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Sample records for nervous system effects

  1. Environmental effects on the central nervous system.

    PubMed Central

    Paulson, G W

    1977-01-01

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

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

    PubMed

    Osipov, Alexey; Utkin, Yuri

    2012-12-01

    The nervous system is a primary target for animal venoms as the impairment of its function results in the fast and efficient immobilization or death of a prey. There are numerous evidences about effects of crude snake venoms or isolated toxins on peripheral nervous system. However, the data on their interactions with the central nervous system (CNS) are not abundant, as the blood-brain barrier (BBB) impedes penetration of these compounds into brain. This updated review presents the data about interaction of snake venom polypeptides with CNS. Such data will be described according to three main modes of interactions: - Direct in vivo interaction of CNS with venom polypeptides either capable to penetrate BBB or injected into the brain. - In vitro interactions of cell or sub-cellular fractions of CNS with crude venoms or purified toxins. - Indirect effects of snake venoms or their components on functioning of CNS under different conditions. Although the venom components penetrating BBB are not numerous, they seem to be the most suitable candidates for the leads in drug design. The compounds with other modes of action are more abundant and better studied, but the lack of the data about their ability to penetrate BBB may substantially aggravate the potentials for their medical perspectives. Nevertheless, many such compounds are used for research of CNS in vitro. These investigations may give invaluable information for understanding the molecular basis of CNS diseases and thus lay the basis for targeted drug design. This aspect also will be outlined in the review. PMID:23270323

  3. Autonomic Nervous System Disorders

    MedlinePlus

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

  4. Autonomic Nervous System Disorders

    MedlinePlus

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

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

    PubMed Central

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

    2012-01-01

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

  6. 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.

  7. Clinical implications of thyroid hormones effects on nervous system development.

    PubMed

    Carreón-Rodríguez, Alfonso; Pérez-Martínez, Leonor

    2012-03-01

    Thyroid hormones have an important role throughout prenatal and postnatal nervous system development. They are involved in several processes such as neurogenesis, gliogenesis, myelination, synaptogenesis, etc., as shown in many cases of deficiency like congenital hypothyroidism or hypothyroxinemia. Those pathologies if untreated could lead to severe damages in cognitive, motor, neudoendocrine functions among other effects. Some could be reversed after adequate supplementation of thyroid hormones at birth, however there are other cellular processes highly sensitive to low levels of thyroid hormones and lasting a limited period of time during which if thyroid hormone action is lacking or deficient, the functional and structural damages would produce permanent defects. PMID:22523832

  8. The effect of octopamine on the locust stomatogastric nervous system.

    PubMed

    Rand, David; Knebel, Daniel; Ayali, Amir

    2012-01-01

    Octopamine (OA) is a prominent neuromodulator of invertebrate nervous systems, influencing multiple physiological processes. Among its many roles in insects are the initiation and maintenance of various rhythmic behaviors. Here, the neuromodulatory effects of OA on the components of the locust stomatogastric nervous system were studied, and one putative source of OA modulation of the system was identified. Bath application of OA was found to abolish the endogenous rhythmic output of the fully isolated frontal ganglion (FG), while stimulating motor activity of the fully isolated hypocerebral ganglion (HG). OA also induced rhythmic movements in a foregut preparation with intact HG innervation. Complex dose-dependent effects of OA on interconnected FG-HG preparations were seen: 10(-5) M OA accelerated the rhythmic activity of both the HG and FG in a synchronized manner, while 10(-4) M OA decreased both rhythms. Intracellular stimulation of an identified octopaminergic dorsal unpaired median neuron in the subesophageal ganglion was found to exert a similar effect on the FG motor output as that of OA application. Our findings suggest a mechanism of regulation of insect gut patterns and feeding-related behavior during stress and times of high energy demand. PMID:22934040

  9. The effect of space radiation of the nervous system

    NASA Astrophysics Data System (ADS)

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

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

  10. 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.

  11. Protective effects and mechanisms of sirtuins in the nervous system

    PubMed Central

    Zhang, Feng; Wang, Suping; Gan, Li; Vosler, Peter S.; Gao, Yanqin; Chen, Jun

    2011-01-01

    Silent information regulator two proteins (sirtuins or SIRTs) are a group of histone deacetylases whose activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD+). They suppress genome-wide transcription, yet upregulate a select set of proteins related to energy metabolism and pro-survival mechanisms, and therefore play a key role in the longevity effects elicited by calorie restriction. Recently, a neuroprotective effect of sirtuins has been reported for both acute and chronic neurological diseases. The focus of this review is to summarize the latest progress regarding the protective effects of sirtuins, with a focus on SIRT1. We first introduce the distribution of sirtuins in the brain and how their expression and activity are regulated. We then highlight their protective effects against common neurological disorders, such as cerebral ischemia, axonal injury, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. Finally, we analyze the mechanisms underlying sirtuin-mediated neuroprotection, centering on their non-histone substrates such as DNA repair enzymes, protein kinases, transcription factors, and coactivators. Collectively, the information compiled here will serve as a comprehensive reference for the actions of sirtuins in the nervous system to date, and will hopefully help to design further experimental research and expand sirtuins as therapeutic targets in the future. PMID:21930182

  12. Effects of radiation on development, especially of the nervous system

    SciTech Connect

    Hicks, S.P.; D'Amato, C.J.

    1980-12-01

    Humans and other organisms are exposed to ionizing radiations from a variety of natural and man-made sources. Radiation may cause mutations and chromosome abnormalities, cell-killing, alterations and transformations in cell growth, and carcinogenetic changes. This paper considers principally the cell-killing and nonlethal cell alterations in developing laboratory mammals and humans, especially the nervous system, that follow irradiation and often lead to malformation and disturbed function, but at certain stages to restitution of the injury. Most of what researchers know about the mechanisms of these radiation effects in man is derived from animal experiments, especially with rats. The few observations in humans have corresponded closely to them. Researchers illustrate the cellular effects and malformative results with an example of cell-killing in the developing cortex of a human fetus exposed to therapeutic radiation in utero; a current timetable of the malformative and other effects of radiation on rats during development from which expectations of human effects might be extrapolated; examples of hydrocephalus produced in rats; low-dose alterations of nerve cells in rats; and a microcephalic Japanese boy exposed in utero to the atomic bomb at Hiroshima in 1945.

  13. The Nervous System Game

    ERIC Educational Resources Information Center

    Corbitt, Cynthia; Carpenter, Molly

    2006-01-01

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

  14. Effects of hyperthermia on the peripheral nervous system: a review.

    PubMed

    Haveman, J; Van Der Zee, J; Wondergem, J; Hoogeveen, J F; Hulshof, M C C M

    2004-06-01

    The present paper overviews the current knowledge about effects of hyperthermia at temperatures used in clinical oncology on the peripheral nervous system. From the experimental studies it may be concluded that the heat sensitivity of the nerve is determined by the sensitivity of the nerve vasculature. These studies show that in order to avoid induction of severe neuropathy, application of heat to the peripheral nerves should not be in excess of doses of 30 min at 44 degrees C or equivalent. Using modern equipment for application of loco-regional hyperthermia the incidence of even mild neurological complications is very low. In hyperthermic isolated limb perfusion (HILP) neurotoxicity is an often-mentioned side effect, this is in spite of the fact that in all studies a relatively mild hyperthermic temperature is used that, based on the experimental studies, should be well tolerated by the nerves and other normal tissues in the limbs. It seems that the neurotoxicity observed after HILP results from thermal enhancement of drug toxicity, very probably combined with effects of a high tourniquet pressure that is used to isolate the blood flow in the leg. Whole body hyperthermia (WBH), using anesthesia and appropriate monitoring to avoid cardiovascular stress is at present considered a safe procedure. Still in the recent past cases of neuropathy after treatment have been described. When chemotherapy, and notably cisplatin, is administered before or during hyperthermia there are several clinical and experimental observations that indicate a limited tolerance of the peripheral nervous tissue in such case. Also previous radiotherapy may limit the tolerance of nerves to hyperthermia, notably when radiation is applied with a large field size. Experimental studies show that combined treatment with radiation and heat leads to enhancement of effects of radiation (enhancement ratio approximately 1.5 at 60 min at 44 degrees C). A clear contraindication for the application of

  15. Central Nervous System Effects of Ginkgo Biloba, a Plant Extract.

    PubMed

    Itil, Turan M.; Eralp, Emin; Tsambis, Elias; Itil, Kurt Z.; Stein, Ulrich

    1996-01-01

    Extracts of Ginkgo biloba (EGb) are among the most prescribed drugs in France and Germany. EGb is claimed to be effective in peripheral arterial disorders and in "cerebral insufficiency." The mechanism of action is not yet well understood. Three of the ingredients of the extract have been isolated and found to be pharmacologically active, but which one alone or in combination is responsible for clinical effects is unknown. The recommended daily dose (3 x 40 mg extract) is based more on empirical data than on clinical dose-findings studies. However, despite these, according to double-blind, placebo-controlled clinical trials, EGb has therapeutic effects, at least, on the diagnostic entity of "cerebral insufficiency," which is used in Europe as synonymous with early dementia. To determine whether EGb has significant pharmacological effects on the human brain, a pharmacodynamic study was conducted using the Quantitative Pharmacoelectroencephalogram (QPEEG(R)) method. It was established that the pharmacological effects (based on a predetermined 7.5--13.0-Hz alpha frequency band in a computer-analyzed electroencephalogram = CEEG(R)) of EGb on the central nervous system (CNS) are significantly different than placebo, and the high and low doses could be discriminated from each other. The 120-mg, but particularly the 240-mg, single doses showed the most consistent CNS effects with an earlier onset (1 h) and longer duration (7 h). Furthermore, it was established that the electrophysiological effects of EGb in CNS are similar to those of well-known cognitive activators such as "nootropics" as well as tacrine, the only marketed "antidementia" drug currently available in the United States. PMID:11856998

  16. Alcoholism and its effects on the central nervous system.

    PubMed

    Mukherjee, Sukhes

    2013-08-01

    Alcohol abuse is a major health problem worldwide, resulting to extensive admissions in many general hospitals. The overall economic cost of alcohol abuse is enormous worldwide. As a small molecule, alcohol can easily cross membrane barriers and reach different parts of the body very quickly. Attainment of its equilibrium concentration in different cellular compartments depends on the respective water content. Alcohol can affect several parts of the brain, but, in general, contracts brain tissues, destroys brain cells, as well as depresses the central nervous system. Excessive drinking over a prolonged period of time can cause serious problems with cognition and memory. Alcohol interacts with the brain receptors, interfering with the communication between nerve cells, and suppressing excitatory nerve pathway activity. Neuro-cognitive deficits, neuronal injury, and neurodegeneration are well documented in alcoholics, yet the underlying mechanisms remain elusive. The effect can be both direct and/ or indirect. In this review we highlighted the role of alcoholism on the CNS and its impact on human health. PMID:23713737

  17. Central nervous system effects of whole-body proton irradiation.

    PubMed

    Sweet, Tara Beth; Panda, Nirlipta; Hein, Amy M; Das, Shoshana L; Hurley, Sean D; Olschowka, John A; Williams, Jacqueline P; O'Banion, M Kerry

    2014-07-01

    Space missions beyond the protection of Earth's magnetosphere expose astronauts to an environment that contains ionizing proton radiation. The hazards that proton radiation pose to normal tissues, such as the central nervous system (CNS), are not fully understood, although it has been shown that proton radiation affects the neurogenic environment, killing neural precursors and altering behavior. To determine the time and dose-response characteristics of the CNS to whole-body proton irradiation, C57BL/6J mice were exposed to 1 GeV/n proton radiation at doses of 0-200 cGy and behavioral, physiological and immunohistochemical end points were analyzed over a range of time points (48 h-12 months) postirradiation. These experiments revealed that proton radiation exposure leads to: 1. an acute decrease in cell division within the dentate gyrus of the hippocampus, with significant differences detected at doses as low as 10 cGy; 2. a persistent effect on proliferation in the subgranular zone, at 1 month postirradiation; 3. a decrease in neurogenesis at doses as low as 50 cGy, at 3 months postirradiation; and 4. a decrease in hippocampal ICAM-1 immunoreactivity at doses as low as 10 cGy, at 1 month postirradiation. The data presented contribute to our understanding of biological responses to whole-body proton radiation and may help reduce uncertainty in the assessment of health risks to astronauts. These findings may also be relevant to clinical proton beam therapy. PMID:24937778

  18. The pleiotropic effects of erythropoietin in the central nervous system.

    PubMed

    Buemi, M; Cavallaro, E; Floccari, F; Sturiale, A; Aloisi, C; Trimarchi, M; Corica, F; Frisina, N

    2003-03-01

    Erythropoietin (Epo) is a hydrophobic sialoglycoproteic hormone produced by the kidney and responsible for the proliferation, maturation, and differentiation of the precursors of the erythroid cell line. Human recombinant erythropoietin (rHuEpo) is used to treat different types of anemia, not only in uremic patients but also in newborns with anemia of prematurity, in patients with cancer-related anemia or myeloproliferative disease, thalassemias, bone marrow transplants, or those with chronic infectious diseases. The pleiotropic functions of Epo are well known. It has been shown that this hormone can modulate the inflammatory and immune response, has direct hemodynamic and vasoactive effects, could be considered a proangiogenic factor because of its interaction with vascular endothelial growth factor, and its ability to stimulate mitosis and motility of endothelial cells. The multifunctional role of Epo has further been confirmed by the discovery in the central nervous system of a specific Epo/Epo receptor (EpoR) system. Both Epo and EpoR are expressed by astrocytes and neurons and Epo is present in the cerebrospinal fluid (CSF). Therefore, novel functions of Epo, tissue-specific regulation, and the mechanisms of action have been investigated. In this review we have tried to summarize the current data on the role of Epo on brain function. We discuss the different sites of cerebral expression and mechanisms of regulation of Epo and its receptor and its role in the development and maturation of the brain. Second, we discuss the neurotrophic and neuroprotective function of Epo in different conditions of neuronal damage, such as hypoxia, cerebral ischemia, and subarachnoid hemorrhage, and the consequent possibility that rHuEpo therapy could soon be used in clinical practice to limit neuronal damage induced by these diseases. PMID:12638727

  19. The effects of Aconitum alkaloids on the central nervous system.

    PubMed

    Ameri, A

    1998-10-01

    Preparations of Aconitum roots are employed in Chinese and Japanese medicine for analgesic, antirheumatic and neurological indications. The recent surge in use of phytomedicine derived from traditional Chinese medicine as well as increasing concerns about possible toxic effects of these compounds have inspired a great deal of research into the mechanisms by which certain Aconitum alkaloids may act on the central nervous system. The pharmacological effects of preparations of Aconitum roots are attributed to several diterpenoid alkaloids. The main alkaloid of these plants is aconitine, a highly toxic diterpenoid alkaloid which is known to suppress the inactivation of voltage-dependent Na+ channels by binding to neurotoxin binding site 2 of the alpha-subunit of the channel protein. In this article the pharmacology of several structurally related Aconitum alkaloids is highlighted and their therapeutic vs toxic potential is discussed. Neurochemical and neurophysiological studies will be reviewed with emphasis on the effects of the alkaloids in regions of the brain that have been implicated in pain transmission and generation of epileptic activity. Considering the chemical structure of the Aconitum alkaloids as well as their mechanism of action, a subdivision in three groups becomes obvious: the first group comprises such alkaloids which possess high toxicity due to two ester boundings at the diterpene skeleton. The members of this group activate voltage-dependent sodium channels already at resting potential and inhibit noradrenaline reuptake. Activation of sodium channels and in consequence excessive depolarization with final inexcitability and suppression of pain transmission account for their antinociceptive properties. The second group comprises less toxic monoesters which have been shown to possess strong antinociceptive, antiarrhythmic and antiepileptiform properties due to a blockade of the voltage-dependent sodium channel. Electrophysiological studies have

  20. Effects of lymphoma on the peripheral nervous system.

    PubMed Central

    Hughes, R A; Britton, T; Richards, M

    1994-01-01

    Peripheral nervous system abnormalities occur in 5% of patients with lymphoma and have a wide differential diagnosis. Herpes zoster is the commonest cause. Vinca alkaloids are the only drugs used in lymphoma which commonly cause neuropathy. Compression or infiltration of nerve roots by lymphoma is a rare presenting feature but becomes more common with advanced disease. Radiation plexopathy does not usually develop until at least 6 months after irradiation and can be difficult to distinguish from neoplastic infiltration. Either multifocal infiltration of nerves or lymphoma-associated vasculitis may present as a peripheral neuropathy. The incidence of Guillain-Barré (GBS) syndrome, and possibly chronic idiopathic demyelinating polyradiculoneuropathy, appears to be increased in association with lymphoma, especially Hodgkin's disease. Subacute sensory neuronopathy and subacute lower motor neuronopathy have both been reported as paraneoplastic syndromes associated with Hodgkin's disease. Treatment of the underlying lymphoma is only rarely followed by recovery of the associated neuropathy. PMID:7932460

  1. Nervous System Lyme Disease.

    PubMed

    Halperin, John J

    2015-12-01

    Nervous system involvement occurs in 10% to 15% of patients infected with the tick-borne spirochetes Borrelia burgdorferi, B afzelii, and B garinii. Peripheral nervous system involvement is common. Central nervous system (CNS) involvement, most commonly presenting with lymphocytic meningitis, causes modest cerebrospinal fluid (CSF) pleocytosis. Parenchymal CNS infection is rare. If the CNS is invaded, however, measuring local production of anti-B burgdorferi antibodies in the CSF provides a useful marker of infection. Most cases of neuroborreliosis can be cured with oral doxycycline; parenteral regimens should be reserved for patients with particularly severe disease. PMID:26593257

  2. Central nervous system effects in acute thallium poisoning.

    PubMed

    Tsai, Yu-Tai; Huang, Chin-Chang; Kuo, Hung-Chou; Wang, Hsuan-Min; Shen, Wu-Shiun; Shih, Tung-Sheng; Chu, Nai-Shin

    2006-03-01

    We report the central nervous system manifestations, neuropsychological studies and brain magnetic resonance image (MRI) findings of two patients with acute thallium intoxication. Neurologically the patients suffered from confusion, disorientation, and hallucination in the acute stage, followed by anxiety, depression, lack of attention, and memory impairment, in addition to peripheral neuropathy. Neuropsychological tests revealed an impairment of memory function, including reversed digital span, memory registration, memory recall, memory recognition, similarity, proverb reasoning, and verbal fluency. High concentrations of thallium were found in the urine, blood, and drinking water of these two patients. Brain MRI showed lesions in the corpus striatum in one patient. During the follow-up periods, the clinical manifestations and neuropsychological studies showed a slowly progressive improvement, and a follow-up brain MRI 1.5 months later demonstrated a resolution of the lesions. We conclude that thallium intoxication might induce encephalopathy, and brain MRI studies demonstrated the acute-stage brain lesions in a severe intoxicated patient. In addition, neuropsychological tests also confirmed memory deficits, although the brain lesions in the corpus striatum might resolve. PMID:16337004

  3. The toxic effects of formaldehyde on the nervous system.

    PubMed

    Songur, Ahmet; Ozen, Oguz Aslan; Sarsilmaz, Mustafa

    2010-01-01

    Formaldehyde (FA) is found in the polluted atmosphere of cities, domestic air (e.g., paint, insulating materials, chipboard and plywood, fabrics, furniture, paper), and cigarette smoke, etc.; therefore, everyone and particularly susceptible children may be exposed to FA. FA is also widely used in industrial and medical settings and as a sterilizing agent, disinfectant, and preservative. Therefore, employees may be highly exposed to it in there settings. Of particular concern to the authors are anatomists and medical students, who can be highly exposed to formaldehyde vapor during dissection sessions. Formaldehyde is toxic over a range of doses; chances of exposure and subsequent harmful effects are increased as (room) temperature increases, because of FA's volatility. Many studies have been conducted to evaluate the effects of FA during systemic and respiratory exposures in rats. This review compiles that literature and emphasizes the neurotoxic effects of FA on neuronal morphology, behavior, and biochemical parameters. The review includes the results of some of the authors' work related to FA neurotoxicity, and such neurotoxic effects from FA exposure were experimentally demonstrated. Moreover, the effectiveness of some antioxidants such as melatonin, fish omega-3, and CAPE was observed in the treatment of the harmful effects of FA. Despite the harmful effects from FA exposure, it is commonly used in Turkey and elsewhere in dissection laboratories. Consequently, all anatomists must know and understand the effects of this toxic agent on organisms and the environment, and take precautions to avoid unnecessary exposure. The reviewed studies have indicated that FA has neurotoxic characteristics and systemic toxic effects. It is hypothesized that inhalation of FA, during the early postnatal period, is linked to some neurological diseases that occur in adults. Although complete prevention is impossible for laboratory workers and members of industries utilizing FA

  4. Novel central nervous system drug delivery systems.

    PubMed

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

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases. PMID:24325540

  5. INTERACTION BETWEEN METHYL MERCURY AND RADIATION EFFECTS ON NERVOUS SYSTEMS

    EPA Science Inventory

    The interaction between methyl mercury and ionizing radiation was investigated in a series of experiments using rats, hamsters, and squirrel monkeys to study the effects produced and possible mechanisms of action. Parameters evaluated included several measurements of behavior, br...

  6. Effects of Inhaled Rosemary Oil on Subjective Feelings and Activities of the Nervous System

    PubMed Central

    Sayorwan, Winai; Ruangrungsi, Nijsiri; Piriyapunyporn, Teerut; Hongratanaworakit, Tapanee; Kotchabhakdi, Naiphinich; Siripornpanich, Vorasith

    2013-01-01

    Rosemary oil is one of the more famous essential oils widely used in aroma-therapy. However, the effects of rosemary oil on the human body, in particular the nervous system, have not been sufficiently studied. This study investigates the effects of the inhalation of rosemary oil on test subjects’ feelings, as well as its effects on various physiological parameters of the nervous system. Twenty healthy volunteers participated in the experiment. All subjects underwent autonomic nervous system (ANS) recording. This consisted of measurements of skin temperature; heart rate; respiratory rate; blood pressure; evaluations of the subjects’ mood states; and electroencephalography (EEG) recordings in the pre-, during treatment, and post-rosemary inhalation periods as compared with control conditions. Our results showed significant increases in blood pressure, heart rate, and respiratory rate after rosemary oil inhalation. After the inhalation treatments, subjects were found to have become more active and stated that they felt “fresher”. The analysis of EEGs showed a reduction in the power of alpha1 (8–10.99 Hz) and alpha2 (11–12.99 Hz) waves. Moreover, an increment in the beta wave (13–30 Hz) power was observed in the anterior region of the brain. These results confirm the stimulatory effects of rosemary oil and provide supporting evidence that brain wave activity, autonomic nervous system activity, as well as mood states are all affected by the inhalation of the rosemary oil. PMID:23833718

  7. Central Nervous System Lipoproteins

    PubMed Central

    Mahley, Robert W.

    2016-01-01

    ApoE on high-density lipoproteins is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS). Normally produced mostly by astrocytes, apoE is also produced under neuropathologic conditions by neurons. ApoE on high-density lipoproteins is critical in redistributing cholesterol and phospholipids for membrane repair and remodeling. The 3 main structural isoforms differ in their effectiveness. Unlike apoE2 and apoE3, apoE4 has markedly altered CNS metabolism, is associated with Alzheimer disease and other neurodegenerative disorders, and is expressed at lower levels in brain and cerebrospinal fluid. ApoE4-expressing cultured astrocytes and neurons have reduced cholesterol and phospholipid secretion, decreased lipid-binding capacity, and increased intracellular degradation. Two structural features are responsible for apoE4 dysfunction: domain interaction, in which arginine-61 interacts ionically with glutamic acid-255, and a less stable conformation than apoE3 and apoE2. Blocking domain interaction by gene targeting (replacing arginine-61 with threonine) or by small-molecule structure correctors increases CNS apoE4 levels and lipid-binding capacity and decreases intracellular degradation. Small molecules (drugs) that disrupt domain interaction, so-called structure correctors, could prevent the apoE4-associated neuropathology by blocking the formation of neurotoxic fragments. Understanding how to modulate CNS cholesterol transport and metabolism is providing important insights into CNS health and disease. PMID:27174096

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

    PubMed Central

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

    2014-01-01

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

  9. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects.

    PubMed

    Nehlig, A; Daval, J L; Debry, G

    1992-01-01

    Caffeine is the most widely consumed central-nervous-system stimulant. Three main mechanisms of action of caffeine on the central nervous system have been described. Mobilization of intracellular calcium and inhibition of specific phosphodiesterases only occur at high non-physiological concentrations of caffeine. The only likely mechanism of action of the methylxanthine is the antagonism at the level of adenosine receptors. Caffeine increases energy metabolism throughout the brain but decreases at the same time cerebral blood flow, inducing a relative brain hypoperfusion. Caffeine activates noradrenaline neurons and seems to affect the local release of dopamine. Many of the alerting effects of caffeine may be related to the action of the methylxanthine on serotonin neurons. The methylxanthine induces dose-response increases in locomotor activity in animals. Its psychostimulant action on man is, however, often subtle and not very easy to detect. The effects of caffeine on learning, memory, performance and coordination are rather related to the methylxanthine action on arousal, vigilance and fatigue. Caffeine exerts obvious effects on anxiety and sleep which vary according to individual sensitivity to the methylxanthine. However, children in general do not appear more sensitive to methylxanthine effects than adults. The central nervous system does not seem to develop a great tolerance to the effects of caffeine although dependence and withdrawal symptoms are reported. PMID:1356551

  10. Different methods for evaluating the effects of microwave radiation exposure on the nervous system.

    PubMed

    Altunkaynak, Berrin Zuhal; Altun, Gamze; Yahyazadeh, Ahmed; Kaplan, Arife Ahsen; Deniz, Omur Gulsum; Türkmen, Aysın Pinar; Önger, Mehmet Emin; Kaplan, Suleyman

    2016-09-01

    Microwave radiation (MWR) leads to hazardous effects on he central nervous system (CNS) for both human and animals. The widespread use of mobile phones has increased the risks of health problems in the CNS caused by radiofrequency (RF) electromagnetic fields. To determine these effects various methodological approaches related to neuroscience such as stereology, immunohistochemistry, and electron microscopy have been used. These approaches examine the effects on cells exposed to MWR at the light microscopic and ultrastructural levels, and novel information is obtained. The main aim of this paper is to discuss possible side effects of MWR in the light of current literature with different methodological approaches. PMID:26686295

  11. [Advance in studies on pharmacological effect of salidroside on nervous system diseases].

    PubMed

    Xie, Hui; Zhu, Da-hui

    2012-09-01

    Salidroside is an extract from Rhodiola crenulata as well as one of major active constituents. In studies of recent years, salidroside showed multiple effects in protecting nerves, scavenging free radicals, regulating central nervous system neurotransmitter, increasing the ability to promote nerve repair and modulating of apoptosis-related gene expression. Hence, it is expected to be applied in treating degenerative nerve diseases and brain ischemic diseases. This essay summarizes studies on pharmacological effects of salidroside on nerve system diseases, providing reference for further studies, development and application of R. crenulata. PMID:23236741

  12. Effects of Petroleum Ether Extract of Amorphophallus paeoniifolius Tuber on Central Nervous System in Mice

    PubMed Central

    Das, S. S.; Sen, Malini; Dey, Y. N.; De, S.; Ghosh, A. K.

    2009-01-01

    The central nervous system activity of the petroleum ether extract of Amorphophallus paeoniifolius tuber was examined in mice, fed normal as well as healthy conditions. The petroleum ether extract of Amorphophallus paeoniifolius tuber at the doses of 100, 300 and 1000 mg/kg showed significant central nervous system activity in mice. PMID:20376218

  13. Nervous System Complexity Baffles Scientists.

    ERIC Educational Resources Information Center

    Fox, Jeffrey L.

    1982-01-01

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

  14. The effects of Crocus sativus (saffron) and its constituents on nervous system: A review.

    PubMed

    Khazdair, Mohammad Reza; Boskabady, Mohammad Hossein; Hosseini, Mahmoud; Rezaee, Ramin; M Tsatsakis, Aristidis

    2015-01-01

    Saffron or Crocus sativus L. (C. sativus) has been widely used as a medicinal plant to promote human health, especially in Asia. The main components of saffron are crocin, picrocrocin and safranal. The median lethal doses (LD50) of C. sativus are 200 mg/ml and 20.7 g/kg in vitro and in animal studies, respectively. Saffron has been suggested to be effective in the treatment of a wide range of disorders including coronary artery diseases, hypertension, stomach disorders, dysmenorrhea and learning and memory impairments. In addition, different studies have indicated that saffron has anti-inflammatory, anti-atherosclerotic, antigenotoxic and cytotoxic activities. Antitussive effects of stigmas and petals of C. sativus and its components, safranal and crocin have also been demonstrated. The anticonvulsant and anti-Alzheimer properties of saffron extract were shown in human and animal studies. The efficacy of C. sativus in the treatment of mild to moderate depression was also reported in clinical trial. Administration of C. sativus and its constituents increased glutamate and dopamine levels in the brain in a dose-dependent manner. It also interacts with the opioid system to reduce withdrawal syndrome. Therefore, in the present article, the effects of C. sativus and its constituents on the nervous system and the possible underlying mechanisms are reviewed. Our literature review showed that C. sativus and its components can be considered as promising agents in the treatment of nervous system disorders. PMID:26468457

  15. The effects of Crocus sativus (saffron) and its constituents on nervous system: A review

    PubMed Central

    Khazdair, Mohammad Reza; Boskabady, Mohammad Hossein; Hosseini, Mahmoud; Rezaee, Ramin; M. Tsatsakis, Aristidis

    2015-01-01

    Saffron or Crocus sativus L. (C. sativus) has been widely used as a medicinal plant to promote human health, especially in Asia. The main components of saffron are crocin, picrocrocin and safranal. The median lethal doses (LD50) of C. sativus are 200 mg/ml and 20.7 g/kg in vitro and in animal studies, respectively. Saffron has been suggested to be effective in the treatment of a wide range of disorders including coronary artery diseases, hypertension, stomach disorders, dysmenorrhea and learning and memory impairments. In addition, different studies have indicated that saffron has anti-inflammatory, anti-atherosclerotic, antigenotoxic and cytotoxic activities. Antitussive effects of stigmas and petals of C. sativus and its components, safranal and crocin have also been demonstrated. The anticonvulsant and anti-Alzheimer properties of saffron extract were shown in human and animal studies. The efficacy of C. sativus in the treatment of mild to moderate depression was also reported in clinical trial. Administration of C. sativus and its constituents increased glutamate and dopamine levels in the brain in a dose-dependent manner. It also interacts with the opioid system to reduce withdrawal syndrome. Therefore, in the present article, the effects of C. sativus and its constituents on the nervous system and the possible underlying mechanisms are reviewed. Our literature review showed that C. sativus and its components can be considered as promising agents in the treatment of nervous system disorders. PMID:26468457

  16. Lavender and the Nervous System

    PubMed Central

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

    2013-01-01

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

  17. Effects on the nervous system among welders exposed to aluminium and manganese.

    PubMed Central

    Sjögren, B; Iregren, A; Frech, W; Hagman, M; Johansson, L; Tesarz, M; Wennberg, A

    1996-01-01

    OBJECTIVES--The purpose was to study the effects on the nervous system in welders exposed to aluminium and manganese. METHODS--The investigation included questionnaires on symptoms, psychological methods (simple reaction time, finger tapping speed and endurance, digit span, vocabulary, tracking, symbol digit, cylinders, olfactory threshold, Luria-Nebraska motor scale), neurophysiological methods (electroencephalography, event related auditory evoked potential (P-300), brainstem auditory evoked potential, and diadochokinesometry) and assessments of blood and urine concentrations of metals (aluminium, lead, and manganese). RESULTS--The welders exposed to aluminium (n = 38) reported more symptoms from the central nervous system than the control group (n = 39). They also had a decreased motor function in five tests. The effect was dose related in two of these five tests. The median exposure of aluminium welders was 7065 hours and they had about seven times higher concentrations of aluminium in urine than the controls. The welders exposed to manganese (n = 12) had a decreased motor function in five tests. An increased latency of event related auditory evoked potential was also found in this group. The median manganese exposure was 270 hours. These welders did not have higher concentrations of manganese in blood than the controls. CONCLUSIONS--The neurotoxic effects found in the groups of welders exposed to aluminium and manganese are probably caused by the aluminium and manganese exposure, respectively. These effects indicate a need for improvements in the work environments of these welders. PMID:8563855

  18. Pharmacokinetics and central nervous system effects of the novel dopamine D2 receptor antagonist JNJ-37822681.

    PubMed

    te Beek, Erik T; Moerland, Matthijs; de Boer, Peter; van Nueten, Luc; de Kam, Marieke L; Burggraaf, Jacobus; Cohen, Adam F; van Gerven, Joop M A

    2012-08-01

    Using the rate of dissociation from the D(2) receptor as a means to screen novel compounds for antipsychotic drug candidates, the centrally acting and fast-dissociating selective dopamine D(2) receptor antagonist JNJ-37822681 was developed. In a blinded, placebo-controlled, randomized first-in-human study, JNJ-37822681 was administered orally to 27 healthy male volunteers at doses of 0.5, 2, 5, 10, 15 and 20 mg. Safety, pharmacokinetics and central nervous system effects were evaluated by measuring prolactin levels, eye movements, adaptive tracking, visual analogue scales, body sway, finger tapping and electroencephalography. JNJ-37822681 was well tolerated and somnolence was the most frequently reported adverse effect. Peak plasma concentrations increased more than proportional to dose, but increases in the area under curve (AUC) were dose-proportional. Prolactin elevations started at doses of 5 mg, whereas small decreases in adaptive tracking were demonstrated at 10 mg doses. At higher doses, JNJ-37822681 caused a small decrease in saccadic peak velocity, smooth pursuit, alertness, finger tapping and electroencephalography activity, and an increase in body sway. This effect profile is likely to be the result of the selectivity of JNJ-37822681 for the D(2) receptor, leading to strong D(2) receptor-mediated elevations in serum prolactin, but fewer effects on more complex central nervous system functions, which are likely to involve multiple neurotransmitters. PMID:21890591

  19. Functional Observational Battery Testing for Nervous System Effects of Drugs and Other Chemicals

    EPA Science Inventory

    Screening for behavioral toxicity, or neurotoxicity, has become standard practice in preclinical safety pharmacology and toxicology. Behavior represents the integrated sum of activities mediated by the nervous system. Current screening batteries, such as the functional observat...

  20. Nervous system effects of dissolved and nanoparticulate cadmium in rats in subacute exposure.

    PubMed

    Horváth, Edina; Oszlánczi, Gábor; Máté, Zsuzsanna; Szabó, Andrea; Kozma, Gábor; Sápi, András; Kónya, Zoltán; Paulik, Edit; Nagymajtényi, László; Papp, András

    2011-07-01

    Cadmium, a toxic heavy metal with various applications in technology, can affect people both by environmental (foodborne) and occupational (inhalation) exposure and can cause nervous system damage. To model this, rats were subacutely treated either with CdCl(2) solution per os (3.0 mg kg(-1) b.w.) or nanoparticulate CdO(2) (particle size ca 65 nm) by intratracheal instillation (0.04 mg kg(-1) b.w.) alone or in sequential combination. Nervous system effects were observed at different levels of function (open field behavior, cortical electrical activity, nerve action potential) and some general toxicological indicators were also measured. Three weeks of oral plus one week of intratracheal exposure caused significant reduction of body weight gain and open field motility. Lengthening of latency of sensory evoked potentials, observed in all treated rats, was also the most significant in the group receiving oral plus intratracheal treatment. Conduction velocity of the tail nerve was likewise decreased in all treated groups. Several of the effects pointed to a potentiating interaction between the two forms of Cd. Modeling environmental and occupational Cd exposure by oral and intratracheal application in rats was feasible, with results suggesting serious negative health effects in humans suffering such a combined exposure. PMID:21351111

  1. Effect of Hinoki and Meniki Essential Oils on Human Autonomic Nervous System Activity and Mood States.

    PubMed

    Chen, Chi-Jung; Kumar, K J Senthil; Chen, Yu-Ting; Tsao, Nai-Wen; Chien, Shih-Chang; Chang, Shang-Tzen; Chu, Fang-Hua; Wang, Sheng-Yang

    2015-07-01

    Meniki (Chamecyparis formosensis) and Hinoki (C. obtusa) are precious conifers with excellent wood properties and distinctive fragrances that make these species popular in Taiwan for construction, interiors and furniture. In the present study, the compositions of essential oils prepared from Meniki and Hinoki were analyzed by gas chromatography-mass spectrometry (GC/MS). Thirty-six compounds were identified from the wood essential oil of Meniki, including Δ-cadinene, γ-cadinene, Δ-cadinol, α-muurolene, calamenene, linalyl acetate and myrtenol; 29 compounds were identified from Hinoki, including α-terpineol, α-pinene, Δ-cadinene, borneol, terpinolene, and limonene. Next, we examined the effect of Meniki and Hinoki essential oils on human autonomic nervous system activity. Sixteen healthy adults received Meniki or Hinoki by inhalation for 5 min, and the physiological and psychological effects were examined. After inhaling Meniki essential oil, participant's systolic blood pressure and heart rate (HR) were decreased, and diastolic blood pressure increased. In addition, sympathetic nervous activity (SNS) was significantly decreased, and parasympathetic activity (PSNS) was significantly increased. On the other hand, after inhaling Hinoki essential oil, systolic blood pressure, heart rate and PSNS were decreased, whereas SNA was increased. Indeed, both Meniki and Hinoki essential oils increased heart rate variability (HRV) in tested adults. Furthermore, in the Profile of Mood States (POMS) test, both Meniki and Hinoki wood essential oils stimulated a pleasant mood status. Our results strongly suggest that Meniki and Hinoki essential oils could be suitable agents for the development of regulators of sympathetic nervous system dysfunctions. PMID:26411036

  2. Hazard effects of nanoparticles in central nervous system: Searching for biocompatible nanomaterials for drug delivery.

    PubMed

    Leite, Paulo Emílio Corrêa; Pereira, Mariana Rodrigues; Granjeiro, José Mauro

    2015-10-01

    Nanostructured materials are widely used in many applications of industry and biomedical fields. Nanoparticles emerges as potential pharmacological carriers that can be applied in the regenerative medicine, diagnosis and drug delivery. Different types of nanoparticles exhibit ability to cross the brain blood barrier (BBB) and accumulate in several brain areas. Then, efforts have been done to develop safer nanocarrier systems to treat disorders of central nervous system (CNS). However, several in vitro and in vivo studies demonstrated that nanoparticles of different materials exhibit a wide range of neurotoxic effects inducing neuroinflammation and cognitive impairment. For this reason, polymeric nanoparticles arise as a promisor alternative due to their biocompatible and biodegradable properties. After an overview of CNS location and neurotoxic effects of translocated nanoparticles, this review addresses the use of polymeric nanoparticles to the treatment of neuroinfectious diseases, as acquired immunodeficiency syndrome (AIDS) and meningitis. PMID:26116398

  3. Brain and nervous system (image)

    MedlinePlus

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

  4. Brain and nervous system (image)

    MedlinePlus

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

  5. Paraneoplastic nervous system syndromes.

    PubMed

    Jaeckle, K A

    1996-05-01

    Recent progress in the understanding of the paraneoplastic neurologic syndromes has included further deliniation of the clinical syndromes and their treatment, attempts at standardization of the diagnostic nomenclature, investigations of pathogenetic mechanisms, and molecular characterization of the paraneoplastic antigens with implications as to their biologic relevance. Despite more than 30 years of investigation, the pathogenesis of these presumably autoimmune conditions remains unclear. Furthermore, no effective therapy has been identified for these conditions, with the possible exception of the opsoclonus-myoclonus ataxia and Lambert-Eaton myasthenic syndromes. Future investigations must focus on the disrupted genetic regulatory events involved in generation and propagation of the autoimmune response, antigen presentation and processing; target cell destruction, and consideration of alternative pathologic causes. Effective management strategies are most likely to develop from a better understanding of the disease pathogenesis, the development of animal model systems, and a creative look beyond the usual therapies employed in autoimmune conditions. PMID:8794147

  6. 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.

  7. Effect of regional myocardial ischemia on sympathetic nervous system as assessed by fluorine-18-metaraminol

    SciTech Connect

    Schwaiger, M.; Guibourg, H.; Rosenspire, K.; McClanahan, T.; Gallagher, K.; Hutchins, G.; Wieland, D.M. )

    1990-08-01

    With the introduction of radiolabeled catecholamine analogues, the noninvasive evaluation of the cardiac sympathetic nervous system has become possible. This study evaluated the effect of regional ischemia on myocardial retention of the new norepinephrine analogue 6-({sup 18}F) fluorometaraminol (FMR) in the open chest dog model. Six dogs were injected intravenously with FMR following 30-min occlusion of the left anterior descending artery. Six sham animals served as control group. Regional myocardial blood flow as determined by microspheres decreased 87% during ischemia (p less than 0.01), but was not significantly different from control myocardium following reperfusion. Regional myocardial 18F activity as determined postmortem was significantly reduced in reperfused myocardium (-34%), which paralleled an 18% reduction of tissue norepinephrine concentration. Thus, short time periods of coronary occlusion affect neuronal function indicating the sensitivity of the sympathetic nerve terminals to ischemia. FMR provides a new tracer approach for the characterization of neuronal integrity in postischemic myocardium.

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

    NASA Astrophysics Data System (ADS)

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

    1994-10-01

    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.

  9. Effect of experimental hyperinsulinemia on sympathetic nervous system activity in the rat

    SciTech Connect

    Young, J.B.

    1988-01-01

    Since insulin acutely stimulates the sympathetic nervous system, a role for sympathetic overactivity has been hypothesized to underlie the association between chronic hyperinsulinemia and hypertension. To assess the effect of sustained hyperinsulinemia on sympathetic function, (/sup 3/H)norepinephrine (NE) turnover was measured in rats injected with insulin for 14d. NE turnover in insulin-treated animals given free access to lab chow and a 10% sucrose solution was compared with that obtained in rats fed chow alone or chow plus sucrose. Sucrose ingestion increased NE turnover in heart, brown adipose tissue, and liver, but exogenous insulin did not augment turnover beyond that seen in animals given sucrose alone. This study, therefore, provides no evidence that chronic hyperinsulinemia, sufficient to induce peripheral insulin resistance, stimulates sympathetic activity more than that produced by chronic sucrose ingestion.

  10. Effects of low-dose prenatal irradiation on the central nervous system

    SciTech Connect

    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 resolving 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.

  11. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  12. The effects of ozone exposure and associated injury mechanisms on the central nervous system.

    PubMed

    Martínez-Lazcano, Juan Carlos; González-Guevara, Edith; del Carmen Rubio, María; Franco-Pérez, Javier; Custodio, Verónica; Hernández-Cerón, Miguel; Livera, Carlos; Paz, Carlos

    2013-01-01

    Ozone (O3) is a component of photochemical smog, which is a major air pollutant and demonstrates properties that are harmful to health because of the toxic properties that are inherent to its powerful oxidizing capabilities. Environmental O3 exposure is associated with many symptoms related to respiratory disorders, which include loss of lung function, exacerbation of asthma, airway damage, and lung inflammation. The effects of O3 are not restricted to the respiratory system or function - adverse effects within the central nervous system (CNS) such as decreased cognitive response, decrease in motor activity, headaches, disturbances in the sleep-wake cycle, neuronal dysfunctions, cell degeneration, and neurochemical alterations have also been described; furthermore, it has also been proposed that O3 could have epigenetic effects. O3 exposure induces the reactive chemical species in the lungs, but the short half-life of these chemical species has led some authors to attribute the injurious mechanisms observed within the lungs to inflammatory processes. However, the damage to the CNS induced by O3 exposure is not well understood. In this review, the basic mechanisms of inflammation and activation of the immune system by O3 exposure are described and the potential mechanisms of damage, which include neuroinflammation and oxidative stress, and the signs and symptoms of disturbances within the CNS caused by environmental O3 exposure are discussed. PMID:23585211

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

    PubMed

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

    2016-01-01

    The consumption of marijuana extracted from Cannabis sativa and indica plants involves an important cultural impact in Mexico. Their psychological stimulatory effect is widely recognized; their biochemical and molecular components interact with CB1 and CB2 (endocannabinoid system) receptors in various central nervous system structures (CNS) and immune cells. The psychoactive element Δ-9-tetrahydrocannabinol (THC) can be reproduced synthetically. Systematic reviews show evidence of therapeutic effectiveness of therapeutic marijuana only for certain symptoms of multiple sclerosis (spasticity, spasms and pain), despite attempts for its widespread use, including refractory childhood epilepsy. Evidence indicates significant adverse effects of smoked marijuana on the structure, functioning and brain connectivity. Cannabis exposure during pregnancy affects fetal brain development, potentially leading to later behavioral problems in children. Neuropsychological tests and advanced imaging techniques show involvement in the learning process in adolescents with substance use. Also, marijuana increases the cognitive impairment in patients with multiple sclerosis. Social and ethical consequences to legally free marijuana for recreational use may be deleterious transcendentally. The medicinal or psychoactive cannabinol no addictive effect requires controlled proven efficacy and safety before regulatory approval studies. PMID:27428345

  14. Classical Neurotransmitters and their Significance within the Nervous System.

    ERIC Educational Resources Information Center

    Veca, A.; Dreisbach, J. H.

    1988-01-01

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

  15. Effects of Fumaric Acids on Cuprizone Induced Central Nervous System De- and Remyelination in the Mouse

    PubMed Central

    Moharregh-Khiabani, Darius; Blank, Alexander; Skripuletz, Thomas; Miller, Elvira; Kotsiari, Alexandra; Gudi, Viktoria; Stangel, Martin

    2010-01-01

    Background Fumaric acid esters (FAE) are a group of compounds which are currently under investigation as an oral treatment for relapsing-remitting multiple sclerosis. One of the suggested modes of action is the potential of FAE to exert a neuroprotective effect. Methodology/Principal Findings We have investigated the impact of monomethylfumarate (MMF) and dimethylfumaric acid (DMF) on de- and remyelination using the toxic cuprizone model where the blood-brain-barrier remains intact and only scattered T-cells and peripheral macrophages are found in the central nervous system (CNS), thus excluding the influence of immunomodulatory effects on peripheral immune cells. FAE showed marginally accelerated remyelination in the corpus callosum compared to controls. However, we found no differences for demyelination and glial reactions in vivo and no cytoprotective effect on oligodendroglial cells in vitro. In contrast, DMF had a significant inhibitory effect on lipopolysaccharide (LPS) induced nitric oxide burst in microglia and induced apoptosis in peripheral blood mononuclear cells (PBMC). Conclusions These results contribute to the understanding of the mechanism of action of fumaric acids. Our data suggest that fumarates have no or only little direct protective effects on oligodendrocytes in this toxic model and may act rather indirectly via the modulation of immune cells. PMID:20668697

  16. [Effect of nociceptin on histamine and serotonin release in the central nervous system].

    PubMed

    Gyenge, Melinda; Hantos, Mónika; Laufer, Rudolf; Tekes, Korniléa

    2006-01-01

    Role in pain sensation of both nociceptin (NC), the bioactive heptadecapeptide sequence of preproorphaninFQ and of histamine has been widely evidenced in the central nervous system (CNS). In the current series of experiments effect of intracerebroventricularly (i.c.v.) administered NC (5.5 nmol/rat) on histamine and serotonin levels in blood plasma, CSF and brain areas (hypothalamus and hippocampus) was studies and compared to the effect of the mast cell degranulator Compound 48/80(100microg/kg, i.c.v.) and the neuroactive peptide Substance P (50nmol/rat, i.c.v.). It was found that all the three compounds increased the histamine level in the CNS, however their activity concerning the mast cell-, and neuronal histamine release is different. NC could release histamine from both the mast cells and the neurons and it decreased CNS serotonin levels. Substance P was found the most potent in increasing CNS histamine levels. Compound 48/80 treatment resulted in elevated histamine levels both in the CNS and blood plasma. It is concluded that the histamine releasing effects of i.c.v. administered NC and SP are limited to the CNS, but in the effect of Compound 48/80 its blood-brain barrier impairing activity is also involved. Data also demonstrate that NC has significant effect on both the histaminergic and serotonergic neurotransmission in the CNS. PMID:17094659

  17. Differential effects of opiates on the incorporation of [14C] thiamine in the central nervous system of the rat.

    PubMed

    Misra, A L; Vadlamani, N L; Pontani, R B

    1977-03-15

    Opiate agonist (morphine), pure antagonist (naloxone), mixed agonist-antagonist (nalorphine) and analgesically inactive enantiomorph (dextrorphan) produced differential stereoselective effects on the incorporation of [14C] thiamine in the central nervous system of the rats. The possible role of thiamine in opiate effects and its implications are discussed. PMID:858372

  18. Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons

    SciTech Connect

    Branch, C.A.; Goldberg, D.A.; Ewing, J.R.; Butt, S.S.; Gayner, J.; Fagan, S.C.

    1994-12-31

    The gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans. We report the acute cardiac and central nervous system effects of trifluoromethane in eight anesthetized baboons. A dose-response effect was established for respiratory rate, electroencephalogram, and cardiac sinus rate, which exhibited a stepwise decrease from 10% trifluoromethane. No spontaneous arrhythmias were noted, and arterial blood pressure remained unchanged at any inspired level. Intravenous epinephrine infusions (1 {mu}g/kg) induced transient cardiac arrhythmia in 1 animal only at 70% FC-23 (v/v) trifluoromethane. Trifluoromethane appears to induce mild dose-related physiological changes at inspired levels of 30% or more, indicative of an anesthetic effect. These data suggest that trifluoromethane may be safe to use in humans, without significant adverse acute effects, at an inspired level of 30%. 23 refs., 3 figs., 3 tabs.

  19. Effects of subthalamic nucleus stimulation and levodopa on the autonomic nervous system in Parkinson's disease

    PubMed Central

    Ludwig, Janne; Remien, Piet; Guballa, Christoph; Binder, Andreas; Binder, Sabine; Schattschneider, Jörn; Herzog, Jan; Volkmann, Jens; Deuschl, Günther; Wasner, Gunnar; Baron, Ralf

    2007-01-01

    Dysfunctions of the autonomic nervous system (ANS) are common in Parkinson's disease (PD). Regarding motor disability, deep brain stimulation of the subthalamic nucleus (STN) is an effective treatment option in long lasting PD. The aims of this study were to examine whether STN stimulation has an influence on functions of the ANS and to compare these effects to those induced by levodopa. Blood pressure (BP) and heart rate (HR) during rest and orthostatic conditions, HR variability (HRV) and breathing‐induced cutaneous sympathetic vasoconstriction (CVC) were tested in 14 PD patients treated with STN stimulation during “ON” and “OFF” condition of the stimulator. The effects of a single dose of levodopa on ANS were tested in 15 PD patients without DBS. STN stimulation had no influence on cardiovascular ANS functions, whereas CVC was significantly increased. In contrast, levodopa significantly lowered BP and HR at rest and enhanced orthostatic hypotension. Further, HRV, skin perfusion and temperature increased after administration of levodopa. Our results suggest that in contrast to levodopa, STN stimulation has only minor effects on autonomic functions. Since less pharmacotherapy is needed after STN stimulation, reduced levodopa intake results in relative improvement of autonomic function in deep brain stimulated PD patients. PMID:17371906

  20. Effects of Low-Level Blast Exposure on the Nervous System: Is There Really a Controversy?

    PubMed Central

    Elder, Gregory A.; Stone, James R.; Ahlers, Stephen T.

    2014-01-01

    High-pressure blast waves can cause extensive CNS injury in human beings. However, in combat settings, such as Iraq and Afghanistan, lower level exposures associated with mild traumatic brain injury (mTBI) or subclinical exposure have been much more common. Yet controversy exists concerning what traits can be attributed to low-level blast, in large part due to the difficulty of distinguishing blast-related mTBI from post-traumatic stress disorder (PTSD). We describe how TBI is defined in human beings and the problems posed in using current definitions to recognize blast-related mTBI. We next consider the problem of applying definitions of human mTBI to animal models, in particular that TBI severity in human beings is defined in relation to alteration of consciousness at the time of injury, which typically cannot be assessed in animals. However, based on outcome assessments, a condition of “low-level” blast exposure can be defined in animals that likely approximates human mTBI or subclinical exposure. We review blast injury modeling in animals noting that inconsistencies in experimental approach have contributed to uncertainty over the effects of low-level blast. Yet, animal studies show that low-level blast pressure waves are transmitted to the brain. In brain, low-level blast exposures cause behavioral, biochemical, pathological, and physiological effects on the nervous system including the induction of PTSD-related behavioral traits in the absence of a psychological stressor. We review the relationship of blast exposure to chronic neurodegenerative diseases noting the paradoxical lowering of Abeta by blast, which along with other observations suggest that blast-related TBI is pathophysiologically distinct from non-blast TBI. Human neuroimaging studies show that blast-related mTBI is associated with a variety of chronic effects that are unlikely to be explained by co-morbid PTSD. We conclude that abundant evidence supports low-level blast as having long

  1. Facilitation of breathing by leptin effects in the central nervous system.

    PubMed

    Bassi, M; Furuya, W I; Zoccal, D B; Menani, J V; Colombari, D S A; Mulkey, D K; Colombari, E

    2016-03-15

    With the global epidemic of obesity, breathing disorders associated with excess body weight have markedly increased. Respiratory dysfunctions caused by obesity were originally attributed to mechanical factors; however, recent studies have suggested a pathophysiological component that involves the central nervous system (CNS) and hormones such as leptin produced by adipocytes as well as other cells. Leptin is suggested to stimulate breathing and leptin deficiency causes an impairment of the chemoreflex, which can be reverted by leptin therapy. This facilitation of the chemoreflex may depend on the action of leptin in the hindbrain areas involved in the respiratory control such as the nucleus of the solitary tract (NTS), a site that receives chemosensory afferents, and the ventral surface of the medulla that includes the retrotrapezoid nucleus (RTN), a central chemosensitive area, and the rostral ventrolateral medulla (RVLM). Although the mechanisms and pathways activated by leptin to facilitate breathing are still not completely clear, evidence suggests that the facilitatory effects of leptin on breathing require the brain melanocortin system, including the POMC-MC4R pathway, a mechanism also activated by leptin to modulate blood pressure. The results of all the studies that have investigated the effect of leptin on breathing suggest that disruption of leptin signalling as caused by obesity-induced reduction of central leptin function (leptin resistance) is a relevant mechanism that may contribute to respiratory dysfunctions associated with obesity. PMID:26095748

  2. Effects of Betel chewing on the central and autonomic nervous systems.

    PubMed

    Chu, N S

    2001-01-01

    Betel chewing has been claimed to produce a sense of well-being, euphoria, heightened alertness, sweating, salivation, a hot sensation in the body and increased capacity to work. Betel chewing also leads to habituation, addiction and withdrawal. However, the mechanisms underlying these effects remain poorly understood. Arecoline, the major alkaloid of Areca nut, has been extensively studied, and several effects of betel chewing are thought to be related to the actions of this parasympathomimetic constituent. However, betel chewing may produce complex reactions and interactions. In the presence of lime, arecoline and guvacoline in Areca nut are hydrolyzed into arecaidine and guvacine, respectively, which are strong inhibitors of GABA uptake. Piper betle flower or leaf contains aromatic phenolic compounds which have been found to stimulate the release of catecholamines in vitro. Thus, betel chewing may affect parasympathetic, GABAnergic and sympathetic functions. Betel chewing produces an increase in heart rate, blood pressure, sweating and body temperature. In addition, EEG shows widespread cortical desynchronization indicating a state of arousal. In autonomic function tests, both the sympathetic skin response and RR interval variation are affected. Betel chewing also increases plasma concentrations of norepinephrine and epinephrine. These results suggest that betel chewing mainly affects the central and autonomic nervous systems. Future studies should investigate both the acute and chronic effects of betel chewing. Such studies may further elucidate the psychoactive mechanisms responsible for the undiminished popularity of betel chewing since antiquity. PMID:11385294

  3. FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system

    PubMed Central

    Brinkmann, Volker

    2009-01-01

    FTY720 (fingolimod) is a first-in-class sphingosine 1-phosphate (S1P) receptor modulator that was highly effective in Phase II clinical trials for Multiple Sclerosis (MS). FTY720 is phosphorylated in vivo by sphingosine kinase-2 to form the active moiety FTY720-phosphate that binds to four of the five G protein-coupled S1P receptor subtypes. Studies using conditional S1P1 receptor-deficient and sphingosine kinase-deficient mice showed that the egress of lymphocytes from lymph nodes requires signalling of lymphocytic S1P1 receptors by the endogenous ligand S1P. The S1P mimetic FTY720-phosphate causes internalization and degradation of cell membrane-expressed S1P1, thereby antagonizing S1P action at the receptor. In models of human MS and demyelinating polyneuropathies, functional antagonism of lymphocytic S1P1 slows S1P-driven egress of lymphocytes from lymph nodes, thereby reducing the numbers of autoaggressive TH17 cells that recirculate via lymph and blood to the central nervous system and the sciatic/ischiatic nerves. Based on its lipophilic nature, FTY720 crosses the blood–brain barrier, and ongoing experiments suggest that the drug also down-modulates S1P1 in neural cells/astrocytes to reduce astrogliosis, a phenomenon associated with neurodegeneration in MS. This may help restore gap-junctional communication of astrocytes with neurons and cells of the blood–brain barrier. Additional effects may result from (down-) modulation of S1P3 in astrocytes and of S1P1 and S1P5 in oligodendrocytes. In conclusion, FTY720 may act through immune-based and central mechanisms to reduce inflammation and support structural restoration of the central nervous system parenchyma. Beyond the autoimmune indications, very recent studies suggest that short-term, low-dose administration of FTY720 could help treat chronic (viral) infections. Differential effects of the drug on the trafficking of naïve, central memory and effector memory T cell subsets are discussed. PMID:19814729

  4. [Vesalius and the nervous system].

