| Background Trumatic brain injury (TBI) is an acute, severe, rapid change injury with high incidences, high death and disability rate in peace age and wartime, and could causes tissue disorganization,brain edema,primary cellular defect and neuroendocrine system change throughout the body . When people live in the hot and humid environment, especially in military fight and long-time high intensity work, the body has great heat production, eccrine sweat glands evaporation difficulty and accepts large apposition heat, which results in body heat disequilibrium, water-electrolyte metabolism disturbance and blood circulation collapse, and finally causes body temperature raise, metabolic rate increase, body fluid loss and internal environment chaos. When combined with TBI, TBE becomes more severe. Southeast China is under the environment of the high temperature (HT)and high humidity (HH) mostly around the year, The further study on TBE in such special environment will promote to investigate the pathophysiologic changes and its mechanism, and improve the level of curing cerebral injury in HT and HH, which lead to doing well in sanitarian and safeguard, having realistic guide significance. Recently discoveried, aquaporin is a membrance protein that has intimate relation for water transport.Among aquaporin, aquaporin-4(AQP4) is the main content at brain.Cerebral distribution of AQP4 imply that it is a main leading to brain tissue water transport. At physiologic and pathologic case, AQP4 of the brain tissue plays important role in buffer kalium ion and maintain intermal fluid balance and adjusting center somotic pressure and forming cerebral edema. Along with AQP4 and drugs being lucubrated about cerebral edema mechanism, gradually,we guess AQP4 may have played a very important role in the forming of brain edema. Therefore, we make efforts to seek a curative mechanism for TBE on the molecular level by studying the AQP4 expressive of post-traumatic brain tissues under the HT and HH environment.Objectives To observe the change of post-traumatic rat brain tissue water content and AQP4 expression under the HT and HH environment, further analyze molecular mechanism of focal PLGA-dexamethasone effect on rats TBE, and provide rationale for it's clinical application.Methods In part one,64 adult male SD rats were randomly divided into normal temperature(25℃,RH 50% )control group (n=16),the TBI under normal temperature group (n=16), the HT and HH (35℃,RH 85 % ) control group (n=16) and the TBI under the HT and HH environment group (n=16). The brain contusion device was adopted from the impact method described by Feeney et al, and brain trauma was made by dropping weight.In normal temperature control group the animals were normal rats and they were put into the 25℃,RH 50% environment, but not given hitting by dropping hammer; In TBI under normal temperature (25℃,RH 50%) group group the rats were put into 25℃,RH 50% environment after given skull operation and hitted by dropping hammer.In HT and HH group were also normal rats but put into 35℃,RH 85% environment. TBI under the HT and HH environment group rats were put into the 35℃,RH 85% environment after given hitting by dropping hammer; All rats in four groups above were decapitated at 6h and 24h time spot, the brains were removed for measurement of brain tissue water content, HE stain observation by microscope ,expression measurement of AQP4 protein and mRNA, observation of electron microscope.In part two,64 SD rats were executed as TBI under the HT and HH environment group.And they were randomly divided into 4 group:the focal PLGA-dexamethasone group,the high-dose dexamethasone intravenous injection group,the 20% mannitol intravenous injection group and the control group. In high-dose dexamethasone and 20% mannitol group ,rats were respectively treated with dexamethasone 5mg/kg and 20% mannitol 2g/kg immediately and were given maintain dosage 6h after hitting.The changes of brain water content (BWC) were measured by the dry-wet method 24h. after hitting. Immunohistochemistry and in situ hybridization method of analyzing photo were used to determine the change of expression of AQP4 protein and AQP4 mRNA. observation of HE stain and electron microscope were executed same as part one.Results The pathological observation showed that the intracranial focal DSP-PLGA implantation can decrease the liquid effusion from cerebral mirco-cerebrovascular and protect the cell and cytoarchitecture form damage, relieve the edema of many organelles such as mitochondrial and endoplasmic reticulum.The expression level of AQP4&mRNA and BWC of TBI group under the HT and HH environment were obviously higher than TBI under normal temperature group, showing significant difference (P<0.01). the expression level of AQP4&mRNA and BWC of PLGA-dexamethasone and mannitol intravenous injection treatment group were obviously lower than control group, showing significant difference (P<0.05): but there were no significant expression difference of AQP4/mRNA between PLGA-dexamethasone group and mannitol intravenous injection group(P>0.05). And the result also revealed:the expression level of AQP4&mRNA and BWC were no significant difference between the high-dose dexamethasone group and control group.Conclusion (1) From the study we can conclude that focal PLGA-dexamethasone has the effect of decreasing brain edema and helps to delay TBE formation after TBI in rats under HT and HH environment. (2) Focal PLGA-dexamethasone and mannitol intravenous injection can decrease AQP4 and mRNA expression at periphery encephaledema.(3) Focal PLGA-dexamethasone may relieve encephaledema and adjust aquatic convey though impacting AQP4 expression, which might be one of the mechanisms of it in the treatment of TBE.
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