<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">vestnovsu</journal-id><journal-title-group><journal-title xml:lang="ru">Вестник Новгородского государственного университета</journal-title><trans-title-group xml:lang="en"><trans-title>Vestnik of Novgorod State University</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2076-8052</issn><publisher><publisher-name>Новгородский государственный университет имени Ярослава Мудрого</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.34680/2076-8052.2024.4(138).573-585</article-id><article-id custom-type="elpub" pub-id-type="custom">vestnovsu-331</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ПАТОЛОГИЧЕСКАЯ ФИЗИОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PATHOPHYSIOLOGY</subject></subj-group></article-categories><title-group><article-title>Перспективные подходы к терапии ишемического инсульта</article-title><trans-title-group xml:lang="en"><trans-title>Promising approaches to ischemic stroke therapy</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6487-9083</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Осиков</surname><given-names>М. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Osikov</surname><given-names>M. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Осиков Михаил Владимирович – доктор медицинских наук, профессор, заведующий кафедрой, ЮУГМУ; Челябинская ОКБ.</p><p>Челябинск</p></bio><bio xml:lang="en"><p>Chelyabinsk</p></bio><email xlink:type="simple">prof.osikov@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0002-1710-3922</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шеломенцев</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Shelomentsev</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шеломенцев Алексей Викторович – ассистент, ЮУГМУ; ЧОКТГВВ.</p><p>Челябинск</p></bio><bio xml:lang="en"><p>Chelyabinsk</p></bio><email xlink:type="simple">avschelomenzew18@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8678-6267</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шишкова</surname><given-names>Ю. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Shishkova</surname><given-names>Yu. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шишкова Юлия Сергеевна – доктор медицинских наук, профессор.</p><p>Челябинск</p></bio><bio xml:lang="en"><p>Chelyabinsk</p></bio><email xlink:type="simple">shishkova_yulia@mail.ru</email><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Южно-Уральский государственный медицинский университет; Челябинская областная клиническая больница</institution><country>Россия</country></aff><aff xml:lang="en"><institution>South Ural State Medical University; Chelyabinsk Regional Clinical Hospital</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Южно-Уральский государственный медицинский университет; Челябинский областной клинический терапевтический госпиталь для ветеранов войн</institution><country>Россия</country></aff><aff xml:lang="en"><institution>South Ural State Medical University; Chelyabinsk Regional Clinical Therapeutic Hospital for War Veterans</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Южно-Уральский государственный медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>South Ural State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>22</day><month>01</month><year>2025</year></pub-date><volume>0</volume><issue>4(138)</issue><fpage>573</fpage><lpage>585</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Осиков М.В., Шеломенцев А.В., Шишкова Ю.С., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Осиков М.В., Шеломенцев А.В., Шишкова Ю.С.</copyright-holder><copyright-holder xml:lang="en">Osikov M.V., Shelomentsev A.V., Shishkova Y.S.