions with the aid of a reaction test, spiral aftereffect, tremor test and mood and sleep questionnaires. In the randomized double-blind study performed with 3 independent groups the volunteers received placebo, 2 X daily 10 mg of pindolol or 1 X daily 10 mg of bisoprolol for a period of 14 days. Bisoprolol is a new highly beta 1-selective adrenoceptor blocker with moderate lipophilia and without intrinsic sympathomimetic activity (ISA). When compared to placebo neither of the beta-adrenoceptor blockers induced any significant changes in mood, vigilance, tremor and reaction times. Moreover, under bisoprolol no negative effect on sleep quality or feeling refreshed after sleep was determined. Under pindolol, on the other hand, a significant impairment of sleep quality was observed after acute dosage and a decrease in feeling refreshed after sleep, continuing up to day 14 of treatment. It is presumed that, as bisoprolol and pindolol have comparable lipophilia, the different intensity with which the two preparations act on the central nervous system is connected with the ISA of pindolol. In the selected doses bisoprolol had a stronger effect on diastolic blood pressure and heart rate than pindolol and placebo.

  3. Growth Cone Biomechanics in Peripheral and Central Nervous System Neurons

    NASA Astrophysics Data System (ADS)

    Urbach, Jeffrey; Koch, Daniel; Rosoff, Will; Geller, Herbert

    2012-02-01

    The growth cone, a highly motile structure at the tip of an axon, integrates information about the local environment and modulates outgrowth and guidance, but little is known about effects of external mechanical cues and internal mechanical forces on growth-cone mediated guidance. We have investigated neurite outgrowth, traction forces and cytoskeletal substrate coupling on soft elastic substrates for dorsal root ganglion (DRG) neurons (from the peripheral nervous system) and hippocampal neurons (from the central) to see how the mechanics of the microenvironment affect different populations. We find that the biomechanics of DRG neurons are dramatically different from hippocampal, with DRG neurons displaying relatively large, steady traction forces and maximal outgrowth and forces on substrates of intermediate stiffness, while hippocampal neurons display weak, intermittent forces and limited dependence of outgrowth and forces on substrate stiffness. DRG growth cones have slower rates of retrograde actin flow and higher density of localized paxillin (a protein associated with substrate adhesion complexes) compared to hippocampal neurons, suggesting that the difference in force generation is due to stronger adhesions and therefore stronger substrate coupling in DRG growth cones.

  4. 3D in vitro modeling of the central nervous system

    PubMed Central

    Hopkins, Amy M.; DeSimone, Elise; Chwalek, Karolina; Kaplan, David L.

    2015-01-01

    There are currently more than 600 diseases characterized as affecting the central nervous system (CNS) which inflict neural damage. Unfortunately, few of these conditions have effective treatments available. Although significant efforts have been put into developing new therapeutics, drugs which were promising in the developmental phase have high attrition rates in late stage clinical trials. These failures could be circumvented if current 2D in vitro and in vivo models were improved. 3D, tissue-engineered in vitro systems can address this need and enhance clinical translation through two approaches: (1) bottom-up, and (2) top-down (developmental/regenerative) strategies to reproduce the structure and function of human tissues. Critical challenges remain including biomaterials capable of matching the mechanical properties and extracellular matrix (ECM) composition of neural tissues, compartmentalized scaffolds that support heterogeneous tissue architectures reflective of brain organization and structure, and robust functional assays for in vitro tissue validation. The unique design parameters defined by the complex physiology of the CNS for construction and validation of 3D in vitro neural systems are reviewed here. PMID:25461688

  5. Fish oil protects the peripheral and central nervous systems against cisplatin-induced neurotoxicity.

    PubMed

    Kamisli, Suat; Ciftci, Osman; Cetin, Asli; Kaya, Kursat; Kamisli, Ozden; Celik, Hamit

    2014-04-01

    The protective effects of fish oil (FO) on cisplatin (CP)-induced central and peripheral neurotoxicity were investigated in rats. Rats (n = 28) were divided equally into four groups, the first group was kept as a control. In the second and third groups, CP and FO were given at doses of 7 mg/kg and 1 softgel/rat/day, respectively. In the fourth group, CP and FO were given together at the same doses. Although CP caused significant oxidative damage, via induction of lipid peroxidation and reduction in the antioxidant defense system potency, FO treatment largely reversed these effects. CP also resulted in histopathological damage, such as apoptosis, and electromyographical changes in the sciatic nerve. FO treatment partially prevented the histopathological and electromyographical effects of CP. CP has severe central and peripheral neurotoxic effects in rats and these effects were largely prevented by FO treatment. Thus, it appears that co-administration of FO with CP may be a useful approach to attenuate the negative effects of CP on the nervous system.

  6. Central nervous system mechanisms linking the consumption of palatable high-fat diets to the defense of greater adiposity.

    PubMed

    Ryan, Karen K; Woods, Stephen C; Seeley, Randy J

    2012-02-08

    The central nervous system (CNS) plays key role in the homeostatic regulation of body weight. Satiation and adiposity signals, providing acute and chronic information about available fuel, are produced in the periphery and act in the brain to influence energy intake and expenditure, resulting in the maintenance of stable adiposity. Diet-induced obesity (DIO) does not result from a failure of these central homeostatic circuits. Rather, the threshold for defended adiposity is increased in environments providing ubiquitous access to palatable, high-fat foods, making it difficult to achieve and maintain weight loss. Consequently, mechanisms by which nutritional environments interact with central homeostatic circuits to influence the threshold for defended adiposity represent critical targets for therapeutic intervention. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Antibodies in Cerebrospinal Fluid of Some Alzheimer Disease Patients Recognize Cholinergic Neurons in the Rat Central Nervous System

    NASA Astrophysics Data System (ADS)

    McRae-Degueurce, Amanda; Booj, Serney; Haglid, Kenneth; Rosengren, Lars; Karlsson, Jan Erik; Karlsson, Ingvar; Wallin, Anders; Svennerholm, Lars; Gottfries, Carl-Gerhard; Dahlstrom, Annica

    1987-12-01

    The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of patients this is indeed the case. The antibodies reported in this study have the following properties: (i) they recognize neuronal populations and components in the medial septum and spinal motor neurons in rats perfused with a mixture that fixes small neurotransmitter molecules; (ii) adsorption of the patient CSF with staphylococcal protein A-Sepharose and using a polyclonal antiserum against human IgG3 indicates that the immunocytochemical reaction in these brain regions is mainly due to the subclass IgG3; and (iii) the CSF immunocytochemical reaction is blocked by preincubation of the sections with a rabbit anti-acetylcholine antiserum. These results provide evidence that antibodies in the CSF of some, but not all, Alzheimer disease patients recognize acetylcholine-like epitopes in cholinergic neurons in the rat central nervous system.

  8. Head capsule, chephalic central nervous system and head circulatory system of an aberrant orthopteran, Prosarthria teretrirostris (Caelifera, Hexapoda).

    PubMed

    Baum, Eileen; Hertel, Wieland; Beutel, Rolf Georg

    2007-01-01

    The head capsule, the circulatory system and the central nervous system of the head of Prosarthria teretrirostris (Proscopiidae) is described in detail, with special consideration of modifications resulting from the aberrant head shape. The transformations of the head are completely different from those found in phasmatodeans, which are also characterised by twig mimesis. The circulatory system is distinctly modified. A hitherto undescribed additional structure in the posterior head region very likely functions as a pulsatile organ. The cephalic central nervous system is strongly elongated, with changes in the position of the suboesophageal ganglion, the corpora cardiaca and the course of the nervus mandibularis. Three-dimensional reconstructions of these two organ systems in combination with the pharynx were made using Alias Maya 6.0 software. Comparisons with other representatives of Caelifera suggest a clade comprising Proscopiidae and Morabinae. The presence of a transverse muscle connecting the antennal ampullae in Prosarthria shows that this structure likely belongs to the groundplan of Orthoptera, even though it is missing in different representatives of this group. The transverse ampullary muscle is a potential synapomorphy of Orthoptera, Phasmatodea and Dictyoptera.

  9. A Drosophila In Vivo Injury Model for Studying Neuroregeneration in the Peripheral and Central Nervous System.

    PubMed

    Li, Dan; Li, Feng; Guttipatti, Pavithran; Song, Yuanquan

    2018-05-05

    The regrowth capacity of damaged neurons governs neuroregeneration and functional recovery after nervous system trauma. Over the past few decades, various intrinsic and extrinsic inhibitory factors involved in the restriction of axon regeneration have been identified. However, simply removing these inhibitory cues is insufficient for successful regeneration, indicating the existence of additional regulatory machinery. Drosophila melanogaster, the fruit fly, shares evolutionarily conserved genes and signaling pathways with vertebrates, including humans. Combining the powerful genetic toolbox of flies with two-photon laser axotomy/dendriotomy, we describe here the Drosophila sensory neuron - dendritic arborization (da) neuron injury model as a platform for systematically screening for novel regeneration regulators. Briefly, this paradigm includes a) the preparation of larvae, b) lesion induction to dendrite(s) or axon(s) using a two-photon laser, c) live confocal imaging post-injury and d) data analysis. Our model enables highly reproducible injury of single labeled neurons, axons, and dendrites of well-defined neuronal subtypes, in both the peripheral and central nervous system.

  10. 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.

  11. Immunohistochemical Analysis in the Rat Central Nervous System and Peripheral Lymph Node Tissue Sections.

    PubMed

    Adzemovic, Milena Z; Zeitelhofer, Manuel; Leisser, Marianne; Köck, Ulricke; Kury, Angela; Olsson, Tomas

    2016-11-14

    Immunohistochemistry (IHC) provides highly specific, reliable and attractive protein visualization. Correct performance and interpretation of an IHC-based multicolor labeling is challenging, especially when utilized for assessing interrelations between target proteins in the tissue with a high fat content such as the central nervous system (CNS). Our protocol represents a refinement of the standard immunolabeling technique particularly adjusted for detection of both structural and soluble proteins in the rat CNS and peripheral lymph nodes (LN) affected by neuroinflammation. Nonetheless, with or without further modifications, our protocol could likely be used for detection of other related protein targets, even in other organs and species than here presented.

  12. Primary central nervous system lymphoma.

    PubMed

    Ahluwalia, Manmeet S; Peereboom, David M

    2010-07-01

    Management goals for patients with primary central nervous system lymphoma (PCNSL) include long-term disease control, management of neurologic complications, and preservation of neurocognitive function. Various treatment options can achieve several of these goals. Chemotherapy as monotherapy or as combination therapy has emerged as the cornerstone of therapy for patients with newly diagnosed PCNSL. Outside of a clinical trial, patients with newly diagnosed PCNSL should receive high-dose intravenous methotrexate (MTX) as a single agent or as part of a combination regimen with radiation therapy reserved for relapse. The regimen should have an adequate MTX dose (>3 g/m(2)) to reach cytotoxic concentrations in the cerebrospinal fluid (CSF) to treat occult leptomeningeal disease (LMD). Alternative modes of chemotherapy delivery for selected patients, preferably in the context of a clinical trial, include high-dose chemotherapy with autologous stem cell rescue and intra-arterial chemotherapy with blood-brain barrier disruption. Whole brain radiation therapy (WBRT) in standard doses and fractionation carries an unacceptable rate of long-term neurocognitive toxicity. However, lower doses in daily divided fractions may offer the possibility of adding this modality with preservation of cognition but should be performed only in the context of a clinical trial. The long-term efficacy and toxicity of this approach is currently under investigation. Certain presentations of PCNSL require different strategies. Patients with ocular lymphoma at diagnosis should receive high-dose MTX as this drug can reach cytotoxic intravitreal concentrations. Recurrence in the eyes is managed with intravitreal chemotherapy including MTX or rituximab or with radiation therapy. The field of treatment (eyes vs whole brain) should be individualized. Intrathecal (IT) MTX should be included in the treatment regimen for those patients with a positive CSF cytology, or in regimens in which lower doses of

  13. Primary lymphoma of the central nervous system and HTLV-I infection.

    PubMed

    Calderón, Enrique J; Japón, Miguel A; Chinchón, Isidoro; Soriano, Vicente; Capote, Francisco J

    2002-01-01

    Only a few cases of AIDS-related primary lymphomas of the central nervous system (CNS) show a T-cell phenotype. We have recently studied two intravenous drug users with HIV infection who had primary CNS T-cell lymphomas. In both cases, the enzyme immunoassay (EIA) for HTLV gave a positive result. In the first case, study by western-blot (WB) and specific PCR confirmed the human T-cell lymphotropic virus type I (HTLV-I) infection and serological study by EIA for HTLV of his mother was negative. In the second case, analysis of ante-mortem serum samples by two different WBs showed an indeterminate pattern suggestive of HTLV-I infection, but adequate samples for PCR were not available. We speculate about the possibility that the horizontal transmission of HTLV-I infection could have facilitated the devepolment of a primary CNS T-cell lymphoma in these HIV patients, although they cannot be strictly considered as ATLL cases.

  14. Helminth parasitic infections of the central nervous system: a diagnostic approach.

    PubMed

    Othman, Ahmad A; Bruschi, Fabrizio; Ganna, Ahmed A

    2014-04-01

    Helminth parasitic infections of the central nervous system (CNS) occur worldwide with high prevalence in tropical and subtropical countries. Clinical evaluation of patients is mandatory, and it is convenient to group the clinical manifestations into syndromes: for example space-occupying lesions, meningitis, and encephalitis. The history should focus on residence or travel to endemic areas, diet, activities, intercurrent medical conditions, and associated clinical clues. Direct parasitological diagnosis can be reached by cerebrospinal fluid and cerebral tissue examination either by microscopy, culture, or immunological techniques. Immunodiagnosis by detection of parasite antibodies or antigens in serum could provide indirect evidence of parasitic infections. In addition, various imaging and radiological techniques e.g., computed tomography (CT) scan and magnetic resonance imaging (MRI) complement the diagnostic work-up of CNS diseases. Finally, the helminthic CNS infections of global impact, such as schistosomiasis, neurotoxocariasis, Strongyloides infection, neurotrichinosis, neurocysticercosis, and echinococcosis will be briefly discussed as regards the principal clinical and diagnostic features.