    PubMed

    Van Laere, J

    1993-01-01

    Before we comment the subject of this lecture, we attract the reader's attention towards two remarks. We first want to point out that, although Vesalius is rightly considered as "the father of anatomy", in physiological matters--such as e.g. the physiology of the nervous system--he remained a faithful follower of Galen. A second preliminary remark explains why the books Vesalius devoted to the nervous system, namely the fourth and seventh books, as well as a part of the third book, don't belong to the best parts of the Fabrica, when we compare them with his Osteology and his Myology. We should not forget that some technical discoveries such as keeping brain-tissue in alcohol in order to harden it and colouring methods of Weigert, Marchi and Nissl, that made a refined macro- and microscopic examination of the nervous system possible, were only invented in the 19th century. The fourth book considers the peripheral nervous system. According to Vesalius, there are seven pairs of brain-nerves. His first pair corresponds to our Nervous opticus; his second pair concerns our Nervi oculomotorius, trochlearis and abducens; this third pair embraces a great part of our Nervus trigeminus; his fourth pair corresponds to our Nervus maxillaris; his fifth pair includes our Nervi facialis and acusticus; his sixth pair includes our Nervi vagus and accessorius; his seventh pair our Nervi hypoglossus and pharyngeus. Vesalius counts thirty pairs of spinal nerves. His description of the Plexus brachialis and the Plexus ischiadicus is closely related to the modern views in these matters. However, his teleologic views about them are remarkable, e.g. about the course of the Nervi recurrentes. The seventh book covers the brain. He successively and truly describes the cerebral membranes, the Ventriculi, the Cerebrum; his description relies on a series of horizontal slices. He also describes the brain-stem and the Cerebellum. Vesalius, who had doubts about the existence of the Plexus

  5. [Effects of radio- and microwaves emitted by wireless communication devices on the functions of the nervous system selected elements].

    PubMed

    Politański, Piotr; Bortkiewicz, Alicja; Zmyślony, Marek

    2016-01-01

    Nervous system is the most "electric" system in the human body. The research of the effects of electromagnetic fields (EMFs) of different frequencies on its functioning have been carried out for years. This paper presents the results of the scientific literature review on the EMF influence on the functioning of the human nervous system with a particular emphasis on the recent studies of the modern wireless communication and data transmission systems. In the majority of the analyzed areas the published research results do not show EMF effects on the nervous system, except for the influence of GSM telephony signal on resting EEG and EEG during patients' sleep and the influence of radiofrequency EMF on the cardiovascular regulation. In other analyzed areas (EMF impact on sleep, the evoked potentials and cognitive processes), there are no consistent results supporting any influence of electromagnetic fields. Neurophysiological studies of the effect of radio- and microwaves on the brain functions in humans are still considered inconclusive. This is among others due to, different exposure conditions, a large number of variables tested, deficiencies in repeatability of research and statistical uncertainties. However, methodological guidelines are already available giving a chance of unifying research that definitely needs to be continued in order to identify biophysical mechanisms of interaction between EMFs and the nervous system. One of the EMF research aspects, on which more and more attention is paid, are inter-individual differences. Med Pr 2016;67(3):411-421. PMID:27364114

  6. Effect of Muslim Prayer (Salat) on α Electroencephalography and Its Relationship with Autonomic Nervous System Activity

    PubMed Central

    Doufesh, Hazem; Ismail, Noor Azina; Wan Ahmad, Wan Azman

    2014-01-01

    Abstract Objectives: This study investigated the effect of Muslim prayer (salat) on the α relative power (RPα) of electroencephalography (EEG) and autonomic nervous activity and the relationship between them by using spectral analysis of EEG and heart rate variability (HRV). Methods: Thirty healthy Muslim men participated in the study. Their electrocardiograms and EEGs were continuously recorded before, during, and after salat practice with a computer-based data acquisition system (MP150, BIOPAC Systems Inc., Camino Goleta, California). Power spectral analysis was conducted to extract the RPα and HRV components. Results: During salat, a significant increase (p<.05) was observed in the mean RPα in the occipital and parietal regions and in the normalized unit of high-frequency (nuHF) power of HRV (as a parasympathetic index). Meanwhile, the normalized unit of low-frequency (nuLF) power and LF/HF of HRV (as sympathetic indices) decreased according to HRV analyses. RPα showed a significant positive correlation in the occipital and parietal electrodes with nuHF and significant negative correlations with nuLF and LF/HF. Conclusions: During salat, parasympathetic activity increased and sympathetic activity decreased. Therefore, regular salat practices may help promote relaxation, minimize anxiety, and reduce cardiovascular risk. PMID:24827587

  7. Neuropsychological assessment for detecting adverse effects of volatile organic compounds on the central nervous system

    SciTech Connect

    Bolla, K.I. )

    1991-11-01

    Because there are no direct biological markers for the substances implicated in indoor air exposure, it is impossible to directly measure if an individual or group of individuals has been exposed to a potentially neurotoxic substance in the workplace. Behavioral changes may be the earliest and only manifestation of central nervous system (CNS) effects and are often too subtle to be revealed by routine physical or neurological examination. Neuropsychological techniques are sensitive to subtle behavioral/cognitive changes that can results from exposure to neurotoxins. These techniques consist of oral and written tests that are administered by a trained examiner on a on-to-one basis. In general, a wide variety of cognitive domains are evaluated. The typical battery generally includes assessing orientation, attention, intelligence, language, visual memory, verbal memory, perception, visuoconstruction, simple motor speed, psychomotor speed, and mood. As with most assessment techniques, the neuropsychological methods have limitations. One major drawback is the availability of appropriate norms that are used to compare the results of a specific individual. Although neuropsychological tests are sensitive to the presence of CNS involvement, they are not specific. Patterns of performance seen with specific instances of neurotoxic exposure may also be seen with a number of other diseases of the CNS such as dementia, cerebrovascular disease, hydrocephalus, or normal aging. Some of the more sensitive neuropsychological tests are presented. Interpretations of test performance as they relate to toxic effects on the CNS are discussed.

  8. Insights Into Effects of Ellagic Acid on the Nervous System: A Mini Review.

    PubMed

    Ahmed, Touqeer; Setzer, William N; Nabavi, Seyed Fazel; Orhan, Ilkay Erdogan; Braidy, Nady; Sobarzo-Sanchez, Eduardo; Nabavi, Seyed Mohammad

    2016-01-01

    Multiple lines of evidence suggest that disease-related neurodegeneration seems to be a multifactorial process that involves different cytotoxic pathways converging in cell death. Neuropathological evidence indicates that neuroinflammation, excitotoxicity, redox-active metals, increased reactive oxygen and nitrogen species, abnormalities in the activity of the ubiquitin-proteasome system, impairments in endogenous antioxidant defense mechanisms, mitochondrial dysfunction, as well as a reduction in the expression of trophic factors in neuronal tissues might play a role in the pathobiology of disease. In addition, increased expression of proapoptotic proteins, which leads to neuronal cell death, plays an important role in the onset and progression of neurodegeneration. With respect to the inefficacy of single-target drugs for the treatment of numerous neurodegenerative disorders, much attention has been paid to natural products with pluripharmacological properties as well as negligible adverse effects. Ellagic acid is known as an important natural phenolic antioxidant, that is widely found in different fruits and vegetables. Recent studies have shown that ellagic acid may invoke a spectrum of cell signaling pathways to attenuate or slow down the development of neurodegenerative disorders. Ellagic acid possesses potent neuroprotective effects through its free radical scavenging properties, iron chelation, activation of different cell signaling pathways, and mitigation of mitochondrial dysfunction. The aim of this review is to critically summarize and analyze the available literature regarding the neuroprotective effects of ellagic acid with emphasis on its molecular mechanisms of action. In addition, we also discuss the biosynthesis, sources, bioavailability, and metabolism, of ellagic acid to provide as accurately as possible the much needed information for assessment of the overall protective effects of this compound in the central nervous system. PMID:26806345

  9. Human nervous system function emulator.

    PubMed

    Frenger, P

    2000-01-01

    This paper describes a modular, extensible, open-systems design for a multiprocessor network which emulates the major functions of the human nervous system. Interchangeable hardware/software components, a socketed software bus with plug-and-play capability and self diagnostics are included. The computer hardware is based on IEEE P996.1 bus cards. Its operating system utilizes IEEE 1275 standard software. Object oriented design techniques and programming are featured. A machine-independent high level script-based command language was created for this project. Neural anatomical structures which were emulated include the cortex, brainstem, cerebellum, spinal cord, autonomic and peripheral nervous systems. Motor, sensory, autoregulatory, and higher cognitive artificial intelligence, behavioral and emotional functions are provided. The author discusses how he has interfaced this emulator to machine vision, speech recognition/speech synthesis, an artificial neural network and a dexterous hand to form an android robotic platform. PMID:10834247

  10. The effect of chronic stress on prenatal development of the central nervous system.

    PubMed

    Giordana, L N; Bozzo, A A; Cots, D S; Monedero Cobeta, I; Rolando, A; Borghi, D; Diaz, T; Gauna, H F; Romanini, M C

    2015-02-01

    The survival of developing embryos depends on the control and maintenance of homeostasis. Stress caused by chronic immobilization during pregnancy in rats may alter the normal development of the nervous system and increase susceptibility to psychiatric disorders. We investigated the effects of chronic stress on cell proliferation in the forebrains of embryos at 12 days of gestation, and in the hippocampus, dentate gyrus and cortex in embryos at 17 and 21 days of gestation. We examined serial sections of the embryonic brains of control and stressed rats at days 12, 17 and 21 of gestation. Brain sections were immunolabeled with anti-PCNA and stereological analysis was performed on 540 images. The results showed no statistical differences on days 12 and 17 of gestation in the proliferation area of the structures studied, whereas on day 21 of gestation, proliferation decreased in the cortex and dentate gyrus of embryos of the stressed group. These changes were related to decreased prolactin and increased corticosterone concentrations in the plasma. PMID:25420890

  11. Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

    2016-01-01

    Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

  12. [Gender and the effects of steroid hormones in the central nervous system].

    PubMed

    Brandt, N; Vierk, R; Fester, L; Zhou, L; Imholz, P; Rune, G M

    2014-09-01

    Degenerative diseases of the central nervous system, the incidence and prevalence of which vary between men and women, often manifest in the hippocampus. Neurosteroids are hormones that are synthesized in the CNS, and it is here that they exert their influence. Estrogen and testosterone are examples of neurosteroid hormones. In the hippocampus, an area of the brain closely associated with learning and memory, the local synthesis of estrogen in females, but not in males, is essential for the plasticity and stability of the synapses. The inhibition of estrogen synthesis in the female hippocampus causes a reduction in long-term potentiation (LTP), an electrophysiological parameter of learning and memory, thus resulting in a significant loss of synapses. In light of this, the fact that estrogen has been attributed with many neuroprotective functions in degenerative diseases of the CNS suggests that therapeutic concepts involving the use of estrogen are possibly only effective in women, but not in men. These findings similarly provide a basis for explaining the gender dimorphism that has been found in certain degenerative illnesses of the CNS. PMID:25091372

  13. Effect of mental fatigue on the central nervous system: an electroencephalography study

    PubMed Central

    2012-01-01

    Background Fatigue can be classified as mental and physical depending on its cause, and each type of fatigue has a multi-factorial nature. We examined the effect of mental fatigue on the central nervous system using electroencephalography (EEG) in eighteen healthy male volunteers. Methods After enrollment, subjects were randomly assigned to two groups in a single-blinded, crossover fashion to perform two types of mental fatigue-inducing experiments. Each experiment consisted of four 30-min fatigue-inducing 0- or 2-back test sessions and two evaluation sessions performed just before and after the fatigue-inducing sessions. During the evaluation session, the participants were assessed using EEG. Eleven electrodes were attached to the head skin, from positions F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, and O2. Results In the 2-back test, the beta power density on the Pz electrode and the alpha power densities on the P3 and O2 electrodes were decreased, and the theta power density on the Cz electrode was increased after the fatigue-inducing mental task sessions. In the 0-back test, no electrodes were altered after the fatigue-inducing sessions. Conclusions Different types of mental fatigue produced different kinds of alterations of the spontaneous EEG variables. Our findings provide new perspectives on the neural mechanisms underlying mental fatigue. PMID:22954020

  14. Effects of hypergravity exposure on the developing central nervous system: possible involvement of thyroid hormone

    NASA Technical Reports Server (NTRS)

    Sajdel-Sulkowska, E. M.; Li, G. H.; Ronca, A. E.; Baer, L. A.; Sulkowski, G. M.; Koibuchi, N.; Wade, C. E.

    2001-01-01

    The present study examined the effects of hypergravity exposure on the developing brain and specifically explored the possibility that these effects are mediated by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10 pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal body, forebrain, and cerebellum mass and neonatal and maternal thyroid status were assessed at each time point. The body mass of centrifuged neonates was comparatively lower at each time point. The mass of the forebrain and the mass of the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by 15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH) level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered, suggesting a moderate hypothyroid condition. Thus, continuous exposure of the developing rats to hypergravity during the embryonic and neonatal periods has a highly significant effect on the developing forebrain and cerebellum and neonatal thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with the hypothesized role of the thyroid hormone in mediating the effect of hypergravity in the developing central nervous system and begin to define the role of TH in the overall response of the developing organism to altered gravity.

  15. Neuroprotective effects of Nigella sativa extracts during germination on central nervous system

    PubMed Central

    Islam, Mohammad Hayatul; Ahmad, Iffat Zareen; Salman, Mohammad Tariq

    2015-01-01

    Background: Nigella sativa Linn. which has many acclaimed medicinal properties is an indigenous herbaceous plant and belongs to the Ranunculaceae family, which grows in countries bordering the Mediterranean Sea, Pakistan and India. Objective: This study was designed to investigate the effects of N. sativa seed extracts of different germination phases on the central nervous system (CNS) responses in experimental animals. Materials and Methods: Anxiolytic, locomotor activity of extracts (1 g/kg of body weight) was evaluated in both stressed and unstressed animal models and antiepileptic effect was evaluated by maximal electroshock seizure model keeping diazepam (20 mg/kg) as a positive control. Antidepressant effect was evaluated by forced swim test and tail suspension test keeping imipramine (15 mg/kg) as a positive control. Results: All tested extracts of N. sativa during different phases of germination (especially 5th day germination phase) showed significant (P < 0.001) anxiolytic effect in comparison to control. Diazepam reduced locomotor activity in control (unstressed) rats but did not show affect in stressed rats while N. sativa extracts from germination phases significantly (P < 0.001) reduced locomotor activity in unstressed as well as stressed animals. All the extracts of N. sativa from different germination phases exhibited significant (P < 0.001) reduction in various phases of epileptic seizure on comparison with the reference standard (diazepam). During antidepressant test, N. sativa extracts exhibited a slight reduction in the immobility of rats. Conclusion: During germination, especially in 5th day germination extract, N. sativa showed significant CNS depressant activity as compared to whole seeds that possibly may be due higher content of secondary metabolites produced during germination. PMID:26109765

  16. Central nervous system effects of meclizine and dimenhydrinate: evidence of acute tolerance to antihistamines.

    PubMed

    Manning, C; Scandale, L; Manning, E J; Gengo, F M

    1992-11-01

    Relative daytime drowsiness and performance impairment produced by meclizine and dimenhydrinate was assessed in 24 healthy male volunteers. Subjects received either dimenhydrinate, 100 mg, at 8:00 AM, 12:00 PM, and 4:00 PM; meclizine, 50 mg, at 8:00 AM, with placebo at 12:00 PM and 4:00 PM; or placebo at all three times in this randomized, double-blind, three-way crossover study. Impairment of mental performance was assessed by choice reaction time testing and digit symbol substitution scores. Drowsiness was self-assessed on the Stanford Sleepiness Scale and on a visual analog scale. Both antihistamines produced changes in digit symbol substitution, recognition time, and subjective assessments of sleepiness different from placebo. Expressed as change from baseline, the greatest reductions in digit symbol substitution scores after dimenhydrinate occurred 3 hours after the first dose (6.6 +/- 7) and were not different from the greatest measured change after meclizine (5.8 +/- 8), which occurred 9 hours after the dose was administered. Similar results were obtained with the other psychometric test scores. Self-rated sleepiness after dimenhydrinate was greatest 1 hour after the first dose, and was significantly greater than the largest degree of sleepiness after meclizine, which occurred at 7 hours after the dose. The effects of the first dose of dimenhydrinate on psychometric test scores were compared with the magnitude of the effects produced by subsequent doses. The magnitude of effect of the first dose of dimenhydrinate was significantly greater than the magnitude of effect produced by subsequent doses. The data suggest the possibility that acute tolerance to central nervous system impairment develops with multiple doses of dimenhydrinate. PMID:1474173

  17. Use of pupil size to determine the effect of electromagnetic acupuncture on activation level of the autonomic nervous system.

    PubMed

    Kim, Soo-Byeong; Choi, Woo-Hyuk; Liu, Wen-Xue; Lee, Na-Ra; Shin, Tae-Min; Lee, Yong-Heum

    2014-06-01

    Magnetic fields are widely considered as a method of treatment to increase the therapeutic effect when applied to acupoints. Hence, this study proposes a new method which creates significant stimulation of acupoints by using weak magnetic fields. We conducted this experiment in order to confirm the effect on the activation level of the autonomic nervous system by measuring pupil sizes in cases of stimulation by using manual acupuncture and electromagnetic acupuncture (EMA) at BL15. We selected 30 Hz of biphasic wave form with 570.1 Gauss. To confirm the biopotential by the magnetic flux density occurring in EMA that affected the activation of the autonomic nervous system, we observed the biopotential induced at the upper and the mid left and right trapezius. We observed a significant decrease in pupil size only in the EMA group (p < 0.05), thus confirming that EMA decreased the pupil size through activation of the parasympathetic nerve in the autonomic nervous system. Moreover, we confirmed that the amplitude of the biopotential which was caused by 570.1 Gauss was higher than ±20 μA. Thus, we can conclude that EMA treatment successfully activates the parasympathetic nerve in the autonomic nervous system by inducing a biotransformation by the induced biopotential. PMID:24929456

  18. Evaluation of the effects of mediastinal radiation therapy on autonomic nervous system.

    PubMed

    Hoca, Ayse; Yildiz, Metin; Ozyigit, Gokhan

    2012-12-01

    In this prospective study, the effects of mediastinal radiation therapy (RT) on autonomic nervous system (ANS) were investigated by heart rate variability (HRV) analysis that is accepted as a non-invasive indicator of ANS. Study was performed with the eligible patients had a histopathologically confirmed diagnosis of malignant disease with no known congestive heart failure, coronary heart disease, hypertension, valvular cardiac disease or arrhythmia history. Electrocardiograms of 14 voluntary patients were recorded for duration of 5 min just before and after irradiation for the first and the 15th fractions. ANS-related HRV analysis parameters were calculated as which were recommended by Task Force of ESC/NASPE (Circulation 93:1043-1065, 1996). HRV parameters that belong to pre- and post-RT treatment of patients were compared statistically. We found that there is not effect of single-dose radiation on HRV parameter. The mean RRI (782.29 ± 115.65-738.93 ± 111.01, P < 0.014) and HF power of HRVs PSD (156.94 ± 229.37-60.71 ± 77.99, P < 0.045) decreased, and LF/HF ratio (1.38 ± 0.79-2.03 ± 1.25, P < 0.039) increased significantly with 28-Gy external radiation dose. As the effect of cumulative dose was investigated on HRV parameters, the above changes were continued to increase with 30-Gy external radiation dose. We found that mediastinal RT involving heart directly in the radiation field decreased vagal and sympathetic ANS activities, and autonomic balance shifted toward sympathetic dominance. PMID:22528518

  19. Infections of the nervous system

    PubMed Central

    Parikh, Vevek; Tucci, Veronica; Galwankar, Sagar

    2012-01-01

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

  20. Effects of gender and game type on autonomic nervous system physiological parameters in long-hour online game players.

    PubMed

    Lin, Tung-Cheng

    2013-11-01

    Online game playing may induce physiological effects. However, the physical mechanisms that cause these effects remain unclear. The purpose of this study was to examine the physiological effects of long-hour online gaming from an autonomic nervous system (ANS) perspective. Heart rate variability (HRV), a valid and noninvasive electrocardiographic method widely used to investigate ANS balance, was used to measure physiological effect parameters. This study used a five-time, repeated measures, mixed factorial design. Results found that playing violent games causes significantly higher sympathetic activity and diastolic blood pressure than playing nonviolent games. Long-hour online game playing resulted in the gradual dominance of the parasympathetic nervous system due to physical exhaustion. Gaming workload was found to modulate the gender effects, with males registering significantly higher sympathetic activity and females significantly higher parasympathetic activity in the higher gaming workload group. PMID:23992474

  1. Neuropsychological assessment for detecting adverse effects of volatile organic compounds on the central nervous system.

    PubMed Central

    Bolla, K I

    1991-01-01

    Because there are no direct biological markers for the substances implicated in indoor air exposure, it is impossible to directly measure if an individual or group of individuals has been exposed to a potentially neurotoxic substance in the workplace. Behavioral changes may be the earliest and only manifestation of central nervous system (CNS) effects and are often too subtle to be revealed by routine physical or neurological examination. Neuropsychological techniques are sensitive to subtle behavioral/cognitive changes that can result from exposure to neurotoxins. These techniques consist of oral and written tests that are administered by a trained examiner on a one-to-one basis. In general, a wide variety of cognitive domains are evaluated. The typical battery generally includes assessing orientation, attention, intelligence, language, visual memory, verbal memory, perception, visuoconstruction, simple motor speed, psychomotor speed, and mood. As with most assessment techniques, the neuropsychological methods have limitations. One major drawback is the availability of appropriate norms that are used to compare the results of a specific individual. Because these tasks are greatly affected by age, intelligence, and in some instances sex, the availability of appropriate norms is mandatory to determine if the CNS has been effected. Although neuropsychological tests are sensitive to the presence of CNS involvement, they are not specific. Patterns of performance seen with specific instances of neurotoxic exposure may also be seen with a number of other diseases of the CNS such as dementia, cerebrovascular disease, hydrocephalus, or normal aging. In addition, neuropsychiatric symptoms such as anxiety and/or depression are often manifested as cognitive difficulties that will mimic the cognitive dysfunction seen with toxicity of the CNS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1821386

  2. Effects of adenosine metabolism in astrocytes on central nervous system oxygen toxicity.

    PubMed

    Chen, Yu-liang; Zhang, Ya-nan; Wang, Zhong-zhuang; Xu, Wei-gang; Li, Run-ping; Zhang, Jun-dong

    2016-03-15

    Hyperbaric oxygen (HBO) is widely used in military operations, especially underwater missions. However, prolonged and continuous inhalation of HBO can cause central nervous system oxygen toxicity (CNS-OT), which greatly limits HBO's application. The regulation of astrocytes to the metabolism of adenosine is involved in epilepsy. In our study, we aimed to observe the effects of HBO exposure on the metabolism of adenosine in the brain. Furthermore, we aimed to confirm the possible mechanism underlying adenosine's mediation of the CNS-OT. Firstly, anesthetized rats exposed to 5 atm absolute HBO for 80 min. The concentrations of extracellular adenosine, ATP, ADP, and AMP were detected. Secondly, free-moving rats were exposed to HBO at the same pressure for 20 min, and the activities of 5'-nucleotidase and ADK in brain tissues were measured. For the mechanism studies, we observed the effects of a series of different doses of drugs related to adenosine metabolism on the latency of CNS-OT. Results showed HBO exposure could increase adenosine content by inhibiting ADK activity and improving 5'-nucleotidase activity. And adenosine metabolism during HBO exposure may be a protective response against HBO-induced CNS-OT. Moreover, the improvement of adenosine concentration, activation of adenosine A1R, or suppression of ADK and adenosine A2AR, which are involved in the prevention of HBO-induced CNS-OT. This is the first study to demonstrate HBO exposure regulated adenosine metabolism in the brain. Adenosine metabolism and adenosine receptors are related to HBO-induced CNS-OT development. These results will provide new potential targets for the termination or the attenuation of CNS-OT. PMID:26806404

  3. HIV Infection Seems to Affect Nervous System

    MedlinePlus

    ... fullstory_159344.html HIV Infection Seems to Affect Nervous System But symptoms tend to subside once antiretroviral drugs ... mild, it is clear that HIV affects the nervous system within days of infection," she said in a ...

  4. Aging changes in the nervous system

    MedlinePlus

    ... ency/article/004023.htm Aging changes in the nervous system To use the sharing features on this page, please enable JavaScript. The brain and nervous system are your body's central control center. They control ...

  5. Effects of rat cytomegalovirus on the nervous system of the early rat embryo.

    PubMed

    Sun, Xiuning; Guan, YingJun; Li, Fengjie; Li, Xutong; Wang, Xiaowen; Guan, Zhiyu; Sheng, Kai; Yu, Li; Liu, Zhijun

    2012-08-01

    The purpose of the study was to investigate the impact of rat cytomegalovirus (RCMV) infection on the development of the nervous system in rat embryos, and to evaluate the involvement of Wnt signaling pathway key molecules and the downstream gene neurogenin 1 (Ngn1) in RCMV infected neural stem cells (NSCs). Infection and control groups were established, each containing 20 pregnant Wistar rats. Rats in the infection group were inoculated with RCMV by intraperitoneal injection on the first day of pregnancy. Rat E20 embryos were taken to evaluate the teratogenic rate. NSCs were isolated from E13 embryos, and maintained in vitro. We found: 1) Poor fetal development was found in the infection group with low survival and high malformation rates. 2) The proliferation and differentiation of NSCs were affected. In the infection group, NSCs proliferated more slowly and had a lower neurosphere formation rate than the control. The differentiation ratio from NSCs to neurons and glial cells was significantly different from that of the control, showed by immunofluorescence staining. 3) Ngn1 mRNA expression and the nuclear β-catenin protein level were significantly lower than the control on day 2 when NSCs differentiated. 4) The Morris water maze test was performed on 4-week pups, and the infected rats were found worse in learning and memory ability. In a summary, RCMV infection caused abnormalities in the rat embryonic nervous system, significantly inhibited NSC proliferation and differentiation, and inhibited the expression of key molecules in the Wnt/β-catenin signaling pathway so as to affect NSCs differentiation. This may be an important mechanism by which RCMV causes embryonic nervous system abnormalities. PMID:22899431

  6. 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,…

  7. Effect of the sympathetic nervous system co-transmitters ATP and norepinephrine on thermoregulatory response to cooling

    PubMed Central

    Kozyreva, Tamara V; Meyta, Ekaterina S; Khramova, Galina M

    2015-01-01

    The existence of co-transmitters of the sympathetic nervous system norepinephrine (NE) and ATP implies variations in the neuromodulator mechanisms of physiological processes. The role of ATP, as a transmitter of the peripheral part of sympathetic nervous system in the formation of thermoregulatory response is not clear. Whether ATP modulates any parameters of thermoregulatory response to cold; if yes, whether co-transmitters of sympathetic nervous system ATP and NE differently modulate thermoregulatory response and on which parameters of cold-defense response the influence of ATP is more pronounced. Experiments were carried out on rats. ATP (10−6), NE (10−3), and their mixture introduced iontophoretically into skin. Their effects on thermoregulatory parameters (temperature parameters, total oxygen consumption, carbon dioxide release, muscle activity, respiratory coefficient) were studied in thermoneutral conditions (without cold load) and under the cooling. In thermoneutral conditions both ATP and NE enhance total metabolism through increase in metabolic rate of lipids, NE effect being more expressed. It was shown that ATP and NE influence predominantly on the different components of the metabolic response to cold. ATP affects to the greatest extent on cold muscular thermogenesis by increasing shivering almost twofold and lowering its initiation temperature thresholds, whereas NE mainly promotes increase in non-shivering thermogenesis. When introducing the mixture of these biological substances the effect of NE is more expressed and the ATP effect is weakened. The obtained results allow to suggest that in vivo the NE effects can be more expressed when the sympathetic nervous system is stimulated by cold. Thus, NE and ATP being co-transmitters and predominantly acting on the different processes of cold thermogenesis (ATP on shivering and NE on non-shivering) may organize the certain sequence of cold defense responses.

  8. Effect of a botanical composition, UP446, on respiratory, cardiovascular and central nervous systems in beagle dogs and rats.

    PubMed

    Yimam, Mesfin; Lee, Young Chul; Jia, Qi

    2016-06-01

    Extensive safety evaluation of UP446, a botanical composition comprised of standardized extracts from roots of Scutellaria baicalensis and heartwoods of Acacia catechu, has been reported previously. Here we carried out additional studies to assess the effect of UP446 on respiratory, cardiovascular and central nervous (CNS) systems. A Functional observational battery (FOB) and whole body plethysmography system in rats and implanted telemetry in dogs were utilized to evaluate the potential CNS, respiratory and cardiovascular toxicity, respectively. UP446 was administered orally at dose levels of 800, 2000 and 5000 mg/kg to SpragueDawley rats and at 4 ascending dose levels (0, 250, 500 and 1000 mg/kg) to beagle dogs. No abnormal effects were observed on the cage side, open field, hand held, and sensori-motor observations suggestive of toxicity in respiratory, cardiovascular and central nervous (CNS) systems. Rectal temperatures were comparable for each treatment groups. Similarly, respiratory rate, tidal volume and minute volume were unaffected by any of the treatment groups. No UP446 related changes were observed on blood pressure, heart rate and electrocardiogram in beagle dogs at dose levels of 250, 500 and 1000 mg/kg. Some minor incidental, non-dose correlated changes were observed in the FOB assessment. These data suggest that UP446 has minimal or no pharmaco-toxicological effect on the respiratory, cardiovascular and central nervous systems. PMID:27012374

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

    NASA Technical Reports Server (NTRS)

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

    2013-01-01

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

  10. Enhancement of the white matter following prophylactic therapy of the central nervous system for leukemia: radiation effects and methotrexate leukoencephalopathy

    SciTech Connect

    Shalen, P.R.; Ostrow, P.T.; Glass, P.J.

    1981-08-01

    The authors report a case of fatal necrotizing leukoencephalopathy following prophylactic therapy of the central nervous system for acute lymphoblastic leukemia. The clinical, CT, and neuropathological findings are described. The CT scan demonstrated symmetrical white-matter enhancement. Histological analysis was consistent with the effects of irradiation and methotrexate. The differential diagnosis of the clinical and CT findings is discussed. Brain biopsy is the diagnostic procedure of choice.

  11. Infections of the nervous system.

    PubMed

    Pruitt, A A

    1998-05-01

    Epidemiologic trends causing infections of the nervous system remain a significant source of morbidity and mortality one half-century after the introduction of penicillin. This article outlines common causes of bacterial meningitis, aseptic meningitis syndrome, encephalitis, abscess, spinal cord syndromes, and cranial and peripheral nerve problems. Recommendations for diagnostic evaluation and both empiric and definitive antimicrobial therapy are offered; controversial management issues are also discussed. The protean manifestations of varicella-zoster virus and Lyme diseases are outlined. In addition, special considerations in the immunocompromised host, including organ transplant recipients, cancer patients, and HIV-positive persons are explained, and antimicrobial therapy is discussed. PMID:9537969

  12. Glucocorticoids and nervous system plasticity

    PubMed Central

    Madalena, Kathryn M.; Lerch, Jessica K.

    2016-01-01

    Glucocorticoid and glucocorticoid receptor (GC/GR) interactions alter numerous aspects of neuronal function. These consequences (e.g., anti-inflammatory vs. pro-inflammatory) can vary depending on the duration of GC exposure or central nervous system (CNS) injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new findings on gender specific immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing. PMID:26981074

  13. Effect of 100 Hz electroacupuncture on salivary immunoglobulin A and the autonomic nervous system

    PubMed Central

    Hideaki, Waki; Tatsuya, Hisajima; Shogo, Miyazaki; Naruto, Yoshida; Hideaki, Tamai; Yoichi, Minakawa; Yoshihiro, Okuma; Kazuo, Uebaba; Hidenori, Takahashi

    2015-01-01

    Background A previous study has reported that low-frequency (LF) electroacupuncture (EA) influences salivary secretory immunoglobulin A (sIgA) and the autonomic nervous system (ANS). The ANS is known to control the secretion volume of sIgA; however, the effect of high-frequency (HF) EA on salivary sIgA has not been determined. We investigated whether HF EA affects salivary sIgA levels and the ANS. Method Sixteen healthy subjects were randomly classified into two groups: a control group and an EA group. After a 5 min rest, subjects in the EA group received EA at 100 Hz bilaterally at LI4 and LI11 for 15 min before resting for a further 40 min post-stimulation. Subjects in the control group rested for a total of 60 min. Measurements of the ANS and sIgA levels in both groups were made before, immediately after, 20 min after, and 40 min after rest or 15 min EA treatment. HF and LF components of heart rate variability were analysed as markers of ANS function. LF/HF ratio and HF were taken as indices of sympathetic and parasympathetic nerve activity, respectively. Salivary protein concentrations and sIgA levels were determined by Bradford protein assay and ELISA, respectively. Results LF/HF ratio was significantly increased immediately after EA. HF was significantly increased at 20 min after EA and sIgA level was significantly increased at 40 min after EA. In addition, HF and salivary sIgA level were positively correlated with each another. Conclusions HF EA exerted sequential positive effects on sympathetic nerve activity, parasympathetic nerve activity, and salivary sIgA level (immediately and after 20 and 40 min, respectively). HF EA may increase salivary sIgA levels by influencing parasympathetic nerve activity. PMID:26449884

  14. Gene-Chemical Interactions in the Developing Mammalian Nervous System: Effects on Proliferation, Neurogenesis and Differentiation

    PubMed Central

    Fox, Donald A.; Opanashuk, Lisa; Zharkovsky, Aleksander; Weiss, Bernie

    2010-01-01

    The orderly formation of the nervous system requires a multitude of complex, integrated and simultaneously occurring processes. Neural progenitor cells expand through proliferation, commit to different cell fates, exit the cell cycle, generate different neuronal and glial cell types, and new neurons migrate to specified areas and establish synaptic connections. Gestational and perinatal exposure to environmental toxicants, pharmacological agents and drugs of abuse produce immediate, persistent or late-onset alterations in behavioral, cognitive, sensory and/or motor functions. These alterations reflect the disruption of the underlying processes of CNS formation and development. To determine the neurotoxic mechanisms that underlie these deficits it is necessary to analyze and dissect the complex molecular processes that occur during the proliferation, neurogenesis and differentiation of cells. This symposium will provide a framework for understanding the orchestrated events of neurogenesis, the coordination of proliferation and cell fate specification by selected genes, and the effects of well-known neurotoxicants on neurogenesis in the retina, hippocampus and cerebellum. These three tissues share common developmental profiles, mediate diverse neuronal activities and function, and thus provide important substrates for analysis. This paper summarizes four invited talks that were presented at the 12th International Neurotoxicology Association meeting held in Jerusalem, Israel during the summer of 2009. Donald A. Fox described the structural and functional alterations following low-level gestational lead exposure in children and rodents that produced a supernormal electroretinogram and selective increases in neurogenesis and cell proliferation of late-born retinal neurons (rod photoreceptors and bipolar cells), but not Müller glia cells, in mice. Lisa Opanashuk discussed how dioxin [TCDD] binding to the arylhydrocarbon receptor [AhR], a transcription factor that

  15. Factors Predicting the Effects of Hybrid Assistive Limb Robot Suit during the Acute Phase of Central Nervous System Injury

    PubMed Central

    CHIHARA, Hideo; TAKAGI, Yasushi; NISHINO, Kazunari; YOSHIDA, Kazumichi; ARAKAWA, Yoshiki; KIKUCHI, Takayuki; TAKENOBU, Yohei; MIYAMOTO, Susumu

    2016-01-01

    To improve the activities of daily living of patients with injury to the central nervous system, physical therapy starting from the acute phase of the injury is important. Recently, the efficacy of physical therapy using a hybrid assistive limb (HAL) robot suit was reported. However, individual differences exist in the effects of HAL. We investigated factors predicting the effects of HAL in 15 patients at our institution with central nervous system injury, primarily due to stroke, who underwent training using HAL during the acute phase. Patients were classified as either “with HAL suitability” or “without HAL suitability” based on scores from 10-m walking speed, gait, satisfaction, and pain. In both groups, Brunnstrom stage before HAL intervention, Fugl-Meyer assessment (FMA), stroke impairment assessment set (SIAS), and functional independence measure (FIM) were evaluated. Although motor function items did not differ significantly, FIM cognitive function items (P = 0.036), visuospatial perception items on SIAS (P = 0.0277), and pain items on SIAS (P = 0.0122) differed significantly between groups. These results indicated that training using HAL does not involve pain in patients with central nervous system injury during the acute phase, and exhibits positive effects in patients without pain and with high communication ability and visuospatial perception function. When conducting HAL intervention, incorporating functional assessment scores (FIM and SIAS), including peripheral items, may be useful to predict the suitability of HAL. PMID:26538291

  16. Aquaporin Biology and Nervous System

    PubMed Central

    Barbara, Buffoli

    2010-01-01

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

  17. Systemic effects of low-power laser irradiation on the peripheral and central nervous system, cutaneous wounds, and burns

    SciTech Connect

    Rochkind, S.; Rousso, M.; Nissan, M.; Villarreal, M.; Barr-Nea, L.; Rees, D.G.

    1989-01-01

    In this paper, we direct attention to the systemic effect of low-power helium-neon (HeNe) laser irradiation on the recovery of the injured peripheral and central nervous system, as well as healing of cutaneous wounds and burns. Laser irradiation on only the right side in bilaterally inflicted cutaneous wounds enhanced recovery in both sides compared to the nonirradiated control group (P less than .01). Similar results were obtained in bilateral burns: irradiating one of the burned sites also caused accelerated healing in the nonirradiated site (P less than .01). However, in the nonirradiated control group, all rats suffered advanced necrosis of the feet and bilateral gangrene. Low-power HeNe laser irradiation applied to a crushed injured sciatic nerve in the right leg in a bilaterally inflicted crush injury, significantly increased the compound action potential in the left nonirradiated leg as well. The statistical analysis shows a highly significant difference between the laser-treated group and the control nonirradiated group (P less than .001). Finally, the systemic effect was found in the spinal cord segments corresponding to the crushed sciatic nerves. The bilateral retrograde degeneration of the motor neurons of the spinal cord expected after the bilateral crush injury of the peripheral nerves was greatly reduced in the laser treated group. The systemic effects reported here are relevant in terms of the clinical application of low-power laser irradiation as well as for basic research into the possible mechanisms involved.

  18. The effects of constrained left versus right monocular viewing on the autonomic nervous system.

    PubMed

    Burtis, D Brandon; Heilman, Kenneth M; Mo, Jue; Wang, Chao; Lewis, Gregory F; Davilla, Maria I; Ding, Mingzhou; Porges, Stephen W; Williamson, John B

    2014-07-01

    Asymmetrical activation of right and left hemispheres differentially influences the autonomic nervous system. Additionally, each hemisphere primarily receives retinocollicular projections from the contralateral eye. To learn if asymmetrical hemispheric activation induced by monocular viewing would influence relative pupillary size and respiratory hippus variability (RHV), a measure of parasympathetic activity, healthy participants had their left, right or neither eye patched. Pupillary sizes were then recorded with infrared pupillography. Pupillary dilation was significantly greater with left than right eye viewing. RHV, however, was not different between eye viewing conditions. These differences in pupil dilatation may have been caused by relatively greater activation of the right hemispheric-mediated sympathetic activity induced by left monocular viewing or relatively greater deactivation of the left hemispheric-mediated parasympathetic activity induced by right eye patching. The absence of an asymmetry in RHV, however, suggests that hemispheric asymmetry of sympathetic activation was primarily responsible for this ocular asymmetry of pupil dilation. PMID:24878321

  19. The Effects of Constrained Left versus Right Monocular Viewing on the Autonomic Nervous System

    PubMed Central

    Burtis, D. Brandon; Heilman, Kenneth M.; Mo, Jue; Wang, Chao; Lewis, Gregory F.; Davilla, Maria I.; Ding, Mingzhou; Porges, Stephen W.; Williamson, John B.

    2014-01-01

    Asymmetrical activation of right and left hemispheres differentially influences the autonomic nervous system. Additionally, each hemisphere primarily receives retinocollicular projections from the contralateral eye. To learn if asymmetrical hemispheric activation induced by monocular viewing would influence relative pupillary size and respiratory hippus variability (RHV), a measure of parasympathetic activity, healthy participants had their left, right or neither eye patched. Pupillary sizes were then recorded with infrared pupillography. Pupillary dilation was significantly greater with left than right eye viewing. RHV, however, was not different between eye viewing conditions. These differences in pupil dilatation may have been caused by relatively greater activation of the right hemispheric-mediated sympathetic activity induced by left monocular viewing or relatively greater deactivation of the left hemispheric-mediated parasympathetic activity induced by right eye patching. The absence of an asymmetry in RHV, however, suggests that hemispheric asymmetry of sympathetic activation was primarily responsible for this ocular asymmetry of pupil dilation. PMID:24878321

  20. Effect of insulin-induced hypoglycaemia on the central nervous system: evidence from experimental studies.

    PubMed

    Jensen, V F H; Bøgh, I B; Lykkesfeldt, J

    2014-03-01

    Insulin-induced hypoglycaemia (IIH) is a major acute complication in type 1 as well as in type 2 diabetes, particularly during intensive insulin therapy. The brain plays a central role in the counter-regulatory response by eliciting parasympathetic and sympathetic hormone responses to restore normoglycaemia. Brain glucose concentrations, being approximately 15-20% of the blood glucose concentration in humans, are rigorously maintained during hypoglycaemia through adaptions such as increased cerebral glucose transport, decreased cerebral glucose utilisation and, possibly, by using central nervous system glycogen as a glucose reserve. However, during sustained hypoglycaemia, the brain cannot maintain a sufficient glucose influx and, as the cerebral hypoglycaemia becomes severe, electroencephalogram changes, oxidative stress and regional neuronal death ensues. With particular focus on evidence from experimental studies on nondiabetic IIH, this review outlines the central mechanisms behind the counter-regulatory response to IIH, as well as cerebral adaption to avoid sequelae of cerebral neuroglycopaenia, including seizures and coma. PMID:24428753

  1. [Primary central nervous system vasculitis].

    PubMed

    Schuster, S; Magnus, T

    2015-12-01

    Primary angiitis of the central nervous system (PACNS) is a rare disorder. However, it is often considered in the differential diagnosis of vascular or inflammatory CNS diseases. Diagnosis is challenging, as specific biomarkers are lacking and the clinical presentation can be variable. A definitive diagnosis can only be established by biopsy of the inflammatory changes in the vascular wall. Alternatively, the diagnosis of PACNS can also be based on the synopsis of clinical, radiological, and laboratory findings. Different subtypes of PACNS have been described in recent years, depending on the size of the affected vessels or histopathological patterns. Based on selective literature research in the database PubMed on the subject of CNS vasculitis, this article reviews the diagnostic characteristics and differential diagnosis of the condition. We suggest a diagnostic algorithm customized to the size of the affected vessels. Lastly, therapeutic options and the outcome of PACNS are briefly outlined. PMID:26589203

  2. Regeneration in the nervous system with erythropoietin

    PubMed Central

    Maiese, Kenneth

    2015-01-01

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

  3. Peripheral Nervous System Manifestations of Infectious Diseases

    PubMed Central

    Brizzi, Kate T.

    2014-01-01

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

  4. Selective and antigen-dependent effects of myelin degeneration on central nervous system inflammation.

    PubMed

    Aboul-Enein, Fahmy; Bauer, Jan; Klein, Matthias; Schubart, Anna; Flügel, Alexander; Ritter, Thomas; Kawakami, Naoto; Siedler, Frank; Linington, Christopher; Wekerle, Hartmut; Lassmann, Hans; Bradl, Monika

    2004-12-01

    Damage to myelin sheath or oligodendrocytes may precede or even provoke inflammation of the central nervous system (CNS), but the extent to which these degenerative changes affect inflammation remains largely undefined. To study these processes in more detail, we used CNS antigen-specific T cells in the presence or absence of anti-myelin antibodies to induce experimental autoimmune encephalomyelitis (EAE) in transgenic Lewis rats with low-grade subclinical myelin degeneration and associated microglia cell activation, and in wild-type Lewis rats with an intact CNS. We found that myelin degeneration affects the localization of inflammatory lesions, the numbers of T cells recruited to these lesions, and the severity of the resulting clinical disease. In addition, myelin degeneration and associated microglia cell activation jointly enhance the susceptibility of the CNS to the action of anti-myelin antibodies. Our data show that even subtle alterations of myelin and oligodendrocytes may massively amplify the extent of demyelination and tissue damage, involving different immune effector mechanisms. A similar causal relationship might also operate in human patients with multiple sclerosis, where T cell-mediated inflammation and antibody-mediated demyelination have been documented, and where genetic factors might determine the susceptibility of the target tissue for immune-mediated injury. PMID:15624765

  5. Effects of diving and oxygen on autonomic nervous system and cerebral blood flow.

    PubMed

    Winklewski, Pawel J; Kot, Jacek; Frydrychowski, Andrzej F; Nuckowska, Magdalena K; Tkachenko, Yurii

    2013-09-01

    Recreational scuba diving is a popular leisure activity with the number of divers reaching several millions worldwide. Scuba diving represents a huge challenge for integrative physiology. In mammalian evolution, physiological reflexes developed to deal with lack of oxygen, rather than with an excess, which makes adaptations to scuba diving more difficult to describe and understand than those associated with breath-hold diving. The underwater environment significantly limits the use of equipment to register the organism's functions, so, in most instances, scientific theories are built on experiments that model real diving to some extent, like hyperbaric exposures, dive reflexes or water immersion. The aim of this review is to summarise the current knowledge related to the influence exerted by physiological conditions specific to diving on the autonomic nervous system and cerebral blood flow. The main factors regulating cerebral blood flow during scuba diving are discussed as follows: 1) increased oxygen partial pressure; 2) immersion-related trigemino-cardiac reflexes and 3) exposure to cold, exercise and stress. Also discussed are the potential mechanisms associated with immersion pulmonary oedema. PMID:24122190

  6. Bendiocarb effect on liver and central nervous system in the chick embryo.

    PubMed

    Petrovova, Eva; Sedmera, David; Lesnik, Frantisek; Luptakova, Lenka

    2009-05-01

    The aim of the study was to investigate toxicity of bendiocarb (2, 3-isopropyledene-dioxyphenyl methylcarbamate) to organs of chicken embryo. The toxic action of bendiocarb was observed on liver and central nervous system (CNS). Bendiocarb was administered to chicken embryos at embryonic day (ED) 3 in a dose 500 microg/egg and 10 ED (800 microg/egg). The observations showed no macroscopic or microscopic changes in the liver and CNS with either dose or day of incubation when the bendiocarb was administered. The liver and CNS were also investigated for caspase activity in relation to application of bendiocarb and no differences in the number of cells with caspase immunopositivity were observed in comparison with the control. The results obtained indicate that bendiocarb administered in the respective doses showed no toxicity to investigated organs. Furthermore, both at the early (3 ED) and the later (10 ED) stages of development no increase in numbers of apoptotic cells in chicken embryos was observed. PMID:19365755

  7. Delayed Effects of Whole Brain Radiotherapy in Germ Cell Tumor Patients With Central Nervous System Metastases

    SciTech Connect

    Doyle, Danielle M. Einhorn, Lawrence H.

    2008-04-01

    Purpose: Central nervous system (CNS) metastases are uncommon in patients with germ cell tumors, with an incidence of 2-3%. CNS metastases have been managed with whole brain radiotherapy (WBRT) and concomitant cisplatin-based combination chemotherapy. Our previous study did not observe serious CNS toxicity (Int J Radiat Oncol Biol Phys 1991;22:17-22). We now report on 5 patients who developed delayed significant CNS toxicity. Patients and Methods: We observed 5 patients with delayed CNS toxicity. The initial diagnosis was between 1981 and 2003. All patients had poor-risk disease according to the International Germ Cell Consensus Collaborative Group criteria. Of the 5 patients, 3 had CNS metastases at diagnosis and 2 developed relapses with CNS metastases. These 5 patients underwent WBRT to 4,000-5,000 cGy in 18-28 fractions concurrently with cisplatin-based chemotherapy. Results: All 5 patients developed delayed symptoms consistent with progressive multifocal leukoencephalopathy. The symptoms included seizures, hemiparesis, cranial neuropathy, headaches, blindness, dementia, and ataxia. The median time from WBRT to CNS symptoms was 72 months (range, 9-228). Head imaging revealed multiple abnormalities consistent with gliosis and diffuse cerebral atrophy. Of the 5 patients, 3 had progressive and 2 stable symptoms. Treatment with surgery and/or steroids had modest benefit. The progressive multifocal leukoencephalopathy resulted in significant debility in all 5 patients, resulting in death (3 patients), loss of work, steroid-induced morbidity, and recurrent hospitalizations. Conclusion: Whole brain radiotherapy is not innocuous in young patients with germ cell tumors and can cause late CNS toxicity.

  8. [Effects of inorganic lead exposure on the autonomic nervous system and on the variability of heart rate among workers at a battery plant].

    PubMed

    Muzi, G; Murgia, N; Dell'Omo, M; Fiordi, T; Sposini, F; Argentino, A; Apostoli, P; Abbritti, G

    2005-01-01

    Inorganic Lead can cause a toxic effect on Central Nervous System, Peripheral Nervous System and Autonomic Nervous System (ANS). A damage of the ANS can determine an heart rate variability (HRV) reduction. In this study 43 battery workers exposed to inorganic lead with mean PbB = 31.63 microg/dl (DS 14.77 microg/dl) and 35 not exposed subjects underwent to an evaluation of heart rate variability by specific tests. Heart rate variability in the exposed group was, for some tests (lying to standing, lying to standing-standing to lying) reduced compared with not exposed subjects and for other tests (Valsalva manouvre, lying to standing-standing to lying) correlated with PbB and Zinc Protoporphyrin (ZPP), but not with BMI, age and smoking habits. This study, like others conducted on similar populations, suggest an effect of occupational inorganic lead exposure on Autonomic Nervous System and heart rate variability PMID:15915655

  9. Autonomic nervous system-mediated effects of galanin-like peptide on lipid metabolism in liver and adipose tissue.

    PubMed

    Hirako, Satoshi; Wada, Nobuhiro; Kageyama, Haruaki; Takenoya, Fumiko; Izumida, Yoshihiko; Kim, Hyounju; Iizuka, Yuzuru; Matsumoto, Akiyo; Okabe, Mai; Kimura, Ai; Suzuki, Mamiko; Yamanaka, Satoru; Shioda, Seiji

    2016-01-01

    Galanin-like peptide (GALP) is a neuropeptide involved in the regulation of feeding behavior and energy metabolism in mammals. While a weight loss effect of GALP has been reported, its effects on lipid metabolism have not been investigated. The aim of this study was to determine if GALP regulates lipid metabolism in liver and adipose tissue via an action on the sympathetic nervous system. The respiratory exchange ratio of mice administered GALP intracerebroventricularly was lower than that of saline-treated animals, and fatty acid oxidation-related gene mRNA levels were increased in the liver. Even though the respiratory exchange ratio was reduced by GALP, this change was not significant when mice were treated with the sympatholytic drug, guanethidine. Lipolysis-related gene mRNA levels were increased in the adipose tissue of GALP-treated mice compared with saline-treated animals. These results show that GALP stimulates fatty acid β-oxidation in liver and lipolysis in adipose tissue, and suggest that the anti-obesity effect of GALP may be due to anorexigenic actions and improvement of lipid metabolism in peripheral tissues via the sympathetic nervous system. PMID:26892462

  10. Autonomic nervous system-mediated effects of galanin-like peptide on lipid metabolism in liver and adipose tissue

    PubMed Central

    Hirako, Satoshi; Wada, Nobuhiro; Kageyama, Haruaki; Takenoya, Fumiko; Izumida, Yoshihiko; Kim, Hyounju; Iizuka, Yuzuru; Matsumoto, Akiyo; Okabe, Mai; Kimura, Ai; Suzuki, Mamiko; Yamanaka, Satoru; Shioda, Seiji

    2016-01-01

    Galanin-like peptide (GALP) is a neuropeptide involved in the regulation of feeding behavior and energy metabolism in mammals. While a weight loss effect of GALP has been reported, its effects on lipid metabolism have not been investigated. The aim of this study was to determine if GALP regulates lipid metabolism in liver and adipose tissue via an action on the sympathetic nervous system. The respiratory exchange ratio of mice administered GALP intracerebroventricularly was lower than that of saline-treated animals, and fatty acid oxidation-related gene mRNA levels were increased in the liver. Even though the respiratory exchange ratio was reduced by GALP, this change was not significant when mice were treated with the sympatholytic drug, guanethidine. Lipolysis-related gene mRNA levels were increased in the adipose tissue of GALP-treated mice compared with saline-treated animals. These results show that GALP stimulates fatty acid β-oxidation in liver and lipolysis in adipose tissue, and suggest that the anti-obesity effect of GALP may be due to anorexigenic actions and improvement of lipid metabolism in peripheral tissues via the sympathetic nervous system. PMID:26892462

  11. Stress, sex, and the enteric nervous system.

    PubMed

    Million, M; Larauche, M

    2016-09-01

    Made up of millions of enteric neurons and glial cells, the enteric nervous system (ENS) is in a key position to modulate the secretomotor function and visceral pain of the gastrointestinal tract. The early life developmental period, through which most of the ENS development occurs, is highly susceptible to microenvironmental perturbation. Over the past decade, accumulating evidence has shown the impact of stress and early life adversity (ELA) on host gastrointestinal pathophysiology. While most of the focus has been on alterations in brain structure and function, limited experimental work in rodents suggest that the enteric nervous system can also be directly affected, as shown by changes in the number, phenotype, and reactivity of enteric nerves. The work of Medland et al. in the current issue of this journal demonstrates that such alterations also occur in pigs, a larger mammalian species with high translational value to human. This work also highlights a sex-differential susceptibility of the ENS to the effect of ELA, which could contribute to the higher prevalence of GI disorders in women. In this mini-review, we will discuss the development and composition of the ENS and related gastrointestinal sensory motor and secretory functions. We will then focus on the influence of stress on the enteric nervous system, with a particular emphasis on neurodevelopmental changes. Finally, we will discuss the influence of sex on those parameters. PMID:27561694

  12. Effects of sarin on the nervous system of subway workers seven years after the Tokyo subway sarin attack.

    PubMed

    Miyaki, Koichi; Nishiwaki, Yuji; Maekawa, Kazuhiko; Ogawa, Yasutaka; Asukai, Nozomu; Yoshimura, Kimio; Etoh, Norihito; Matsumoto, Yukio; Kikuchi, Yuriko; Kumagai, Nami; Omae, Kazuyuki

    2005-07-01

    This study was designed to assess the after effects of sarin exposure on the nervous system in victims of the Tokyo Subway Sarin Attack, which occurred on 20 March, 1995. We performed a similar study 3 yr after the disaster. This time, we newly enrolled 36 staff of the Teito Rapid Transit Authority (Tokyo Eidan subway) to assess the 7 yr after effects on the nervous system, and merged previous data including unpublished data to enhance statistical power. New subjects consisted of 23 male exposed subjects and 13 referent subjects matched for age and working types. Neurobehavioral tests for psychomotor function and memory, stabilometry, and Benton visual retention test were performed. As reported previously, the exposed group performed significantly less well in the psychomotor function test (tapping) than the referent group (117.8 +/- 1.2 vs. 105.6 +/- 1.2 msec). Using merged data, this phenomenon was also observed in a dose-dependent manner and the exposed group performed significantly less well in the backward digit span test (4.47 +/- 1.17 vs. 5.11 +/- 1.65 digits). These results indicate that chronic decline of psychomotor function and memory function still exist 7 yr after the sarin exposure. PMID:16096354

  13. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

    SciTech Connect

    Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J. )

    1990-10-15

    Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy.

