Influence of arachidonic acid derivatives on vascular dynamics and synaptic activity

Lukin P.O., Verisokin A.Yu., Brazhe A.R.1, Verveyko D.V.

Kursk State University, Department of Theoretical Physics,,,

1Lomonosov Moscow State University, Biological Faculty,

The functioning of the nervous tissue of the cerebral cortex is determined by a complex of interdependent processes associated with changes in neuronal activity and astrocytic activity. Without balanced ion flows, normal activity of nervous tissue is impossible. The release of potassium ions by neurons into the intercellular space and the entry of sodium ions into them, the excess potassium ions uptake by astrocytes and blood vessels, and the uptake of a large number of anions by astrocytes determine the integral functioning of the neurogliovascular unit: neuron, astrocyte, blood vessel and intercellular space. We base on the model we proposed earlier in [1] and build a minimalistic model of the neurogliovascular unit, taking into account a wide range of connections between its elements, including the influence of the synthesis of arachidonic acid and its derivatives on vascular tone and on synaptic and astrocytic activities.

The model presented in the work includes the following set of processes: (i) a minimalistic representation of neural activity and the functioning of sodium-potassium channels; (ii) glutamate release and its effect on IP3 production in astrocytes; (iii) IP3-dependent calcium dynamics in astrocytes, production of arachidonic acid and its diffusion through the intercellular space to blood vessels; (iv) synthesis of vasodilatory metabolites of arachidonic acid (EETs, PGE2), synthesis of a vasoconstrictor metabolite (20-HETE); (v) dependence of the radius of the blood vessel on nitric oxide, potassium and arachidonic acid metabolites; (vi) dynamics of the partial pressure of oxygen; (vii) the influence of ATP on the functioning of the sodium-potassium channel.

The pathways of arachidonic acid metabolites influence on the vascular dynamics and activity of the neurogliovascular unit have been ascertained. Comparison with available experimental data confirmed the correspondence of the numerical solution of the model to the observed effects. Control of the activity of nervous tissue through the regulation of the synthesis of arachidonic acid and its derivatives can be further used in the development of new therapeutic approaches to reduce the degenerative consequences of ischemic brain damage.

This work is supported by the RSCF grant the Russian Science Foundation grant (project No. 22-74-00146).


1. Verisokin, A. Yu., Verveyko, D. V., Postnov, D. E., Brazhe, A. R. Modeling of Astrocyte Networks: Toward Realistic Topology and Dynamics // Front.Cell.Neurosci. 15, 645068 (2021)


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