Effects of hyperbaric oxygen on blood-brain barrier and the expression of MMP-9 mRNA following acute brain injury

Abstract

Objective To observe effects of hyperbaric oxygen (HBO) on blood-brain barrier and the expression of MMP-9 mRNA following acute brain injury (ABI) and also to explore the mechanism involved in the treatment of ABI.Methods Forty SD rats were selected for the experiment.Following development of the ABI model by using free-fall hit method,the animals were randomly divided into 4 groups:the normal control group,the 24 h ABI group,the 24 h HBO therapy group and the 24 h normoxic nitrogen rich therapy group,each consisting of 10 animals.(1) The animals in the normal control group were simply housed in the chamber and received all the same treatments,except for high pressure and high level of oxygen breathing.(2) One hour after ABI,the animals in the 24 h ABI group were put into the hyperbaric chamber and received all the same treatments except for high pressure and high level of oxygen breathing,then they were killed 24 h after injury for collection of samples.(3) The animals in the ABI and 24 h HBO therapy groups were also housed in the hyperbaric chamber 1 h and 12 h after brain injury,and stayed at 0.25 MPa for a duration of 40 min,then they were sacrificed 24 h after injury.(4) The animals in the 24 h normoxic nitrogen rich therapy group were exposed to the 0.25 MPa normoxic nitrogen rich environment for a duration of 40 min,1 h and 12 h after brain injury,then 6 of the animals were killed 24 h after injury for the measurement of water content and RT-PCR,and 4 of the animals were killed for Evans blue detection (EB).Results Water contents both in the injured side and non-injured side of the brain following acute brain injury were 77.39 mg and 72.25 mg respectively,and statistical significance could be noticed when compared with the 24 h HBO therapy group(70.83 mg、70.27 mg) (P ＜ 0.05).Following 0.25 MPa HBO treatment of ABI,water content of the brain tissue decreased when compared with that of the non-treatment group (water contents of the brain tissue were 70.83 for the injured side and 77.39 for the non-injured side,P ＜0.01).Changes in brain tissue EB after HBO treatment were as follows:EB increased significantly both in the injured side and non-injured side of the hemisphere,and the hippocampus,following ABI and various treatments (P ＜ 0.05,P ＜0.01).As shown in the study,EB in the injured side and non-injured side of the hemisphere and the hippocampus decreased,when compared with those of the non-treatment group,following 0.25 MPa HBO therapy (P ＜ 0.01).Changes in the expression of MMP-9 mRNA were as follows:the expression of MMP-9 mRNA in the injured side and non-injured side of the hemisphere and hippocampus all increased significantly,following ABI and various treatment (P ＜ 0.05,P ＜0.01).After 0.25 MPa HBO treatment of ABI,the expression of MMP-9 mRNA in the injured side and non-injured side of the hemisphere and hippocampus decreased,when compared with that of the non-treatment group (P ＜ 0.01).Conclusions HBO treatment of ABI could protect the blood-brain barrier,thus alleviating cerebral edema.One of the mechanisms involved might be the reduction in the expression of MMP-9 mRNA through HBO treatment. Key words: Hyperbaric oxygen; Acute brain injury; Water content; Blood brain barrier; mutrix metallo proteinases 9; Gene expression