Neuroprotective Effect of Kinase Inhibition in Ischemic Factor Modeling In Vitro

激酶抑制在体外缺血因子模型中的神经保护作用

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作者:Elena V Mitroshina, Maria M Loginova, Maria O Savyuk, Mikhail I Krivonosov, Tatiana A Mishchenko, Viktor S Tarabykin, Mikhail V Ivanchenko, Maria V Vedunova

Abstract

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.

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