1. Academic Validation
  2. Neuroprotective Effect of Kinase Inhibition in Ischemic Factor Modeling In Vitro

Neuroprotective Effect of Kinase Inhibition in Ischemic Factor Modeling In Vitro

  • Int J Mol Sci. 2021 Feb 14;22(4):1885. doi: 10.3390/ijms22041885.
Elena V Mitroshina 1 Maria M Loginova 1 Maria O Savyuk 1 Mikhail I Krivonosov 2 Tatiana A Mishchenko 1 Viktor S Tarabykin 1 3 Mikhail V Ivanchenko 2 Maria V Vedunova 1
Affiliations

Affiliations

  • 1 Institute of Biology and Biomedicine, Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, Russia.
  • 2 Institute of Information, Technology, Mathematics and Mechanics, Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, Russia.
  • 3 Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
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.

Keywords

functional neural network activity; hypoxia; ischemia; neuroprotection; primary hippocampal cultures; protein kinase inhibitors.

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