Long-Term Persistence of Increased Number of γH2AX+ Peripheral Blood Lymphocytes in Monkeys Exposed to Negative Factors of Space Flights: Ionizing Radiation and Simulated Hypogravity.

We studied the influence of ionizing radiation and hypogravity as negative factors of space flights on DNA damage in peripheral blood lymphocytes of rhesus monkeys at different times after exposure (from 1 to 446 days). The proportion of cells with high numbers of DNA double-strand breaks (DSB), positive for the surrogate DSB marker-protein γH2AX, was monitored using flow cytometry. Some animals were exposed to 7-day antiorthostatic hypokinesia simulating hypogravity, the others to a combined effect of antiorthostatic hypokinesia, whole-body γ-irradiation (2.34 cGy/h, dose 1 Gy), and irradiation of the head with 12C ions (450 MeV, dose 1 Gy). Exposure to antiorthostatic hypokinesia led to a significant increase in the proportion of γH2AX+ lymphocytes only on the first day after exposure, whereas after combined exposure, increased numbers of damaged lymphocytes were recorded up to 42 days after exposure.

Combined Effects of Irradiation and Hindlimb Suspension on Erythroid Lineage Precursors from Rat Bone Marrow.

Erythroid precursors from the femoral bone marrow of Wistar rats were characterized after 30-day hindlimb suspension, fractionated γ-radiation, and their combination. After hindlimb suspension, the total content of myeloid CFU decreased; activity of erythroid differon also considerably suppressed, which manifested in a decrease in the number of erythroid burst-forming units and area of colonies formed by erythrocyte precursors. After irradiation and combined exposure to these two factors, no significant differences from the control were revealed; optical density of formed colonies slightly increased in all experimental groups. Thus, suppression of the erythroid lineage was most pronounced during hindlimb unloading. The combined effect of radiation and hindlimb suspension produced no appreciable negative effect on erythropoiesis in rat bone marrow.

Effect of 30-Day Hindlimb Unloading and Hypergravity on Bone Marrow Stromal Progenitors in C57Bl/6N Mice.

We studied the effect of 30-day hindlimb unloading and subsequent simulated hypergravity on the cellularity and proliferative, clonogenic, and differentiation potential of bone marrow stromal progenitors in mice. Clonogenic and differentiation activity of stromal cells decreased after unloading; proliferative and differentiation activity of bone marrow stromal progenitors increased after hypergravity simulation. Our findings demonstrated negative effect of unloading on functional activity of mouse bone marrow stromal progenitors. Short-term hypergravity after unloading produced a stimulating effect on the bone marrow stromal progenitors.

Combined effects of antiorthostatic suspension and ionizing radiation on the behaviour and neurotransmitters changes in different brain structures of rats.

Space flight factors (SFF) significantly affect the operating activity of astronauts during deep space missions. In contrast to an orbital flight, leaving the Earth's magnetic field is fraught with the dangers of exposure to ionizing radiation and more specifically, the high-energy nuclei component of galactic cosmic rays. Microgravity, just another critical non-radiation factor, significantly affects the normal functioning of the CNS. Some morphological structures of the brain, such as the prefrontal cortex and the hippocampus, that are rich in monoaminergic and acetylcholinergic neurones, are the most sensitive to the effects of ionizing radiation and non-radiation spaceflight factors (SFF). In this work we have studied the combined effects of microgravity (in antiorthostatic suspension model, AS) and irradiation (γ-ray and protons in spread-out Bragg peak) on the behaviour, cognitive abilities, and metabolism of monoamines and acetylcholine in the key structures of the rat's brain. Irradiation (as independently as combined with AS) resulted in the decrease of thigmotaxis in rats. Learning problems, caused by the malfunctioning of the working memory but not the spatial memory, were observed in response to AS as well as to the SFF in combination. Analysis of monoamines metabolism showed that the serotoninergic system was the most affected by the SFF. Concentration of acetylcholine in the hippocampus significantly increased in the groups of irradiated rats, and in the groups which were exposed to the SFF in combination, compared to the rats exposed only to AS.

