Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/ijms22041885
Keywords
protein kinase inhibitors; primary hippocampal cultures; functional neural network activity; neuroprotection; ischemia; hypoxia
Funding
- Russian Science Foundation (RSF) [18-75-10071]
- Russian Science Foundation [18-75-10071] Funding Source: Russian Science Foundation
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The study found that FLT4 kinase blockade showed the most significant neuroprotective effect in hypoxia simulation, providing new opportunities for research on therapeutic strategies for cerebrovascular accidents.
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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