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://vestnovsu.elpub.ru/jour/article/view/331">https://vestnovsu.elpub.ru/jour/article/view/331</self-uri><abstract><p>В статье проводится анализ данных о перспективных подходах терапии ишемического инсульта, представленных в рецензируемых источниках, индексированных в базах данных Pubmed и Российского индекса научного цитирования за период 2019-2024 гг. Продемонстрировано, что микробиота кишечника усиливает нейропротекцию посредством нейрональных путей, подавляет воспаление, активность гипоталамо-гипофизарно-надпочечниковой оси. Анализ представленных данных позволяет полагать, что микробиота кишечника может служить новой терапевтической мишенью в лечении ишемического инсульта. Авторы констатируют, что мелатонин является перспективной терапевтической молекулой в лечении ишемического инсульта. Мелатонин способен ингибировать оксидативный стресс. Мелатонин тормозит нейровоспаление в ишемизированной ткани головного мозга путем подавления пути SIRT1, ингибирования фенотипической поляризации микроглии до М2, снижения синтеза провоспалительных цитокинов. Авторы отметили, что мелатонин является активным участником нейрогенеза в зоне ишемического повреждения через активацию МТ1 и МТ2 рецепторов, а также прямого активирующего влияния на кальмодулинкиназу 2 типа. В анализе отражена роль стволовых клеток. Стволовые клетки, в частности нейронные клетки-предшественники человека, способны восстанавливать утраченную нервную ткань посредством высокого нейрорегенераторного потенциала, формируют синаптические связи с интактными нейронами головного мозга. Стволовые клетки костного мозга обладают выраженной миграционной способностью, что позволяет доставлять их в очаг ишемического повреждения мозга путем внутривенного введения; мезенхимальные стволовые клетки помимо высокого пролиферативного потенциала модулируют нейровоспаление посредством синтеза противоспалительных цитокинов.</p></abstract><trans-abstract xml:lang="en"><p>The article analyzes data on promising approaches to the treatment of ischemic stroke (IS) presented in peer-reviewed sources indexed in the Pubmed and Russian Science Citation Index databases for the period 2019–2024. It has been demonstrated that the intestinal microbiota enhances neuroprotection through neuronal pathways, suppresses inflammation, and the activity of the hypothalamic-pituitary-adrenal axis. Analysis of the presented data suggests that the intestinal microbiota can serve as a new therapeutic target in the treatment of ischemic stroke. The authors state that melatonin is a promising therapeutic molecule in the treatment of IS. Melatonin is able to inhibit oxidative stress. Melatonin inhibits neuroinflammation in ischemic brain tissue by suppressing the SIRT1 pathway, inhibiting the phenotypic polarization of microglia to M2, and reducing the synthesis of proinflammatory cytokines. The authors noted that melatonin is an active participant in neurogenesis in the ischemic injury zone through activation of MT1 and MT2 receptors, as well as direct activating effect on calmodulin kinase type 2. The analysis reflects the role of stem cells. Stem cells, in particular human neural progenitor cells, are able to restore lost nervous tissue through high neuroregenerative potential, form synaptic connections with intact neurons of the brain. Bone marrow stem cells have a pronounced migration capacity, which allows them to be delivered to the site of ischemic brain damage by intravenous administration; mesenchymal stem cells, in addition to high proliferative potential, modulate neuroinflammation through the synthesis of anti-inflammatory cytokines.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>ишемический инсульт</kwd><kwd>кишечная микробиота</kwd><kwd>мелатонин</kwd><kwd>стволовые клетки</kwd></kwd-group><kwd-group xml:lang="en"><kwd>ischemic stroke</kwd><kwd>gut microbiota</kwd><kwd>melatonin</kwd><kwd>stem cells</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Feigin V. L., Brainin M,. Norrving B., Martins S., Sacco R. L., Hacke W., Fisher M., Pandian J., Lindsay P. World Stroke Organization (WSO): Global Stroke Fact Sheet 2022 // Internatinal Journal of Stroke. 2022. 17 (1). 18-29. DOI: 10.1177/17474930211065917</mixed-citation><mixed-citation xml:lang="en">Feigin V. L., Brainin M., Norrving B., Martins S., Sacco R. L., Hacke W., Fisher M., Pandian J., Lindsay P. World Stroke Organization (WSO): Global Stroke Fact Sheet 2022 // Internatinal Journal of Stroke. 