Results for “CENTRAL NERVOUS SYSTEM” — Page 16

NASA NTRS1992

Plasticity of the human otolith-ocular reflex

The eye movement response to earth vertical axis rotation in the dark, a semicircular canal stimulus, can be altered by prior exposure to combined visual-vestibular stimuli. Such plasticity of the vestibulo-ocular reflex has not been described for earth horizontal axis rotation, a dynamic otolith stimulus. Twenty normal human subjects underwent one of two types of adaptation paradigms designed either to attenuate or enhance the gain of the semicircular canal-ocular reflex prior to undergoing otolith-ocular reflex testing with horizontal axis rotation. The adaptation paradigm paired a 0.2 Hz sinusoidal rotation about a vertical axis with a 0.2 Hz optokinetic stripe pattern that was deliberately mismatched in peak velocity. Pre- and post-adaptation horizontal axis rotations were at 60 degrees/s in the dark and produced a modulation in the slow component velocity of nystagmus having a frequency of 0.17 Hz due to putative stimulation of the otolith organs. Results showed that the magnitude of this modulation component response was altered in a manner similar to the alteration in semicircular canal-ocular responses. These results suggest that physiologic alteration of the vestibulo-ocular reflex using deliberately mismatched visual and semicircular canal stimuli induces changes in both canal-ocular and otolith-ocular responses. We postulate, therefore, that central nervous system pathways responsible for controlling the gains of canal-ocular and otolith-ocular reflexes are shared.

Non-NASA Center↗

NASA NTRS2004

CNS development under altered gravity: cerebellar glial and neuronal protein expression in rat neonates exposed to hypergravity

The future of space exploration depends on a solid understanding of the developmental process under microgravity, specifically in relation to the central nervous system (CNS). We have previously employed a hypergravity paradigm to assess the impact of altered gravity on the developing rat cerebellum. The present study addresses the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of selected glial and neuronal cerebellar proteins in rat neonates exposed to hypergravity (1.5 G) from embryonic day (E)11 to postnatal day (P)6 or P9 (the time of maximal cerebellar changes) comparing them against their expression in rat neonates developing under normal gravity. Proteins were analyzed by quantitative Western blots of cerebellar homogenates; RNA analysis was performed in the same samples using quantitative PCR. Densitometric analysis of Western blots suggested a reduction in glial (glial acidic protein, GFAP) and neuronal (neuronal cell adhesion molecule, NCAM-L1, synaptophysin) proteins, but the changes in individual cerebellar proteins in hypergravity-exposed neonates appeared both age- and gender-specific. RNA analysis suggested a reduction in GFAP and synaptophysin mRNAs on P6. These data suggest that exposure to hypergravity may interfere with the expression of selected cerebellar proteins. These changes in protein expression may be involved in mediating the effect of hypergravity on the developing rat cerebellum. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

NASA Program Fundamental Space Biology↗

NASA NTRS2005

DNA Damage by Ionizing Radiation: Tandem Double Lesions by Charged Particles

Oxidative damages by ionizing radiation are the source of radiation-induced carcinogenesis, damage to the central nervous system, lowering of the immune response, as well as other radiation-induced damages to human health. Monte Carlo track simulations and kinetic modeling of radiation damages to the DNA employ available molecular and cellular data to simulate the biological effect of high and low LET radiation io the DNA. While the simulations predict single and double strand breaks and base damages, so far all complex lesions are the result of stochastic coincidence from independent processes. Tandem double lesions have not yet been taken into account. Unlike the standard double lesions that are produced by two separate attacks by charged particles or radicals, tandem double lesions are produced by one single attack. The standard double lesions dominate at the high dosage regime. On the other hand, tandem double lesions do not depend on stochastic coincidences and become important at the low dosage regime of particular interest to NASA. Tandem double lesions by hydroxyl radical attack of guanine in isolated DNA have been reported at a dosage of radiation as low as 10 Gy. The formation of two tandem base lesions was found to be linear with the applied doses, a characteristic of tandem lesions. However, tandem double lesions from attack by a charged particle have not been reported.

