Izvestiya of Saratov University.

Physics

ISSN 1817-3020 (Print)
ISSN 2542-193X (Online)


For citation:

Verveyko D. V., Verisokin A. Y., Lagosha S. V., Brazhe A. R. Competitive bidirectional pathways of vascular tone regulation via arachidonic acid metabolites. Izvestiya of Saratov University. Physics , 2023, vol. 23, iss. 2, pp. 141-149. DOI: 10.18500/1817-3020-2023-23-2-141-149, EDN: IWWZMM

This is an open access article distributed under the terms of Creative Commons Attribution 4.0 International License (CC-BY 4.0).
Published online: 
30.06.2023
Full text:
(downloads: 72)
Language: 
English
Article type: 
Article
UDC: 
577.35
EDN: 
IWWZMM

Competitive bidirectional pathways of vascular tone regulation via arachidonic acid metabolites

Autors: 
Verveyko Darya V., Kursk State University
Verisokin Andrey Yu., Kursk State University
Lagosha Stanislav V., Lomonosov Moscow State University
Brazhe Alexey R., Lomonosov Moscow State University
Abstract: 

Background and Objectives: The processes taking place in each element of a neurogliovascular unit will have repercussions in the entire unit. Astrocytes produce arachidonic acid, and its metabolites play a key role in neurogliovascular dynamics with a possibility for bidirectional control, specifically EETs and PGE2 have a vasodilatory effect while 20-HETE acts as a vasoconstrictor. We develop a minimalistic model of model of neurogliovascular unit which takes into account the effect of arachidonic acid metabolites on the blood vessel radius, determining the blood flow and further activity of the elements. Materials and Methods: In order to test the model, we simulate two scenarios of model behavior, including an external influence leading to an increase in neuronal potassium, and an external influence on EETs. Results: We have proposed a mathematical model of the neurogliovascular unit, which accounts for IP3-dependent calcium dynamics in the astrocyte, neuronal activity, and vascular dynamics, and relies on arachidonic acid and its metabolites as vasoactive substances. Numerical simulations have demonstrated the plausibility of such a control loop involving the elements of the neurogliovascular unit and associated with the influence of arachidonic acid metabolites on vascular tone and indirectly on synaptic activity. We conclude that the model can be used for further theoretical studies of the regulatory mechanisms pertaining to cerebral perfusion.

