Effect Of Different Therapeutic Window Of Hyperbaric Oxygen On Perihematomal Edema And Expression Of Aquaporin-4in Rats After Intracerebral Hemorrhage

Objective:Hyperbaric oxygen(HBO) therapy is a physical therapy inwhich a person exposed to above1atmospheric pressure in a cabin andbreathes with high pressure and high concentrations of oxygen, achievingthe purpose of the treatment of disease by increasing the oxygen content in thebody. Intracerebral hemorrhage(ICH) is protopathic, nontraumatic hemorrhagewithin the brain parenchyma, which accounted for20%-30%of acutecerebrovascular disease, in the acute phase of case fatality rate of about30%-40%.Surgical treatment decompression for cerebellar hemorrhages iswidely accepted as potentially life-saving in acute phase,but no provenmeidical or surgical treatment for ICH is efficent.Brain edema is a series ofthe protopathic cause the secondery pathophysiologic change afterintracerebral hemorrhage,and causing the nerve injury deteriorates again andresulting the increase of mortality. So relieving brain edema caused by ICH isthe key points in clinical therapy. Clinical research show that HBO mayrelieve the brain edema after the intracerebral hemorrhage and improve theneurological function impairment. But there is not have vast clinical andpreclinical research date support.Aquaporin is a species of membrance transport protein that maintence thewater balance out of and into the cells through changes the permeability of cellmembrance. In central nervous system(CNS), aquaporin-4(AQP4) is mainlydistributed in astrocyte and ependymocyte. Secondly it is expressed insupraoptic nucleus, paraventricular nucleus and the thirsty central.Research finding, the expression of AQP4up regulation is associatedwith the permeability of Blood Brain Barrier(BBB) and the formation of thebrain edema. The fundamental research find that HBO could inhibit the expression of AQP4around the hematoma, thereby relieving the formation ofbran edema after ICH.The previous studies of our team show that the suitable compression ofHBO is2.0atmosphere absolute.In this experiment, the models of ICH isinduced by collagenase Ⅶ, the compression of therapy is2.0ATA, To studythe effect of different therapeutic window of hyperbaric oxygen onperihematomal edema and expression of aquaporin-4in rats with intracerebralhemorrhage.Which therapeutic window of HBO is the best for the theatmentof ICH is further discussed.Methods:1A total of185male wistar rats with experimental intracerebralhemorrhage were randomly divided as normal group(n=5),sham operationgroup(n=60), control group(n=60) and HBO therapy group(n=60). The HBOtherapy was applied at different times (6hour,1,2or3days) after the opration.The HBO therapy group were again divided as HBO+6h group, HBO+1dgroup, HBO+2d group and HBO+3d group, with15rats in each group. Thecontrol group and the sham group were divided like the HBO therapy group.Rats were sacrificed after1,3,5sessions of HBO. Each time point had5rats.The control groups and the sham groups were without any treatment.2The rat model of ICH was established by collagenase-induced method.3The neurologic defect for the rat models of ICH induced by collagenaseafter6hours was evaluated by LongaFZ scoring method. No sign was rated as0point. The contralateral body of inserting needle could not be fully extendedwas denoted by1point. The injury side limb was palsy with tailgatingphenomenon was denoted by2points. Rats that appeared hemiparalysissymptoms was denoted by3points. If the rats loss of consciousness the scorewas denoted by4ponts. The LongaFZ score above2points, the ICH modelscan be taken to the experiment.4The oxygen treatment was administered by using100%oxygen at2.0ATA in a steady pressure for60min,once daily. Rats were sacrificed after1,3,5sessions of HBO. Each time points had5rats. 5Dry-wet method was used to measuring the water content of the braintissue, immunohistochemical staining was used to detected the expression ofAQP4.Results：1The brain water content at the perihematomal brain tissue in shamgroup showed no significant difference as compared with that in normal groupafter HBO therapy1day,3days and5days(P＞0.05).HBO therapy groupssignificantly reduced the brain water content in the perihematomal brain tissuecompared with ICH control group(P＜0.05).However,the effect of HBOoxygen treatment on HBO+6h group was superior to that HBO+1d group,HBO+2d group and HBO+3d group after HBO therapy1day,3days and5days(P＜0.05).2The level of AQP4expression at the perihematomal brain tissue insham group showed no significant difference as compared with that in normalgroup after HBO therapy1day,3days and5days(P＞0.05). HBO therapygroups significantly reduced the expression of AQP4in the perihematomalbrain tissue compared with ICH control group(P＜0.05). However, the effectof HBO oxygen treatment on HBO+6h group was superior to that HBO+1dgroup, HBO+2d group and HBO+3d group after HBO therapy1day,3days and5days(P＜0.05).Conclusion:In our experimental, the rats of ICH models were induced bycollagenase Ⅶ, intervened with different time when started HBO therapyafter ICH. The brain water content and the level of AQP4expression aroundthe perihematomal brain tissue were measured. There is certain correlationbetween brain water content and the expression of AQP4around theperihematal brain tissue. The therapy of hyperbaric oxygen is in favour ofreduce brain edema after ICH. The HBO therapy stared at6hours after ICHmay be better than1day,2days and3days.The mechanism of the HBO therapyfor alleviating cerebral edema around the perihematomal may be concernedwith lowering AQP4expression.