  15. SIV Infection Impairs the Central Nervous System in Chinese Rhesus Macaques.

    PubMed

    Liu, Hang; Xiao, Qian-Hao; Liu, Jin-Biao; Li, Jie-Liang; Zhou, Li; Xian, Qiao-Yang; Wang, Yong; Zhang, Jing; Wang, Xu; Ho, Wen-Zhe; Zhuang, Ke

    2016-09-01

    The central nervous system (CNS) impairment is a consequence seen in SIV infection of rhesus macaques of Indian-origin, which is more common in infected macaques with rapid disease progression than in those with conventional disease progression. Here, we investigated the CNS damages in SIVmac239-infected Chinese rhesus macaques. We demonstrated that SIV infection of Chinese macaques could cause neuropathological impairments, which was evidenced by appearance of SIV-RNA positive cells, the infiltration of activated macrophages and abundant multinucleated giant cells (MNGCs) in the different regions of the brains. The animals with high viremia and short survival time (average of 16 weeks, rapid progression, RP) had severer neuropathological changes than those with conventional progression (CP). As compared with the RP animals, CP macaques had lower viremia and much longer survival time (average of 154 weeks). These findings indicate that SIVmac239 infection of Chinese rhesus macaque can be used as a suitable animal model and alternative resource for nueroAIDS research.

  16. Peripherally derived FGF21 promotes remyelination in the central nervous system

    PubMed Central

    Kuroda, Mariko; Maedera, Noriko; Koyama, Yoshihisa; Hamaguchi, Machika; Fujimura, Harutoshi; Konishi, Morichika; Itoh, Nobuyuki; Mochizuki, Hideki

    2017-01-01

    Demyelination in the central nervous system (CNS) leads to severe neurological deficits that can be partially reversed by spontaneous remyelination. Because the CNS is isolated from the peripheral milieu by the blood-brain barrier, remyelination is thought to be controlled by the CNS microenvironment. However, in this work we found that factors derived from peripheral tissue leak into the CNS after injury and promote remyelination in a murine model of toxin-induced demyelination. Mechanistically, leakage of circulating fibroblast growth factor 21 (FGF21), which is predominantly expressed by the pancreas, drives proliferation of oligodendrocyte precursor cells (OPCs) through interactions with β-klotho, an essential coreceptor of FGF21. We further confirmed that human OPCs expressed β-klotho and proliferated in response to FGF21 in vitro. Vascular barrier disruption is a common feature of many CNS disorders; thus, our findings reveal a potentially important role for the peripheral milieu in promoting CNS regeneration. PMID:28825598

  17. Applications of DNA-Based Liquid Biopsy for Central Nervous System Neoplasms.

    PubMed

    Wang, Joanna; Bettegowda, Chetan

    2017-01-01

    The management of central nervous system malignancies remains reliant on histopathological analysis and neuroimaging, despite their complex genetic profile. The intratumoral heterogeneity displayed by these tumors necessitates a more sophisticated method of tumor analysis and monitoring, with the ability to assess tumors over space and time. Circulating biomarkers, including circulating tumor cells, circulating tumor DNA, and extracellular vesicles, hold promise as a type of real-time liquid biopsy able to provide dynamic information not only regarding tumor burden to monitor disease progression and treatment response, but also regarding genetic profile to enable changes in management to match a constantly evolving tumor. In numerous cancer types, including glioma, they have demonstrated their clinical utility as a minimally invasive means for diagnosis, prognostication, and prediction. In addition, they can be used in the laboratory to probe mechanisms of acquired drug resistance and tumor invasion and dissemination. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  18. LRP-1-mediated intracellular antibody delivery to the Central Nervous System

    NASA Astrophysics Data System (ADS)

    Tian, Xiaohe; Nyberg, Sophie; S. Sharp, Paul; Madsen, Jeppe; Daneshpour, Nooshin; Armes, Steven P.; Berwick, Jason; Azzouz, Mimoun; Shaw, Pamela; Abbott, N. Joan; Battaglia, Giuseppe

    2015-07-01

    The blood-brain barrier (BBB) is by far the most important target in developing new approaches to improve delivery of drugs and diagnostic tools into the Central Nervous System (CNS). Here we report the engineering of pH- sensitive polymersomes (synthetic vesicles formed by amphiphilic copolymers) that exploit endogenous transport mechanisms to traverse the BBB, enabling delivery of large macromolecules into both the CNS parenchyma and CNS cells. We achieve this by targeting the Low Density Lipoprotein Receptor-Related Protein 1 (LRP-1) receptor. We show that LRP-1 is associated with endothelial transcytosis that does not involve acidification of cargo in membrane-trafficking organelles. By contrast, this receptor is also associated with traditional endocytosis in CNS cells, thus aiding the delivery of relevant cargo within their cytosol. We prove this using IgG as a model cargo, thus demonstrating that the combination of appropriate targeting combined with pH-sensitive polymersomes enables the efficient delivery of macromolecules into CNS cells.

  19. A psychodynamic model of behavior after acute central nervous system damage.

    PubMed

    Groswasser, Z; Stern, M J

    1998-02-01

    This article describes a conceptual psychodynamic model for understanding the neurobehavioral manifestations of acute central nervous system damage (ACNSD) displayed by patients during the rehabilitation process. According to the proposed model, patientsO behavioral responses are viewed as their only means of emotional expression and therefore may not be considered entirely abnormal when viewed from the perspective of patientsO interpersonal contexts. An improved understanding of the dynamic processes through which recovering patients with ACNSD journey may lead to better interaction between the patient and the therapeutic environment, the interdisciplinary team, and family members. Combining this proposed psychodynamic model with an emerging understanding of the neurobehavioral foundations of aggression and depression may also lead to a more rational approach to intervention with various psychopharmacologic agents. During the rehabilitation process, understanding patients' cognitive deficits, motivational drives, and emotional needs and proper implementation of medical and environmental treatment can ultimately lead to a better psychosocial outcome.

  20. Heterogeneity of D-Serine Distribution in the Human Central Nervous System

    PubMed Central

    Suzuki, Masataka; Imanishi, Nobuaki; Mita, Masashi; Hamase, Kenji; Aiso, Sadakazu; Sasabe, Jumpei

    2017-01-01

    D-serine is an endogenous ligand for N-methyl-D-aspartate glutamate receptors. Accumulating evidence including genetic associations of D-serine metabolism with neurological or psychiatric diseases suggest that D-serine is crucial in human neurophysiology. However, distribution and regulation of D-serine in humans are not well understood. Here, we found that D-serine is heterogeneously distributed in the human central nervous system (CNS). The cerebrum contains the highest level of D-serine among the areas in the CNS. There is heterogeneity in its distribution in the cerebrum and even within the cerebral neocortex. The neocortical heterogeneity is associated with Brodmann or functional areas but is unrelated to basic patterns of cortical layer structure or regional expressional variation of metabolic enzymes for D-serine. Such D-serine distribution may reflect functional diversity of glutamatergic neurons in the human CNS, which may serve as a basis for clinical and pharmacological studies on D-serine modulation. PMID:28604057

  1. Herpes Simplex Virus Infections of the Central Nervous System.

    PubMed

    Whitley, Richard J

    2015-12-01

    This article summarizes knowledge of herpes simplex virus (HSV) infections of the central nervous system (CNS). Disease pathogenesis, detection of DNA polymerase chain reaction (PCR) for diagnosis and prognosis, and approaches to therapy warrant consideration. HSV infection of the CNS is one of few treatable viral diseases. Clinical trials indicate that outcome following neonatal herpes simplex virus type 2 (HSV-2) infections of the CNS is significantly improved when 6 months of suppressive oral acyclovir therapy follows IV antiviral therapy. In contrast, herpes simplex virus type 1 (HSV-1) infections of the brain do not benefit from extended oral antiviral therapy. This implies a difference in disease pathogenesis between HSV-2 and HSV-1 infections of the brain. PCR detection of viral DNA in the CSF is the gold standard for diagnosis. Use of PCR is now being adopted as a basis for determining the duration of therapy in the newborn. HSV infections are among the most common encountered by humans; seropositivity occurs in 50% to 90% of adult populations. Herpes simplex encephalitis, however, is an uncommon result of this infection. Since no new antiviral drugs have been introduced in nearly 3 decades, much effort has focused on learning how to better use acyclovir and how to use existing databases to establish earlier diagnosis.

  2. Microparticles: A New Perspective in Central Nervous System Disorders

    PubMed Central

    Schindler, Stephanie M.; Little, Jonathan P.

    2014-01-01

    Microparticles (MPs) are a heterogeneous population of small cell-derived vesicles, ranging in size from 0.1 to 1 μm. They contain a variety of bioactive molecules, including proteins, biolipids, and nucleic acids, which can be transferred between cells without direct cell-to-cell contact. Consequently, MPs represent a novel form of intercellular communication, which could play a role in both physiological and pathological processes. Growing evidence indicates that circulating MPs contribute to the development of cancer, inflammation, and autoimmune and cardiovascular diseases. Most cell types of the central nervous system (CNS) have also been shown to release MPs, which could be important for neurodevelopment, CNS maintenance, and pathologies. In disease, levels of certain MPs appear elevated; therefore, they may serve as biomarkers allowing for the development of new diagnostic tools for detecting the early stages of CNS pathologies. Quantification and characterization of MPs could also provide useful information for making decisions on treatment options and for monitoring success of therapies, particularly for such difficult-to-treat diseases as cerebral malaria, multiple sclerosis, and Alzheimer's disease. Overall, studies on MPs in the CNS represent a novel area of research, which promises to expand the knowledge on the mechanisms governing some of the physiological and pathophysiological processes of the CNS. PMID:24860829

  3. Pharmacological evaluation of Pachyrrhizus erosus (L) seeds for central nervous system depressant activity.

    PubMed

    Abid, Mohd; Hrishikeshavan, H J; Asad, Mohammed

    2006-01-01

    The research work deals with the screening of ethanol and chloroform extracts of Pachyrrhizus erosus seeds for central nervous system (CNS) depressant activity. The Pachyrrhizus erosus seed is known to contain rotinoids, flavonoids and phenylfuranocoumarin derivatives as chemical components and is reported to have antifungal, antisecretory, insecticides, antibacterial and spasmolytic activity. Since seeds of Pachyrrhizus erosus is used as folk medicine in treatment of insomnia, we made an attempt to study its CNS depressant effect. The different activities studied were potentiation of pentobarbitone-induced sleep, test for locomotor activity, effect on muscle co-ordination, antiaggressive and antianxiety activities. The result of the study reflected that ethanol extract of the seeds (150 mg/kg, p.o) decreased locomotor activity, produced muscle relaxation and showed antianxiety and antiaggressive activity.

  4. Primary Sjogren's syndrome with central nervous system involvement.

    PubMed

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

    2009-08-01

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

  5. NEUROSARCOIDOSIS MASQUERADING AS A CENTRAL NERVOUS SYSTEM TUMOR.

    PubMed

    Elia, Maxwell; Kombo, Ninani; Huang, John

    2017-01-01

    To report a case of neurosarcoidosis with an isolated brain lesion mimicking a low-grade glioma. A 38-year-old woman presented with 2 weeks of blurry vision in the left eye. Ophthalmic examination, visual field testing, fluorescein angiography, laboratory testing, and MRI of the brain were performed. Ophthalmic examination revealed left-sided optic nerve infiltration, and MRI of the brain demonstrated a solitary lesion in the brain. The visual symptoms and ophthalmic examination improved significantly with initiation of high-dose oral prednisone. Because the MRI appearance was concerning for malignancy, a brain biopsy was performed. Pathology demonstrated gliosis consistent with a low-grade central nervous system (CNS) glioma. One year later, after initial loss to ophthalmic follow-up, the right optic nerve became involved, and the patient was again treated successfully for presumed ocular sarcoidosis. At this time, serial neuroimaging demonstrated enlargement of the CNS lesion, prompting rebiopsy. Rebiopsy demonstrated a noncaseating granuloma, confirming the diagnosis of neurosarcoidosis. The patient was treated with 20 mg of methotrexate weekly and a prednisone taper with improvement in visual and neurologic symptoms. The authors present an unusual case of neurosarcoidosis masquerading as a CNS glioma. In cases of solitary CNS granulomas, radiographically differentiating neurosarcoidosis from a glioma can be challenging. In this case, serial ophthalmic examination identifying sequential involvement of both optic nerves helped to identify the underlying cause of the CNS disease as sarcoidosis.

  6. Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy

    PubMed Central

    2011-01-01

    Gene expression analysis has proven to be a very useful tool to gain knowledge of the factors involved in the pathogenesis of diseases, particularly in the initial or preclinical stages. With the aim of finding new data on the events occurring in the Central Nervous System in animals affected with Bovine Spongiform Encephalopathy, a comprehensive genome wide gene expression study was conducted at different time points of the disease on mice genetically modified to model the bovine species brain in terms of cellular prion protein. An accurate analysis of the information generated by microarray technique was the key point to assess the biological relevance of the data obtained in terms of Transmissible Spongiform Encephalopathy pathogenesis. Validation of the microarray technique was achieved by RT-PCR confirming the RNA change and immunohistochemistry techniques that verified that expression changes were translated into variable levels of protein for selected genes. Our study reveals changes in the expression of genes, some of them not previously associated with prion diseases, at early stages of the disease previous to the detection of the pathological prion protein, that might have a role in neuronal degeneration and several transcriptional changes showing an important imbalance in the Central Nervous System homeostasis in advanced stages of the disease. Genes whose expression is altered at early stages of the disease should be considered as possible therapeutic targets and potential disease markers in preclinical diagnostic tool development. Genes non-previously related to prion diseases should be taken into consideration for further investigations. PMID:22035425

  7. [Primary central nervous system diffuse large B cell lymphoma: a clinicopathologic and molecular study].