[The problems of experimental investigation of spaceflight factors combined influence on animals organism functions].

The brief analytic review of exceedingly important, tough, but the insufficient investigated problem of experimental investigation of spaceflight factors (SF) combined influence on animal organism functions is the content of this paper. The basic limited factor for interplanetary spaceflights is ionizing radiation. Therefore, in the paper studies the matters of the effects of combined influence and the different nonradiation SF. In this case the possible disturbances of central nervous system functions are the most important, because they present the basic danger for space mission performance and the cosmonauts life directly in spaceflight. Besides of that, in the paper studies the matters of character of interaction and mutual modifications of the combined effects of different SF: hypodynamia, G force, vibration, hypoxia, hyperthermia. The effects of this factor may have additive, potentiative, synergic or antagonistic character. In studies of SF combined influence effects the accentuation of the key factor and organism system that is targeted for this factor influence is necessary.

[Effect of space flight factors simulated in ground-based experiments on the behavior, discriminant learning, and exchange of monoamines in different brain structures of rats].

Experimental treatment (long-term fractionated γ-irradiation, antiorthostatic hypodynamia, and the combination of these factors) simulating the effect of space flight in ground-based experiments rapidly restored the motor and orienting-investigative activity of animals (rats) in "open-field" tests. The study of the dynamics of discriminant learning of rats of experimental groups did not show significant differences from the control animals. It was found that the minor effect of these factors on the cognitive performance of animals correlated with slight changes in the concentration ofmonoamines in the brain structures responsible for the cognitive, emotional, and motivational functions.

[Overall logarithmic index for the characterization of adaptation and regulatory systems straining under chronic action of extreme environmental factors].

The article advertizes some optional capabilities of the overall logarithmic index as an integral parameter for quantifying adaptation processes triggered by chronic exposure to stress factors of varying intensity. Consideration is given to the principles of damage formation in different systems of organism with time and subsequent compensatory processes depending on the level of regulation system straining, rate of functional potential depletion, probability of remote consequences such as early aging, increased risk of lethality and reduction of the mean remaining life expectancy. The overall logarithmic index will be used to analyze the transition from normal to active insufficient adaptation, and possible adaptation failure because of a drastic decline of organism resistance. In fact, an attempt was made to use the index to quantify adaptation cost, loss of resistance, and possible increase of the risk of remote consequences.

[Effects of exposure to high-energy protons on rat's behavior and underlying neurochemical mechanisms].

Effects of 1.5 and 3 Gy from high-energy protons (165 MeV) on rat's motor and oriented trying activities, rate of the Y-labyrinth learning with electric pain stimulation, and levels of monoamines and their metabolites in different brain structures were studied. The experimental results showed that irradiation with these proton doses caused considerable inhibition of the motor and oriented trying activities, and strengthening of passive defense reactions in the open field test; however, no significant change was induced in the learning rate or monoamines turnover. Apparently, emotional and motivational systems were affected to a greater degree than cognitive functions.

[The problems of studying the effects of far long-duration space mission factors on the higher nervous activity in model experiments with animals].

The article presents the analysis of difficulty with studying the CNS functional changes caused by ionizing radiations solely and in combination with the other spaceflight factors, and discusses optional methods of modeling the basic elements of operator's work in experiments with animals, primates specifically, as well as of data extrapolation on humans.

[Radiation lesion formation and character of repair processes in the hematopoietic system of primates exposed to continuous and fractionated gamma-irradiation by equally effective doses].