Acknowledgments: 
This work was supported by the Russian Science Foundation (project No. 22-74-00146).
Reference: 
  1.  Kettenmann H., Hanisch U. K., Noda M., Verkhratsky A. Physiology of microglia. Physiol. Rev., 2010, vol. 91, pp. 461–553. https://doi.org/10.1152/physrev.00011.2010
  2. Li Z., McConnell H. L. Stackhouse T. L., Pike M. M., Zhang W., Mishra A. Increased 20-HETE signaling suppresses capillary neurovascular coupling after ischemic stroke in regions beyond the infarct. Front. Cell. Neurosci., 2021, vol. 15, article no. 762843. eCollection 2021. https://doi.org/10.3389/fncel.2021.762843
  3. Petzold G. C., Murthy V. N. Role of astrocytes in neurovascular coupling. Neuron, 2011, vol. 71, pp. 782–97. https://doi.org/10.1016/j.neuron.2011.08.009
  4. Koehler R. C., Gebremedhin D., Harder D. R. Role of astrocytes in cerebrovascular regulation. J. Appl. Physiol., 2006, vol. 100, pp. 307–317. https://doi.org/10.1152/japplphysiol.00938.2005. https://doi.org/10.1126/science.1156120
  5. Schummers J., Yu H., Sur M. Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science, 2008, vol. 320, pp. 1638–1643. https://doi.org/10.1126/science.1156120
  6. Shen X. Y., Gao Z. K., Han Y., Yuan M., Guo Y. S., Bi X. Activation and Role of Astrocytes in Ischemic Stroke. Front. Cell. Neurosci., 2021, vol. 15, article no. 755955. https://doi.org/10.3389/fncel.2021.755955
  7. Abusnaina A., Abdullah R. Spiking Neuron Models: A Review. JDCTA, 2014, vol. 8, pp. 14–21. https://doi.org/10.3390/brainsci12070863
  8. Manninen T., Havela R., Linne M. L. Computational Models for Calcium-Mediated Astrocyte Functions. Front. Comput. Neurosci., 2018, vol. 12, article no. 14. https://doi.org/10.3389/fncom.2018.00014
  9. Huneau C., Benali H., Chabriat H. Investigating Human Neurovascular Coupling Using Functional Neuroimaging: A Critical Review of Dynamic Models. Front. Neurosci., 2015, vol. 9, pp. 467. https://doi.org/10.3389/fnins.2015.00467
  10. Iadecola C., Yang G., Ebner T. J., Chen G. Local and propagated vascular responses evoked by focal synaptic activity in cerebellar cortex. J. Neurophysiol., 1997, vol. 78, pp. 651–659. https://doi.org/10.1152/jn.1997.78.2.651
  11. Iadecola C. The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease, Neuron, 2017, vol. 96, pp. 17–42. https://doi.org/10.1016/j.neuron.2017.07.030
  12. Farr H., David T. Models of neurovascular coupling via potassium and EET signaling. J. Theor. Biol., 2011, vol. 286, pp. 13–23. https://doi.org/10.1016/j.jtbi.2011.07.006
  13. Kenny A., Plank M. J., David T. The role of astrocytic calcium and TRPV4 channels in neurovascular coupling. J. Comput. Neurosci., 2018, vol. 44, pp. 97–114. https://doi.org/10.1007/s10827-017-0671-7
  14. Chander B. S., Chakravarthy V. S. A computational model of neuro-glio-vascular loop interactions. PLoS ONE, 2012, vol. 7, article no. e48802. https://doi.org/10.1371/journal.pone.0048802
  15. Tesler F., Linne M.-L., Destexhe A. A key role of astrocytic calcium dynamics to link neuronal activity with the BOLD signal. bioRxiv, 2021, article no. 04.23.441146. https://doi.org/10.1101/2021.04.23.441146
  16. Nippert A., Biesecker K., Newman E. Mechanisms Mediating Functional Hyperemia in the Brain. Neuroscientist, 2018, vol. 24, pp. 73–83. https://doi.org/10.1177/1073858417703033
  17. Ullah G., Jung P., Cornell-Bell A. H. Anti-phase calcium oscillations in astrocytes via inositol (1, 4, 5)-trisphosphate regeneration. Cell Calcium, 2006, vol. 39, pp. 197–208. https://doi.org/10.1016/j.ceca.2005.10.009
  18. Verisokin A. Yu., Verveyko D. V., Postnov D. E., Brazhe A. R. Modeling of astrocyte networks: towards realistic topology and dynamics. Front. Cell. Neurosci., 2021, vol. 15, article no. 645068. https://doi.org/10.3389/fncel.2021.645068
  19. MacVicar B. A., Newman E. A. Astrocyte regulation of blood flow in the brain. Cold Spring Harb. Perspect. Biol., 2015, vol. 7, article no. a020388. https://doi.org/10.1101/cshperspect.a020388
  20. Chen K., Pittman R. N., Popel A. S. Nitric oxide in the vasculature: where does it come from and where does it go? A quantitative perspective. Antioxid. Redox Signal, 2008, vol. 10, pp. 1185–1198. https://doi.org/10.1089/ars.2007.1959
  21. Picón-Pagès P., Garcia-Buendia J., Muñoz F. J. Functions and dysfunctions of nitric oxide in brain. Biochim. Biophys. Acta Mol. Basis Dis., 2019, vol. 1865, pp. 1949–1967. https://doi.org/10.1016/j.bbadis.2018.11.007
  22. Wieroсska J. M. Cieњlik P., Kalinowski L. Nitric Oxide-Dependent Pathways as Critical Factors in the Consequences and Recovery after Brain Ischemic Hypoxi. Biomolecules, 2021, vol. 11, no. 8, article no. 1097. https://doi.org/10.3390/biom11081097
  23. Chizhov A. V., Zefirov A. V., Amakhin D. V., Smirnova E. Y., Zaitsev A. V. Minimal model of interictal and ictal discharges “Epileptor-2”. PLoS Comput. Biol., 2018, vol. 14, article no. e1006186. https://doi.org/10.1371/journal.pcbi.1006186
  24. Cressman J. R., Ullah G. Ziburkus J., Schiff S. J., Barreto E. The influence of sodium and potassium dynamics on excitability, seizures, and the stability of persistent states: I. Single neuron dynamics. J. Comput. Neurosci., 2009, vol. 26, no. 2, pp. 159–170. https://doi.org/10.1007/s10827-008-0132-4
  25. Jiang C., Haddad G. G. Oxygen deprivation inhibits a K+ channel independently of cytosolic factors in rat central neurons. J. Physiol., vol. 481, pp. 15–26. https://doi.org/10.1113/jphysiol.1994.sp020415
  26. Attwell D., Buchan A., Charpak S., Lauritzen M., MacVicar B. A., Newman E. Glial and neuronal control of brain blood flow. Nature, 2010, vol. 468, pp. 232–243. https://doi.org/10.1038/nature09613
Received: 
03.03.2023
Accepted: 
24.03.2023
Published: 
30.06.2023