    PubMed

    Ma, Z P; Ainiwaer, Babayi; Liu, Z Y; Shi, X L; Cui, W L; Zhang, W; Li, X X

    2016-11-08

    Objective: To investigate clinicopathologic characteristics, immunophenotype and EB virus-related molecular genetic alterations in primary central nervous system diffuse large B cell lymphoma (DLBCL) along with correlation with clinical prognosis. Methods: A total of 30 cases of primary central nervous system DLBCL were retrospectively studied by retrieving clinical data, histological evaluation and immunophenotyping by EnVision two steps methods. The expression of EBER mRNA was detected by in situ hybridization and bcl-2, bcl-6 and C-MYC gene abnormalities were analyzed by interphase fluorescence in situ hybridization. Results: The cases included 18 males and 12 females (sex ratio of 1.5∶1.0) with an age ranging from 24 to 78 years (average age of 52 years, the median age of 53 years). The single primary clinical presentation was focal neurologic deficits. Tumor locations were supratentorial (21 cases), subtentorial (7 cases), involving both locations in 2 cases. Diffuse growth pattern was observed with large lymphoid cells mostly resembling centroblasts with abundant basophilic cytoplasm with oval to round, vesicular nuclei containing fine chromatin. An angiocentric and angiodestructive growth pattern was also present. Other features included perivascular space invasion. Immunohistochemical staining using a panel of CD10, bcl-6 and MUM1, six cases were germinal center-like (GCB) and 24 cases were non-germinal central-like (non-GCB). The positive rates of bcl-2, bcl-6 and C-MYC were 53.3% (16/30), 80.0% (24/30) and 20.0% (6/30), respectively. Genetic alterations were detected by FISH and the gene arrangement rates of bcl-2, bcl-6 and C-MYC were 3.3% (1/30), 16.7% (5/30) and 3.3% (1/30), respectively. There were 19 cases in stage 0-1 disease and 11 cases had stage 2-3 disease. Postoperative follow-up for average 13.6 months showed the median survival of 10 months, one-year survival of 46.7% and 16 patients died within a year. Conclusions: The clinical prognosis

  8. Cytokines in the central nervous system: regulatory roles in neuronal function, cell death and repair.

    PubMed

    Sei, Y; Vitković, L; Yokoyama, M M

    1995-01-01

    Recent evidence suggests that neurons and glia can synthesize and secrete cytokines, which play critical roles in maintaining homeostasis in the central nervous system (CNS) by mediating the interaction between cells via autocrine or paracrine mechanisms. Circulating cytokines and soluble receptors also regulate neuronal function via endocrine mechanisms. Disturbance of the cytokine-mediated interaction between cells may lead to neuronal dysfunction and/or cell death and contribute to the pathogenesis of the CNS diseases (e.g., ischemia, Alzheimer's disease and HIV encephalopathy). Defining the molecular pathways of cytokine dysregulation and neurotoxicity may help to elucidate potential therapeutic interventions for many devastating CNS diseases.

  9. Central nervous system infection after Onyx embolisation of arterio-venous malformations in two paediatric patients.

    PubMed

    Pulhorn, H; Hartley, J C; Shanmuganathan, M; Lee, C H; Harkness, W; Thompson, D N P

    2014-09-01

    Increasingly, Onyx is used for endovascular embolization of aneurysms and arterio-venous malformations. Although reports in the literature on the use of Onyx are favourable, there have been so far no reports on the central nervous system (CNS) infection rate after embolisation with Onyx and no recommendations as to the management of these infections. We present two cases of paediatric patients who acquired CNS infection with Pseudomonas aeruginosa after Onyx embolisation of AVMs and describe their subsequent management. Presence of established infection after Onyx embolisation should be dealt with by removal of infected material, administration of appropriate antibiotic therapy and supportive treatment.

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

    PubMed

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

    2017-07-01

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

  11. 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.

  12. Central nervous system histoplasmosis: Multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment.

    PubMed

    Wheat, Joseph; Myint, Thein; Guo, Ying; Kemmer, Phebe; Hage, Chadi; Terry, Colin; Azar, Marwan M; Riddell, James; Ender, Peter; Chen, Sharon; Shehab, Kareem; Cleveland, Kerry; Esguerra, Eden; Johnson, James; Wright, Patty; Douglas, Vanja; Vergidis, Pascalis; Ooi, Winnie; Baddley, John; Bamberger, David; Khairy, Raed; Vikram, Holenarasipur R; Jenny-Avital, Elizabeth; Sivasubramanian, Geetha; Bowlware, Karen; Pahud, Barbara; Sarria, Juan; Tsai, Townson; Assi, Maha; Mocherla, Satish; Prakash, Vidhya; Allen, David; Passaretti, Catherine; Huprikar, Shirish; Anderson, Albert

    2018-03-01

    Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.

  13. Factors associated with survival among patients with AIDS-related primary central nervous system lymphoma

    PubMed Central

    Uldrick, Thomas S.; Pipkin, Sharon; Scheer, Susan; Hessol, Nancy A.

    2014-01-01

    Objective AIDS-related primary central nervous system lymphoma (AR-PCNSL) has a poor prognosis. Improved understanding of specific patient, infectious, diagnostic, and treatment-related factors that affect overall survival (OS) are required to improve outcomes. Design Population-based registry linkage study. Methods Adult cases from the San Francisco AIDS registry (1990–2000) were matched with the California Cancer Registry (1985–2002) to ascertain AR-PCNSL data. Survival time was assessed through 31 December 2007. Risk factors and temporal trends for death were measured using two-sided Kaplan–Meier and Cox analyses. Results Two hundred and seven AR-PCNSL patients were identified: 68% were white, 20% Hispanic, 10% African–American, and 2% Asian. Nineteen percent of patients had central nervous system (CNS) opportunistic infections diagnosed prior to AR-PCNSL. Fifty seven percent of patients received radiation and/or chemotherapy and 12% used HAART prior to or within 30 days of AR-PCSNL diagnosis. One hundred and ninety-nine patients died (34 deaths/100 person-years). In adjusted analysis, prior CNS opportunistic infections diagnosis increased risk of death (hazard ratio 1.9, P = 0.0006) whereas radiation and/or chemotherapy decreased risk (hazard ratio 0.6, P <0.0001). AR-PCNSL diagnosis 1999–2002 had a lower mortality risk (hazard ratio = 0.4, P = 0.02) compared to 1990–1995. African–Americans had an increased risk of death compared to whites or Asians (hazard ratio = 2.0, P = 0.007). Conclusion OS among AR-PCSNL patients improved over time but remains poor, especially among African–Americans. Prospective evaluation of curative therapy in AR-PCNSL is urgently needed. Accurate diagnosis of CNS mass lesions in patients with AIDS is required and for those with AR-PCNSL, antiretroviral therapy with concomitant AR-PCNSL therapy, and antimicrobial supportive care may improve OS. PMID:24076659

  14. 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.

  15. Expression of VGF mRNA in the adult rat central nervous system.

    PubMed

    Snyder, S E; Salton, S R

    1998-04-27

    VGF is a secretory peptide precursor that is expressed and processed by neuronal cells in a cell type-specific fashion. In addition, VGF transcription and secretion are rapidly and relatively selectively induced by neurotrophins and depolarization in vitro. To gain insight into the possible function(s) of VGF in the nervous system, we have carried out a detailed examination of the distribution of VGF mRNA in the adult rat central nervous system by using in situ hybridization. Robust expression was detected in many neurons throughout the brain and spinal cord, in several types of neurons in the retina, and in presumptive chromaffin cells of the adrenal medulla. In the brain, prominent expression of VGF mRNA was observed in neurons of the main and accessory olfactory bulbs; in the anterior olfactory nucleus; in the induseum griseum and taenia tecta; in the olfactory tubercle; in CA1-CA3, the hilus of the dentate gyrus, and the subicular complex of the hippocampal formation; in the piriform, periamygdaloid, transitional, and lateral entorhinal cortices; in the endopiriform nucleus; in the hypothalamus, particularly the preoptic, periventricular, supraoptic, suprachiasmatic, and arcuate nuclei; and in a number of septal, thalamic, amygdaloid, and brainstem nuclei. Labeling was also seen in neurons of the neocortex and transitional cortical areas, particularly in layer V, and in basal ganglia and cerebellum. These data demonstrate that VGF mRNA is expressed much more extensively in the brain than has been described in previous RNA or immunohistochemical studies, and, furthermore, that VGF is widely expressed in the spinal cord and retina.

  16. Role of Fractionated External Beam Radiotherapy in Hemangioblastoma of the Central Nervous System

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

    Koh, Eng-Siew; Nichol, Alan; Millar, Barbara-Ann

    2007-12-01

    Purpose: To assess the clinical outcomes and toxicity in patients receiving fractionated external beam radiotherapy (EBRT) for hemangioblastoma of the central nervous system, treated at two Canadian radiation oncology institutions. Methods and Materials: Between January 1980 and December 2004, the data of all patients receiving EBRT for central nervous system hemangioblastoma were retrospectively reviewed. The patient, tumor, and treatment characteristics were collected and overall survival, disease-free survival, and EBRT-related toxicities assessed. Results: A total of 18 cases, 5 associated with von Hippel-Lindau disease (VHL) and 13 sporadic (non-VHL), with a total 31 lesions, were documented. These were located in themore » cerebellum in 20 and spinal cord in 8 patients. EBRT was delivered for recurrence in 12, adjuvantly for residual disease in 4, and definitively in 2. The EBRT schedules ranged from 50.0 to 55.8 Gy in 1.8-2.0-Gy daily fractions (n = 17), typically with parallel-opposed fields to the cerebellar target volumes and direct posterior fields for spinal disease. At a median follow-up of 5.1 years (range, 0.1-14.5), the 5-year OS rate was 69% (95% confidence interval [CI], 50-96%), decreasing to 30% (95% CI, 10-87%) at 10 years. The disease-free survival rate at 5 and 10 years was 57% (95% CI, 37-87%) and 30% (95% CI, 11-83%), respectively. The outcomes differed according to VHL status. The 5-year OS rate was 100% for those with VHL compared with 55% (95% CI, 32-95%) for those with non-VHL disease (log-rank p = 0.003), and the 5-year disease-free survival rate was 80% (95% CI, 52-100%) with VHL compared with 48% (95% CI, 26-89%) without (log-rank p = 0.036). Conclusions: Fractionated EBRT has a role in the management of extensive intracranial and/or spinal cord disease, the adjuvant treatment of residual postoperative disease, and the treatment of recurrence. More favorable outcomes were reported for VHL-associated lesions than for sporadic cases.« less

  17. Central nervous system infection following allogeneic hematopoietic stem cell transplantation.

    PubMed

    Hanajiri, Ryo; Kobayashi, Takeshi; Yoshioka, Kosuke; Watanabe, Daisuke; Watakabe, Kyoko; Murata, Yutaka; Hagino, Takeshi; Seno, Yasushi; Najima, Yuho; Igarashi, Aiko; Doki, Noriko; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

    2017-03-01

    Here, we described the clinical characteristics and outcomes of central nervous system (CNS) infections occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a single institution over the previous 6 years. Charts of 353 consecutive allogeneic transplant recipients were retrospectively reviewed for CNS infection. A total of 17 cases of CNS infection were identified at a median of 38 days (range, 10-1028 days) after allo-HSCT. Causative pathogens were human herpesvirus-6 (n=6), enterococcus (n=2), staphylococcus (n=2), streptococcus (n=2), varicella zoster virus (n=1), cytomegalovirus (n=1), John Cunningham virus (n=1), adenovirus (n=1), and Toxoplasma gondii (n=1). The cumulative incidence of CNS infection was 4.1% at 1 year and 5.5% at 5 years. Multivariate analysis revealed that high-risk disease status was a risk factor for developing CNS infection (p=.02), and that overall survival at 3 years after allo-HSCT was 33% in patients with CNS infection and 53% in those without CNS infection (p=.04). Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

  18. Thermoresponsive Copolypeptide Hydrogel Vehicles for Central Nervous System Cell Delivery.

    PubMed

    Zhang, Shanshan; Burda, Joshua E; Anderson, Mark A; Zhao, Ziru; Ao, Yan; Cheng, Yin; Sun, Yi; Deming, Timothy J; Sofroniew, Michael V

    2015-08-10

    Biomaterial vehicles have the potential to facilitate cell transplantation in the central nervous system (CNS). We have previously shown that highly tunable ionic diblock copolypeptide hydrogels (DCH) can provide sustained release of hydrophilic and hydrophobic molecules in the CNS. Here, we show that recently developed non-ionic and thermoresponsive DCH called DCH T exhibit excellent cytocompatibility. Neural stem cell (NSC) suspensions in DCH T were easily injected as liquids at room temperature. DCH T with a viscosity tuned to prevent cell sedimentation and clumping significantly increased the survival of NSC passed through injection cannulae. At body temperature, DCH T self-assembled into hydrogels with a stiffness tuned to that of CNS tissue. After injection in vivo , DCH T significantly increased by three-fold the survival of NSC grafted into healthy CNS. In injured CNS, NSC injected as suspensions in DCH T distributed well in non-neural lesion cores, integrated with healthy neural cells at lesion perimeters and supported regrowing host nerve fibers. Our findings show that non-ionic DCH T have numerous advantageous properties that make them useful tools for in vivo delivery of cells and molecules in the CNS for experimental investigations and potential therapeutic strategies.

  19. 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.

  20. B-cell posttransplant lymphoproliferative disorder isolated to the central nervous system is Epstein-Barr virus positive and lacks p53 and Myc expression by immunohistochemistry.

    PubMed

    Sundin, Andrew; Grzywacz, Bartosz J; Yohe, Sophia; Linden, Michael A; Courville, Elizabeth L

    2017-03-01

    In this retrospective study from one institution, we performed a clinicopathological study of a cohort of patients with posttransplant lymphoproliferative disorder (PTLD) confined to the central nervous system. We also identified a comparison cohort of patients with de novo primary diffuse large B-cell lymphoma of the central nervous system. We performed a detailed morphologic review, evaluated Epstein-Barr virus (EBV) by in situ hybridization, and interpreted a panel of immunohistochemical stains in a subset of cases including Hans classification markers (CD10, BCL6, MUM1), p53, CD30, Myc, and BCL2. All 17 of the posttransplant and none of 11 de novo cases were EBV positive (P < .005). Morphologic patterns identified in the PTLD cases were monomorphic diffuse large B-cell lymphoma pattern (10 patients) and "T-cell-rich" pattern (7 patients). The monomorphic posttransplant cases were more likely to be Myc negative (P = .015) and CD30 positive (P < .005) than the de novo cases, and showed a similarly low rate of p53 positivity by immunohistochemistry. No prognostic factors for overall survival were identified. Central nervous system PTLD is EBV positive, typically lacks p53 and Myc expression by immunohistochemistry, and can present with numerous background T lymphocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Intermittent hypoxia promotes recovery of respiratory motor function in spinal cord-injured mice depleted of serotonin in the central nervous system.