Huo, Winifred M.↗

NASA NTRS2005

Managing Space Radiation Risks On Lunar and Mars Missions: Risk Assessment and Mitigation

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Cucinotta, F. A.↗

NASA NTRS2006

The NASA Space Radiation Research Program

We present a comprehensive overview of the NASA Space Radiation Research Program. This program combines basic research on the mechanisms of radiobiological action relevant for improving knowledge of the risks of cancer, central nervous system and other possible degenerative tissue effects, and acute radiation syndromes from space radiation. The keystones of the NASA Program are five NASA Specialized Center's of Research (NSCOR) investigating space radiation risks. Other research is carried out through peer-reviewed individual investigations and in collaboration with the US Department of Energies Low-Dose Research Program. The Space Radiation Research Program has established the Risk Assessment Project to integrate data from the NSCOR s and other peer-reviewed research into quantitative projection models with the goals of steering research into data and scientific breakthroughs that will reduce the uncertainties in current risk projections and developing the scientific knowledge needed for future individual risk assessment approaches and biological countermeasure assessments or design. The NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory was created by the Program to simulate space radiation on the ground in support of the above research programs. New results from NSRL will be described.

Cucinotta, Francis A.↗

NASA NTRS2005

Managing Space Radiation Risks on Lunar and Mars Missions: Risk Assessment and Mitigation

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Cucinotta, F. A.↗

NASA NTRS2006

Space Radiation

Astronauts receive the highest occupational radiation exposure. Effective protections are needed to ensure the safety of astronauts on long duration space missions. Increased cancer morbidity or mortality risk in astronauts may be caused by occupational radiation exposure. Acute and late radiation damage to the central nervous system (CNS) may lead to changes in motor function and behavior, or neurological disorders. Radiation exposure may result in degenerative tissue diseases (non-cancer or non-CNS) such as cardiac, circulatory, or digestive diseases, as well as cataracts. Acute radiation syndromes may occur due to occupational radiation exposure.

Wu, Honglu↗

NASA NTRS2006

Managing Space Radiation Risks on Lunar and Mars Missions: Risk Assessment and Mitigation

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Cucinotta, F. A.↗

NASA NTRS2007

Sensorimotor Adaptation Following Exposure to Ambiguous Inertial Motion Cues

The central nervous system must resolve the ambiguity of inertial motion sensory cues in order to derive accurate spatial orientation awareness. Adaptive changes in how inertial cues from the otolith system are integrated with other sensory information lead to perceptual and postural disturbances upon return to Earth s gravity. The primary goals of this ground-based research investigation are to explore physiological mechanisms and operational implications of tilt-translation disturbances during and following re-entry, and to evaluate a tactile prosthesis as a countermeasure for improving control of whole-body orientation during tilt and translation motion.

Wood, S. J.↗

NASA NTRS2007

NASA Strategy to Safely Live and Work in the Space Radiation Environment

This viewgraph document reviews the radiation environment that is a significant potential hazard to NASA's goals for space exploration, of living and working in space. NASA has initiated a Peer reviewed research program that is charged with arriving at an understanding of the space radiation problem. To this end NASA Space Radiation Laboratory (NSRL) was constructed to simulate the harsh cosmic and solar radiation found in space. Another piece of the work was to develop a risk modeling tool that integrates the results from research efforts into models of human risk to reduce uncertainties in predicting risk of carcinogenesis, central nervous system damage, degenerative tissue disease, and acute radiation effects acute radiation effects.

