Preconditioning using mild repetitive hypobaric hypoxia is known to increase a tolerance of brain neurons to severe hypoxia and other injurious exposures. In the present study, the effects of mild hypoxic preconditioning on the expression of transcription factors NF-kappaB and phosphorylated CREB (pCREB) has been studied in the neocortex of rats exposed to severe hypobaric hypoxia. As revealed by quantitative immunocytochemistry, the injurious severe hypobaric hypoxia (180 Torr, 3 h) remarkably reduced the neocortical levels of pCREB and NF-kappaB. The three-trial hypoxic preconditioning (360 Torr, 2 h, 3 days) induced persistent up-regulation of pCREB and NF-kappaB expression in the neocortex of rats 3-24 h following the severe hypoxia. In addition, the preconditioning alone which was not followed by the severe hypoxia, considerably increased neocortical pCREB and NF-kappaB levels. The findings suggest a role for transcription factors cAMP response element-binding protein and NF-kappaB in the neuroprotective mechanisms activated by the hypoxic preconditioning.

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