| Popis: |
Introduction: The present study aimed to test the hypothesis that hypercapnia, independently and/or in combination with hypoxia, can activate the signaling pathways for adaptation to hypoxia/ischemia related to inhibiting proapoptotic (caspase-dependent and caspase-independent) and inducing antiapoptotic factors. Methods: Following exposure to permissive hypercapnia and/or normobaric hypoxia, the intensity of apoptosis was evaluated in experimental ischemia models in vivo and in vitro. The percentages of caspase-3, apoptosis-inducing factor (AIF), Bax, and Bcl-2 in astrocytes and neurons derived from male Wistar rats were also calculated. In vitro, cells were subjected to various types of respiratory exposure (hypoxia and/or hypercapnia for 24 or 12 hours), as well as further sublethal chemical hypoxia. The percentages of these molecules in nerve cells in the ischemic penumbra of the brain after photothrombotic injury were also calculated. Results: It was established that the intensity of apoptosis decreased in the ischemic penumbra, mostly due to the hypercapnic component. It was also discovered that the levels of caspase-3, AIF, and Bax decreased in this area, whereas the level of Bcl-2 increased following exposure to hypercapnia and hypercapnic hypoxia. Discussion: The integrative assessment of the intensity of apoptosis/necrosis in astrocyte and neuron cultures showed that a combination of hypercapnia and hypoxia had the maximum neuroprotective effect. The levels of the mediators of apoptosis in astrocyte and neuron cultures after modeling chemical hypoxia in vitro were calculated. According to the results, the exposure modes combining permissive hypercapnia and normobaric hypoxia also have the most pronounced inhibitory effects on the apoptotic signaling pathways. |