Cucinotta, Francis↗

NASA NTRS2007

Special Issue: 4th International Workshop on Space Radiation (IWSRR)

This special issue of the journal "Radiation and Environmental Biophysics" contains 20 peer-reviewed papers contributed by leading space radiation researcher's world-wide attending the 4th IWSRR. Manuscripts cover a broad range of topics ranging from radiation environments and transport in shielding and planetary surfaces to new results in understanding the biological effects of protons and high-charge and energy (HZE) nuclei on the risk of cancer, and degenerative diseases such as central nervous system effects, heart disease, and cataracts. The issue provides a snapshot of the state-of-the-art of the research in this field, demonstrating both the important results gathered in the past few years with experiments at accelerators, and the need for more research to quantify the risk and develop countermeasures.

Cucinotta, Francis A.↗

NASA NTRS2008

Closing the Phenotypic Gap between Transformed Neuronal Cell Lines in Culture and Untransformed Neurons

Studies of neuronal dysfunction in the central nervous system (CNS) are frequently limited by the failure of primary neurons to propagate in vitro. Neuronal cell lines can be substituted for primary cells but they often misrepresent normal conditions. We hypothesized that a dimensional (3-D) cell culture system would drive the phenotype of transformed neurons closer to that of untransformed cells. In our studies comparing 3-D versus 2-dimensional (2-D) culture, neuronal SH-SY5Y (SY) cells underwent distinct morphological changes combined with a significant drop in their rate of cell division. Expression of the proto-oncogene N-myc and the RNA binding protein HuD was decreased in 3-D culture as compared to standard 2-D conditions. We observed a decline in the anti-apoptotic protein Bcl-2 in 3-D culture, coupled with increased expression of the pro-apoptotic proteins Bax and Bak. Moreover, thapsigargin (TG)-induced apoptosis was enhanced in the 3-D cells. Microarray analysis demonstrated significantly differing mRNA levels for over 700 genes in the cells of each culture type. These results indicate that a 3-D culture approach narrows the phenotypic gap between neuronal cell lines and primary neurons. The resulting cells may readily be used for in vitro research of neuronal pathogenesis.

Myers, Tereance A.↗

NASA NTRS2008

Science Goals in Radiation Protection for Exploration

Space radiation presents major challenges to future missions to the Earth s moon or Mars. Health risks of concern include cancer, degenerative and performance risks to the central nervous system, heart and lens, and the acute radiation syndromes. The galactic cosmic rays (GCR) contain high energy and charge (HZE) nuclei, which have been shown to cause qualitatively distinct biological damage compared to terresterial radiation, such as X-rays or gamma-rays, causing risk estimates to be highly uncertain. The biological effects of solar particle events (SPE) are similar to terresterial radiation except for their biological dose-rate modifiers; however the onset and size of SPEs are difficult to predict. The high energies of GCR reduce the effectiveness of shielding, while SPE s can be shielded however the current gap in radiobiological knowledge hinders optimization. Methods used to project risks on Earth must be modified because of the large uncertainties in projecting health risks from space radiation, and thus impact mission requirements and costs. We describe NASA s unique approach to radiation safety that applies probabilistic risk assessments and uncertainty based criteria within the occupational health program for astronauts and to mission design. The two terrestrial criteria of a point estimate of maximum acceptable level of risk and application of the principle of As Low As Reasonably Achievable (ALARA) are supplemented by a third requirement that protects against risk projection uncertainties using the upper 95% confidence level (CL) in radiation risk projection models. Exploration science goals in radiation protection are centered on ground-based research to achieve the necessary biological knowledge, and in the development of new technologies to improve SPE monitoring and optimize shielding. Radiobiology research is centered on a ground based program investigating the radiobiology of high-energy protons and HZE nuclei at the NASA Space Radiation Laboratory (NSRL) located at DoE s Brookhaven National Laboratory in Upton, NY. We describe recent NSRL results that are closing the knowledge gap in HZE radiobiology and improving exploration risk estimates. Linking probabilistic risk assessment to research goals makes it possible to express risk management objectives in terms of quantitative metrics, which include the number of days in space without exceeding a given risk level within well defined confidence limits, and probabilistic assessments of the effectiveness of design trade spaces such as material type, mass, solar cycle, crew selection criteria, and biological countermeasures. New research in SPE alert and risk assessment, individual radiation sensitivity, and biological countermeasure development are described.