  14. Central Nervous System Complications of Oncologic Therapy.

    PubMed

    Hoeffner, Ellen G

    2016-08-01

    Traditional and newer agents used to treat cancer can cause significant toxicity to the central nervous system. MRI of the brain and spine is the imaging modality of choice for patients with cancer who develop neurologic symptoms. It is important to be aware of the agents that can cause neurotoxicity and their associated imaging findings so that patients are properly diagnosed and treated. In some instances conventional MRI may not be able to differentiate posttreatment effects from disease progression. In these instances advanced imaging techniques may be helpful, although further research is still needed. PMID:27444003

  15. Adverse effects of cigarette and noncigarette smoke exposure on the autonomic nervous system: mechanisms and implications for cardiovascular risk.

    PubMed

    Middlekauff, Holly R; Park, Jeanie; Moheimani, Roya S

    2014-10-21

    This review summarizes the detrimental effects of cigarette and noncigarette emission exposure on autonomic function, with particular emphasis on the mechanisms of acute and chronic modulation of the sympathetic nervous system. We propose that the nicotine and fine particulate matter in tobacco smoke lead to increased sympathetic nerve activity, which becomes persistent via a positive feedback loop between sympathetic nerve activity and reactive oxidative species. Furthermore, we propose that baroreflex suppression of sympathetic activation is attenuated in habitual smokers; that is, the baroreflex plays a permissive role, allowing sympathoexcitation to occur without restraint in the setting of increased pressor response. This model is also applicable to other nontobacco cigarette emission exposures (e.g., marijuana, waterpipes [hookahs], electronic cigarettes, and even air pollution). Fortunately, emerging data suggest that baroreflex sensitivity and autonomic function may be restored after smoking cessation, providing further evidence in support of the health benefits of smoking cessation. PMID:25323263

  16. Fampridine-PR (prolonged released 4-aminopyridine) is not effective in patients with inflammatory demyelination of the peripheral nervous system.

    PubMed

    Leussink, Verena-Isabell; Stettner, Mark; Warnke, Clemens; Hartung, Hans-Peter

    2016-06-01

    Fampridine-PR is a voltage-gated potassium channel inhibitor potentially improving nerve conduction in demyelinated axons. Based on its established clinical efficacy in patients with demyelination in the central nervous system, we assessed if fampridine-PR is also effective in patients with inflammatory demyelination of the peripheral nerve. In this small open-label study, 10 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were treated with fampridine-PR 10 mg BID for 28 days and assessed clinically as well as by nerve conduction studies. In this study, Fampridine-PR failed to improve CIDP based on clinical measures and nerve conduction studies. Our findings suggest that Fampridine-PR appears to be ineffective in demyelinating polyneuropathies. These observations may indicate a more complex mode of action beyond improving action potential conduction in demyelinated axons. PMID:26968589

  17. Nutritional stimulation of the autonomic nervous system.

    PubMed

    Luyer, Misha D P; Habes, Quirine; van Hak, Richard; Buurman, Wim

    2011-09-14

    Disturbance of the inflammatory response in the gut is important in several clinical diseases ranging from inflammatory bowel disease to postoperative ileus. Several feedback mechanisms exist that control the inflammatory cascade and avoid collateral damage. In the gastrointestinal tract, it is of particular importance to control the immune response to maintain the balance that allows dietary uptake and utilization of nutrients on one hand, while preventing invasion of bacteria and toxins on the other hand. The process of digestion and absorption of nutrients requires a relative hyporesponsiveness of the immune cells in the gut to luminal contents which is not yet fully understood. Recently, the autonomic nervous system has been identified as an important pathway to control local and systemic inflammation and gut barrier integrity. Activation of the pathway is possible via electrical or via pharmacological interventions, but is also achieved in a physiological manner by ingestion of dietary lipids. Administration of dietary lipids has been shown to be very effective in reducing the inflammatory cascade and maintaining intestinal barrier integrity in several experimental studies. This beneficial effect of nutrition on the inflammatory response and intestinal barrier integrity opens new therapeutic opportunities for treatment of certain gastrointestinal disorders. Furthermore, this neural feedback mechanism provides more insight in the relative hyporesponsiveness of the immune cells in the gut. Here, we will discuss the regulatory function of the autonomic nervous system on the inflammatory response and gut barrier function and the potential benefit in a clinical setting. PMID:22025873

  18. Nutritional stimulation of the autonomic nervous system

    PubMed Central

    Luyer, Misha DP; Habes, Quirine; van Hak, Richard; Buurman, Wim

    2011-01-01

    Disturbance of the inflammatory response in the gut is important in several clinical diseases ranging from inflammatory bowel disease to postoperative ileus. Several feedback mechanisms exist that control the inflammatory cascade and avoid collateral damage. In the gastrointestinal tract, it is of particular importance to control the immune response to maintain the balance that allows dietary uptake and utilization of nutrients on one hand, while preventing invasion of bacteria and toxins on the other hand. The process of digestion and absorption of nutrients requires a relative hyporesponsiveness of the immune cells in the gut to luminal contents which is not yet fully understood. Recently, the autonomic nervous system has been identified as an important pathway to control local and systemic inflammation and gut barrier integrity. Activation of the pathway is possible via electrical or via pharmacological interventions, but is also achieved in a physiological manner by ingestion of dietary lipids. Administration of dietary lipids has been shown to be very effective in reducing the inflammatory cascade and maintaining intestinal barrier integrity in several experimental studies. This beneficial effect of nutrition on the inflammatory response and intestinal barrier integrity opens new therapeutic opportunities for treatment of certain gastrointestinal disorders. Furthermore, this neural feedback mechanism provides more insight in the relative hyporesponsiveness of the immune cells in the gut. Here, we will discuss the regulatory function of the autonomic nervous system on the inflammatory response and gut barrier function and the potential benefit in a clinical setting. PMID:22025873

  19. Measurement of the effect of Isha Yoga on cardiac autonomic nervous system using short-term heart rate variability

    PubMed Central

    Muralikrishnan, Krishnan; Balakrishnan, Bhavani; Balasubramanian, Kabali; Visnegarawla, Fehmida

    2012-01-01

    Background: Beneficial effects of Yoga have been postulated to be due to modulation of the autonomic nervous system. Objective: To assess the effect of Isha Yoga practices on cardiovascular autonomic nervous system through short-term heart rate variability (HRV). Design of the Study: Short-term HRV of long-term regular healthy 14 (12 males and 2 females) Isha Yoga practitioners was compared with that of age- and gender-matched 14 (12 males and 2 females) non-Yoga practitioners. Methods and Materials: ECG Lead II and respiratory movements were recorded in both groups using Polyrite during supine rest for 5 min and controlled deep breathing for 1 minute. Frequency domain analysis [RR interval is the mean of distance between subsequent R wave peaks in ECG], low frequency (LF) power, high frequency (HF) power, LF normalized units (nu), HF nu, LF/HF ratio] and time domain analysis [Standard Deviation of normal to normal interval (SDNN), square of mean squared difference of successive normal to normal intervals (RMSSD), normal to normal intervals which are differing by 50 ms (NN50), and percentage of NN50 (pNN50)] of HRV variables were analyzed for supine rest. Time domain analysis was recorded for deep breathing. Results: Results showed statistically significant differences between Isha Yoga practitioners and controls in both frequency and time domain analyses of HRV indices, with no difference in resting heart rate between the groups. Conclusions: Practitioners of Isha Yoga showed well-balanced beneficial activity of vagal efferents, an overall increased HRV, and sympathovagal balance, compared to non-Yoga practitioners during supine rest and deep breathing. PMID:22707866

  20. Animal-microbe interactions and the evolution of nervous systems.

    PubMed

    Eisthen, Heather L; Theis, Kevin R

    2016-01-01

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

  1. Central nervous system effects of haloperidol on THC in healthy male volunteers.

    PubMed

    Liem-Moolenaar, Marieke; te Beek, Erik T; de Kam, Marieke L; Franson, Kari L; Kahn, René S; Hijman, Ron; Touw, Daan; van Gerven, Joop M A

    2010-11-01

    In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their combination were investigated in 35 healthy, male mild cannabis users, measuring Positive and Negative Syndrome Scale, Visual Analogue Scales for alertness, mood, calmness and psychedelic effects, saccadic and smooth pursuit eye measurements, electroencephalography, Body Sway, Stroop test, Visual and Verbal Learning Task, hormone levels and pharmacokinetics. Compared with placebo, THC significantly decreased smooth pursuit, Visual Analogue Scales alertness, Stroop test performance, immediate and delayed word recall and prolactin concentrations, and significantly increased positive and general Positive and Negative Syndrome Scale score, Visual Analogue Scales feeling high, Body Sway and electroencephalography alpha. Haloperidol reversed the THC-induced positive Positive and Negative Syndrome Scale increase to levels observed with haloperidol alone, but not THC-induced 'high' feelings. Compared with placebo, haloperidol significantly decreased saccadic peak velocity, smooth pursuit, Visual Analogue Scales mood and immediate and delayed word recall and significantly increased Body Sway, electroencephalography theta and prolactin levels. THC-induced increases in positive Positive and Negative Syndrome Scale but not in Visual Analogue Scales feeling high were reversed by haloperidol. This indicates that psychotic-like effects induced by THC are mediated by dopaminergic systems, but that other systems are involved in 'feeling high'. Additionally, the clear reductions of psychotic-like symptoms by a clinically relevant dose of haloperidol suggest that THC administration may be a useful pharmacological cannabinoid model for psychotic effects in healthy volunteers. PMID:20142302

  2. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

    The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body. PMID:25026144

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

    PubMed

    Schmutzhard, E

    2010-02-01

    Central nervous system infections and infestations by protozoa and helminths constitute a problem of increasing importance throughout all of central European and northern/western countries. This is partially due to the globalisation of our society, tourists and business people being more frequently exposed to parasitic infection/infestation in tropical countries than in moderate climate countries. On top of that, migrants may import chronic infestations and infections with parasitic pathogens, eventually also--sometimes exclusively--involving the nervous system. Knowledge of epidemiology, initial clinical signs and symptoms, diagnostic procedures as well as specific chemotherapeutic therapies and adjunctive therapeutic strategies is of utmost important in all of these infections and infestations of the nervous systems, be it by protozoa or helminths. This review lists, mainly in the form of tables, all possible infections and infestations of the nervous systems by protozoa and by helminths. Besides differentiating parasitic diseases of the nervous system seen in migrants, tourists etc., it is very important to have in mind that disease-related (e.g. HIV) or iatrogenic immunosuppression has led to the increased occurrence of a wide variety of parasitic infections and infestations of the nervous system (e. g. babesiosis, Chagas disease, Strongyloides stercoralis infestation, toxoplasmosis, etc.). PMID:20111855

  4. 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.

  5. Distinct or shared actions of peptide family isoforms: II. Multiple pyrokinins exert similar effects in the lobster stomatogastric nervous system.

    PubMed

    Dickinson, Patsy S; Kurland, Sienna C; Qu, Xuan; Parker, Brett O; Sreekrishnan, Anirudh; Kwiatkowski, Molly A; Williams, Alex H; Ysasi, Alexandra B; Christie, Andrew E

    2015-09-01

    Many neuropeptides are members of peptide families, with multiple structurally similar isoforms frequently found even within a single species. This raises the question of whether the individual peptides serve common or distinct functions. In the accompanying paper, we found high isoform specificity in the responses of the lobster (Homarus americanus) cardiac neuromuscular system to members of the pyrokinin peptide family: only one of five crustacean isoforms showed any bioactivity in the cardiac system. Because previous studies in other species had found little isoform specificity in pyrokinin actions, we examined the effects of the same five crustacean pyrokinins on the lobster stomatogastric nervous system (STNS). In contrast to our findings in the cardiac system, the effects of the five pyrokinin isoforms on the STNS were indistinguishable: they all activated or enhanced the gastric mill motor pattern, but did not alter the pyloric pattern. These results, in combination with those from the cardiac ganglion, suggest that members of a peptide family in the same species can be both isoform specific and highly promiscuous in their modulatory capacity. The mechanisms that underlie these differences in specificity have not yet been elucidated; one possible explanation, which has yet to be tested, is the presence and differential distribution of multiple receptors for members of this peptide family. PMID:26206359

  6. Distinct or shared actions of peptide family isoforms: II. Multiple pyrokinins exert similar effects in the lobster stomatogastric nervous system

    PubMed Central

    Dickinson, Patsy S.; Kurland, Sienna C.; Qu, Xuan; Parker, Brett O.; Sreekrishnan, Anirudh; Kwiatkowski, Molly A.; Williams, Alex H.; Ysasi, Alexandra B.; Christie, Andrew E.

    2015-01-01

    ABSTRACT Many neuropeptides are members of peptide families, with multiple structurally similar isoforms frequently found even within a single species. This raises the question of whether the individual peptides serve common or distinct functions. In the accompanying paper, we found high isoform specificity in the responses of the lobster (Homarus americanus) cardiac neuromuscular system to members of the pyrokinin peptide family: only one of five crustacean isoforms showed any bioactivity in the cardiac system. Because previous studies in other species had found little isoform specificity in pyrokinin actions, we examined the effects of the same five crustacean pyrokinins on the lobster stomatogastric nervous system (STNS). In contrast to our findings in the cardiac system, the effects of the five pyrokinin isoforms on the STNS were indistinguishable: they all activated or enhanced the gastric mill motor pattern, but did not alter the pyloric pattern. These results, in combination with those from the cardiac ganglion, suggest that members of a peptide family in the same species can be both isoform specific and highly promiscuous in their modulatory capacity. The mechanisms that underlie these differences in specificity have not yet been elucidated; one possible explanation, which has yet to be tested, is the presence and differential distribution of multiple receptors for members of this peptide family. PMID:26206359

  7. [Pharmacological studies of guanabenz. Effects on the peripheral nervous and other organ systems].

    PubMed

    Ohata, K; Murata, T; Sakamoto, H; Kohno, S; Hojo, M; Yoshida, Y; Nagasaka, Y; Akimoto, Y; Shimada, A; Teramoto, N; Tatsumi, H

    1983-01-01

    General pharmacological properties of guanabenz (GUB), a new anti-hypertensive agent, were studied in comparison with those of clonidine (CLD) and guanethidine (GUD). Intravenous or peroral administration of GUB caused a contraction of the nictitating membrane in cats and mydriasis in mice, while it produced an inhibitions of the gastrointestinal motility in dogs; the motility of isolated rabbit ileum; and chacol transport, salivation and gastric acid secretion in rats. GUB had no or slight inhibitory actions on contractile responses induced by peripheral sympathetic or parasympathetic nerve stimulation in various organs; however, it had antagonistic actions against the norepinephrine-induced contraction of isolated guinea-pig vas deferens. The contractile responses to epinephrine and tyramine in the nictitating membrane and to sympathetic nerve stimulation in isolated guinea-pig vas deferens were potentiated by GUB. GUB specifically antagonized the serotonin-induced contraction of the isolated rat fundus strip and nonspecifically inhibited acetylcholine, histamine or Ba2+-induced contractions of isolated guinea-pig ileum at higher concentrations. GUB exhibited local anesthetic actions and diuretic effects, but had no particular actions on neuromuscular transmission, isolated rat uterus, guinea-pig tracheal muscle and the hematic system. These effects of GUB were found to be almost identical with but less potent than those of CLD. The effects of GUD were basically different from GUB. PMID:6852682

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. Building a scientific framework for studying hormonal effects on behavior and on the development of the sexually dimorphic nervous system

    EPA Science Inventory

    There has been increasing concern that low-dose exposure to hormonally active chemicals disrupts sexual differentiation of the brain and peripheral nervous system. There also has been active drug development research on the therapeutic potential of hormone therapy on behaviors. T...

  10. 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

  11. Neuroimaging and Neuromonitoring Effects of Electro and Manual Acupuncture on the Central Nervous System: A Literature Review and Analysis

    PubMed Central

    Scheffold, Brigitte Elisabeth; Hsieh, Ching-Liang; Litscher, Gerhard

    2015-01-01

    The aim of this review is to provide an overview of the different effects of manual and electroacupuncture on the central nervous system in studies with different neuroimaging interventions. The Database PubMed was searched from 1/1/2000 to 1/6/2014 with restriction to human studies in English language. Data collection for functional magnetic resonance (fMRI) studies was restricted to the period from 1/1/2010 to 1/6/2014 due to a recently published review which included all published randomized and nonrandomized controlled clinical studies as well as observational studies with control groups, no blinding required. Only studies comparing manual or electroacupuncture with sham acupuncture were eligible. All participants were healthy adult men and women. A majority of 25 studies compared manual versus sham, a minority of 7 trials compared electro versus sham and only 1 study compared electro versus manual acupuncture. In 29 out of 33 studies verum acupuncture results were found to present either more or different modulation effects on neurological components measured by neuroimaging and neuromonitoring methods than sham acupuncture. Only four studies reported no effects of verum in comparison to sham acupuncture. Evaluation of the very heterogeneous results shows evidence that verum acupuncture elicits more modulation effects on neurological components than sham acupuncture. PMID:26339269

  12. [Role of hormonal and seasonal factors in the effect of vitamin E on cholinesterase activity in the nervous system].

    PubMed

    Teplyĭ, D L; Savich, V F

    1975-01-01

    Tests were set up on 73 Citellus fulvus to study the influence exerted by different doses of vitamin E (4 and 8 mg) introduced per os on the activity of the total cholinesterase in various divisions of the central nervous system and also the part played by the hormonal and seasonal factors in this effect. Each test series lasted 30 days (in spring, summer and autumn). The cholinesterase activity was determined after Vensen and Segonzak (1968). The results of the experiments revealed some characteristic trends in the change of the cholinesterase activity occurring under the effect of vitamin E that depended upon a number of factors, such as: the dose of tocopherol, the sex of the animal, time of the year, the brain division under study and the seasonal dynamics of the initial activity. It is shown that in the brain sectors where a material difference existed in the cholinesterase activity between the control males and females it vanished under the effect of tocopherol. On the other hand, in the brain sectors where no such difference existed, it appeared under the effect of tocopherol. The regular character of changes in the cholinesterase activity of the brain and spinal cord produced by different doses of vitamin E suggest the possibility of the brain cholinesterase activity disorders to a play a part in the development of neuro-muscular pathology in cases of the E vitamin deficiency. PMID:1210181

  13. Neuroimaging and Neuromonitoring Effects of Electro and Manual Acupuncture on the Central Nervous System: A Literature Review and Analysis.

    PubMed

    Scheffold, Brigitte Elisabeth; Hsieh, Ching-Liang; Litscher, Gerhard

    2015-01-01

    The aim of this review is to provide an overview of the different effects of manual and electroacupuncture on the central nervous system in studies with different neuroimaging interventions. The Database PubMed was searched from 1/1/2000 to 1/6/2014 with restriction to human studies in English language. Data collection for functional magnetic resonance (fMRI) studies was restricted to the period from 1/1/2010 to 1/6/2014 due to a recently published review which included all published randomized and nonrandomized controlled clinical studies as well as observational studies with control groups, no blinding required. Only studies comparing manual or electroacupuncture with sham acupuncture were eligible. All participants were healthy adult men and women. A majority of 25 studies compared manual versus sham, a minority of 7 trials compared electro versus sham and only 1 study compared electro versus manual acupuncture. In 29 out of 33 studies verum acupuncture results were found to present either more or different modulation effects on neurological components measured by neuroimaging and neuromonitoring methods than sham acupuncture. Only four studies reported no effects of verum in comparison to sham acupuncture. Evaluation of the very heterogeneous results shows evidence that verum acupuncture elicits more modulation effects on neurological components than sham acupuncture. PMID:26339269

  14. Effect of Forest Walking on Autonomic Nervous System Activity in Middle-Aged Hypertensive Individuals: A Pilot Study

    PubMed Central

    Song, Chorong; Ikei, Harumi; Kobayashi, Maiko; Miura, Takashi; Taue, Masao; Kagawa, Takahide; Li, Qing; Kumeda, Shigeyoshi; Imai, Michiko; Miyazaki, Yoshifumi

    2015-01-01

    There has been increasing attention on the therapeutic effects of the forest environment. However, evidence-based research that clarifies the physiological effects of the forest environment on hypertensive individuals is lacking. This study provides scientific evidence suggesting that a brief forest walk affects autonomic nervous system activity in middle-aged hypertensive individuals. Twenty participants (58.0 ± 10.6 years) were instructed to walk predetermined courses in forest and urban environments (as control). Course length (17-min walk), walking speed, and energy expenditure were equal between the forest and urban environments to clarify the effects of each environment. Heart rate variability (HRV) and heart rate were used to quantify physiological responses. The modified semantic differential method and Profile of Mood States were used to determine psychological responses. The natural logarithm of the high-frequency component of HRV was significantly higher and heart rate was significantly lower when participants walked in the forest than when they walked in the urban environment. The questionnaire results indicated that, compared with the urban environment, walking in the forest increased “comfortable”, “relaxed”, “natural” and “vigorous” feelings and decreased “tension-anxiety,” “depression,” “anxiety-hostility,” “fatigue” and “confusion”. A brief walk in the forest elicited physiological and psychological relaxation effects on middle-aged hypertensive individuals. PMID:25739004

  15. The Human Sympathetic Nervous System Response to Spaceflight

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  16. Pharmacological effects of primaquine ureas and semicarbazides on the central nervous system in mice and antimalarial activity in vitro.

    PubMed

    Kedzierska, Ewa; Orzelska, Jolanta; Perković, Ivana; Knežević, Danijel; Fidecka, Sylwia; Kaiser, Marcel; Zorc, Branka

    2016-02-01

    New primaquine (PQ) urea and semicarbazide derivatives 1-4 were screened for the first time for central nervous system (CNS) and antimalarial activity. Behavioural tests were performed on mice. In vitro cytotoxicity on L-6 cells and activity against erythrocytic stages of Plasmodium falciparum was determined. Compound 4 inhibited 'head-twitch' responses and decreased body temperature of mice, which suggests some involvement of the serotonergic system. Compound 4 protected mice against clonic seizures and was superior in the antimalarial test. A hybrid of two PQ urea 2 showed a strong antimalarial activity, confirming the previous findings of the high activity of bis(8-aminoquinolines) and other bisantimalarial drugs. All the compounds decreased the locomotor activity of mice, what suggests their weak depressive effects on the CNS, while PQ derivatives 1 and 2 increased amphetamine-induced hyperactivity. None of the compounds impaired coordination, what suggests a lack of their neurotoxicity. All the tested compounds presented an antinociceptive activity in the 'writhing' test. Compounds 3 and 4 were active in nociceptive tests, and those effects were reversed by naloxone. Compound 4 could be a useful lead compound in the development of CNS active agents and antimalarials, whereas compound 3 may be considered as the most promising lead for new antinociceptive agents. PMID:26501210

  17. Antihypertensive drugs and the sympathetic nervous system.

    PubMed

    Del Colle, Sara; Morello, Fulvio; Rabbia, Franco; Milan, Alberto; Naso, Diego; Puglisi, Elisabetta; Mulatero, Paolo; Veglio, Franco

    2007-11-01

    Hypertension has been associated with several modifications in the function and regulation of the sympathetic nervous system (SNS). Although it is unclear whether this dysfunction is primary or secondary to the development of hypertension, these alterations are considered to play an important role in the evolution, maintenance, and development of hypertension and its target organ damage. Several pharmacological antihypertensive classes are currently available. The main drugs that have been clearly shown to affect SNS function are beta-blockers, alpha-blockers, and centrally acting drugs. On the contrary, the effects of ACE inhibitors (ACE-Is), AT1 receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics on SNS function remain controversial. These properties are pharmacologically and pathophysiologically relevant and should be considered in the choice of antihypertensive treatments and combination therapies in order to achieve, beyond optimal blood pressure control, a normalization of SNS physiology and the most effective prevention of target organ damage. PMID:18030057

  18. Sex-specific effects of intranasal oxytocin on autonomic nervous system and emotional responses to couple conflict

    PubMed Central

    Nater, Urs M.; Schaer, Marcel; La Marca, Roberto; Bodenmann, Guy; Ehlert, Ulrike; Heinrichs, Markus

    2013-01-01

    Unhappy couple relationships are associated with impaired individual health, an effect thought to be mediated through ongoing couple conflicts. Little is known, however, about the underlying mechanisms regulating psychobiological stress, and particularly autonomic nervous system (ANS) reactivity, during negative couple interaction. In this study, we tested the effects of the neuropeptide oxytocin on ANS reactivity during couple conflict in a standardized laboratory paradigm. In a double-blind, placebo-controlled design, 47 heterosexual couples (total n = 94) received oxytocin or placebo intranasally prior to instructed couple conflict. Participants’ behavior was videotaped and salivary alpha-amylase (sAA), a measure of sympathetic activity, and emotional arousal were repeatedly measured during the experiment. Oxytocin significantly reduced sAA during couple conflict in women, whereas men showed increases in sAA levels (sex × group interaction: B = −49.36, t = −2.68, P = 0.009). In men, these increases were related to augmented emotional arousal (r = 0.286, P = 0.028) and more positive behavior (r = 0.291, P = 0.026), whereas there was no such association in women. Our results imply sex-specific effects of oxytocin on sympathetic activity, to negative couple interaction, with the neuropeptide reducing sAA responses and emotional arousal in women while increasing them in men. PMID:22842905

  19. Reactions of the nervous system to magnetic fields

    NASA Technical Reports Server (NTRS)

    Kholodov, Y. A.

    1974-01-01

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

  20. Effects of methylmercuric chloride of low concentration on the rat nervous system

    SciTech Connect

    Yamamura, K.; Maehara, N.; Ohno, H.; Ueno, N.; Kohyama, A.; Satoh, T.; Shimoda, A.; Kishi, R.

    1987-06-01

    In an earlier study the authors reported the effects of 20 ..mu..g/g of MeHg on the rat. After 2-week exposure to 20 ..mu..g/g MeHg, effects on behavior, pathological changes of brain and prolongation of EEP (early potential of evoked potential) latency were observed. So, in this experiment, they planned to expose rats to lower concentrations of MeHg. They therefore investigated the effects of MeHg exposure at a low concentration on behavioral indices, neurological signs, the circadian rhythm of behaviors, EEP, and pathology of the visual cortex and the sciatic nerve in rats.

  1. The effect of quinidine, a strong P-glycoprotein inhibitor, on the pharmacokinetics and central nervous system distribution of naloxegol.

    PubMed

    Bui, Khanh; She, Fahua; Zhou, Diansong; Butler, Kathleen; Al-Huniti, Nidal; Sostek, Mark

    2016-04-01

    Naloxegol is a PEGylated, oral, peripherally acting μ-opioid receptor antagonist approved in the United States for treatment of opioid-induced constipation in patients with noncancer pain. Naloxegol is metabolized by CYP3A, and its properties as a substrate for the P-glycoprotein (PGP) transporter limit its central nervous system (CNS) permeability. This double-blind, randomized, 2-part, crossover study in healthy volunteers evaluated the effect of quinidine (600 mg PO), a CYP3A/PGP transporter inhibitor, on the pharmacokinetics and CNS distribution of naloxegol (25 mg PO). In addition, the effects of quinidine on morphine (5 mg/70 kg IV)-induced miosis and exposure to naloxegol were assessed. Coadministration of quinidine and naloxegol increased naloxegol's AUC 1.4-fold and Cmax 2.5-fold but did not antagonize morphine-induced miosis, suggesting that PGP inhibition does not increase the CNS penetration of naloxegol. Naloxegol pharmacokinetics was unaltered by coadministration of morphine and either quinidine or placebo; conversely, pharmacokinetics of morphine and its metabolites (in the presence of quinidine) were unaltered by coadministration of naloxegol. Naloxegol was safe and well tolerated, alone or in combination with quinidine, morphine, or both. The observed increase in exposure to naloxegol in the presence of quinidine is primarily attributed to quinidine's properties as a weak CYP3A inhibitor. PMID:26248047

  2. [The effect of thiamine deficiency on the actions of drugs affecting the central nervous system in rats (author's transl)].

    PubMed

    Onodera, K; Sakurada, S; Ando, R; Takahashi, N; Tadano, T; Kisara, K; Ogura, Y

    1980-03-01

    Male Wistar rats, 35-days-old, maintained on a thiamine deficient diet for 30 days showed marked growth inhibition and a heart rate less than 70% of that of control rats. We examined the effect of thiamine deficiency on the action of drugs effecting the central nervous system at this period. In thiamine deficient rats treated with chloral hydrate 200 mg/kg, ketamine 100 mg/kg sodium pentobarbital 50 mg/kg, and hexobarbital 100 mg/kg, the sleeping time increased. Pretreatment with 15 mg/kg of the metabolic enzymes inhibitor, SKF-525A, 30 min prior to the hexobarbital administration resulted in prolongation of sleeping time in all groups. The thiamine deficient rats slept almost 3.5 times longer than did the control group. Pretreatment with 100 mg/kg of the metabolic enzyme inducer, sodium phenobarbital, 48 hours prior to hexobarbital treatment resulted in decreased sleeping time in all groups, as compared with only hexobarbital treatment. In the thiamine deficient rats the catalepsy and ptosis induced by the i.p. administration of tetrabenazine 50 mg/kg was reduced even when the control and pair-fed groups responded to this drug at the drug peak time. The spontaneous neuronal activity of lateral hypothalamus was most sensitive to the administration of 5-hydroxytryptophan in thiamine deficient rats. PMID:6967442

  3. Glutamate metabolism of astrocytes during hyperbaric oxygen exposure and its effects on central nervous system oxygen toxicity.

    PubMed

    Chen, Yu-Liang; Li, Dan; Wang, Zhong-Zhuang; Xu, Wei-Gang; Li, Run-Ping; Zhang, Jun-Dong

    2016-01-20

    Hyperbaric oxygen (HBO) has been used widely in many underwater missions and clinical work. However, exposure to extremely high oxygen pressure may cause central nervous system oxygen toxicity (CNS-OT). The regulation of astrocyte glutamate metabolism is closely related to epilepsy. This study aimed to observe the effects of HBO exposure on glutamate metabolism in astrocytes and confirm the role of glutamate metabolism in CNS-OT. Anesthetized rats were exposed to 5 atmosphere absolute HBO for 80 min and microdialysis samples of brain interstitial fluid were continuously collected. Extracellular glutamate and glutamine concentrations were also detected. Freely moving rats were exposed to HBO of the same pressure for 20 min and glutamine synthetase (GS) activity in brain tissues was measured. Finally, we observed the effects of different doses of drugs related to glutamate metabolism on the latency of CNS-OT. Results showed that HBO exposure significantly increased glutamate content, whereas glutamine content was significantly reduced. Moreover, HBO exposure significantly reduced GS activity. Glutamate transporter-1 (GLT-1) selective antagonist ceftriaxone prolonged CNS-OT latency, whereas GLT-1 selective inhibitor dihydrokainate shortened CNS-OT latency. In summary, HBO exposure improved glutamate concentration and reduced glutamine concentration by inhibition of GS activity. GLT-1 activation also participated in the prevention of HBO-induced CNS-OT. Our research will provide a potential new target to terminate or attenuate CNS-OT. PMID:26619231

  4. The Injured Nervous System: A Darwinian Perspective

    PubMed Central

    Weil, Zachary M.; Norman, Greg J.; DeVries, A. Courtney; Nelson, Randy J.

    2008-01-01

    Much of the permanent damage that occurs in response to nervous system damage (trauma, infection, ischemia, etc.) is mediated by endogenous secondary processes that can contribute to cell death and tissue damage (excitotoxicity, oxidative damage and inflammation). For humans to evolve mechanisms to minimize secondary pathophysiological events following CNS injuries, selection must occur for individuals who survive such insults. Two major factors limit the selection for beneficial responses to CNS insults: for many CNS disease states the principal risk factor is advanced, post-reproductive age and virtually all severe CNS traumas are fatal in the absence of modern medical intervention. An alternative hypothesis for the persistence of apparently maladaptive responses to CNS damage is that the secondary exacerbation of damage is the result of unavoidable evolutionary constraints. That is, the nervous system could not function under normal conditions if the mechanisms that caused secondary damage (e.g., excitotoxicity) in response to injury were decreased or eliminated. However, some vertebrate species normally inhabit environments (e.g. hypoxia in underground burrows) that could potentially damage their nervous systems. Yet, profound neuroprotective mechanisms have evolved in these animals indicating that natural selection can occur for traits that protect animals from nervous system damage. Many of the secondary processes and regeneration-inhibitory factors that exacerbate injuries likely persist because they have been adaptive over evolutionary time in the healthy nervous system. Therefore, it remains important that researchers consider the role of the processes in the healthy or developing nervous system to understand how they become dysregulated following injury. PMID:18602443

  5. Emerging infections of the central nervous system.

    PubMed

    Lyons, Jennifer; McArthur, Justin

    2013-12-01

    Emerging infections affecting the central nervous system often present as encephalitis and can cause substantial morbidity and mortality. Diagnosis requires not only careful history taking, but also the application of newly developed diagnostic tests. These diseases frequently occur in outbreaks stemming from viruses that have mutated from an animal host and gained the ability to infect humans. With globalization, this can translate to the rapid emergence of infectious clusters or the establishment of endemicity in previously naïve locations. Since these infections are often vector borne and effective treatments are almost uniformly lacking, prevention is at least as important as prompt diagnosis and institution of supportive care. In this review, we focus on some of the recent literature addressing emerging and resurging viral encephalitides in the United States and around the world-specifically, West Nile virus, dengue, polio, and cycloviruses. We also discuss new, or "emerging," techniques for the precise and rapid diagnosis of encephalitides. PMID:24136412

  6. EFFECTS OF TRIMETHYLTIN ON DOPAMINERGIC AND SEROTONERGIC FUNCTION IN THE CENTRAL NERVOUS SYSTEM

    EPA Science Inventory

    The effects of trimethyltin (TMT) administration on regional concentrations of dopamine (DA), serotonin (5-HT), and their metabolites were determined. Acute administration of 3 or 7 mg/kg TMT (as the chloride) to adult male Long-Evans rats caused alterations in both dopaminergic ...

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

    PubMed

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

    2015-11-19

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

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

    PubMed Central

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

    2015-01-01

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

  9. Central nervous system effects of prenatal selective serotonin reuptake inhibitors: sensing the signal through the noise

    PubMed Central

    Gur, Tamar L.; Kim, Deborah R.

    2013-01-01

    Rationale Women are increasingly prescribed selective serotonin reuptake inhibitors (SSRIs) during pregnancy, with potential implications for neurodevelopment. Whether prenatal SSRI exposure has an effect on neurodevelopment and behavior in the offspring is an important area of investigation. Objectives The aim of this paper was to review the existing preclinical and clinical literature of prenatal SSRI exposure on serotonin-related behaviors and markers in the offspring. The goal is to determine if there is a signal in the literature that could guide clinical care and/or inform research. Results Preclinical studies (n = 4) showed SSRI exposure during development enhanced depression-like behavior. Half of rodent studies examining anxiety-like behavior (n = 13) noted adverse effects with SSRI exposure. A majority of studies of social behavior (n = 4) noted a decrease in sociability in SSRI exposed offspring. Human studies (n = 4) examining anxiety in the offspring showed no adverse effects of prenatal SSRI exposure. The outcome of one study suggested that children with autism were more likely to have a mother who was prescribed an SSRI during pregnancy. Conclusions Preclinical findings in rodents exposed to SSRIs during development point to an increase in depression- and anxiety-like behavior and alteration in social behaviors in the offspring, though both the methods used and the findings were not uniform. These data are not robust enough to discourage use of SSRIs during human pregnancy, particularly given the known adverse effects of maternal mental illness on pregnancy outcomes and infant neurodevelopment. Future research should focus on consistent animal models and prospective human studies with larger samples. PMID:23681158

  10. Riboflavin transport in the central nervous system. Characterization and effects of drugs.

    PubMed Central

    Spector, R

    1980-01-01

    The relationship of riboflavin transport to the transport of other substances including drugs in rabbit choroid plexus, the anatomical locus of the blood-cerebrospinal fluid barrier, and brain cells were studied in vivo and in vitro. In vitro, the ability of rabbit choroid plexus to transport riboflavin from the medium (cerebrospinal fluid surface) through the choroid plexus epithelial cells into the extracellular and vascular spaces of the choroid plexus was documented using fluorescence microscopy. These studies provided further evidence that riboflavin is transported from cerebrospinal fluid to blood via the choroid plexus. The transport of [14C]riboflavin by the isolated choroid plexus was inhibited by thiol agents, ouabain, theophylline, various flavins (lumiflavin and lumichrome > sugar containing flavins), and cyclic organic acids including penicillin and fluorescein. Riboflavin inhibited [14C]penicillin transport competitively and the inhibition constant (K1) for riboflavin equaled the concentration of riboflavin at which the saturable transport system for riboflavin is 50% saturated (KT). These and other data suggest that riboflavin, penicillin, and possibly fluorescein are transported by the same transport system in choroid plexus. In vivo, the intra-ventricular injection or riboflavin and [14C]penicillin inhibited [14C]penicillin transport from cerebrospinal fluid. In vitro, various flavins (riboflavin > other sugar-containing flavins > lumiflavin > lumichrome) inhibited [14C]riboflavin accumulation by brain slices. These studies support the notions that: (a) riboflavin accumulation by choroid plexus (active transport) is quite different from that in brain cells (facilitated diffusion and intracellular trapping), and (b) therapeutically important cyclic organic acids (e.g., penicillin) are transported fom cerebrospinal fluid by the riboflavin transport system in choroid plexus. Images PMID:7419721

  11. Late effects of 2.2 GeV protons on the central nervous system.

    NASA Technical Reports Server (NTRS)

    Lippincott, S. W.; Calvo, W.

    1971-01-01

    Investigation of late pathological effects of high-energy (2.2 GeV) protons on the brain of rabbits, in a postirradiation period of up to 16 months following exposure at fluxes of 30, 100, and 1000 billion protons per sq cm. At the latter two irradiation-intensity levels, the kinds of brain lesions inflicted include large venous dilatation, thickening of vessel walls with deposit of amorphous PAS positive substance, thrombosis, perivascular infiltration of leukocytes and macrophages, mobilization of microglia cells, gliosis, demyelinization, and multiple small pseudocyst formation.

  12. Serotonin release from the neuronal cell body and its long-lasting effects on the nervous system

    PubMed Central

    De-Miguel, Francisco F.; Leon-Pinzon, Carolina; Noguez, Paula; Mendez, Bruno

    2015-01-01

    Serotonin, a modulator of multiple functions in the nervous system, is released predominantly extrasynaptically from neuronal cell bodies, axons and dendrites. This paper describes how serotonin is released from cell bodies of Retzius neurons in the central nervous system (CNS) of the leech, and how it affects neighbouring glia and neurons. The large Retzius neurons contain serotonin packed in electrodense vesicles. Electrical stimulation with 10 impulses at 1 Hz fails to evoke exocytosis from the cell body, but the same number of impulses at 20 Hz promotes exocytosis via a multistep process. Calcium entry into the neuron triggers calcium-induced calcium release, which activates the transport of vesicle clusters to the plasma membrane. Exocytosis occurs there for several minutes. Serotonin that has been released activates autoreceptors that induce an inositol trisphosphate-dependent calcium increase, which produces further exocytosis. This positive feedback loop subsides when the last vesicles in the cluster fuse and calcium returns to basal levels. Serotonin released from the cell body is taken up by glia and released elsewhere in the CNS. Synchronous bursts of neuronal electrical activity appear minutes later and continue for hours. In this way, a brief train of impulses is translated into a long-term modulation in the nervous system. PMID:26009775

  13. Destructive Effects of Prenatal WIN 55212-2 Exposure on Central Nervous System of Neonatal Rats

    PubMed Central

    Shabani, Mohammad; Divsalar, Kouros; Janahmadi, Mahyar

    2012-01-01

    Background Cannabinoid, particularly hashish and WIN 55212-2 (WIN), consumption during embryonic period may affect fetal growth, and the development of motor functioning, memory and cognitive functions. Therefore, the present study aimed to evaluate the effects of WIN 55212-2 during embryonic period on behavioral responses, as well as tissue and memory changes among neonatal rats. Methods WIN treated groups subcutaneously received daily doses of 0.5 or 1 mg/kg WIN suspended in 1% Tween-80-saline (1 ml/kg) from days 5 to 20 of pregnancy. The vehicle group received 1% Tween-80-saline from days 5 to 20 of pregnancy. Three, five and seven weeks after birth, the effects of maternal WIN consumption on infants' body weight, mortality, histological changes, motor functioning, and memory function were assessed. Findings Prenatal WIN consumption was associated with atrophy of cerebellum cortex in granular and Purkinje cells layers. WIN treatment of pregnant rats produced a significant decrease in the rearing frequency of the offspring, but significantly increased the grooming frequency at 22, 36 and 50 days of age. During the acquisition trials, approach latencies were not significantly different between all groups of rats (50 days old). When the trial was repeated 24 hours and seven days later (retention trial), the avoidance latencies of the WIN-exposed group were significantly shorter than those of the control and vehicle animals. The mortality percent was increased significantly and litter size was decreased significantly in WIN (1 mg/kg) treated rats compared to the control, vehicle and WIN (0.5 mg/kg) treatment groups. Conclusion These findings suggested that prenatal exposure to WIN probably induces long-term alterations in histological, motor functioning, and learning and memory parameters. PMID:24494131

  14. The Effect of Lavender Aromatherapy on Autonomic Nervous System in Midlife Women with Insomnia

    PubMed Central

    Chien, Li-Wei; Cheng, Su Li; Liu, Chi Feng

    2012-01-01

    The objective of this study is to determine the effects of 12 weeks of lavender aromatherapy on self-reported sleep and heart rate variability (HRV) in the midlife women with insomnia. Sixty-seven women aged 45–55 years, with a CPSQI (Chinese version of Pittsburgh Sleep Quality Index) greater than 5, were recruited from communities in Taiwan. The experimental group (n = 34) received lavender inhalation, 20 min each time, twice per week, for 12 weeks, with a total of 24 times. The control group (n = 33) received health education program for sleep hygiene with no intervention. The study of HRV was analyzed by time- and frequency-domain methods. Significant decrease in mean heart rate (HR) and increases in SDNN (standard deviation of the normal-to-normal (NN) intervals), RMSDD (square root of the mean squared differences of successive NN intervals), and HF (high frequency) of spectral powers analysis after lavender inhalation were observed in the 4th and 12th weeks of aromatherapy. The total CPSQI score of study subjects was significantly decreased in the experimental group (P < 0.001), while no significant difference was observed across the same time period (P = 0.776) in the control group. Resting HR and HRV measurements at baseline 1 month and 3 months after allocation showed no significant difference between the experimental and control groups. The study demonstrated that lavender inhalation may have a persistent short-term effect on HRV with an increase in parasympathetic modulation. Women receiving aromatherapy experienced a significant improvement in sleep quality after intervention. However, lavender aromatherapy does not appear to confer benefit on HRV in the long-term followup. PMID:21869900

  15. Effects of maternal lead exposure on central nervous system maturation in postnatal rats

    SciTech Connect

    Coleman, J.C.

    1984-01-01

    Pups from female rats exposed to 40-to-80 mg of lead per liter in their drinking water (low-lead group) and 160-to-320 mg of lead per liter water (high-lead group) were examined at 1 to 18 days of age. Maximal electroshock seizure (MES) patterns were determined and, upon recovery, whole blood, plasma, cerebrospinal fluid (CSF) and cerebral cortex samples were collected. Approximately one-half of the pups was used to determine the cerebral cortical extracellular water space (ECS). The other half was used to determine whole blood lead concentrations, plasma electrolytes (Na/sup +/, K/sup +/ and Cl/sup -/), CSF electrolytes, and cerebral cortical lead content, electrolytes, total water spaces, protein content, DNA content, carbonic anhydrase (CA) activity, and sodium- potassium-activated adenosinetriphosphatase (Na/sup +//K/sup +/-ATPase) activity. Neither the low- nor the high-lead groups had significant changes in body weight, body length, hematocrit or cerebral wet weight at any age studied. Whole blood and cerebral cortical lead contents were increased, dose-dependently, at each day of age. Hyperexcitability as measured by MES was observed in lead-exposed pups at 6, 9 and 12 days of age. These observations demonstrate that prenatal and postnatal exposure to lead causes increased susceptibility to MES and alterations in normal developmental patterns of the cerebral cortex. Such alterations appear to result from the greater vulnerability of the glial population to the adverse effects of lead than are neutrons. Thus, effects on the glia can account for the electrolyte imbalances, cellular edema and hyperexcitability resulting from exposure to lead.

  16. Central Nervous System Effects of Iso-6-spectaline Isolated from Senna Spectabilis var. Excelsa (Schrad) in Mice.

    PubMed

    Silva, Fo; Silva, Mgv; Cerqueira, Gs; Sabino, Eb; Almeida, Aac; Costa, Jp; Freitas, Rm

    2011-07-01

    The central nervous system (CNS) depressant and anticonvulsant activities of iso-6-spectaline (SPEC) were investigated in animal models. The SPEC from Senna spectabilis var. excelsa (Schrad) (0.1, 0.5 and 1.0 mg/ kg) injected by oral route (p.o.) in mice caused a significant decrease in the motor activity up to 30 days after the administration and in the dose of 1.0 mg/kg significantly reduced the remaining time on the Rota-rod apparatus. Additionally, SPEC (0.1, 0.5 and 1.0 mg/kg, p.o.) was also capable of promoting increase of latency for development of convulsions induced by pentylenetetrazole. This SPEC was also capable of promoting an increase of latency for development of convulsions induced by picrotoxin at highest dose. In the same way, the anticonvulsant effect of SPEC was affected by pretreatment with flumazenil, a selective antagonist of the benzodiazepine site of the GABA(A) receptor. These results suggest possible CNS depressant and anticonvulsant activities in mice that needs further investigation. PMID:21897664

  17. Negative emotionality and cortisol during adolescent pregnancy and its effects on infant health and autonomic nervous system reactivity.

    PubMed

    Ponirakis, A; Susman, E J; Stifter, C A

    1998-09-01

    This research examined the relations among maternal emotionality, biology, and infant outcome and autonomic nervous system reactivity (cardiac vagal tone). The sample consisted of 27 pregnant adolescents and their 3-week-old infants. Measures of anxiety, depression, anger, and saliva cortisol were obtained from the adolescents both pre- and postnatally. Infant outcome measures consisted of gestational age at delivery, birth weight, number of risk factors at birth and at 24 hr, Apgar score at 1 and 5 min, abnormalities on newborn physical exam, number of resuscitation measures used on the infant, and cardiac vagal tone. Significant relations were found among the adolescent's emotionality, infant physical outcomes, and cardiac vagal tone. Higher concentrations of adolescent cortisol were associated with lower infant Apgar scores and an increased need for resuscitation measures performed on the infant. The positive association between negative emotions and better infant outcomes also was found and may reflect the sensitivity of the adolescents to their feelings and needs during pregnancy. Social support during pregnancy mediated the effects of maternal negative emotionality and infant cardiac vagal tone. PMID:9742411

  18. Effects of different forms of central nervous system prophylaxis on neuropsychologic function in childhood leukemia

    SciTech Connect

    Rowland, J.H.; Glidewell, O.J.; Sibley, R.F.; Holland, J.C.; Tull, R.; Berman, A.; Brecher, M.L.; Harris, M.; Glicksman, A.S.; Forman, E.

    1984-12-01

    A comparison of the late effects on intellectual and neuropsychologic function of three different CNS prophylaxis regimens was conducted in 104 patients treated for childhood acute lymphocytic leukemia. Of the children studied, 33 were randomized to treatment with intrathecal (IT) methotrexate alone, 36 to IT methotrexate plus 2,400 rad cranial irradiation, and 35 to IT methotrexate plus intravenous intermediate dose methotrexate. All patients were in their first (complete) continuous remission, were a minimum of one year post-CNS prophylaxis and had no evidence of CNS disease at the time of evaluation. In contrast to the other two treatment groups, children whose CNS prophylaxis included cranial irradiation attained significantly lower mean Full Scale IQs, performed more poorly on the Wide Range Achievement Test, a measure of school abilities, and exhibited a greater number of difficulties on a variety of other neuropsychologic measures. The poorer performance of the irradiated group was independent of sex of the patient, time since treatment and age at diagnosis. These data suggest that the addition of 2,400 rad cranial irradiation to CNS prophylaxis in ALL puts these children at greater risk for mild global loss in intellectual and neuropsychologic ability.

  19. Investigation of radiofrequency/microwave effects upon the central nervous system. Final report

    SciTech Connect

    Shelton, W.W.

    1980-06-26

    A study to determine the effect of pulsed electromagnetic energy upon brain calcium behavior was undertaken. An innovative approach for loading the cerebral tissues with radiocalcium was introduced. Intraventricular injections through the skull placed Ca-45 solution directly into the right lateral ventricle. Two hours later, companion frontal lobe samples were placed in separate glass breakers containing physiologic solution for a 20-min exposure to pulsed electromagnetic energy. An efflux value was calculated for each sample. A second experimental procedure involved whole-body irradiation of the animals two hours following the intraventricular injections. Animals were then irradiated with pulsed electromagnetic energy at a power density of 10 mW/cm squared, a pulse repetition frequency of 16 Hz, and carrier frequency of 2.45 GHz. Following exposure, frontal lobe and parieto-occipital tissue samples were taken and analysed for radioactivity. Statistical treatment of the first sets of experiments failed to reveal any perturbation in calcium efflux behavior. Data from the second set are still being evaluated.

  20. Delayed effects of neutron irradiation on central nervous system microvasculature in the rat

    SciTech Connect

    Goodman, J.H.; McGregor, J.M.; Clendenon, N.R.; Gordon, W.A.; Yates, A.J.; Gahbauer, R.A.; Barth, R.F.; Fairchild, R.G.

    1988-01-01

    Pathologic examination of a series of 14 patients with malignant gliomas treated with BNCT showed well demarcated zones of radiation damage characterized by coagulation necrosis. Beam attenuation was correlated with edema, loss of parenchymal elements, demyelination, leukocytosis, and peripheral gliosis. Vascular disturbances consisted of endothelial swelling, medial and adventitial proliferation, fibrin impregnation, frequent thrombosis, and perivascular inflammation. Radiation changes appeared to be acute and delayed. The outcome of the patients in this series was not significantly different from the natural course of the disease, even though two of the patients had no residual tumor detected at the time of autopsy. The intensity of the vascular changes raised a suspicion that boron may have sequestered in vessel walls, resulting in selectively high doses of radiation to these structures (Asbury et al., 1972), or that there may have been high blood concentrations of boron at the time of treatment. The potential limiting effects of a vascular ischemic reaction in Boron Neutron Capture Therapy (BNCT) prompted the following study to investigate the delayed response of microvascular structures in a rat model currently being used for pre-clinical investigations. 8 refs., 3 figs., 1 tab.

  1. Effects of different "relaxing" music styles on the autonomic nervous system.

    PubMed

    Perez-Lloret, Santiago; Diez, Joaquín; Domé, María Natalia; Delvenne, Andrea Alvarez; Braidot, Nestor; Cardinali, Daniel P; Vigo, Daniel Eduardo

    2014-01-01

    The objective of this study was to assess the effects on heart rate variability (HRV) of exposure to different styles of "relaxing" music. Autonomic responses to musical stimuli were correlated with subjective preferences regarding the relaxing properties of each music style. Linear and nonlinear HRV analysis was conducted in 25 healthy subjects exposed to silence or to classical, new age or romantic melodies in a random fashion. At the end of the study, subjects were asked to choose the melody that they would use to relax. The low-to-high-frequency ratio was significantly higher when subjects were exposed to "new age" music when compared with silence (3.4 ± 0.3 vs. 2.6 ± 0.3, respectively, P < 0.02), while no differences were found with "classical" or "romantic" melodies (2.1 ± 0.4 and 2.2 ± 0.3). These results were related to a reduction in the high frequency component with "new age" compared to silence (17.4 ± 1.9 vs. 23.1 ± 1.1, respectively P < 0.004). Significant differences across melodies were also found for nonlinear HRV indexes. Subjects' preferences did not correlate with autonomic responses to melodies. The results suggest that "new age" music induced a shift in HRV from higher to lower frequencies, independently on the music preference of the listener. PMID:25209037

  2. Effect of repetitive SCUBA diving on humoral markers of endothelial and central nervous system integrity.

    PubMed

    Bilopavlovic, Nada; Marinovic, Jasna; Ljubkovic, Marko; Obad, Ante; Zanchi, Jaksa; Pollock, Neal W; Denoble, Petar; Dujic, Zeljko

    2013-07-01

    During SCUBA diving decompression, there is a significant gas bubble production in systemic veins, with rather frequent bubble crossover to arterial side even in asymptomatic divers. The aim of the current study was to investigate potential changes in humoral markers of endothelial and brain damage (endothelin-1, neuron-specific enolase and S-100β) after repetitive SCUBA diving with concomitant assessment of venous gas bubble production and subsequent arterialization. Sixteen male divers performed four open-water no-decompression dives to 18 msw (meters of sea water) lasting 49 min in consecutive days during which they performed moderate-level exercise. Before and after dives 1 and 4 blood was drawn, and bubble production and potential arterialization were echocardiographically evaluated. In addition, a control dive to 5 msw was performed with same duration, water temperature and exercise load. SCUBA diving to 18 msw caused significant bubble production with arterializations in six divers after dive 1 and in four divers after dive 4. Blood levels of endothelin-1 and neuron-specific enolase did not change after diving, but levels of S-100β were significantly elevated after both dives to 18 msw and a control dive. Creatine kinase activity following a control dive was also significantly increased. Although serum S-100β levels were increased after diving, concomitant increase of creatine kinase during control, almost bubble-free, dive suggests the extracranial release of S-100β, most likely from skeletal muscles. Therefore, despite the significant bubble production and sporadic arterialization after open-water dives to 18 msw, the current study found no signs of damage to neurons or the blood-brain barrier. PMID:23400567

  3. Results of a United States and Soviet Union joint project on nervous system effects of microwave radiation.

    PubMed Central

    Mitchell, C L; McRee, D I; Peterson, N J; Tilson, H A; Shandala, M G; Rudnev, M I; Varetskii, V V; Navakatikyan, M I

    1989-01-01

    During the course of a formal program of cooperation between the United States and the Soviet Union concerning the biological effects of physical factors in the environment, it was concluded that duplicate projects should be initiated with the general goal of determining the most sensitive and valid test procedures for evaluating the effects of microwave radiation on the central nervous system. This report details an initial step in this direction. Male rats of the Fischer 344 strain were exposed or sham exposed to 10 mW/cm2 continuous wave microwave radiation at 2.45 GHz for a period of 7 hr. Animals were subjected to behavioral, biochemical, or electrophysiological measurements during and/or immediately after exposure. Behavioral tests used were passive avoidance and activity in an open field. Biochemical measurements were ATPase (Na+, K+; Mg2+, Ca2+) and K+ alkaline phosphatase activities. Electrophysiological measurements consisted of EEG frequency analysis. Neither group observed a significant effect of microwave irradiation on open field activity. Both groups observed changes in variability of the data obtained using the passive avoidance procedure, but not in the same parameters. The U.S. group, but not the USSR group, found significantly less Na+,K+-ATPase activity in the microwave-exposed animals compared to the sham exposed animals. Both groups found incidences of statistically significant effects in the power spectral analysis of EEG frequency, but not at the same frequency. The failure of both groups to substantiate the results of the other reinforces our contention that such duplicate projects are important and necessary. Images FIGURE 3. FIGURE 4. PMID:2527152

  4. Results of a United States and Soviet Union joint project on nervous system effects of microwave radiation

    SciTech Connect

    Mitchell, C.L.; McRee, D.I.; Peterson, N.J.; Tilson, H.A.; Shandala, M.G.; Rudnev, M.I.; Varetskii, V.V.; Navakatikyan, M.I. )

    1989-05-01

    During the course of a formal program of cooperation between the United States and the Soviet Union concerning the biological effects of physical factors in the environment, it was concluded that duplicate projects should be initiated with the general goal of determining the most sensitive and valid test procedures for evaluating the effects of microwave radiation on the central nervous system. This report details an initial step in this direction. Male rats of the Fischer 344 strain were exposed or sham exposed to 10 mW/cm2 continuous wave microwave radiation at 2.45 GHz for a period of 7 hr. Animals were subjected to behavioral, biochemical, or electrophysiological measurements during and/or immediately after exposure. Behavioral tests used were passive avoidance and activity in an open field. Biochemical measurements were ATPase (Na+, K+; Mg2+, Ca2+) and K+ alkaline phosphatase activities. Electrophysiological measurements consisted of EEG frequency analysis. Neither group observed a significant effect of microwave irradiation on open field activity. Both groups observed changes in variability of the data obtained using the passive avoidance procedure, but not in the same parameters. The U.S. group, but not the USSR group, found significantly less Na+,K+-ATPase activity in the microwave-exposed animals compared to the sham exposed animals. Both groups found incidences of statistically significant effects in the power spectral analysis of EEG frequency, but not at the same frequency. The failure of both groups to substantiate the results of the other reinforces our contention that such duplicate projects are important and necessary.

