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At least 793 records · Page 44

Technical and commerical challenges in high Tc SQUIDs and their industrial applications

A SQUID is the most sensitive device for measuring changes in magnetic flux. Since its discovery in the sixties, scientists have made consistent efforts to apply SQUID's to various applications. Instruments that are the most sensitive in their respective categories have been built, such as SQUID DC susceptometer that is now manufactured by Quantum Design, pico-voltmeter which could measure 10(exp -14) volts, and gravitational wave detectors. One of the most successful applications of SQUID's is in magnetoencephalography, a non-invasive technique for investigating neuronal activity in the living human brain. This technique employs a multi-channel SQUID magnetometer that maps the weak magnetic field generated by small current when information is processed in brain, and its performance is marvelous.

Lu, D. F.↗

Effect of Ablation of Area Postrema on Frequency and Latency of Motion Sickness-Induced Emesis in the Squirrel Monkey

Twelve young adult squirrel monkeys of the Bolivian subspecies were subjected to continuous counter-clockwise horizontal rotary motion at 25 rpm, together with a sinusoidal vertical excursion of 6 in. every 2 sec (0.5 Hz). Each animal was exposed to this motion regimen for a period of 60 min once each week for three consecutive weeks. Following the third weekly motion test bilateral ablation of the Area Postrema (AP) was performed in eight of the animals by thermal cautery. Two control animals were sham-operated after the third motion test while two additional controls were given the motion tests as noted above but were not operated. The four controls were considered as a single group for statistical analyses of results of the motion tests. After a recovery period of 30 to 40 days, and at a comparable interval in the non-operated controls, each animal was again tested for motion sensitivity for three consecutive weeks. The brains of all of the animals were then fixed by left ventriculal cardiac perfusion with Bouin's fluid and processed for histological evaluation of the bilateral AP ablation in comparison with the control brains. Five of the AP-ablated animals postoperatively were completely refractory to the motion stimuli, two exhibited a decreased number of emetic responses, and one exhibited the same number of responses before and after the AP lesions. The controls exhibited no significant difference in emetic sensitivity on the second series of three weekly tests than on the first series. The results of this investigation appear to be in agreement with the observations of Wang and Chinn in the dog indicating that the integrity of the AP (CTZ) is essential to the emetic response to motion.

Brizzee, K. R.↗

Gravity Sensor Plasticity in the Space Environment

The ability of the brain to learn from experience and to adapt to new environments is recognized to be profound. This ability, called 'neural plasticity,' depends directly on properties of neurons (nerve cells) that permit them to change in dimension, sprout new parts called spines, change the shape and/or size of existing parts, and to generate, alter, or delete synapses. (Synapses are communication sites between neurons.) These neuronal properties are most evident during development, when evolution guides the laying down of a general plan of the nervous system. However, once a nervous system is established, experience interacts with cellular and genetic mechanisms and the internal milieu to produce unique neuronal substrates that define each individual. The capacity for experience-related neuronal growth in the brain, as measured by the potential for synaptogenesis, is speculated to be in the trillions of synapses, but the range of increment possible for any one part of the nervous system is unknown. The question has been whether more primitive endorgans such as gravity sensors of the inner ear have a capacity for adaptive change, since this is a form of learning from experience.

Ross, Muriel D.↗

Effects of Weightlessness on Vestibular Development of Quail

The lack of gravity is known to alter vestibular responses in developing and adult vertebrates. One cause of these altered responses may be changes in the connections between the vestibular receptor and the brain. Therefore we propose to investigate the effects of gravity on the formations of connections between the gravity receptors of the ear and the brain in developing quail incubated in space beginning at an age before these connections are established (incubation day three) until near the time of hatching, when they are to some extent functional. This investigation will make use of a novel technique, the diffusion of a lipophilic dye, DiI, in fixed tissue. This technique can thus be used to analyze the connections in specimens fixed in orbit, thus eliminating changes due to the earth's gravity. The evaluation of the data will enable us to detect gross deviations from normal patterns as well as detailed quantitative deviations.