Cucinotta, Francs A.↗

NASA NTRS2006

A Strategy to Safely Live and Work in the Space Radiation Environment

The goal of the National Aeronautics and Space Agency and the Space Radiation Project is to ensure that astronauts can safely live and work in the space radiation environment. The space radiation environment poses both acute and chronic risks to crew health and safety, but unlike some other aspects of space travel, space radiation exposure has clinically relevant implications for the lifetime of the crew. The term safely means that risks are sufficiently understood such that acceptable limits on mission, post-mission and multi-mission consequences (for example, excess lifetime fatal cancer risk) can be defined. The Space Radiation Project strategy has several elements. The first element is to use a peer-reviewed research program to increase our mechanistic knowledge and genetic capabilities to develop tools for individual risk projection, thereby reducing our dependency on epidemiological data and population-based risk assessment. The second element is to use the NASA Space Radiation Laboratory to provide a ground-based facility to study the understanding of health effects/mechanisms of damage from space radiation exposure and the development and validation of biological models of risk, as well as methods for extrapolation to human risk. The third element is a risk modeling effort that integrates the results from research efforts into models of human risk to reduce uncertainties in predicting risk of carcinogenesis, central nervous system damage, degenerative tissue disease, and acute radiation effects. To understand the biological basis for risk, we must also understand the physical aspects of the crew environment. Thus the fourth element develops computer codes to predict radiation transport properties, evaluate integrated shielding technologies and provide design optimization recommendations for the design of human space systems. Understanding the risks and determining methods to mitigate the risks are keys to a successful radiation protection strategy.

Corbin, Barbara J.↗

NASA NTRS2009

Bioavailability of Promethazine during Spaceflight

Promethazine (PMZ) is the choice anti-motion sickness medication for treating space motion sickness (SMS) during flight. The side effects associated with PMZ include dizziness, drowsiness, sedation, and impaired psychomotor performance which could impact crew performance and mission operations. Early anecdotal reports from crewmembers indicate that these central nervous system side effects of PMZ are absent or greatly attenuated in microgravity, potentially due to changes in pharmacokinetics (PK) and pharmacodynamics in microgravity. These changes could also affect the therapeutic effectiveness of drugs in general and PMZ, in particular. In this investigation, we examined bioavailability and associated pharmacokinetics of PMZ in astronauts during and after space flight. Methods. Nine astronauts received, per their preference, PMZ (25 or 50 mg as intramuscular injection, oral tablet, or rectal suppository) on flight day one for the treatment of SMS and subsequently collected saliva samples and completed sleepiness scores for 72 h post dose. Thirty days after the astronauts returned to Earth, they repeated the protocol. Bioavailability and PK parameters were calculated and compared between flight and ground. Results. Maximum concentration (Cmax) was lower and time to reach Cmax (tmax) was longer in flight than on the ground. Area under the curve (AUC), a measure of bioavailability, was lower and biological half-life (t1/2) was longer in flight than on the ground. Conclusion. Results indicate that bioavailability of PMZ is reduced during spaceflight. Number of samples, sampling method, and sampling schedule significantly affected PK parameter estimates.

Boyd, Jason L.↗

NASA NTRS2009

Sensorimotor Adaptations Following Exposure to Ambiguous Inertial Motion Cues

The central nervous system must resolve the ambiguity of inertial motion sensory cues in order to derive accurate spatial orientation awareness. We hypothesize that multi-sensory integration will be adaptively optimized in altered gravity environments based on the dynamics of other sensory information available, with greater changes in otolith-mediated responses in the mid-frequency range where there is a crossover of tilt and translation responses. The primary goals of this ground-based research investigation are to explore physiological mechanisms and operational implications of tilt-translation disturbances during and following re-entry, and to evaluate a tactile prosthesis as a countermeasure for improving control of whole-body orientation.