2022. 17 (1). 18-29. DOI: 10.1177/17474930211065917</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Игнатьева В. И., Вознюк И. А., Шамалов Н. А., Резник А. В., Виницкий А. А., Деркач Е. В. Социально-экономическое бремя инсульта в Российской Федерации // Журнал неврологии и психиатрии им. С. С. Корсакова. Спецвыпуски. 2023. 123 (8. 2). 5-15. DOI: 10.17116/jnevro20231230825</mixed-citation><mixed-citation xml:lang="en">Ignatyeva V. I., Voznyuk I. A., Shamalov N. A,. Reznik A. V., Vinitskiy A. A,. Derkach E. V. Sotsial'no-ekonomicheskoe bremyainsul'ta v Rossiiskoi Federatsii [Social and economic burden of stroke in Russian Federation] // Journal of Neurology and Psychiatry named after S. S. Korsakov. Special issues. 2023. 123 (8. 2). 5-15. DOI: 10.17116/jnevro20231230825</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">An H., Zhou B,. Ji X. Mitochondrial quality control in acute ischemic stroke // Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism. 2021. 41 (12). 3157-3170. DOI: 10.1177/0271678X211046992</mixed-citation><mixed-citation xml:lang="en">An H., Zhou B,. Ji X. Mitochondrial quality control in acute ischemic stroke // Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism. 2021. 41 (12). 3157-3170. DOI: 10.1177/0271678X211046992</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Cao Y., Yue X., Jia M., Wang J. Neuroinflammation and anti-inflammatory therapy for ischemic stroke // Heliyon. 2023. 9 (2). e17986. DOI: 10.1016/j.heliyon.2023.e17986</mixed-citation><mixed-citation xml:lang="en">Cao Y., Yue X., Jia M., Wang J. Neuroinflammation and anti-inflammatory therapy for ischemic stroke // Heliyon. 2023. 9 (2). e17986. DOI: 10.1016/j.heliyon.2023.e17986</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Candelario-Jalil E., Dijkhuizen R. M,. Magnus T. Neuroinflammation, Stroke, Blood-Brain Barrier Dysfunction, and Imaging Modalities // Stroke. 2022. 53 (5). 1473-1486. DOI: 10.1161/STROKEAHA.122.036946</mixed-citation><mixed-citation xml:lang="en">Candelario-Jalil E., Dijkhuizen R. M,. Magnus T. Neuroinflammation, Stroke, Blood-Brain Barrier Dysfunction, and Imaging Modalities // Stroke. 2022. 53 (5). 1473-1486. DOI: 10.1161/STROKEAHA.122.036946</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Jayaraj R. L., Azimullah S., Beiram R., Jalal F. Y., Rosenberg G. A. Neuroinflammation: friend and foe for ischemic stroke // Journal of Neuroinflammation. 2019.16 (1).142. DOI: 10.1186/s12974-019-1516-2</mixed-citation><mixed-citation xml:lang="en">Jayaraj R. L., Azimullah S., Beiram R., Jalal F. Y., Rosenberg G. A. Neuroinflammation: friend and foe for ischemic stroke // Journal of Neuroinflammation. 2019.16 (1).142. DOI: 10.1186/s12974-019-1516-2</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Paul S., Candelario-Jalil E. Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies // Experimental Neurology. 2021. 335 (2). 113518. DOI: 10.1016/j.expneurol.2020.113518</mixed-citation><mixed-citation xml:lang="en">Paul S., Candelario-Jalil E. Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies // Experimental Neurology. 2021. 335 (2). 113518. DOI: 10.1016/j.expneurol.2020.113518</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Kharitonova T. V., Melo T. P., Andersen G., Egido J. A., Castillo J., Wahlgren N. Importance of cerebral artery recanalization in patients with stroke with and without neurological improvement after intravenous thrombolysis // Stroke. 2013. 44 (9). 2513-2528. DOI: 10.1161/STROKEAHA.111.000048</mixed-citation><mixed-citation xml:lang="en">Kharitonova T. V., Melo T. P., Andersen G., Egido J. A., Castillo J., Wahlgren N. Importance of cerebral artery recanalization in patients with stroke with and without neurological improvement after intravenous thrombolysis // Stroke. 2013. 44 (9). 