Fritzsch, Bernd↗

Noninvasive Intracranial Volume and Pressure Measurements Using Ultrasound

Prevention of secondary brain injuries following head can be accomplished most easily when intracranial pressure (ICP) is monitored. However, current measurement techniques are invasive and thus not practical in the combat environment. The Pulsed Phase Lock Loop (PPLL) devise, which was developed and patented, uses a unique, noninvasive ultrasonic phase comparison method to measure slight changes in cranial volume which occur with changes in ICP. Year one studies involved instrument improvements and measurement of altered intracranial distance with altered ICP in fresh cadavera. Our software was improved to facilitate future studies of normal subjects and trauma patients. Our bench studies proved that PPLL output correlated highly with changes in path length across a model cranium. Cadaveric studies demonstrated excellent compact, noninvasive devise for monitoring changes in intracranial distance may aid in the early detection of elevated ICP, decreasing risk of secondary brain injury and infection, and returning head-injured patients to duty.

Hargens, A. R.↗

Neural Control Mechanisms and Body Fluid Homeostasis

The goal of the proposed research was to study the nature of afferent signals to the brain that reflect the status of body fluid balance and to investigate the central neural mechanisms that process this information for the activation of response systems which restore body fluid homeostasis. That is, in the face of loss of fluids from intracellular or extracellular fluid compartments, animals seek and ingest water and ionic solutions (particularly Na(+) solutions) to restore the intracellular and extracellular spaces. Over recent years, our laboratory has generated a substantial body of information indicating that: (1) a fall in systemic arterial pressure facilitates the ingestion of rehydrating solutions and (2) that the actions of brain amine systems (e.g., norepinephrine; serotonin) are critical for precise correction of fluid losses. Because both acute and chronic dehydration are associated with physiological stresses, such as exercise and sustained exposure to microgravity, the present research will aid in achieving a better understanding of how vital information is handled by the nervous system for maintenance of the body's fluid matrix which is critical for health and well-being.

Johnson, Alan Kim↗

STS-90 Day 04 Highlights

On this forth day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk continue work with the Escher Staircase Behavior Testing of Adult Rats experiment. This is the first of two behavior testing sessions with the adult rats being used for this experiment. The rats will have a 'hyper drive' unit placed on their head which has recording electrodes made of microscopic wires that are positioned in the brain to record activity in the hippocampus. The hippocampus is that portion of the brain used to develop spatial maps to help us navigate from one place to the other. With the 'hyper drive' units in place, the rats will then be put through a maze or on a track. While the rat is maneuvering on the maze or track, the cell activity of the hippocampus will be measured and recorded.

Source record↗

Turnover of Biogenic Amines in the Hypothalamus of Rats during Pyrogen Fever

Many pharmacological studies have implicated the biogenic amines in the hypothalamus as playing a role in the production of fever, but few investigations of endogenous neurochemicals have been made during fever. Turnover rates of transmitters utilizing radioactive precursors may be one of the most accurate measurements of activity in brain regions. The present study was designed to measure the turnover of 5-hydroxytryptamine (5-HT) norepinephrine (NE) and dopamine (DA) in the hypothalamus of rats during pyrogen fever. Salmonella typhosa (Wyeth, 8 units) was previously found in our laboratory to produce a significant hyperthermia in most rats by 2.5 hours. This pyrogen (N = l2) or saline control (N = 8) was injected intraperitoneally and the rats killed 2.75 hours later. Rectal temperatures (Tr) were monitored continuously with thermocouples taped to the tail and recorded automatically every 3 minutes. Half of each group received an injection of radioactive precursors, (3)H-tryptophan (0.5 mCi) and (3)H-tryptophan (1.0 mCi), via an indwelling jugular catheter 60 minutes before killing, and the other half at 90 minutes. The rats were killed by near freezing in liquid nitrogen and the brains dissected in the cold. Turnover was measured by the method of Lane (Life Sci 21, 1101, 1977). At the time of killing most of the pyrogen group showed a significant (p < .02) increase (mean +/- s.e.m.) in Tr above pre injection levels (0.75 +/- 0.13 C, N = 10). The saline group showed no change (-0.025 +/- 0.16, N = 8), and the difference between groups was also significant. No significant differences were found in the levels of the amines between the pyrogen and saline groups. A significant difference was found in the specific activity of NE between the 60 minute pyrogen and saline groups (4.41 +/- 0.41 vs 2.6 +/- 0.51 dpm/pmole) but no change in turnover. This suggests an increased accumulation of (3)H-NE in the pyrogen group, but no change in utilization. An increased turnover of DA for the pyrogen group (44.5 vs 19.2 pmole/mg protein/hr) was found. However, DA is mainly a precursor in the hypothalamus and measurement was near the limit of sensitivity for the assay; these limitations Must be considered in interpreting this data. The most significant finding was an increase in the turnover of 5-HT in the pyrogen group (41.3 vs 7.3 pmole/mg protein/hr), indicating a resynthetization rate of 77% of the total pool per hour. These results suggest that at the time point measured, an increase in the utilization of 5-HT in the hypothalamus is-correlated with pyrogen fever.