  5. The effect of a single session of whole-body vibration training in recreationally active men on the excitability of the central and peripheral nervous system.

    PubMed

    Chmielewska, Daria; Piecha, Magdalena; Błaszczak, Edward; Król, Piotr; Smykla, Agnieszka; Juras, Grzegorz

    2014-06-28

    Vibration training has become a popular method used in professional sports and recreation. In this study, we examined the effect of whole-body vibration training on the central nervous system and muscle excitability in a group of 28 active men. Subjects were assigned randomly to one of two experimental groups with different variables of vibrations. The chronaximetry method was used to evaluate the effect of a single session of whole-body vibration training on the excitability of the rectus femoris and brachioradialis muscles. The examination of the fusing and flickering frequencies of the light stimulus was performed. An increase in the excitability of the quadriceps femoris muscle due to low intensity vibrations (20 Hz frequency, 2 mm amplitude) was noted, and a return to the initial values was observed 30 min after the application of vibration. High intensity vibrations (60 Hz frequency, 4 mm amplitude) caused elongations of the chronaxy time; however, these differences were not statistically significant. Neither a low intensity vibration amplitude of 2 mm (frequency of 20 Hz) nor a high intensity vibration amplitude of 4 mm (frequency of 60 Hz) caused a change in the excitability of the central nervous system, as revealed by the average frequency of the fusing and flickering of the light stimulus. A single session of high intensity whole-body vibration did not significantly decrease the excitability of the peripheral nervous system while the central nervous system did not seem to be affected. PMID:25114735

  6. 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

  7. Illuminating viral infections in the nervous system

    PubMed Central

    McGavern, Dorian B.; Kang, Silvia S.

    2016-01-01

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

  8. 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.

  9. [Effect of cerebrum compositum preparation on functional state of the central nervous system in elderly patients with ischemic stroke].

    PubMed

    Kuznetsova, S M; Lukach, O I

    2004-01-01

    The article presents the results obtained after having treated patients with ischemic stroke during a rehabilitation period with cerebrum compositum. It has been also studied its influence on psychoemotional condition, bioelectrical activity of brain and cerebral hemodynamics. The results of the conducted trial prove cerebrum compositum remedy to have a harmonious influence on bioelectrical activity of brain and cerebral hemodynamics as well as it improves psychological state, alleviates anxiety and enhances initiative and physical activity of the treated patients. Positive complex influence on functional state of central nervous system of the medication ensure us to recommend cerebrum compositum during rehabilitation of patients having stroke positive anamnesis. PMID:15605833

  10. Carbon monoxide and the nervous system.

    PubMed

    Raub, J A; Benignus, V A

    2002-12-01

    Carbon monoxide (CO) is a colorless, tasteless, odorless, and non-irritating gas formed when carbon in fuel is not burned completely. It enters the bloodstream through the lungs and attaches to hemoglobin (Hb), the body's oxygen carrier, forming carboxyhemoglobin (COHb) and thereby reducing oxygen (O(2)) delivery to the body's organs and tissues. High COHb concentrations are poisonous. Central nervous system (CNS) effects in individuals suffering acute CO poisoning cover a wide range, depending on severity of exposure: headache, dizziness, weakness, nausea, vomiting, disorientation, confusion, collapse, and coma. At lower concentrations, CNS effects include reduction in visual perception, manual dexterity, learning, driving performance, and attention level. Earlier work is frequently cited to justify the statement that CO exposure sufficient to produce COHb levels of ca. 5% would be sufficient to produce visual sensitivity reduction and various neurobehavioral performance deficits. In a recent literature re-evaluation, however, the best estimate was that [COHb] would have to rise to 15-20% before a 10% reduction in any behavioral or visual measurement could be observed. This conclusion was based on (1) critical review of the literature on behavioral and sensory effects, (2) review and interpretation of the physiological effects of COHb on the CNS, (3) extrapolation from the effects of hypoxic hypoxia to the effects of CO hypoxia, and (4) extrapolation from rat behavioral effects of CO to humans. Also covered in this review article are effects of chronic CO exposure, the discovery of neuroglobin, a summary of the relatively new role for endogenous CO in neurotransmission and vascular homeostasis, groups which might be especially sensitive to CO, and recommendations on further research. The interested reader is directed to other published reviews of the literature on CO and historically seminal references that form our understanding of this ubiquitous gas. PMID

  11. [Diagnostic imaging of central nervous system vasculitis].

    PubMed

    Yokota, Hajime; Yamada, Kei

    2015-03-01

    Vasculitis involving the central nervous system presents with infarction and hemorrhage, which are often nonspecific findings. Laboratory examinations are essential for diagnosis of vasculitis in addition to comprehensive and systematic review of the clinical course. Although most findings tend to be nonspecific, enhancement and thickening of the vascular wall indicate vasculitis. Visualization of the vascular wall requires selection of the appropriate imaging modality and mode of image acquisition. Contrast-enhanced CT, MRI, and FDG-PET are useful for visualizing large vessel vasculitis, while CT, MRI, and angiography are effective for medium vessel vasculitis. The use of ultrasound is limited to evaluating vessels on the body surface. Although relatively thick vessels can be demonstrated by angiography, complete survey of small vessels is difficult. Here, we summarize the characteristics of each imaging modality and imaging findings of typical vasculitides-Takayasu arteritis, giant cell arteritis, ANCA-associated vasculitis, Behçet's disease, primary angiitis of the CNS, and vasculitis associated with systemic disease. Differential diagnoses are also shown, including infective endocarditis, tuberculous meningitis, Ehlers-Danlos syndrome, and reversible cerebral vasoconstriction syndrome. PMID:25846439

  12. The effects of the glycine reuptake inhibitor R213129 on the central nervous system and on scopolamine-induced impairments in psychomotor and cognitive function in healthy subjects.

    PubMed

    Liem-Moolenaar, M; Zoethout, R W M; de Boer, P; Schmidt, M; de Kam, M L; Cohen, A F; Franson, K L; van Gerven, J M A

    2010-11-01

    In this study the effects of R213129, a selective glycine transporter 1 inhibitor, on central nervous system function were investigated in healthy males in the absence and presence of scopolamine. This was a double-blind, placebo-controlled, 4-period crossover ascending dose study evaluating the following endpoints: body sway, saccadic and smooth pursuit eye movements, pupillometry, electroencephalography, visual analogue scales for alertness, mood, calmness and psychedelic effects, adaptive tracking, finger tapping, Visual and Verbal Learning Task, Stroop test, hormone levels and pharmacokinetics. R213129 dose levels were selected based on exposure levels that blocked the GlyT1 sites >50% in preclinical experiments. Forty-three of the 45 included subjects completed the study. Scopolamine significantly affected almost every central nervous system parameter measured in this study. R213129 alone compared with placebo did not elicit pharmacodynamic changes. R213129 had some small effects on scopolamine-induced central nervous system impairments. Scopolamine-induced finger tapping impairment was further enhanced by 3 mg R213129 with 2.0 taps/10 seconds (95% CI -4.0, -0.1), electroencephalography alpha power was increased by 10 mg R213129 with respectively 12.9% (0.7, 26.6%), scopolamine-induced impairment of the Stroop test was partly reversed by 10 mg R213129 with 59 milliseconds (-110, -7). Scopolamine produced robust and consistent effects in psychomotor and cognitive function in healthy volunteers. The most logical reason for the lack of R213129 effects seems to be that the central nervous system concentrations were too low. The effects of higher doses in healthy volunteers and the clinical efficacy in patients remain to be established. PMID:20142308

  13. Plants and the central nervous system.

    PubMed

    Carlini, E A

    2003-06-01

    This review article draws the attention to the many species of plants possessing activity on the central nervous system (CNS). In fact, they cover the whole spectrum of central activity such as psychoanaleptic, psycholeptic and psychodysleptic effects, and several of these plants are currently used in therapeutics to treat human ailments. Among the psychoanaleptic (stimulant) plants, those utilized by human beings to reduce body weight [Ephedra spp. (Ma Huang), Paullinia spp. (guaraná), Catha edulis Forssk. (khat)] and plants used to improve general health conditions (plant adaptogens) were scrutinized. Many species of hallucinogenic (psychodysleptic) plants are used by humans throughout the world to achieve states of mind distortions; among those, a few have been used for therapeutic purposes, such as Cannabis sativa L., Tabernanthe iboga Baill. and the mixture of Psychotria viridis Ruiz and Pav. and Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton. Plants showing central psycholeptic activities, such as analgesic or anxiolytic actions (Passiflora incarnata L., Valeriana spp. and Piper methysticum G. Forst.), were also analysed.Finally, the use of crude or semipurified extracts of such plants instead of the active substances seemingly responsible for their therapeutic effect is discussed. PMID:12895668

  14. Effect of amygdala kindling on the central nervous system effects of tiagabine: EEG effects versus brain GABA levels

    PubMed Central

    Cleton, A; Altorf, B A; Voskuyl, R A; Danhof, M

    2000-01-01

    The objective of this investigation was to determine the influence of amygdala kindling on the pharmacodynamics of tiagabine in vivo, using quantitative EEG parameters and extracellular GABA concentrations as pharmacodynamic endpoints. In integrated pharmacokinetic/pharmacodynamic (PK/PD) studies the time course of these effects was determined in conjunction with plasma concentrations following intravenous administration of 10 mg kg−1. An ‘effect compartment' model was used to derive individual concentration–effect relationships. Tiagabine produced an increase in the amplitude of the 11.5–30 Hz frequency band of the EEG. The relationship between concentration and EEG effect was non-linear and described by the Hill equation. In kindled rats the EC50 was reduced to 291 ng ml−1 from the original value of 521 ng ml−1 in controls. The values of all other parameters were unchanged. In kindled rats the baseline extracellular GABA concentration was increased to 1.58 μM from 0.74 μM in controls. The relationships between tiagabine concentration and extracellular GABA concentration were again non-linear and described by the Hill equation. No differences were observed between kindled rats and controls. In the synaptoneurosmal preparation in vitro no changes in the functioning of the GABA transporter were observed. It is concluded that unlike the situation with midazolam, there is no resistance to the EEG effect of tiagabine in the kindling model of experimental epilepsy. The observed shift in the concentration–EEG effect relationship to lower concentrations can presumably be explained by the increase in the baseline GABA levels. PMID:10882388

  15. Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects

    PubMed Central

    Michlig, Stéphanie; Merlini, Jenny Meylan; Beaumont, Maurice; Ledda, Mirko; Tavenard, Aude; Mukherjee, Rajat; Camacho, Susana; le Coutre, Johannes

    2016-01-01

    Various lines of published evidence have already demonstrated the impact of TRPV1 agonists on energetic metabolism through the stimulation of the sympathetic nervous system (SNS). This study presents a trial investigating if stimulation of the two related sensory receptors TRPA1 and TRPM8 could also stimulate the SNS and impact the energetic metabolism of healthy subjects. The trial was designed to be double-blinded, randomized, cross-over, placebo-controlled with healthy subjects and the impact on the energetic metabolism and the autonomic nervous system (ANS) of cinnamaldehyde, capsaicin and a cooling flavor was measured during the 90 min after ingestion. Energy expenditure and substrate oxidation were measured by indirect calorimetry. An exploratory method to measure ANS activity was by facial thermography and power spectral analysis of heart rate variability using ECG was also used. Following cinnamaldehyde ingestion, energy expenditure was increased as compared to placebo. Furthermore, postprandial fat oxidation was maintained higher compared to placebo after cinnamaldehyde and capsaicin ingestion. Similar peripheral thermoregulation was observed after capsaicin and cinnamaldehyde ingestion. Unlike capsaicin, the dose of cinnamaldehyde was not judged to be sensorially ‘too intense’ by participants suggesting that Cinnamaldehyde would be a more tolerable solution to improve thermogenesis via spicy ingredients as compared to capsaicin. PMID:26883089

  16. Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects.

    PubMed

    Michlig, Stéphanie; Merlini, Jenny Meylan; Beaumont, Maurice; Ledda, Mirko; Tavenard, Aude; Mukherjee, Rajat; Camacho, Susana; le Coutre, Johannes

    2016-01-01

    Various lines of published evidence have already demonstrated the impact of TRPV1 agonists on energetic metabolism through the stimulation of the sympathetic nervous system (SNS). This study presents a trial investigating if stimulation of the two related sensory receptors TRPA1 and TRPM8 could also stimulate the SNS and impact the energetic metabolism of healthy subjects. The trial was designed to be double-blinded, randomized, cross-over, placebo-controlled with healthy subjects and the impact on the energetic metabolism and the autonomic nervous system (ANS) of cinnamaldehyde, capsaicin and a cooling flavor was measured during the 90 min after ingestion. Energy expenditure and substrate oxidation were measured by indirect calorimetry. An exploratory method to measure ANS activity was by facial thermography and power spectral analysis of heart rate variability using ECG was also used. Following cinnamaldehyde ingestion, energy expenditure was increased as compared to placebo. Furthermore, postprandial fat oxidation was maintained higher compared to placebo after cinnamaldehyde and capsaicin ingestion. Similar peripheral thermoregulation was observed after capsaicin and cinnamaldehyde ingestion. Unlike capsaicin, the dose of cinnamaldehyde was not judged to be sensorially 'too intense' by participants suggesting that Cinnamaldehyde would be a more tolerable solution to improve thermogenesis via spicy ingredients as compared to capsaicin. PMID:26883089

  17. Maintaining Genome Stability in the Nervous System

    PubMed Central

    McKinnon, Peter J.

    2014-01-01

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

  18. 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

  19. Computed tomography of the central nervous system

    SciTech Connect

    Bentson, J.R.

    1982-01-01

    The objective of this chapter is to review the most pertinent articles published during the past year on the subject of computed tomography of the central nervous system. The chapter contains sections on pediatric computed tomography, and on the diagnostic use of CT in white matter disease, in infectious disease, for intracranial aneurysms, trauma, and intracranial tumors. Metrizamide flow studies and contrast enhancement are also examined. (KRM)

  20. Zygomycotic invasion of the central nervous system.

    PubMed

    Sasaki, Tomoaki; Mineta, Masayuki; Kobayashi, Keigo; Ando, Masakatsu; Obata, Masahiko

    2010-06-01

    Zygomycosis is an opportunistic fungal infection that affects the central nervous system (CNS). In this report, we present three cases of zygomycosis with CNS involvement. In two patients zygomycosis developed after neurosurgery, and in the third patient zygomycosis developed after bone marrow transplantation for leukemia. All patients developed persistent fever and neurological deficits. They presented with progressive cerebral infarction accompanied by hemorrhage. Intraoperative findings and histopathological examinations revealed that zygomycotic hyphae caused mycotic aneurysm, vasculitis, and venous occlusion. PMID:20585927

  1. LGI proteins in the nervous system

    PubMed Central

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

    2013-01-01

    The development and function of the vertebrate nervous system depend on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. LGI1-4 (leucine-rich glioma inactivated proteins) play important roles in these processes. They are secreted proteins consisting of an LRR (leucine-rich repeat) domain and a so-called epilepsy-associated or EPTP (epitempin) domain. Both domains are thought to function in protein–protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in ADLTE (autosomal dominant lateral temporal (lobe) epilepsy) also referred to as ADPEAF (autosomal dominant partial epilepsy with auditory features). LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodelling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here, we review our current knowledge about this important family of proteins, and the progress made towards understanding their functions. PMID:23713523

  2. LGI proteins in the nervous system.

    PubMed

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

    2013-01-01

    The development and function of the vertebrate nervous system depend on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. LGI1-4 (leucine-rich glioma inactivated proteins) play important roles in these processes. They are secreted proteins consisting of an LRR (leucine-rich repeat) domain and a so-called epilepsy-associated or EPTP (epitempin) domain. Both domains are thought to function in protein-protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in ADLTE (autosomal dominant lateral temporal (lobe) epilepsy) also referred to as ADPEAF (autosomal dominant partial epilepsy with auditory features). LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodelling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here, we review our current knowledge about this important family of proteins, and the progress made towards understanding their functions. PMID:23713523

  3. Comparative anatomy of the autonomic nervous system.

    PubMed

    Nilsson, Stefan

    2011-11-16

    This short review aims to point out the general anatomical features of the autonomic nervous systems of non-mammalian vertebrates. In addition it attempts to outline the similarities and also the increased complexity of the autonomic nervous patterns from fish to tetrapods. With the possible exception of the cyclostomes, perhaps the most striking feature of the vertebrate autonomic nervous system is the similarity between the vertebrate classes. An evolution of the complexity of the system can be seen, with the segmental ganglia of elasmobranchs incompletely connected longitudinally, while well developed paired sympathetic chains are present in teleosts and the tetrapods. In some groups the sympathetic chains may be reduced (dipnoans and caecilians), and have yet to be properly described in snakes. Cranial autonomic pathways are present in the oculomotor (III) and vagus (X) nerves of gnathostome fish and the tetrapods, and with the evolution of salivary and lachrymal glands in the tetrapods, also in the facial (VII) and glossopharyngeal (IX) nerves. PMID:20444653

  4. Radiation response of the central nervous system

    SciTech Connect

    Schultheiss, T.E.; Kun, L.E.; Stephens, L.C.

    1995-03-30

    This report reviews the anatomical, pathophysiological, and clinical aspects of radiation injury to the central nervous system (CNS). Despite the lack of pathoGyomonic characteristics for CNS radiation lesions, demyelination and malacia are consistently the dominant morphological features of radiation myelopathy. In addition, cerebral atrophy is commonly observed in patients with neurological deficits related to chemotherapy and radiation, and neurocognitive deficits are associated with diffuse white matter changes. Clinical and experimental dose-response information have been evaluated and summarized into specific recommendations for the spinal cord and brain. The common spinal cord dose limit of 45 Gn in 22 to 25 fractions is conservative and can be relaxed if respecting this limit materially reduces the probability of tumor control. It is suggested that the 5% incidence of radiation myelopathy probably lies between 57 and 61 Gy to the spinal cord in the absence of dose modifying chemotherapy. A clinically detectable length effect for the spinal cord has not been observed. The effects of chemotherapy and altered fractionation are also discussed. Brain necrosis in adults is rarely noted below 60 Gy in conventional fractionation, with imaging and clinical changes being observed generally only above 50 Gy. However, neurocognitive effects are observed at lower doses, especially in children. A more pronounced volume effect is believed to exist in the brain than in the spinal cord. Tumor progression may be hard to distinguish from radiation and chemotherapy effects. Diffuse white matter injury can be attributed to radiation and associated with neurological deficits, but leukoencephalopathy is rarely observed in the absence of chemotherapy. Subjective, objective, management, and analytic (SOMA) parameters related to radiation spinal cord and brain injury have been developed and presented on ordinal scales. 140 refs., 3 figs., 6 tabs.

  5. 3D printed nervous system on a chip.

    PubMed

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

    2016-04-21

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

  6. Assessment of the Effects of Combination Therapy with Ciprofloxacin and Fenbufen on the Central Nervous Systems of Healthy Volunteers by Quantitative Electroencephalography

    PubMed Central

    Kamali, F.; Ashton, C. H.; Marsh, V. R.; Cox, J.

    1998-01-01

    The potential effects of concurrent administration of fenbufen and ciprofloxacin on central nervous system activity in healthy young subjects were investigated by electroencephalography (EEG). Visual analog scales (VAS) were used to assess subjective measures of concentration, vigilance, tension, and irritability. When ciprofloxacin was administered in combination with fenbufen, none of the EEG parameters or VAS ratings measured were significantly different from those measured when the drugs were administered alone. PMID:9593161

  7. NERVOUS-SYSTEM SPECIFIC PROTEINS AS BIOCHEMICAL INDICATORS OF NEUROTOXICITY

    EPA Science Inventory

    Recent advances in neuroimmunology and protein purification methodology have led to the identification of nervous-system specific proteins. Their intimate relationship to the cellular and functional heterogeneity of the nervous system, makes these proteins ideal biochemical marke...

  8. What Are the Parts of the Nervous System?

    MedlinePlus

    ... Research Planning Scientific Resources Research A-Z Topics Neuroscience Overview Condition Information Parts of the nervous system ... functions does the nervous system control? Why study neuroscience? What are the areas of neuroscience? NICHD Research ...

  9. The BIRN Project: Imaging the Nervous System

    SciTech Connect

    Ellisman, Mark

    2006-05-22

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

  10. The BIRN Project: Imaging the Nervous System

    SciTech Connect

    Ellisman, Mark

    2006-05-22

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

  11. Lysophosphatidic Acid signaling in the nervous system.

    PubMed

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

    2015-02-18

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

  12. Sympathetic nervous system regulation of the tumour microenvironment

    PubMed Central

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

    2016-01-01

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

  13. Neuropeptide Y (NPY) and the central nervous system: distribution effects and possible relationship to neurological and psychiatric disorders.

    PubMed

    Wahlestedt, C; Ekman, R; Widerlöv, E

    1989-01-01

    1. NPY is a 36 amino acid tyrosine-rich peptide. It is one of the most abundant and widely distributed neuropeptides known today within the central nervous system with particularly high concentrations in the hypothalamus and in several limbic regions. 2. NPY seems to coexist with other on neurotransmitters like somatostatin, galanin, GABA and the catecholamines noradrenaline and adrenaline in discrete brain regions. 3. NPY binding sites are widely distributed in the brain. However they do not always overlap with the distribution of NPY-like immunoreactivity. 4. NPY is suggested to be involved in a large number of neuroendocrine functions, stress responses, circadian rhythms, central autonomic functions, eating and drinking behaviour, and sexual and motor behaviour. 5. Psychotropic drugs and neurotoxins can alter the NPY concentrations in discrete brain regions. 6. It is possible that NPY is related to various neurological and psychiatric illnesses, like Huntington's chorea, Alzheimer's disease, Parkinson's disease, eating disorders, and major depressive illness. PMID:2664885

  14. Neuroimaging in Central Nervous System Lymphoma.

    PubMed

    Nabavizadeh, Seyed Ali; Vossough, Arastoo; Hajmomenian, Mehrdad; Assadsangabi, Reza; Mohan, Suyash

    2016-08-01

    Primary central nervous system lymphoma (PCNSL) is a rare aggressive high-grade type of extranodal lymphoma. PCNSL can have a variable imaging appearance and can mimic other brain disorders such as encephalitis, demyelination, and stroke. In addition to PCNSL, the CNS can be secondarily involved by systemic lymphoma. Computed tomography and conventional MRI are the initial imaging modalities to evaluate these lesions. Recently, however, advanced MRI techniques are more often used in an effort to narrow the differential diagnosis and potentially inform diagnostic and therapeutic decisions. PMID:27443998

  15. Viral Diseases of the Central Nervous System

    PubMed Central

    Swanson, Phillip A.; McGavern, Dorian B.

    2015-01-01

    Virus-induced diseases of the central nervous system (CNS) represent a significant burden to human health worldwide. The complexity of these diseases is influenced by the sheer number of different neurotropic viruses, the diverse routes of CNS entry, viral tropism, and the immune system. Using a combination of human pathological data and experimental animal models, we have begun to uncover many of the mechanisms that viruses use to enter the CNS and cause disease. This review highlights a selection of neurotropic viruses that infect the CNS and explores the means by which they induce neurological diseases such as meningitis, encephalitis, and myelitis. PMID:25681709

  16. Radiation Damage to the Nervous System: a delayed therapeutic hazard

    SciTech Connect

    Gilbert, H.A.; Kagan, A.R.

    1980-01-01

    This volume represents a good overview of an important issue - late effects of radiation on the nervous system, a topic of interest to everybody who deals with neurooncologic problems. The book is well edited and includes almost all relevant subjects ranging from diagnostic and dosimetric considerations to treatment of radiation brain necrosis.

  17. Photoplethysmographic measurements from central nervous system tissue

    NASA Astrophysics Data System (ADS)

    Phillips, J. P.; Kyriacou, P. A.; Chang, S. H.; Maney, K.; George, K. J.; Langford, R. M.

    2007-10-01

    A new system for measuring the oxygen saturation of blood within tissue has been developed, for a number of potential patient monitoring applications. This proof of concept project aims to address the unmet need of real-time measurement of oxygen saturation in the central nervous system (CNS) for patients recovering from neurosurgery or trauma, by developing a fibre optic signal acquisition system for internal placement through small apertures. The development and testing of a two-wavelength optical fibre reflectance photoplethysmography (PPG) system is described together with measurements in rats and preliminary results from a clinical trial of the system in patients undergoing neurosurgery. It was found that good quality red and near-infrared PPG signals could be consistently obtained from the rat spinal cord (n=6) and human cerebral cortex (n=4) using the fibre optic probe. These findings justify further development and clinical evaluation of this fibre optic system.

  18. The central nervous system of ascidian larvae.

    PubMed

    Hudson, Clare

    2016-09-01

    Ascidians are marine invertebrate chordates. Their tadpole larvae contain a dorsal tubular nervous system, resulting from the rolling up of a neural plate. Along the anterior-posterior (A-P) axis, the central nervous system (CNS) is organized into a sensory vesicle, neck, trunk ganglion, and tail nerve cord and consists of approximately only 330 cells, of which around 100 are thought to be neurons. The organization of distinct neuronal cell types and neurotransmitter gene expression within the CNS has been described. The unique developmental mode of ascidians, with a small number of cells and a fixed cell division pattern, allows individual cells to be traced throughout development. This feature has led to the complete documentation of the cell lineages of certain cell types in the CNS. Thus, a step-by-step understanding of nervous system development from the initial stages of neural induction to the neurogenesis of individual neurons is a feasible goal. The genetic control of neural fate induction and early neural plate patterning are now well understood. The molecular mechanisms specifying the cholinergic neurons of the trunk ganglion as well as the pigment cells of the sensory organs are also well elucidated. In addition, studies have begun on the morphogenetic processes of neurulation. Remaining challenges include building an embryonic atlas integrating gene expression patterns, cell lineage, and neuronal cell types as well as developing the gene regulatory networks of cell fate specification and integrating them with the genetic control of morphogenesis. WIREs Dev Biol 2016, 5:538-561. doi: 10.1002/wdev.239 For further resources related to this article, please visit the WIREs website. PMID:27328318

  19. Vascularisation of the central nervous system

    PubMed Central

    Tata, Mathew; Ruhrberg, Christiana; Fantin, Alessandro

    2015-01-01

    The developing central nervous system (CNS) is vascularised through the angiogenic invasion of blood vessels from a perineural vascular plexus, followed by continued sprouting and remodelling until a hierarchical vascular network is formed. Remarkably, vascularisation occurs without perturbing the intricate architecture of the neurogenic niches or the emerging neural networks. We discuss the mouse hindbrain, forebrain and retina as widely used models to study developmental angiogenesis in the mammalian CNS and provide an overview of key cellular and molecular mechanisms regulating the vascularisation of these organs. PMID:26222953

  20. Catastrophic primary central nervous system vasculitis.

    PubMed

    Salvarani, Carlo; Brown, Robert D; Morris, Jonathan M; Huston, John; Hunder, Gene G

    2014-01-01

    Primary central nervous system vasculitis (PCNSV) is an uncommon condition that affects the brain and the spinal cord. It is heterogeneous in presenting characteristics and outcomes. We report a patient with a catastrophic rapidly progressive course refractory to intensive treatment with pulses of methylprednisolone and iv cyclophosphamide. The condition rapidly deteriorated and the patient died 6 weeks after presentation. Rapidly progressive PCNSV represents the worst end of the clinical spectrum of PCNSV. These patients are characterised by bilateral, multiple, large cerebral vessel lesions on angiograms and multiple bilateral cerebral infarctions. PMID:24854370

  1. Histoplasmosis of the central nervous system.

    PubMed Central

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

    1992-01-01

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

  2. Did the ctenophore nervous system evolve independently?

    PubMed

    Ryan, Joseph F

    2014-08-01

    Recent evidence supports the placement of ctenophores as the most distant relative to all other animals. This revised animal tree means that either the ancestor of all animals possessed neurons (and that sponges and placozoans apparently lost them) or that ctenophores developed them independently. Differentiating between these possibilities is important not only from a historical perspective, but also for the interpretation of a wide range of neurobiological results. In this short perspective paper, I review the evidence in support of each scenario and show that the relationship between the nervous system of ctenophores and other animals is an unsolved, yet tractable problem. PMID:24986234

  3. Physiology of the Autonomic Nervous System

    PubMed Central

    2007-01-01

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

  4. [Sports injuries of the nervous system].

    PubMed

    Lang, C; Stefan, H

    1999-08-01

    Almost 1% of all Germans suffer sports injuries each year, almost 5% of all peripheral nerve lesions are due to sports. A review is given on various activities detailing the specific risks for traumata of the central and peripheral nervous system. Specifically these are volleyball, handball, basketball, American football, soccer, bowling, hockey, baseball, tennis, golf, javelin, fencing, wrestling, judo, boxing, running, jumping, dancing, mountain climbing, weight lifting, gymnastics, horse-back riding, swimming, rowing, skiing, skating, shooting, (motor) biking, car racing, flying, and sports for the disabled. The knowledge of typical traumata should enable the neurologist to rapidly and reliably recognize related lesions and to contribute to their prevention or improvement. PMID:10478302

  5. Microglia: Architects of the Developing Nervous System.

    PubMed

    Frost, Jeffrey L; Schafer, Dorothy P

    2016-08-01

    Microglia are resident macrophages of the central nervous system (CNS), representing 5-10% of total CNS cells. Recent findings reveal that microglia enter the embryonic brain, take up residence before the differentiation of other CNS cell types, and become critical regulators of CNS development. Here, we discuss exciting new work implicating microglia in a range of developmental processes, including regulation of cell number and spatial patterning of CNS cells, myelination, and formation and refinement of neural circuits. Furthermore, we review studies suggesting that these cellular functions result in the modulation of behavior, which has important implications for a variety of neurological disorders. PMID:27004698

  6. Mold Infections of the Central Nervous System

    PubMed Central

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

    2016-01-01

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

  7. Central nervous system penetration-effectiveness rank does not reliably predict neurocognitive impairment in HIV-infected individuals

    PubMed Central

    Libertone, Raffaella; Lorenzini, Patrizia; Balestra, Pietro; Pinnetti, Carmela; Ricottini, Martina; Maddalena Plazzi, Maria; Menichetti, Samanta; Zaccarelli, Mauro; Nicastri, Emanuele; Bellagamba, Rita; Ammassari, Adriana; Antinori, Andrea

    2014-01-01

    Introduction Central nervous system (CNS) penetration-effectiveness (CPE) rank was proposed in 2008 as an estimate of penetration of ARV regimen into the CNS, and validated as predictor of CSF HIV-1 replication. Results on predictive role of CPE on neurocognitive and clinical outcome were conflicting. Materials and Methods Retrospective, cross-sectional analysis of neurocognitive profile in HIV-infected cART-treated patients. All patients underwent neuropsychological (NP) assessment by standardized battery of 14 tests on 5 different domains. People were classified as having NCI if they scored >1 standard deviation (SD) below the normal mean in at least two tests, or >2 SD below in one test. Linear and logistic regression analyses were fitted using as outcome Npz8 and impaired/not impaired respectively. Results A total of 660 HIV-infected cART-treated individuals from 2009 to 2014, contributing a total of 1003 tests (mean age 49 (IQR 43–56), male 82%; median current CD4 586/mm3; 18% HCV infected; HIV-RNA <40 cp/mL in 84%). Current ARV regimen was 2NRTIs+1NNRTI 50.3%, 2NRTI+1PI/r in 32.6%, NRTI sparing in 11.1%. Mean CPE of current regimens was 6.6 (95% CI 6.5–6.7). As per test multivariable analysis, higher CPE values were associated to poor NP tasks (Beta=−0,09; 95% CI −0,14 −0,03; p=0.002 at multivariable linear regression). The association between higher CPE and increased NCI risk was confirmed at multivariable logistic regression, with a 1.24-fold risk of NCI occurrence for each point increase of CPE of current regimen at the time of NP testing (see Table 1). In a sensitivity analysis performed only on patients at the first NP test, the association between higher CPE and poor NP tasks and enhanced NCI risk was only marginally confirmed (Beta=−0,05; [−0,12–0,02]; p=0,19; OR 1,13 [0,95–1,34]; p=0.17). Older age, longer time from HIV diagnosis, current CD4 count <350 cell/mm3 and lower education level were all associated to an increased risk of

  8. Neural Circuit Recording from an Intact Cockroach Nervous System

    PubMed Central

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

    2013-01-01

    The cockroach ventral nerve cord preparation is a tractable system for neuroethology experiments, neural network modeling, and testing the physiological effects of insecticides. This article describes the scope of cockroach sensory modalities that can be used to assay how an insect nervous system responds to environmental perturbations. Emphasis here is on the escape behavior mediated by cerci to giant fiber transmission in Periplaneta americana. This in situ preparation requires only moderate dissecting skill and electrophysiological expertise to generate reproducible recordings of neuronal activity. Peptides or other chemical reagents can then be applied directly to the nervous system in solution with the physiological saline. Insecticides could also be administered prior to dissection and the escape circuit can serve as a proxy for the excitable state of the central nervous system. In this context the assays described herein would also be useful to researchers interested in limb regeneration and the evolution of nervous system development for which P. americana is an established model organism. PMID:24300738

  9. Novel nervous system mechanisms in visceral pain.

    PubMed

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

    2016-03-01

    Visceral hypersensitivity is an important factor underlying abdominal pain in functional gastrointestinal disorders such as irritable bowel syndrome (IBS) and can result from aberrant signaling from the gut to the brain or vice versa. Over the last two decades, research has identified several selective, intertwining pathways that underlie IBS-related visceral nociception, including specific receptors on afferent and efferent nerve fibers such as transient receptor potential channels (TRP) channels, opioid, and cannabinoid receptors. In this issue of Neurogastroenterology and Motility Gil et al. demonstrate that in an animal model with reduced descending inhibitory control, the sympathetic nervous system outflow is enhanced, contributing to visceral and somatic hypersensitivity. They also provide evidence that interfering with the activation of adrenergic receptors on sensory nerves can be an interesting new strategy to treat visceral pain in IBS. This mini-review places these findings in a broader perspective by providing an overview of promising novel mechanisms to alter the nervous control of visceral pain interfering with afferent or efferent neuronal signaling. PMID:26891060

  10. Central nervous system phenotypes in craniosynostosis

    PubMed Central

    Aldridge, Kristina; Marsh, Jeffrey L; Govier, Daniel; Richtsmeier, Joan T

    2002-01-01

    Though reduction in the number of cranial elements through loss of a suture is a recognized trend in vertebrate evolution, the premature closure of cranial sutures in humans, craniosynostosis, is considered a pathological condition. Previous research on craniosynostosis has focused primarily on the skeletal phenotype, but the intimate relationship between the developing central nervous system (CNS) and skull is well documented. We investigate the morphology of the CNS in patients with isolated craniosynostosis through an analysis of cortical and subcortical features using 3-D magnetic resonance images (MRI). Results show that a distinct CNS phenotype can be defined for specific diagnostic categories. Many differences in CNS morphology observed in the patient samples may be anticipated based on skeletal morphology, but others are not reflected in the skull. We propose a developmental approach to determining the cause of premature suture fusion, which includes investigation of the craniofacial complex as a system, rather than study of isolated tissues. PMID:12171474

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

    PubMed

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

    2015-01-01

    Systemized data on epidemiology, pathogenesis, clinical manifestation, diagnostics and therapy of VZV-vasculopathy--a disease, occurring due to damage of arteries of the central nervous system by Varicella Zoster virus, are presented in the review. A special attention in the paper is given to the effect of vaccine prophylaxis of chicken pox and herpes zoster on the frequency of development and course of VZV-vasculopathy. PMID:26259280

  12. Effects of Electroacupuncture on Pain Threshold of Laboring Rats and the Expression of Norepinephrine Transporter and α2 Adrenergic Receptor in the Central Nervous System

    PubMed Central

    Lin, Shike; Feng, Yuanyuan; Zhang, Qi; Wang, Meili; Wang, Yu

    2016-01-01

    To observe the effects of electroacupuncture on pain threshold of laboring rats and the expression of norepinephrine transporter and α2 adrenergic receptor in the central nervous system to determine the mechanism of the analgesic effect of labor. 120 pregnant rats were divided into 6 groups: a control group, 4 electroacupuncture groups, and a meperidine group. After interventions, the warm water tail-flick test was used to observe pain threshold. NE levels in serum, NET, and α2AR mRNA and protein expression levels in the central nervous system were measured. No difference in pain threshold was observed between the 6 groups before intervention. After intervention, increased pain thresholds were observed in all groups except the control group with a higher threshold seen in the electroacupuncture groups. Serum NE levels decreased in the electroacupuncture and MP groups. Increases in NET and α2AR expression in the cerebral cortex and decreases in enlarged segments of the spinal cord were seen. Acupuncture increases uptake of NE via cerebral NET and decreases its uptake by spinal NET. The levels of α2AR are also increased and decreased, respectively, in both tissues. This results in a decrease in systemic NE levels and may be the mechanism for its analgesic effects. PMID:27547232

  13. Cryptococcosis of the central nervous system

    PubMed Central

    Edwards, V. E.; Sutherland, J. M.; Tyrer, J. H.

    1970-01-01

    (1) A survey of cryptococcal infections of the nervous system in Queensland, Australia, revealed the nine year prevalence rate for the Australian aboriginal to be some 17 times greater than that of the white population. Uncommon in the first decade of life, the disease was developed by 79% of 29 patients between 20 and 59 years, males being affected twice as commonly as females. (2) Cryptococcosis appears to be more common in Australia than in the United Kingdom, and in Queensland the nine year incidence of neurological cryptococcosis was 4·7 per 100,000 in the tropical north compared with 1·8 per 100,000 in the southern parts of the State. Because of this, and since 20 of the 29 patients were regarded as having outdoor occupations, it is suggested that a high environmental exposure to the fungus may be associated with an animal reservoir and with dry, dusty conditions. It is also possible that geographical and occupational factors rather than racial predisposition account for the high incidence of the disease in the Australian aborigine. However, individual resistance and susceptibility are probably also important factors, since the clinical disease appears to be positively correlated with certain other diseases, or with steroid therapy, which would impair the immune responses of the body. (3) Headache is the outstanding symptom of neurological cryptococcosis and fever or evidence of meningeal reaction, though often present, may be absent. An awareness of the possibility of neurological cryptococcosis in the differential diagnosis of various intracranial disorders should lead to identification of the encapsulated C. neoformans in the cerebrospinal fluid. Although in eight of 26 patients the lumbar cerebrospinal fluid was sterile on repeated examination, in five cases C. neoformans was found on direct examination of cerebrospinal fluid obtained by ventricular puncture. The remaining three died before further investigations could be performed. (4) Before the

  14. Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure

    PubMed Central

    Azher, Seema; Margolis, Frank L.; Patel, Kamakshi; Mousa, Ahmad; Majid, Arshad

    2013-01-01

    Carnosine-like peptides (carnosine-LP) are a family of histidine derivatives that are present in the nervous system of various species and that exhibit antioxidant, anti-matrix-metalloproteinase, anti-excitotoxic, and free-radical scavenging properties. They are also neuroprotective in animal models of cerebral ischemia. Although the function of carnosine-LP is largely unknown, the hypothesis has been advanced that they play a role in the developing nervous system. Since the zebrafish is an excellent vertebrate model for studying development and disease, we have examined the distribution pattern of carnosine-LP in the adult and developing zebrafish. In the adult, immunoreactivity for carnosine-LP is specifically concentrated in sensory neurons and non-sensory cells of the olfactory epithelium, the olfactory nerve, and the olfactory bulb. Robust staining has also been observed in the retinal outer nuclear layer and the corneal epithelium. Developmental studies have revealed immunostaining for carnosine-LP as early as 18 h, 24 h, and 7 days post-fertilization in, respectively, the olfactory, corneal, and retinal primordia. These data suggest that carnosine-LP are involved in olfactory and visual function. We have also investigated the effects of chronic (7 days) exposure to carnosine on embryonic development and show that 0.01 μM to 10 mM concentrations of carnosine do not elicit significant deleterious effects. Conversely, treatment with 100 mM carnosine results in developmental delay and compromised larval survival. These results indicate that, at lower concentrations, exogenously administered carnosine can be used to explore the role of carnosine in development and developmental disorders of the nervous system. PMID:19440736

  15. Differential effects of methylmercury, thiols, and vitamins on galactosidases of nervous and non-nervous tissues

    SciTech Connect

    Vijayalakshmi, K.; Bapu, C.; Sood, P.P.

    1992-07-01

    A rational pharmacological attack on heavy metal poisoning has only been possible with the advent of non-toxic binding of chelating agents. In the recent past, a number of chelators have been used to detoxicate the mercury content from the body. When all the well known chelators were subjected for their therapeutic capacities in the central nervous system, most of the findings were discouraging. In a recent study we have demonstrated the superiority of vitamins over thiol compounds in methylmercury mobilization, which otherwise has been considered difficult and often an impossible task for clinicians as well as toxicologists. Biochemical lesions are considered to be the most primary effects of methylmercury toxication, and lysosomes are the critical cellular organelles which are easily ruptured and release enzymes. In the present study, the biochemical analyses of two lysosomal enzymes (alpha and beta-galactosidases) in various nervous and non-nervous tissues of mice during methylmercury toxication as well as detoxication with vitamins and thiols have been studied in the light of previous investigation related to methylmercury mobilization with these agents. 11 refs., 2 figs.

  16. Varicella Zoster Virus in the Nervous System

    PubMed Central

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

    2015-01-01

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

  17. 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.

  18. 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. PMID:26475775

  19. The autonomic nervous system and renal physiology

    PubMed Central

    D’Elia, John A; Weinrauch, Larry A

    2013-01-01

    Research in resistant hypertension has again focused on autonomic nervous system denervation – 50 years after it had been stopped due to postural hypotension and availability of newer drugs. These (ganglionic blockers) drugs have all been similarly stopped, due to postural hypotension and yet newer antihypertensive agents. Recent demonstration of the feasibility of limited regional transcatheter sympathetic denervation has excited clinicians due to potential therapeutic implications. Standard use of ambulatory blood pressure recording equipment may alter our understanding of the diagnosis, potential treatment strategies, and health care outcomes – when faced with patients whose office blood pressure remains in the hypertensive range – while under treatment with three antihypertensive drugs at the highest tolerable doses, plus a diuretic. We review herein clinical relationships between autonomic function, resistant hypertension, current treatment strategies, and reflect upon the possibility of changes in our approach to resistant hypertension. PMID:24039445

  20. Environmentally related disorders of the nervous system

    SciTech Connect

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

    1990-03-01

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

  1. Subcortical cytoskeleton periodicity throughout the nervous system.

    PubMed

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

    2016-01-01

    Superresolution fluorescence microscopy recently revealed a ~190 nm periodic cytoskeleton lattice consisting of actin, spectrin, and other proteins underneath the membrane of cultured hippocampal neurons. Whether the periodic cytoskeleton lattice is a structural feature of all neurons and how it is modified when axons are ensheathed by myelin forming glial cells is not known. Here, STED nanoscopy is used to demonstrate that this structure is a commonplace of virtually all neuron types in vitro. To check how the subcortical meshwork is modified during myelination, we studied sciatic nerve fibers from adult mice. Periodicity of both actin and spectrin was uncovered at the internodes, indicating no substantial differences between unmyelinated and myelinated axons. Remarkably, the actin/spectrin pattern was also detected in glial cells such as cultured oligodendrocyte precursor cells. Altogether our work shows that the periodic subcortical cytoskeletal meshwork is a fundamental characteristic of cells in the nervous system and is not a distinctive feature of neurons, as previously thought. PMID:26947559

  2. [Histopathology of central nervous system cavernomas].

    PubMed

    Mosnier, J-F; Brunon, J; Nuti, C

    2007-06-01

    Central nervous system cavernomas are vascular malformations, which occur in two circumstances: sporadic forms and familial autosomal dominant forms. The lesion consists of enlarged, closely packed vessels without interposition of brain parenchyma, surrounded by hemosiderin and gliosis, calcified in few cases. In 80% of sporadic forms the lesion is unique, multiple lesions are rare (median: 4). In familial forms the lesions are always multiple. Cavernomas are often associated with other vascular malformations, especially with venous developmental anomalies. The size of cavernomas is variable from 1 mm to several centimeters. About 70% of cases are supratentorial and 30% in the posterior fossa, particularly in the brain stem. Macroscopic and histopathological findings are typical and the diagnostic is generally easy. PMID:17498756

  3. Scaffolds for central nervous system tissue engineering

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  4. Gangliosides of the Vertebrate Nervous System.

    PubMed

    Schnaar, Ronald L

    2016-08-14

    Gangliosides, sialylated glycosphingolipids, found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Composed of a sialylated glycan attached to a ceramide lipid, the same four structures-GM1, GD1a, GD1b, and GT1b-represent the vast majority (>90%) of gangliosides in the brains of all mammals and birds. Primarily found on the outer surface of the plasma membrane with their glycans facing outward, gangliosides associate laterally with each other, sphingomyelin, cholesterol, and select proteins in lipid rafts-the dynamic functional subdomains of the plasma membrane. The functions of gangliosides in the human nervous system are revealed by congenital mutations in ganglioside biosynthetic genes. Mutations in ST3GAL5, which codes for an enzyme early in brain ganglioside biosynthesis, result in an early-onset seizure disorder with profound motor and cognitive decay, whereas mutations in B4GALNT1, a gene encoding a later step, result in hereditary spastic paraplegia accompanied by intellectual deficits. The molecular functions of brain gangliosides include regulation of receptors in the same membrane via lateral (cis) associations and regulation of cell-cell recognition by trans interaction with ganglioside binding proteins on apposing cells. Gangliosides also affect the aggregation of Aβ (Alzheimer's disease) and α-synuclein (Parkinson's Disease). As analytical, biochemical, and genetic tools advance, research on gangliosides promises to reveal mechanisms of molecular control related to nerve and glial cell differentiation, neuronal excitability, axon outgrowth after nervous system injury, and protein folding in neurodegenerative diseases. PMID:27261254

  5. Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection.

    PubMed

    Vidlak, Debbie; Kielian, Tammy

    2012-01-01

    Although IL-17A (commonly referred to as IL-17) has been implicated in the pathogenesis of central nervous system (CNS) autoimmune disease, its role during CNS bacterial infections remains unclear. To evaluate the broader impact of IL-17 family members in the context of CNS infection, we utilized IL-17 receptor (IL-17R) knockout (KO) mice that lack the ability to respond to IL-17, IL-17F and IL-17E (IL-25). In this article, we demonstrate that IL-17R signaling regulates bacterial clearance as well as natural killer T (NKT) cell and gamma-delta (γδ) T cell infiltrates during Staphylococcus aureus-induced brain abscess formation. Specifically, when compared with wild-type (WT) animals, IL-17R KO mice exhibited elevated bacterial burdens at days 7 and 14 following S. aureus infection. Additionally, IL-17R KO animals displayed elevated neutrophil chemokine production, revealing the ability to compensate for the lack of IL-17R activity. Despite these differences, innate immune cell recruitment into brain abscesses was similar in IL-17R KO and WT mice, whereas IL-17R signaling exerted a greater influence on adaptive immune cell recruitment. In particular, γδ T cell influx was increased in IL-17R KO mice at day 7 post-infection. In addition, NK1.1high infiltrates were absent in brain abscesses of IL-17R KO animals and, surprisingly, were rarely detected in the livers of uninfected IL-17R KO mice. Although IL-17 is a key regulator of neutrophils in other infection models, our data implicate an important role for IL-17R signaling in regulating adaptive immunity during CNS bacterial infection. PMID:22704602

  6. Evaluation of the Effects of the Aqueous Extract of Vitex doniana Root-Bark on the Peripheral and Central Nervous System of Laboratory Animals

    NASA Astrophysics Data System (ADS)

    Abdulrahman, F. I.; Onyeyili, P. A.; Sandabe, U. K.; Ogugbuaja, V. O.

    Aim of this study to investigate the effects of aqueous extract of Vitrex doniana on the peripheral and central nervous systems and possibility to use it as folk medicine. The aqueous extract of Vitex doniana was soxhlet extracted with distilled water and concentrated in vacuo to give a yield of 8.5% w/w. The LD50 following intraperitoneal administration was estimated to be 980 mg kgG1. The aqueous extract of Vitex doniana from the study produced substantial depressant effects on both the peripheral and central nervous system. The aqueous extract induced sleep on its own at dose of 400 mg kgG1 and potentiated sodium thiopental sleeping time in a dose dependant manner. It also showed significant (p< 0.05) muscle relaxant activities and produced analgesia and weal anesthetic effect. The extract was able to confer 80% protection to rats treated with convulsive dose of PTZ, while it conferred 100% protection to rats treated with convulsion dose of strychnine.

  7. Myelin synthesis in the peripheral nervous system.

    PubMed

    Garbay, B; Heape, A M; Sargueil, F; Cassagne, C

    2000-06-01

    By imposing saltatory conduction on the nervous impulse, the principal role of the myelin sheath is to allow the faster propagation of action potentials along the axons which it surrounds. Peripheral nervous system (PNS) myelin is formed by the differentiation of the plasma membrane of Schwann cells. One of the biochemical characteristics that distinguishes myelin from other biological membranes is its high lipid-to-protein ratio. All the major lipid classes are represented in the myelin membrane, while several myelin-specific proteins have been identified. During development, the presence of axons is required for the initiation of myelination, but the nature of the axonal signal is still unknown. The only certainties are that this signal is synthesized by axons whose diameter is greater than 0.7 microm, and that the signal(s) include(s) a diffusible molecule. Morphological studies have provided us with information concerning the timing of myelination, the mechanism by which immature Schwann cells differentiate into a myelinating phenotype and lay down the myelin sheath around the axon, and the accumulation and the structure of the myelin membrane. The last 20 years have seen the identification and the cDNA and gene cloning of the major PNS myelin proteins, which signalled the beginning of the knock-out decade: transgenic null-mutant mice have been created for almost every protein gene. The study of these animals shows that the formation of myelin is considerably less sensitive to molecular alterations than the maintenance of myelin. During the same period, important data has been gathered concerning the synthesis and function of lipids in PNS myelin, although this field has received relatively little attention compared with that of their protein counterparts. PMID:10727776

  8. Experimental study of the mechanism and indices of harmful effects of certain chemical substances on the central nervous system

    PubMed Central

    Bokina, A. I.; Merkur'yeva, R. V.; Eksler, N. D.; Oleynik, A. A.; Pinigina, I. I.

    1979-01-01

    The task of the second stage of Soviet-American cooperation on the problem of environmental health science was to explain the question of the comparative sensitivity of methods used in both countries, as well as the indices of harmful effects for the same toxic substance (carbon disulfide), with the purpose of determining the most informative methods of assessing the influence of atmospheric pollutants on organisms. The application of neurophysiological research methods (recording total electrical activity of the cortex and cortical structures of the brain, studying amplitude-time characteristics of averaged evoked potentials of the optical cortex, investigating sensory and convulsive thresholds) has made it possible to explain the neurophysiological basis of the effect of carbon disulfide on the central nervous system—the perturbation of cortical inhibition processes and the increase of excitation in amygdalate structures, both of which play an important role in the fixation process of temporary connection. The compilation of data from neurophysiological and neurochemical investigations show that neurophysiological changes are associated primarily with a decrease in enzymic breakdown of free neuraminic acid. The study of the average evoked potentials in humans during exposure to carbon disulfide concentrations of 0.09 mg/m3 revealed a tendency to decrease the short latent amplitude components and increase the long latent amplitude components of the averaged evoked potentials. The study of operant behavior in rats revealed a characteristic change in the instrumental alimentary reactions under long-term (3 months) exposure of carbon disulfide to a concentration of 16 mg/m3. In this manner, the following were developed in experiments with animals and research on humans: indices of the harmful effects of neurotropic toxic substances, a change in operant behavior, a decrease in the amplitude of total electrical activity, a change in time-amplitude parameters of

  9. Simvastatin Hydroxy Acid Fails to Attain Sufficient Central Nervous System Tumor Exposure to Achieve a Cytotoxic Effect: Results of a Preclinical Cerebral Microdialysis Study.

    PubMed

    Patel, Yogesh T; Jacus, Megan O; Davis, Abigail D; Boulos, Nidal; Turner, David C; Vuppala, Pradeep K; Freeman, Burgess B; Gilbertson, Richard J; Stewart, Clinton F

    2016-04-01

    3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors were potent hits against a mouse ependymoma cell line, but their effectiveness against central nervous system tumors will depend on their ability to cross the blood-brain barrier and attain a sufficient exposure at the tumor. Among 3-hydroxy-3-methylglutaryl coenzyme A inhibitors that had activity in vitro, we prioritized simvastatin (SV) as the lead compound for preclinical pharmacokinetic studies based on its potential for central nervous system penetration as determined from in silico models. Furthermore, we performed systemic plasma disposition and cerebral microdialysis studies of SV (100 mg/kg, p.o.) in a murine model of ependymoma to characterize plasma and tumor extracellular fluid (tECF) pharmacokinetic properties. The murine dosage of SV (100 mg/kg, p.o.) was equivalent to the maximum tolerated dose in patients (7.5 mg/kg, p.o.) based on equivalent plasma exposure of simvastatin acid (SVA) between the two species. SV is rapidly metabolized in murine plasma with 15 times lower exposure compared with human plasma. SVA exposure in tECF was <33.8 ± 11.9 µg/l per hour, whereas the tumor to plasma partition coefficient of SVA was <0.084 ± 0.008. Compared with in vitro washout IC50 values, we did not achieve sufficient exposure of SVA in tECF to suggest tumor growth inhibition; therefore, SV was not carried forward in subsequent preclinical efficacy studies. PMID:26802130

  10. [Effect of artificial mountain climate on the functional state of higher regions of the central nervous system in man].

    PubMed

    Berezovskiĭ, V A; Levashov, M I

    2009-01-01

    The study included 97 patients with vegetative vascular dystonia and chronic non-specific pulmonary diseases exposed to artificial high-altitude climate in an Orotron climatic chamber during 2 weeks. Atmospheric conditions maintained in the chamber had the following parameters: partial pressure of oxygen--147-160 gPa, relative humidity--60-70%, air temperature--16-18 degrees C, light aeroion content--up to 6000 cub.cm. It was shown that the exposure to artificial mountain climatic conditions enhanced functional mobility of nervous processes and decreased the length of the sensorimotor reactions of the patients. Individual differences in the change of parameters being measured depended on the degree of initial functional flexibility of nervous processes. PMID:19517597

  11. Regulation of sympathetic nervous system function after cardiovascular deconditioning

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  12. Prenatal diagnosis of central nervous system abnormalities.