The article is dedicated to comparison of the biological effectiveness of continuous and fractionated gamma-irradiation of rhesus macaques by equally effective doses. These radiation conditions are broadly used in radiobiological experiments. Specifically, they are applied in modeling radiation effects on cosmonauts during extended exploration mission. A model of radiation damage and repair on the cell, tissue and organism levels, i.e., a model of effective residual dose responsible for change in mammals' resistance to irradiation of varying duration was used to calculate equally effective doses in the experiment with primates subject to continuous and fractionated exposure. The authors publish data related to formation of radiation lesion and rate of ensuing hemopoiesis reparation. Two groups of animals were compared in resistance modification followed after testing by acute irradiation. The test was to reproduce a radiation situation for cosmonauts in the event of a cannonade of powerful solar proton events resulting in an effective residual dose of 1 Sv total The experiment evidenced close resemblance of the hemopoietic effects in primates exposed to the compared radiation conditions.

[The organism tolerance to extreme factors: physiological basis, regulation, prediction].

The modern ideas about organism reactivity and tolerance, approaches to their estimation and prediction were observed in the paper. The ionizing radiation used as the basic factor, because this factor is the most convenient for the experimental investigation and experimental modeling of the different factors. The individual radiotolerance were observed as the reflection and the component of the organism general nonspecific tolerance. The enough voluminous of different physical factors combined influences were investigated, their reciprocally modified influences to the organism tolerance were estimated. The investigation of mammalian organism tolerance types and tactics of adaptation to the repeated influence of the stress-factors opens the new way to their estimation and prediction. The enough simple and reliable method of the individual tolerance (in particular, with used of the hormonal regulation system indices) were devised. This method is more effective than methods devised earlier.

[Problems of ensuring human radiation safety during interplanetary flights].

The work contains the analyses and discussion of the main sources of space radiation specified for interplanetary flights, the dosimetric functionals used for describing the processes of radiation lesions and reparation of the organism in the conditions of the complex radiation impact with a broad charge composition of cosmic rays and a peculiar spatial and temporal dose behavior. It represents the results of calculations of the radiation risks during the flight and the total lifelong radiation risk with taking into account all the delayed unfavorable biological consequences. The main uncertainties in the calculated values of radiation risk leading to its undervaluation are analyzed. In addition, also provided is the range of theoretical and experimental investigations necessary for the adjustment of coefficient values used in the algorithm of radiation risk calculations, as well as in the nomenclature of experiments for estimating the individual resistance of man to the extreme influence and investigations aimed at estimating and increasing the reliability of the operator activity of cosmonauts.

[Radiation physiology of higher nervous activity: results and perspectives].

Reflex forming and stabilization, the typological peculiarities of the experimental animals' higher nervous activity were discussed. The problems of the central nervous system functional reactions to irradiation in small doses, the chronic irradiation in particular, influence to higher nervous activity of heavy particles irradiation and neurochemical mechanisms of the disturbances in the central nervous system require further experimental investigations.

[The dynamics of the rats higher nervous activity disturbances after total influence of electrons and gamma-rays in doses 5-100 Gy].

The dynamics of using of stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after total influence of high energy electrons and of gamma-rays in doses 5-100 Gy were investigated. The quality structure of higher nervous activity disturbances after the influence of these kinds of ionizing radiation was identical. Therefore the tendency to disturbances aggravating after the electron radiation influence in the periods of the initial depression and of relatively normalization was revealed, especially after the irradiation in dose 50 Gy. The effective compensation of the functional disturbances in the central nervous system at the first 5-10 min after irradiation was after influence of electron radiation in doses about 30 Gy and after the influence of gamma-radiation in doses about 50 Gy. The irradiation of rats in doses 10 Gy and 5 Gy caused qualitative different dynamics of radiation disturbances in rats higher nervous activity. The differences in rats higher nervous activity after influence of electron and of gamma-radiation in these doses did not manifest distinctly.

[Dynamics of the rats higher nervous activity disturbances after partial influence of high energy electrons in high doses].

The dynamics of the disturbances of stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after total and partial (the head or body irradiated) influence of high energy electrons in dose 100 Gy was investigated. The head irradiation, the same way as total irradiation, provoked the early effects of disturbances of higher nervous activity, specifically, initial shock-like effect--the "early transient incapacitation" (ETI). The head shielding, on the contrary, prevents these disturbances. At the same times the body irradiation in dose 10 Gy (this dose don't provoke ETI effect) provoked practically the same disturbances of higher nervous activity as the total irradiation. Consequently, in animals irradiated in super-lethal doses the early disturbances of higher nervous activity provoked of direct influence of ionizing radiation to the brain. In animals irradiated in lesser doses these disturbances caused of non direct effects basically.