    PubMed

    Komnenov, Dragana; Solarewicz, Julia Z; Afzal, Fareeza; Nantwi, Kwaku D; Kuhn, Donald M; Mateika, Jason H

    2016-08-01

    We examined the effect of repeated daily exposure to intermittent hypoxia (IH) on the recovery of respiratory and limb motor function in mice genetically depleted of central nervous system serotonin. Electroencephalography, diaphragm activity, ventilation, core body temperature, and limb mobility were measured in spontaneously breathing wild-type (Tph2(+/+)) and tryptophan hydroxylase 2 knockout (Tph2(-/-)) mice. Following a C2 hemisection, the mice were exposed daily to IH (i.e., twelve 4-min episodes of 10% oxygen interspersed with 4-min normoxic periods followed by a 90-min end-recovery period) or normoxia (i.e., sham protocol, 21% oxygen) for 10 consecutive days. Diaphragm activity recovered to prehemisection levels in the Tph2(+/+) and Tph2(-/-) mice following exposure to IH but not normoxia [Tph2(+/+) 1.3 ± 0.2 (SE) vs. 0.3 ± 0.2; Tph2(-/-) 1.06 ± 0.1 vs. 0.3 ± 0.1, standardized to prehemisection values, P < 0.01]. Likewise, recovery of tidal volume and breathing frequency was evident, although breathing frequency values did not return to prehemisection levels within the time frame of the protocol. Partial recovery of limb motor function was also evident 2 wk after spinal cord hemisection. However, recovery was not dependent on IH or the presence of serotonin in the central nervous system. We conclude that IH promotes recovery of respiratory function but not basic motor tasks. Moreover, we conclude that spontaneous or treatment-induced recovery of respiratory and motor limb function is not dependent on serotonin in the central nervous system in a mouse model of spinal cord injury.

  2. Glucose transporter distribution in the vessels of the central nervous system of the axolotl Ambystoma mexicanum (Urodela: Ambystomatidae).

    PubMed

    Lazzari, Maurizio; Bettini, Simone; Ciani, Franco; Franceschini, Valeria

    2008-10-01

    The GLUT-1 isoform of the glucose transporter is commonly considered a reliable molecular marker of blood-brain barrier endothelia in the neural vasculature organized in a three-dimensional network of single vessels. The central nervous system of the axolotl Ambystoma mexicanum is characterized by a vascular architecture that contains both single and paired vessels. The presence and distribution of the GLUT-1 transporter are studied in this urodele using both immunoperoxidase histochemistry and immunogold technique. Light microscopy reveals immunopositivity in both parenchymal and meningeal vessels. The transverse-sectioned pairs of vessels do not show the same size. Furthermore, in the same pair, the two elements often differ in diameter. The main regions of the central nervous system show a different percentage of the paired structures. Only immunogold cytochemistry reveals different staining intensity in the two adjoined elements of a vascular pair. Colloidal gold particles show an asymmetric distribution in the endothelia of both single and paired vessels. These particles are more numerous on the abluminal surface than on the luminal one. The particle density is calculated in both vascular types. The different values could indicate functional differences between single and paired vessels and between the two adjoined elements of a pair, regarding glucose transport.

  3. Serotonin 5-HT7 receptor agents: structure-activity relationships and potential therapeutic applications in central nervous system disorders

    PubMed Central

    Leopoldo, Marcello; Lacivita, Enza; Berardi, Francesco; Perrone, Roberto; Hedlund, Peter B.

    2010-01-01

    Since its discovery in the 1940s in serum, the mammalian intestinal mucosa, and in the central nervous system, serotonin (5-HT) has been shown to be involved in virtually all cognitive and behavioral human functions, and alterations in its neurochemistry have been implicated in the etiology of a plethora of neuropsychiatric disorders. The cloning of 5-HT receptor subtypes has been of importance in enabling them to be classified as specific protein molecules encoded by specific genes. The 5-HT7 receptor is the most recently classified member of the serotonin receptor family. Since its identification, it has been the subject of intense research efforts driven by its presence in functionally relevant regions of the brain. The availability of some selective antagonists and agonists, in combination with genetically modified mice lacking the 5-HT7 receptor, has allowed for a better understanding of the pathophysiological role of this receptor. This paper reviews data on localization and pharmacological properties of the 5-HT7 receptor, and summarizes the results of structure-activity relationship studies aimed at the discovery of selective 5-HT7 receptor ligands. Additionally, an overview of the potential therapeutic applications of 5-HT7 receptor agonists and antagonists in central nervous system disorders is presented. PMID:20923682

  4. The soft mechanical signature of glial scars in the central nervous system

    NASA Astrophysics Data System (ADS)

    Moeendarbary, Emad; Weber, Isabell P.; Sheridan, Graham K.; Koser, David E.; Soleman, Sara; Haenzi, Barbara; Bradbury, Elizabeth J.; Fawcett, James; Franze, Kristian

    2017-03-01

    Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Mammalian glial scars supposedly form a chemical and mechanical barrier to neuronal regeneration. While tremendous effort has been devoted to identifying molecular characteristics of the scar, very little is known about its mechanical properties. Here we characterize spatiotemporal changes of the elastic stiffness of the injured rat neocortex and spinal cord at 1.5 and three weeks post-injury using atomic force microscopy. In contrast to scars in other mammalian tissues, CNS tissue significantly softens after injury. Expression levels of glial intermediate filaments (GFAP, vimentin) and extracellular matrix components (laminin, collagen IV) correlate with tissue softening. As tissue stiffness is a regulator of neuronal growth, our results may help to understand why mammalian neurons do not regenerate after injury.

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

    PubMed Central

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

    2018-01-01

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

  6. [The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose].

    PubMed

    Baykal, Mehmet; Gökmen, Necati; Doğan, Alper; Erbayraktar, Serhat; Yılmaz, Osman; Ocmen, Elvan; Erdost, Hale Aksu; Arkan, Atalay

    The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n=6), Group 1/10 (n=6), and Group 1/100 (n=6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. The rocuronium bromide seizure threshold value was found to be 0.056±0.009μmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286μmoL/kg -1 . A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures. Publicado por Elsevier Editora Ltda.

  7. The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose.

    PubMed

    Baykal, Mehmet; Gökmen, Necati; Doğan, Alper; Erbayraktar, Serhat; Yılmaz, Osman; Ocmen, Elvan; Erdost, Hale Aksu; Arkan, Atalay

    The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n=6), Group 1/10 (n=6), and Group 1/100 (n=6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. The rocuronium bromide seizure threshold value was found to be 0.056±0.009μmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286μmoL/kg -1 . A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures. Published by Elsevier Editora Ltda.

  8. 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

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

    PubMed

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

    2008-07-01

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

  10. 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.

  11. Central nervous system involvement in AIDS-related lymphomas.

    PubMed

    Barta, Stefan K; Joshi, Jitesh; Mounier, Nicolas; Xue, Xiaonan; Wang, Dan; Ribera, Josep-Maria; Navarro, Jose-Tomas; Hoffmann, Christian; Dunleavy, Kieron; Little, Richard F; Wilson, Wyndham H; Spina, Michele; Galicier, Lionel; Noy, Ariela; Sparano, Joseph A

    2016-06-01

    Central nervous system (CNS) involvement is reportedly more common in acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARL). We describe factors and outcomes associated with CNS involvement at baseline (CNS(B) ) and relapse (CNS(R) ) in 886 patients with newly diagnosed ARL. Of 886 patients, 800 received either intrathecal (IT) therapy for CNS(B) or IT prophylaxis. CNS(B) was found in 13%. CNS(B) was not associated with reduced overall survival (OS). There was no difference in the prevalence of CNS(B) between the pre-combination antiretroviral therapy (cART) and cART eras. 5·3% of patients experienced CNS(R) at a median of 4·2 months after diagnosis (12% if CNS(B) ; 4% if not). Median OS after CNS(R) was 1·6 months. On multivariate analysis, only CNS(B) [hazard ratio (HR) 3·68, P = 0·005] and complete response to initial therapy (HR 0·14, P < 0·0001) were significantly associated with CNS(R) . When restricted to patients without CNS(B) , IT CNS prophylaxis with 3 vs. 1 agent did not significantly impact the risk of CNS(R) . Despite IT CNS prophylaxis, 5% of patients experienced CNS(R) . Our data confirms that CNS(R) in ARL occurs early and has a poor outcome. Complete response to initial therapy was associated with a reduced frequency of CNS(R) . Although CNS(B) conferred an increased risk for CNS(R) , it did not impact OS. © 2016 John Wiley & Sons Ltd.

  12. Current Management of Primary Central Nervous System Lymphoma

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

    Schultz, Christopher J.; Bovi, Joseph, E-mail: jbovi@mcw.ed

    2010-03-01

    Primary central nervous cell lymphoma (PCNSL) is an uncommon neoplasm of the brain, leptomeninges, and rarely the spinal cord. Initially thought to be characteristically associated with congenital, iatrogenic, or acquired immunosuppression, PCNSL is now recognized with increasing frequency in immunocompetent individuals. The role of surgery is limited to establishing diagnosis, as PCNSL is often multifocal with a propensity to involve the subarachnoid space. A whole-brain radiation volume has empirically been used to adequately address the multifocal tumor frequently encountered at the time of PCNSL diagnosis. Despite high rates of response after whole-brain radiotherapy (WBRT), rapid recurrence is common and long-termmore » survival is the exception. Chemotherapy alone or in combination with WBRT has more recently become the treatment of choice. Most effective regimens contain high-dose methotrexate and or other agents that are capable of penetrating the blood-brain barrier. High response rates and improved survival with the use of chemotherapy has led to treatment strategies that defer or eliminate WBRT in hopes of lessening the risk of neurotoxicity attributed to WBRT. Unfortunately, elimination of WBRT is also associated with a higher rate of relapse. Combined chemotherapy and WBRT regimens are now being explored that use lower total doses of radiation and altered fractionation schedules with the aim of maintaining high rates of tumor control while minimizing neurotoxicity. Pretreatment, multifactor prognostic indices have recently been described that may allow selection of treatment regimens that strike an appropriate balance of risk and benefit for the individual PCNSL patient.« less

  13. Central nervous system (CNS) neuroblastoma. A case-based update.

    PubMed

    Bianchi, Federico; Tamburrini, Gianpiero; Gessi, Marco; Frassanito, Paolo; Massimi, Luca; Caldarelli, Massimo

    2018-05-01

    Primary central nervous system (CNS) neuroblastoma is a rare intracranial tumor affecting children mainly in the first years of life. It is usually a supratentorial tumor with a wide spectrum of clinical presentation, seizures, and focal neurological deficits being the most common presenting signs. A 2-year-old child was admitted to our ward after a generalized seizure. Neurological examination was normal. Radiological studies showed a small DWI hyperintense lesion of the right rectus gyrus. Follow-up brain MRI 8 months later showed a huge growth of the tumor (90 × 80 × 65 mm) with polycyclic and apparently defined margins, cystic components, and diffuse contrast enhancement. Complete tumor removal was performed in two planned surgical steps. Histological diagnosis was CNS neuroblastoma. At a follow-up of 8 months, the child is in good clinical and neurological condition and is completing chemotherapy treatment according to the SIOP PNET 4 protocol. A thorough review of the literature confirms that primary CNS neuroblastoma has to be considered a distinct entity. The disease related mortality is 12.5%, lower than the one usually reported for other previously described as PNETs tumors. The most relevant factors influencing prognosis are the possibility of obtaining a complete tumor removal and age more than 3 years, which allows to include radiotherapy among treatment options.

  14. Magnetic resonance imaging findings of central nervous system in lysosomal storage diseases: A pictorial review.

    PubMed

    Fagan, Nathan; Alexander, Allen; Irani, Neville; Saade, Charbel; Naffaa, Lena

    2017-06-01

    Lysosomal storage diseases (LSD) are a complex group of genetic disorders that are a result of inborn errors of metabolism. These errors result in a variety of metabolic dysfunction and build-up certain molecules within the tissues of the central nervous system (CNS). Although, they have discrete enzymatic deficiencies, symptomology and CNS imaging findings can overlap with each other, which can become challenging to radiologists. The purpose of this paper is to review the most common CNS imaging findings in LSD in order to familiarize the radiologist with their imaging findings and help narrow down the differential diagnosis. © 2016 The Royal Australian and New Zealand College of Radiologists.

  15. Non-Viral Nucleic Acid Delivery Strategies to the Central Nervous System

    PubMed Central

    Tan, James-Kevin Y.; Sellers, Drew L.; Pham, Binhan; Pun, Suzie H.; Horner, Philip J.

    2016-01-01

    With an increased prevalence and understanding of central nervous system (CNS) injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver all types of nucleic acids. Nevertheless, there are still a number of barriers to nucleic acid delivery. In this focused review, we explore the in vivo challenges hindering non-viral nucleic acid delivery to the CNS and the strategies and vehicles used to overcome them. Advantages and disadvantages of different routes of administration including: systemic injection, cerebrospinal fluid injection, intraparenchymal injection and peripheral administration are discussed. Non-viral vehicles and treatment strategies that have overcome delivery barriers and demonstrated in vivo gene transfer to the CNS are presented. These approaches can be used as guidelines in developing synthetic gene delivery vectors for CNS applications and will ultimately bring non-viral vectors closer to clinical application. PMID:27847462

  16. Type17 T-cells in Central Nervous System Autoimmunity and Tumors

    PubMed Central

    Okada, Hideho; Khoury, Samia J.

    2012-01-01

    Interleukin-17 (IL-17) producing Type17 T-cells, specifically T-helper (Th)17 cells reactive to central nervous system (CNS) autoantigens, manifest a higher migratory capability to the CNS parenchyma compared with other T-cell subpopulations due to their ability to penetrate the blood brain barrier (BBB). In the field of cancer immunotherapy, there are now a number of cell therapy approaches including early studies using T-cells transduced with chimeric antigen receptors in hematologic malignancy, suggesting that the use of T-cells or genetically modified T-cells could have a significant role in effective cancer therapy. However, the successful application of this strategy in solid tumors, such as CNS tumors, requires careful consideration of critical factors to improve the tumor-homing of T-cells. The current review is dedicated to discuss recent findings on the role of Type17 T-cells in CNS autoimmunity and cancer. The insight gained from these findings may lead to the development of novel therapeutic and prophylactic strategies for CNS autoimmunity and tumors. PMID:22454247

  17. The central nervous system--an additional consideration in 'rotator cuff tendinopathy' and a potential basis for understanding response to loaded therapeutic exercise.

    PubMed

    Littlewood, Chris; Malliaras, Peter; Bateman, Marcus; Stace, Richmond; May, Stephen; Walters, Stephen

    2013-12-01

    Tendinopathy is a term used to describe a painful tendon disorder but despite being a well-recognised clinical presentation, a definitive understanding of the pathoaetiology of rotator cuff tendinopathy remains elusive. Current explanatory models, which relate to peripherally driven nocioceptive mechanisms secondary to structural abnormality, or failed healing, appear inadequate on their own in the context of current literature. In light of these limitations this paper presents an extension to current models that incorporates the integral role of the central nervous system in the pain experience. The role of the central nervous system (CNS) is described and justified along with a potential rationale to explain the favourable response to loaded therapeutic exercises demonstrated by previous studies. This additional consideration has the potential to offer a useful way to explain pain to patients, for clinicians to prescribe appropriate therapeutic management strategies and for researchers to advance knowledge in relation to this clinically challenging problem. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2012-02-15

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

  19. 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.