    PubMed

    Angtuaco, E E; Angtuaco, T L; Angtuaco, E J

    1994-01-01

    Fetal anomalies have been the subject of innumerable publications both in the prenatal and neonatal literature. This has significantly increased in the last 10 years, mainly because of the advent of high-resolution ultrasound equipment and improvement of scanning techniques. In addition, guidelines issued by professional organizations involved in prenatal diagnosis have encouraged a more universal approach to the imaging and documentation of prenatal findings. The fetal central nervous system is the most frequently investigated organ system, mainly because of its easy accessibility and prominence even in the early stages of embryologic development. The biparietal diameter was the first fetal measurement to be widely used in determining gestational age. As investigators gained more experience, the appearance of ultrasound images achieved the resolution that allows direct comparisons with gross specimens and more recent sophisticated techniques of computed tomography and magnetic resonance imaging. Now endovaginal ultrasound can document early first trimester development and compare it to known embryologic landmarks. Interest in demonstrating the ultrasound counterpart of central nervous system structures in the early stages of development has resulted in a plethora of articles proving the unique ability of ultrasound in imaging the developing fetus. In view of all these developments, the beginning ultrasound specialist is faced with the challenge and responsibility not only of being familiar with the literature but also of the mastery of scanning techniques that allow accurate prenatal diagnosis. It is therefore helpful to review key developmental milestones in embryologic life and correlate them with the corresponding prenatal ultrasound appearance. In addition, the changing appearance of the developing fetus has created a need for a systematic approach in the evaluation of structures so routine protocols can be established. This has been the subject of other

  13. Oxidation of ion channels in the aging nervous system.

    PubMed

    Patel, Rahul; Sesti, Federico

    2016-05-15

    Ion channels are integral membrane proteins that allow passive diffusion of ions across membranes. In neurons and in other excitable cells, the harmonious coordination between the numerous types of ion channels shape and propagate electrical signals. Increased accumulation of reactive oxidative species (ROS), and subsequent oxidation of proteins, including ion channels, is a hallmark feature of aging and may contribute to cell failure as a result. In this review we discuss the effects of ROS on three major types of ion channels of the central nervous system, namely the potassium (K(+)), calcium (Ca(2+)) and sodium (Na(+)) channels. We examine two general mechanisms through which ROS affect ion channels: via direct oxidation of specific residues and via indirect interference of pathways that regulate the channels. The overall status of the present studies indicates that the interaction of ion channels with ROS is multimodal and pervasive in the central nervous system and likely constitutes a general mechanism of aging susceptibility. PMID:26947620

  14. [The role of metalloprotease in pathogenesis of nervous system diseases].

    PubMed

    Mirowska, D; Członkowska, A

    2001-01-01

    Matrix Metalloproteases (MMPs) comprise a big family of proteolytic enzymes secreted into extracellular matrix and involved in remodelling of many tissues. The MMPs' activity is regulated on many levels. It is also determined by specific inhibitors known as tissue inhibitors of metalloproteases (TIMPs). Several studies revealed that MMPs have a role not only in physiological processes but also in pathophysiology of nervous system diseases, such as multiplex sclerosis, Guillan-Barré syndrome and strokes. Concerning demyelination MMPs are responsible for degradation of myelin components and facilitation of immune cells migration into inflammatory sites by degrading vascular basement membrane. We still investigate substances with positive clinical effect on the nervous system diseases due to MMPs inactivation. PMID:11464705

  15. 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

  16. Regulation of cadherin expression in nervous system development

    PubMed Central

    Paulson, Alicia F; Prasad, Maneeshi S; Thuringer, Amanda Henke; Manzerra, Pasquale

    2014-01-01

    This review addresses our current understanding of the regulatory mechanisms for classical cadherin expression during development of the vertebrate nervous system. The complexity of the spatial and temporal expression patterns is linked to morphogenic and functional roles in the developing nervous system. While the regulatory networks controlling cadherin expression are not well understood, it is likely that the multiple signaling pathways active in the development of particular domains also regulate the specific cadherins expressed at that time and location. With the growing understanding of the broader roles of cadherins in cell–cell adhesion and non-adhesion processes, it is important to understand both the upstream regulation of cadherin expression and the downstream effects of specific cadherins within their cellular context. PMID:24526207

  17. Central nervous system adaptation to exercise training

    NASA Astrophysics Data System (ADS)

    Kaminski, Lois Anne

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

  18. Central Nervous System Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Boulware, David R.; Marais, Suzaan; Scriven, James; Wilkinson, Robert J.; Meintjes, Graeme

    2013-01-01

    Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS) develops in 9 %–47 % of persons with HIV infection and a CNS opportunistic infection who start antiretroviral therapy and is associated with a mortality rate of 13 %–75 %. These rates vary according to the causative pathogen. Common CNS-IRIS events occur in relation to Cryptococcus, tuberculosis (TB), and JC virus, but several other mycobacteria, fungi, and viruses have been associated with IRIS. IRIS symptoms often mimic the original infection, and diagnosis necessitates consideration of treatment failure, microbial resistance, and an additional neurological infection. These diagnostic challenges often delay IRIS diagnosis and treatment. Corticosteroids have been used to treat CNS-IRIS, with variable responses; the best supportive evidence exists for the treatment of TB-IRIS. Pathogenic mechanisms vary: Cryptococcal IRIS is characterized by a paucity of cerebrospinal inflammation prior to antiretroviral therapy, whereas higher levels of inflammatory markers at baseline predispose to TB meningitis IRIS. This review focuses on advances in the understanding of CNS-IRIS over the past 2 years. PMID:24173584

  19. Time Perception Mechanisms at Central Nervous System

    PubMed Central

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

    2016-01-01

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

  20. 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. PMID:27127597

  1. Subcortical cytoskeleton periodicity throughout the nervous system

    PubMed Central

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

    2016-01-01

    Superresolution fluorescence microscopy recently revealed a ~190 nm periodic cytoskeleton lattice consisting of actin, spectrin, and other proteins underneath the membrane of cultured hippocampal neurons. Whether the periodic cytoskeleton lattice is a structural feature of all neurons and how it is modified when axons are ensheathed by myelin forming glial cells is not known. Here, STED nanoscopy is used to demonstrate that this structure is a commonplace of virtually all neuron types in vitro. To check how the subcortical meshwork is modified during myelination, we studied sciatic nerve fibers from adult mice. Periodicity of both actin and spectrin was uncovered at the internodes, indicating no substantial differences between unmyelinated and myelinated axons. Remarkably, the actin/spectrin pattern was also detected in glial cells such as cultured oligodendrocyte precursor cells. Altogether our work shows that the periodic subcortical cytoskeletal meshwork is a fundamental characteristic of cells in the nervous system and is not a distinctive feature of neurons, as previously thought. PMID:26947559

  2. In vivo peripheral nervous system insulin signaling

    PubMed Central

    Grote, Caleb W.; Ryals, Janelle M.; Wright, Douglas E.

    2014-01-01

    Alterations in peripheral nervous system (PNS) insulin support may contribute to diabetic neuropathy (DN); yet, PNS insulin signaling is not fully defined. Here, we investigated in vivo insulin signaling in the PNS and compared the insulin-responsiveness to that of muscle, liver, and adipose. Nondiabetic mice were administered increasing doses of insulin to define a dose response relationship between insulin and Akt activation in the DRG and sciatic nerve. Resulting EC50 doses were used to characterize the PNS insulin signaling time course and make comparisons between insulin signaling in the PNS and other peripheral tissues (i.e., muscle, liver, adipose). The results demonstrate that the PNS is responsive to insulin and that differences in insulin signaling pathway activation exist between PNS compartments. At a therapeutically relevant dose, Akt was activated in the muscle, liver, and adipose at 30 minutes, correlating with the changes in blood glucose levels. Interestingly, the sciatic nerve showed a similar signaling profile as insulin-sensitive tissues, however there was not a comparable activation in the DRG or spinal cord. These results present new evidence regarding PNS insulin signaling pathways in vivo and provide a baseline for studies investigating the contribution of disrupted PNS insulin signaling to DN pathogenesis. PMID:24028189

  3. Diabetes and the enteric nervous system.

    PubMed

    Chandrasekharan, B; Srinivasan, S

    2007-12-01

    Diabetes is associated with several changes in gastrointestinal (GI) motility and associated symptoms such as nausea, bloating, abdominal pain, diarrhoea and constipation. The pathogenesis of altered GI functions in diabetes is multifactorial and the role of the enteric nervous system (ENS) in this respect has gained significant importance. In this review, we summarize the research carried out on diabetes-related changes in the ENS. Changes in the inhibitory and excitatory enteric neurons are described highlighting the role of loss of inhibitory neurons in early diabetic enteric neuropathy. The functional consequences of these neuronal changes result in altered gastric emptying, diarrhoea or constipation. Diabetes can also affect GI motility through changes in intestinal smooth muscle or alterations in extrinsic neuronal control. Hyperglycaemia and oxidative stress play an important role in the pathophysiology of these ENS changes. Antioxidants to prevent or treat diabetic GI motility problems have therapeutic potential. Recent research on the nerve-immune interactions demonstrates inflammation-associated neurodegeneration which can lead to motility related problems in diabetes. PMID:17971027

  4. Early animal evolution and the origins of nervous systems

    PubMed Central

    Budd, Graham E.

    2015-01-01

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

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

    PubMed

    Budd, Graham E

    2015-12-19

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

  6. Activation of Latent Human Immunodeficiency Virus by the Histone Deacetylase Inhibitor Panobinostat: A Pilot Study to Assess Effects on the Central Nervous System

    PubMed Central

    Rasmussen, Thomas A.; Tolstrup, Martin; Møller, Holger Jon; Brinkmann, Christel R.; Olesen, Rikke; Erikstrup, Christian; Laursen, Alex L.; Østergaard, Lars; Søgaard, Ole S.

    2015-01-01

    In a substudy of a clinical trial, we assessed whether activation of latent human immunodeficiency virus (HIV) by the histone deacetylase inhibitor panobinostat had detrimental effects on the central nervous system (CNS). Adults infected with HIV received oral panobinostat 20 mg 3 times per week every other week for 8 weeks. In cerebrospinal fluid (CSF), we assayed panobinostat concentration, HIV RNA, and the level of neuroinflammatory or degenerative biomarkers in 11 individuals before and during study therapy. Neither panobinostat nor HIV RNA was detected in CSF. In addition, there was no change from baseline in CSF biomarkers. Thus, panobinostat administration was not associated with CNS adverse effects as assessed by CSF biomarkers. PMID:26034779

  7. N-glycosylation in Regulation of the Nervous System

    PubMed Central

    Scott, Hilary; Panin, Vladislav M.

    2015-01-01

    Summary Protein N-glycosylation can influence the nervous system in a variety of ways by affecting functions of glycoproteins involved in nervous system development and physiology. The importance of N-glycans for different aspects of neural development has been well documented. For example, some N-linked carbohydrate structures were found to play key roles in neural cell adhesion and axonal targeting during development. At the same time, the involvement of glycosylation in the regulation of neural physiology remains less understood. Recent studies have implicated N-glycosylation in the regulation of neural transmission, revealing novel roles of glycans in synaptic processes and the control of neural excitability. N-Glycans were found to markedly affect the function of several types of synaptic proteins involved in key steps of synaptic transmission, including neurotransmitter release, reception and uptake. Glycosylation also regulates a number of channel proteins, such as TRP channels that control responses to environmental stimuli and voltage-gated ion channels, the principal determinants of neuronal excitability. Sialylated carbohydrate structures play a particularly prominent part in the modulation of voltage gated ion channels. Sialic acids appear to affect channel functions via several mechanisms, including charge interactions, as well as other interactions that probably engage steric effects and interactions with other molecules. Experiments also indicated that some structural features of glycans can be particularly important for their function. Since glycan structures can vary significantly between different cell types and depends on the metabolic state of the cell, it is important to analyze glycan functions using in vivo approaches. While the complexity of the nervous system and intricacies of glycosylation pathways can create serious obstacles for in vivo experiments in vertebrates, recent studies have indicated that more simple and experimentally

  8. The Biphasic Effects of Moderate Alcohol Consumption with a Meal on Ambiance-Induced Mood and Autonomic Nervous System Balance: A Randomized Crossover Trial

    PubMed Central

    Schrieks, Ilse C.; Stafleu, Annette; Kallen, Victor L.; Grootjen, Marc; Witkamp, Renger F.; Hendriks, Henk F. J.

    2014-01-01

    Background The pre-drinking mood state has been indicated to be an important factor in the mood effects of alcohol. However, for moderate alcohol consumption there are no controlled studies showing this association. Also, the mood effects of consuming alcohol combined with food are largely unknown. The aim of this study was to investigate the effects of moderate alcohol combined with a meal on ambiance-induced mood states. Furthermore effects on autonomic nervous system activity were measured to explore physiological mechanisms that may be involved in changes of mood state. Methods In a crossover design 28 women (age 18–45 y, BMI 18.5–27 kg/m2) were randomly allocated to 4 conditions in which they received 3 glasses of sparkling white wine (30 g alcohol) or alcohol-free sparkling white wine while having dinner in a room with either a pleasant or unpleasant created ambiance. Subjects filled out questionnaires (B-BAES, POMS and postprandial wellness questionnaire) at different times. Skin conductance and heart rate variability were measured continuously. Results Moderate alcohol consumption increased happiness scores in the unpleasant, but not in the pleasant ambiance. Alcohol consumption increased happiness and stimulation feelings within 1 hour and increased sedative feelings and sleepiness for 2.5 hour. Skin conductance was increased after alcohol within 1 hour and was related to happiness and stimulation scores. Heart rate variability was decreased after alcohol for 2 hours and was related to mental alertness. Conclusion Mood inductions and autonomic nervous system parameters may be useful to evaluate mood changes by nutritional interventions. Moderate alcohol consumption elevates happiness scores in an unpleasant ambiance. However, drinking alcohol during a pleasant mood results in an equally positive mood state. Trial Registration Clinicaltrials.gov NCT01426022. PMID:24465955

  9. Melatonin Metabolism in the Central Nervous System

    PubMed Central

    Hardeland, Rüdiger

    2010-01-01

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

  10. Evaluation of the effects of plant-derived essential oils on central nervous system function using discrete shuttle-type conditioned avoidance response in mice.

    PubMed

    Umezu, Toyoshi

    2012-06-01

    Although plant-derived essential oils (EOs) have been used to treat various mental disorders, their central nervous system (CNS) acting effects have not been clarified. The present study compared the effects of 20 kinds of EOs with the effects of already-known CNS acting drugs to examine whether the EOs exhibited CNS stimulant-like effects, CNS depressant-like effects, or neither. All agents were tested using a discrete shuttle-type conditioned avoidance task in mice. Essential oils of peppermint and chamomile exhibited CNS stimulant-like effects; that is, they increased the response rate (number of shuttlings/min) of the avoidance response. Linden also increased the response rate, however, the effect was not dose-dependent. In contrast, EOs of orange, grapefruit, and cypress exhibited CNS depressant-like effects; that is, they decreased the response rate of the avoidance response. Essential oils of eucalyptus and rose decreased the avoidance rate (number of avoidance responses/number of avoidance trials) without affecting the response rate, indicating that they may exhibit some CNS acting effects. Essential oils of 12 other plants, including juniper, patchouli, geranium, jasmine, clary sage, neroli, lavender, lemon, ylang-ylang, niaouli, vetivert and frankincense had no effect on the avoidance response in mice. PMID:22086772

  11. Mechanosensitivity in the enteric nervous system

    PubMed Central

    Mazzuoli-Weber, Gemma; Schemann, Michael

    2015-01-01

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

  12. Is There Anything "Autonomous" in the Nervous System?

    ERIC Educational Resources Information Center

    Rasia-Filho, Alberto A.

    2006-01-01

    The terms "autonomous" or "vegetative" are currently used to identify one part of the nervous system composed of sympathetic, parasympathetic, and gastrointestinal divisions. However, the concepts that are under the literal meaning of these words can lead to misconceptions about the actual nervous organization. Some clear-cut examples indicate…

  13. Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome.

    PubMed

    Weng, Z J; Wu, L Y; Zhou, C L; Dou, C Z; Shi, Y; Liu, H R; Wu, H G

    2015-09-01

    The aim of this study is to investigate the role of the purinergic receptor P2X3 in the peripheral and central nervous systems during acupuncture treatment for the visceral pain of irritable bowel syndrome (IBS). A total of 24 8-day-old Sprague-Dawley (SD) neonatal male rats (SPF grade) were stimulated using colorectal distention (CRD) when the rats were awake. The modeling lasted for 2 weeks with one stimulation per day. After 6 weeks, the rats were randomly divided into three groups of eight each: (1) the normal group (NG, n = 8); (2) the model group (MG, n = 8); and (3) the model + electroacupuncture group (EA, n = 8) that received electroacupuncture at a needling depth of 5 mm at the Shangjuxu (ST37, bilateral) and Tianshu (ST25, bilateral) acupoints. The parameters of the Han's acupoint nerve stimulator (HANS) were as follows: sparse-dense wave with a frequency of 2/100 Hz, current of 2 mA, 20 min/stimulation, and one stimulation per day; the treatment was provided for seven consecutive days. At the sixth week after the treatment, the abdominal withdrawal reflex (AWR) score was determined; immunofluorescence and immunohistochemistry were used to measure the expression of the P2X3 receptor in myenteric plexus neurons, prefrontal cortex, and anterior cingulate cortex; and, a real-time PCR assay was performed to measure the expression of P2X3 messenger RNA (mRNA) in the dorsal root ganglion (DRG) and spinal cord. After stimulation with CRD, the expression levels of the P2X3 receptor in the inter-colonic myenteric plexus, DRG, spinal cord, prefrontal cortex, and anterior cingulate cortex were upregulated, and the sensitivity of the rats to IBS visceral pain was increased. Electroacupuncture (EA) could downregulate the expression of the P2X3 receptor and ease the sensitivity to visceral pain. The P2X3 receptor plays an important role in IBS visceral pain. The different levels of P2X3 in the peripheral enteric nervous system and central nervous system mediate the

  14. General Information about Childhood Central Nervous System Embryonal Tumors

    MedlinePlus

    ... System Embryonal Tumors Treatment (PDQ®)–Patient Version General Information About Childhood Central Nervous System Embryonal Tumors Go ... in patients with a high-risk tumor. The information from tests and procedures done to detect (find) ...

  15. Evolution of eumetazoan nervous systems: insights from cnidarians

    PubMed Central

    Kelava, Iva; Rentzsch, Fabian; Technau, Ulrich

    2015-01-01

    Cnidarians, the sister group to bilaterians, have a simple diffuse nervous system. This morphological simplicity and their phylogenetic position make them a crucial group in the study of the evolution of the nervous system. The development of their nervous systems is of particular interest, as by uncovering the genetic programme that underlies it, and comparing it with the bilaterian developmental programme, it is possible to make assumptions about the genes and processes involved in the development of ancestral nervous systems. Recent advances in sequencing methods, genetic interference techniques and transgenic technology have enabled us to get a first glimpse into the molecular network underlying the development of a cnidarian nervous system—in particular the nervous system of the anthozoan Nematostella vectensis. It appears that much of the genetic network of the nervous system development is partly conserved between cnidarians and bilaterians, with Wnt and bone morphogenetic protein (BMP) signalling, and Sox genes playing a crucial part in the differentiation of neurons. However, cnidarians possess some specific characteristics, and further studies are necessary to elucidate the full regulatory network. The work on cnidarian neurogenesis further accentuates the need to study non-model organisms in order to gain insights into processes that shaped present-day lineages during the course of evolution. PMID:26554048

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

    PubMed Central

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

    2016-01-01

    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. PMID:27032544

  17. 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. PMID:27032544

  18. 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

  19. THERMAL INFLUENCES ON NERVOUS SYSTEM FUNCTION

    EPA Science Inventory

    The effects of cooling and warming on neural function are reviewed. he literature is presented progressively from the subcellular through the cellular level to the neural systems level. emporal measures relevant to membrane activity, action potentials, synaptic transmission and e...

  20. Combination Treatment with Progesterone and Vitamin D Hormone May Be More Effective than Monotherapy for Nervous System Injury and Disease

    PubMed Central

    Cekic, Milos; Sayeed, Iqbal; Stein, Donald G.

    2010-01-01

    More than two decades of pre-clinical research and two recent clinical trials have shown that progesterone (PROG) and its metabolites exert beneficial effects after traumatic brain injury (TBI) through a number of metabolic and physiological pathways that can reduce damage in many different tissues and organ systems. Emerging data on 1,25-dihydroxyvitamin D3 (VDH), itself a steroid hormone, have begun to provide evidence that, like PROG, it too is neuroprotective, although some of its actions may involve different pathways. Both agents have high safety profiles, act on many different injury and pathological mechanisms, and are clinically relevant, easy to administer, and inexpensive. Furthermore, vitamin D deficiency is prevalent in a large segment of the population, especially the elderly and institutionalized, and can significantly affect recovery after CNS injury. The combination of PROG and VDH in pre-clinical and clinical studies is a novel and compelling approach to TBI treatment. PMID:19394357

  1. Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair

    PubMed Central

    Siebert, Justin R.; Conta Steencken, Amanda; Osterhout, Donna J.

    2014-01-01

    Chondroitin sulfate proteoglycans (CSPGs) are widely expressed in the normal central nervous system, serving as guidance cues during development and modulating synaptic connections in the adult. With injury or disease, an increase in CSPG expression is commonly observed close to lesioned areas. However, these CSPG deposits form a substantial barrier to regeneration and are largely responsible for the inability to repair damage in the brain and spinal cord. This review discusses the role of CSPGs as inhibitors, the role of inflammation in stimulating CSPG expression near site of injury, and therapeutic strategies for overcoming the inhibitory effects of CSPGs and creating an environment conducive to nerve regeneration. PMID:25309928

  2. Electricity in the treatment of nervous system disease.

    PubMed

    Fodstad, H; Hariz, M

    2007-01-01

    Electricity has been used in medicine for almost two millenniums beginning with electrical chocks from the torpedo fish and ending with the implantation of neuromodulators and neuroprostheses. These implantable stimulators aim to improve functional independence and quality of life in various groups of disabled people. New indications for neuromodulation are still evolving and the field is rapidly advancing. Thanks to modern science and computer technology, electrotherapy has reached a degree of sophistication where it can be applied relatively safely and effectively in a variety of nervous system diseases, including pain, movement disorders, epilepsy, Tourette syndrome, psychiatric disease, addiction, coma, urinary incontinence, impotence, infertility, respiratory paralysis, tinnitus and blindness. PMID:17691352

  3. The eye and visual nervous system: anatomy, physiology and toxicology.

    PubMed Central

    McCaa, C S

    1982-01-01

    The eyes are at risk to environmental injury by direct exposure to airborne pollutants, to splash injury from chemicals and to exposure via the circulatory system to numerous drugs and bloodborne toxins. In addition, drugs or toxins can destroy vision by damaging the visual nervous system. This review describes the anatomy and physiology of the eye and visual nervous system and includes a discussion of some of the more common toxins affecting vision in man. Images FIGURE 1. FIGURE 2. PMID:7084144

  4. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity

    PubMed Central

    Panossian, Alexander; Wikman, Georg

    2010-01-01

    Adaptogens were initially defined as substances that enhance the “state of non-specific resistance” in stress, a physiological condition that is linked with various disorders of the neuroendocrine-immune system. Studies on animals and isolated neuronal cells have revealed that adaptogens exhibit neuroprotective, anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity. In addition, a number of clinical trials demonstrate that adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly in tolerance to mental exhaustion and enhanced attention. Indeed, recent pharmacological studies of a number of adaptogens have provided a rationale for these effects also at the molecular level. It was discovered that the stress—protective activity of adaptogens was associated with regulation of homeostasis via several mechanisms of action, which was linked with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of stress response, such as molecular chaperons (e.g., HSP70), stress-activated c-Jun N-terminal protein kinase 1 (JNK1), Forkhead box O (FOXO) transcription factor DAF-16, cortisol and nitric oxide.

  5. The effect of various stimulated altitudes on the turnover of norepinephrine and dopamine in the central nervous system of rats.

    PubMed

    Prioux-Guyonneau, M; Cretet, E; Jacquot, C; Rapin, J R; Cohen, Y

    1979-06-12

    The elimination rate constant, half-life and turnover time of dopamine (DA) and norepinephrine (NE) were determined, after inhibiting their biosynthesis by alpha-methyl-para-tyrosine (alpha MT), in the hypothalamus, striatum and the remainder of the brain of rats exposed to different degrees of hypobaric hypoxia, corresponding to altitudes of 1,800, 3,800, 5,200 and 7,000 meters. The effects varied as a function of the degree of hypoxia and the brain region studied. The turnover time of NE in the hypothalamus remained unchanged, regardless of the altitude, while in the rest of the brain the rate constant of neurotransmitter elimination decreased inversely as a linear function of the degree of hypoxia. On the contrary, the changes of the DA turnover time in the striatum and the rest of the brain, were biphasic, being accelerated by moderate altitudes (1,800 m) and retarded by the two highest simulated altitudes studied as a function of hypoxia. The differential effects of hypoxia on NE and DA turnovers are attributed to different sensitivities of the respective enzyme systems. PMID:573440

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

    NASA Astrophysics Data System (ADS)

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

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

  7. Nervous system in the fibrillar theory of Giorgio Baglivi.

    PubMed

    Zurak, N

    2000-01-01

    The drafts, epistles, headwords, and conceptual basis known as the fibrillar theory of Giorgio Baglivi, published in his book entitled De fibra motrice et morbosa, were analyzed in an attempt to re-evaluate Baglivi's contribution, generally considered quite modest, to the development of scientific thought on the nervous system functions. The analysis revealed Baglivi's identification of the reflex organization, vegetative nervous system function, and neural aspect of the vasomotor function to be surprisingly valuable. I believe that the lucidity and genuine contemporariness of Baglivi's standpoints arise the question of the historical precedence in the discovery of these functions (it is usually attributed to F.X. Bichat for vegetative nervous system, and to Claude Bernard for vasomotor nerves). In the light of these facts, the need of an expert revision of the history of discovering nervous system functions is suggested. PMID:11624709

  8. Prevent Diabetes Problems: Keep Your Nervous System Healthy

    MedlinePlus

    ... Neurological Disorders and Stroke American Diabetes Association JDRF Diabetes Disease Organizations Many organizations provide support to patients ... PDF, 293 KB). Alternate Language URL Español Prevent diabetes problems: Keep your nervous system healthy Page Content ...

  9. 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

  10. 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

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

    PubMed Central

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

    1997-01-01

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

  12. CXCL12 Signaling in the Development of the Nervous System

    PubMed Central

    Mithal, Divakar S.; Banisadr, Ghazal; Miller, Richard J.

    2015-01-01

    Chemokines are small, secreted proteins that have been shown to be important regulators of leukocyte trafficking and inflammation. All the known effects of chemokines are transduced by action at a family of G protein coupled receptors. Two of these receptors, CCR5 and CXCR4, are also known to be the major cellular receptors for HIV-1. Consideration of the evolution of the chemokine family has demonstrated that the chemokine Stromal cell Derived Factor-1 or SDF1 (CXCL12) and its receptor CXCR4 are the most ancient members of the family and existed in animals prior to the development of a sophisticated immune system. Thus, it appears that the original function of chemokine signaling was in the regulation of stem cell trafficking and development. CXCR4 signaling is important in the development of many tissues including the nervous system. Here we discuss the manner in which CXCR4 signaling can regulate the development of different structures in the central and peripheral nervous systems and the different strategies employed to achieve these effects. PMID:22270883

  13. Preliminary investigation of the central nervous system effects of 'Tira-capeta' (Removing the Devil), a cigarette used by some Quilombolas living in Pantanal Wetlands of Brazil.

    PubMed

    Rodrigues, Eliana; Gianfratti, Bruno; Tabach, Ricardo; Negri, Giuseppina; Mendes, Fúlvio R

    2008-09-01

    During an ethnopharmacological survey carried out among some Quilombolas living in Brazil, 48 plants with possible central nervous system (CNS) action were cited. A mixture of nine plants, known as 'Tira-capeta' (Removing the Devil) cigarette, has been utilized for years as a tonic for the brain. The effects observed after consuming this cigarette are: dizziness, lightness sensation, humor changes, yawns, heavy eyes, hunger, sleep and relaxation. This study aimed to verify the effects of a hydroalcohol extract of 'Tira-capeta' cigarette (ETC), as well as to evaluate the phytochemical profile. The phytochemical screening carried out through characterization reactions, thin layer chromatography and high efficiency liquid chromatography indicated the presence of tannins, phenolic acids, flavonoids, saponins and alkaloids; tannins and phenolic acids being the principal constituents. The pharmacological tests showed that ETC induced a biphasic effect, with intense initial stimulation of the CNS, followed by a general depressor state; decreased the latency for sleeping and increased the total sleeping time (50, 100 and 500 mg/kg), without causing prejudice in motor coordination (doses up to 200 mg/kg); induced catalepsy in mice, verified 10 and 50 min after drug administration (500 mg/kg). Also, no anxiolytic or anxiogenic effects were verified in rats submitted to the elevated plus-maze. PMID:18570235

  14. Source characterization of nervous system active pharmaceutical ingredients in healthcare wastewaters

    EPA Science Inventory

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

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

    PubMed

    Strausfeld, Nicholas J; Hirth, Frank

    2015-12-19

    In 1665, Robert Hooke demonstrated in Micrographia the power of the microscope and comparative observations, one of which revealed similarities between the arthropod and vertebrate eyes. Utilizing comparative observations, Saint-Hilaire in 1822 was the first to propose that the ventral nervous system of arthropods corresponds to the dorsal nervous system of vertebrates. Since then, studies on the origin and evolution of the nervous system have become inseparable from studies about Metazoan origins and the origins of organ systems. The advent of genome sequence data and, in turn, phylogenomics and phylogenetics have refined cladistics and expanded our understanding of Metazoan phylogeny. However, the origin and evolution of the nervous system is still obscure and many questions and problems remain. A recurrent problem is whether and to what extent sequence data provide reliable guidance for comparisons across phyla. Are genetic data congruent with the geological fossil records? How can we reconcile evolved character loss with phylogenomic records? And how informative are genetic data in relation to the specification of nervous system morphologies? These provide some of the background and context for a Royal Society meeting to discuss new data and concepts that might achieve insights into the origin and evolution of brains and nervous systems. PMID:26554035

  16. The Effects of Bee Venom Acupuncture on the Central Nervous System and Muscle in an Animal hSOD1G93A Mutant

    PubMed Central

    Cai, MuDan; Choi, Sun-Mi; Yang, Eun Jin

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is caused by the degeneration of lower and upper motor neurons, leading to muscle paralysis and respiratory failure. However, there is no effective drug or therapy to treat ALS. Complementary and alternative medicine (CAM), including acupuncture, pharmacopuncture, herbal medicine, and massage is popular due to the significant limitations of conventional therapy. Bee venom acupuncture (BVA), also known as one of pharmacopunctures, has been used in Oriental medicine to treat inflammatory diseases. The purpose of this study is to investigate the effect of BVA on the central nervous system (CNS) and muscle in symptomatic hSOD1G93A transgenic mice, an animal model of ALS. Our findings show that BVA at ST36 enhanced motor function and decreased motor neuron death in the spinal cord compared to that observed in hSOD1G93A transgenic mice injected intraperitoneally (i.p.) with BV. Furthermore, BV treatment at ST36 eliminated signaling downstream of inflammatory proteins such as TLR4 in the spinal cords of symptomatic hSOD1G93A transgenic mice. However, i.p. treatment with BV reduced the levels of TNF-α and Bcl-2 expression in the muscle hSOD1G93A transgenic mice. Taken together, our findings suggest that BV pharmacopuncture into certain acupoints may act as a chemical stimulant to activate those acupoints and subsequently engage the endogenous immune modulatory system in the CNS in an animal model of ALS. PMID:25781653

  17. Effects of simulated microgravity on human brain nervous tissue.

    PubMed

    Wang, Xianghan; Du, Jianxin; Wang, Demei; Zeng, Fan; Wei, Yukui; Wang, Fuli; Feng, Chengcheng; Li, Nuomin; Dai, Rongji; Deng, Yulin; Quan, Zhenzhen; Qing, Hong

    2016-08-01

    During spaceflight, the negative effects of space microgravity on astronauts are becoming more and more prominent, and especially, of which on the nervous system is urgently to be solved. For this purpose tissue blocks and primary cells of nervous tissues obtained from glioma of patients were cultivated after culturing for about 7days, explanted tissues and cells were then randomly divided into two groups, one for static culture (control group, C), and the other for rotary processing for 1day, 3days, 5days, 7days and 14days (experiment group, E). Figures captured by inverted microscope revealed that, with short time rotating for 1day or 3days, morphology changes of tissue blocks were not obvious. When the rotary time was extended to 7days or 14days, it was found that cell somas is significantly larger and the ability of adhesion is declined in comparison with that in control group. Additionally, the arrangement of cells migrated from explanted tissues was disorganized, and the migration distance became shorter. In immunofluorescence analysis, β-tubulin filaments in control group appeared to organize into bundles. While in experiment group, β-tubulin was highly disorganized. In conclusion, simulated microgravity treatment for a week affected the morphology of nervous tissue, and caused highly disorganized distribution of cytoskeleton and the increase of cell apoptosis. These morphological changes might be one of the causes of apoptosis induced by simulated microgravity. PMID:27268042

  18. Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis

    PubMed Central

    Díaz-Balzac, Carlos A.; Lázaro-Peña, María I.; Vázquez-Figueroa, Lionel D.; Díaz-Balzac, Roberto J.; García-Arrarás, José E.

    2016-01-01

    The Echinodermata comprise an interesting branch in the phylogenetic tree of deuterostomes. Their radial symmetry which is reflected in their nervous system anatomy makes them a target of interest in the study of nervous system evolution. Until recently, the study of the echinoderm nervous system has been hindered by a shortage of neuronal markers. However, in recent years several markers of neuronal and fiber subpopulations have been described. These have been used to identify subpopulations of neurons and fibers, but an integrative study of the anatomical relationship of these subpopulations is wanting. We have now used eight commercial antibodies, together with three antibodies produced by our group to provide a comprehensive and integrated description and new details of the echinoderm neuroanatomy using the holothurian Holothuria glaberrima (Selenka, 1867) as our model system. Immunoreactivity of the markers used showed: (1) specific labeling patterns by markers in the radial nerve cords, which suggest the presence of specific nerve tracts in holothurians. (2) Nerves directly innervate most muscle fibers in the longitudinal muscles. (3) Similar to other deuterostomes (mainly vertebrates), their enteric nervous system is composed of a large and diverse repertoire of neurons and fiber phenotypes. Our results provide a first blueprint of the anatomical organization of cells and fibers that form the holothurian neural circuitry, and highlight the fact that the echinoderm nervous system shows unexpected diversity in cell and fiber types and their distribution in both central and peripheral nervous components. PMID:26987052

  19. Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis.

    PubMed

    Díaz-Balzac, Carlos A; Lázaro-Peña, María I; Vázquez-Figueroa, Lionel D; Díaz-Balzac, Roberto J; García-Arrarás, José E

    2016-01-01

    The Echinodermata comprise an interesting branch in the phylogenetic tree of deuterostomes. Their radial symmetry which is reflected in their nervous system anatomy makes them a target of interest in the study of nervous system evolution. Until recently, the study of the echinoderm nervous system has been hindered by a shortage of neuronal markers. However, in recent years several markers of neuronal and fiber subpopulations have been described. These have been used to identify subpopulations of neurons and fibers, but an integrative study of the anatomical relationship of these subpopulations is wanting. We have now used eight commercial antibodies, together with three antibodies produced by our group to provide a comprehensive and integrated description and new details of the echinoderm neuroanatomy using the holothurian Holothuria glaberrima (Selenka, 1867) as our model system. Immunoreactivity of the markers used showed: (1) specific labeling patterns by markers in the radial nerve cords, which suggest the presence of specific nerve tracts in holothurians. (2) Nerves directly innervate most muscle fibers in the longitudinal muscles. (3) Similar to other deuterostomes (mainly vertebrates), their enteric nervous system is composed of a large and diverse repertoire of neurons and fiber phenotypes. Our results provide a first blueprint of the anatomical organization of cells and fibers that form the holothurian neural circuitry, and highlight the fact that the echinoderm nervous system shows unexpected diversity in cell and fiber types and their distribution in both central and peripheral nervous components. PMID:26987052

  20. Role of the nervous system in cancer metastasis

    PubMed Central

    LI, SHA; SUN, YANLAI; GAO, DONGWEI

    2013-01-01

    The notion that tumors lack innervation was proposed several years ago. However, nerve fibers are irregulatedly found in some tumor tissues. Their terminals interaction with cancer cells are considered to be neuro-neoplastic synapses. Moreover, neural-related factors, which are important players in the development and activity of the nervous system, have been found in cancer cells. Thus, they establish a direct connection between the nervous system and tumor cells. They modulate the process of metastasis, including degradation of base membranes, cancer cell invasion, migration, extravasation and colonization. Peripheral nerve invasion provides another pathway for the spread of cancer cells when blood and lymphatic metastases are absent, which is based on the interactions between the microenvironments of nerve fibers and tumor cells. The nervous system also modulates angiogenesis, the tumor microenvironment, bone marrow, immune functions and inflammatory pathways to influence metastases. Denervation of the tumor has been reported to enhance cancer metastasis. Stress, social isolation and other emotional factors may increase distant metastasis through releasing hormones from the brain, the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Disruption of circadian rhythms will also promote cancer metastasis through direct and indirect actions of the nervous system. Therefore, the nervous system plays an important role in cancer metastasis. PMID:23599747

  1. Safety, tolerability, pharmacokinetics, and pharmacodynamic effects of naloxegol at peripheral and central nervous system receptors in healthy male subjects: A single ascending-dose study.

    PubMed

    Eldon, Michael A; Kugler, Alan R; Medve, Robert A; Bui, Khanh; Butler, Kathleen; Sostek, Mark

    2015-11-01

    This randomized, double-blind, placebo-controlled, ascending-dose, crossover study evaluated single oral doses of naloxegol (NKTR-118; 8, 15, 30, 60, 125, 250, 500, and 1000 mg), a PEGylated derivative of naloxone, for safety and tolerability, antagonism of peripheral and central nervous system (CNS) effects of intravenous morphine, and pharmacokinetics. Healthy men were randomized 1:1 to naloxegol or naloxegol-matching placebo administered with morphine and lactulose in a 2-period crossover design. Periods were separated by a 5- to 7-day washout. Assessments included safety, tolerability, orocecal transit time (OCTT), pupillary miosis, and pharmacokinetics. The study was completed by 46 subjects. The most common adverse events were somnolence, dizziness, headache, and nausea. Greater reversal of morphine-induced delay in OCTT occurred with increasing naloxegol dose, demonstrating dose-ordered antagonism of morphine's peripheral gastrointestinal effects. Forty-four subjects showed no reversal of pupillary miosis; 2 showed potential partial reversal at 250 and 1000 mg, indicating negligible antagonism of morphine's CNS effects at doses ≤ 125 mg. Rapid absorption, linear pharmacokinetics up to 1000 mg, and low to moderate between-subject pharmacokinetic variability was observed. The pharmacokinetics of morphine or its glucuronide metabolites were unaltered by concurrent naloxegol administration. Naloxegol was generally safe and well tolerated at single doses up to 1000 mg. PMID:27137715

  2. Placebo- and amitriptyline-controlled evaluation of central nervous system effects of the NK1 receptor antagonist aprepitant and intravenous alcohol infusion at pseudo-steady state.

    PubMed

    te Beek, Erik T; Tatosian, Daniel; Majumdar, Anup; Selverian, Diana; Klaassen, Erica S; Petty, Kevin J; Gargano, Cynthia; van Dyck, Kristien; McCrea, Jacqueline; Murphy, Gail; van Gerven, Joop M A

    2013-08-01

    Recent interest in NK1 receptor antagonists has focused on a potential role in the treatment of drug addiction and substance abuse. In the present study, the potential for interactions between the NK1 receptor antagonist aprepitant and alcohol, given as an infusion at a target level of 0.65 g/L, was evaluated. Amitriptyline was included as positive control to provide an impression of the profile of central nervous system (CNS) effects. In a double-blind, randomized, placebo- and amitriptyline-controlled study, the pharmacokinetics and CNS effects of aprepitant and alcohol were investigated in 16 healthy volunteers. Cognitive and psychomotor function tests included the visual verbal learning test (VVLT), Bond and Lader visual analogue scales (VAS), digit symbol substitution test (DSST), visual pattern recognition, binary choice reaction time, critical flicker fusion (CFF), body sway, finger tapping, and adaptive tracking. Alcohol impaired finger tapping and body sway. Amitriptyline impaired DSST performance, VAS alertness, CFF, body sway, finger tapping, and adaptive tracking. No impairments were found after administration of aprepitant. Co-administration of aprepitant with alcohol was generally well tolerated and did not cause significant additive CNS effects, compared with alcohol alone. Therefore, our study found no indications for clinically relevant interactions between aprepitant and alcohol. PMID:23775877

  3. Autoantibodies to nervous system-specific proteins are elevated in sera of flight crew members: biomarkers for nervous system injury.

    PubMed

    Abou-Donia, Mohamed B; Abou-Donia, Martha M; ElMasry, Eman M; Monro, Jean A; Mulder, Michel F A

    2013-01-01

    This descriptive study reports the results of assays performed to detect circulating autoantibodies in a panel of 7 proteins associated with the nervous system (NS) in sera of 12 healthy controls and a group of 34 flight crew members including both pilots and attendants who experienced adverse effects after exposure to air emissions sourced to the ventilation system in their aircrafts and subsequently sought medical attention. The proteins selected represent various types of proteins present in nerve cells that are affected by neuronal degeneration. In the sera samples from flight crew members and healthy controls, immunoglobin (IgG) was measured using Western blotting against neurofilament triplet proteins (NFP), tubulin, microtubule-associated tau proteins (tau), microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and glial S100B protein. Significant elevation in levels of circulating IgG-class autoantibodies in flight crew members was found. A symptom-free pilot was sampled before symptoms and then again afterward. This pilot developed clinical problems after flying for 45 h in 10 d. Significant increases in autoantibodies were noted to most of the tested proteins in the serum of this pilot after exposure to air emissions. The levels of autoantibodies rose with worsening of his condition compared to the serum sample collected prior to exposure. After cessation of flying for a year, this pilot's clinical condition improved, and eventually he recovered and his serum autoantibodies against nervous system proteins decreased. The case study with this pilot demonstrates a temporal relationship between exposure to air emissions, clinical condition, and level of serum autoantibodies to nervous system-specific proteins. Overall, these results suggest the possible development of neuronal injury and gliosis in flight crew members anecdotally exposed to cabin air emissions containing organophosphates. Thus, increased

  4. [Components of plastic disrupt the function of the nervous system].

    PubMed

    Szychowski, Konrad Andrzej; Wójtowicz, Anna Katarzyna

    2013-01-01

    Development of the chemical industry leads to the development of new chemical compounds, which naturally do not exist in the environment. These chemicals are used to reduce flammability, increase plasticity, or improve solubility of other substances. Many of these compounds, which are components of plastic, the new generation of cosmetics, medical devices, food packaging and other everyday products, are easily released into the environment. Many studies have shown that a major lipophilicity characterizes substances such as phthalates, BPA, TBBPA and PCBs. This feature allows them to easily penetrate into living cells, accumulate in the tissues and the organs, and affect human and animal health. Due to the chemical structures, these compounds are able to mimic some endogenous hormones such as estradiol and to disrupt the hormone homeostasis. They can also easily pass the placental barrier and the blood-brain barrier. As numerous studies have shown, these chemicals disturb the proper functions of the nervous system from the earliest moments of life. It has been proven that these compounds affect neurogenesis as well as the synaptic transmission process. As a consequence, they interfere with the formation of the sex of the brain, as well as with the learning processes, memory and behavior. Additionally, the cytotoxic and pro-apoptotic effect may cause neurodegenerative diseases. This article presents the current state of knowledge about the effects of phthalates, BPA, TBBPA, and PCBs on the nervous system. PMID:23752602

  5. Autophagy in the central nervous system: implications for neurodegenerative disorders.

    PubMed

    Xilouri, Maria; Stefanis, Leonidas

    2010-12-01

    The autophagy-lysosomal pathway is a major proteolytic pathway that in mammalian systems mainly comprises of macroautophagy and chaperone-mediated autophagy. The former is relatively non-selective and involves bulk degradation of proteins and organelles, whereas the latter is selective for certain cytosolic proteins. These autophagy pathways are important in development, differentiation, cellular remodeling and survival during nutrient starvation. Autophagy is crucial for neuronal homeostasis and acts as a local housekeeping process, since neurons are post-mitotic cells and require effective protein degradation to prevent accumulation of toxic aggregates. A growing body of evidence now suggests that dysfunction of autophagy causes accumulation of abnormal proteins and/or damaged organelles. Such accumulation has been linked to synaptic dysfunction, cellular stress and neuronal death. Abnormal autophagy may be involved in the pathology of both chronic nervous system disorders, such as proteinopathies (Alzheimer's, Parkinson's, Huntington's disease) and acute brain injuries. Although autophagy is generally beneficial, its aberrant activation may also exert a detrimental role in neurological diseases depending on the environment and the insult, leading to autophagic neuronal death. In this review we summarize the current knowledge regarding the role of autophagy-lysosomal pathway in the central nervous system and discuss the implication of autophagy dysregulation in human neurological diseases and animal models. PMID:20942791

  6. The effects of a glycine reuptake inhibitor R231857 on the central nervous system and on scopolamine-induced impairments in cognitive and psychomotor function in healthy subjects.

    PubMed

    Liem-Moolenaar, M; Zoethout, R W M; de Boer, P; Schmidt, M; de Kam, M L; Cohen, A F; Franson, K L; van Gerven, J M A

    2010-11-01

    The effects of the selective inhibitor of the glycine transporter 1, R231857, in development for schizophrenia, on the central nervous system (CNS) were investigated in healthy males in the absence and presence of scopolamine. This was a double-blind, placebo-controlled, four-period crossover ascending dose study. Pharmacokinetics, body sway, saccadic and smooth pursuit eye movements, pupillometry, pharmacoelectroencephalogram (EEG), Visual Analogue Scales (VAS) for alertness, mood, calmness and psychedelic effects, adaptive tracking, finger tapping, Stroop test, Visual and Verbal Learning Task (VVLT) and hormone levels were assessed. R231857 was administered alone and together with scopolamine to investigate the potential reversal of anticholinergic CNS impairment by the glycine reuptake inhibitor. Forty-two of the 45 included subjects completed the study. Scopolamine significantly affected almost every CNS parameter measured in this study. R231857 alone showed some pharmacodynamic changes compared with placebo. Although these effects might be an indication that R231857 penetrated the CNS, they were not consistent or dose-related. R231857 had some small effects on scopolamine-induced CNS-impairment, which were also not clearly dependent on dose. Scopolamine proved to be an accurate, reproducible and safe model to induce CNS impairment by an anticholinergic mechanism. R231857 lacked consistent dose-related effects in this study, probably because CNS concentrations were too low to produce significant/ reproducible CNS-effects or to affect the scopolamine challenge in healthy volunteers. The effects of higher doses in healthy volunteers and the clinical efficacy in patients remain to be established. PMID:19648218

  7. Cyclodextrin-Complexed Ocimum basilicum Leaves Essential Oil Increases Fos Protein Expression in the Central Nervous System and Produce an Antihyperalgesic Effect in Animal Models for Fibromyalgia

    PubMed Central

    Nascimento, Simone S.; Araújo, Adriano A. S.; Brito, Renan G.; Serafini, Mairim R.; Menezes, Paula P.; DeSantana, Josimari M.; Lucca Júnior, Waldecy; Alves, Pericles B.; Blank, Arie F.; Oliveira, Rita C. M.; Oliveira, Aldeidia P.; Albuquerque-Júnior, Ricardo L. C.; Almeida, Jackson R. G. S.; Quintans-Júnior, Lucindo J.

    2014-01-01

    O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia. PMID:25551603

  8. Cyclodextrin-complexed Ocimum basilicum leaves essential oil increases Fos protein expression in the central nervous system and produce an antihyperalgesic effect in animal models for fibromyalgia.

    PubMed

    Nascimento, Simone S; Araújo, Adriano A S; Brito, Renan G; Serafini, Mairim R; Menezes, Paula P; DeSantana, Josimari M; Lucca, Waldecy; Alves, Pericles B; Blank, Arie F; Oliveira, Rita C M; Oliveira, Aldeidia P; Albuquerque, Ricardo L C; Almeida, Jackson R G S; Quintans, Lucindo J

    2015-01-01

    O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia. PMID:25551603

  9. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on growth and craniofacial proportion

    SciTech Connect

    Schunior, A.; Zengel, A.E.; Mullenix, P.J.; Tarbell, N.J.; Howes, A.; Tassinari, M.S. )

    1990-10-15

    Many long term survivors of childhood acute lymphoblastic leukemia have short stature, as well as craniofacial and dental abnormalities, as side effects of central nervous system prophylactic therapy. An animal model is presented to assess these adverse effects on growth. Cranial irradiation (1000 cGy) with and without prednisolone (18 mg/kg i.p.) and methotrexate (2 mg/kg i.p.) was administered to 17- and 18-day-old Sprague-Dawley male and female rats. Animals were weighed 3 times/week. Final body weight and body length were measured at 150 days of age. Femur length and craniofacial dimensions were measured directly from the bones, using calipers. For all exposed groups there was a permanent suppression of weight gain with no catch-up growth or normal adolescent growth spurt. Body length was reduced for all treated groups, as were the ratios of body weight to body length and cranial length to body length. Animals subjected to cranial irradiation exhibited microcephaly, whereas those who received a combination of radiation and chemotherapy demonstrated altered craniofacial proportions in addition to microcephaly. Changes in growth patterns and skeletal proportions exhibited sexually dimorphic characteristics. The results indicate that cranial irradiation is a major factor in the growth failure in exposed rats, but chemotherapeutic agents contribute significantly to the outcome of growth and craniofacial dimensions.

  10. Beneficial Effects of Multitarget Iron Chelator on Central Nervous System and Gastrocnemius Muscle in SOD1(G93A) Transgenic ALS Mice.

    PubMed

    Golko-Perez, Sagit; Amit, Tamar; Youdim, Moussa B H; Weinreb, Orly

    2016-08-01

    Accumulation of evidence has demonstrated high levels of iron in the central nervous system of both sporadic and familial amyotrophic lateral sclerosis (ALS) patients and in ALS mouse models. In accordance, iron chelation therapy was found to exert beneficial effects on ALS mice. Our group has designed and synthesized series of multifunctional non-toxic, brain permeable iron-chelating compounds for neurodegenerative diseases. Recent study has shown that co-administration of one of these drugs, VAR10303 with high calorie/energy-supplemented diet (VAR-ced), initiated after the appearance of disease symptoms improved motor performance, extended survival, and attenuated iron accumulation and motoneuron loss in SOD1(G93A) mice. Since VAR was found to exert diverse pharmacological properties associated with mitochondrial biogenesis in the gastrocnemius (GNS) muscle, we further assessed in the current study the impact of VAR-ced on additional neurorescue-associated molecular targets in the GNS and frontal cortex in SOD1(G93A) mice. The results show that VAR-ced treatment upregulated the expression of various HIF-1α-target glycolytic genes and elevated the levels of Bcl-2, neurotrophic factors, and AKT/GSK3β signaling in the GNS and frontal cortex of SOD1(G93A) mice, suggesting that these protective regulatory parameters regulated by VAR-ced treatment may be associated with the beneficial effects of the drug observed on ALS mice. PMID:27173029

  11. [Neurocognitive Disorders Caused by Central Nervous System Lupus Erythematosus].

    PubMed

    Nishimura, Katsuji

    2016-04-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple biological systems that has primary and secondary effects on the central nervous system. Neuropsychiatric manifestations of SLE (NPSLE) are common and are associated with a worse prognosis, more cumulative organ damage, and decreased quality of life. The neurocognitive disorders of NPSLE include an acute confusional state and cognitive dysfunction. The pathogenic mechanisms underlying NPSLE are likely to be multifactorial and may involve vasculopathy of predominantly small intracranial blood vessels, autoantibody production, and intrathecal production of proinflammatory cytokines. No disease-specific diagnostic markers or diagnostic gold standard is known for NPSLE. Thus, the first step of the diagnostic work-up is to exclude non-SLE-related conditions. The correct diagnosis is derived from careful analysis of the clinical, laboratory, and imaging data on a case-by-case basis. This article reviews the current literature, especially on the neurocognitive disorders of NPSLE. PMID:27056854

  12. Breast Cancer Metastasis to the Central Nervous System

    PubMed Central

    Weil, Robert J.; Palmieri, Diane C.; Bronder, Julie L.; Stark, Andreas M.; Steeg, Patricia S.

    2005-01-01

    Clinically symptomatic metastases to the central nervous system (CNS) occur in ∼10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding. PMID:16192626

  13. Breast cancer metastasis to the central nervous system.

    PubMed

    Weil, Robert J; Palmieri, Diane C; Bronder, Julie L; Stark, Andreas M; Steeg, Patricia S

    2005-10-01

    Clinically symptomatic metastases to the central nervous system (CNS) occur in approximately 10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding. PMID:16192626

  14. Multifaceted interactions between adaptive immunity and the central nervous system.

    PubMed

    Kipnis, Jonathan

    2016-08-19

    Neuroimmunologists seek to understand the interactions between the central nervous system (CNS) and the immune system, both under homeostatic conditions and in diseases. Unanswered questions include those relating to the diversity and specificity of the meningeal T cell repertoire; the routes taken by immune cells that patrol the meninges under healthy conditions and invade the parenchyma during pathology; the opposing effects (beneficial or detrimental) of these cells on CNS function; the role of immune cells after CNS injury; and the evolutionary link between the two systems, resulting in their tight interaction and interdependence. This Review summarizes the current standing of and challenging questions related to interactions between adaptive immunity and the CNS and considers the possible directions in which these aspects of neuroimmunology will be heading over the next decade. PMID:27540163

  15. The effects of a single intravenous injection of novel activin A/BMP-2 (AB204) on toxicity and the respiratory and central nervous systems.

