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.

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.

MeSH terms

  • Animals
  • Cell Hypoxia
  • Cell Survival / drug effects
  • Cells, Cultured
  • Elongation Factor 2 Kinase / antagonists & inhibitors
  • Elongation Factor 2 Kinase / genetics
  • Elongation Factor 2 Kinase / metabolism
  • Gene Expression Regulation, Enzymologic
  • Hippocampus / cytology
  • Hippocampus / embryology
  • I-kappa B Kinase / antagonists & inhibitors
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • Ischemia / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological*
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / enzymology
  • Neuroprotective Agents / pharmacology
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Vascular Endothelial Growth Factor Receptor-3 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-3 / genetics
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism

Substances

  • Neuroprotective Agents
  • Protein Kinase Inhibitors
  • Protein Kinases
  • Vascular Endothelial Growth Factor Receptor-3
  • src-Family Kinases
  • I-kappa B Kinase
  • Eef2k protein, mouse
  • Elongation Factor 2 Kinase