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

    PubMed

    Mechoulam, R; Lichtman, A H

    2003-10-03

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

  1. 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.

  2. 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.

  3. Acute and prolonged complement activation in the central nervous system during herpes simplex encephalitis.

    PubMed

    Eriksson, Charlotta E; Studahl, Marie; Bergström, Tomas

    2016-06-15

    Herpes simplex encephalitis (HSE) is characterized by a pronounced inflammatory activity in the central nervous system (CNS). Here, we investigated the acute and prolonged complement system activity in HSE patients, by using enzyme-linked immunosorbent assays (ELISAs) for numerous complement components (C). We found increased cerebrospinal fluid concentrations of C3a, C3b, C5 and C5a in HSE patients compared with healthy controls. C3a and C5a concentrations remained increased also compared with patient controls. Our results conclude that the complement system is activated in CNS during HSE in the acute phase, and interestingly also in later stages supporting previous reports of prolonged inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. [Autochthonous acute viral and bacterial infections of the central nervous system (meningitis and encephalitis)].

    PubMed

    Pérez-Ruiz, Mercedes; Vicente, Diego; Navarro-Marí, José María

    2008-07-01

    Rapid diagnosis of acute viral and bacterial infections of the central nervous system (meningitis and encephalitis) is highly important for the clinical management of the patient and helps to establish early therapy that may solve life-threatening situations, to avoid unnecessary empirical treatments, to reduce hospital stay, and to facilitate appropriate interventions in the context of public health. Molecular techniques, especially real-time polymerase chain reaction, have become the fastest and most sensitive diagnostic procedures for autochthonous viral meningitis and encephalitis, and their role is becoming increasingly important for the diagnosis and control of most frequent acute bacterial meningitides. Automatic and closed systems may encourage the widespread and systematic use of molecular techniques for the diagnosis of these neurological syndromes in most laboratories.

  5. Syndromic craniosynostosis: neuropsycholinguistic abilities and imaging analysis of the central nervous system.

    PubMed

    Maximino, Luciana Paula; Ducati, Luis Gustavo; Abramides, Dagma Venturini Marques; Corrêa, Camila de Castro; Garcia, Patrícia Fernandes; Fernandes, Adriano Yacubian

    2017-12-01

    To characterize patients with syndromic craniosynostosis with respect to their neuropsycholinguistic abilities and to present these findings together with the brain abnormalities. Eighteen patients with a diagnosis of syndromic craniosynostosis were studied. Eight patients had Apert syndrome and 10 had Crouzon syndrome. They were submitted to phonological evaluation, neuropsychological evaluation and magnetic resonance imaging of the brain. The phonological evaluation was done by behavioral observation of the language, the Peabody test, Token test and a school achievement test. The neuropsychological evaluation included the WISC III and WAIS tests. Abnormalities in language abilities were observed and the school achievement test showed abnormalities in 66.67% of the patients. A normal intelligence quotient was observed in 39.3% of the patients, and congenital abnormalities of the central nervous system were observed in 46.4% of the patients. Abnormalities of language abilities were observed in the majority of patients with syndromic craniosynostosis, and low cognitive performance was also observed.

  6. Primary central nervous system lymphoma in immunocompetent individuals: a single center experience.

    PubMed

    Aki, Hilal; Uzunaslan, Didem; Saygin, Caner; Batur, Sebnem; Tuzuner, Nukhet; Kafadar, Ali; Ongoren, Seniz; Oz, Buge

    2013-01-01

    Primary central nervous system lymphoma (PCNSL) is defined as the involvement of brain, leptomeninges, eyes or spinal cord by non-Hodgkin lymphoma. The role of various prognostic markers in predicting adverse outcome is debated. To investigate the clinical and immunohistochemical findings of immunocompetent PCNSL cases (39 cases) diagnosed at the study center, and evaluate the influence of potential prognostic factors on overall survival (OS) of patients. Data regarding patient characteristics, neuroimaging, pathological and immunohistochemical features and follow-up were obtained from patient records. The influence of potential prognostic parameters on OS was investigated by log-rank test and Cox regression analysis. Patients who received combined chemotherapy and radiotherapy had a significantly better OS when compared to chemotherapy alone. Other variables included in this study were not associated with a significant survival advantage. In this study, we failed to demonstrate a relationship between different clinicopathological variables and OS of patients. Prospective studies with large patient series are needed to investigate other potential prognostic factors.

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

    PubMed

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

    2016-12-01

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

  8. Intraoperative consultation of central nervous system lesions. Frozen section, cytology or both?

    PubMed

    Sharifabadi, Ali Haidari; Haeri, Hayedeh; Zeinalizadeh, Mehdi; Zargari, Neda; Razavi, Amirnader Emami; Shahbazi, Nargess; Tahvildari, Malahat; Azmoudeh-Ardalan, Farid

    2016-03-01

    Frozen section is the traditional method of assessing central nervous system (CNS) lesions intraoperatively. Our aim is to determine the diagnostic accuracy of frozen section and/or cytological evaluation of CNS lesions in our center. A total of 157 patients with CNS lesions underwent open surgical biopsy or excision in our center during a period of 2 years (2012-2013). All specimens were studied cytologically; of these specimens, 146 cases were also examined by frozen section. Cytology and frozen section slides were studied separately by two general pathologists who were blind to final diagnoses. The final diagnoses were based on permanent sections and IHC studies. The accuracy rates of frozen section analysis and cytological evaluation were 87% and 86%, respectively. If the two methods were considered together, the accuracy rate improved to about 95%. Cytological evaluation is an acceptable alternative to frozen section analysis and also a great supplement to the diagnosis of CNS lesions. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. [Neuroimaging of Langerhans cell histiocytosis in the central nervous system of children].

    PubMed

    De La Hoz Polo, M; Rebollo Polo, M; Fons Estupiña, C; Muchart López, J; Cruz Martinez, O

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare disease characterized by the accumulation within tissues of anomalous dendritic cells similar to Langerhans cells. The clinical presentation varies, ranging from the appearance of a single bone lesion to multisystemic involvement. Central nervous system (CNS) involvement, manifesting as diabetes insipidus secondary to pituitary involvement, has been known since the original description of the disease. Two types of CNS lesions are currently differentiated. The first, pseudotumoral lesions with infiltration by Langerhans cells, most commonly manifests as pituitary infiltration. The second, described more recently, consists of neurodegenerative lesions of the CNS associated with neurologic deterioration. This second type of lesion constitutes a complication of the disease; however, there is no consensus about the cause of this complication. Our objective was to describe the radiologic manifestations of LCH in the CNS in pediatric patients. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  10. Management of pediatric central nervous system emergencies: a review for general radiologists.

    PubMed

    Rebollo Polo, M

    2016-05-01

    To review the most common and most important diseases and disorders of the central nervous system (CNS) in pediatric emergencies, discussing the indications for different imaging tests in each context. In pediatric patients, acute neurologic symptoms (seizures, deteriorating level of consciousness, focal neurologic deficits, etc.) can appear in diverse clinical situations (trauma, child abuse, meningoencephalitis, ischemia…). It is important to decide on the most appropriate neuroimaging diagnostic algorithm for each situation and age group, as well as to know the signs of the most typical lesions that help us in the etiological differential diagnosis. Pediatric patients' increased vulnerability to ionizing radiation and the possible need for sedation in studies that require more time are factors that should be taken into account when indicating an imaging test. It is essential to weigh the risks and benefits for the patient and to avoid unnecessary studies. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  11. HIV life cycle, innate immunity and autophagy in the central nervous system.

    PubMed

    Meulendyke, Kelly A; Croteau, Joshua D; Zink, M Christine

    2014-11-01

    In this era of modern combination antiretroviral therapy (cART) HIV-associated neurocognitive disorders (HAND) continue to affect a large portion of the infected population. In this review, we highlight recent discoveries that help to define the interplay between HIV life cycle, the innate immune system and cellular autophagy in the context of the central nervous system (CNS). Investigators have recently elucidated themes in HAND, which place it in a unique framework. Cells of macrophage lineage and probably astrocytes play a role in disseminating virus through the CNS. Each of these cell types responds to a diverse population of constantly evolving virus existing in an inflammatory environment. This occurs though the failure of both host antiviral mechanisms, such as autophagy, and innate immunological signalling pathways to control viral replication. The newest findings detailed in this review help define why HIV CNS disease is a difficult target for therapeutics and create hope that these new mechanisms may be exploited to attenuate viral replication and eliminate disease.

  12. Cardiovascular and behavioral effects produced by administration of liposome-entrapped GABA into the rat central nervous system.

    PubMed

    Vaz, G C; Bahia, A P C O; de Figueiredo Müller-Ribeiro, F C; Xavier, C H; Patel, K P; Santos, R A S; Moreira, F A; Frézard, F; Fontes, M A P

    2015-01-29

    Liposomes are nanosystems that allow a sustained release of entrapped substances. Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter of the central nervous system (CNS). We developed a liposomal formulation of GABA for application in long-term CNS functional studies. Two days after liposome-entrapped GABA was injected intracerebroventricularly (ICV), Wistar rats were submitted to the following evaluations: (1) changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) to ICV injection of bicuculline methiodide (BMI) in anesthetized rats; (2) changes in cardiovascular reactivity to air jet stress in conscious rats; and (3) anxiety-like behavior in conscious rats. GABA and saline-containing pegylated liposomes were prepared with a mean diameter of 200 nm. Rats with implanted cannulas targeted to lateral cerebral ventricle (n = 5-8/group) received either GABA solution (GS), empty liposomes (EL) or GABA-containing liposomes (GL). Following (48 h) central microinjection (2 μL, 0.09 M and 99 g/L) of liposomes, animals were submitted to the different protocols. Animals that received GL demonstrated attenuated response of RSNA to BMI microinjection (GS 48 ± 9, EL 43 ± 9, GL 11 ± 8%; P < 0.05), blunted tachycardia in the stress trial (ΔHR: GS 115 ± 14, EL 117 ± 10, GL 74 ± 9 bpm; P<0.05) and spent more time in the open arms of elevated plus maze (EL 6 ± 2 vs. GL 18 ± 5%; P = 0.028) compared with GS and EL groups. These results indicate that liposome-entrapped GABA can be a potential tool for exploring the chronic effects of GABA in specific regions and pathways of the central nervous system. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. [Investigation of bacterial and viral etiology in community acquired central nervous system infections with molecular methods].

    PubMed

    Kahraman, Hasip; Tünger, Alper; Şenol, Şebnem; Gazi, Hörü; Avcı, Meltem; Örmen, Bahar; Türker, Nesrin; Atalay, Sabri; Köse, Şükran; Ulusoy, Sercan; Işıkgöz Taşbakan, Meltem; Sipahi, Oğuz Reşat; Yamazhan, Tansu; Gülay, Zeynep; Alp Çavuş, Sema; Pullukçu, Hüsnü

    2017-07-01

    In this multicenter prospective cohort study, it was aimed to evaluate the bacterial and viral etiology in community-acquired central nervous system infections by standart bacteriological culture and multiplex polymerase chain reaction (PCR) methods. Patients hospitalized with central nervous system infections between April 2012 and February 2014 were enrolled in the study. Demographic and clinical information of the patients were collected prospectively. Cerebrospinal fluid (CSF) samples of the patients were examined by standart bacteriological culture methods, bacterial multiplex PCR (Seeplex meningitis-B ACE Detection (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Group B streptococci) and viral multiplex PCR (Seeplex meningitis-V1 ACE Detection kits herpes simplex virus-1 (HSV1), herpes simplex virus-2 (HSV2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein Barr virus (EBV) and human herpes virus 6 (HHV6)) (Seeplex meningitis-V2 ACE Detection kit (enteroviruses)). Patients were classified as purulent meningitis, aseptic meningitis and encephalitis according to their clinical, CSF (leukocyte level, predominant cell type, protein and glucose (blood/CSF) levels) and cranial imaging results. Patients who were infected with a pathogen other than the detection of the kit or diagnosed as chronic meningitis and other diseases during the follow up, were excluded from the study. A total of 79 patients (28 female, 51 male, aged 42.1 ± 18.5) fulfilled the study inclusion criteria. A total of 46 patients were classified in purulent meningitis group whereas 33 were in aseptic meningitis/encephalitis group. Pathogens were detected by multiplex PCR in 41 patients. CSF cultures were positive in 10 (21.7%) patients (nine S.pneumoniae, one H.influenzae) and PCR were positive for 27 (58.6%) patients in purulent meningitis group. In this group one type of bacteria were detected in 18 patients (14 S.pneumoniae, two N

  14. The blood-brain barrier in the cerebrum is the initial site for the Japanese encephalitis virus entering the central nervous system.

    PubMed

    Liu, Tsan-Hsiun; Liang, Li-Ching; Wang, Chien-Chih; Liu, Huei-Chung; Chen, Wei-June

    2008-11-01

    Japanese encephalitis (JE) virus is a member of the encephalitic flaviviruses and frequently causes neurological sequelae in a proportion of patients who survive the acute phase of the infection. In the present study, we molecularly identified viral infection in the brain of mice with rigidity of hindlimbs and/or abnormal gait, in which JE virus particles appeared within membrane-bound vacuoles of neurons throughout the central nervous system. Deformation of tight junctions (TJs) shown as dissociation of endothelial cells in capillaries, implying that the integrity of the blood-brain barrier (BBB) has been compromised by JE virus infection. BBB permeability evidently increased in the cerebrum, but not in the cerebellum, of JE virus-infected mice intravenously injected with the tracer of Evans blue dye. This suggests that the permeability of the BBB differentially changed in response to viral infection, leading to the entry of JE virions and/or putatively infected leukocytes from the periphery to the cerebrum as the initial site of infection in the central nervous system (CNS). Theoretically, the virus spread to the cerebellum soon after the cerebrum became infected.

  15. Are evoked potentials in patients with adult-onset pompe disease indicative of clinically relevant central nervous system involvement?