Penn, P. E.↗

Effects of Weightlessness on Vestibular Development: Summary of Research on NIH.R1

In our original application we proposed to investigate the effects of gravity on the formation of connections between the gravity receptors of the ear and the brain in rat pups raised in space beginning at an age before these connections are made until near the time of birth, when they are to some extent functional. We used the neuronal tracer, Dil, which could be applied to tissue obtained immediately after landing of the space shuttle, thus minimizing changes due to the earth's gravity. We hoped to determine whether the vestibular system develops in two phases, as do other sensory systems (such as the visual system). In these other systems the first phase of development is controlled genetically and the second phase is controlled by environmental stimulation. Our data collected strongly supports the idea that the vestibular system has these same two phases of development. The tissue obtained from the NIH.R1 experiment was of exceptionally high quality for our analysis. Therefore, we expanded our investigation into the ultrastructural effects of microgravity on vestibular development. For the sake of clarity we will subdivide our summary into two categories: (1) analysis of the branching pattern of axons between the vestibular nerve and the gravistatic receptors of the ear in flight and control animals, and (2) analysis of the branching pattern of axons between the vestibular nerve and the brain in flight and control animals.

Fritzsch, Bernd↗

Effect of Flow on Gene Regulation in Smooth Muscle Cells and Macromolecular Transport Across Endothelial Cell Monolayers

Endothelial cells line all of the vessels of the circulatory system, providing a non-thrombogenic conduit for blood flow; they regulate many complex functions in the vasculature, such as coagulation, fibrinolysis, platelet aggregation, vessel tone and growth, and leukocyte traffic; and they form the principal barrier to transport of substances between the blood and the surrounding tissue space. The permeability of endothelial cell changes with environmental stimuli; shear stress, in particular, applied either in vivo, or in vitro, induces changes in protein expression and secretion of vasoactive factors by endothelial cells. The ability to study the effects of shear on the macromolecular permeability of the cerebral vasculature is particularly important, since in no other place is the barrier function of the endothelium more important than in the brain. The endothelial cells of this organ have developed special barrier properties that keep the cerebral system from experiencing any drastic change in composition; together with glial cells, they form the blood brain barrier (BBB). We have studied the effect of flow on bovine BBB using flow chambers and tissue culture systems.

McIntire, Larry V.↗

Ultrasound as a Noninvasive Method to Assess Changes of Intracranial Volume and Pressure During Simulated Microgravity

Headaches are commonly experienced by astronauts in microgravity and by subjects undergoing head-down tilt (simulated microgravity on Earth). Exposure to microgravity probably elevates blood pressure and flow in the head which may increase intracranial volume (ICV) and pressure (ICP) and in turn cause headache. Due to the slightly compliant nature of the cranial vault and the encasement of brain and its vasculature within this vault, any increase of ICV will increase ICP and slightly distend the cranium. Previous studies document perivascular edema and increased ICP in rhesus monkeys during head-down tilt. Elevated ICP has also been reported in humans during head-down tilt. ICP measurements in healthy humans are rare because of the invasiveness of currently-available measurement techniques. Therefore, we proposed a noninvasive ultrasound technique to assess changes of ICV and JCP. The ultrasound principle is based on compliance of the cranial vault. A 450 kHz ultrasound stimulus is transmitted through the cranium by a transducer every 7.5-10 msec. The ultrasound wave enters the brain tissue, reflects off the opposite side of the cranium and is received by the same transducer. The detected wave is compared for phase quadrature (90 deg.to transmitted wave). Because the electronic circuitry of the device maintains a 90 deg. phase (phi), any alterations in the detected wave caused by an increase of ICV and ICP will be reflected as a change in the wave frequency. Phase shift is directly proportional to path length of the wave, DELTA x, which is expressed as DELTA x = phi lambda/2 pi where lambda is wavelength. Elevated ICV and ICP expand the cranial vault and increase path length of the wave (a measure of intracranial distance). Increased path length equals reduced frequency of the detected wave. Reduced frequency is then related to elevated ICP. This technique has potential uses for ICP studies of astronauts in space and head trauma patients on Earth.

