Effects And Mechanism Of High +Gx On Learning And Memory Ability In Rats During Simulated Spaceship Emergency Return To The Earth

During spaceship emergency return to the earth, it can cause 15-21G overload. This may exceed physiological tolerance of human beings. Furthermore, high G exposure may induce not only physiological but also pathological changes of brain. In the field of aerospace medicine, harmful effects caused by high G overload on cosmonauts are becoming more and more important and drawing greater attention from aerospace medical specialists than ever before.The function of brain plays an important role in spaceflight for cosmonauts. It can influence spaceflight mission accomplishment and cosmonauts' safety. During spaceflight, cosmonauts must bear two kinds of acceleration, which are +Gx (ventral-to-dorsal direction) and +Gz (cranial-to -caudal direction). Among these accelerations, +Gx can reach more than 14.5G On the other hand, the acceleration from cranial-to-caudal direction may exceed 5G and last for long time. In addition, spaceship may meet an emergency in flight and must return to the earth in the light of ballistic trajectory, and the maximal acceleration produced by spaceship can reach 14G. In this instance, cosmonauts can bear the acceleration from ventral-to-dorsal direction. However, the acceleration from cranial-to-caudal direction can reach more than 3.5G and last for more than 100 seconds. These circumstances have exceeded human tolerance and may have a great influence on cosmonauts' mission accomplishment. It has reported that when man was relaxed and the onset rate was lG/s, human +Gz tolerance ranges from 3.1Gto 4.0G Human +Gz tolerance may increase after countermeasures were taken, such as anti-Gsuit and anti-maneuvers. If judgment criterions are severe dyspnea, unbearable bosom sorrow or obvious arrhythmia, ordinary person can bear 10-12G +Gx overload. In the same way, human +Gx tolerance may increase after countermeasures were taken such as anti-Gsuit and positive pressure breathing. Some person may tolerate more than +15Gx overload. Therefore above exposure in high G circumstances during spaceflight may induce human body injury and more effective mearsures must be taken.During spaceship emergency return to the earth, spaceship can produce high G overload and last for long time. It is full of difficulties to do some human experiments under real circumstance. Therefore it is indispensable to carry out experiments upon animals. Learning and memory are extremely important brain functions for animal and human being, which can reflect the normal function of central nervous system. According to previous study, exposure to sustained acceleration may induce brain injury and impairment of learning and memory. However, influences of +Gx exposure and +Gx stress after weightlessness on brain have not been reported yet. Therefore, it's of great practical significance to explore the effects and mechanism of high G overload produced by spaceship on human brain during emergency return to the earth. This research work plays an importance role in spaceflight mission accomplishment and cosmonaut's safety. The purpose of the present study was to find out the characteristics of changes of learning and memory during simulated spaceship emergency return to the earth, to further verify the mechanism, and to provide medicine evaluation for high G overload.Male Sprague-Dawley rats (offered by animal experimental center of Institute of Space Medico-Engineering) were exposed to +Gx on animal centrifuge. Changes of learning and memory in rats were observed at the time of immediately, Id and 3d after +Gx stress exposure by use of Y-maze test and step-through test. After undergoing +Gx stress, rats were anatomized. Morphological changes in cerebral cortex and hippocampus were observed by means of microscope and electron microscope. The apoptosis in cerebral cortex and hippocampus were detected by terminal deoxynuleotide transferase -mediated dUTP nick end labeling(Tunel) technique. The expression changes of related gene bcl-2, p53 and GFAP in cerebral cortex and hippocampi werealso detected by immunohistochemical method. The main findings are as follows:1. +15Gx/180s and simulated weightlessness for 7 days may affect the ability of learning and memory of rats. The effects of +15Gx/180s can be aggravated after simulated weightlessness for 7 days We investigated the effects of high +Gx on learning and memory in rats during simulated spaceship emergency return to the earth. The results showed that, in Y-maze test, as compared with control group, percentage of right reactions decreased significantly(P<0.01) and reaction time lengthened significantly(P<0.01) in Hypergravity (+15Gx/180s) After Simulated Weightlessness (HASW) group at all time. As compared with +15Gx group or simulated weightlessness group, percentage of right reactions decreased significantry(P<0.05) and reaction time lengthened significantly (P<0.05) immediately after stress. In step-through test, as compared with control group, total time(TT) lengthened significantly(P<0.01) in HASW group immediately and Id after stress; Latent time(LT) shortened significantly(P<0.01) and number of errors(NE) increased significantly (PO.01) at all the time after stress. As compared with +15Gx group, total time (TT) lengthened significantly (PO.05) immediately and Id after stress. As compared with simulated weightlessness group, total time(TT) lengthened significantly(P<0.05) and number of errors (NE) increased significantly (PO.05) immediately after stress. It is suggested that +15Gx/180s and simulated weightlessness may descend the ability of learning and memory of rats. Simulated weightlessness for 7 days can aggravate the effect of+Gx on learning and memory ability in rats.2. +15Gx/180s exposure may induce neuron injury in rat brain, which may be aggravated after simulated weightlessness for 7 days We investigated the morphological change of brain neuronal cell after +Gx exposure during simulated spaceship emergency return in rats. The results showed that, there were no obvious changes in neuronal morphology immediately after +15Gx exposure. On the first day after +15Gx exposure, there were slight changes of brain neuronal morphology, and changes becameevident on the third day. The numbers of ischemic neurons increased on the third day after exposure. Neuron injury and ultrastructure change were observed immediately and on the first day after simulated weightlessness for 7 days. The injuries reduced on the third day after simulated weightlessness. A number of degenerated neurons and ultrastructure change were observed in HASW group immediately and on the first day after stress.The injuries were aggravated and the numbers of degenerated neurons increased obviously on the third day after exposure. It is suggested that +15Gx/180s exposure may induce neuron injury in rat brain. The injuries may be aggravated after simulated weightlessness for 7 days.3. +15Gx/180s exposure may induce apoptosis in rat cerebral cortex and hippocampus, which can be accelerated after simulated weightlessness for 7 days We investigated the role of apoptosis in the mechanism of brain damage induced by +Gx exposure during simulated spaceship emergency return in rats. The results showed that, apoptotic cells were observed in cerebral cortex and hippocampus on the first day after +15Gx exposure(P<0.01), most evidently on the third day(P<0.01). These changes were also observed after simulated weightlessness for 7 days (P<0.01), most evidently on the first day(P<0.01). It was more obivious in HASW group on the third day after stress(P<0.01). As compared with +15Gx group or simulated weightlessness group, the numbers of apoptosis cells increased significantly (PO.01) after stress. It is suggested that +15Gx/180s exposure may induce apoptosis in rat cerebral cortex and hippocampus. This process can be accelerated after simulated weightlessness for 7 days.4. +15Gx/180s exposure may induce expression changes of bcl-2 and p53 in rat cerebral cortex and hippocampus, which can be aggravated after simulated weightlessness for 7 days We investigated the role of bcl-2 and p53 in the mechanism of brain apoptosis induced by +Gx exposure during simulated spaceship emergency return in rats. The results showed that, expression changes of bcl-2 and p53 were observed in cerebral cortex and hippocampus on the first day after +15Gx exposure, most evidently on thethird day. These changes were also observed after simulated weightlessness for 7 days, most evidently on the first day. It was more obivious in HASW group on the third day after stress. As compared with +15Gx group or simulated weightlessness group, these changes were more obivious after stress. It is suggested that +15Gx/180s exposure may induce expression changes of bcl-2 and p53 in rat cerebral cortex and hippocampus. These changes in rat brain can be aggravated after simulated weightlessness for 7 days.5. +15Gx/180s exposure and simulated weightlessness for 7 days may induce expression changes of GFAP in rat cerebral cortex and hippocampus. The effects of +15Gx/180s may be aggravated after simulated weightlessness for 7 days We investigated glial fibrillary acidic protein expression induced by high +Gx exposure during simulated weightlessness in rats. The results showed that, expression changes of GFAP were observed in cerebral cortex and hippocampus on the first day after +15Gx exposure, most evidently on the third day. They are most small type astrocytes. The numbers of GFAP reactive neurons increased after simulated weightlessness for 7 days, mostly being small type astrocytes. The GFAP reactions were strong in HASW group, the numbers of hypertrophic type astrocytes were highest in cerebral cortex and hippocampus. As compared with +15Gx group or simulated weightlessness group, these changes were more obivious after stress. It is suggested that +15Gx/180s exposure and simulated weightlessness for 7 days may induce expression changes of GFAP in rat cerebral cortex and hippocampus. These changes may be aggravated after simulated weightlessness for 7 days.In conclusion, we investigated the effects and mechanism of high +Gx on learning and memory ability in rats during simulated spaceship emergency return to the earth by means of animal centrifuge, Y-maze test, step-through test, morphological changes and imrnunohistochemical methods. The study has elucidated following questions: +15Gx/180s and simulated weightlessness may affect the ability of learning and memory of rats, which can be aggravated after simulated weightlessness for 7 days. The morphological...