    PubMed

    Wirsching, Andreas; Müller-Felber, Wolfgang; Schoser, Benedikt

    2014-08-01

    Pompe disease is a multisystem autosomal recessive glycogen storage disease. Autoptic findings in patients with classic infantile and late-onset Pompe disease have proven that accumulation of glycogen can also be found in the peripheral and central nervous system. To assess the functional role of these pathologic findings, multimodal sensory evoked potentials were analyzed. Serial recordings for brainstem auditory, visual, and somatosensory evoked potentials of 11 late-onset Pompe patients were reviewed. Data at the onset of the enzyme replacement therapy with alglucosidase alfa were compared with follow-up recordings at 12 and 24 months. Brainstem auditory evoked potentials showed a delayed peak I in 1/10 patients and an increased I-III and I-V interpeak latency in 1/10 patients, respectively. The III-V interpeak latencies were in the normal range. Visual evoked potentials were completely normal. Median somatosensory evoked potentials showed an extended interpeak latency in 3/9 patients. Wilcoxon tests comparing age-matched subgroups found significant differences in brainstem auditory evoked potentials and visual evoked potentials. We found that the majority of recordings for evoked potentials were within the ranges for standard values, therefore reflecting the lack of clinically relevant central nervous system involvement. Regular surveillance by means of evoked potentials does not seem to be appropriate in late-onset Pompe patients.

  16. 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.

  17. Interleukin-6 levels in the central nervous system are negatively correlated with fat mass in overweight/obese subjects.

    PubMed

    Stenlöf, Kaj; Wernstedt, Ingrid; Fjällman, Ted; Wallenius, Ville; Wallenius, Kristina; Jansson, John-Olov

    2003-09-01

    Recently, we demonstrated that intracerebroventricular injection of IL-6 increases energy expenditure and decreases body fat in rodents. Therefore, IL-6 may play a role in appetite and body weight control in the central nervous system. In the present study we evaluated cerebrospinal fluid (CSF) and serum IL-6 levels in humans in relation to body fat content and to CSF and serum levels of leptin. Thirty-two healthy overweight/obese male subjects with a body mass index range of 29.3-36.0 kg/m(2) were studied. Total and sc body fat were measured by dual energy x-ray absorptiometry and computed tomography, respectively. CSF IL-6 levels were in some individuals higher than serum IL-6 levels and correlated negatively with total body weight, sc and total body fat. In contrast, CSF leptin levels were 30-60 times lower than serum leptin levels and correlated positively with serum leptin, body weight, sc and total body fat. Furthermore, there was a negative correlation between CSF IL-6 and leptin. In conclusion, CSF IL-6 differs in many ways from CSF leptin. CSF IL-6 may be locally produced rather than serum derived, and body fat-regulating regions in the central nervous system may be exposed to insufficient IL-6 levels in more severe obesity.

  18. Central Nervous System Fibrosis Is Associated with Fibrocyte-Like Infiltrates

    PubMed Central

    Aldrich, Amy; Kielian, Tammy

    2011-01-01

    Fibrotic wall formation is essential for limiting pathogen dissemination during brain abscess development. However, little is known about the regulation of fibrotic processes in the central nervous system (CNS). Most CNS injury responses are associated with hypertrophy of resident astrocytes, a process termed reactive gliosis. Studies of fibrosis outside the CNS have identified two bone marrow–derived cell types, fibrocytes and alternatively activated M2 macrophages, as key mediators of fibrosis. The current study used bone marrow chimeras generated from green fluorescent protein transgenic mice to evaluate the appearance of these cell types and whether bone marrow–derived cells were capable of acquiring fibrotic characteristics during brain abscess development. Immunofluorescence staining revealed partial overlap between green fluorescent protein, α-smooth muscle actin, and procollagen, suggesting that a population of cells forming the brain abscess capsule originate from a bone marrow precursor. In addition, the influx of fibrocyte-like cells into brain abscesses immediately preceded the onset of fibrotic encapsulation. Fibrotic wall formation was also associated with increased numbers of alternatively activated M2 microglia and macrophages. To our knowledge, this is the first study demonstrating that bone marrow–derived infiltrates are capable of expressing fibrotic molecules during CNS inflammation. PMID:22015460

  19. Central nervous system infections and stroke -- a population-based analysis.

    PubMed

    Chien, L-N; Chi, N-F; Hu, C-J; Chiou, H-Y

    2013-10-01

    Chronic central nervous system (CNS) infections have been found to associate with cerebrovascular complications. Acute CNS infections are more common than chronic CNS infections, but whether they could increase the risk of vascular diseases has not been studied. The study cohort comprised all adult patients with diagnoses of CNS infections from Taiwan National Health Insurance Research Database during 2000-2009 (n = 533). The comparison group were matched by age, sex, urbanization, diagnostic year, and vascular risk factors of cases (cases and controls = 1:5). Patients were tracked for at least 1 year. Kaplan-Meier analysis was used to compare the risk of stroke and acute myocardial infarction (AMI) after adjusting censoring subjects. After adjusting the patients demographic characteristics and comorbidities, the risk of patients with CNS infections developing stroke was 2.75-3.44 times greater than their comparison group. More than 70% of the stroke events were occurring within 1 year after CNS infections. The risk of AMI was not found as we compared patients with and without CNS infections. The population-based cohort study suggested that adult patients with CNS infections have higher risk to develop stroke but not AMI, and the risk is marked within a year after infections. © 2013 John Wiley & Sons A/S.

  20. Cystic Fibrosis and the Nervous System.

    PubMed

    Reznikov, Leah R

    2017-05-01

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

  1. Ultrastructural networks in growth cones and neurites of cultured central nervous system neurons.

    PubMed Central

    Tsui, H C; Ris, H; Klein, W L

    1983-01-01

    We have examined growth cones and neurites of cultured central nervous system neurons by high-voltage electron microscopy. Embryonic chicken retina cells were cultured on polylysine-treated and Formvar-coated gold grids for 2-6 days, fixed, and critical point dried. Growth cones and neurites were examined as unembedded whole mounts. Three-dimensional images from stereo-pair electron micrographs of these regions showed a high degree of ultrastructural articulation, with distinct, non-tapering filaments (5-9 nm in diameter) joining both cytoskeletal and membranous components. In the central regions of growth cones, interconnected structures included microtubules, large membranous sacs (up to 400 nm), and irregular vesicles (25-75 nm). A denser filamentous network was prevalent at the edges of growth cones. This network, which frequently adjoined the surface membrane, linked vesicles of uniform size (35-40 nm). Such vesicles often were seen densely packed in growth cone protrusions that were about the size of small synaptic boutons. Prevalent structural interconnections within growth cones conceivably could play a logistic role in specific membrane assembly, intracellular transport, endocytosis, and secretion. Because such processes are not unique to growth cones, the extensive linkages we have observed may have implications for cytoplasmic structure in general. Images PMID:6577454

  2. Ultrastructural networks in growth cones and neurites of cultured central nervous system neurons.

    PubMed

    Tsui, H C; Ris, H; Klein, W L

    1983-09-01

    We have examined growth cones and neurites of cultured central nervous system neurons by high-voltage electron microscopy. Embryonic chicken retina cells were cultured on polylysine-treated and Formvar-coated gold grids for 2-6 days, fixed, and critical point dried. Growth cones and neurites were examined as unembedded whole mounts. Three-dimensional images from stereo-pair electron micrographs of these regions showed a high degree of ultrastructural articulation, with distinct, non-tapering filaments (5-9 nm in diameter) joining both cytoskeletal and membranous components. In the central regions of growth cones, interconnected structures included microtubules, large membranous sacs (up to 400 nm), and irregular vesicles (25-75 nm). A denser filamentous network was prevalent at the edges of growth cones. This network, which frequently adjoined the surface membrane, linked vesicles of uniform size (35-40 nm). Such vesicles often were seen densely packed in growth cone protrusions that were about the size of small synaptic boutons. Prevalent structural interconnections within growth cones conceivably could play a logistic role in specific membrane assembly, intracellular transport, endocytosis, and secretion. Because such processes are not unique to growth cones, the extensive linkages we have observed may have implications for cytoplasmic structure in general.

  3. Wasp manipulates cockroach behavior by injecting venom cocktail into prey central nervous system.

    PubMed

    Haspel, G; Libersat, F

    2004-01-01

    The parasitoid wasp Ampulex compressa induces behavioral changes in the cockroach prey by injecting venom into its central nervous system. In contrast to most other venomous predators, the wasp's sting does not induce paralysis. Rather, the two consecutive stings in the thoracic and head ganglia induce three stereotypic behavioral effects. The prey behavior is manipulated in a way beneficial to the wasp and its offspring by providing a living meal for its newborn larva. The first sting in the thorax causes a transient front leg paralysis lasting a few minutes. This paralysis prevents the cockroach from fighting with its front legs, thereby facilitating the second sting in the head. A postsynaptic block of central synaptic transmission mediates this leg paralysis. Following the head sting, dopamine identified in the venom induces 30 minutes of intense grooming that appears to prevent the cockroach from straying until the last and third behavioral effect of hypokinesia commences. In this lethargic state that lasts about three weeks, the cockroach does not respond to various stimuli nor does it initiates movement. However, other specific behaviors of the prey are unaffected. We propose that the venom represses the activity of head ganglia neurons thereby removing the descending excitatory drive to specific thoracic neurons.

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

    PubMed Central

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

    2015-01-01

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

  5. Staphylococcus aureus Central Nervous System Infections in Children.

    PubMed

    Vallejo, Jesus G; Cain, Alexandra N; Mason, Edward O; Kaplan, Sheldon L; Hultén, Kristina G

    2017-10-01

    Central nervous system (CNS) infections caused by Staphylococcus aureus are uncommon in pediatric patients. We review the epidemiology, clinical features and treatment in 68 patients with a S. aureus CNS infection evaluated at Texas Children's Hospital. Cases of CNS infection in children with positive cerebrospinal fluid cultures or spinal epidural abscess (SEA) for S. aureus at Texas Children's Hospital from 2001 to 2013 were reviewed. Seventy cases of S. aureus CNS infection occurred in 68 patients. Forty-nine cases (70%) were secondary to a CNS device, 5 (7.1%) were postoperative meningitis, 9 (12.8%) were hematogenous meningitis and 7 (10%) were SEAs. Forty-seven (67.2%) were caused by methicillin-sensitive S. aureus (MSSA) and 23 (32.8%) by methicillin-resistant S. aureus (MRSA). Community-acquired infections were more often caused by MRSA that was clone USA300/pvl. Most patients were treated with nafcillin (MSSA) or vancomycin (MRSA) with or without rifampin. Among patients with MRSA infection, 50% had a serum vancomycin trough obtained with the median level being 10.6 μg/mL (range: 5.4-15.7 μg/mL). Only 1 death was associated with S. aureus infection. The epidemiology of invasive of S. aureus infections continues to evolve with MSSA accounting for most of the infections in this series. The majority of cases were associated with neurosurgical procedures; however, hematogenous S. aureus meningitis and SEA occurred as community-acquired infections in patients without predisposing factors. Patients with MRSA CNS infections had a favorable response to vancomycin, but the beneficial effect of combination therapy or targeting vancomycin trough concentrations of 15-20 μg/mL remains unclear.

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

    PubMed

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

    2014-09-23

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

  7. 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.

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

    PubMed

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

    2014-04-01

    Positron emission tomography (PET) and PET/computed tomography (PET-CT) studies with (11)C- or (18)F-labeled choline derivatives are used for PET imaging in glioblastoma patients. However, the nature of the choline transport system in glioblastoma is poorly understood. In this study, we performed a functional characterization of [methyl-(3)H]choline uptake and sought to identify the transporters that mediate choline uptake in the human glioblastoma cell lines A-172 and U-251MG. In addition, we examined the influence of anti-cancer drugs and central nervous system drugs on the transport of [methyl-(3)H]choline. High- and low-affinity choline transport systems were present in A-172 cells, U-251MG cells and astrocytes, and these were Na(+)-independent and pH-dependent. Cell viability in A-172 cells was not affected by choline deficiency. However, cell viability in U-251MG cells was significantly inhibited by choline deficiency. Both A-172 and U-251MG cells have two different choline transporters, choline transporter-like protein 1 (CTL1) and CTL2. In A-172 cells, CTL1 is predominantly expressed, whereas in U-251MG cells, CTL2 is predominantly expressed. Treatment with anti-cancer drugs such as cisplatin, etoposide and vincristine influenced [methyl-(3)H]choline uptake in U-251MG cells, but not A-172 cells. Central nervous system drugs such as imipramine, fluvoxamine, paroxetine, reboxetine, citalopram and donepezil did not affect cell viability or [methyl-(3)H]choline uptake. The data presented here suggest that CTL1 and CTL2 are functionally expressed in A-172 and U-251MG cells and are responsible for [methyl-(3)H]choline uptake that relies on a directed H(+) gradient as a driving force. Furthermore, while anti-cancer drugs altered [methyl-(3)H]choline uptake, central nervous system drugs did not affect [methyl-(3)H]choline uptake. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Retinal oximetry measures systemic hypoxia in central nervous system vessels in chronic obstructive pulmonary disease

    PubMed Central

    Bragason, David; Hardarson, Sveinn Hakon; Vacchiano, Charles; Gislason, Thorarinn; Kristjansdottir, Jona Valgerdur; Kristjansdottir, Gudrun; Stefánsson, Einar

    2017-01-01

    Background Determination of the blood oxyhemoglobin saturation in the retinal vessels of the eye can be achieved through spectrophotometric retinal oximetry which provides access to the state of oxyhemoglobin saturation in the central nervous system circulation. The purpose of this study was to test the capability of the Oxymap T1 oximeter to detect systemic hypoxemia and the effect of supplemental oxygen on retinal vessel oxyhemoglobin saturation. Methods Oxygen saturation of hemoglobin in retinal arterioles and venules was measured in 11 subjects with severe chronic obstructive pulmonary disease (COPD) on long term oxygen therapy. Measurements were made with and without their daily supplemental oxygen. Eleven healthy age and gender matched subjects were measured during ambient air breathing for comparison of oxyhemoglobin saturation in retinal arterioles and venules. Retinal arteriolar oxyhemoglobin saturation in COPD subjects inspiring ambient air was compared with finger pulse oximetry and blood samples from radial artery. Results COPD subjects had significantly lower oxyhemoglobin saturation during ambient air breathing than healthy controls in both retinal arterioles (87.2%±4.9% vs. 93.4%±4.3%, p = 0.02; n = 11) and venules (45.0%±10.3% vs. 55.2%±5.5%, p = 0.01). Administration of their prescribed supplemental oxygen increased oxyhemoglobin saturation in retinal arterioles (87.2%±4.9% to 89.5%±6.0%, p = 0.02) but not in venules (45.0%±10.3% to 46.7%±12.8%, p = 0.3). Retinal oximetry values were slightly lower than radial artery blood values (mean percentage points difference = -5.0±5.4, 95% CI: -15.68 to 5.67) and finger pulse oximetry values (-3.1±5.5, 95% CI: -14.05 to 7.84). Conclusions The noninvasive Oxymap T1 retinal oximetry detects hypoxemia in central nervous system vessels in patients with severe COPD compared with healthy controls. The instrument is sensitive to changes in oxygen breathing but displays slightly lower measures than finger

  10. Gpr124 is essential for blood-brain barrier integrity in central nervous system disease.

    PubMed

    Chang, Junlei; Mancuso, Michael R; Maier, Carolina; Liang, Xibin; Yuki, Kanako; Yang, Lu; Kwong, Jeffrey W; Wang, Jing; Rao, Varsha; Vallon, Mario; Kosinski, Cynthia; Zhang, J J Haijing; Mah, Amanda T; Xu, Lijun; Li, Le; Gholamin, Sharareh; Reyes, Teresa F; Li, Rui; Kuhnert, Frank; Han, Xiaoyuan; Yuan, Jenny; Chiou, Shin-Heng; Brettman, Ari D; Daly, Lauren; Corney, David C; Cheshier, Samuel H; Shortliffe, Linda D; Wu, Xiwei; Snyder, Michael; Chan, Pak; Giffard, Rona G; Chang, Howard Y; Andreasson, Katrin; Kuo, Calvin J

    2017-04-01

    Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling. Constitutive activation of Wnt-β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.