Murthy, G.↗

Estimating the Single-Trial Characteristics of Event-Related Responses: Evaluation of the MCERP Algorithm

Single-trial event-related responses collected during the course of an experiment are typically averaged before analysis resulting in a rather crude picture of event-related brain dynamics. It has been quite clear for some time that these responses exhibit trial-to-trial variability: however, the computational techniques necessary to deal with such responses in noisy conditions have not been available. To this end we have developed the multiple-component, event-related potential model (mcERP), which assumes that the each event-related response consists of a sum of multiple evoked components each described by a stereotypical waveshape. These waveshapes are allowed to vary in amplitude and onset latency from trial to trial, which allows us to capture, to first-order, the trial-dependent variations in event-related brain dynamics. We have constructed many sets of synthetic data designed to simulate intracortical recordings from a 15 channel, linear-array multielectrode implanted acutely in V1 of an awake-behaving macaque undergoing visual stimulation with a red light flash. This synthetic data was used to characterize the performance of the mcERP algorithm. First we quantified the degree to which such trial-to-trial variability aids in the identification of multiple components, and we demonstrate that amplitude variability is a more important factor in component separation than latency variability. Second, we quantified the behavior of the algorithm under two distinct signal-to-noise ratio (SNR) conditions: Gaussian noise independently present in each channel, and highly correlated (1/f distributed), far-field noise presented identically in each channel of the array. The mcERP algorithm was found to be robust to noise accurately identifying all component waveshapes and their associated single-trial characteristics down to SNR levels of -20dB for Gaussian noise and -7dB for 1/f far-field noise. Comparisons of the performance of this algorithm with factor analysis (FA) and independent component analysis (ICA) will be described by Knuth et al. (SFN abstracts, 2002). In addition, the advantages of application of mcERP to real data will be described by Shah et al, (these abstracts, 2002: SFN abstracts, 2002).

Knuth, K. H.↗

Crawling Aid

The Institute for the Achievement of Human Potential developed a device known as the Vehicle for Initial Crawling (VIC); the acronym is a tribute to the crawler's inventor, Hubert "Vic" Vykukal; is an effective crawling aid. The VIC is used by brain injured children who are unable to crawl due to the problems of weight-bearing and friction, caused by gravity. It is a rounded plywood frame large enough to support the child's torso, leaving arms and legs free to move. On its underside are three aluminum discs through which air is pumped to create an air-bearing surface that has less friction than a film of oil. Upper side contains the connection to the air supply and a pair of straps which restrain the child and cause the device to move with him. VIC is used with the intent to recreate the normal neurological connection between brain and muscles. Over repetitive use of the device the child develops his arm and leg muscles as well as coordination. Children are given alternating therapy, with and without the VIC until eventually the device is no longer needed.

Source record↗

Understanding How Astronauts Adapt to Space and to Earth: Anatomical Studies of Central Vestibular Adaptation

Significant changes take place in the nervous systems of astronauts during and following exposure to microgravity. These changes, particularly in the part of the brain that controls balance, the vestibular system, can cause sensations of rotation, dizziness, and vertigo, as well as space adaptation syndrome. Adaptation to the microgravity environment usually occurs within one week, and a subsequent re-adaptation period of several days is often required upon return to Earth. In order to realize long-term spaceflight, effective countermeasures for these symptoms must be developed. The structural changes that take place in one of the vestibular regions of the brain (the cerebellar cortex) during the process of adaptation to Earth's gravity remain unclear and are the subject of an experiment being conducted on STS-107 by Dr. Gay Holstein of the Mount Sinai School of Medicine in New York. Using the rat as a model, Dr. Holstein and her team will seek to identify the cellular changes underlying the vestibular changes experienced by astronauts.