2513-2528. DOI: 10.1161/STROKEAHA.111.000048</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Barthels D., Das H. Current advances in ischemic stroke research and therapies // Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2018. 1866 (4). 165260. DOI: 10.1016/j.bbadis.2018.09.012</mixed-citation><mixed-citation xml:lang="en">Barthels D., Das H. Current advances in ischemic stroke research and therapies // Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2018. 1866 (4). 165260. DOI: 10.1016/j.bbadis.2018.09.012</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou G., Wang Y., Gao S,. Fu X., Cao Y., Peng Y., Zhuang J., Hu J., Shao A., Wang L. Potential Mechanisms and Perspectives in Ischemic Stroke Treatment Using Stem Cell Therapies // Frontiers in Cell and Devlopmental Biology. 2021. 9. 646927. DOI: 10.3389/fcell.2021.646927</mixed-citation><mixed-citation xml:lang="en">Zhou G., Wang Y., Gao S,. Fu X., Cao Y., Peng Y., Zhuang J., Hu J., Shao A., Wang L. Potential Mechanisms and Perspectives in Ischemic Stroke Treatment Using Stem Cell Therapies // Frontiers in Cell and Devlopmental Biology. 2021. 9. 646927. DOI: 10.3389/fcell.2021.646927</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Damasceno P. K. F., de Santana T. A., Santos G. C., Orge I. D., Silva D. N., Albuquerque J. F., Golinelli G., Grisendi G., Pinelli M., Ribeiro dos Santos R., Dominici M., Soares M. B. P. Genetic engineering as a strategy to improve the therapeutic efficacy of mesenchymal stem/stromal cells in regenerative medicine // Frontiers in cell and development biology. 2020. 8. 737-750. DOI: 10.3389/fcell.2020.00737</mixed-citation><mixed-citation xml:lang="en">Damasceno P. K. F., de Santana T. A., Santos G. C., Orge I. D., Silva D. N., Albuquerque J. F., Golinelli G., Grisendi G., Pinelli M., Ribeiro dos Santos R., Dominici M., Soares M. B. P. Genetic engineering as a strategy to improve the therapeutic efficacy of mesenchymal stem/stromal cells in regenerative medicine // Frontiers in cell and development biology. 2020. 8. 737-750. DOI: 10.3389/fcell.2020.00737</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Go V., Bowley B. G. E., Pessina M. A., Zhang Z. G., Chopp M., Finklestein S. P., Rosene D. L., Medalla M., Buller B., Moore T. L. Extracellular vesicles from mesenchymal stem cells reduce microglial-mediated neuroinflammation after cortical injury in aged Rhesus monkeys// Geroscience. 2020. 42 (1). 1-17. DOI: 10.1007/s11357-019-00115-w</mixed-citation><mixed-citation xml:lang="en">Go V., Bowley B. G. E., Pessina M. A., Zhang Z. G., Chopp M., Finklestein S. P., Rosene D. L., Medalla M., Buller B., Moore T. L. Extracellular vesicles from mesenchymal stem cells reduce microglial-mediated neuroinflammation after cortical injury in aged Rhesus monkeys// Geroscience. 2020. 42 (1). 1-17. DOI: 10.1007/s11357-019-00115-w</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Rascón-Ramírez F. J., Esteban-García N., Barcia J. A., Trondin A., Nombela C., Sánchez-Sánchez-Rojas L. Are We Ready for Cell Therapy to Treat Stroke? // Frontiers in Cell and Developmental Biology. 2021. 9. 621645. DOI: 10.3389/fcell.2021.621645</mixed-citation><mixed-citation xml:lang="en">Rascón-Ramírez F. J., Esteban-García N., Barcia J. A., Trondin A., Nombela C., Sánchez-Sánchez-Rojas L. Are We Ready for Cell Therapy to Treat Stroke? // Frontiers in Cell and Developmental Biology. 2021. 9. 621645. DOI: 10.3389/fcell.2021.621645</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Honarpisheh P, Bryan R. M., McCullough L. D. Aging Microbiota-Gut-Brain Axis in Stroke Risk and Outcome // Circulation Research. 2022. 130 (8). 1112-1144. DOI: 10.1161/CIRCRESAHA.122.319983</mixed-citation><mixed-citation xml:lang="en">Honarpisheh P, Bryan R. M., McCullough L. D. Aging Microbiota-Gut-Brain Axis in Stroke Risk and Outcome // Circulation Research. 2022. 130 (8). 1112-1144. DOI: 10.1161/CIRCRESAHA.122.319983</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Yuan B., Lu X.J., Wu Q. Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention // Frontiers in Immunology. 2020. 12. 