    PubMed

    Yoon, Byung-Hak; Lee, Jae Hyup; Na, Kyuheum; Ahn, Chihoon; Cho, Jongho; Ahn, Hyun Chan; Choi, Jungyoun; Oh, Hyosun; Kim, Byong Moon; Choe, Senyon

    2016-07-01

    The purpose of this study was to determine the effects of a single intravenous injection of a novel osteoinductive material, activin A/BMP-2 (AB204), to rodents on toxicity and their respiratory functions and central nervous system (CNS). A single intravenous injection of AB204 was given to Sprague-Dawley (SD) rats in doses of 0, 0.625, 2.5 and 10 mg/kg to observe the mortality rate, the general symptoms for 14 days. The experimental groups were also given 0.2, 0.4 and 0.8 mg/kg of AB204, respectively, and the respiration rate, the tidal volume and the minute volume were measured for 240 min. The experimental groups of imprinting control region (ICR) mice were given a single intravenous injection of 0.2, 0.4 and 0.8 mg/kg of AB204, respectively. Their body temperature was taken and general behaviors were observed to evaluate the effect of AB204 on the CNS for 240 min. The study on toxicity of a single intravenous injection found no death or abnormal symptoms, abnormal findings from autopsy, or abnormal body weight gain or loss in all the experimental groups. No abnormal variation associated with the test substance was observed in the respiration rate, the tidal volume, the minute volume, body temperature or the general behaviors. On the basis of these results, the approximate lethal dose of AB204 for a single intravenous injection exceeds 10 mg/kg for SD rats and a single intravenous injection of ≤0.8 mg/kg AB204 has no effect on their respiratory system for SD rat and no effect on their CNS for ICR mice. PMID:26446865

  16. Markers of inflammation, Vitamin E and peripheral nervous system function

    PubMed Central

    Di Iorio, Angelo; Cherubini, Antonio; Volpato, Stefano; Sparvieri, Eleonora; Lauretani, Fulvio; Franceschi, Claudio; Senin, Umberto; Abate, Giuseppe; Paganelli, Roberto; Martin, Antonio; Andres-Lacueva, Cristina; Ferrucci, Luigi

    2009-01-01

    Background Aging of the peripheral nervous system is associated with several morphologic and functional changes, including a decrease of the nerve conduction velocity. There is evidence that these changes contribute to age-related-decline in muscle strength, sensory discrimination, and autonomic responses. The aim of this study was to characterize the decline in nerve conduction velocity in the peripheral nervous system over the aging process and to identify factors that, independent of age, affect nerve conduction velocity. Methods We measured motor nerve conduction velocity of the right superficial peroneal nerve using a standard neurophysiologic technique in a population-based sample of subjects aged between 20 and 103 years old enrolled in the InCHIANTI study. Results Average conduction velocities in the peripheral nerve decreased linearly with age in both sexes. We found that diabetes, cognitive impairment, uric acid, sIL-6R and α-tocopherol were significant predictors of nerve conduction velocity independently of the potential confounding effect of age, sex, sex × age interaction term, height, lymphocytes, neutrophils number, α1 and α2-globulin serum protein. Conclusion Our findings are consistent with the hypothesis that inflammation and inadequate antioxidant defenses are associated with accelerated decline of nerve conduction velocity over the aging process. PMID:16112778

  17. Genomic characterization of primary central nervous system lymphoma.

    PubMed

    Fukumura, Kazutaka; Kawazu, Masahito; Kojima, Shinya; Ueno, Toshihide; Sai, Eirin; Soda, Manabu; Ueda, Hiroki; Yasuda, Takahiko; Yamaguchi, Hiroyuki; Lee, Jeunghun; Shishido-Hara, Yukiko; Sasaki, Atsushi; Shirahata, Mitsuaki; Mishima, Kazuhiko; Ichimura, Koichi; Mukasa, Akitake; Narita, Yoshitaka; Saito, Nobuhito; Aburatani, Hiroyuki; Nishikawa, Ryo; Nagane, Motoo; Mano, Hiroyuki

    2016-06-01

    Primary central nervous system lymphoma (PCNSL) is a rare malignancy confined to the central nervous system (CNS), and majority of PCNSL is pathologically classified as diffuse large B-cell lymphoma (DLBCL). We have now performed whole-exome sequencing for 41 tumor tissues of DLBCL-type PCNSL and paired normal specimens and also RNA-sequencing for 30 tumors, revealing a very high frequency of nonsynonymous somatic mutations in PIM1 (100 %), BTG2 (92.7 %), and MYD88 (85.4 %). Many genes in the NF-κB pathway are concurrently mutated within the same tumors. Further, focal deletion or somatic mutations in the HLA genes are associated with poor prognosis. Copy number amplification and overexpression of genes at chromosome 7q35 were both found to predict short progression-free survival as well. Oncogenic mutations in GRB2 were also detected, the effects of which in cultured cells were attenuated by inhibitors of the downstream kinases MAP2K1 and MAP2K2. Individuals with tumors positive for MYD88 mutations also harbored the same mutations at a low frequency in peripheral blood mononuclear cells, suggesting that MYD88 mutation-positive precancerous cells originate outside of the CNS and develop into lymphoma after additional genetic hits that confer adaptation to the CNS environment. PMID:26757737

  18. [Primary central nervous system post-transplant lymphoproliferative disorders].

    PubMed

    Honda, Masaya; Koga, Michiaki; Kanda, Takashi

    2014-08-01

    The post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous disease entity of lymphoid and plasmacytic proliferations that can occur after solid organ and bone marrow/stem cell transplantation. PTLD sometimes involves the central nervous system (CNS), but primary occurrence in central nervous system (PCNS-PTLD) is rare. The Epstein-Barr virus (EBV) plays a causative role, and up to 90% of the tumors are associated with this virus. Diagnosing PCNS-PTLD is often challenging based solely on computed tomography, magnetic resonance imaging, and physical findings; therefore, direct biopsy of the lesion is usually necessary to make a definitive diagnosis. The optimal therapy for PCNS-PTLD remains unknown. Dose reduction or discontinuation of immunosuppressive agents is effective for approximately half of PTLD patients, but not for most patients with PCNS-PTLD. It has been noted that CNS involvement is a poor prognostic factor, but early diagnosis and initiation of chemotherapy or radiotherapy seem critical for maximizing the likelihood of a favorable outcome. PMID:25082316

  19. A Rare Case of Central Nervous System Tuberculosis

    PubMed Central

    Haftka, Alexis; Porter, Ashleigh

    2014-01-01

    Intracranial abscess is an extremely rare form of central nervous system (CNS) tuberculosis (TB). We describe a case of central nervous system tuberculous abscess in absence of human immunodeficiency virus (HIV) infection. A 82-year-old Middle Eastern male from Yemen was initially brought to the emergency room due to altered mental status and acute renal failure. Cross-sectional imaging revealed multiple ring enhancing lesions located in the left cerebellum and in bilateral frontal lobe as well as in the inferior parietal lobe on the left. The patient was placed on an empiric antibiotic regimen. Preliminary testing for infectious causes was negative. Chest radiography and CT of chest showed no positive findings. He was not on any immunosuppressive medications and human immunodeficiency virus (HIV) enzyme immunoassay (EIA) test was negative. A subsequent MRI one month later showed profound worsening of the lesions with increasing vasogenic edema and newly found mass effect impinging on the fourth ventricle. Brain biopsy showed focal exudative cerebellitis and inflamed granulation tissue consistent with formation of abscesses. The diagnosis of CNS TB was finally confirmed by positive acid-fast bacilli (AFB) cultures. The patient was started on standard tuberculosis therapy but expired due to renal failure and cardiac arrest. PMID:25478256

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

    PubMed

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

    2015-07-16

    One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction. PMID:26030524

  1. Studies on the subcommissural organ area in the rat: the effects aldosterone infused into the central nervous system

    SciTech Connect

    Dundore, R.L.

    1985-01-01

    D-aldosterone (5 ng/..mu..l/hr) was infused for six days into the area of the subcommissural organ (SCO) of conscious rats to test the hypothesis that the SCO and the adrenal zona glomerulosa are related functionally in a negative feedback manner. Aldosterone increased urinary sodium loss and the sodium/potassium ratio. These effects still occurred when cannulae were displaced caudally up to 1 mm from the targeted SCO area. Aldosterone decreased the cross-sectional area of the adrenal medulla without affecting chromaffin cell density. Adrenal content of corticosterone was increased. These effects were highly dependent upon proper cannula placement and were not observed when the tip of the cannula was not in contact with the cerebrospinal fluid of the pineal recess over the rostral two-thirds of the SCO. Aldosterone infused intracerebroventricularly (ivt) into a lateral ventricle had no effect on sodium excretion, adrenal corticosterone concentration or adrenal morphology. After the infusion of radiolabelled aldosterone into the SCO area, the majority of the radioactivity was restricted to an area about 1-2 mm in diameter from the SCO. Iron-dextran injected intraperiotoneally did not accumulate in the SCO; therefore, the blood-brain barrier is intact. It is concluded that the effects of aldosterone were dependent upon the area of the brain in which it was infused. Aldosterone increased sodium excretion by an action in the SCO and/or adjacent structures. A relationship between mineralocorticoids and the adrenal modulla mediated by the SCO is also postulated. With regard to the blood-brain and brain-CSF barriers, the SCO more closely resembles general brain tissue than other circumventricular organs.

  2. The NO hypothesis: Possible effects of a short-lived, rapidly diffusible signal in the development and function of the nervous system

    SciTech Connect

    Gally, J.A.; Montague, P.R.; Reeke, G.N. Jr.; Edelman, G.M. )

    1990-05-01

    Several observations suggest that the Ca{sup 2+}-dependent postsynaptic release of nitric oxide (NO) may be important in the formation and function of the vertebrate nervous system. The authors explore here the hypothesis that the release of NO and its subsequent diffusion may be critically related to three aspects of nervous system function: (i) synaptic plasticity and long-term potentiation in certain regions of the adult nervous system, (ii) the control of cerebral blood flow in such regions, and (iii) the establishment and activity-dependent refinement of axonal projections during the later stages of development. In this paper, they detail and analyze the basic assumptions underlying this NO hypothesis and describe a computer simulation of a minimal version of the hypothesis. In the simulation, a 3-dimensional volume of neuropil is presented with patterned afferent input; NO is produced, diffuses, and is destroyed; and synaptic strengths are determined by a set of synaptic rules based on the correlation of synaptic depolarization and NO levels. According to the hypothesis, voltage-dependent postsynaptic release of this rapidly diffusing substance links the activities of neurons in a local volume of tissue, regardless of whether the neurons are directly connected by synapses. This property is demonstrated in the simulation, and it is this property this is exploited in the hypothesis to account for certain aspects of long-term potentiation and activity-dependent sharpening of axonal arbors.

  3. Effects of triprolidine and dipipanone in the cold induced pain test, and the central nervous system of healthy volunteers.

    PubMed

    Telekes, A; Holland, R L; Withington, D A; Peck, A W

    1987-07-01

    1 Twelve healthy volunteers took part in a study of the interaction between the antihistamine triprolidine and the opioid dipipanone in the cold induced pain (CP) test and tests of sedation. They received placebo, triprolidine 2.5 mg, dipipanone 8 mg or the combination of the two active treatments according to a double-blind, randomised, balanced, crossover design. 2 Antihistamine activity was demonstrated by triprolidine reducing the size of wheals and flares produced by intradermal histamine 1.6 micrograms. However, triprolidine produced no analgesia in the CP test, nor did it enhance the analgesia produced by dipipanone alone. 3 Neither treatment alone produced statistically significant sedation, assessed by visual analogue scales (VAS), side effect check list, body sway and reaction times. However, the combination did cause significant sedation. 4 Dipipanone reduced pupil size, depressed respiration, and decreased salivation. Triprolidine had no effects on pupil size and respiration, but reduced salivation slightly. It was concluded that histaminergic (H1) mechanisms are unlikely to be involved in pain produced by cold. PMID:3620284

  4. The central nervous system effects of carbon disulfide in male albino rats utilizing the tritiated 2-deoxyglucose method

    SciTech Connect

    Wells, W.E. III.

    1989-01-01

    The methodology employed was the autoradiographic 2-deoxyglucose method. Due to the coupling between functional activity and energy metabolism, these autoradiographs can be likened to a stain for functional activity under varying physiological and pathological states. Exposure regimes consisted of intraperitoneal injections of: (1) 400 milligrams of carbon disulfide per kilogram body weight five days per week for eight weeks; (2) 600 milligrams of carbon disulfide per kilogram body weight for five consecutive days; (3) 800 milligrams of carbon disulfide per kilogram body weight for only a single injection. Qualitative and quantitative analyses of the autoradiograms were employed. Appropriate statistical techniques were then be used to test for significant differences in the optical densities of structures between experimental and control radiographs. The results indicate a significant effect across all levels of analyses for the eight week group and the five day group for the auditory and olfactory central pathways.

  5. Neurochemical effects of a 20 kHz magnetic field on the central nervous system in prenatally exposed mice

    SciTech Connect

    Dimberg, Y.

    1995-09-01

    C57/B1 mice were exposed during pregnancy (gestation days 0--19) to a 20 kHz magnetic field (MF). The asymmetric sawtooth-waveform magnetic field in the exposed racks had a flux density of 15 {micro}T (peak to peak). After 19 days, the exposure was terminated, and the mice were housed individually under normal laboratory conditions. On postnatal day (PD) 1, PD21, and PD308, various neurochemical markers in the brains of the offspring were investigated and the brains weighed. No significant difference was found in the whole brain weight at PD1 or PD21 between exposed offspring and control animals. However, on PD308, a significant decrease in weight of the whole brain was detected in exposed animals. No significant differences were found in the weight of cortex, hippocampus, septum, or cerebellum on nay of the sampling occasions, nor were any significant differences detected in protein-, DNA-level, nerve growth factor (NGF), acetylcholine esterase- (AChE), or 2{prime},3{prime}-cyclic nucleotide 3{prime}-phosphodiesterase- (CNP; marker for oligodendrocytes) activities on PD21 in cerebellum. Cortex showed a more complex pattern of response to MF: MF treatment resulted in a decrease in DNA level and increases in the activities of CNP, AChE, and NGF protein. On PD308, the amount of DNA was significantly reduced in MF-treated cerebellum and CNP activity was still enhanced in MF-treated cortex compared to controls. Most of the effect of MF treatment during the embryonic period were similar to those induced by ionizing radiation but much weaker. However, the duration of the exposure required to elucidate the response of different markers to MF seems to be greater and effects appear later during development compared to responses to ionizing radiation.

  6. Effect of hypergravity on expression of the immediate early gene, c-fos, in central nervous system of medaka (Oryzias latipes)

    NASA Astrophysics Data System (ADS)

    Sayaka, Shimomura-Umemura; Ijiri, Kenichi

    2006-01-01

    Immediate-early genes serve as useful neurobiological tools for mapping brain activity induced by a sensory stimulation. In this study, we have examined brain activity related to gravity perception of medaka (Oryzias latipes) by use of c-fos. The gene, which is homologous to the c-fos genes of other vertebrates, was identified in medaka. Functionally important domains are highly conserved among all the vertebrate species analyzed. Intraperitoneal administration of kainic acid transiently induced the c-fos mRNAs in medaka brains. The results indicate that the expression of c-fos can be utilized as a suitable anatomical marker for the increased neural activities in the central nervous system of medaka. Fish were continuously exposed to 3 g hypergravity by centrifugation. Investigation of c-fos mRNA expression indicated that c-fos mRNA significantly increased 30 min after a start of 3 g exposure. The distribution of its transcripts within the brains was analyzed by an in situ hybridization method. The 3-g treated medakas displayed c-fos positive cells in their brainstem regions, which are related to vestibular function, such as torus semicircularis, nucleus tangentialis, posterior octavu nucleus, and inferior olive. Our results established a method to follow the effect of gravity stimulation, which can be used to investigate gravity perception.

  7. Neuroprotective effects of the catalytic subunit of telomerase: A potential therapeutic target in the central nervous system.

    PubMed

    González-Giraldo, Yeimy; Forero, Diego A; Echeverria, Valentina; Gonzalez, Janneth; Ávila-Rodriguez, Marco; Garcia-Segura, Luis Miguel; Barreto, George E

    2016-07-01

    Senescence plays an important role in neurodegenerative diseases and involves key molecular changes induced by several mechanisms such as oxidative stress, telomere shortening and DNA damage. Potential therapeutic strategies directed to counteract these molecular changes are of great interest for the prevention of the neurodegenerative process. Telomerase is a ribonucleoprotein composed of a catalytic subunit (TERT) and a RNA subunit (TERC). It is known that the telomerase is involved in the maintenance of telomere length and is a highly expressed protein in embryonic stages and decreases in adult cells. In the last decade, a growing number of studies have shown that TERT has neuroprotective effects in cellular and animal models after a brain injury. Significantly, differences in TERT expression between controls and patients with major depressive disorder have been observed. More recently, TERT has been associated with the decrease in reactive oxygen species and DNA protection in mitochondria of neurons. In this review, we highlight the role of TERT in some neurodegenerative disorders and discuss some studies focusing on this protein as a potential target for neuroprotective therapies. PMID:27095058

  8. Parasympathetic nervous system activity predicts mood repair use and its effectiveness among adolescents with and without histories of major depression.

    PubMed

    Yaroslavsky, Ilya; Rottenberg, Jonathan; Bylsma, Lauren M; Jennings, J Richard; George, Charles; Baji, Ildikó; Benák, István; Dochnal, Roberta; Halas, Kitti; Kapornai, Krisztina; Kiss, Enikő; Makai, Attila; Varga, Hedvig; Vetró, Ágnes; Kovacs, Maria

    2016-04-01

    Depressive disorders that onset in the juvenile years have been linked to far-reaching adverse consequences, making it imperative to elucidate key mechanisms and contributory factors. Excessive use of regulatory responses that exacerbate sadness (maladaptive mood repair) or insufficient use of regulatory responses that reduce it (adaptive mood repair) may reflect behavioral mechanisms of depression risk. Cardiac vagal control, indexed by patterns of respiratory sinus arrhythmia (RSA), has received attention as a putative physiological risk factor for depression. Although mood repair and RSA are related, the nature of this relationship is not well characterized in the context of depression risk. Therefore, we tested alternative models of the relationships between RSA patterns (at rest and in response to a sad film), trait mood repair, and the effectiveness of a mood repair response in the laboratory (state mood repair) among adolescents with depression histories (n = 210) and emotionally healthy peers (n = 161). In our data, a mediation model best explained the association between the key constructs: Adolescents with normative RSA patterns exhibited lower levels of depression and trait maladaptive mood repair, and benefited more from instructed (state) mood repair in the laboratory. By contrast, adolescents with atypical RSA patterns exhibited higher levels of depression and dispositional maladaptive mood repair, which, in turn, mediated the relations of RSA patterns and depression symptoms. Atypical RSA patterns also predicted reduced benefits from laboratory mood repair. (PsycINFO Database Record PMID:26950752

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

    PubMed

    Blustein, Daniel; Rosenthal, Nikolai; Ayers, Joseph

    2013-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. Interferons, Signal Transduction Pathways, and the Central Nervous System

    PubMed Central

    Nallar, Shreeram C.

    2014-01-01

    The interferon (IFN) family of cytokines participates in the development of innate and acquired immune defenses against various pathogens and pathogenic stimuli. Discovered originally as a proteinaceous substance secreted from virus-infected cells that afforded immunity to neighboring cells from virus infection, these cytokines are now implicated in various human pathologies, including control of tumor development, cell differentiation, and autoimmunity. It is now believed that the IFN system (IFN genes and the genes induced by them, and the factors that regulate these processes) is a generalized alarm of cellular stress, including DNA damage. IFNs exert both beneficial and deleterious effects on the central nervous system (CNS). Our knowledge of the IFN-regulated processes in the CNS is far from being clear. In this article, we reviewed the current understanding of IFN signal transduction pathways and gene products that might have potential relevance to diseases of the CNS. PMID:25084173

  13. Chronic lead and brain development: intraocular brain grafts as a method to reveal regional and temporal effects in the central nervous system

    SciTech Connect

    Bjoerklund, H.; Olson, L.; Seiger, A.; Hoffer, B.

    1980-06-01

    A model is presented for selective studies of regional and temporal effects of chronic lead exposure on brain development, based on intraocular brain tissue grafting. Adult rat recipients were given lead acetate (1 to 2%) in their drinking water. Controls received sodium acetate in the drinking water or tap water. One week later, developing brain tissues obtained prenatally from different regions of the central nervous system were homologously grafted to the anterior chamber of the eye. Survival, vascularization, and growth were followed in oculo by repeated measurements of graft size. Growth curves were thus obtained for grafts from isolated selected brain areas, grafted at different stages of development to recipients on different concentrations of lead. Lead treatment (1%) caused a significant and pronounced delay of growth of the substantia nigra area during the second and third week postgrafting, approximately corresponding to the first 2 weeks after birth. Grafts of the hippocampal formation showed a slight impairment of growth following lead treatment while there were no detectable effects on size of cerebellar grafts. Grafts of the developing parietal cerebral cortex were inhibited in their growth in host animals given 2% lead while there was a small but significant increase in size following 1% lead. These results demonstrate the applicability of the grafting technique for studies of chronic low level lead intoxication. The method has revealed highly significant effects of lead on growth of certain selected brain areas and will be used for further histological, biochemical, and electrophysiological analysis of chronic lead effects on development of defined brain areas.

  14. Enterovirus Infections of the Central Nervous System Review

    PubMed Central

    Rhoades, Ross E.; Tabor-Godwin, Jenna M.; Tsueng, Ginger; Feuer, Ralph

    2011-01-01

    Enteroviruses (EV) frequently infect the central nervous system (CNS) and induce neurological diseases. Although the CNS is composed of many different cell types, the spectrum of tropism for each EV is considerable. These viruses have the ability to completely shut down host translational machinery and are considered highly cytolytic, thereby causing cytopathic effects. Hence, CNS dysfunction following EV infection of neuronal or glial cells might be expected. Perhaps unexpectedly given their cytolytic nature, EVs may establish a persistent infection within the CNS, and the lasting effects on the host might be significant with unanticipated consequences. This review will describe the clinical aspects of EV-mediated disease, mechanisms of disease, determinants of tropism, immune activation within the CNS, and potential treatment regimes. PMID:21251690

  15. Studies on central nervous system serotonin receptors in mood disorders.

    PubMed

    Young, A; Goodwin, G M

    1991-01-01

    The evidence from studies of central nervous system serotonin (5-HT) receptors is reviewed and the role of these in the pathogenesis of mood disorders is discussed. Clinical evidence indicates that 5-HT function is abnormal in mood disorders. 5-HT precursors and selective inhibitors of 5-HT uptake are effective antidepressives and inhibition of 5-HT synthesis can block the action of antidepressives. Studies of 5-HT in experimental animals after chronic administration of antidepressive treatments suggest that intact 5-HT neurons are necessary for the action of these treatments. Multiple 5-HT receptor subtypes have recently been identified and the effects of chronic antidepressive treatment on some receptor subtypes function in experimental animals have been established. The increasing availability of powerful new in vivo imaging techniques like single photon emission tomography (SPET), and positron emission tomography (PET) may make possible a more direct examination of 5-HT receptor function in patients suffering from mood disorders. PMID:2029163

  16. Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and allostasis in epilepsy, depression, and post-traumatic stress disorder.

    PubMed

    Streeter, C C; Gerbarg, P L; Saper, R B; Ciraulo, D A; Brown, R P

    2012-05-01

    A theory is proposed to explain the benefits of yoga practices in diverse, frequently comorbid medical conditions based on the concept that yoga practices reduce allostatic load in stress response systems such that optimal homeostasis is restored. It is hypothesized that stress induces (1) imbalance of the autonomic nervous system (ANS) with decreased parasympathetic nervous system (PNS) and increased sympathetic nervous system (SNS) activity, (2) underactivity of the gamma amino-butyric acid (GABA) system, the primary inhibitory neurotransmitter system, and (3) increased allostatic load. It is further hypothesized that yoga-based practices (4) correct underactivity of the PNS and GABA systems in part through stimulation of the vagus nerves, the main peripheral pathway of the PNS, and (5) reduce allostatic load. Depression, epilepsy, post traumatic stress disorder (PTSD), and chronic pain exemplify medical conditions that are exacerbated by stress, have low heart rate variability (HRV) and low GABAergic activity, respond to pharmacologic agents that increase activity of the GABA system, and show symptom improvement in response to yoga-based interventions. The observation that treatment resistant cases of epilepsy and depression respond to vagal nerve stimulation corroborates the need to correct PNS underactivity as part of a successful treatment plan in some cases. According to the proposed theory, the decreased PNS and GABAergic activity that underlies stress-related disorders can be corrected by yoga practices resulting in amelioration of disease symptoms. This has far-reaching implications for the integration of yoga-based practices in the treatment of a broad array of disorders exacerbated by stress. PMID:22365651

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

    PubMed

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

    2015-01-01

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

  18. Monophyletic Origin of the Metazoan Nervous System: Characterizing

    NASA Astrophysics Data System (ADS)

    Watkins, Russell; Beckenbach, Andrew

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

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

    PubMed Central

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

    2015-01-01

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

  20. Heterotopic ossification after central nervous system trauma

    PubMed Central

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

    2013-01-01

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

  1. Effect of immunomodulation on the fate of tumor cells in the central nervous system and systemic organs of mice. Distribution of (/sup 125/I)5-iodo-2'-deoxyuridine-labeled KHT tumor cells after left intracardial injection

    SciTech Connect

    Conley, F.K.

    1982-08-01

    The effect of systemic immunomodulation on tumor cell arrest and retention in the central nervous system was studied by following radioactively labeled tumor cells. KHT mouse sarcoma tumor cells were labeled in vitro with (/sup 125/I)IdUrd, and 1x10/sup 5/ tumor cells were injected into the left side of the hearts of syngeneic C3H mice. Experimental groups consisted of untreated normal mice, mice pretreated iv with Corynebacterium parvum, and mice chronically infected with Toxoplasma gondii; in this model both groups of immunomodulated mice are protected from developing systemic metastatic tumor, but only Toxoplasma-infected mice have protection against metastatic brain tumor. At time intervals from 1 to 96 hours, groups of mice from each experimental group were killed, and the brain and other organs were monitored for radioactivity to determine the number of viable tumor cells that had been present at the time of death. Normal mice demonstrated significant retention of tumor cells in the brain and kidneys plus adrenals at 96 hours. By contrast, in both groups of immunomodulated mice tumor cells were rapidly eliminated from systemic organs, but tumor cells were significantly retained in the central nervous system even at 96 hours after tumor cell injections. The results indicated that generalized immunomodulation had more effect in elimination of tumor cells from systemic organs than from the brain and that the elimination of tumor cells from the brain in Toxoplasma-infected mice was a delayed phenomenon.

  2. Hepatic nervous system and neurobiology of the liver.

    PubMed

    Jensen, Kendal Jay; Alpini, Gianfranco; Glaser, Shannon

    2013-04-01

    The liver has a nervous system containing both afferent and efferent neurons that are involved in a number of processes. The afferent arm includes the sensation of lipids, glucose, and metabolites (after eating and drinking) and triggers the nervous system to make appropriate physiological changes. The efferent arm is essential for metabolic regulation, modulation of fibrosis and biliary function and the control of a number of other processes. Experimental models have helped us to establish how: (i) the liver is innervated by the autonomic nervous system; and (ii) the cell types that are involved in these processes. Thus, the liver acts as both a sensor and effector that is influenced by neurological signals and ablation. Understanding these processes hold significant implications in disease processes such as diabetes and obesity, which are influenced by appetite and hormonal signals. PMID:23720325

  3. Guidance Receptors in the Nervous and Cardiovascular Systems.

    PubMed

    Rubina, K A; Tkachuk, V A

    2015-10-01

    Blood vessels and nervous fibers grow in parallel, for they express similar receptors for chemokine substances. Recently, much attention is being given to studying guidance receptors and their ligands besides the growth factors, cytokines, and chemokines necessary to form structures in the nervous and vascular systems. Such guidance molecules determine trajectory for growing axons and vessels. Guidance molecules include Ephrins and their receptors, Neuropilins and Plexins as receptors for Semaphorins, Robos as receptors for Slit-proteins, and UNC5B receptors binding Netrins. Apart from these receptors and their ligands, urokinase and its receptor (uPAR) and T-cadherin are also classified as guidance molecules. The urokinase system mediates local proteolysis at the leading edge of cells, thereby providing directed migration. T-cadherin is a repellent molecule that regulates the direction of growing axons and blood vessels. Guidance receptors also play an important role in the diseases of the nervous and cardiovascular systems. PMID:26567567

  4. Signals that initiate myelination in the developing mammalian nervous system.

    PubMed

    Colello, R J; Pott, U

    1997-08-01

    The myelination of axons by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system is essential for the establishment of saltatory conduction. In the absence or destruction of the myelin sheath, as seen in demyelinating diseases, impulse conduction is impeded resulting in severe sensory and motor deficits. Axon myelination is the culmination of a sequence of events that begins with the differentiation of glial cells and proceeds to the transcription and translation of myelin genes, the elaboration of a myelin sheath, and the recognition and ensheathment of axons. This review examines the regulatory mechanisms for each of these steps and compares and contrasts the role of the axon in initiating myelination in the central and peripheral nervous system. PMID:9396006

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

    PubMed

    Goldstein, David S

    2013-01-01

    This chapter conveys several concepts and points of view about the scientific and medical significance of differential alterations in activities of components of the autonomic nervous system in stress and disease. The use of terms such as "the autonomic nervous system," "autonomic failure," "dysautonomia," and "autonomic dysfunction" imply the existence of a single entity; however, the autonomic nervous system has functionally and neurochemically distinctive components, which are reflected in differential responses to stressors and differential involvement in pathophysiologic states. One can conceptualize the autonomic nervous system as having at least five components: the sympathetic noradrenergic system, the sympathetic cholinergic system, the parasympathetic cholinergic system, the sympathetic adrenergic system, and the enteric nervous system. Evidence has accumulated for differential noradrenergic vs. adrenergic responses in various situations. The largest sympathetic adrenergic system responses are seen when the organism encounters stressors that pose a global or metabolic threat. Sympathetic noradrenergic system activation dominates the responses to orthostasis, moderate exercise, and exposure to cold, whereas sympathetic adrenergic system activation dominates those to glucoprivation and emotional distress. There seems to be at least as good a justification for the concept of coordinated adrenocortical-adrenomedullary responses as for coordinated adrenomedullary-sympathoneural responses in stress. Fainting reactions involve differential adrenomedullary hormonal vs. sympathetic noradrenergic activation. Parkinson disease entails relatively selective dysfunction of the sympathetic noradrenergic system, with prominent loss of noradrenergic nerves in the heart, yet normal adrenomedullary function. Allostatic load links stress with degenerative diseases, and Parkinson disease may be a disease of the elderly because of allostatic load. PMID:24095112

  6. [Role of drug transporters in the central nervous system].

    PubMed

    Erdő, Franciska; Temesszentandrási-Ambrus, Csilla; Beéry, Erzsébet

    2016-03-01

    Although the presence of blood-brain barrier in the mammalian organisms was discovered in the early 1900s, its precise structure and the drug transporter proteins localized in the blood-brain barrier were identified only in the last decades. Beside the ATP-binding cassette transporter proteins responsible for the protection of the brain, the Solute Carrier transporters play also an important role in the function of the central nervous system by its feeding, energy supply and cleaning function during the metabolism. This review provides an overview on the main types of transporters located in the brain, on their localization in different cell types and the main techniques for their investigation. In the second part of this article various neurodegenerative disorders and the pathology-related transporter proteins are presented. In the light of recent experimental results new therapeutic strategies may come into the focus of research for the treatment of disorders currently without effective therapy. PMID:26920327

  7. Pathogen-inspired drug delivery to the central nervous system

    PubMed Central

    McCall, Rebecca L; Cacaccio, Joseph; Wrabel, Eileen; Schwartz, Mary E; Coleman, Timothy P; Sirianni, Rachael W

    2014-01-01

    For as long as the human blood-brain barrier (BBB) has been evolving to exclude bloodborne agents from the central nervous system (CNS), pathogens have adopted a multitude of strategies to bypass it. Some pathogens, notably viruses and certain bacteria, enter the CNS in whole form, achieving direct physical passage through endothelial or neuronal cells to infect the brain. Other pathogens, including bacteria and multicellular eukaryotic organisms, secrete toxins that preferentially interact with specific cell types to exert a broad range of biological effects on peripheral and central neurons. In this review, we will discuss the directed mechanisms that viruses, bacteria, and the toxins secreted by higher order organisms use to enter the CNS. Our goal is to identify ligand-mediated strategies that could be used to improve the brain-specific delivery of engineered nanocarriers, including polymers, lipids, biologically sourced materials, and imaging agents. PMID:25610755

  8. Regulation of gene expression in the nervous system

    SciTech Connect

    Giuffrida Stella, A.M.; Perez-Polo, J.R.; deVellis, J.

    1990-01-01

    This book offers an up-to-date account of the latest research findings concerned with the regulatory mechanisms of gene expression in neuronal and glial cells under different conditions. The book explores the cellular and neurobiological aspects of important phenomena of the nervous system and its role in health, disease and injury. Contributions form prominent scientists in the field address a variety of specific topics concerned with gene expression in the nervous system - from growth, hormonal and trophic factors to neural tissue reactions in injury or aging.

  9. 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. PMID:25312338

  10. Inflammation and cutaneous nervous system involvement in hypertrophic scarring

    PubMed Central

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

    2015-01-01

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

  11. Role of Neuroactive Steroids in the Peripheral Nervous System

    PubMed Central

    Melcangi, Roberto Cosimo; Giatti, Silvia; Pesaresi, Marzia; Calabrese, Donato; Mitro, Nico; Caruso, Donatella; Garcia-Segura, Luis Miguel

    2011-01-01

    Several reviews have so far pointed out on the relevant physiological and pharmacological role exerted by neuroactive steroids in the central nervous system. In the present review we summarize observations indicating that synthesis and metabolism of neuroactive steroids also occur in the peripheral nerves. Interestingly, peripheral nervous system is also a target of their action. Indeed, as here reported neuroactive steroids are physiological regulators of peripheral nerve functions and they may also represent interesting therapeutic tools for different types of peripheral neuropathy. PMID:22654839

  12. 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

  13. Brain-computer interface after nervous system injury.

    PubMed

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

    2014-12-01

    Brain-computer interface (BCI) has proven to be a useful tool for providing alternative communication and mobility to patients suffering from nervous system injury. BCI has been and will continue to be implemented into rehabilitation practices for more interactive and speedy neurological recovery. The most exciting BCI technology is evolving to provide therapeutic benefits by inducing cortical reorganization via neuronal plasticity. This article presents a state-of-the-art review of BCI technology used after nervous system injuries, specifically: amyotrophic lateral sclerosis, Parkinson's disease, spinal cord injury, stroke, and disorders of consciousness. Also presented is transcending, innovative research involving new treatment of neurological disorders. PMID:25193343

  14. Infectious diseases of the nervous system: pathogenesis and worldwide impact.

    PubMed

    Berkhout, Ben

    2008-11-01

    The 2008 Infectious Diseases of the Nervous System: Pathogenesis and World Impact conference was held at the Pasteur Institute of Paris, and was the first worldwide conference on neuroinfections. While viral encephalitis and bacterial meningitis are being actively studied in the developed world, much less attention is paid to the often fatal nervous system infections caused by neurotropic viruses, parasites and mycobacteria that represent important health problems in tropical regions. This meeting fostered worldwide interactions between scientists and stimulated the exchange of the latest research results on these neglected neurotropic pathogens. PMID:18988120

  15. Central nervous system manifestations of Angiostrongylus cantonensis infection

    PubMed Central

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

    2014-01-01

    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. PMID:25312338

  16. The central nervous system effects of the partial GABA-Aα2,3-selective receptor modulator AZD7325 in comparison with lorazepam in healthy males

    PubMed Central

    Chen, Xia; Jacobs, Gabriël; de Kam, Marieke; Jaeger, Judith; Lappalainen, Jaakko; Maruff, Paul; Smith, Mark A; Cross, Alan J; Cohen, Adam; van Gerven, Joop

    2014-01-01

    Aims AZD7325 is a novel α2,3-subtype-selective partial GABA-A-receptor modulator. This study investigated the pharmacodynamics of single oral doses of AZD7325 2 mg and 10 mg on the central nervous system (CNS) compared with placebo and lorazepam 2 mg. Methods This double-blind, randomized, four way crossover study enrolled 16 healthy males and administered two validated CNS test batteries to measure drug effects on cognitive, neurophysiologic and psychomotor function and subjective feelings. The pharmacological selectivity of AZD7325 was compared with lorazepam by plotting saccadic peak velocity change from baseline (ΔSPV) against body sway (ΔSway) and visual analogue scale for alertness(ΔVASalertness). This analysis has previously been used to identify α2,3-subtype-selectivity. Results In contrast with the robust impairment caused by lorazepam (all P < 0.05 vs. placebo), neither dose of AZD7325 induced statistically significant effects on any pharmacodynamic measurements. Lorazepam-induced SPV-reduction was linearly related to changes in other neurophysiologic biomarkers. In contrast, the slopes of the regression lines were flatter for AZD7325, particularly for the Δlog(Sway) −ΔSPV relation (estimate slope, AZD7325 10 mg vs. lorazepam, difference [95% confidence interval], P value −0.00036 vs. −0.00206, 0.001704 [0.000639, 0.002768], P = 0.0018) and the ΔVASalertness−ΔSPV relationship (0.01855 vs. 0.08216, −0.06360 [−0.1046, −0.02257], P = 0.0024). AZD7325 10 mg and lorazepam induced different response patterns on VAS ‘feeling high’ and electro-encephalography. Conclusion The characteristic ΔSPV-relative effect profiles of AZD7325 vs. lorazepam suggest anxio-selectivity related to α2,3-selective GABAA agonism. However, exploration of higher doses may be warranted. The paucity of effects on most CNS−PD parameters also indicates a mitigated side effect pattern, with potentially lower cognitive and neurophysiological side

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

    SciTech Connect

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

    2015-11-17

    The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervous systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

    The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervous systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of

  19. The Function of the Autonomic Nervous System during Spaceflight

    PubMed Central

    Mandsager, Kyle Timothy; Robertson, David; Diedrich, André

    2015-01-01

    Introduction Despite decades of study, a clear understanding of autonomic nervous system activity in space remains elusive. Differential interpretation of fundamental data have driven divergent theories of sympathetic activation and vasorelaxation. Methods This paper will review the available in-flight autonomic and hemodynamic data in an effort to resolve these discrepancies. The NASA NEUROLAB mission, the most comprehensive assessment of autonomic function in microgravity to date, will be highlighted. The mechanisms responsible for altered autonomic activity during spaceflight, which include the effects of hypovolemia, cardiovascular deconditioning, and altered central processing, will be presented. Results The NEUROLAB experiments demonstrated increased sympathetic activity and impairment of vagal baroreflex function during short-duration spaceflight. Subsequent non-invasive studies of autonomic function during spaceflight have largely reinforced these findings, and provide strong evidence that sympathetic activity is increased in space relative to the supine position on Earth. Others have suggested that microgravity induces a state of relative vasorelaxation and increased vagal activity when compared to upright posture on Earth. These ostensibly disparate theories are not mutually exclusive, but rather directly reflect different pre-flight postural controls. Conclusion When these results are taken together, they demonstrate that the effectual autonomic challenge of spaceflight is small, and represents an orthostatic stress less than that of upright posture on Earth. In-flight countermeasures, including aerobic and resistance exercise, as well as short-arm centrifugation have been successfully deployed to counteract these mechanisms. Despite subtle changes in autonomic activity during spaceflight, underlying neurohumoral mechanisms of the autonomic nervous system remain intact and cardiovascular function remains stable during long-duration flight. PMID:25820827

  20. Sympathetic nervous system and inflammation: a conceptual view.

    PubMed

    Jänig, Wilfrid

    2014-05-01

    The peripheral sympathetic nervous system is organized into function-specific pathways that transmit the activity from the central nervous system to its target tissues. The transmission of the impulse activity in the sympathetic ganglia and to the effector tissues is target cell specific and guarantees that the centrally generated command is faithfully transmitted. This is the neurobiological basis of autonomic regulations in which the sympathetic nervous system is involved. Each sympathetic pathway is connected to distinct central circuits in the spinal cord, lower and upper brain stem and hypothalamus. In addition to its conventional functions, the sympathetic nervous system is involved in protection of body tissues against challenges arising from the environment as well as from within the body. This function includes the modulation of inflammation, nociceptors and above all the immune system. Primary and secondary lymphoid organs are innervated by sympathetic postganglionic neurons and processes in the immune tissue are modulated by activity in these sympathetic neurons via adrenoceptors in the membranes of the immune cells (see Bellinger and Lorton, 2014). Are the primary and secondary lymphoid organs innervated by a functionally specific sympathetic pathway that is responsible for the modulation of the functioning of the immune tissue by the brain? Or is this modulation of immune functions a general function of the sympathetic nervous system independent of its specific functions? Which central circuits are involved in the neural regulation of the immune system in the context of neural regulation of body protection? What is the function of the sympatho-adrenal system, involving epinephrine, in the modulation of immune functions? PMID:24525016

  1. Central nervous system blastomycosis in a dog

    PubMed Central

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

    2009-01-01

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

  2. The sympathetic nervous system alterations in human hypertension.

    PubMed

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-03-13

    Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves. PMID:25767284

  3. 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.…

  4. 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…

  5. Homology and Convergence in Vertebrate and Invertebrate Nervous Systems

    NASA Astrophysics Data System (ADS)

    Sandeman, David

    Each year the meeting of the American Neuroscience Society attracts over 20,000 members, reflecting the explosion of interest in this field that has occurred over the past few decades. Researchers from many disciplines are focusing their skills on the investigation of every aspect of nervous systems, and neuroscience now encompasses the entire range of endeavour from the study of the single molecules that make up neural membranes to the non-invasive observation of neural function in animals behaving in their natural environments. Advances over the past three decades in our understanding of nervous systems are impressive and come from a multifaceted approach to the study of both vertebrate and invertebrate animals. An almost unexpected by-product of the parallel investigation of vertebrate and invertebrate nervous systems that is explored in this article is the emergent view of an intricate web of evolutionary homology and convergence exhibited in the structure and function of the nervous systems of these two large, paraphyletic groups of animals.

  6. Parasitic Central Nervous System Infections in Immunocompromised Hosts

    PubMed Central

    Walker, Melanie; Zunt, Joseph R.

    2009-01-01

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

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

    ERIC Educational Resources Information Center

    Carey, Joseph, Ed.

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

  8. THE SYMPATHETIC NERVOUS SYSTEM ALTERATIONS IN HUMAN HYPERTENSION

    PubMed Central

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-01-01

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

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

    ERIC Educational Resources Information Center

    Weiss, Alan; And Others

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

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

    PubMed

    Sotelo, Julio

    2015-02-01

    From all biological constituents of complex organisms, two are highly sophisticated: the nervous and the immune systems. Interestingly, their goals and processes appear to be distant from each other; however, their physiological mechanisms keep notorious similarities. Both construct intelligence, learn from experience, and keep memory. Their precise responses to innumerable stimuli are delicately modulated, and the exposure of the individual to thousands of potential challenges integrates their functionality; they use a large part of their constituents not in excitatory activities but in the maintenance of inhibitory mechanisms to keep silent vast intrinsic potentialities. The nervous and immune systems are integrated by a basic cell lineage (neurons and lymphocytes, respectively) but each embodies countless cell subgroups with different and specialized deeds which, in contrast with cells from other organs, labyrinthine molecular arrangements conduct to "one cell, one function". Also, nervous and immune actions confer identity that differentiates every individual from countless others in the same species. Both systems regulate and potentiate their responses aided by countless biological resources of variable intensity: hormones, peptides, cytokines, pro-inflammatory molecules, etc. How the immune and the nervous systems buildup memory, learning capability, and exquisite control of excitatory/inhibitory mechanisms constitute major intellectual challenges for contemporary research. PMID:25398574

  11. Early Malnutrition and Central Nervous System Function

    ERIC Educational Resources Information Center

    Scrimshaw, Nevin S.

    1969-01-01

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

  12. Systems-Level View of Cocaine Addiction: The Interconnection of the Immune and Nervous Systems

    PubMed Central

    Marasco, Christina C.; Goodwin, Cody R.; Winder, Danny; Schramm-Sapyta, Nicole; McLean, John A.; Wikswo, John P.

    2014-01-01

    The human body is a complex assembly of physiological systems designed to manage the multidirectional transport of both information and nutrients. An intricate interplay between the nervous, circulatory, and secretory systems is therefore necessary to sustain life, allow delivery of nutrients and therapeutic drugs, and eliminate metabolic waste products and toxins. These systems also provide vulnerable routes for modification by substances of abuse. Addictive substances are, by definition, neurologically active, but as they and their metabolites are spread throughout the body via both the nervous, circulatory, respiratory and digestive systems, there is abundant opportunity for interaction with numerous cell and tissue types. Cocaine is one such substance that exerts a broad physiological effect. While a great deal of the research concerning addiction has addressed the neurological effects of cocaine use, only a few studies have been aimed at delineating the role that cocaine plays in various body systems. In this paper, we probe the current research regarding cocaine and the immune system, and map a systems-level view to outline a broader perspective of the biological response to cocaine. Specifically, our overview of the neurological and immunomodulatory effects of the drug will allow a broader perspective of the biological response to cocaine. The focus of this review is on the connection between the nervous and immune systems and the role this connection plays in the long-term complications of cocaine use. By describing the multiplicity of these connections, we hope to inspire detailed investigations into the immunological interplay in cocaine addiction. PMID:24903164

  13. Systems-level view of cocaine addiction: the interconnection of the immune and nervous systems.

    PubMed

    Marasco, Christina C; Goodwin, Cody R; Winder, Danny G; Schramm-Sapyta, Nicole L; McLean, John A; Wikswo, John P

    2014-11-01

    The human body is a complex assembly of physiological systems designed to manage the multidirectional transport of both information and nutrients. An intricate interplay between the nervous, circulatory, and secretory systems is therefore necessary to sustain life, allow delivery of nutrients and therapeutic drugs, and eliminate metabolic waste products and toxins. These systems also provide vulnerable routes for modification by substances of abuse. Addictive substances are, by definition, neurologically active, but as they and their metabolites are spread throughout the body via the nervous, circulatory, respiratory and digestive systems, there is abundant opportunity for interaction with numerous cell and tissue types. Cocaine is one such substance that exerts a broad physiological effect. While a great deal of the research concerning addiction has addressed the neurological effects of cocaine use, only a few studies have been aimed at delineating the role that cocaine plays in various body systems. In this paper, we probe the current research regarding cocaine and the immune system, and map a systems-level view to outline a broader perspective of the biological response to cocaine. Specifically, our overview of the neurological and immunomodulatory effects of the drug will allow a broader perspective of the biological response to cocaine. The focus of this review is on the connection between the nervous and immune systems and the role this connection plays in the long-term complications of cocaine use. By describing the multiplicity of these connections, we hope to inspire detailed investigations into the immunological interplay in cocaine addiction. PMID:24903164

  14. Influence of G-forces on venous and nervous systems

    NASA Technical Reports Server (NTRS)

    Dyskin, Y. A.; Prives-Bardina, R. A.; Tikhonova, L. P.

    1975-01-01

    Cats and rabbits were subjected to rotation in the centrifuge. Controls were maintained to determine the individual tolerance to g-forces. Thickening of the vascular wall was found to occur due to the g-forces' effect, as well as other vascular changes. Nervous changes included edema and chromatolysis of the nerve cells.

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

    PubMed Central

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas

    2013-01-01

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

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

    PubMed

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas

    2013-01-01

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

  17. Itch signaling in the nervous system.

    PubMed

    Jeffry, Joseph; Kim, Seungil; Chen, Zhou-Feng

    2011-08-01

    Itch is a major somatic sensation, along with pain, temperature, and touch, detected and relayed by the somatosensory system. Itch can be an acute sensation, associated with mosquito bite, or a chronic condition, like atopic dermatitis (29, 59). The origins of the stimulus can be localized in the periphery or systemic, and associated with organ failure or cancer. Itch is also a perception originating in the brain. Itch is broadly characterized as either histamine-dependent (histaminergic) or histamine-independent (nonhistaminergic), both of which are relayed by subsets of C fibers and by the second-order neurons expressing gastrin-releasing peptide receptor (GRPR) and spinothalamic track (STT) neurons in the spinal cord of rodents. Historically, itch research has been primarily limited to clinical and psychophysical studies and to histamine-mediated mechanisms. In contrast, little is known about the signaling mechanisms underlying nonhistaminergic itch, despite the fact that the majority of chronic itch are mediated by nonhistaminergic mechanisms. During the past few years, important progress has been made in understanding the molecular signaling of itch, largely due to the introduction of mouse genetics. In this review, we examine some of the molecular mechanisms underlying itch sensation with an emphasis on recent studies in rodents. PMID:21841076

  18. Itch Signaling in the Nervous System

    PubMed Central

    Jeffry, Joseph; Kim, Seungil; Chen, Zhou-Feng

    2013-01-01

    Itch is a major somatic sensation, along with pain, temperature and touch, detected and relayed by the somatosensory system. Itch can be an acute sensation, associated with mosquito bite, or a chronic condition, like atopic dermatitis (29, 59). The origins of the stimulus can be localized in the periphery or systemic, and associated with organ failure or cancer. Itch is also a perception originating in the brain. Itch is broadly characterized as either histamine-dependent (histaminergic) or histamine-independent (nonhistaminergic), both of which are relayed by subsets of C-fibers, and by the second-order neurons expressing gastrin-releasing peptide receptor (GRPR) and spinothalamic track (STT) neurons in the spinal cord of rodents. Historically, itch research has been primarily limited to clinical and psychophysical studies, and to histamine-mediated mechanisms. In contrast, little is known about signaling mechanisms underlying nonhistaminergic itch, despite the fact that the majority of chronic itch are mediated by nonhistaminergic mechanisms. During the past few years, important progress has been made in understanding of molecular signaling of itch, largely due to the introduction of mouse genetics. In this review, we examine some of molecular mechanisms underlying itch sensation with an emphasis on recent studies in rodents. PMID:21841076

  19. The role of the autonomic nervous system in Tourette Syndrome

    PubMed Central

    Hawksley, Jack; Cavanna, Andrea E.; Nagai, Yoko

    2015-01-01

    Tourette Syndrome (TS) is a neurodevelopmental disorder, consisting of multiple involuntary movements (motor tics) and one or more vocal (phonic) tics. It affects up to one percent of children worldwide, of whom about one third continue to experience symptoms into adulthood. The central neural mechanisms of tic generation are not clearly understood, however recent neuroimaging investigations suggest impaired cortico-striato-thalamo-cortical activity during motor control. In the current manuscript, we will tackle the relatively under-investigated role of the peripheral autonomic nervous system, and its central influences, on tic activity. There is emerging evidence that both sympathetic and parasympathetic nervous activity influences tic expression. Pharmacological treatments which act on sympathetic tone are often helpful: for example, Clonidine (an alpha-2 adrenoreceptor agonist) is often used as first choice medication for treating TS in children due to its good tolerability profile and potential usefulness for co-morbid attention-deficit and hyperactivity disorder. Clonidine suppresses sympathetic activity, reducing the triggering of motor tics. A general elevation of sympathetic tone is reported in patients with TS compared to healthy people, however this observation may reflect transient responses coupled to tic activity. Thus, the presence of autonomic impairments in patients with TS remains unclear. Effect of autonomic afferent input to cortico-striato-thalamo-cortical circuit will be discussed schematically. We additionally review how TS is affected by modulation of central autonomic control through biofeedback and Vagus Nerve Stimulation (VNS). Biofeedback training can enable a patient to gain voluntary control over covert physiological responses by making these responses explicit. Electrodermal biofeedback training to elicit a reduction in sympathetic tone has a demonstrated association with reduced tic frequency. VNS, achieved through an implanted device

  20. The role of the autonomic nervous system in Tourette Syndrome.

    PubMed

    Hawksley, Jack; Cavanna, Andrea E; Nagai, Yoko

    2015-01-01

    Tourette Syndrome (TS) is a neurodevelopmental disorder, consisting of multiple involuntary movements (motor tics) and one or more vocal (phonic) tics. It affects up to one percent of children worldwide, of whom about one third continue to experience symptoms into adulthood. The central neural mechanisms of tic generation are not clearly understood, however recent neuroimaging investigations suggest impaired cortico-striato-thalamo-cortical activity during motor control. In the current manuscript, we will tackle the relatively under-investigated role of the peripheral autonomic nervous system, and its central influences, on tic activity. There is emerging evidence that both sympathetic and parasympathetic nervous activity influences tic expression. Pharmacological treatments which act on sympathetic tone are often helpful: for example, Clonidine (an alpha-2 adrenoreceptor agonist) is often used as first choice medication for treating TS in children due to its good tolerability profile and potential usefulness for co-morbid attention-deficit and hyperactivity disorder. Clonidine suppresses sympathetic activity, reducing the triggering of motor tics. A general elevation of sympathetic tone is reported in patients with TS compared to healthy people, however this observation may reflect transient responses coupled to tic activity. Thus, the presence of autonomic impairments in patients with TS remains unclear. Effect of autonomic afferent input to cortico-striato-thalamo-cortical circuit will be discussed schematically. We additionally review how TS is affected by modulation of central autonomic control through biofeedback and Vagus Nerve Stimulation (VNS). Biofeedback training can enable a patient to gain voluntary control over covert physiological responses by making these responses explicit. Electrodermal biofeedback training to elicit a reduction in sympathetic tone has a demonstrated association with reduced tic frequency. VNS, achieved through an implanted device

  1. Cardiovascular and nervous system changes during meditation

    PubMed Central

    Steinhubl, Steven R.; Wineinger, Nathan E.; Patel, Sheila; Boeldt, Debra L.; Mackellar, Geoffrey; Porter, Valencia; Redmond, Jacob T.; Muse, Evan D.; Nicholson, Laura; Chopra, Deepak; Topol, Eric J.

    2015-01-01

    Background: A number of benefits have been described for the long-term practice of meditation, yet little is known regarding the immediate neurological and cardiovascular responses to meditation. Wireless sensor technology allows, for the first time, multi-parameter and quantitative monitoring of an individual's responses during meditation. The present study examined inter-individual variations to meditation through continuous monitoring of EEG, blood pressure, heart rate and its variability (HRV) in novice and experienced meditators. Methods: Participants were 20 experienced and 20 novice meditators involved in a week-long wellness retreat. Monitoring took place during meditation sessions on the first and last full days of the retreat. All participants wore a patch that continuously streamed ECG data, while half of them also wore a wireless EEG headset plus a non-invasive continuous blood pressure monitor. Results: Meditation produced variable but characteristic EEG changes, significantly different from baseline, even among novice meditators on the first day. In addition, although participants were predominately normotensive, the mean arterial blood pressure fell a small (2–3 mmHg) but significant (p < 0.0001) amount during meditation. The effect of meditation on HRV was less clear and influenced by calculation technique and respiration. No clear relationship between EEG changes, HRV alterations, or mean blood pressure during meditation was found. Conclusion: This is the first study to investigate neurological and cardiovascular responses during meditation in both novice and experienced meditators using novel, wearable, wireless devices. Meditation produced varied inter-individual physiologic responses. These results support the need for further investigation of the short- and long-term cardiovascular effects of mental calm and individualized ways to achieve it. PMID:25852526

  2. Temporal Encoding in a Nervous System

    PubMed Central

    Aldworth, Zane N.; Dimitrov, Alexander G.; Cummins, Graham I.; Gedeon, Tomáš; Miller, John P.

    2011-01-01

    We examined the extent to which temporal encoding may be implemented by single neurons in the cercal sensory system of the house cricket Acheta domesticus. We found that these neurons exhibit a greater-than-expected coding capacity, due in part to an increased precision in brief patterns of action potentials. We developed linear and non-linear models for decoding the activity of these neurons. We found that the stimuli associated with short-interval patterns of spikes (ISIs of 8 ms or less) could be predicted better by second-order models as compared to linear models. Finally, we characterized the difference between these linear and second-order models in a low-dimensional subspace, and showed that modification of the linear models along only a few dimensions improved their predictive power to parity with the second order models. Together these results show that single neurons are capable of using temporal patterns of spikes as fundamental symbols in their neural code, and that they communicate specific stimulus distributions to subsequent neural structures. PMID:21573206

  3. Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system.

