Preventive Effects Of Heat Acclimation On High Altitude Cerebral Edema In Rats

BackgroundIn recent years,with the implementation of the national development of the western region,a growing number of people have to face a serious threat when ascending to high altitude environment.High altitude cerebral edema（HACE）is a severe form of acute altitude sickness caused by hypobaric hypoxia.The primary symptoms of HACE are cognitive disorder,ataxia,headache,and vomiting,etc.As the condition progresses,symptom and signs become worse.If coma ensues,death may come in a few hours or days in untreated case.So the prevention of high altitude cerebral edema is of great significance for military personnel,workers and tourists who are rapidly advancing plateau.Heat acclimation（HA）is a conserved adaptive response to exposure to moderately high ambient temperature,which is beneficial to the person who lives in the extreme heat environment.Generally,Heat acclimated humans have a higher tolerance to the heat by a series of physiological changes,such as sweating begins at a lower core temperature and a decrease in salt sweat sodium concentration loss.When they takes a break,heart rate decreases,heart function increases,core body temperature decreases,and basal meta bolic rate decreases.HA not only protects from damaging of heat stress,but also protects against various stresses such as trauma,ischemia/reperfusion,and hypoxia.This is called heat acclimation cross-tolerance.Some studies have shown that HA can reduce the brain damage caused by traumatic brain injury,while whether it has a protective effect on high altitude cerebral edema is unknown,and there is still no relevant research.So,it is very important to verify the effect of HA on brain damage caused by hypobaric hypoxia and explore the possible mechanism.Therefore,we investigate the effects and mechanism of heat acclimation on rats with hypobaric hypoxia by establishing a model of HACE and HA.It may be used for the prevention and clinical treatment of high altitude cerebral edema in the future.Methods1.Adult male SD rats were exposed to the environment that temperature is（34±1）°C for 30 days to establish a rat model of HA.The HACE rat model was established by exposure to hypoxia（7600m）for 24h.Rats were randomly divided into normal control group（C group）,hypoxia group（H group）,heat acclimation group（HA group）and heat acclimation combine with hypoxia group（HHA group）.2.Open field test was used to investigate the alteration of behavior in the rats.The brain water content,pathological change by HE staining,neuronal degeneration by Fluoro-Jade B（FJB）staining and ultrastructure change by transmission electron microscope were measured.3.Blood samples were used to detect blood routine,blood gas and oxygen dissociation curves.4.Brain tissues were used to test MDA content and Lactic acid content.Detect the expression changes of HSP70 and AQP4 in the brain.Results1.The HA rat model and the HACE rat model were successfully established under the conditions of temperature（34±1）°C for 30 days and hypoxia（7600m）for 24h.2.The heat acclimatization has a protective effect on high altitude cerebral edema caused by hypobaric hypoxia.The spontaneous activity of the rats is not significantly inhibited in hypoxia condition when the rats are acclimated to heat.Compared with the H rats,the water content of the brain in HHA rats is significantly decreased（P<0.05）;the degree of pathological damage and neuronal degeneration in brain tissue were significantly attenuated.With regard to the brain water content of rats in HA group and C group,there was no significant difference between the two groups（P>0.05）.This indicates that HA does not cause rat brain edema.3.Blood routine:compared with group C,hemoglobin,erythrocyte,hematocrit,and neutrophil percentage were significantly increased in group H;hemoglobin,erythrocyte and hematocrit were further increased in HHA group compared with group H.However,the percentage of neutrophils was significantly reduced.Blood gas analysis:compared with group C,SaO₂ and PaO₂ were significantly lower in group H;compared with group H,SaO₂and PaO₂ were significantly increased in HHA group.Oxygen dissociation curve:compared with group C,the oxygen dissociation curve of group H shifted right;compared with group H,the oxygen dissociation curve of HHA group further shifted right.4.Compared with group C,malonaldehyde（MDA）content,lactic acid content and AQP4 protein expression were significantly increased in H brain tissue;Compared with group H,MDA content,lactic acid content and AQP4 protein expression were significantly decreased in HHA group,while HSP70 protein expression significantly increased.Conclusion1.Heat acclimation rat model can be successfully established under continuous exposure for 30 days at temperature（34±1）°C.High altitude cerebral edema can be successfully established after exposure to hypobaric hypoxia（7600m）for 24h.2.Heat acclimation（34°C,30d）can prevent High altitude cerebral edema（7600m,24h）in rats.3.Heat acclimation has a protective role on brain edema caused by hypoxia in rats,which may due to the up-regulation of oxygen supply and oxygen carrying capacity.4.Heat acclimation rats reduce the expression of aquaporin 4 under hypobaric hypoxia,while up-regulating the expression of heat shock protein 70,thereby alleviating brain damage caused by hypobaric hypoxia.