800796. DOI: 10.3389/fimmu.2021.800796</mixed-citation><mixed-citation xml:lang="en">Yuan B., Lu X.J., Wu Q. Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention // Frontiers in Immunology. 2020. 12. 800796. DOI: 10.3389/fimmu.2021.800796</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Long J., Wang J., Li Y., Chen S. Gut microbiota in ischemic stroke: Where we stand and challenges ahead // Frontiers in Nutrition. 2022. 9. 008514. DOI: 10.3389/fnut.2022.1008514</mixed-citation><mixed-citation xml:lang="en">Long J., Wang J., Li Y., Chen S. Gut microbiota in ischemic stroke: Where we stand and challenges ahead // Frontiers in Nutrition. 2022. 9. 008514. DOI: 10.3389/fnut.2022.1008514</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Wang J., Liu X.,Li Q. Interventional strategies for ischemic stroke based on the modulation of the gut microbiota // Frontiers in Neuroscience. 2023. 17. 1158057. DOI: 10.3389/fnins.2023.1158057</mixed-citation><mixed-citation xml:lang="en">Wang J., Liu X.,Li Q. Interventional strategies for ischemic stroke based on the modulation of the gut microbiota // Frontiers in Neuroscience. 2023. 17. 1158057. DOI: 10.3389/fnins.2023.1158057</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Kılıç E., Çağlayan B., Caglar Beker M. Physiological and pharmacological roles of melatonin in the pathophysiological components of cellular injury after ischemic stroke // Turkis Journal of Medical Sciences. 2020. 50 (SI-2). 1655-1664. DOI: 10.3906/sag-2008-32</mixed-citation><mixed-citation xml:lang="en">Kılıç E., Çağlayan B., Caglar Beker M. Physiological and pharmacological roles of melatonin in the pathophysiological components of cellular injury after ischemic stroke // Turkis Journal of Medical Sciences. 2020. 50 (SI-2). 1655-1664. DOI: 10.3906/sag-2008-32</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Liu L., Cao Q., Gao W., Li B., Xia Z., Zhao B. Melatonin protects against focal cerebral ischemia-reperfusion injury in diabetic mice by ameliorating mitochondrial impairments: involvement of the Akt-SIRT3-SOD2 signaling pathway // Aging (Albany NY). 2021. 13 (12). 16105-16123. DOI: 10.18632/aging.203137</mixed-citation><mixed-citation xml:lang="en">Liu L., Cao Q., Gao W., Li B., Xia Z., Zhao B. Melatonin protects against focal cerebral ischemia-reperfusion injury in diabetic mice by ameliorating mitochondrial impairments: involvement of the Akt-SIRT3-SOD2 signaling pathway // Aging (Albany NY). 2021. 13 (12). 16105-16123. DOI: 10.18632/aging.203137</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Melatonin mediates mucosal immune cells, microbial metabolism, and rhythm crosstalk: A therapeutic target to reduce intestinal inflammation // Medicine Research Reviews. 2020. 40 (8). 606-632. DOI: 10.1002/med.21628</mixed-citation><mixed-citation xml:lang="en">Melatonin mediates mucosal immune cells, microbial metabolism, and rhythm crosstalk: A therapeutic target to reduce intestinal inflammation // Medicine Research Reviews. 2020. 40 (8). 606-632. DOI: 10.1002/med.21628</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Fülling C., Dinan T. G., Cryan J. F. Gut Microbe to Brain Signaling: What Happens in Vagus… // Neuron. 2019. 101 (6). 998-1002. DOI: 10.1016/j.neuron.2019.02.008</mixed-citation><mixed-citation xml:lang="en">Fülling C., Dinan T. G., Cryan J. F. Gut Microbe to Brain Signaling: What Happens in Vagus… // Neuron. 2019. 101 (6). 998-1002. DOI: 10.1016/j.neuron.2019.02.008</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Obata Y., Castaño Á., Boeing S., Bon-Frauches A. C., Fung C., Fallesen T., de Agüero M. G., Yilmaz B., Lopes R., Huseynova A., Horswell S., Maradana M. R., Boesmans W., Berghe P. V., Murray A. J., Stockinger B., Macpherson A. J. Vassilis Pachnis V. Neuronal programming by microbiota regulates intestinal physiology // Nature. 2020. 578 (7794). 