    PubMed

    Calcagno, Andrea; Di Perri, Giovanni; Bonora, Stefano

    2014-10-01

    HIV-positive patients may be effectively treated with highly active antiretroviral therapy and such a strategy is associated with striking immune recovery and viral load reduction to very low levels. Despite undeniable results, the central nervous system (CNS) is commonly affected during the course of HIV infection, with neurocognitive disorders being as prevalent as 20-50 % of treated subjects. This review discusses the pathophysiology of CNS infection by HIV and the barriers to efficacious control of such a mechanism, including the available data on compartmental drug penetration and on pharmacokinetic/pharmacodynamic relationships. In the reviewed articles, a high variability in drug transfer to the CNS is highlighted with several mechanisms as well as methodological issues potentially influencing the observed results. Nevirapine and zidovudine showed the highest cerebrospinal fluid (CSF) to plasma ratios, although target concentrations are currently unknown for the CNS. The use of the composite CSF concentration effectiveness score has been associated with better virological outcomes (lower HIV RNA) but has been inconsistently associated with neurocognitive outcomes. These findings support the CNS effectiveness of commonly used highly antiretroviral therapies. The use of antiretroviral drugs with increased CSF penetration and/or effectiveness in treating or preventing neurocognitive disorders however needs to be assessed in well-designed prospective studies. PMID:25200312

  4. Pathology of the peripheral nervous system.

    PubMed

    Fernandez; Marchese; Palma; Lauretti; Procaccini; Pallini

    1999-01-26

    In this review, the first four papers deal with an important chapter in peripheral nerve surgery: cranial nerve reconstruction after injury occurring during skull base surgery. The last paper discusses the problem of peripheral nerves affected by a ganglion cyst. Damage to a cranial nerve is no longer considered to be an absolutely irreparable event. The first two studies are related to facial nerve management during the surgical treatment of vestibular schwannomas. The most common mechanisms responsible for facial nerve injury during tumor removal and the technical means to avoid them are cited. The importance of intraoperative neurophysiologic monitoring to save the facial nerve is stressed. A comparison between microsurgery and radiosurgery results in the conclusion that for vestibular schwannomas, the first choice of treatment is microsurgery. These two large and exceptional series show that by using a refined technique it is possible to obtain both total tumor removal and preservation of the facial nerve in most of the vestibular schwannomas. In the minority of patients in whom the facial nerve is severed, there are several therapeutic options to re-establish facial nerve function. After facial nerve reconstruction, performed immediately during the same tumor operation, a satisfactory reinnervation was obtained in 74% of the cases. After facial nerve reanimation, using as donor nerve the hypoglossus and performed 1 week after the tumor operation, a satisfactory reinnervation was obtained in 96% of the cases. The other two papers deal with the intraoperative transection of the trochlear and abducens nerve during surgery for skull base tumors. These two cranial nerves, owing to their simply organized motor nerve system (they are purely motor nerves and supply one muscle each), show quite a good expectation of functional recovery. The behavior of ganglion cysts involving peripheral nerves is the topic of the last paper reviewed. These cysts are benign lesions

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

    PubMed

    Wray, Gregory A

    2015-12-19

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

  6. Molecular mechanisms regulating myelination in the peripheral nervous system.

    PubMed

    Pereira, Jorge A; Lebrun-Julien, Frédéric; Suter, Ueli

    2012-02-01

    Glial cells and neurons are engaged in a continuous and highly regulated bidirectional dialog. A remarkable example is the control of myelination. Oligodendrocytes in the central nervous system (CNS) and Schwann cells (SCs) in the peripheral nervous system (PNS) wrap their plasma membranes around axons to organize myelinated nerve fibers that allow rapid saltatory conduction. The functionality of this system is critical, as revealed by numerous neurological diseases that result from deregulation of the system, including multiple sclerosis and peripheral neuropathies. In this review we focus on PNS myelination and present a conceptual framework that integrates crucial signaling mechanisms with basic SC biology. We will highlight signaling hubs and overarching molecular mechanisms, including genetic, epigenetic, and post-translational controls, which together regulate the interplay between SCs and axons, extracellular signals, and the transcriptional network. PMID:22192173

  7. 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

  8. 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

  9. Quest for the basic plan of nervous system circuitry

    PubMed Central

    Swanson, Larry W.

    2007-01-01

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

  10. Intranasal treatment of central nervous system dysfunction in humans.

    PubMed

    Chapman, Colin D; Frey, William H; Craft, Suzanne; Danielyan, Lusine; Hallschmid, Manfred; Schiöth, Helgi B; Benedict, Christian

    2013-10-01

    One of the most challenging problems facing modern medicine is how to deliver a given drug to a specific target at the exclusion of other regions. For example, a variety of compounds have beneficial effects within the central nervous system (CNS), but unwanted side effects in the periphery. For such compounds, traditional oral or intravenous drug delivery fails to provide benefit without cost. However, intranasal delivery is emerging as a noninvasive option for delivering drugs to the CNS with minimal peripheral exposure. Additionally, this method facilitates the delivery of large and/or charged therapeutics, which fail to effectively cross the blood-brain barrier (BBB). Thus, for a variety of growth factors, hormones, neuropeptides and therapeutics including insulin, oxytocin, orexin, and even stem cells, intranasal delivery is emerging as an efficient method of administration, and represents a promising therapeutic strategy for the treatment of diseases with CNS involvement, such as obesity, Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, anxiety, autism spectrum disorders, seizures, drug addiction, eating disorders, and stroke. PMID:23135822

  11. Functional structure and dynamics of the human nervous system

    NASA Technical Reports Server (NTRS)

    Lawrence, J. A.

    1981-01-01

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

  12. Effects of physical training on functional activity of 5-HT1B receptors in rat central nervous system: role of 5-HT-moduline.

    PubMed

    Chennaoui, M; Grimaldi, B; Fillion, M P; Bonnin, A; Drogou, C; Fillion, G; Guezennec, C Y

    2000-06-01

    The effect of physical exercise was examined on the sensitivity of 5-HT1B receptors and on 5-HT-moduline tissue concentration in the central nervous system of rats. Rats were trained for 7 consecutive weeks to run on a treadmill. Three groups of animals were selected: group 1, sedentary rats (controls); group 2, animals running for 1 h at 18 m/min for 5 days per week (moderate training) and group 3, animals running for 2 h, at 30 m/min on a 7% grade for 5 days per week (intensive training). The animals were sacrificed 24 h after the last running. Rat brains were dissected out to obtain hippocampus and substantia nigra and kept at -80 degrees C until use. 5-HT1B receptor activity was determined by studying [35S]GTPgammaS binding in a substantia nigra membrane preparation from individual animals, after stimulation by a selective 5-HT1B receptor agonist (CP 93,129). 5-HT-moduline tissue content in hippocampus from individual animals was determined by ELISA using a polyclonal anti-5-HT-moduline antibody. In moderately trained animals (n=5), the CP 93,129-stimulated [35S]GTPgammaS binding curve was shifted to the right compared with controls (n=6), whereas the binding was totally suppressed in intensely trained animals (n=5). In parallel, 5-HT-moduline tissue concentration in the hippocampus was slightly increased in moderately trained animals (117.3 +/- 8.9%) (n=5), whereas it was significantly increased in intensely trained animals (182.6 +/- 29.5%) (n=5) compared to controls (100 +/- 6.11%) (n=6). These results show that 5-HT1B receptors are slightly desensitized in moderately trained animals and totally desensitized in intensely trained animals; moreover, they suggest that the observed desensitization is related to an increase of 5-HT-moduline tissue content; this mechanism may play a role in various pathophysiological conditions. PMID:10882034

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

    PubMed

    Strausfeld, Nicholas J; Hirth, Frank

    2016-01-01

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

  14. Multiple Sclerosis and the Blood-Central Nervous System Barrier

    PubMed Central

    Palmer, Alan M.

    2013-01-01

    The central nervous system (CNS) is isolated from the blood system by a physical barrier that contains efflux transporters and catabolic enzymes. This blood-CNS barrier (BCNSB) plays a pivotal role in the pathophysiology of multiple sclerosis (MS). It binds and anchors activated leukocytes to permit their movement across the BCNSB and into the CNS. Once there, these immune cells target particular self-epitopes and initiate a cascade of neuroinflammation, which leads to the breakdown of the BCNSB and the formation of perivascular plaques, one of the hallmarks of MS. Immunomodulatory drugs for MS are either biologics or small molecules, with only the latter having the capacity to cross the BCNSB and thus have a propensity to cause CNS side effects. However, BCNSB penetration is a desirable feature of MS drugs that have molecular targets within the CNS. These are nabiximols and dalfampridine, which target cannabinoid receptors and potassium channels, respectively. Vascular cell adhesion molecule-1, present on endothelial cells of the BCNSB, also serves as a drug discovery target since it interacts with α4-β1-integrin on leucocytes. The MS drug natalizumab, a humanized monoclonal antibody against α4-β1-integrin, blocks this interaction and thus reduces the movement of immune cells into the CNS. This paper further elaborates on the role of the BCNSB in the pathophysiology and pharmacotherapy of MS. PMID:23401746

  15. Human neural progenitor cells in central nervous system lesions.

    PubMed

    Åkesson, Elisabet; Sundström, Erik

    2016-02-01

    Various immature cells can be isolated from human embryonic and fetal central nervous system (CNS) residual tissue and potentially be used in cell therapy for a number of neurological diseases and CNS insults. Transplantation of neural stem and progenitor cells is essential for replacing lost cells, particularly in the CNS with very limited endogenous regenerative capacity. However, while dopamine released from transplanted cells can substitute the lost dopamine neurons in the experimental models of Parkinson's disease, stem and progenitor cells primarily have a neuroprotective effect, probably through the release of trophic factors. Understanding the therapeutic effects of transplanted cells is crucial to determine the design of clinical trials. During the last few years, a number of clinical trials for CNS diseases and insults such as amyotrophic lateral sclerosis (ALS), stroke, and spinal cord trauma using neural progenitor cells have been initiated. Data from these early studies will provide vital information on the safety of transplanting these cells, which still is a major concern. That the beneficial results observed in experimental models also can be repeated in the clinical setting is highly hoped for. PMID:26803559

  16. Mesoscopic organization reveals the constraints governing Caenorhabditis elegans nervous system.

    PubMed

    Pan, Raj Kumar; Chatterjee, Nivedita; Sinha, Sitabhra

    2010-01-01

    One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. The coordination of many different co-occurring processes at this level underlies the command and control of overall network activity. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations such as, optimizing for resource constraints (viz., total wiring cost) and communication efficiency (i.e., network path length). Even including information about the genetic relatedness of the cells cannot account for the observed modular structure. Comparison with other complex networks designed for efficient transport (of signals or resources) implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including its key

  17. Blocking Neurogenic Inflammation for the Treatment of Acute Disorders of the Central Nervous System

    PubMed Central

    Lewis, Kate Marie; Turner, Renée Jade

    2013-01-01

    Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis. PMID:23819099

  18. The nervous system of Xenacoelomorpha: a genomic perspective.

    PubMed

    Perea-Atienza, Elena; Gavilán, Brenda; Chiodin, Marta; Abril, Josep F; Hoff, Katharina J; Poustka, Albert J; Martinez, Pedro

    2015-02-15

    Xenacoelomorpha is, most probably, a monophyletic group that includes three clades: Acoela, Nemertodermatida and Xenoturbellida. The group still has contentious phylogenetic affinities; though most authors place it as the sister group of the remaining bilaterians, some would include it as a fourth phylum within the Deuterostomia. Over the past few years, our group, along with others, has undertaken a systematic study of the microscopic anatomy of these worms; our main aim is to understand the structure and development of the nervous system. This research plan has been aided by the use of molecular/developmental tools, the most important of which has been the sequencing of the complete genomes and transcriptomes of different members of the three clades. The data obtained has been used to analyse the evolutionary history of gene families and to study their expression patterns during development, in both space and time. A major focus of our research is the origin of 'cephalized' (centralized) nervous systems. How complex brains are assembled from simpler neuronal arrays has been a matter of intense debate for at least 100 years. We are now tackling this issue using Xenacoelomorpha models. These represent an ideal system for this work because the members of the three clades have nervous systems with different degrees of cephalization; from the relatively simple sub-epithelial net of Xenoturbella to the compact brain of acoels. How this process of 'progressive' cephalization is reflected in the genomes or transcriptomes of these three groups of animals is the subject of this paper. PMID:25696825

  19. Central nervous system infection in the pediatric population

    PubMed Central

    Sahu, Rabi Narayan; Kumar, Raj; Mahapatra, A. K.

    2009-01-01

    Infection of the central nervous system is a life-threatening condition in the pediatric population. Almost all agents can cause infection within the central nervous system and the extent of infection ranges from diffuse involvement of the meninges, brain, or the spinal cord to localized involvement presenting as a space-occupying lesion. Modern imaging techniques define the anatomic region infected, the evolution of the disease, and help in better management of these patients. Acute bacterial meningitis remains a major cause of mortality and long-term neurological disability. Fortunately, the incidence of infection after clean craniotomy is < 5%, but it leads to significant morbidity as well as fiscal loss. The most significant causative factor in postcraniotomy infections is postoperative CSF leak. Cerebral abscess related to organic congenital heart disease is one of the leading causes of morbidity and mortality in the pediatric population. The administration of prophylactic antibiotics is indicated for contaminated and clean-contaminated wounds. PMID:21887170

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

    PubMed Central

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

    2015-01-01

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

  1. [Molecular physiology of glycine receptors in nervous system of vertebrates].

    PubMed

    2014-03-01

    Glycine receptor is the anion-selective channel, providing fast synaptic transmission in the central nervous system of vertebrates. Together with the nicotinic acetylcholine, GABA and serotonin (5-HT3R) receptors, it belongs to the superfamily of pentameric cys-loop receptors. It has been cloned one beta and four alpha subunits of glycine receptor, which are specifically distributed in different areas of the nervous system. Due to their specific molecular properties and distribution, different subunits ensure important physiological functions: from control of motor activity and regulation of neuronal differentiation to sensory information processing and modulation of pain sensitivity. In this review we briefly describe main functions of these transmembrane proteins, their distribution and molecular architecture. Special attention is paid to recent studies on the molecular physiology of these receptors, as well as on presenting of molecular domains responsible for their modulation and dysfunction. PMID:25508361

  2. [Molecular physiology of glycine receptors in nervous system of vertebrates].

    PubMed

    Maleeva, G V; Brezhestovskiĭ, P D

    2014-03-01

    Glycine receptor is the anion-selective channel, providing fast synaptic transmission in the central nervous system of vertebrates. Together with the nicotinic acetylcholine, GABA and serotonin (5-HT3R) receptors, it belongs to the superfamily of pentameric cys-loop receptors. It has been cloned one beta and four alpha subunits of glycine receptor, which are specifically distributed in different areas of the nervous system. Due to their specific molecular properties and distribution, different subunits ensure important physiological functions: from control of motor activity and regulation of neuronal differentiation to sensory information processing and modulation of pain sensitivity. In this review we briefly describe main functions of these transmembrane proteins, their distribution and molecular architecture. Special attention is paid to recent studies on the molecular physiology of these receptors, as well as on presenting of molecular domains responsible for their modulation and dysfunction. PMID:25464730

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  5. Learning by Heart: Students Use Heart Rate Patterns To Identify Nervous System Imbalances.

    ERIC Educational Resources Information Center

    Ackerly, Spafford C.

    2001-01-01

    Introduces a science unit on heart rate variability (HVR) patterns. Uses spectral analysis to determine the effects of environmental stimulants such as music and emotional stress on heart rate. Observes relaxation techniques and their effects on the autonomous nervous system. (Contains 12 references.) (YDS)

  6. Eph-ephrin signaling in nervous system development

    PubMed Central

    Cramer, Karina S.; Miko, Ilona J.

    2016-01-01

    Ephrins and Eph receptors enable contact-mediated interactions between cells at every stage of nervous system development. In spite of their broad binding affinities, Eph proteins facilitate specificity in neuronal migration and axon targeting. This review focuses on recent studies that demonstrate how these proteins interact with each other, and with other signaling pathways, to guide specificity in a diverse set of developmental processes. PMID:27092247

  7. The role of leptin in central nervous system diseases

    PubMed Central

    Li, Xiao-Mei; Yan, Hai-Jing; Guo, Yi-Shan

    2016-01-01

    Leptin is a peptide hormone produced by adipose tissue and acts in brain centers to control critical physiological functions. Leptin receptors are especially abundant in the hypothalamus and trigger specific neuronal subpopulations, and activate several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway. Although most studies focus on its role in energy intake and expenditure, leptin also plays a critical role in many central nervous system diseases. PMID:26885866

  8. The central nervous system in childhood chronic kidney disease.

    PubMed

    Gipson, Debbie S; Duquette, Peter J; Icard, Phil F; Hooper, Stephen R

    2007-10-01

    Neurodevelopmental deficits in pediatric and adult survivors of childhood onset chronic kidney disease (CKD) have been documented for many years. This paper reviews the available literature on central nervous system involvement incurred in childhood CKD. The studies reviewed include recent work in neuroimaging, electrophysiology, and neuropsychology, along with commentary on school functioning and long-term outcomes. The paper concludes with suggestions for monitoring the neurodevelopmental status and pursuing appropriate early interventions for children with CKD. PMID:17072652

  9. Centralization of the deuterostome nervous system predates chordates.

    PubMed

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

    2009-08-11

    The origin of the chordate central nervous system (CNS) is unknown. One theory is that a CNS was present in the first bilaterian and that it gave rise to both the ventral cord of protostomes and the dorsal cord of deuterostomes. Another theory proposes that the chordate CNS arose by a dramatic process of dorsalization and internalization from a diffuse nerve net coextensive with the skin of the animal, such as enteropneust worms (Hemichordata, Ambulacraria) are supposed to have. We show here that juvenile and adult enteropneust worms in fact have a bona fide CNS, i.e., dense agglomerations of neurons associated with a neuropil, forming two cords, ventral and dorsal. The latter is internalized in the collar as a chordate-like neural tube. Contrary to previous assumptions, the greater part of the adult enteropneust skin is nonneural, although elements of the peripheral nervous system (PNS) are found there. We use molecular markers to show that several neuronal types are anatomically segregated in the CNS and PNS. These neuroanatomical features, whatever their homologies with the chordate CNS, imply that nervous system centralization predates the evolutionary separation of chordate and hemichordate lineages. PMID:19559615

  10. FoxO Proteins in the Nervous System

    PubMed Central

    Maiese, Kenneth

    2015-01-01

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

  11. Plasticity and neural stem cells in the enteric nervous system.

    PubMed

    Schäfer, Karl-Herbert; Van Ginneken, Chris; Copray, Sjef

    2009-12-01

    The enteric nervous system (ENS) is a highly organized part of the autonomic nervous system, which innervates the whole gastrointestinal tract by several interconnected neuronal networks. The ENS changes during development and keeps throughout its lifespan a significant capacity to adapt to microenvironmental influences, be it in inflammatory bowel diseases or changing dietary habits. The presence of neural stem cells in the pre-, postnatal, and adult gut might be one of the prerequisites to adapt to changing conditions. During the last decade, the ENS has increasingly come into the focus of clinical neural stem cell research, forming a considerable pool of neural crest derived stem cells, which could be used for cell therapy of dysganglionosis, that is, diseases based on the deficient or insufficient colonization of the gut by neural crest derived stem cells; in addition, the ENS could be an easily accessible neural stem cell source for cell replacement therapies for neurodegenerative disorders or traumatic lesions of the central nervous system. PMID:19943347

  12. [American trypanosomiasis (Chagas disease) and the nervous system].

    PubMed

    Spina-Franca, A

    1988-01-01

    Ten to twelve million people irregularly distributed mainly through extensive rural areas of Latin America are afflicted by American trypanosomiasis (Chagas disease). Trypanosoma cruzi is the etiological agent, and it is naturally transmitted to humans by hematophagous hemiptera of Triatominae sub-family. These hemiptera feed by biting and usually defecate in the area near the puncture wound. Mucous membranes of breaks in the continuity of skin serve as passage ways for the parasite present in the excrement of the bug. Acute and chronic forms of American trypanosomiasis occur. Nervous system involvement in the acute form may give rise to meningoencephalitis. Central and/or peripheral signs of nervous system involvement can occur in the chronic form. Neuronal depopulation due to cell destruction by direct parasitism during the acute stage of the disease is the main pathogenetic way pointed out to explain chronic forms of nervous system involvement. Chronic Chagas cardiopathy usually produces mural thrombi. Fragments of thrombus situated in the left ventricle may become detached and migrate with the bloodstream to cause embolic phenomena in distant vessels--as in brain vessels--thus causing embolic cerebrovascular insults. Data on clinical and experimental studies are critically analysed. PMID:3143493

  13. FoxO proteins in the nervous system.

    PubMed

    Maiese, Kenneth

    2015-01-01

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

  14. Herpesvirus infections of the central nervous system in immunocompromised patients

    PubMed Central

    Strank, Cornelia

    2012-01-01

    Human herpesviruses may cause infections of the central nervous system during primary infection or following reactivation from a latent state. Especially in immunosuppressed patients the infection can take a life-threatening course, and therefore early diagnosis of herpesvirus-associated neurological diseases should have high priority. Clinical presentation in these patients is usually without typical features, making diagnosis even more challenging. Therefore general broad testing for different herpesviruses in cerebrospinal fluid samples is highly recommended. In addition, determination of the virus DNA level in the cerebrospinal fluid by quantitative assays seems to be of high importance to determine prognosis. Moreover, it might help to differentiate between specific virus-associated disease and unspecific presence of virus in the cerebrospinal fluid, especially in immunocompromised patients. Polymerase chain reaction analysis of cerebrospinal fluid has revolutionized the diagnosis of nervous system viral infections, particularly those caused by human herpesviruses. This review summarizes the role human herpesviruses play in central nervous system infections in immunocompromised patients, with a focus on the clinical manifestation of encephalitis. PMID:22973424

  15. Gangliosides in the Nervous System: Biosynthesis and Degradation

    NASA Astrophysics Data System (ADS)

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

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

  16. Restoring nervous system structure and function using tissue engineered living scaffolds

    PubMed Central

    Struzyna, Laura A.; Harris, James P.; Katiyar, Kritika S.; Chen, H. Isaac; Cullen, D. Kacy

    2015-01-01

    Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following nervous system injury or neurodegenerative disease. Disconnection of axon pathways – the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals – is a common feature of many neurological disorders and injury. However, functional axonal regeneration rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engineered “living scaffolds”, which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration – mimicking key developmental mechanisms– or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery. PMID:26109930

  17. Restoring nervous system structure and function using tissue engineered living scaffolds.

    PubMed

    Struzyna, Laura A; Harris, James P; Katiyar, Kritika S; Chen, H Isaac; Cullen, D Kacy

    2015-05-01

    Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following nervous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regeneration rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engineered "living scaffolds", which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery. PMID:26109930

  18. New approaches in primary central nervous system lymphoma

    PubMed Central

    Fraser, Eleanor; Gruenberg, Katherine; Rubenstein, James L.

    2016-01-01

    Primary central nervous system lymphoma (PCNSL) has long been associated with an inferior prognosis compared to other aggressive non-Hodgkin’s lymphomas (NHLs). However, during the past 10 years an accumulation of clinical experience has demonstrated that long-term progression-free survival (PFS) can be attained in a major proportion of PCNSL patients who receive dose-intensive consolidation chemotherapy and avoid whole brain radiotherapy. One recent approach that has reproducibly demonstrated efficacy for newly diagnosed PCNSL patients is an immunochemotherapy combination regimen used during induction that consists of methotrexate, temozolomide, and rituximab followed by consolidative infusional etoposide plus high-dose cytarabine (EA), administered in first complete remission (CR). Other high-dose chemotherapy-based consolidative regimens have shown efficacy as well. Our goal in this review is to update principles of diagnosis and management as well as data regarding the molecular pathogenesis of PCNSL, information that may constitute a basis for development of more effective therapies required to make additional advances in this phenotype of aggressive NHL. PMID:25841718

  19. Early CT findings of global central nervous system hypoperfusion

    SciTech Connect

    Kjos, B.O.; Brant-Zawadzki, M.; Young, R.G.

    1983-12-01

    The early computed tomographic (CT) findings of acute global central nervous system hypoperfusion were studied in 10 patients. The findings could be characterized as: (1) diffuse mass effect with effacement of the cerebral sulci and of the brainstem cisterns (nine patients); (2) global decrease in the cortical gray-matter density from edema, causing loss of the normal gray-white matter differentiation (six patients); (3) low-density lesions of the basal ganglia bilaterally (five patients); and (4) decreased gray-matter density in watershed distributions bilaterally (two patients). Subsequent contrast-enhanced scans in three of the 10 patients demonstrated selective enhancement of the cerebral cortex or the basal ganglia or both. The CT findings seen in this study predicted a poor outcome; nine of the 10 patients died from the insult. The abnormal CT findings can be ascribed to increased vulnerability of the cerebral cortex and basal ganglia to hypotensive episodes. This vulnerability is due to the large metabolic demand of these regions and their characteristic local cerebral blood flow.

  20. Role of Wnt Signaling in Central Nervous System Injury.

    PubMed

    Lambert, Catherine; Cisternas, Pedro; Inestrosa, Nibaldo C

    2016-05-01

    The central nervous system (CNS) is highly sensitive to external mechanical damage, presenting a limited capacity for regeneration explained in part by its inability to restore either damaged neurons or the synaptic network. The CNS may suffer different types of external injuries affecting its function and/or structure, including stroke, spinal cord injury, and traumatic brain injury. These pathologies critically affect the quality of life of a large number of patients worldwide and are often fatal because available therapeutics are ineffective and produce limited results. Common effects of the mentioned pathologies involves the triggering of several cellular and metabolic responses against injury, including infiltration of blood cells, inflammation, glial activation, and neuronal death. Although some of the underlying molecular mechanisms of those responses have been elucidated, the mechanisms driving these processes are poorly understood in the context of CNS injury. In the last few years, it has been suggested that the activation of the Wnt signaling pathway could be important in the regenerative response after CNS injury, activating diverse protective mechanisms including the stimulation of neurogenesis, blood brain structure consolidation and the recovery of cognitive brain functions. Because Wnt signaling is involved in several physiological processes, the putative positive role of its activation after injury could be the basis for novel therapeutic approaches to CNS injury. PMID:25976365

  1. 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.

  2. Microglia in central nervous system repair after injury.

    PubMed

    Jin, Xuemei; Yamashita, Toshihide

    2016-05-01

    Accumulating evidence suggests that immune cells perform crucial inflammation-related functions including clearing dead tissue and promoting wound healing. Thus, they provide a conducive environment for better neuronal regeneration and functional recovery after adult mammalian central nervous system (CNS) injury. However, activated immune cells can also induce secondary damage of intact tissue and inhibit post-injury CNS repair. The inflammation response is due to the microglial production of cytokines and chemokines for the recruitment of peripheral immune cell populations, such as monocytes, neutrophils, dendritic cells and T lymphocytes. Interestingly, microglia and T lymphocytes can be detected at the injured site in both the early and later stages after nerve injury, whereas other peripheral immune cells infiltrate the injured parenchyma of the brain and spinal cord only in the early post-injury phase, and subsequently disappear. This suggests that microglia and T cells may play crucial roles in the post-injury functional recovery of the CNS. In this review, we summarize the current studies on microglia that examined neuronal regeneration and the molecular signalling mechanisms in the injured CNS. Better understanding of the effects of microglia on neural regeneration will aid the development of therapy strategies to enhance CNS functional recovery after injury. PMID:26861995

  3. The role of microbiome in central nervous system disorders.

    PubMed

    Wang, Yan; Kasper, Lloyd H

    2014-05-01

    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

  4. Ion Channel Expression in the Developing Enteric Nervous System

    PubMed Central

    Stamp, Lincon A.; Fegan, Emily; Dent, Stephan; Cooper, Edward C.; Lomax, Alan E.; Anderson, Colin R.; Bornstein, Joel C.; Young, Heather M.; McKeown, Sonja J.

    2015-01-01

    The enteric nervous system arises from neural crest-derived cells (ENCCs) that migrate caudally along the embryonic gut. The expression of ion channels by ENCCs in embryonic mice was investigated using a PCR-based array, RT-PCR and immunohistochemistry. Many ion channels, including chloride, calcium, potassium and sodium channels were already expressed by ENCCs at E11.5. There was an increase in the expression of numerous ion channel genes between E11.5 and E14.5, which coincides with ENCC migration and the first extension of neurites by enteric neurons. Previous studies have shown that a variety of ion channels regulates neurite extension and migration of many cell types. Pharmacological inhibition of a range of chloride or calcium channels had no effect on ENCC migration in cultured explants or neuritogenesis in vitro. The non-selective potassium channel inhibitors, TEA and 4-AP, retarded ENCC migration and neuritogenesis, but only at concentrations that also resulted in cell death. In summary, a large range of ion channels is expressed while ENCCs are colonizing the gut, but we found no evidence that ENCC migration or neuritogenesis requires chloride, calcium or potassium channel activity. Many of the ion channels are likely to be involved in the development of electrical excitability of enteric neurons. PMID:25798587

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

    MedlinePlus

    ... Research Planning Scientific Resources Research A-Z Topics Neuroscience Overview Condition Information Parts of the nervous system ... functions does the nervous system control? Why study neuroscience? What are the areas of neuroscience? NICHD Research ...

  6. ALTEA: anomalous long term effects in astronauts. A probe on the influence of cosmic radiation and microgravity on the central nervous system during long flights.

    PubMed

    Narici, L; Bidoli, V; Casolino, M; De Pascale, M P; Furano, G; Morselli, A; Picozza, P; Reali, E; Sparvoli, R; Licoccia, S; Romagnoli, P; Traversa, E; Sannita, W G; Loizzo, A; Galper, A; Khodarovich, A; Korotkov, M G; Popov, A; Vavilov, N; Avdeev, S; Salnitskii, V P; Shevchenko, O I; Petrov, V P; Trukhanov, K A; Boezio, M; Bonvicini, W; Vacchi, A; Zampa, N; Battiston, R; Mazzenga, G; Ricci, M; Spillantini, P; Castellini, G; Carlson, P; Fuglesang, C

    2003-01-01

    The ALTEA project participates to the quest for increasing the safety of manned space flights. It addresses the problems related to possible functional damage to neural cells and circuits due to particle radiation in space environment. Specifically it aims at studying the functionality of the astronauts' Central Nervous Systems (CNS) during long space flights and relating it to the peculiar environments in space, with a particular focus on the particle flux impinging in the head. The project is a large international and multidisciplinary collaboration. Competences in particle physics, neurophysiology, psychophysiology, electronics, space environment, data analyses will work together to construct the fully integrated vision electrophysiology and particle analyser system which is the core device of the project: an helmet-shaped multi-sensor device that will measure concurrently the dynamics of the functional status of the visual system and passage of each particle through the brain within a pre-determined energy window. ALTEA is scheduled to fly in the International Space Station in late 2002. One part of the multi-sensor device, one of the advanced silicon telescopes, will be launched in the ISS in early 2002 and serve as test for the final device and as discriminating dosimeter for the particle fluences within the ISS. PMID:12577991

  7. Fourier domain OCT imaging of American cockroach nervous system

    NASA Astrophysics Data System (ADS)

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

    2012-01-01

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

  8. A thermodynamic model of the sympathetic and parasympathetic nervous systems.

    PubMed

    Recordati, Giorgio

    2003-01-31

    In light of the nonequilibrium thermodynamics by I. Prigogine, the autonomic nervous system as a whole may be viewed as a dissipative structure progressively assembled in the course of evolution, plastically and rhythmically interfaced between forebrain, internal and external environments, to regulate energy, matter and information exchanges. In the present paper, this hypothesis is further pursued to verify whether the two main divisions of the autonomic nervous system, the sympathetic and parasympathetic systems, may support different types of exchange with the external environment. Previous data from hypothalamic stimulation experiments, studies of locus coeruleus function and available data on behavioral functional organization indicate that (1) tight engagement with the external environment, (2) high level of energy mobilization and utilization and (3) information mainly related to exteroceptive sensory stimulation characterize a behavioral prevalence of sympathoadrenal activation. On the other hand, (1) disengagement from the external environment, (2) low levels of internal energy and (3) dominance of proprioceptive information characterize a behavioral prevalence of vagal tone. Behavioral matter exchanges such as feeding, drinking, micturition and defecation are equally absent at the extreme of sympathoadrenal and vagally driven behaviors. The autonomic nervous system as a whole is genetically determined, but the sympathoadrenal system has been mainly designed to organize the visceral apparatus for an action to be performed by the biological system in the external environment and to deal with the novelty of task and of the environment, while the functional role of the parasympathetic is to prepare the visceral apparatus for an action to be performed by the biological system on itself, for recovery and self-protection (homeostasis), and is reinforced by repetition of phylo- and ontogenetically determined patterns. The available clinical data further support

  9. 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.

  10. 75 FR 75681 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-06

    ... HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System Drugs... and circulation) of the central nervous system. The BBB is an area consisting of specialized...

  11. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients.

    PubMed

    Bourre, J M

    2006-01-01

    The objective of this update is to give an overview of the effects of dietary nutrients on the structure and certain functions of the brain. As any other organ, the brain is elaborated from substances present in the diet (sometimes exclusively, for vitamins, minerals, essential amino-acids and essential fatty acids, including omega- 3 polyunsaturated fatty acids). However, for long it was not fully accepted that food can have an influence on brain structure, and thus on its function, including cognitive and intellectuals. In fact, most micronutrients (vitamins and trace-elements) have been directly evaluated in the setting of cerebral functioning. For instance, to produce energy, the use of glucose by nervous tissue implies the presence of vitamin B1; this vitamin modulates cognitive performance, especially in the elderly. Vitamin B9 preserves brain during its development and memory during ageing. Vitamin B6 is likely to benefit in treating premenstrual depression. Vitamins B6 and B12, among others, are directly involved in the synthesis of some neurotransmitters. Vitamin B12 delays the onset of signs of dementia (and blood abnormalities), provided it is administered in a precise clinical timing window, before the onset of the first symptoms. Supplementation with cobalamin improves cerebral and cognitive functions in the elderly; it frequently improves the functioning of factors related to the frontal lobe, as well as the language function of those with cognitive disorders. Adolescents who have a borderline level of vitamin B12 develop signs of cognitive changes. In the brain, the nerve endings contain the highest concentrations of vitamin C in the human body (after the suprarenal glands). Vitamin D (or certain of its analogues) could be of interest in the prevention of various aspects of neurodegenerative or neuroimmune diseases. Among the various vitamin E components (tocopherols and tocotrienols), only alpha-tocopherol is actively uptaken by the brain and is

  12. School reentry for children with acquired central nervous systems injuries.

    PubMed

    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 education is not necessarily a special classroom, but an individualized set of educational needs, determined by a multidisciplinary school team, to promote educational success. The purpose of this article is to inform those pediatricians and pediatric allied health professionals treating children with CNS injury of the systems in place to support successful school reentry and their role in contributing to developing an appropriate educational plan. PMID:19489086

  13. Role of the autonomic nervous system in tumorigenesis and metastasis

    PubMed Central

    Magnon, Claire

    2015-01-01

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

  14. Gemella morbillorum: an underestimated aetiology of central nervous system infection?

    PubMed

    Benedetti, Paolo; Rassu, Mario; Branscombe, Michele; Sefton, Armine; Pellizzer, Giampietro

    2009-12-01

    A case is reported of cerebellar abscess and diffuse cerebritis due to Gemella morbillorum. The clinical course was 'biphasic', developing with an acute meningeal infection followed shortly afterwards by suppuration in the cerebellar and cerebral parenchyma; this pattern seemed to suggest a latent survival of the aetiological agent, probably within the central nervous system (CNS), despite systemic antibiotic therapy. Based upon a review of cases so far described, infections of the CNS caused by G. morbillorum appear to be an emerging reality. PMID:19713361

  15. Changes in Nicotinic Neurotransmission during Enteric Nervous System Development.

    PubMed

    Foong, Jaime Pei Pei; Hirst, Caroline S; Hao, Marlene M; McKeown, Sonja J; Boesmans, Werend; Young, Heather M; Bornstein, Joel C; Vanden Berghe, Pieter

    2015-05-01

    Acetylcholine-activating pentameric nicotinic receptors (nAChRs) are an essential mode of neurotransmission in the enteric nervous system (ENS). In this study, we examined the functional development of specific nAChR subtypes in myenteric neurons using Wnt1-Cre;R26R-GCaMP3 mice, where all enteric neurons and glia express the genetically encoded calcium indicator, GCaMP3. Transcripts encoding α3, α4, α7, β2, and β4 nAChR subunits were already expressed at low levels in the E11.5 gut and by E14.5 and, thereafter, α3 and β4 transcripts were the most abundant. The effect of specific nAChR subtype antagonists on evoked calcium activity in enteric neurons was investigated at different ages. Blockade of the α3β4 receptors reduced electrically and chemically evoked calcium responses at E12.5, E14.5, and P0. In addition to the α3β4 antagonist, antagonists to α3β2 and α4β2 also significantly reduced responses by P10-11 and in adult preparations. Therefore, there is an increase in the diversity of functional nAChRs during postnatal development. However, an α7 nAChR antagonist had no effect at any age. Furthermore, at E12.5 we found evidence for unconventional receptors that were responsive to the nAChR agonists 1-dimethyl-4-phenylpiperazinium and nicotine, but were insensitive to the general nicotinic blocker, hexamethonium. Migration, differentiation, and neuritogenesis assays did not reveal a role for nAChRs in these processes during embryonic development. In conclusion, there are significant changes in the contribution of different nAChR subunits to synaptic transmission during ENS development, even after birth. This is the first study to investigate the development of cholinergic transmission in the ENS. PMID:25948261

  16. The Pathogenesis of Saffold Virus in AG129 Mice and the Effects of Its Truncated L Protein in the Central Nervous System

    PubMed Central

    Tan, Shawn Zheng Kai; Chua, Kaw Bing; Xu, Yishi; Prabakaran, Mookkan

    2016-01-01

    Saffold Virus (SAFV) is a human cardiovirus that has been suggested to cause severe infection of the central nervous system (CNS). Compared to a similar virus, Theiler’s murine encephalomyelitis virus (TMEV), SAFV has a truncated Leader (L) protein, a protein essential in the establishment of persistent CNS infections. In this study, we generated a chimeric SAFV by replacing the L protein of SAFV with that of TMEV. We then compared the replication in cell cultures and pathogenesis in a mouse model. We showed that both SAFV and chimeric SAFV are able to infect Vero and Neuro2a cells well, but only chimeric SAFV was able to infect RAW264.7. We then showed that mice lacking IFN-α/β and IFN-γ receptors provide a good animal model for SAFV infection, and further identified the locality of the infection to the ventral horn of the spine and several locations in the brain. Lastly, we showed that neither SAFV nor chimeric SAFV causes persistence in this model. Overall, our results provide a strong basis on which the mechanisms underlying Saffold virus induced neuropathogenesis can be further studied and, hence, facilitating new information about its pathogenesis. PMID:26901216

  17. Applications of Nanotechnology to the Central Nervous System

    NASA Astrophysics Data System (ADS)

    Blumling, James P., II

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

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

    PubMed

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

    2015-09-01

    Zinc finger E-box binding homeobox (Zeb) 2 is a transcription factor, identified due its ability to bind Smad proteins, and consists of multiple functional domains which interact with a variety of transcriptional co-effectors. The complex nature of the Zeb2, both at its genetic and protein levels, underlie its multifunctional properties, with Zeb2 capable of acting individually or as part of a transcriptional complex to repress, and occasionally activate, target gene expression. This review introduces Zeb2 as an essential regulator of nervous system development. Zeb2 is expressed in the nervous system throughout its development, indicating its importance in neurogenic and gliogenic processes. Indeed, mutation of Zeb2 has dramatic neurological consequences both in animal models, and in humans with Mowat-Wilson syndrome, which results from heterozygous ZEB2 mutations. The mechanisms by which Zeb2 regulates the induction of the neuroectoderm (CNS primordium) and the neural crest (PNS primordium) are reviewed herein. We then describe how Zeb2 acts to direct the formation, delamination, migration and specification of neural crest cells. Zeb2 regulation of the development of a number of cerebral regions, including the neocortex and hippocampus, are then described. The diverse molecular mechanisms mediating Zeb2-directed development of various neuronal and glial populations are reviewed. The role of Zeb2 in spinal cord and enteric nervous system development is outlined, while its essential function in CNS myelination is also described. Finally, this review discusses how the neurodevelopmental defects of Zeb2 mutant mice delineate the developmental dysfunctions underpinning the multiple neurological defects observed in Mowat-Wilson syndrome patients. PMID:26193487

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

    PubMed Central

    Lake, Jonathan I.

    2013-01-01

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

  20. [Molecular Approaches for the Diagnosis of Central Nervous System Infections].

    PubMed

    Ohkusu, Kiyofumi

    2015-07-01

    In recent years, molecular microbiology techniques have proven to be a useful supplement to conventional assays not only in identification of strains from culture, but also in direct detection of pathogens from clinical specimens. This review explores the application of molecular diagnostic techniques for infectious diseases in certain clinical contexts. It aims to assess how these molecular techniques can be integrated to enhance diagnostic capabilities for infectious diseases of the central nervous system. Finally, it emphasizes the need for close collaboration between physicians and clinical microbiologists when considering molecular diagnostics from unusual specimens/cases, because assays must be customized according to the clinical settings. PMID:26160810

  1. Near misdiagnosis of glioblastoma as primary central nervous system lymphoma.

    PubMed

    Bhatt, Vijaya Raj; Shrestha, Rajesh; Shonka, Nicole; Bociek, R Gregory

    2014-08-01

    Primary central nervous system (CNS) lymphoma, most frequently a diffuse large B-cell lymphoma, is a rare aggressive lymphoma confined to the CNS, thus requiring differentiation from other brain malignancies such as glioblastoma. Although stereotactic biopsy can confirm the diagnosis, this is invasive, not always feasible and can be inconclusive after steroid use. Hence, cranial magnetic resonance imaging (MRI) with contrast and cerebrospinal fluid analysis are frequently used to make a prompt diagnosis. We report a case of a woman with two brain masses who presented unique diagnostic challenge. PMID:24883157

  2. Near Misdiagnosis of Glioblastoma as Primary Central Nervous System Lymphoma

    PubMed Central

    Bhatt, Vijaya Raj; Shrestha, Rajesh; Shonka, Nicole; Bociek, R. Gregory

    2014-01-01

    Primary central nervous system (CNS) lymphoma, most frequently a diffuse large B-cell lymphoma, is a rare aggressive lymphoma confined to the CNS, thus requiring differentiation from other brain malignancies such as glioblastoma. Although stereotactic biopsy can confirm the diagnosis, this is invasive, not always feasible and can be inconclusive after steroid use. Hence, cranial magnetic resonance imaging (MRI) with contrast and cerebrospinal fluid analysis are frequently used to make a prompt diagnosis. We report a case of a woman with two brain masses who presented unique diagnostic challenge. PMID:24883157

  3. Extracellular vesicles round off communication in the nervous system

    PubMed Central

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

    2016-01-01

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

  4. Neuroactive steroids and the peripheral nervous system: An update.

    PubMed

    Giatti, Silvia; Romano, Simone; Pesaresi, Marzia; Cermenati, Gaia; Mitro, Nico; Caruso, Donatella; Tetel, Marc J; Garcia-Segura, Luis Miguel; Melcangi, Roberto C

    2015-11-01

    In the present review we summarize observations to date supporting the concept that neuroactive steroids are synthesized in the peripheral nervous system, regulate the physiology of peripheral nerves and exert notable neuroprotective actions. Indeed, neuroactive steroids have been recently proposed as therapies for different types of peripheral neuropathy, like for instance those occurring during aging, chemotherapy, physical injury and diabetes. Moreover, pharmacological tools able to increase the synthesis of neuroactive steroids might represent new interesting therapeutic strategy to be applied in case of peripheral neuropathy. PMID:25824325

  5. Fulminant Demyelinating Diseases of the Central Nervous System.

    PubMed

    Bevan, Carolyn J; Cree, Bruce A

    2015-12-01

    Fulminant demyelinating diseases of the central nervous system include acute disseminated encephalomyelitis, the related acute hemorrhagic leukoencephalitis, multiple sclerosis variants, neuromyelitis optica spectrum disorders, and idiopathic transverse myelitis. These syndromes are often managed with similar acute treatments including high-dose corticosteroids and plasmapheresis; however, long-term management varies. Although the prognosis of fulminant demyelinating disease was historically poor, outcomes today may be improved due to earlier diagnosis, rapid implementation of anti-inflammatory therapies such as high-dose corticosteroids and plasmapheresis, and improved supportive care. PMID:26595866

  6. 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

  7. Herpesvirus Transport to the Nervous System and Back Again

    PubMed Central

    Smith, Gregory

    2013-01-01

    Herpes simplex virus, varicella zoster virus, and pseudorabies virus are neurotropic pathogens of the Alphaherpesvirinae subfamily of the Herpesviridae. These viruses efficiently invade the peripheral nervous system and establish lifelong latency in neurons resident in peripheral ganglia. Primary and recurrent infections cycle virus particles between neurons and the peripheral tissues they innervate. This remarkable cycle of infection is the topic of this review. In addition, some of the distinguishing hallmarks of the infections caused by these viruses are evaluated in terms of their underlying similarities. PMID:22726218

  8. [Metastasis tumors of the central nervous system: molecular biology].

    PubMed

    Bello, M Josefa; González-Gómez, P; Rey, J A

    2004-12-01

    Metastases in the nervous system represent an important and growing problem in the clinical practice, being the cause of a great mortality in the developed countries. This article reviews the few data available on the molecular mechanisms involved in the pathogenesis of these tumours, leading to oncogene activation, inactivation of tumour suppressor genes, not only by the classical mechanisms, but also by the tumour cell epigenetic balance alteration. We conclude that all this knowledge will lead in the future to a better diagnosis, treatment and clinic evolution of these patients. PMID:15632995

  9. Septins in the glial cells of the nervous system.

    PubMed

    Patzig, Julia; Dworschak, Michelle S; Martens, Ann-Kristin; Werner, Hauke B

    2014-02-01

    The capacity of cytoskeletal septins to mediate diverse cellular processes is related to their ability to assemble as distinct heterooligomers and higher order structures. However, in many cell types the functional relevance of septins is not well understood. This minireview provides a brief overview of our current knowledge about septins in the non-neuronal cells of the vertebrate nervous system, collectively termed 'glial cells', i.e., astrocytes, microglia, oligodendrocytes, and Schwann cells. The dysregulation of septins observed in various models of myelin pathology is discussed with respect to implications for hereditary neuralgic amyotrophy (HNA) caused by mutations of the human SEPT9-gene. PMID:24047595

  10. Nonviral Gene Therapy of the Nervous System: Electroporation.

    PubMed

    Ding, Xue-Feng; Fan, Ming

    2016-01-01

    Electroporation has been widely used to efficiently transfer foreign genes into the mammalian central nervous system (CNS), and thus plays an important role in gene therapeutic studies on some brain disorders. A lot of work concerning electroporation is focused on gene transfer into rodent brains. This technique involves an injection of nucleic acids into the brain ventricle or specific area and then applying appropriate electrical field to the injected area. Here, we briefly introduced the advantages and the basic procedures of gene transfer into the rodent brain using electroporation. Better understanding of electroporation in rodent brain may further facilitate gene therapeutic studies on brain disorders. PMID:26611596

  11. Neuroplasticity. Key to recovery after central nervous system injury.

    PubMed Central

    Dobkin, B H

    1993-01-01

    After an injury to the central nervous system, physical and cognitive impairments and disabilities often abate. These gains may be partly mediated by mechanisms that allow reorganizing of the structure and function within gray and white matter. The potential to enhance neurologic recovery by manipulating the brain and spinal cord must now be considered in clinical practice. Today's rehabilitation routines may not encourage maximum recovery. Indeed, some commonly used physical and pharmacologic methods could inhibit the restoration of motor activities such as walking. On the other hand, therapies that use our expanding knowledge of neuroplasticity could lead to better results for patients. PMID:8351906

  12. Central nervous system regeneration: from leech to opossum.

    PubMed

    Mladinic, M; Muller, K J; Nicholls, J G

    2009-06-15

    A major problem of neurobiology concerns the failure of injured mammalian spinal cord to repair itself. This review summarizes work done on two preparations in which regeneration can occur: the central nervous system of an invertebrate, the leech, and the spinal cord of an immature mammal, the opossum. The aim is to understand cellular and molecular mechanisms that promote and prevent regeneration. In the leech, an individual axon regrows successfully to re-establish connections with its synaptic target, while avoiding other neurons. Functions that were lost are thereby restored. Moreover, pairs of identified neurons become re-connected with appropriate synapses in culture. It has been shown that microglial cells and nitric oxide play key roles in leech CNS regeneration. In the opossum, the neonatal brain and spinal cord are so tiny that they survive well in culture. Fibres grow across spinal cord lesions in neonatal animals and in vitro, but axon regeneration stops abruptly between postnatal days 9 and 12. A comprehensive search has been made in spinal cords that can and cannot regenerate to identify genes and establish their locations. At 9 days, growth-promoting genes, their receptors and key transcription molecules are up-regulated. By contrast at 12 days, growth-inhibitory molecules associated with myelin are prominent. The complete sequence of the opossum genome and new methods for transfecting genes offer ways to determine which molecules promote and which inhibit spinal cord regeneration. These results lead to questions about how basic research on mechanisms of regeneration could be 'translated' into effective therapies for patients with spinal cord injuries. PMID:19525562

  13. The Adrenergic Nervous System in Heart Failure: Pathophysiology and Therapy

    PubMed Central

    Lymperopoulos, Anastasios; Rengo, Giuseppe; Koch, Walter J.

    2013-01-01

    Heart failure (HF), the leading cause of death in the western world, develops when a cardiac injury or insult impairs the ability of the heart to pump blood and maintain tissue perfusion. It is characterized by a complex interplay of several neurohormonal mechanisms that get activated in the syndrome in order to try and sustain cardiac output in the face of decompensating function. Perhaps the most prominent among these neurohormonal mechanisms is the adrenergic (or sympathetic) nervous system (ANS), whose activity and outflow are enormously elevated in HF. Acutely, and if the heart works properly, this activation of the ANS will promptly restore cardiac function. However, if the cardiac insult persists over time, chances are the ANS will not be able to maintain cardiac function, the heart will progress into a state of chronic decompensated HF, and the hyperactive ANS will continue to “push” the heart to work at a level much higher than the cardiac muscle can handle. From that point on, ANS hyperactivity becomes a major problem in HF, conferring significant toxicity to the failing heart and markedly increasing its morbidity and mortality. The present review discusses the role of the ANS in cardiac physiology and in HF pathophysiology, the mechanisms of regulation of ANS activity and how they go awry in chronic HF, methods of measuring ANS activity in HF, the molecular alterations in heart physiology that occur in HF along with their pharmacological and therapeutic implications, and, finally, drugs and other therapeutic modalities used in HF treatment that target or affect the ANS and its effects on the failing heart. PMID:23989716

  14. Control of the Cutaneous Circulation by the Central Nervous System.

    PubMed

    Blessing, William; McAllen, Robin; McKinley, Michael

    2016-01-01

    The central nervous system (CNS), via its control of sympathetic outflow, regulates blood flow to the acral cutaneous beds (containing arteriovenous anastomoses) as part of the homeostatic thermoregulatory process, as part of the febrile response, and as part of cognitive-emotional processes associated with purposeful interactions with the external environment, including those initiated by salient or threatening events (we go pale with fright). Inputs to the CNS for the thermoregulatory process include cutaneous sensory neurons, and neurons in the preoptic area sensitive to the temperature of the blood in the internal carotid artery. Inputs for cognitive-emotional control from the exteroceptive sense organs (touch, vision, sound, smell, etc.) are integrated in forebrain centers including the amygdala. Psychoactive drugs have major effects on the acral cutaneous circulation. Interoceptors, chemoreceptors more than baroreceptors, also influence cutaneous sympathetic outflow. A major advance has been the discovery of a lower brainstem control center in the rostral medullary raphé, regulating outflow to both brown adipose tissue (BAT) and to the acral cutaneous beds. Neurons in the medullary raphé, via their descending axonal projections, increase the discharge of spinal sympathetic preganglionic neurons controlling the cutaneous vasculature, utilizing glutamate, and serotonin as neurotransmitters. Present evidence suggests that both thermoregulatory and cognitive-emotional control of the cutaneous beds from preoptic, hypothalamic, and forebrain centers is channeled via the medullary raphé. Future studies will no doubt further unravel the details of neurotransmitter pathways connecting these rostral control centers with the medullary raphé, and those operative within the raphé itself. © 2016 American Physiological Society. Compr Physiol 6:1161-1197, 2016. PMID:27347889

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

    PubMed

    Dorban, Gauthier; Antoine, Nadine; Defaweux, Valérie

    2010-01-01

    Prion disease pathogenesis has been largely studied since the inter-species transmissibility of the infectious protein (PrPSc), the oral uptake as natural route of infection and the exceptional implication in a problem of public health were highlighted. Two sequential preclinical stages are observed before the development of irreversible and fatal lesions in the central nervous system: the lymphoinvasion and the neuroinvasion. The first is characterized by the accumulation of PrPSc within lymphoid tissues and the second by PrPSc scattering the peripheral nervous system towards the central nervous system. The mechanisms involved in the communication between the immune and the peripheral nervous system are still debated. Recent studies even suggest that neuroinvasion can occur through the hematogenous route, independently of the peripheral nervous system. This review analyses (i) the role of immune cells, implicated in prion pathogenesis: dendritic cells as PrPSc vehicle, follicular dendritic cells as PrPSc accumulator and nerve fibres as PrPSc driver and (ii) the respective relations they maintain with peripheral nerve fibres to migrate to the brain. PMID:20619163

  16. Gut Commensalism, Cytokines, and Central Nervous System Demyelination

    PubMed Central

    Ochoa-Repáraz, Javier; Kasper, Lloyd H.