Wood, S. J.↗

NASA NTRS2009

Biophysics Representation of the Two-Hit Model of Alzheimer's Disease for the Exploration of Late CNS Risks from Space Radiation

A concern for long-term space travel outside the Earth s magnetic field is the late effects to the central nervous system (CNS) from galactic cosmic ray (GCR) or solar particle events (SPE). Human epidemiology data is severely limited for making CNS risk estimates and it is not clear such effects occur following low LET exposures. We are developing systems biology models based on biological information on specific diseases, and experimental data for proton and heavy ion radiation. A two-hit model of Alzheimer s disease (AD) has been proposed by Zhu et al.(1), which is the framework of our model. Of importance is that over 50% of the US population over the age of 75-y have mild to severe forms of AD. Therefore we recommend that risk assessment for a potential AD risk from space radiation should focus on the projection of an earlier age of onset of AD and the prevention of this possible acceleration through countermeasures. In the two-hit model, oxidative stress and aberrant cell cycle-related abnormalities leading to amyloid-beta plaques and neurofibrillary tangles are necessary and invariant steps in AD. We have formulated a stochastic cell kinetics model of the two-hit AD model. In our model a population of neuronal cells is allowed to undergo renewal through neurogenesis and is susceptible to oxidative stress or cell cycle abnormalities with age-specific accumulation of damage. Baseline rates are fitted to AD population data for specific ages, gender, and for persons with an apolipoprotein 4 allele. We then explore how low LET or heavy ions may increase either of the two-hits or neurogenesis either through persistent oxidative stress, direct mutation, or through changes to the micro-environment, and suggest possible ways to develop accurate quantitative estimates of these processes for predicting AD risks following long-term space travel.

Cucinotta, Francis A.↗

NASA NTRS2010

NASA Self-Assessment of Space Radiation Research

Space exploration involves unavoidable exposures to high-energy galactic cosmic rays whose penetration power and associated secondary radiation makes radiation shielding ineffective and cost prohibitive. NASA recognizing the possible health dangers from cosmic rays notified the U.S. Congress as early as 1959 of the need for a dedicated heavy ion accelerator to study the largely unknown biological effects of galactic cosmic rays on astronauts. Information and scientific tools to study radiation health effects expanded over the new decades as NASA exploration programs to the moon and preparations for Mars exploration were carried out. In the 1970 s through the early 1990 s a more than 3-fold increase over earlier estimates of fatal cancer risks from gamma-rays, and new knowledge of the biological dangers of high LET radiation were obtained. Other research has increased concern for degenerative risks to the central nervous system and other tissues at lower doses compared to earlier estimates. In 1996 a review by the National Academy of Sciences Space Science Board re-iterated the need for a dedicated ground-based accelerator facility capable of providing up to 2000 research hours per year to reduce uncertainties in risks projections and develop effective mitigation measures. In 1998 NASA appropriated funds for construction of a dedicated research facility and the NASA Space Radiation Laboratory (NSRL) opened for research in October of 2003. This year marks the 8th year of NSRL research were about 1000 research hours per year have been utilized. In anticipation of the approaching ten year milestone, funded investigators and selected others are invited to participate in a critical self-assessment of NSRL research progress towards NASA s goals in space radiation research. A Blue and Red Team Assessment format has been integrated into meeting posters and special plenary sessions to allow for a critical debate on the progress of the research and major gaps areas. Blue teams will highlight progress and important new knowledge gained. Red teams will challenge the Blue teams on proposed highlights and point to Gaps not considered. We will review the current space radiation Risks and Gaps under investigation at NASA, critical data sets and research highlights anticipated, and possible goals for future research at NSRL.

Cucinotta, Francis A.↗