Holstein, Gay↗

The Effect of Spaceflight on the Ultrastructure of the Cerebellum

In weightlessness, astronauts and cosmonauts may experience postural illusions as well as motion sickness symptoms known as the space adaptation syndrome. Upon return to Earth, they have irregularities in posture and balance. The adaptation to microgravity and subsequent re-adaptation to Earth occurs over several days. At the cellular level, a process called neuronal plasticity may mediate this adaptation. The term plasticity refers to the flexibility and modifiability in the architecture and functions of the nervous system. In fact, plastic changes are thought to underlie not just behavioral adaptation, but also the more generalized phenomena of learning and memory. The goal of this experiment was to identify some of the structural alterations that occur in the rat brain during the sensory and motor adaptation to microgravity. One brain region where plasticity has been studied extensively is the cerebellar cortex-a structure thought to be critical for motor control, coordination, the timing of movements, and, most relevant to the present experiment, motor learning. Also, there are direct as well as indirect connections between projections from the gravity-sensing otolith organs and several subregions of the cerebellum. We tested the hypothesis that alterations in the ultrastructural (the structure within the cell) architecture of rat cerebellar cortex occur during the early period of adaptation to microgravity, as the cerebellum adapts to the absence of the usual gravitational inputs. The results show ultrastructural evidence for neuronal plasticity in the central nervous system of adult rats after 24 hours of spaceflight. Qualitative studies conducted on tissue from the cerebellar cortex (specifically, the nodulus of the cerebellum) indicate that ultrastructural signs of plasticity are present in the cerebellar zones that receive input from the gravity-sensing organs in the inner ear (the otoliths). These changes are not observed in this region in cagematched ground control animals. The specific changes include the formation of lamellar bodies, profoundly enlarged Purkinje cell mitochondria, the presence of inter-neuronal cellular protrusions in the molecular layer, and signs of degeneration in the distal dendrites of the Purkinje cells. Since these morphologic signs are not apparent in the control animals, they are not likely to be due to caging or tissue processing effects. The particular nature of the structural alterations in the nodulus, most notably the formation of lamellar bodies and the presence of degeneration, further suggests that excitotoxicity (damaging overstimulation of neurons) may play a role in the short-term neural response to spaceflight. These findings suggest a structural basis for the neuronal and synaptic plasticity accompanying the central nervous system response to altered gravity and help identify the cellular bases underlying the vestibular abnormalities experienced by astronauts during periods of adaptation and re-adaptation to different gravitational forces. Also, since the short- and long-term changes in neural structure occurring during such periods of adaptation resemble the neuronal alterations that occur in some neurologic disorders such as stroke, these findings may offer guidance in the development of strategies for rehabilitation and treatment of such disorders.

Holstein, Gay R.↗

Motor System Development Depends on Experience: A Microgravity Study of Rats

Animals move about their environment by sensing their surroundings and making adjustments according to need. All animals take the force of gravity into account when the brain and spinal cord undertake the planning and execution of movements. To what extent must animals learn to factor in the force of gravity when making neural calculations about movement? Are animals born knowing how to respond to gravity, or must the young nervous system learn to enter gravity into the equation? To study this issue, young rats were reared in two different gravitational environments (the one-G of Earth and the microgravity of low Earth orbit) that necessitated two different types of motor operations (movements) for optimal behavior. We inquired whether those portions of the young nervous system involved in movement, the motor system, can adapt to different gravitational levels and, if so, the cellular basis for this phenomenon. We studied two groups of rats that had been raised for 16 days in microgravity (eight or 14 days old at launch) and compared their walking and righting (ability to go from upside down to upright) and brain structure to those of control rats that developed on Earth. Flight rats were easily distinguished from the age-matched ground control rats in terms of both motor function and central nervous system structure. Mature surface righting predominated in control rats on the day of landing (R+O), while immature righting predominated in the flight rats on landing day and 30 days after landing. Some of these changes appear to be permanent. Several conclusions can be drawn from these studies: (1) Many aspects of motor behavior are preprogrammed into the young nervous system. In addition, several aspects of motor behavior are acquired as a function of the interaction of the developing organism and the rearing environment; (2) Widespread neuroanatomical differences between one-G- and microgravity-reared rats indicate that there is a structural basis for the adaptation to the rearing environment. These observations provide support for the idea that an animal's motor system adapts for optimal function within the environment experienced during a critical period in early postnatal life.