[Certain mechanisms of development of types of body tolerance to acute hypobaric hypoxia].

The regulatory mechanisms of individual rat resistance to acute hypobaric hypoxia were studied using the functional indices of the central nervous system (neurochemical and behavioral) and the hematopoietic system. The resistance to hypoxia was evaluated by the time of attitudinal reflex maintenance and recovery after decompression to a simulated altitude of 11200 m. Animals with different types of tolerance to hypoxia demonstrated different metabolic backgrounds of neurochemical processes (which were most balanced in moderately resistant rats). This agrees with the differences in active behavior and adaptive efficiency of these animals exposed to mild open-field stress. High functional activity of erythropoiesis and early leukocytic response were observed in hypoxia-tolerant rats.

[The sexual peculiarities of organism resistance types to the acute hypobaric hypoxia repeated influences].

The experimental investigation of the differences of the rats males and females reactions individual peculiarities to the acute hypobaric hypoxia repeated influences carried out. The time of the pose reflex preservation and restoration and the hypobaric hypothermia value during the lifting to 11,200 m "altitude" used for the resistance to hypoxia criterions. In experiments was showed that the males some more reactivity than females. But low resistance to the first influence females adapted to the repeated influence hypoxia the most effective. They preserve compensator reserve of organism and quickly restore of the disturbed functions.

[Disorders in rat's higher nervous activity in the course of chronic gamma-irradiation].

Investigations of early disorders in rat's higher nervous activity in the course of chronic gamma-irradiation (elaboration of the conditioned defensive reflex of avoidance "under the ray") showed that already in 10-15 minutes since the beginning of exposure (total dose of approx. 0.75-1.15 Gy) the conditioned reflex parameters degraded significantly with a general trend toward an increased excitation and disruption of active inhibition in the higher sections of the central nervous system (CNS). The most dramatic disorders occurred in the middle of the period of exposure (total dose of approx. 4-5 Gy). There were some individual differences in the CNS functional reaction to irradiation.

Some neurotropic effects of low-intensity electromagnetic waves in rats with different typological characteristics of higher nervous activity.

The effects of low-intensity electromagnetic waves (4200 MHz, modulated with quasichaotic signals at 20-20,000 Hz, energy density 15 microW/cm2; specific energy absorption not greater than 15 mJ/kg) on the neurochemical systems of the brain and on behavioral reactions were studied in experimental animals with different typological characteristics of higher nervous activity. These studies showed that electromagnetic waves produced marked changes in the state and activity of the monoaminergic mediator systems which were in general terms concordant with changes at the integrative level (mostly selective inhibitory effects). The nature of these processes depended to a significant extent on the typological characteristics of the animals.

[Modulation by ultralow intensity electromagnetic fields on pharmacologic effects of psychotropic drugs]. / Moduliruiushchee vliianie élektromagnitnykh polei sverkhnizkoi intensivnosti na farmakologicheskie éffekty nekotorykh psikhotropnykh preparatov.

The ultralow-intensity electromagnetic fields (EMF, frequency of 4200, modulated by a quasistochastic signal in the range of 20-20,000 Hz, power density of 15 microW/cm2, specific body absorption rate up to 4.5 mJ/kg) potentiated the hypnogenic effect of hexenal. The exposure to the EMF shortened the time of falling asleep induced by this drug and increased sleep duration in rats. The exposure to the EMF also potentiated haloperidol catalepsy: it decreased the drug threshold dose and increased the catalepsy duration. The EMF influence on the haloperidol effects was of a prolonged character: it was manifest in a selected suppression of the emotional excitation in the open-field test within 24 hours after the exposure.