The Effectiveness And Mechanism Of Cerebral Ischemic Tolerance Induced By Hyperbaric Oxygen

[Object]: We studied the effectiveness and mechanism of cerebral ischemic tolerance induced by hyperbaric oxygen (HBO) in a rat focal cerebral ischemic model. [methods]: Sprague-Dawley rats were pretreated with HBO (100% O2, 2 atmospheres absolute, 1 hour once every other day for five sessions) or with room air. In experiment 1, rats were subjected to ET-1 injection or sham surgery. Post-injury neurobehavioral scores, brain water content, infarction volumes and HE staining were detected to assess the effectiveness of cerebral ischemic tolerance induced by HBO preconditioning. In experiment 2, rats and matched room air controls were killed at 24 h after HBO preconditioning. Brain levels of hypoxia-inducible factor la and its downstream target gene erythropoietin (EPO) analyzed by Western blotting and RT-PCR as well as HIF-la DNA-binding and transcriptional activities were determined in the ipsilateral hemisphere.[Results]: HBO preconditioning significantly improved the neurobehavioral function, decreased the brain water content, reduced the infarction volumes and attenuated the brain, injury after cerebral ischemia. 24 h after the last HBO pretreatment. HBO induced a marked increase in the HIF-la mRNA level, protein expression and DNA-binding activities. EPO mRNA level, protein expression were also significantly increased, while the mRNA level of VEGF and Glut-1 showed no significant increase. [Conclusion]: This observation indicates that the neuroprotection induced by HBO-preconditioning may be mediated by an upregulation of HIF-la and its target gene EPO.