  11. 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.

  12. Central nervous system vasculitis caused by propylthiouracil therapy: a case report and literature review.

    PubMed

    Vanek, C; Samuels, M H

    2005-01-01

    Antineutrophil cytoplasmic antibodies (ANCA) are associated with vasculitis, including vasculitis induced by drugs such as the thionamides. The affected organ systems in thionamide-induced vasculitis have been primarily renal, musculoskeletal, and dermatologic. We describe the first case of thionamide-induced central nervous system vasculitis presenting as confusion, with complete resolution after discontinuation of propylthiouracil. We review the literature and summarize 42 additional cases of thionamide-induced ANCA-positive vasculitis since 1992. Propylthiouracil was responsible in 93% of cases and the predominant ANCA pattern on immunofluorescent staining was perinuclear (p-ANCA). Clinical improvement occurred after drug discontinuation in 93%, steroid therapy was used in some cases. The mean duration of treatment with thionamides was 35 months prior to presentation. Long-term medical treatment with thionamides for hyperthyroidism may increase the risk of this severe side effect.

  13. 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

  14. Development and regulation of chloride homeostasis in the central nervous system.

    PubMed

    Watanabe, Miho; Fukuda, Atsuo

    2015-01-01

    γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter of the mature central nervous system (CNS). The developmental switch of GABAergic transmission from excitation to inhibition is induced by changes in Cl(-) gradients, which are generated by cation-Cl(-) co-transporters. An accumulation of Cl(-) by the Na(+)-K(+)-2Cl(-) co-transporter (NKCC1) increases the intracellular Cl(-) concentration ([Cl(-)]i) such that GABA depolarizes neuronal precursors and immature neurons. The subsequent ontogenetic switch, i.e., upregulation of the Cl(-)-extruder KCC2, which is a neuron-specific K(+)-Cl(-) co-transporter, with or without downregulation of NKCC1, results in low [Cl(-)]i levels and the hyperpolarizing action of GABA in mature neurons. Development of Cl(-) homeostasis depends on developmental changes in NKCC1 and KCC2 expression. Generally, developmental shifts (decreases) in [Cl(-)]i parallel the maturation of the nervous system, e.g., early in the spinal cord, hypothalamus and thalamus, followed by the limbic system, and last in the neocortex. There are several regulators of KCC2 and/or NKCC1 expression, including brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF), and cystic fibrosis transmembrane conductance regulator (CFTR). Therefore, regionally different expression of these regulators may also contribute to the regional developmental shifts of Cl(-) homeostasis. KCC2 and NKCC1 functions are also regulated by phosphorylation by enzymes such as PKC, Src-family tyrosine kinases, and WNK1-4 and their downstream effectors STE20/SPS1-related proline/alanine-rich kinase (SPAK)-oxidative stress responsive kinase-1 (OSR1). In addition, activation of these kinases is modulated by humoral factors such as estrogen and taurine. Because these transporters use the electrochemical driving force of Na(+) and K(+) ions, topographical interaction with the Na(+)-K(+) ATPase and its modulators such as creatine kinase (CK) should modulate

  15. Advanced diffusion MRI and biomarkers in the central nervous system: a new approach.

    PubMed

    Martín Noguerol, T; Martínez Barbero, J P

    The introduction of diffusion-weighted sequences has revolutionized the detection and characterization of central nervous system (CNS) disease. Nevertheless, the assessment of diffusion studies of the CNS is often limited to qualitative estimation. Moreover, the pathophysiological complexity of the different entities that affect the CNS cannot always be correctly explained through classical models. The development of new models for the analysis of diffusion sequences provides numerous parameters that enable a quantitative approach to both diagnosis and prognosis as well as to monitoring the response to treatment; these parameters can be considered potential biomarkers of health and disease. In this update, we review the physical bases underlying diffusion studies and diffusion tensor imaging, advanced models for their analysis (intravoxel coherent motion and kurtosis), and the biological significance of the parameters derived. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Space-brain: The negative effects of space exposure on the central nervous system.

    PubMed

    Jandial, Rahul; Hoshide, Reid; Waters, J Dawn; Limoli, Charles L

    2018-01-01

    Journey to Mars will be a large milestone for all humankind. Throughout history, we have learned lessons about the health dangers associated with exploratory voyages to expand our frontiers. Travelling through deep space, the final frontier, is planned for the 2030s by NASA. The lessons learned from the adverse health effects of space exposure have been encountered from previous, less-lengthy missions. Prolonged multiyear deep space travel to Mars could be encumbered by significant adverse health effects, which could critically affect the safety of the mission and its voyagers. In this review, we discuss the health effects of the central nervous system by space exposure. The negative effects from space radiation and microgravity have been detailed. Future aims and recommendations for the safety of the voyagers have been discussed. With proper planning and anticipation, the mission to Mars can be done safely and securely.

  17. Complex Homology and the Evolution of Nervous Systems

    PubMed Central

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

    2016-01-01

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

  18. Role of proteoglycans in neuro-inflammation and central nervous system fibrosis.

    PubMed

    Heindryckx, Femke; Li, Jin-Ping

    2018-01-31

    Fibrosis is defined as the thickening and scarring of connective tissue, usually as a consequence of tissue damage. The central nervous system (CNS) is special in the sense that fibrogenic cells are restricted to vascular and meningeal areas. Inflammation and the disruption of the blood-brain barrier can lead to the infiltration of fibroblasts and trigger fibrotic response. While the initial function of the fibrotic tissue is to restore the blood-brain barrier and to limit the site of injury, it also demolishes the structure of extracellular matrix and impedes the healing process by producing inhibitory molecules and forming a physical and biochemical barrier that prevents axon regeneration. As a major constituent in the extracellular matrix, proteoglycans participate in the neuro-inflammation, modulating the fibrotic process. In this review, we will discuss the pathophysiology of fibrosis during acute injuries of the CNS, as well as during chronic neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and age-related neurodegeneration with focus on the functional roles of proteoglycans. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  19. Unlocking the early fossil record of the arthropod central nervous system

    PubMed Central

    Edgecombe, Gregory D.; Ma, Xiaoya; Strausfeld, Nicholas J.

    2015-01-01

    Extant panarthropods (euarthropods, onychophorans and tardigrades) are hallmarked by stunning morphological and taxonomic diversity, but their central nervous systems (CNS) are relatively conserved. The timing of divergences of the ground pattern CNS organization of the major panarthropod clades has been poorly constrained because of a scarcity of data from their early fossil record. Although the CNS has been documented in three-dimensional detail in insects from Cenozoic ambers, it is widely assumed that these tissues are too prone to decay to withstand other styles of fossilization or geologically older preservation. However, Cambrian Burgess Shale-type compressions have emerged as sources of fossilized brains and nerve cords. CNS in these Cambrian fossils are preserved as carbon films or as iron oxides/hydroxides after pyrite in association with carbon. Experiments with carcasses compacted in fine-grained sediment depict preservation of neural tissue for a more prolonged temporal window than anticipated by decay experiments in other media. CNS and compound eye characters in exceptionally preserved Cambrian fossils predict divergences of the mandibulate and chelicerate ground patterns by Cambrian Stage 3 (ca 518 Ma), a dating that is compatible with molecular estimates for these splits. PMID:26554038

  20. Spinal primary central nervous system lymphoma: Case report and literature review.

    PubMed

    Feng, Li; Chen, Dingbang; Zhou, Hongyan; Shen, Cunzhou; Wang, Haiyan; Sun, Xunsha; Liang, Xiulin; Chen, Ling

    2018-04-01

    Primary central nervous system lymphoma (PCNSL) is a very rare tumor of increasing incidence. It is often misdiagnosed due to the unspecific presentation or unavailable biopsy, and results in poor prognosis. PCNSL involved the spinal cord is extremely sparse. Here we report a gentleman presented with one-year history of progressive tremor in the left limbs and slight dysarthria as well as three-month history of paraparesis, tinnitus and insomnia. MR images disclosed the swollen cerebellum and cauda equine, with contrast enhancement in both meninges and nerve roots. The cerebrospinal fluid (CSF) revealed extremely high protein level. Tubercular meningitis was considered and anti-tuberculosis therapy was given for weeks but without relief. With progressive deterioration, the PCNSL was eventually presumed according to positive CSF cytology and exclusion of systemic involvement. However, the patient passed away within days. We then reviewed the current diagnostic methods of PCNSL. The biopsy, as the gold standard for PCNSL diagnosis, is not eligible for all patients suspected PCNSL. The presurgical diagnostic algorithm of PCNSL has been fixed by clinicians and we suggest the early and repeated CSF cytology should be included for definitive diagnosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Central nervous system infection by Listeria monocytogenes in patients with systemic lupus erythematosus: analysis of 26 cases, including the report of a new case.

    PubMed

    Horta-Baas, Gabriel; Guerrero-Soto, Omar; Barile-Fabris, Leonor

    2013-01-01

    Infections in patients with systemic lupus erythematosus cause significant morbidity. Infection due to Listeria monocytogenes (LM) is considered an opportunistic disease, and has been published on rare occasions in patients with SLE. To review the presentation of listeria infections in the central nervous system (CNS) in SLE patients. We conducted a literature review, selecting cases with central nervous system infection and confirmation of LM infection through culture. Twenty six cases are described. The most common presentation was meningitis, with meningoencephalitis and brain abscesses being less frequent. The predisposing factors are: use of glucocorticoids, immunosuppressants, renal replacement therapy and the activity flares. CNS infection by listeria is rare and sometimes fatal. The atypical presentation may lead to a delay in diagnosis and appropriate treatment. L. monocytogenes should be included in the differential diagnosis of patients with SLE with neurological manifestations. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  2. 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

  3. Examination of West Nile Virus Neuroinvasion and Neuropathogenesis in the Central Nervous System of a Murine Model.

    PubMed

    Sultana, Hameeda

    2016-01-01

    West Nile virus (WNV) is a neurotropic virus that causes inflammation and neuronal loss in the Central Nervous System leading to encephalitis and death. In this chapter, detailed methods to detect WNV in the murine brain tissue by quantitative real-time polymerase chain reaction and viral plaque assays are described. Determination of WNV neuropathogenesis by Hematoxylin and Eosin staining and immunohistochemical procedures are provided. In addition, TUNEL assays to determine neuronal loss during WNV neuropathogenesis are discussed in detail. Collectively, the methods mentioned in this chapter provide an overview to understand neuroinvasion and neuropathogenesis in a murine model of WNV infection.

  4. Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

    PubMed Central

    Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja

    2016-01-01

    The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach. PMID:27164089

  5. Applications of human umbilical cord blood cells in central nervous system regeneration.

    PubMed

    Herranz, Antonio S; Gonzalo-Gobernado, Rafael; Reimers, Diana; Asensio, Maria J; Rodríguez-Serrano, Macarena; Bazán, Eulalia

    2010-03-01

    In recent decades, there has been considerable amount of information about embryonic stem cells (ES). The dilemma facing scientists interested in the development and use of human stem cells in replacement therapies is the source of these cells, i.e. the human embryo. There are many ethical and moral problems related to the use of these cells. Hematopoietic stem cells from umbilical cord blood have been proposed as an alternative source of embryonic stem cells. After exposure to different agents, these cells are able to express antigens of diverse cellular lineages, including the neural type. The In vitro manipulation of human umbilical cord blood (hUCB) cells has shown their stem capacity and plasticity. These cells are easily accessible, In vitro amplifiable, well tolerated by the host, and with more primitive molecular characteristics that give them great flexibility. Overall, these properties open a promising future for the use of hUCB in regenerative therapies for the Central Nervous System (CNS). This review will focus on the available literature concerning umbilical cord blood cells as a therapeutic tool for the treatment of neurodegenerative diseases.

  6. Clinical effects of air pollution on the central nervous system; a review.

    PubMed

    Babadjouni, Robin M; Hodis, Drew M; Radwanski, Ryan; Durazo, Ramon; Patel, Arati; Liu, Qinghai; Mack, William J

    2017-09-01

    The purpose of this review is to describe recent clinical and epidemiological studies examining the adverse effects of urban air pollution on the central nervous system (CNS). Air pollution and particulate matter (PM) are associated with neuroinflammation and reactive oxygen species (ROS). These processes affect multiple CNS pathways. The conceptual framework of this review focuses on adverse effects of air pollution with respect to neurocognition, white matter disease, stroke, and carotid artery disease. Both children and older individuals exposed to air pollution exhibit signs of cognitive dysfunction. However, evidence on middle-aged cohorts is lacking. White matter injury secondary to air pollution exposure is a putative mechanism for neurocognitive decline. Air pollution is associated with exacerbations of neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. Increases in stroke incidences and mortalities are seen in the setting of air pollution exposure and CNS pathology is robust. Large populations living in highly polluted environments are at risk. This review aims to outline current knowledge of air pollution exposure effects on neurological health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. A large, nationwide, longitudinal study of central nervous system diseases among Korean workers exposed to manganese.

