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The Effects of Intranasal Implantation of Mesenchymal Stem Cells on Nitric Monoxide Levels in the Hippocampus, Control of Cognitive Functions, and Motor Activity in a Model of Cerebral Ischemia in Rats

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Abstract

Hypoxia occurs in situations of disbalance between metabolic needs and the supply of oxygen to organs and tissues of the body. In this regard, tissue hypoxia and ischemia are essential components of the pathogenesis of many diseases. One of the promising areas of research into the mechanisms of ischemia is attempting to weaken the negative effect of hypoxia and ischemia in the brain by using a variety of techniques that activate neuroprotective mechanisms. Here, we aimed to assess the dynamics of restoration of motor activity control in an experimental model of ischemic stroke in rats (cerebral ischemia, CI) after intranasal perineural implantation of mesenchymal stem cells into the receptive field of the olfactory nerve. It was found that the perineural administration of MSCs to rats in the acute period of cerebral ischemia was accompanied by clear signs of recovery of cognitive and motor functions within 1 and 3 days after the operation. On the seventh day after ischemia modeling, rats with the introduction of MSCs had no distinctive features in the control of motor activity compared to the period before the operation in the same rats. In the hippocampus of rats after modeling ischemia, a significant decrease in the content of NO by about 50% relative to the initial level is observed after 1 day. In the hippocampus of rats in which ischemia was modeled with simultaneous intranasal administration of MSC, a significant decrease in NO content by 39% relative to the initial level was also observed after 1 day. The content of NO increases slightly, but the difference in the level of NO relative to ischemic rats was not significant. The copper content in the hippocampus in the rats of these two groups did not change. There was a tendency to increase the efficiency of the antioxidant system 1 day after ischemia in both studied groups, and this effect was more pronounced with intranasal administration of MSC.

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Acknowledgements

The authors thanks the colleagues S.G. Pashkevich and M.O. Dosina from the Institute of Physiology of the National Academy of Sciences of Belarus for technical assistance.

Funding

Ischemia modeling was carried out at the Brain Center, Institute of Physiology of the National Academy of Sciences of Belarus (Minsk, Belarus); the work was supported by the State Committee on Science and Technology of the Republic of Belarus (No. M19LITG-002). Measuring the EPR spectra of the samples was carried out at Zavoisky Physical-Technical Institute, KazSC RAS (Kazan), within the framework of a state assignment. The storage of samples and processing of the results were carried out at Kazan Federal University (Kazan, Russia) and funded by framework of fulfilling the state assignment no. 0671–2020-0059.

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Authors and Affiliations

  1. Department of Human and Animals, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation

    Guzel Yafarova, Vyacheslav Andrianov, Tatiana Bogodvid, Chihab Abdulla, Vladimir Kulchitsky & Khalil Gainutdinov

  2. Brain Center, Institute of Physiology, National Academy of Sciences, Minsk, Belarus

    Yulia Tokalchik, Tatiana Filipovich & Aleksandra Zamaro

  3. Zavoisky Physical-Technical Institute of the Russian Academy of Sciences, Kazan, Russian Federation

    Vyacheslav Andrianov, Lyeh Bazan & Khalil Gainutdinov

  4. Volga Region State University of Physical Culture, Sport and Tourism, Kazan, Russian Federation

    Tatiana Bogodvid

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  1. Guzel Yafarova
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Contributions

Guzel Yafarova carried out the interpretation of the results of measuring the behavioral changes and compared them with the results of NO level; prepared Fig. 1; and helped in drafting the manuscript.

Yulia Tokalchik participated in the simulation of ischemia and in measuring behavioral changes after this operation and participated in its interpretation and in extraction of brain samples for further measurements by EPR spectroscopy.

Tatiana Filipovich participated in the simulation of ischemia and in measuring behavioral changes after this operation and participated in its interpretation and in extraction of brain samples for further measurements by EPR spectroscopy.

Vyacheslav Andrianov carried out calculations and analysis of nitric oxide (NO) and copper signals in EPR spectra of the samples’ intensity; performed the statistical analysis; prepared Figs. 2, 3, 4, and 5; participated in interpretation of the results; and helped in drafting the manuscript.

Lyeh Bazan carried out measurements of EPR spectra of samples and participated in their interpretation.

Tatiana Bogodvid did the literature search, participated in the analysis of results and interpretation the role of NO in brain ischemia and protective actions at the NO level, and helped in drafting the manuscript.

Abdulla Chihab helped in drafting the manuscript and was responsible for its editing.

Aleksandra Zamaro participated in the simulation of ischemia and in measuring behavioral changes after this operation and participated in its interpretation and in extraction of brain samples for further measurements by EPR spectroscopy.

Vladimir Kulchitsky conceived the study, participated in its design and coordination, helped in drafting the manuscript, and was responsible for final approval.

Khalil Gainutdinov conceived the study, was responsible for the conception of its design and coordination, helped in drafting the manuscript, and did the literature search and final approval.

All authors read and approved the final manuscript.

Corresponding author

Correspondence to Khalil Gainutdinov.

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Competing interests

The authors declare no competing interests.

Ethics Approval and Consent to Participate

The experimental procedures (using anesthesia methods) are in compliance with the National Institutes of Health Guide for Care and Use of Laboratory Animals (Publication No. 85–23, revised 1985) and the UK Animals Scientific Procedures Act 1986 or the European Communities Council Directive of 24 November 1986 (86/609/EEC). The methods are approved by the Scientific Council of the Institute of Physiology of the National Academy of Sciences of Belarus (protocol No. 8, 26.08.2010).

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All authors agree to publish the results and approved the final manuscript.

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Yafarova, G., Tokalchik, Y., Filipovich, T. et al. The Effects of Intranasal Implantation of Mesenchymal Stem Cells on Nitric Monoxide Levels in the Hippocampus, Control of Cognitive Functions, and Motor Activity in a Model of Cerebral Ischemia in Rats. BioNanoSci. 13, 393–404 (2023). https://doi.org/10.1007/s12668-023-01072-7

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