    2014-01-01

    There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination. PMID:25084177

  17. 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. PMID:25084177

  18. Ion Channels as Drug Targets in Central Nervous System Disorders

    PubMed Central

    Waszkielewicz, A.M; Gunia, A; Szkaradek, N; Słoczyńska, K; Krupińska, S; Marona, H

    2013-01-01

    Ion channel targeted drugs have always been related with either the central nervous system (CNS), the peripheral nervous system, or the cardiovascular system. Within the CNS, basic indications of drugs are: sleep disorders, anxiety, epilepsy, pain, etc. However, traditional channel blockers have multiple adverse events, mainly due to low specificity of mechanism of action. Lately, novel ion channel subtypes have been discovered, which gives premises to drug discovery process led towards specific channel subtypes. An example is Na+ channels, whose subtypes 1.3 and 1.7-1.9 are responsible for pain, and 1.1 and 1.2 – for epilepsy. Moreover, new drug candidates have been recognized. This review is focusing on ion channels subtypes, which play a significant role in current drug discovery and development process. The knowledge on channel subtypes has developed rapidly, giving new nomenclatures of ion channels. For example, Ca2+ channels are not any more divided to T, L, N, P/Q, and R, but they are described as Cav1.1-Cav3.3, with even newer nomenclature α1A-α1I and α1S. Moreover, new channels such as P2X1-P2X7, as well as TRPA1-TRPV1 have been discovered, giving premises for new types of analgesic drugs. PMID:23409712

  19. Central- and autonomic nervous system coupling in schizophrenia.

    PubMed

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

    2016-05-13

    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. 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…

  1. Does the Sympathetic Nervous System Adapt to Chronic Altitude Exposure?

    PubMed

    Sander, Mikael

    2016-01-01

    During continued exposure to hypobaric hypoxia in acclimatizing lowlanders increasing norepinephrine levels indirectly indicate sympathoexcitation, and in a few subjects serial measurements have suggested some adaptation over time. A few studies have provided direct microneurographic evidence for markedly increased muscle sympathetic nervous activity (MSNA) after 1-50 days of exposure of lowlanders to altitudes of 4100-5260 m above sea level. Only one study has provided two MSNA-measurements over time (10 and 50 days) in altitude (4100 m above sea level) and continued robust sympathoexcitation without adaptation was found in acclimatizing lowlanders. In this study, norepinephrine levels during rest and exercise also remained highly elevated over time. In comparison, acute exposure to hypoxic breathing (FiO2 0.126) at sea level caused no change in sympathetic nervous activity, although the same oxygen saturation in arterial blood (around 90 %) was present during acute (FiO2 0.126) and chronic hypoxic exposure (4100 m above sea level). These findings strongly suggest that the chemoreflex-mechanisms underlying acute hypoxia-induced increases in MSNA are sensitized over time. Collectively, the MSNA data suggests that sensitization of the sympathoexcitatory chemoreflex is evident but not complete within the first 24 h, but is complete after 10 days of altitude exposure. After return from high altitude to sea level the MSNA remains significantly elevated for at least 5 days but completely normalized after 3 months. The few MSNA measurements in high altitude natives have documented high sympathetic activity in all subjects studied. Because serial measurements of MSNA in high altitude natives during sea level exposure are lacking, it is unclear whether the sympathetic nervous system have somehow adapted to lifelong altitude exposure. PMID:27343109

  2. The origin and evolution of chordate nervous systems.

    PubMed

    Holland, Linda Z

    2015-12-19

    In the past 40 years, comparisons of developmental gene expression and mechanisms of development (evodevo) joined comparative morphology as tools for reconstructing long-extinct ancestral forms. Unfortunately, both approaches typically give congruent answers only with closely related organisms. Chordate nervous systems are good examples. Classical studies alone left open whether the vertebrate brain was a new structure or evolved from the anterior end of an ancestral nerve cord like that of modern amphioxus. Evodevo plus electron microscopy showed that the amphioxus brain has a diencephalic forebrain, small midbrain, hindbrain and spinal cord with parts of the genetic mechanisms for the midbrain/hindbrain boundary, zona limitans intrathalamica and neural crest. Evodevo also showed how extra genes resulting from whole-genome duplications in vertebrates facilitated evolution of new structures like neural crest. Understanding how the chordate central nervous system (CNS) evolved from that of the ancestral deuterostome has been truly challenging. The majority view is that this ancestor had a CNS with a brain that gave rise to the chordate CNS and, with loss of a discrete brain, to one of the two hemichordate nerve cords. The minority view is that this ancestor had no nerve cord; those in chordates and hemichordates evolved independently. New techniques such as phylostratigraphy may help resolve this conundrum. PMID:26554041

  3. Dietary Glutamate: Interactions With the Enteric Nervous System

    PubMed Central

    Wang, Guo-Du; Wang, Xi-Yu; Xia, Yun

    2014-01-01

    Background/Aims Digestion of dietary protein elevates intraluminal concentrations of glutamate in the small intestine, some of which gain access to the enteric nervous system (ENS). Glutamate, in the central nervous system (CNS), is an excitatory neurotransmitter. A dogma that glutamatergic neurophysiology in the ENS recapitulates CNS glutamatergic function persists. We reassessed the premise that glutamatergic signaling in the ENS recapitulates its neurotransmitter role in the CNS. Methods Pharmacological analysis of actions of receptor agonists and antagonists in concert with immunohistochemical localization of glutamate transporters and receptors was used. Analysis focused on intracellularly-recorded electrical and synaptic behavior of ENS neurons, on stimulation of mucosal secretion by secretomotor neurons in the submucosal plexus and on muscle contractile behavior mediated by musculomotor neurons in the myenteric plexus. Results Immunoreactivity for glutamate was expressed in ENS neurons. ENS neurons expressed immunoreactivity for the EAAC-1 glutamate transporter. Neither L-glutamate nor glutamatergic receptor agonists had excitatory actions on ENS neurons. Metabotropic glutamatergic receptor agonists did not directly stimulate neurogenic mucosal chloride secretion. Neither L-glutamate nor the metabotropic glutamatergic receptor agonist, aminocyclopentane-1,3-dicarboxylic acid (ACPD), changed the mean amplitude of spontaneously occurring contractions in circular or longitudinal strips of intestinal wall from either guinea pig or human small intestinal preparations. Conclusions Early discoveries, for excitatory glutamatergic neurotransmission in the CNS, inspired enthusiasm that investigation in the ENS would yield discoveries recapitulating the CNS glutamatergic story. We found this not to be the case. PMID:24466444

  4. Probing disorders of the nervous system using reprogramming approaches

    PubMed Central

    Ichida, Justin K; Kiskinis, Evangelos

    2015-01-01

    The groundbreaking technologies of induced pluripotency and lineage conversion have generated a genuine opportunity to address fundamental aspects of the diseases that affect the nervous system. These approaches have granted us unrestricted access to the brain and spinal cord of patients and have allowed for the study of disease in the context of human cells, expressing physiological levels of proteins and under each patient's unique genetic constellation. Along with this unprecedented opportunity have come significant challenges, particularly in relation to patient variability, experimental design and data interpretation. Nevertheless, significant progress has been achieved over the past few years both in our ability to create the various neural subtypes that comprise the nervous system and in our efforts to develop cellular models of disease that recapitulate clinical findings identified in patients. In this Review, we present tables listing the various human neural cell types that can be generated and the neurological disease modeling studies that have been reported, describe the current state of the field, highlight important breakthroughs and discuss the next steps and future challenges. PMID:25925386

  5. Detection of BMAA in the human central nervous system.

    PubMed

    Berntzon, L; Ronnevi, L O; Bergman, B; Eriksson, J

    2015-04-30

    Amyotrophic lateral sclerosis (ALS) is an extremely devastating neurodegenerative disease with an obscure etiology. The amino acid β-N-methylamino-l-alanine (BMAA) produced by globally widespread phytoplankton has been implicated in the etiology of human motor neuron diseases [corrected]. BMAA was recently proven to be present in Baltic Sea food webs, ranging from plankton to larger Baltic Sea organisms, some serving as important food items (fish) for humans. To test whether exposure to BMAA in a Baltic Sea setting is reflected in humans, blood and cerebrospinal fluid (CSF) from individuals suffering from ALS were analyzed, together with sex- and age-matched individuals not inflicted with ALS. Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and multiple reaction monitoring (MRM), in conjunction with diagnostic transitions revealed BMAA in three (12%) of the totally 25 Swedish individuals tested, with no preference for those suffering from ALS. The three BMAA-positive samples were all retrieved from the CSF, while BMAA was not detected in the blood. The data show that BMAA, potentially originating from Baltic Sea phytoplankton, may reach the human central nervous system, but does not lend support to the notion that BMAA is resident specifically in ALS-patients. However, while dietary exposure to BMAA may be intermittent and, if so, difficult to detect, our data provide the first demonstration of BMAA in the central nervous system of human individuals ante mortem quantified with UHPLC-MS/MS, and therefore calls for extended research efforts. PMID:25725357

  6. Control of Bone Remodeling by the Peripheral Sympathetic Nervous System

    PubMed Central

    Campbell, Preston; Ma, Yun

    2013-01-01

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

  7. Probing disorders of the nervous system using reprogramming approaches.

    PubMed

    Ichida, Justin K; Kiskinis, Evangelos

    2015-06-01

    The groundbreaking technologies of induced pluripotency and lineage conversion have generated a genuine opportunity to address fundamental aspects of the diseases that affect the nervous system. These approaches have granted us unrestricted access to the brain and spinal cord of patients and have allowed for the study of disease in the context of human cells, expressing physiological levels of proteins and under each patient's unique genetic constellation. Along with this unprecedented opportunity have come significant challenges, particularly in relation to patient variability, experimental design and data interpretation. Nevertheless, significant progress has been achieved over the past few years both in our ability to create the various neural subtypes that comprise the nervous system and in our efforts to develop cellular models of disease that recapitulate clinical findings identified in patients. In this Review, we present tables listing the various human neural cell types that can be generated and the neurological disease modeling studies that have been reported, describe the current state of the field, highlight important breakthroughs and discuss the next steps and future challenges. PMID:25925386

  8. TrkB/BDNF signalling patterns the sympathetic nervous system

    PubMed Central

    Kasemeier-Kulesa, Jennifer C.; Morrison, Jason A.; Lefcort, Frances; Kulesa, Paul M.

    2015-01-01

    The sympathetic nervous system is essential for maintaining mammalian homeostasis. How this intricately connected network, composed of preganglionic neurons that reside in the spinal cord and post-ganglionic neurons that comprise a chain of vertebral sympathetic ganglia, arises developmentally is incompletely understood. This problem is especially complex given the vertebral chain of sympathetic ganglia derive secondarily from the dorsal migration of ‘primary' sympathetic ganglia that are initially located several hundred microns ventrally from their future pre-synaptic partners. Here we report that the dorsal migration of discrete ganglia is not a simple migration of individual cells but a much more carefully choreographed process that is mediated by extensive interactions of pre-and post-ganglionic neurons. Dorsal migration does not occur in the absence of contact with preganglionic axons, and this is mediated by BDNF/TrkB signalling. Thus BDNF released by preganglionic axons acts chemotactically on TrkB-positive sympathetic neurons, to pattern the developing peripheral nervous system. PMID:26404565

  9. Engineering Biomaterial Properties for Central Nervous System Applications

    NASA Astrophysics Data System (ADS)

    Rivet, Christopher John

    Biomaterials offer unique properties that are intrinsic to the chemistry of the material itself or occur as a result of the fabrication process; iron oxide nanoparticles are superparamagnetic, which enables controlled heating in the presence of an alternating magnetic field, and a hydrogel and electrospun fiber hybrid material provides minimally invasive placement of a fibrous, artificial extracellular matrix for tissue regeneration. Utilization of these unique properties towards central nervous system disease and dysfunction requires a thorough definition of the properties in concert with full biological assessment. This enables development of material-specific features to elicit unique cellular responses. Iron oxide nanoparticles are first investigated for material-dependent, cortical neuron cytotoxicity in vitro and subsequently evaluated for alternating magnetic field stimulation induced hyperthermia, emulating the clinical application for enhanced chemotherapy efficacy in glioblastoma treatment. A hydrogel and electrospun fiber hybrid material is first applied to a rat brain to evaluate biomaterial interface astrocyte accumulation as a function of hybrid material composition. The hybrid material is then utilized towards increasing functional engraftment of dopaminergic progenitor neural stem cells in a mouse model of Parkinson's disease. Taken together, these two scenarios display the role of material property characterization in development of biomaterial strategies for central nervous system repair and regeneration.

  10. Astrocyte scar formation aids central nervous system axon regeneration.

    PubMed

    Anderson, Mark A; Burda, Joshua E; Ren, Yilong; Ao, Yan; O'Shea, Timothy M; Kawaguchi, Riki; Coppola, Giovanni; Khakh, Baljit S; Deming, Timothy J; Sofroniew, Michael V

    2016-04-14

    Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration. PMID:27027288

  11. Fine structure of synaptogenesis in the vertebrate central nervous system.

    PubMed

    Vaughn, J E

    1989-01-01

    This article reviews studies of the formation of synaptic junctions in the vertebrate central nervous system. It is focused on electron microscopic investigations of synaptogenesis, although insights from other disciplines are interwoven where appropriate, as are findings from developing peripheral and invertebrate nervous systems. The first part of the review is concerned with the morphological maturation of synapses as described from both qualitative and quantitative perspectives. Next, epigenetic influences on synaptogenesis are examined, and later in the article the concept of epigenesis is integrated with that of hierarchy. It is suggested that the formation of synaptic junctions may take place as an ordered progression of epigenetically modulated events wherein each level of cellular affinity becomes subordinate to the one that follows. The ultimate determination of whether a synapse is maintained, modified or dissolved would be made by the changing molecular fabric of its junctional membranes. In closing, a hypothetical model of synaptogenesis is proposed, and an hierarchial order of events is associated with a speculative synaptogenic sequence. Key elements of this hypothesis are 1) epigenetic factors that facilitate generally appropriate interactions between neurites; 2) independent expression of surface specializations that contain sufficient information for establishing threshold recognition between interacting neurites; 3) exchange of molecular information that biases the course of subsequent junctional differentiation and ultimately results in 4) the stabilization of synaptic junctions into functional connectivity patterns. PMID:2655146

  12. The WHO classification of tumors of the nervous system.

    PubMed

    Kleihues, Paul; Louis, David N; Scheithauer, Bernd W; Rorke, Lucy B; Reifenberger, Guido; Burger, Peter C; Cavenee, Webster K

    2002-03-01

    The new World Health Organization (WHO) classification of nervous system tumors, published in 2000, emerged from a 1999 international consensus conference of neuropathologists. New entities include chordoid glioma of the third ventricle, cerebellar liponeurocytoma, atypical teratoid/rhabdoid tumor, and perineurioma. Several histological variants were added, including tanycytic ependymoma, large cell medulloblastoma, and rhabdoid meningioma. The WHO grading scheme was updated and, for meningiomas, extensively revised. In recognition of the emerging role of molecular diagnostic approaches to tumor classification, genetic profiles have been emphasized, as in the distinct subtypes of glioblastoma and the already clinically useful 1p and 19q markers for oligodendroglioma and 22q/INI1 for atypical teratoid/rhabdoid tumors. In accord with the new WHO Blue Book series, the actual classification is accompanied by extensive descriptions and illustrations of clinicopathological characteristics of each tumor type, including molecular genetic features, predictive factors, and separate chapters on inherited tumor syndromes. The 2000 WHO classification of nervous system tumors aims at being used and implemented by the neuro-oncology and biomedical research communities worldwide. PMID:11895036

  13. 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. PMID:24715483

  14. Central Nervous System Control of Gastrointestinal Motility and Secretion and Modulation of Gastrointestinal Functions

    PubMed Central

    Browning, Kirsteen N.; Travagli, R. Alberto

    2016-01-01

    Although the gastrointestinal (GI) tract possesses intrinsic neural plexuses that allow a significant degree of autonomy over GI functions, the central nervous system (CNS) provides extrinsic neural inputs that regulate, modulate, and control these functions. While the intestines are capable of functioning in the absence of extrinsic inputs, the stomach and esophagus are much more dependent upon extrinsic neural inputs, particularly from parasympathetic and sympathetic pathways. The sympathetic nervous system exerts a predominantly inhibitory effect upon GI muscle and provides a tonic inhibitory influence over mucosal secretion while, at the same time, regulates GI blood flow via neurally mediated vasoconstriction. The parasympathetic nervous system, in contrast, exerts both excitatory and inhibitory control over gastric and intestinal tone and motility. Although GI functions are controlled by the autonomic nervous system and occur, by and large, independently of conscious perception, it is clear that the higher CNS centers influence homeostatic control as well as cognitive and behavioral functions. This review will describe the basic neural circuitry of extrinsic inputs to the GI tract as well as the major CNS nuclei that innervate and modulate the activity of these pathways. The role of CNS-centered reflexes in the regulation of GI functions will be discussed as will modulation of these reflexes under both physiological and pathophysiological conditions. Finally, future directions within the field will be discussed in terms of important questions that remain to be resolved and advances in technology that may help provide these answers. PMID:25428846

  15. Nervous system Lyme disease, chronic Lyme disease, and none of the above.

    PubMed

    Halperin, John J

    2016-03-01

    Lyme borreliosis, infection with the tick-borne spirochete Borrelia burgdorferi sensu lato, causes nervous system involvement in 10-15 % of identified infected individuals. Not unlike the other well-known spirochetosis, syphilis, infection can be protracted, but is microbiologically curable in virtually all patients, regardless of disease duration. Diagnosis relies on 2-tier serologic testing, which after the first 4-6 weeks of infection is both highly sensitive and specific. After this early, acute phase, serologic testing should rely only on IgG reactivity. Nervous system involvement most commonly presents with meningitis, cranial neuritis and radiculoneuritis, but can also present with a broader array of peripheral nervous system manifestations. Central nervous system infection typically elicits a cerebrospinal fluid pleocytosis and, often, intrathecal production of specific antibody, findings that should not be expected in disease not affecting the CNS. Treatment with recommended courses of oral or, when necessary, parenteral antibiotics is highly effective. The attribution of chronic, non-specific symptoms to "chronic Lyme disease", in the absence of specific evidence of ongoing B. burgdorferi infection, is inappropriate and unfortunate, leading not only to unneeded treatment and its associated complications, but also to missed opportunities for more appropriate management of patients' often disabling symptoms. PMID:26377699

  16. The Nervous System Uses Nonspecific Motor Learning in Response to Random Perturbations of Varying Nature

    PubMed Central

    Wert, Daniel; Körding, Konrad

    2010-01-01

    We constantly make small errors during movement and use them to adapt our future movements. Movement experiments often probe this error-driven learning by perturbing movements and analyzing the after-effects. Past studies have applied perturbations of varying nature such as visual disturbances, position- or velocity-dependent forces and modified inertia properties of the limb. However, little is known about how the specific nature of a perturbation influences subsequent movements. For a single perturbation trial, the nature of a perturbation may be highly uncertain to the nervous system, given that it receives only noisy information. One hypothesis is that the nervous system can use this rough estimate to partially correct for the perturbation on the next trial. Alternatively, the nervous system could ignore uncertain information about the nature of the perturbation and resort to a nonspecific adaptation. To study how the brain estimates and responds to incomplete sensory information, we test these two hypotheses using a trial-by-trial adaptation experiment. On each trial, the nature of the perturbation was chosen from six distinct types, including a visuomotor rotation and different force fields. We observed that corrective forces aiming to oppose the perturbation in the following trial were independent of the nature of the perturbation. Our results suggest that the nervous system uses a nonspecific strategy when it has high uncertainty about the nature of perturbations during trial-by-trial learning. PMID:20861427

  17. Role of ubiquitin-proteasome-mediated proteolysis in nervous system disease

    PubMed Central

    Hegde, Ashok N.; Upadhya, Sudarshan C.

    2010-01-01

    Proteolysis by the ubiquitin-proteasome pathway (UPP) is now widely recognized as a molecular mechanism controlling myriad normal functions in the nervous system. Also, this pathway is intimately linked to many diseases and disorders of the brain. Among the diseases connected to the UPP are neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases. Perturbation in the UPP is also believed to play a causative role in mental disorders such as Angelman syndrome. The pathology of neurodegenerative diseases is characterized by abnormal deposition of insoluble protein aggregates or inclusion bodies within neurons. The ubiquitinated protein aggregates are believed to result from dysfunction of the UPP or from structural changes in the protein substrates which prevent their recognition and degradation by the UPP. An early effect of abnormal UPP in diseases of the nervous system is likely to be impairment of synaptic function. Here we discuss the UPP and its physiological roles in the nervous system and how alterations in the UPP relate to development of nervous system diseases. PMID:20674814

  18. Causal interactions between the cerebral cortex and the autonomic nervous system.

    PubMed

    Yu, XiaoLin; Zhang, Chong; Zhang, JianBao

    2014-05-01

    Mental states such as stress and anxiety can cause heart disease. On the other hand, meditation can improve cardiac performance. In this study, the heart rate variability, directed transfer function and corrected conditional entropy were used to investigate the effects of mental tasks on cardiac performance, and the functional coupling between the cerebral cortex and the heart. When subjects tried to decrease their heart rate by volition, the sympathetic nervous system was inhibited and the heart rate decreased. When subjects tried to increase their heart rate by volition, the parasympathetic nervous system was inhibited and the sympathetic nervous system was stimulated, and the heart rate increased. When autonomic nervous system activity was regulated by mental tasks, the information flow from the post-central areas to the pre-central areas of the cerebral cortex increased, and there was greater coupling between the brain and the heart. Use of directed transfer function and corrected conditional entropy techniques enabled analysis of electroencephalographic recordings, and of the information flow causing functional coupling between the brain and the heart. PMID:24691996

  19. Autonomic Nervous System Reactivity During Speech Repetition Tasks: Heart Rate Variability and Skin Conductance.

    PubMed

    Mackersie, Carol L; Calderon-Moultrie, Natalie

    2016-01-01

    Cognitive and emotional challenges may elicit a physiological stress response that can include arousal of the sympathetic nervous system (fight or flight response) and withdrawal of the parasympathetic nervous system (responsible for recovery and rest). This article reviews studies that have used measures of electrodermal activity (skin conductance) and heart rate variability (HRV) to index sympathetic and parasympathetic activity during auditory tasks. In addition, the authors present results from a new study with normal-hearing listeners examining the effects of speaking rate on changes in skin conductance and high-frequency HRV (HF-HRV). Sentence repetition accuracy for normal and fast speaking rates was measured in noise using signal to noise ratios that were adjusted to approximate 80% accuracy (+3 dB fast rate; 0 dB normal rate) while monitoring skin conductance and HF-HRV activity. A significant increase in skin conductance level (reflecting sympathetic nervous system arousal) and a decrease in HF-HRV (reflecting parasympathetic nervous system withdrawal) were observed with an increase in speaking rate indicating sensitivity of both measures to increased task demand. Changes in psychophysiological reactivity with increased auditory task demand may reflect differences in listening effort, but other person-related factors such as motivation and stress may also play a role. Further research is needed to understand how psychophysiological activity during listening tasks is influenced by the acoustic characteristics of stimuli, task demands, and by the characteristics and emotional responses of the individual. PMID:27355761

  20. A Role of Ginseng and Its Constituents in the Treatment of Central Nervous System Disorders

    PubMed Central

    Rokot, Natasya Trivena; Kairupan, Timothy Sean; Cheng, Kai-Chun; Runtuwene, Joshua; Kapantow, Nova Hellen; Amitani, Marie; Morinaga, Akinori; Amitani, Haruka; Asakawa, Akihiro

    2016-01-01

    Ginseng, a perennial plant belonging to the Panax genus of the Araliaceae family, has been used in China, Korea, and Japan as a traditional herbal medicine for thousands of years. Ginseng is recorded to have exhibited a wide variety of beneficial pharmacological effects and has become a popular and worldwide known health supplement and drug. The protective effects of ginseng on central nervous system are discussed in this review. Ginseng species and ginsenosides and their intestinal metabolism and bioavailability are concisely introduced. The molecular mechanisms of the effects of ginseng on central nervous system, mainly focused on the neuroprotection properties of ginseng, memory, and learning enhanced properties, and the effects on neurodegenerative disorders are presented. Thus, ginseng and its constituents are of potential merits in the treatment of cerebral disorders.

  1. Control of Prosthetic Hands via the Peripheral Nervous System

    PubMed Central

    Ciancio, Anna Lisa; Cordella, Francesca; Barone, Roberto; Romeo, Rocco Antonio; Bellingegni, Alberto Dellacasa; Sacchetti, Rinaldo; Davalli, Angelo; Di Pino, Giovanni; Ranieri, Federico; Di Lazzaro, Vincenzo; Guglielmelli, Eugenio; Zollo, Loredana

    2016-01-01

    This paper intends to provide a critical review of the literature on the technological issues on control and sensorization of hand prostheses interfacing with the Peripheral Nervous System (i.e., PNS), and their experimental validation on amputees. The study opens with an in-depth analysis of control solutions and sensorization features of research and commercially available prosthetic hands. Pros and cons of adopted technologies, signal processing techniques and motion control solutions are investigated. Special emphasis is then dedicated to the recent studies on the restoration of tactile perception in amputees through neural interfaces. The paper finally proposes a number of suggestions for designing the prosthetic system able to re-establish a bidirectional communication with the PNS and foster the prosthesis natural control. PMID:27092041

  2. Development-Inspired Reprogramming of the Mammalian Central Nervous System

    PubMed Central

    Amamoto, Ryoji; Arlotta, Paola

    2014-01-01

    In 2012, John Gurdon and Shinya Yamanaka shared the Nobel Prize for the exciting demonstration that the identity of differentiated cells is not irreversibly determined but can be changed back to a pluripotent state under appropriate instructive signals. The principle that differentiated cells can revert to an embryonic state and even be converted directly from one cell-type into another not only turns fundamental principles of development on their head but also has profound implications for regenerative medicine. Replacement of diseased tissue with newly reprogrammed cells and modeling of human disease are concrete opportunities. Here, we focus on the central nervous system to consider whether and how reprogramming of cell identity may impact regeneration and modeling of a system historically considered immutable and hardwired. PMID:24482482

  3. [Construction of nervous system relative protein and gene secondary database].

    PubMed

    Wang, Pan; Chen, Xinhao; Liu, Xiangming

    2007-10-01

    Along with the rapid research of neural molecular biology, abundant data are produced so that the collection and coordination of high-throughout data about nervous system relative proteins and genes are imperative. Through analyzing the biological primary databases maintained by NCBI and RCSB as the main data source and designing a new data model, a local specialized secondary database is constructed, which mainly includes nucleotide sequences, protein sequences and protein structures, and is established on Sun Blade 2000 System and Oracle 9i. All programs are developed by Java technology. A method of web information automatic retrieval with XML is proposed for sequence data collection and submission to the database. JSP + JavaBean technology is used to support data promulgation on Internet. The establishment of this database provides an excellent platform for the research of neural molecular biology and the pathogenesis of related diseases. PMID:18027688

  4. Primary Central Nervous System Vasculitis With Optic Nerve Involvement.

    PubMed

    Benson, Christy E; Knezevic, Alexander; Lynch, Shannon C

    2016-06-01

    A 20-year-old woman presented with headache, decreased vision, eye pain, and urinary retention. During her clinical course, visual acuity declined to 20/800, right eye, and 20/50, left eye, associated with bilateral optic disc edema. Brain magnetic resonance imaging revealed enhancement of the leptomeninges, right optic nerve, and right side of the optic chiasm. Extensive evaluation of the central nervous system (CNS) for an infectious cause was negative. Brain biopsy showed a pattern consistent with vasculitis. The patient was treated with prednisone and cyclophosphamide, resulting in improvement of her vision and systemic symptoms. Primary CNS vasculitis is a rare condition that may affect the anterior visual pathways. PMID:26693942

  5. Central Nervous System and its Disease Models on a Chip.

    PubMed

    Yi, YoonYoung; Park, JiSoo; Lim, Jaeho; Lee, C Justin; Lee, Sang-Hoon

    2015-12-01

    Technologies for microfluidics and biological microelectromechanical systems have been rapidly progressing over the past decade, enabling the development of unique microplatforms for in vitro human central nervous system (CNS) and related disease models. Most fundamental techniques include manipulation of axons, synapses, and neuronal networks, and different culture conditions are possible, such as compartmental, co-culturing, and 3D. Various CNS disease models, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), epilepsy, N-methyl-D-aspartate receptor (NMDAR) encephalitis, migraine, diffuse axonal injury, and neuronal migration disorders, have been successfully established on microplatforms. In this review, we summarize fundamental technologies and current existing CNS disease models on microplatforms. We also discuss possible future directions, including application of these methods to pathological studies, drug screening, and personalized medicine, with 3D and personalized disease models that could generate more realistic CNS disease models. PMID:26497426

  6. Control of Prosthetic Hands via the Peripheral Nervous System.

    PubMed

    Ciancio, Anna Lisa; Cordella, Francesca; Barone, Roberto; Romeo, Rocco Antonio; Bellingegni, Alberto Dellacasa; Sacchetti, Rinaldo; Davalli, Angelo; Di Pino, Giovanni; Ranieri, Federico; Di Lazzaro, Vincenzo; Guglielmelli, Eugenio; Zollo, Loredana

    2016-01-01

    This paper intends to provide a critical review of the literature on the technological issues on control and sensorization of hand prostheses interfacing with the Peripheral Nervous System (i.e., PNS), and their experimental validation on amputees. The study opens with an in-depth analysis of control solutions and sensorization features of research and commercially available prosthetic hands. Pros and cons of adopted technologies, signal processing techniques and motion control solutions are investigated. Special emphasis is then dedicated to the recent studies on the restoration of tactile perception in amputees through neural interfaces. The paper finally proposes a number of suggestions for designing the prosthetic system able to re-establish a bidirectional communication with the PNS and foster the prosthesis natural control. PMID:27092041

  7. Optimizing Central Nervous System Drug Development Using Molecular Imaging.

    PubMed

    Hargreaves, R J; Hoppin, J; Sevigny, J; Patel, S; Chiao, P; Klimas, M; Verma, A

    2015-07-01

    Advances in multimodality fusion imaging technologies promise to accelerate the understanding of the systems biology of disease and help in the development of new therapeutics. The use of molecular imaging biomarkers has been proven to shorten cycle times for central nervous system (CNS) drug development and thereby increase the efficiency and return on investment from research. Imaging biomarkers can be used to help select the molecules, doses, and patients most likely to test therapeutic hypotheses by stopping those that have little chance of success and accelerating those with potential to achieve beneficial clinical outcomes. CNS imaging biomarkers have the potential to drive new medical care practices for patients in the latent phases of progressive neurodegenerative disorders by enabling the detection, preventative treatment, and tracking of disease in a paradigm shift from today's approaches that have to see the overt symptoms of disease before treating it. PMID:25869938

  8. New trend in neuroscience: low-power laser effect on peripheral and central nervous system (basic science, preclinical and clinical studies).

    PubMed

    Rochkind, S; Ouaknine, G E

    1992-03-01

    The present review summarizes findings in our continuing study of the use of low-power laser irradiation (LPLI) in the treatment of severely injured peripheral (PNS) and central nervous systems (CNS). The radiation method was proposed by Rochkind and has been modified over the last 13 years. LPLI in specific wavelengths and energy density maintains the electrophysiological activity of severely injured peripheral nerve in rats, preventing scar formation (at injury site) as well as degenerative changes in the corresponding motor neurons of the spinal cord, thus accelerating regeneration of the injured nerve. Laser irradiation applied to the spinal cord of dogs following severe spinal cord injury and implantation of a segment of the peripheral nerve into the injured area diminished glial scar formation, induced axonal sprouting in the injured area and restoration of locomotor function. The use of laser irradiation in mammalian CNS transplantation shows that laser therapy prevents extensive glial scar formation (a limiting factor in CNS regeneration) between a neural transplant and the host brain or spinal cord. Abundant capillaries developed in the laser-irradiated transplants, and was of crucial importance in their survival. Intraoperative clinical use of laser therapy following surgical treatment of the tethered spinal cord (resulting from myelomeningocele, lipomyelomeningocele, thickened filum terminale or fibrous scar) increases functional activity of the irradiated spinal cord. In a previous experimental work, we showed that direct laser treatment on nerve tissue promotes restoration of the electrophysiological activity of the severely injured peripheral nerve, prevents degenerative changes in neurons of the spinal cord and induces proliferation of astrocytes and oligodendrocytes. This suggested a higher metabolism in neurons and improved ability for myelin production under the influence of laser treatment. The tethering of the spinal cord causes mechanical

  9. Exosome-mediated inflammasome signaling after central nervous system injury.

    PubMed

    de Rivero Vaccari, Juan Pablo; Brand, Frank; Adamczak, Stephanie; Lee, Stephanie W; Perez-Barcena, Jon; Wang, Michael Y; Bullock, M Ross; Dietrich, W Dalton; Keane, Robert W

    2016-01-01

    Neuroinflammation is a response against harmful effects of diverse stimuli and participates in the pathogenesis of brain and spinal cord injury (SCI). The innate immune response plays a role in neuroinflammation following CNS injury via activation of multiprotein complexes termed inflammasomes that regulate the activation of caspase 1 and the processing of the pro-inflammatory cytokines IL-1β and IL-18. We report here that the expression of components of the nucleotide-binding and oligomerization domain (NOD)-like receptor protein-1 (NLRP-1) inflammasome, apoptosis speck-like protein containing a caspase recruitment domain (ASC), and caspase 1 are significantly elevated in spinal cord motor neurons and cortical neurons after CNS trauma. Moreover, NLRP1 inflammasome proteins are present in exosomes derived from CSF of SCI and traumatic brain-injured patients following trauma. To investigate whether exosomes could be used to therapeutically block inflammasome activation in the CNS, exosomes were isolated from embryonic cortical neuronal cultures and loaded with short-interfering RNA (siRNA) against ASC and administered to spinal cord-injured animals. Neuronal-derived exosomes crossed the injured blood-spinal cord barrier, and delivered their cargo in vivo, resulting in knockdown of ASC protein levels by approximately 76% when compared to SCI rats treated with scrambled siRNA. Surprisingly, siRNA silencing of ASC also led to a significant decrease in caspase 1 activation and processing of IL-1β after SCI. These findings indicate that exosome-mediated siRNA delivery may be a strong candidate to block inflammasome activation following CNS injury. We propose the following signaling cascade for inflammasome activation in peripheral tissues after CNS injury: CNS trauma induces inflammasome activation in the nervous system and secretion of exosomes containing inflammasome protein cargo into cerebral spinal fluid. The inflammasome containing exosomes then fuse with target

  10. Autonomic nervous system correlates in movement observation and motor imagery

    PubMed Central

    Collet, C.; Di Rienzo, F.; El Hoyek, N.; Guillot, A.

    2013-01-01

    The purpose of the current article is to provide a comprehensive overview of the literature offering a better understanding of the autonomic nervous system (ANS) correlates in motor imagery (MI) and movement observation. These are two high brain functions involving sensori-motor coupling, mediated by memory systems. How observing or mentally rehearsing a movement affect ANS activity has not been extensively investigated. The links between cognitive functions and ANS responses are not so obvious. We will first describe the organization of the ANS whose main purposes are controlling vital functions by maintaining the homeostasis of the organism and providing adaptive responses when changes occur either in the external or internal milieu. We will then review how scientific knowledge evolved, thus integrating recent findings related to ANS functioning, and show how these are linked to mental functions. In turn, we will describe how movement observation or MI may elicit physiological responses at the peripheral level of the autonomic effectors, thus eliciting autonomic correlates to cognitive activity. Key features of this paper are to draw a step-by step progression from the understanding of ANS physiology to its relationships with high mental processes such as movement observation or MI. We will further provide evidence that mental processes are co-programmed both at the somatic and autonomic levels of the central nervous system (CNS). We will thus detail how peripheral physiological responses may be analyzed to provide objective evidence that MI is actually performed. The main perspective is thus to consider that, during movement observation and MI, ANS activity is an objective witness of mental processes. PMID:23908623

  11. Long-term effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the peripheral nervous system. Clinical and neurophysiological controlled study on subjects with chloracne from the Seveso area.

    PubMed

    Barbieri, S; Pirovano, C; Scarlato, G; Tarchini, P; Zappa, A; Maranzana, M

    1988-01-01

    This work was set up to investigate the possible presence of peripheral nervous system involvement as a long-term effect of the exposure to dioxin in 152 subjects with chloracne from the Seveso area; 123 age- and sex-matched subjects living in nearby towns with similar environmental pollution formed the control group. The accident in Seveso took place in July, 1976, and this study was carried out from October, 1982, to May, 1983. Although a peripheral neuropathy was not found in any of the subjects, a significant increase of the number of individuals presenting at least two bilateral clinical signs (p less than 0.05) or one abnormal electrophysiological parameter (p less than 0.02) was found in the Seveso group. Principal component analysis did not show any subdivision between these two groups. The Fisher approach to discriminant analysis reveals a clear subdivision between the group of the most exposed subjects and randomly selected subgroups of control subjects. In conclusion, clinical and electrophysiological signs of peripheral nervous system involvement occur with a statistically increased frequency in the Seveso population 6 years after the accident, although a peripheral neuropathy was not evident in any of the chloracne patients using the World Health Organization diagnostic criteria. PMID:2829044

  12. Autonomic Nervous System Responses to Viewing Green and Built Settings: Differentiating Between Sympathetic and Parasympathetic Activity.

    PubMed

    van den Berg, Magdalena M H E; Maas, Jolanda; Muller, Rianne; Braun, Anoek; Kaandorp, Wendy; van Lien, René; van Poppel, Mireille N M; van Mechelen, Willem; van den Berg, Agnes E

    2015-12-01

    This laboratory study explored buffering and recovery effects of viewing urban green and built spaces on autonomic nervous system activity. Forty-six students viewed photos of green and built spaces immediately following, and preceding acute stress induction. Simultaneously recorded electrocardiogram and impedance cardiogram signal was used to derive respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP), indicators of respectively parasympathetic and sympathetic activity. The findings provide support for greater recovery after viewing green scenes, as marked by a stronger increase in RSA as a marker of parasympathetic activity. There were no indications for greater recovery after viewing green scenes in PEP as a marker of sympathetic activity, and there were also no indications of greater buffering effects of green space in neither RSA nor PEP. Overall, our findings are consistent with a predominant role of the parasympathetic nervous system in restorative effects of viewing green space. PMID:26694426

  13. Autonomic Nervous System Responses to Viewing Green and Built Settings: Differentiating Between Sympathetic and Parasympathetic Activity

    PubMed Central

    van den Berg, Magdalena M.H.E.; Maas, Jolanda; Muller, Rianne; Braun, Anoek; Kaandorp, Wendy; van Lien, René; van Poppel, Mireille N.M.; van Mechelen, Willem; van den Berg, Agnes E.

    2015-01-01

    This laboratory study explored buffering and recovery effects of viewing urban green and built spaces on autonomic nervous system activity. Forty-six students viewed photos of green and built spaces immediately following, and preceding acute stress induction. Simultaneously recorded electrocardiogram and impedance cardiogram signal was used to derive respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP), indicators of respectively parasympathetic and sympathetic activity. The findings provide support for greater recovery after viewing green scenes, as marked by a stronger increase in RSA as a marker of parasympathetic activity. There were no indications for greater recovery after viewing green scenes in PEP as a marker of sympathetic activity, and there were also no indications of greater buffering effects of green space in neither RSA nor PEP. Overall, our findings are consistent with a predominant role of the parasympathetic nervous system in restorative effects of viewing green space. PMID:26694426

  14. [Malignant lymphoma in the central nervous system: overview].

    PubMed

    Namekawa, Michito

    2014-08-01

    Malignant lymphoma can affect the central nervous system (CNS) in three different ways: as a consequence (relapse or invasion) of systemic lymphoma, as a primary CNS lymphoma (PCNSL) without systemic involvement, and through intravascular lymphomatosis (IVL). It is essential to distinguish PCNSL from the others, since the therapeutic strategy for treating this disease differs. FDG-PET/CT fusion imagery is a powerful tool for detecting systemic lesions. If a marked elevation of lactate dehydrogenase and the soluble IL-2 receptor suggests IVL, a random skin biopsy can permit a differential diagnosis. It is not certain why PCNSL occurs solely in the CNS, where there is no lymphatic system. The special environment, so-called "sanctuary site", where is free from attack of the immune system and penetration of chemotherapeutic agents by blood-brain barrier is deeply related to malignant transformation. The prognoses for patients with CNS invasion of systemic lymphoma and those with PCNSL remain bleak in the post-rituximab era. Over half of the patients who received high-dose methotrexate will subsequently relapse. Therefore, novel therapeutic strategies are earnestly sought. PMID:25082313

  15. Development of the nervous system in hatchlings of Spadella cephaloptera (Chaetognatha), and implications for nervous system evolution in Bilateria.

    PubMed

    Rieger, Verena; Perez, Yvan; Müller, Carsten H G; Lacalli, Thurston; Hansson, Bill S; Harzsch, Steffen

    2011-06-01

    Chaetognaths (arrow worms) play an important role as predators in planktonic food webs. Their phylogenetic position is unresolved, and among the numerous hypotheses, affinities to both protostomes and deuterostomes have been suggested. Many aspects of their life history, including ontogenesis, are poorly understood and, though some aspects of their embryonic and postembryonic development have been described, knowledge of early neural development is still limited. This study sets out to provide new insights into neurogenesis of newly hatched Spadella cephaloptera and their development during the following days, with attention to the two main nervous centers, the brain and the ventral nerve center. These were examined with immunohistological methods and confocal laser-scan microscopic analysis, using antibodies against tubulin, FMRFamide, and synapsin to trace the emergence of neuropils and the establishment of specific peptidergic subsystems. At hatching, the neuronal architecture of the ventral nerve center is already well established, whereas the brain and the associated vestibular ganglia are still rudimentary. The development of the brain proceeds rapidly over the next 6 days to a state that resembles the adult pattern. These data are discussed in relation to the larval life style and behaviors such as feeding. In addition, we compare the larval chaetognath nervous system and that of other bilaterian taxa in order to extract information with phylogenetic value. We conclude that larval neurogenesis in chaetognaths does not suggest an especially close relationship to either deuterostomes or protostomes, but instead displays many apomorphic features. PMID:21671921

  16. Outcomes of persons with blastomycosis involving the central nervous system.

    PubMed

    Bush, Jonathan W; Wuerz, Terry; Embil, John M; Del Bigio, Marc R; McDonald, Patrick J; Krawitz, Sherry

    2013-06-01

    Blastomyces dermatitidis is a dimorphic fungus which is potentially life-threatening if central nervous system (CNS) dissemination occurs. Sixteen patients with proven or probable CNS blastomycosis are presented. Median duration of symptoms was 90 days; headache and focal neurologic deficit were the most common presenting symptoms. Magnetic resonance imaging (MRI) consistently demonstrated an abnormality, compared to 58% of computed tomography scans. Tissue culture yielded the pathogen in 71% of histology-confirmed cases. All patients who completed treatment of an amphotericin B formulation and extended azole-based therapy did not relapse. Initial nonspecific symptoms lead to delayed diagnosis of CNS blastomycosis. A high index of suspicion is necessary if there is history of contact with an area where B. dermatitidis is endemic. Diagnostic tests should include MRI followed by biopsy for tissue culture and pathology. Optimal treatment utilizes a lipid-based amphotericin B preparation with an extended course of voriconazole. PMID:23566338

  17. 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

  18. Fungal Infections of the Central Nervous System: A Pictorial Review

    PubMed Central

    Gavito-Higuera, Jose; Mullins, Carola Birgit; Ramos-Duran, Luis; Olivas Chacon, Cristina Ivette; Hakim, Nawar; Palacios, Enrique

    2016-01-01

    Fungal infections of the central nervous system (CNS) pose a threat to especially immunocompromised patients and their development is primarily determined by the immune status of the host. With an increasing number of organ transplants, chemotherapy, and human immunodeficiency virus infections, the number of immunocompromised patients as susceptible hosts is growing and fungal infections of the CNS are more frequently encountered. They may result in meningitis, cerebritis, abscess formation, cryptococcoma, and meningeal vasculitis with rapid disease progression and often overlapping symptoms. Although radiological characteristics are often nonspecific, unique imaging patterns can be identified through computer tomography as a first imaging modality and further refined by magnetic resonance imaging. A rapid diagnosis and the institution of the appropriate therapy are crucial in helping prevent an often fatal outcome. PMID:27403402

  19. Magnetic resonance imaging in central nervous system tuberculosis

    PubMed Central

    Trivedi, Richa; Saksena, Sona; Gupta, Rakesh K

    2009-01-01

    Tuberculosis (TB) in any form is a devastating disease, which in its most severe form involves the central nervous system (CNS), with a high mortality and morbidity. Early diagnosis of CNS TB is necessary for appropriate treatment to reduce this morbidity and mortality. Routine diagnostic techniques involve culture and immunological tests of the tissue and biofluids, which are time-consuming and may delay definitive management. Noninvasive imaging modalities such as computed tomography (CT) scan and magnetic resonance imaging (MRI) are routinely used in the diagnosis of neurotuberculosis, with MRI offering greater inherent sensitivity and specificity than CT scan. In addition to conventional MRI imaging, magnetization transfer imaging, diffusion imaging, and proton magnetic resonance spectroscopy techniques are also being evaluated for better tissue characterization in CNS TB. The current article reviews the role of various MRI techniques in the diagnosis and management of CNS TB. PMID:19881100

  20. Building global capacity for brain and nervous system disorders research.

    PubMed

    Cottler, Linda B; Zunt, Joseph; Weiss, Bahr; Kamal, Ayeesha Kamran; Vaddiparti, Krishna

    2015-11-19

    The global burden of neurological, neuropsychiatric, substance-use and neurodevelopmental disorders in low- and middle-income countries is worsened, not only by the lack of targeted research funding, but also by the lack of relevant in-country research capacity. Such capacity, from the individual to the national level, is necessary to address the problems within a local context. As for many health issues in these countries, the ability to address this burden requires development of research infrastructure and a trained cadre of clinicians and scientists who can ask the right questions, and conduct, manage, apply and disseminate research for practice and policy. This Review describes some of the evolving issues, knowledge and programmes focused on building research capacity in low- and middle-income countries in general and for brain and nervous system disorders in particular. PMID:26580329

  1. Cell fate control in the developing central nervous system

    SciTech Connect

    Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie

    2014-02-01

    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 treatments 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.

  2. Fractals in the Nervous System: Conceptual Implications for Theoretical Neuroscience

    PubMed Central

    Werner, Gerhard

    2010-01-01

    This essay is presented with two principal objectives in mind: first, to document the prevalence of fractals at all levels of the nervous system, giving credence to the notion of their functional relevance; and second, to draw attention to the as yet still unresolved issues of the detailed relationships among power-law scaling, self-similarity, and self-organized criticality. As regards criticality, I will document that it has become a pivotal reference point in Neurodynamics. Furthermore, I will emphasize the not yet fully appreciated significance of allometric control processes. For dynamic fractals, I will assemble reasons for attributing to them the capacity to adapt task execution to contextual changes across a range of scales. The final Section consists of general reflections on the implications of the reviewed data, and identifies what appear to be issues of fundamental importance for future research in the rapidly evolving topic of this review. PMID:21423358

  3. Excitability tuning of axons in the central nervous system.

    PubMed

    Ohura, Shunsuke; Kamiya, Haruyuki

    2016-05-01

    The axon is a long neuronal process that originates from the soma and extends towards the presynaptic terminals. The pioneering studies on the squid giant axon or the spinal cord motoneuron established that the axon conducts action potentials faithfully to the presynaptic terminals with self-regenerative processes of membrane excitation. Recent studies challenged the notion that the fundamental understandings obtained from the study of squid giant axons are readily applicable to the axons in the mammalian central nervous system (CNS). These studies revealed that the functional and structural properties of the CNS axons are much more variable than previously thought. In this review article, we summarize the recent understandings of axon physiology in the mammalian CNS due to progress in the subcellular recording techniques which allow direct recordings from the axonal membranes, with emphasis on the hippocampal mossy fibers as a representative en passant axons typical for cortical axons. PMID:26493201

  4. Targeting protein kinases in central nervous system disorders

    PubMed Central

    Chico, Laura K.; Van Eldik, Linda J.; Watterson, D. Martin

    2010-01-01

    Protein kinases are a growing drug target class in disorders in peripheral tissues, but the development of kinase-targeted therapies for central nervous system (CNS) diseases remains a challenge, largely owing to issues associated specifically with CNS drug discovery. However, several candidate therapeutics that target CNS protein kinases are now in various stages of preclinical and clinical development. We review candidate compounds and discuss selected CNS protein kinases that are emerging as important therapeutic targets. In addition, we analyse trends in small-molecule properties that correlate with key challenges in CNS drug discovery, such as blood–brain barrier penetrance and cytochrome P450-mediated metabolism, and discuss the potential of future approaches that will integrate molecular-fragment expansion with pharmacoinformatics to address these challenges. PMID:19876042

  5. Electrical stimuli in the central nervous system microenvironment.

    PubMed

    Thompson, Deanna M; Koppes, Abigail N; Hardy, John G; Schmidt, Christine E

    2014-07-11

    Electrical stimulation to manipulate the central nervous system (CNS) has been applied as early as the 1750s to produce visual sensations of light. Deep brain stimulation (DBS), cochlear implants, visual prosthetics, and functional electrical stimulation (FES) are being applied in the clinic to treat a wide array of neurological diseases, disorders, and injuries. This review describes the history of electrical stimulation of the CNS microenvironment; recent advances in electrical stimulation of the CNS, including DBS to treat essential tremor, Parkinson's disease, and depression; FES for the treatment of spinal cord injuries; and alternative electrical devices to restore vision and hearing via neuroprosthetics (retinal and cochlear implants). It also discusses the role of electrical cues during development and following injury and, importantly, manipulation of these endogenous cues to support regeneration of neural tissue. PMID:25014787

  6. Magnetic resonance imaging of the central nervous system

    SciTech Connect

    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 in 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.

  7. Role of radiology in central nervous system stimulation

    PubMed Central

    Pereira, E A C; Young, V E L; Hogarth, K M; Quaghebeur, G

    2015-01-01

    Central nervous system (CNS) stimulation is becoming increasingly prevalent. Deep brain stimulation (DBS) has been proven to be an invaluable treatment for movement disorders and is also useful in many other neurological conditions refractory to medical treatment, such as chronic pain and epilepsy. Neuroimaging plays an important role in operative planning, target localization and post-operative follow-up. The use of imaging in determining the underlying mechanisms of DBS is increasing, and the dependence on imaging is likely to expand as deep brain targeting becomes more refined. This article will address the expanding role of radiology and highlight issues, including MRI safety concerns, that radiologists may encounter when confronted with a patient with CNS stimulation equipment in situ. PMID:25715044

  8. 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.

  9. Zinc in the central nervous system: From molecules to behavior

    PubMed Central

    Gower-Winter, Shannon D.; Levenson, Cathy W.

    2012-01-01

    The trace metal zinc is a biofactor that plays essential roles in the central nervous system across the lifespan from early neonatal brain development through the maintenance of brain function in adults. At the molecular level, zinc regulates gene expression through transcription factor activity and is responsible for the activity of dozens of key enzymes in neuronal metabolism. At the cellular level, zinc is a modulator of synaptic activity and neuronal plasticity in both development and adulthood. Given these key roles, it is not surprising that alterations in brain zinc status have been implicated in a wide array of neurological disorders including impaired brain development, neurodegenerative disorders such as Alzheimer’s disease, and mood disorders including depression. Zinc has also been implicated in neuronal damage associated with traumatic brain injury, stroke, and seizure. Understanding the mechanisms that control brain zinc homeostasis is thus critical to the development of preventive and treatment strategies for these and other neurological disorders. PMID:22473811

  10. Emerging Viral Infections of the Central Nervous System

    PubMed Central

    Tyler, Kenneth L.

    2010-01-01

    The first part of this review ended with a discussion of new niches for known viruses as illustrated by viral central nervous system (CNS) disease associated with organ transplant and the syndrome of human herpesvirus 6–associated posttransplant acute limbic encephalitis. In this part, we begin with a continuation of this theme, reviewing the association of JC virus–associated progressive multifocal leukoencephalopathy (PML) with novel immunomodulatory agents. This part then continues with emerging viral infections associated with importation of infected animals (monkeypox virus), then spread of vectors and enhanced vector competence (chikungunya virus [CHIK]), and novel viruses causing CNS infections including Nipah and Hendra viruses and bat lyssaviruses (BLV). PMID:19752295

  11. Recovery from central nervous system changes following volatile substance misuse.

    PubMed

    Dingwall, Kylie M; Cairney, Sheree

    2011-01-01

    This review examines cognitive, neurological, and neuroanatomical recovery associated with abstinence from volatile substance misuse (VSM). Articles describing functional or structural brain changes longitudinally or cross-sectional reports comparing current and abstinent users were identified and reviewed. A significant lack of empirical studies investigating central nervous system recovery following VSM was noted. The few case reports and group studies identified indicated that cognitive and neurological impairments appear to follow a progression of decline and progression of recovery model, with the severity of impairment related to the duration and severity of misuse, blood lead levels among leaded petrol misusers, and the duration of abstinence for recovery. By contrast, severe neurological impairment known as lead encephalopathy from sniffing leaded petrol occurred as more catastrophic or abrupt damage to cerebellar processes that may never fully recover. Neuroanatomical damage may not recover even with prolonged abstinence. PMID:21609150

  12. Cysticercosis of the central nervous system: clinical and therapeutic considerations.

    PubMed Central

    Torrealba, G; Del Villar, S; Tagle, P; Arriagada, P; Kase, C S

    1984-01-01

    In a group of forty cases of cysticercosis of the central nervous system, 59% presented with intracranial hypertension due to obstructive hydrocephalus. Ventricular or cisternal cysts, and chronic cysticercus meningitis were the most common causes of hydrocephalus. Seizures occurred in 40% of the patients, in one-half of them in association with CT-detected parenchymatous cysts. In 20% of the cases progressive mental deterioration was the main clinical feature, at times associated with hydrocephalus. CT scan provided the highest diagnostic yield, being abnormal in 90% of cases. Long term prognosis was poor, with a mortality rate of 38% over a 40-month follow-up period. The most common cause of death (60%) was meningitis. CSF shunting is the treatment of choice for hydrocephalus, irrespective of its mechanism. Surgical resection is indicated in some cases with a single superficial (cortical) or posterior fossa cyst. Supratentorial cysts carry a relatively benign prognosis. Images PMID:6470720

  13. 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

  14. Are astrocytes executive cells within the central nervous system?

    PubMed

    Sica, Roberto E; Caccuri, Roberto; Quarracino, Cecilia; Capani, Francisco

    2016-08-01

    Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS) by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations signal that some of the primary degenerative diseases of the CNS, like frontotemporal dementia, Parkinson's disease, Alzheimer's dementia, Huntington's dementia, primary cerebellar ataxias and amyotrophic lateral sclerosis, all of which affect the human species exclusively, may be due to astroglial dysfunction. This hypothesis is supported by observations that demonstrated that the killing of neurons by non-neural cells plays a major role in the pathogenesis of those diseases, at both their onset and their progression. Furthermore, recent findings suggest that astrocytes might be involved in the pathogenesis of some psychiatric disorders as well. PMID:27556379

  15. Rosai-Dorfman Disease of the Central Nervous System

    PubMed Central

    Sandoval-Sus, Jose D.; Sandoval-Leon, Ana C.; Chapman, Jennifer R.; Velazquez-Vega, Jose; Borja, Maria J.; Rosenberg, Shai; Lossos, Alexander; Lossos, Izidore S.

    2014-01-01

    Abstract Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is an uncommon benign idiopathic lymphoproliferative disorder. The histologic hallmark of RDD is the finding of emperipolesis displayed by lesional histiocytes. While RDD most commonly affects lymph nodes, extranodal involvement of multiple organs has been reported, including the central nervous system (CNS). However, CNS involvement in RDD is rare and is not well characterized. As a result, therapeutic approaches to CNS involvement in RDD are not well established. Herein we report 6 cases of RDD with isolated CNS involvement and review the literature on RDD with CNS involvement. One of the presented cases exhibited intramedullary involvement of the spinal cord—a very rare form of RDD with CNS involvement. PMID:24797172

  16. 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. PMID:26483059

  17. D-serine in the developing human central nervous system.

    PubMed

    Fuchs, Sabine A; Dorland, Lambertus; de Sain-van der Velden, Monique G; Hendriks, Margriet; Klomp, Leo W J; Berger, Ruud; de Koning, Tom J

    2006-10-01

    To elucidate the role of D-serine in human central nervous system, we analyzed D-serine, L-serine, and glycine concentrations in cerebrospinal fluid of healthy children and children with a defective L-serine biosynthesis (3-phosphoglycerate dehydrogenase deficiency). Healthy children showed high D-serine concentrations immediately after birth, both absolutely and relative to glycine and L-serine, declining to low values at infancy. D-Serine concentrations were almost undetectable in untreated 3-phosphoglycerate dehydrogenase-deficient patients. In one patient treated prenatally, D-serine concentration was nearly normal at birth and the clinical phenotype was normal. These observations suggest a pivotal role for D-serine in normal and aberrant human brain development. PMID:17068790

  18. Tuberculous Panophthalmitis with Lymphadenitis and Central Nervous System Tuberculoma

    PubMed Central

    Srichatrapimuk, Sirawat; Wattanatranon, Duangkamon

    2016-01-01

    Tuberculosis (TB) is a serious infectious disease that spreads globally. The ocular manifestations of TB are uncommon and diverse. TB panophthalmitis has been rarely reported. Here, we described a 38-year-old Thai man presenting with panophthalmitis of the right eye. Further investigation showed that he had concurrent TB lymphadenitis and central nervous system (CNS) tuberculoma, as well as HIV infection, with a CD4 cell count of 153 cells/mm3. Despite the initial response to antituberculous agents, the disease had subsequently progressed and enucleation was required. The pathological examination revealed acute suppurative granulomatous panophthalmitis with retinal detachment. Further staining demonstrated acid-fast bacilli in the tissue. Colonies of Mycobacterium tuberculosis were obtained from tissue culture. He was treated with antiretroviral agents for HIV infection and 12 months of antituberculous agents. Clinicians should be aware of the possibility of TB in the differential diagnosis of endophthalmitis and panophthalmitis, especially in regions where TB is endemic. PMID:27051539

  19. Central nervous system infections caused by varicella-zoster virus.

    PubMed

    Chamizo, Francisco J; Gilarranz, Raúl; Hernández, Melisa; Ramos, Diana; Pena, María José

    2016-08-01

    We carried out a clinical and epidemiological study of adult patients with varicella-zoster virus central nervous system infection diagnosed by PCR in cerebrospinal fluid. Twenty-six patients were included. Twelve (46.2 %) patients were diagnosed with meningitis and fourteen (53.8 %) with meningoencephalitis. Twelve (46.2 %) had cranial nerves involvement (mainly the facial (VII) and vestibulocochlear (VIII) nerves), six (23.1 %) had cerebellar involvement, fourteen (53.8 %) had rash, and four (15.4 %) developed Ramsay Hunt syndrome. Three (11.5 %) patients had sequelae. Length of stay was significantly lower in patients diagnosed with meningitis and treatment with acyclovir was more frequent in patients diagnosed with meningoencephalitis. We believe routine detection of varicella-zoster virus, regardless of the presence of rash, is important because the patient may benefit from a different clinical management. PMID:26769041

  20. Central nervous system hypoxia in children due to near drowning

    SciTech Connect

    Fitch, S.J.; Gerald, B.; Magill, H.L.; Tonkin, I.L.D.

    1985-09-01

    Fourteen children who experienced acute, profound central nervous system hypoxia secondary to near drowning, aspiration, or respiratory arrest underwent CT examination. During the first week after the episode, the most frequent finding was a loss of gray-white matter differentiation. Other findings included effacement of sulci and cisterns, focal areas of edema in the cerebral cortex or basal ganglia, and hemorrhagic infarctions of the basal ganglia. Subsequent CT scans obtained from two weeks to five months after the hypoxic episode showed progression of cerebral loss from cortical infarction with gyral hemorrhage and enhancement to global parenchymal atrophy. The prognosis is poor in these patients: seven children experienced severe neurologic deficits and seven died.