Effect Of Different Atmosphere Absolute Hyperbaric Oxygen On Perihematomal Edema And Expression Of Aquaporin-4in Rats With Intracerebral Hemorrhage

Objective:Hyperbaric oxygen(HBO) therapy is delivered by a procedurein which pure oxygen is administered at greater than atmospheric pressure,achieving the purpose of the treatment of disease by using the physical,chemi-cal,biological and physiological function of oxygen.Intracerebral hemorrhage(ICH) accounts for21%~48%of all cerebrovascular disease,is a common andfrequently occurring disease of the nervous system.The therapy for ICHdepends mainly on drugs,part of the patients need the implementation ofsurgery.But so far neither medical therapy nor surgical therapy can make a fullrecovery of the patients who suffer from ICH.Brain edema is the primarysecondary pathophysiologic change after intracerebral hemorrhage.Alleviatingbrain edema effectively can reduce secondary brain injury and promote therecovery of nerve function impairment after ICH.Clinical research indicatesthat HBO can reduce the brain edema after ICH and promote the recovery ofnerve function impairment.But there is short of the evidence of basedmedicine.Aquaporin is a kind of membrane protein that mediates water transportbetween biological membrane inside and outside.Expression of aquaporin hasspecificity in different tissues and organs.Aquaporin-4(AQP4) is mainlydistributed in brain tissue and rich expressed in capillaries,perivascular andglial cell that directly contacted with the cerebral pia mater.In recent years,studies show that AQP4and cerebral edema caused by traumatic brain injuryand ischemic stroke have certain relevance.Animal studies found that HBOcan effectively reduce perihematomal brain edema after ICH,and itsmechanism is relevant with reducing the level of AQP4expression inperihematomal brain tissue. In this experiment,ICH models were induced by collagenaseⅦ,intervened with different atmosphere absolute of the HBO therapy.Thebrain water content and the level of AQP4expression in perihematomal braintissue were determined.The influence and possible mechanism of the HBOtherapy to perihematomal cerebral edema after ICH can be furtherproved.Which atmosphere absolute of HBO is more suitable for the treatmentof ICH is further discussed.Methods:1The ninety-six experimental Sprague-Dawley rats were randomlydivided as normal contral group(n=6),ICH control group (n=18),ICH withnormobaric oxygen treatment(ICH+1.0ATA) group(n=18) and ICH with HBOtherapy group(n=54).The rats in the HBO therapy group were again divided asICH with1.8ATA HBO therapy,ICH with2.0ATA HBO therapy and ICH with2.2ATA HBO therapy,with18rats in each.The oxygen treatment wasadministered by using90%oxygen at different ATA in a steady pressure for60minutes,once daily.Rats except for normal contral group were sacrificed bydecapition at the time points of1d,3d,5d.Each time point had6rats.2The collagenase-induced method was used to set up the rat models ofICH.3The LongaFZ scoring method was used to evaluate the nerve functiondeficit for the rats injected with collagenase after24hours.No sign wasrated as zero point.The left side body can’t be fully extended was rated as onepoint.The contralateral limb was paralysis with tailgating phenomenon wasrated as two points.Rats that can’t stand with falling to the side was rated asthree points. Disturbance of consciousness was rated as four points.If theLongaFZ score was equal or greater than two points,the ICH models can beconsidered successfully.4The therapy of HBO:The rats with ICH were puted into the specialwooden box,the wooden box was puted into medical hyperbaric oxygenchamber.Pressure of hyperbaric oxygen chamber was according to thedifferent groups. The time of raising the pressure was30minutes.Oxygen was discharged into the wooden box directly when5minutes before the pressurewas stabilized.The flow of oxygen was10L/min.The time of oxygeninhalation,when the pressure was stabilized,was60minutes.Then the pressurewould be reduced in30minutes with the rate of0.01Mpa/min.The HBOtherapy was given for rats with ICH once daily except for the rats that in theICH control group.5The water content of the brain tissue was measured by dry-wetmethod.The expression of AQP4in the perihematomal brain tissue wasdetected by immunohistochemical staining.Results:1The brain water content at the perihematomal brain tissue in1.0ATAoxygen treatment group showed no significant difference as compared withthat in ICH control group at days1,3and5post-ICH(P>0.05).HBO therapygroup significantly reduced the brain water content in the perihematomal braintissue compared with ICH control group and1.0ATA oxygen treatment groupat days1,3and5post-ICH(P<0.05),however,the effect of HBO with2.0ATAwas superior to that1.8ATA and2.2ATA at days3and5post-ICH(P<0.05).2The level of AQP4expression at the perihematomal brain tissue in1.0ATA oxygen treatment group showed no significant difference ascompared with that in ICH control group at days1,3and5post-ICH(P>0.05).HBO therapy group significantly reduced the level of AQP4expression in the perihematomal brain tissue compared with ICH controlgroup and1.0ATA oxygen treatment group at days1,3and5post-ICH(P<0.05),however,the effect of HBO with2.0ATA was superior to that1.8ATAand2.2ATA at days3and5post-ICH(P<0.05).Conclusion:In this experiment,ICH models were induced by collagenaseⅦ,intervened with different ATA of the HBO therapy.The brain water contentand the level of AQP4expression in perihematomal brain tissue weredetermined.There is certain correlation between brain water content and theexpression of AQP4in the perihematomal brain tissue.The therapy ofhyperbaric oxygen and normobaric oxygen is helpful to reduce brain edema after ICH and the effect of hyperbaric oxygen therapy is better than that ofnormobaric oxygen therapy.The therapy of HBO with2.0ATA may be moresuitable for the treatment of ICH than1.8ATA and2.2ATA.The mechanism ofthe HBO treatment for reducing cerebral edema in the perihematomal braintissue may be related to lowering AQP4expression.