Institute of Biology and Biomedicine, Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, Russia.
Institute of Information, Technology, Mathematics and Mechanics, Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, Russia.
Int J Mol Sci. 2021 Feb 14;22(4):1885. doi: 10.3390/ijms22041885.
The contribution of many neuronal kinases to the adaptation of nerve cells to ischemic damage and their effect on functional neural network activity has not yet been studied. The aim of this work is to study the role of the four kinases belonging to different metabolic cascades (SRC, Ikkb, eEF2K, and FLT4) in the adaptive potential of the neuron-glial network for modeling the key factors of ischemic damage. We carried out a comprehensive study on the effects of kinases blockade on the viability and network functional calcium activity of nerve cells under ischemic factor modeling in vitro. Ischemic factor modelling was performed on day 14 of culturing primary hippocampal cells obtained from mouse embryos (E18). The most significant neuroprotective effect was shown in the blockade of FLT4 kinase in the simulation of hypoxia. The studies performed revealed the role of FLT4 in the development of functional dysfunction in cerebrovascular accidents and created new opportunities for the study of this enzyme and its blockers in the formation of new therapeutic strategies.
许多神经元激酶对神经细胞适应缺血性损伤的贡献及其对功能性神经网络活动的影响尚未得到研究。本工作的目的是研究属于不同代谢级联的四种激酶(SRC、Ikkb、eEF2K 和 FLT4)在神经元-神经胶质网络适应潜能中的作用,以模拟缺血性损伤的关键因素。我们在体外缺血因子模型中对激酶阻断对神经细胞活力和网络功能钙活性的影响进行了全面研究。缺血因子模型是在培养的来自 E18 期小鼠胚胎的原代海马细胞第 14 天进行的。在模拟缺氧时,阻断 FLT4 激酶显示出最显著的神经保护作用。进行的研究揭示了 FLT4 在脑血管意外中功能障碍发展中的作用,并为研究该酶及其抑制剂在形成新的治疗策略中的作用创造了新的机会。