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The Influence of Intravenous Transplantation of Mesenchymal Stem Cells on the Functional Activity of KATP Channels of Pial Arteries after Ischemia/Reperfusion of the Brain

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Abstract

The aim of this work was to study the effect of intravenous transplantation of human mesenchymal stem cells (hMSCs) on the functional state of KATP channels of smooth-muscle cells of cerebral arteries at different times of the postischemic period. Using a device for intravital visualization of pial vessels, the reaction of arteries to the KATP-channel blocker glibenclamide (GC), the activator of the same channels of pinacidil (PI), acetylcholine (ACh), and ACh against a background of GC action (ACh/GC) 7, 14, and 21 days after cerebral ischemia/reperfusion (I/R) and intravenous hMSC transplantation. On exposure to GC 7 days after I/R, two to five times fewer arteries narrowed than in the SO group and 1.5 times fewer expanded after PI. The introduction of hMSCs on the day of I/R of the brain after 7 days had no effect on the functioning of KATP channels: the constrictor reaction to GC and the dilator reaction to PI in this group were the same as in animals that underwent I/R. Fourteen days after I/R, the number of narrowed pial arteries on GС was 1.5–2 times less than in SO rats; the number of arteries that responded with dilatation to PI was 2–2.5 times less. In the cell-therapy group, for 14 days after I/R, the number of pial arteries that narrowed under the influence of GС and expanded under that of PI almost completely corresponded to those in SO rats. On day 21 after I/R, complete recovery of pial-artery responses to GC to the level in LO rats was observed. In the cell-therapy group, the reactivity of the pial arteries fully corresponded to the indicators in the SO group of animals. The functional state of KATP channels after I/R of the brain was assessed by comparing the dilator reactions of the pial arteries when exposed to pure ACh and ACh against a background of KATP channels being blocked with glibenclamide (ACh/GC). In SO animals, GC blocked the dilator reaction to ACh. The application of ACh against the background of GC increased the number of dilatations 7–14 days after I/R. After 21 days, the number of dilated vessels on exposure to ACh and ACh/GC was the same. In animals with transplanted hMSCs, excluding the first 7 days, GC blocked the dilator reaction of the pial arteries to ACh in the same way as in the SO group. It can be concluded that I/R of the rat cerebral cortex reduces the contribution of KATP channels to maintaining the basal tone of the pial arterial vessels. Changes persist for 14 days after ischemic exposure. At the same time, in the period from 7 to 21 days after I/R, the role of KATP channels in the dilatation of pial arteries on ACh decreased and by day 21 channels practically did not participate in the dilator response. Intravenous transplantation of hMSCs on the day of brain I/R results in earlier (as early as after 14 days) restoration of participation of SMC KATP channels in maintaining the basal tone and ACh-mediated dilatation of pial arteries.

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Funding

The work was supported by the program “Fundamental Scientific Research for Long-Term Development and Ensuring the Competitiveness of Society and the State” (47_110_DRiOK), topic 64.1 (0134-2019-0001) “Disclosure of the Mechanisms of Interaction between Molecular–Cellular and Systemic Regulation of the Functions of Internal Organs.”

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Authors and Affiliations

  1. Pavlov Institute of Physiology, Russian Academy of Sciences, 199034, St. Petersburg, Russia

    I. B. Sokolova & O. P. Gorshkova

  2. OOO Trans-Technologies, 192148, St. Petersburg, Russia

    N. N. Pavlichenko

Authors
  1. I. B. Sokolova
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  2. O. P. Gorshkova
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  3. N. N. Pavlichenko
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Correspondence to I. B. Sokolova.

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Conflict of interest. The authors declare that they have no conflicts of interest.

Statement on the welfare of animals. Experiments on rats were carried out in accordance with regulations established by Ministry of Health and Social Development of the Russian Federation no. 708n dated August 23, 2010 (“Rules of Laboratory Practice”) and Directive 2010/63/EU of the European Parliament and the Council of the European Union on the protection of animals used for scientific purposes, as well as recommendations of the bioethical commission of the Pavlov Institute of Physiology, Russian Academy of Sciences.

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Translated by I. Fridlyanskaya

Abbreviations: AP, arterial pressure; SMC, smooth-muscle cell; I/R, ischemia/reperfusion; SO, sham-operated; MSC and hMSC, mesenchymal stem cell and human MSC, respectively; ACh, acetylcholine; ACh/GC, action of acetylcholine against the background of pinacidil; GC, glibenclamide; PI, pinacidil.

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Sokolova, I.B., Gorshkova, O.P. & Pavlichenko, N.N. The Influence of Intravenous Transplantation of Mesenchymal Stem Cells on the Functional Activity of KATP Channels of Pial Arteries after Ischemia/Reperfusion of the Brain. Cell Tiss. Biol. 16, 223–232 (2022). https://doi.org/10.1134/S1990519X22030105

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