Neuroprotective Effects And Mechanisms Of Hyperbaric Oxygen And Hypobaric Hypoxia Preconditioning On Ischemic Brain Injury

Background and Purposes:Pretreating with one kind of stimulus can enhance the tolerance of body to impaired factor which called preconditioning.Ischemia and hypoxia preconditioning have been shown their protective advantages on ischemic neuronal damage,but there exists moral problem.Therefore,it is very important to find a new method.The protection of hyperbaric oxygen preconditioning(HBOP) on cerebral ischemia has been demonstrated in few studies,But its mechanism is unclear.More important are the advantages and disadvantages of neuroprotective effects between HBOP and hypobaric hypoxia preconditioning(HHP) remains unclear.Therefore,we designed the following model to make the above problems clear.The right middle cerebral artery occlusion(MCAO) rabbit modle which established by Bederson was used in our prevent experiment to evaluate the neuroprotective effects of HBOP and HHP on cerebral ischemia and determine their mechanisms.,the neurological deficits,signal intensity of magnetic resonance imaging(MRI),pathological changes, infarct size,Pressure of brain tissue oxygen(PbtO2) and in vivo microdialysis around infarcted area were detected in rabbits after permanent MCAO as well as which were treated by HBOP or HHP before MCAO.Materials and methods:1.72 male rabbits with body weight 2 to 2.5 kg and age 3 to 4 months were randomly divided into three groups:simple MCAO group(n=24),HBOP+MCAO group(n=24) and HHP+MCAO group(n=24).2.Before MCAO,preconditioning were performed,the animals in HBOP+MCAO group had been kept in hypobaric hypoxia oxygen chamber for 5d(100%O₂, 250Kpa,1hr/d),while the animals in HHP+MCAO group had been kept in hyperbaric oxygen chamber for 3 d(4000m,61.6Kpa). 3.Then the MCAO model were made according to Bederson's method.4.The neurological deficits,signal intensity of MRI,pathological changes and infarct size were detected at 1,3,10,20d respectively after permanent MCAO in rabbits of three groups.5.The PbtO₂ at the edge of the infarcted region was monitored with LICOX CMP tissue oxygen pressure monitor(TOPM) at 1,3,10d after permanent MCAO in rabbits.6.Microdialysis of interstitial fluid of brain at the edge of infarcted region,including the concentration of glucose,lactate,pyruvate,glutamate were monitored,and the ratio of lactate/pyruvate was calculated.Results:1.All animals of the three groups are male and the reliability of MCAO model was well.2.Compared with simple MCAO group,the score of neurological deficits decreased significantly in HBOP group and HHP group at all time points(1,3,10,20d)(P＜0.05).3.T2WI of MRI of the animals in three groups were showed High signal around the right temporal and parietal lobes at all time points(1,3,10,20d),Infarcted size and signal intensity reduced at 3 d after permanent MCAO(P＜0.05).Compared with the simple MCAO group,the abnormal signal zones of T2WI in MRI which represented the ischemia and infarcted size were reduced significantly in HBOP group and HHP group at 3,10 d after permanent MCAO.4.The results of TTC staining indicated infarcted regions appeared in right side of brain after permanent MCAO,there were no statistical differences in the three groups in infarcted size at 1 d,and the infarcted size arrived the top in 3 d after permanent MCAO. Compared with simple MCAO group,size reduced significantly in HBOP+MCAO group and HHP+MCAO group at 3,10,20 d after permanent MCAO(P＜0.05).5.Pathology at 1d showed that,in the simple MCAO group,the color of cerebral ischemia were white,almostly no normal cell could be seen in infarcted region in 10 d.But clear boundary could be found in HBOP+MCAO group and HHP+MCAO group at 10,20 d after permanent MCAO.6.PbtO₂ around the infarcted regions in the simple MCAO group significantly decreased at 1,3,10 d after permanent MCAO(P＜0.05),which were significantly increased after HBOP and HHP(P＜0.05).PbtO₂ in preconditioning groups come to normal quicker than simple MCAO group.7.The variations of the components in the microdialysis fluid from the interstitial brain in the simple MCAO group,HBOP+MCAO group and HHP+MCAO group were not the same. Glucose productions decreased at 1d after MCAO,the two preconditioning groups recovered to normal at 3 d,there were statistically significant between the two preconditioning group and simple MCAO group;while the simple MCAO group still decreased at 20 d and were significantly lower than the left(P＜0.05).The lactate production increased at 1,3d,pyruvate increased at 1,3d, glyceral increased at 1d,there were statistically significant between two preconditioning groups and simple MCAO group.The glutamate concentration increased after MCAO,peaking at 3d,the difference of the glutamate concentration between the HBOP+MCAO group and the other two groups was statistically significant at 1,10d(P＜0.05).Conclusions:1.Because of the characteristics of high survival rate and easy to breed,the MCAO model prepared by improved Bederson's method is very useful,and it can imitate the clinical changes of cerebral ischemia.2.HBOP and HHP can improve neurologic deficits and reduce infarcted volume after permanent MCAO in rabbits.There are no significant differences on the neuroprotective effects of HBOP and HHP on cerebral ischemia.3.HBOP and HHP can improve the PbtO₂ around the infracted zone after MCAO in rabbits4.HBOP and HHP can improve the energy metabolism and neurotransimitters disorders around the infracted zone after MCAO in rabbits5.The variations of the components of the microdialysis interstitial fluid from the brain support the presence of "biochemical penumbra" around the infracted zone after MCAO,which suggested disorders of the toxicities of excitatory amino acids probably be one of the important mechanisms of cerebral ischemia injuries and the neuroprotective effects of HBOP and HHP maybe due to they could facilitate the recovery of "ischemia penumbra" and "biochemical penumbra" around the infracted zone.