Walton, Kerry D.↗

Development of the Aortic Baroreflex in Microgravity

Baroreceptors sense pressure in blood vessels and send this information to the brain. The primary baroreceptors are located in the main blood vessel leaving the heart (the aorta) and in the arteries in the neck (the carotid arteries). The brain uses information from the baroreceptors to determine whether blood pressure should be raised or lowered. These reflex responses are called baroreflexes. Changing position within a gravity field (i.e., moving from lying to sitting or standing) powerfully stimulates the baroreflexes. In weightlessness, the amount of stimuli that the baroreflexes receive is dramatically reduced. If this reduction occurs when the pathways that control the baroreflexes are being formed, it is possible that either the structure or function of the baroreceptors may be permanently changed. To study the effect of microgravity on structural and functional development of the aortic baroreflex system, we studied young rats (eight days old at launch) that flew on the Space Shuttle Columbia for 16 days. Six rats were studied on landing day; another six were studied after re-adapting to Earth's gravity for 30 days. On both landing day and 30 days after landing, we tested the sensitivity of the rats' baroreflex response. While the rats were anaesthetized, we recorded their arterial pressure, heart rate, and aortic nerve activity. After the tissues were preserved with perfusion fixation, we also examined the baroreflex structures. On landing day, we found that, compared to the controls, the flight rats had: fewer unmyelinated nerve fibers in their aortic nerves lower baroreflex sensitivity significantly lower contraction ability and wall tension of the aorta a reduced number of smooth muscle cells in the aorta. In the 30-day recovery group, the sensitivity of the baroreflex showed no difference between the flight rats and the control groups, although the unmyelinated fibers of the aortic nerve remained reduced in the flight rats. The results show that spaceflight does affect the development of the aortic baroreflex. The sensitivity of the reflex may be suppressed; however, the function of the blood pressure control system can re-adapt to Earth's gravity if the rats return before maturation. The structural differences in the input pathway of the reflex (Le., the reduction in nerve fibers) may remain permanently.

Shimizu, Tsuyoshi↗

Hippocampal place cell instability after lesions of the head direction cell network

The occurrence of cells that encode spatial location (place cells) or head direction (HD cells) in the rat limbic system suggests that these cell types are important for spatial navigation. We sought to determine whether place fields of hippocampal CA1 place cells would be altered in animals receiving lesions of brain areas containing HD cells. Rats received bilateral lesions of anterodorsal thalamic nuclei (ADN), postsubiculum (PoS), or sham lesions, before place cell recording. Although place cells from lesioned animals did not differ from controls on many place-field characteristics, such as place-field size and infield firing rate, the signal was significantly degraded with respect to measures of outfield firing rate, spatial coherence, and information content. Surprisingly, place cells from lesioned animals were more likely modulated by the directional heading of the animal. Rotation of the landmark cue showed that place fields from PoS-lesioned animals were not controlled by the cue and shifted unpredictably between sessions. Although fields from ADN-lesioned animals tended to have less landmark control than fields from control animals, this impairment was mild compared with cells recorded from PoS-lesioned animals. Removal of the prominent visual cue also led to instability of place-field representations in PoS-lesioned, but not ADN-lesioned, animals. Together, these findings suggest that an intact HD system is not necessary for the maintenance of place fields, but lesions of brain areas that convey the HD signal can degrade this signal, and lesions of the PoS might lead to perceptual or mnemonic deficits, leading to place-field instability between sessions.

NASA Program Biomedical Research and Countermeasur↗