Hypercapnia and Hypoxia Stimulate Proliferation of Astrocytes and Neurons In Vitro
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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 6, October, 2020 GENERAL PATHOLOGY AND PATHOLOGICAL PHYSIOLOGY 755
Hypercapnia and Hypoxia Stimulate Proliferation of Astrocytes and Neurons In Vitro P. P. Tregub1,2, A. V. Morgun1, E. D. Osipova1, V. P. Kulikov2, N. A. Malinovskaya1, and D. A. Kuzovkov1
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 6, pp. 695-699, June, 2020 Original article submitted April 26, 2020 We compared proliferative activity and hypoxic tolerance in a co-culture of neurons and astrocytes in vitro after preliminary exposure to normobaric hypoxia and/or permissive hypercapnia in vivo. Preliminary hypoxic exposure increased the cell index throughout the 72-h period of observation, the effect of hypercapnia was observed on days 1 and 3 of the experiment, and the effect of hypercapnic hypoxia was noted only on day 1. Preliminary hypoxic exposure has a protective effect on nerve cells under conditions of chemical hypoxia. This suggests that hypercapnia and hypoxia activate proliferative activity of nerve cells, which can be viewed as a mechanism of their neuroprotective effectiveness. Key Words: hypoxia; hypercapnia; xCelligence; proliferation; neuroprotection Hypercapnia, especially in combination with oxygen deficiency, is superior to hypoxia alone in increasing brain tolerance to ischemia [12]. However, the mechanisms and signaling pathways of the neuroprotective effectiveness of hypercapnia and its combination with hypoxia remain poorly understood. It is known that normobaric hypoxia stimulates proliferation of endothelial cells of human umbilical cord vein and their basal secretory activity [1,2], while hypercapnia increases synthetic activity of nerve cells in the peri-infarction region after focal photothrombotic stroke [5]. Bearing in mind that stem and progenitor cells characterized by high proliferative and reparative potential in ischemic injuries are still present in the brain during the postnatal period [9], the study of these cells under physiological and hypoxic conditions in vitro will help to understand the peculiarities of neuron-astroglia interaction and the potential role in the mechanism of neuroprotection after preliminary exposure to hypoxia and hypercapnia. Moreover, increased 1 V. F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of the Russian Federation, Krasnoyarsk, Russia; 2Altai Medical Institute of Postgraduate Education, Barnaul, Russia. Address for correspondence: [email protected]. P. P. Tregub
proliferative activity is an important component of ischemic tolerance of the nervous tissue, because it reduces the consequences of trophic disturbances in glial cells and increases the expression of neurotransmitters, which makes a great contribution into reparation of neurons in the phase of paranecrosis and necrobiosis [9]. Therefore, we studied immature (progenitor) brain cells obtained from experimental animals previously breathing gas mixtures with different composition. Our aim was assess
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