The Effect Of Hyperbaric Oxygen Preconditioning On Focal Cerebral Ischemic Reperfusion Injury In Rat

Ischemic stroke, which is one of the most common diseases in department of neurologyand the most frequent complication for heart disease, hypertension and diabetes, takes asmuch as70%of cerebral stoke and causes high mobility and mortality. Primary, secondaryprevention of the ischemic stroke is focus on in clinic,because the brain injury from theischemic stroke can not be cured reversibly by nowadays’ medical techniques and havelimited methods for treatment. As a result, the prevention became more and more importantfor the therapy and prognosis.There are varieties of methods for ischemic preconditioning, for example, ischemic,hyperthermia, sub-hypothermia, inhibition of cortex diffusion and some chemicals like,adenosine and neurotoxin. However, these methods have negative effect to the brain andsome of the mechanisms are not fully understood. Most of the conclusions of the studies arefrom animal experiment, so the safety and effectiveness to the human is still to be verified.Recently, Hyberbaric Oxygen is widely studied by scientists as a way ofpreconditioning. It has been already used in clinic as the treatment for CO intoxication, airembolisom, decompression, asphysia, ischemia of intestine and torsion of testis. It has beenproved that the pressure lower than3.0ATA and the time less than2h are safe and the HBOcan be used as ways for prevention. The mechanisms for HBO preconditioning to ischemictolerance are complicated and not well studied.Objective: To examine protective effect and mechanism of short term HBOpreconditioning on focal cerebral ischemic reperfusion injury.Method: Male Wister rats were preconditioned with3.0ATA100%O₂hyperbaricoxygenataions once（60min） every day for5successive days and subjected to right middlecerebral arterial occulusion （MCAO） in2hours ischemia and24hours reperfusion after thelast HBO. Neurological deficit scores were taken24hours after the right MCAO（Rogers DCtest）.TTC stain was used to examine the volume of infarction, HE and Nissle stain were usedto examine cell survival. Western blot analysis was used to investigate p38protein、phosphorylated p38expression and TUNEL stain was used to study the apoptosis.Result:1)General status:HBO+MCAO group present better neurobehavior status afterHBO preconditioning than MCAO group; The neurological deficit scores of HBO+MCAO group was significantly lower than MCAO group （P＜0.01）；The infarciton rate ofHBO+MCAO group was significantly lower than MCAO group （P＜0.01）.2) Nisslstain:The number of survival neuron in HBO+MCAO group was more than MCAO group（P＜0.01）.3) TUNEL stain:The number of TUNEL positive cells in penumbra inHBO+MCAO group and SB+MCAO group was lower than MCAO group （P＜0.01P＜0.01）. There was no difference of TUNEL positive cells between HBO+SB+MCAOgroup and MCAO group.4)The expression of p-p38and p38α/βof sham group waslower than MCAO group（P＜0.01）; The expression of p-p38and p38α/βofHBO+MCAO group and SB+MCAO group was lower than MCAO group（P＜0.01, P＜0.01）；There was no difference of the expression of p-p38and p38α/βbetweenHBO+SB+MCAO group and MCAO group.（P＞0.05）.Conclusion:1. Short-term HBO preconditioning alleviates cerebral ischemic reperfusiondamage by inhibiting cell apoptosis induced by cerebral ischemic reperfusion.2. HBO preconditioning alleviates cerebral ischemic reperfusion damage byinhibiting phosphorylation of p38.3. Using p38phosphorylation inhibitor SB203580before HBO preconditioningdiminishes HBO protective effect on cerebral ischemic reperfusion damage...