Hypercapnia potentiates HIF-1alpha activation in the brain of rats exposed to intermittent hypoxia.

The mechanisms and signalling pathways of the neuroprotective effect of hypercapnia and its combination with hypoxia are poorly understood. The study aims to test the hypothesis about the potentiating effect of hypercapnia on hypoxia adaptation systems directly related to hypoxia-induced factor 1alpha (HIF-1alpha). In this study we assessed HIF-1alpha content in hippocampal extracts and astrocytes obtained from Wistar male rats exposed to different respiratory conditions (7- or 15-fold of hypoxia and/or hypercapnia). In addition, HIF-1alpha content in astrocytes was assessed in in vitro model of chemical hypoxia as well as in the cerebral cortex after photothrombotic damage of this brain region. This study indicates increased levels of HIF1alpha in hippocampal extracts, astrocytes, and in cells of the near-stroke region of the cerebral cortex in rats exposed to hypoxia and hypercapnic hypoxia, but not hypercapnia alone. In in vitro study, hypercapnia facilitates the effects of acute chemical hypoxia observed in astrocytes. Thus, hypercapnia does not increase the level of transcription factor HIF-1alpha. However, the combined effects of hypercapnia and hypoxia in in vitro simulations of acute chemical hypoxia potentiate the accumulation of HIF-1alpha.