    PubMed

    Yoon, Jin-Ha; Ahn, Yeon-Soon

    2015-03-01

    In occupational epidemiologic studies, the low incidence and chronic process of central nervous system (CNS) diseases has complicated the determination of the relationship between increased morbidity and manganese (Mn) exposure. Therefore, through this large cohort study, we evaluated CNS disease morbidity among Korean workers exposed to Mn Data were collected from Mn-associated specialized medical check-up 2000 and 2004 in Korea. The number of workers admitted to hospital because of clinically diagnosed CNS disease was analyzed in male workers exposed to Mn (n = 104,544). As a control reference population, 2% of Korean men were randomly selected and their hospital admission data were analyzed. For Mn-exposed workers, Standardized admission ratios (SARs) for CNS disease, as determined by ICD-10 classifications, were estimated in reference to the control population During follow up, 64 workers admitted because of CNS diseases. Chronic exposure to Mn (≥ 10 years) was significantly associated with the SAR (95% CI) of extrapyramidal and movement disorders (SAR: 2.03, 95% CI: 1.05-3.55), in particular, other extrapyramidal and movement disorders (SAR: 4.81, 95% CI: 1.29-12.32). Also borderline association (SAR = 4.88, 90% CI: 1.05-7.04) was noted for secondary Parkinsonism among workers with chronic Mn exposure. SARs (95% CI) for other degenerative nervous system diseases were significantly higher in Mn-exposed workers compared with the control population (SAR: 3.60, 95% CI: 1.16-8.40) CONCLUSION: In conclusion, Mn-exposed workers exhibited significantly elevated SARs for degenerative nervous system diseases and extrapyramidal and movement disorders, compared to the age-matched reference population, suggesting a relatedness with Mn exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. 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.

  9. Bile Acid Signaling Pathways from the Enterohepatic Circulation to the Central Nervous System

    PubMed Central

    Mertens, Kim L.; Kalsbeek, Andries; Soeters, Maarten R.; Eggink, Hannah M.

    2017-01-01

    Bile acids are best known as detergents involved in the digestion of lipids. In addition, new data in the last decade have shown that bile acids also function as gut hormones capable of influencing metabolic processes via receptors such as FXR (farnesoid X receptor) and TGR5 (Takeda G protein-coupled receptor 5). These effects of bile acids are not restricted to the gastrointestinal tract, but can affect different tissues throughout the organism. It is still unclear whether these effects also involve signaling of bile acids to the central nervous system (CNS). Bile acid signaling to the CNS encompasses both direct and indirect pathways. Bile acids can act directly in the brain via central FXR and TGR5 signaling. In addition, there are two indirect pathways that involve intermediate agents released upon interaction with bile acids receptors in the gut. Activation of intestinal FXR and TGR5 receptors can result in the release of fibroblast growth factor 19 (FGF19) and glucagon-like peptide 1 (GLP-1), both capable of signaling to the CNS. We conclude that when plasma bile acids levels are high all three pathways may contribute in signal transmission to the CNS. However, under normal physiological circumstances, the indirect pathway involving GLP-1 may evoke the most substantial effect in the brain. PMID:29163019

  10. Long-term survivors of primary central nervous system lymphoma.

    PubMed

    Yamanaka, Ryuya; Morii, Ken; Sano, Masakazu; Homma, Jumpei; Yajima, Naoki; Tsukamoto, Yoshihiro; Ogura, Ryouske; Natsumeda, Manabu; Aoki, Hiroshi; Akiyama, Katsuhiko; Saitoh, Takafumi; Hondoh, Hiroaki; Kawaguchi, Atsushi; Takahashi, Hitoshi; Fujii, Yukihiko

    2017-02-23

    In this study, we provide long-term outcome data of patients with primary central nervous system lymphoma. The long-term outcomes of PCNSL patients diagnosed between 1982 and 2006 were reviewed. Neurological late neurotoxicity symptoms, neuroradiological brain atrophy and leukoencephalopathy were evaluated. Surviving patients completed the Quality of Life Questionnaire-30 and Brain Cancer Module-20. The differences in overall survival were assessed using the Kaplan-Meier method and log-rank test. The differences between groups in terms of each investigated parameter were analyzed using the Wilcoxon signed-rank test. Among 112 PCNSL patients, there were 33 (29.4%) long-term (> 5 years) survivors. The median survival of all long-term survivors was 105.7 months; of these, 8 (7.1%) were alive at the latest follow-up, with a mean survival time of 170.2 months (range, 121.8–286.4). Clinical assessment revealed severe neurotoxicity in 14 patients (42.4%), moderate neurotoxicity in 5 (15.1%), and normal status in 14 (42.4%). Correlations were seen between the neuroradiological imaging score changes and neurocognitive condition (P=0.0001), neurocognitive condition and the whole brain irradiation dose (P=0.0004), and atrophy and the whole brain irradiation dose (P=0.0035). A more severe clinical condition was found to be associated with increasing age and whole brain irradiation dose in long-term survivors with PCNSL. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  11. Central nervous system activity of Illicium verum fruit extracts.

    PubMed

    Chouksey, Divya; Upmanyu, Neeraj; Pawar, R S

    2013-11-01

    To research the acute toxicity of Illicium verum (I. verum) fruit extracts and its action on central nervous system. The TLC and HPTLC techniques were used as fingerprints to determine the chemical components present in I. verum. Male albino rats and mice were utilized for study. The powdered material was successively extracted with n-hexane, ethyl acetate and methanol using a Soxhlet extractor. Acute toxicity studies were performed as per OECD guidelines. The CNS activity was evaluated on parameters of general behavior, sleeping pattern, locomotor activity, anxiety and myocoordination activity. The animals were trained for seven days prior to experiments and the divided into five groups with six animals in each. The drug was administered by intraperitoneal route according to body weight. The dosing was done as prescribed in each protocol. Toxicity studies reported 2 000 mg/kg as toxicological dose and 1/10 of the same dose was taken as therapeutic dose Intraperitoneal injection of all extracts at dose of 200 mg prolonged phenobarbitone induced sleeping time, produced alteration in general behavior pattern, reduced locomotor activity and produced anxiolytic effects but the extracts do not significantly alter muscles coordination activity. The three extracts of I. verum at the dose of 200 mg, methanol extract was found to produce more prominent effects, then hexane and ethylacetate extracts. The observation suggested that the extracts of I. verum possess potent CNS depressant action and anxiolytic effect without interfering with motor coordination. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  12. Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia

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

    Walker, Gary V.; Shihadeh, Ferial; Kantarjian, Hagop

    Purpose: To determine the benefit of radiation therapy (RT) in resolution of neurologic symptoms and deficits and whether the type of RT fields influences central nervous system (CNS) control in adults with CNS leukemia. Methods and Materials: A total of 163 adults from 1996 to 2012 were retrospectively analyzed. Potential associations between use of radiation and outcome were investigated by univariate and multivariate analysis. Results: The median survival time was 3.8 months after RT. Common presenting symptoms were headache in 79 patients (49%), cranial nerve VII deficit in 46 (28%), and cranial nerve II deficit in 44 (27%). RT was deliveredmore » to the base of skull in 48 patients (29%), to the whole brain (WB) in 67 (41%), and to the craniospinal axis (CS) in 48 (29%). Among 149 patients with a total of 233 deficits, resolution was observed in 34 deficits (15%), improvement in 126 deficits (54%), stability in 34 deficits (15%), and progression in 39 deficits (17%). The 12-month CNS progression-free survival was 77% among those receiving CS/WB and 51% among those receiving base of skull RT (P=.02). On multivariate analysis, patients who did not undergo stem cell transplantation after RT and base of skull RT were associated with worse CNS progression-free survival. Conclusions: Improvement or resolution of symptoms occurred in two thirds of deficits after RT. Comprehensive radiation to the WB or CS seems to offer a better outcome, especially in isolated CNS involvement.« less

  13. Diagnosis and management of primary central nervous system lymphoma.

    PubMed

    Han, Catherine H; Batchelor, Tracy T

    2017-11-15

    Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma (NHL) that is confined to the brain, eyes, spinal cord, or leptomeninges without systemic involvement. The overall prognosis, diagnosis, and management of PCNSL differ from those for other types of NHL. Prompt diagnosis and initiation of treatment are vital for improving clinical outcomes. PCNSL is responsive to radiation therapy; however, whole-brain radiotherapy (WBRT) inadequately controls the disease when it is used alone, and its delayed neurotoxicity causes neurocognitive impairment, especially in elderly patients. High-dose methotrexate (HD-MTX)-based induction chemotherapy with or without autologous stem cell transplantation (ASCT) or reduced-dose WBRT leads to durable disease control and less neurotoxicity. The optimal treatment has yet to be defined; however, HD-MTX-based induction chemotherapy is considered standard for newly diagnosed PCNSL. Ongoing randomized trials are addressing the roles of rituximab and consolidative treatment with ASCT or reduced-dose WBRT. Despite high tumor response rates with the initial treatment, many patients relapse with a very poor prognosis. The optimal treatment for refractory or relapsed PCNSL is poorly defined. The choice of salvage treatment depends on a patient's age, previous treatment and response, performance status, and comorbidities at the time of relapse. This review provides an overview of the clinical features, diagnosis, pathology, and management of PCNSL in immunocompetent patients, and it focuses on recent advances in treatment. Cancer 2017;123:4314-24. © 2017 American Cancer Society. © 2017 American Cancer Society.

  14. Complex Homology and the Evolution of Nervous Systems.

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. Death receptor Fas (CD95) signaling in the central nervous system: tuning neuroplasticity?

    PubMed

    Reich, Arno; Spering, Christopher; Schulz, Jörg B

    2008-09-01

    For over a decade, neuroscientific research has focused on processes of apoptosis and its contribution to the pathophysiology of neurological diseases. In the central nervous system, the degree of intrinsic mitochondrial-mediated apoptotic signaling expresses a cell's individual metabolic stress, whereas activation of the extrinsic death receptor-induced cascade is regarded as a sign of imbalanced cellular networks. Under physiological conditions, most neurons possess death receptors without being sensitive to receptor-mediated apoptosis. This paradox raises two questions: what is the evolutionary advantage of expressing potentially harmful proteins? How is their signaling controlled? This review summarizes the functional relevance of FasL-Fas signaling--a quintessential death ligand/receptor system--in different neurological disease models ranging from traumatic, inflammatory and ischemic to neurodegenerative processes. Furthermore, it outlines alternative non-apoptotic Fas signaling, shedding new light on its neuroplastic capacity. Finally, receptor-proximal regulatory proteins are introduced and identified as potential protagonists of disease-modifying neurological therapies.

  17. Increased presence of T lymphocytes in central nervous system of EPM affected horses.

    PubMed

    Scott, Patricia; Witonsky, Sharon; Robertson, John; Daft, Barbara

    2005-12-01

    Equine protozoal myeloencephalitis (EPM), caused by Sarcocystis neurona infection in the central nervous system (CNS), affects up to 1% of all horses during their lifetimes. Neither the protective immune response nor the immunopathology associated with the disease is well understood. To begin to clarify the pathogenesis of the disease, immunohistochemical staining for B and T lymphocytes was performed on spinal cord sections obtained from 17 horses, all of which were all positive for S. neurona based on immunohistochemical staining. Fifteen of the 17 horses included in the study were killed due to neurologic dysfunction; 2 of the 17 horses were killed because of fractures. All 17 horses had histologic changes consistent with S. neurona infection. A significantly greater number of T cells were seen in sections from S. neurona-infected versus control horses. Because this was a small descriptive study, we were not able to determine the mechanisms of enhanced T-cell recruitment in the sections from the S. neurona-infected horses.

  18. Administration of secretin for autism alters dopamine metabolism in the central nervous system.

    PubMed

    Toda, Yoshihiro; Mori, Kenji; Hashimoto, Toshiaki; Miyazaki, Masahito; Nozaki, Satoshi; Watanabe, Yasuyoshi; Kuroda, Yasuhiro; Kagami, Shoji

    2006-03-01

    We evaluated the clinical effects of intravenously administered secretin in 12 children with autism (age range: 4-6 years, median age: 9 years, boy:girl=8:4). In addition, we investigated the association between improvement in symptoms and changes in the cerebrospinal fluid (CSF) homovanillic acid (HVA),5-hydroxyindole-3-acetic acid (5-HIAA), and 6R-5,6,7,8-tetrahydro-L-biopterin (BH(4)) levels after administration. After administration of secretin, the Autism Diagnostic Interview-Revised (ADI-R) score improved in 7 of the 12 children. However, the score deteriorated in 2 of the 12 children (in the item of 'restricted and repetitive, stereotyped interests and behaviors'). The HVA and BH(4) levels in CSF were increased in all children with improvement in the ADI-R score. In contrast, no patient without the elevation of the BH(4) level showed improvement in the score. These findings suggest that secretin activated metabolic turnover of dopamine in the central nervous system via BH(4), improving symptoms.

  19. The Influence of Nicotinamide on Health and Disease in the Central Nervous System

    PubMed Central

    Fricker, Rosemary A; Green, Emma L; Jenkins, Stuart I; Griffin, Síle M

    2018-01-01

    Nicotinamide, the amide form of vitamin B3 (niacin), has long been associated with neuronal development, survival, and function in the central nervous system (CNS), being implicated in both neuronal death and neuroprotection. Here, we summarise a body of research investigating the role of nicotinamide in neuronal health within the CNS, with a focus on studies that have shown a neuroprotective effect. Nicotinamide appears to play a role in protecting neurons from traumatic injury, ischaemia, and stroke, as well as being implicated in 3 key neurodegenerative conditions: Alzheimer’s, Parkinson’s, and Huntington’s diseases. A key factor is the bioavailability of nicotinamide, with low concentrations leading to neurological deficits and dementia and high levels potentially causing neurotoxicity. Finally, nicotinamide’s potential mechanisms of action are discussed, including the general maintenance of cellular energy levels and the more specific inhibition of molecules such as the nicotinamide adenine dinucleotide-dependent deacetylase, sirtuin 1 (SIRT1). PMID:29844677

  20. Central nervous system activity of the ethanol leaf extract of Sida acuta in rats.

    PubMed

    Ibironke, G F; Umukoro, A S; Ajonijebu, D C

    2014-03-01

    The study investigated the pharmacological effects of ethanol extract of Sida acuta leaves on central nervous system activities in mice. Adult male mice (18 - 25g) were used for the study. The extract was administered orally in male mice and evaluated in the following tests: forced swimming, tail suspension, formalin-induced paw licking, acetic acid--induced mouse writhing and apomorphine-induced stereotypy. The results revealed a reduction in the frequency of abdominal constrictions induced by acetic acid, decreased licking times in both phases of the formalin test, reduction in immobility times in forced swimming and tail suspension tests. However, the extract produced no effect on apomorphine-induced stereotyped behaviour. These results suggest that the ethanol extract of Sida acuta contains psychoactive substances with analgesic and antidepressant-like properties which may be beneficial in the management of pain.