284-289. DOI: 10.1038/s41586-020-1975-8</mixed-citation><mixed-citation xml:lang="en">Obata Y., Castaño Á., Boeing S., Bon-Frauches A. C., Fung C., Fallesen T., de Agüero M. G., Yilmaz B., Lopes R., Huseynova A., Horswell S., Maradana M. R., Boesmans W., Berghe P. V., Murray A. J., Stockinger B., Macpherson A. J. Vassilis Pachnis V. Neuronal programming by microbiota regulates intestinal physiology // Nature. 2020. 578 (7794). 284-289. DOI: 10.1038/s41586-020-1975-8</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Rusch J. A., Layden B. T., Dugas L. R. Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis // Frontiers in Endocrinology. 2023. 14. 1130689. DOI: 10.3389/fendo.2023.1130689</mixed-citation><mixed-citation xml:lang="en">Rusch J. A., Layden B. T., Dugas L. R. Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis // Frontiers in Endocrinology. 2023. 14. 1130689. DOI: 10.3389/fendo.2023.1130689</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang Y., Yang H., Li S., Li W, Wang Y. Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: A cohort study in the UK Biobank. PLOS // Medicine. 2021. 18 (11). e1003830. DOI: 10.1371/journal.pmed.1003830</mixed-citation><mixed-citation xml:lang="en">Zhang Y., Yang H., Li S., Li W, Wang Y. Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: A cohort study in the UK Biobank. PLOS // Medicine. 2021. 18 (11). e1003830. DOI: 10.1371/journal.pmed.1003830</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Ling L., Alattar A., Tan Z., Shah F.A., Ali T., Alshaman R., Koh P.O., Li S. A Potent Antioxidant Endogenous Neurohormone Melatonin, Rescued MCAO by Attenuating Oxidative Stress-Associated Neuroinflammation // Frontiers in Pharmacology. 2020. 21. 1220. DOI: 10.3389/fphar.2020.01220</mixed-citation><mixed-citation xml:lang="en">Ling L., Alattar A., Tan Z., Shah F.A., Ali T., Alshaman R., Koh P.O., Li S. A Potent Antioxidant Endogenous Neurohormone Melatonin, Rescued MCAO by Attenuating Oxidative Stress-Associated Neuroinflammation // Frontiers in Pharmacology. 2020. 21. 1220. DOI: 10.3389/fphar.2020.01220</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Suofu Y., Jauhari A., Nirmala E. S., Mullins W. A., Wang X., Li F., Carlisle D. L., Friedlander R. M. Neuronal melatonin type 1 receptor overexpression promotes M2 microglia polarization in cerebral ischemia/reperfusion-induced injury // Neuroscience Letters. 2023. 795. 137043. DOI: 10.1016/j.neulet.2022.137043</mixed-citation><mixed-citation xml:lang="en">Suofu Y., Jauhari A., Nirmala E. S., Mullins W. A., Wang X., Li F., Carlisle D. L., Friedlander R. M. Neuronal melatonin type 1 receptor overexpression promotes M2 microglia polarization in cerebral ischemia/reperfusion-induced injury // Neuroscience Letters. 2023. 795. 137043. DOI: 10.1016/j.neulet.2022.137043</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Tozihi M., Shademan B., Yousefi H,. Avci C. B., Nourazarian A., Dehghan G. Melatonin: a promising neuroprotective agent for cerebral ischemia-reperfusion injury // Frontiers in Aging Neuroscience. 2023. 15. 1227513. DOI: 10.3389/fnagi.2023.1227513</mixed-citation><mixed-citation xml:lang="en">Tozihi M., Shademan B., Yousefi H,. Avci C. B., Nourazarian A., Dehghan G. Melatonin: a promising neuroprotective agent for cerebral ischemia-reperfusion injury // Frontiers in Aging Neuroscience. 2023. 15. 1227513. DOI: 10.3389/fnagi.2023.1227513</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Liu Z. J., Ran Y. Y., Qie S. Y., Gong W. J., Gao F. H., Ding Z. T., Xi J. N. Melatonin protects against ischemic stroke by modulating microglia/macrophage polarization toward anti-inflammatory phenotype through STAT3 pathway // CNS Neuroscience &amp;Therapeutics. 2019. 25 (12). 1353-1362. DOI: 10.1111/cns.13261</mixed-citation><mixed-citation xml:lang="en">Liu Z. J., Ran Y. Y., Qie S. Y., Gong W. J., Gao F. H., Ding Z. T., Xi J. N. Melatonin protects against ischemic stroke by modulating microglia/macrophage polarization toward anti-inflammatory phenotype through STAT3 pathway // CNS Neuroscience &amp;Therapeutics. 2019. 25 (12). 1353-1362. DOI: 10.1111/cns.13261</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Merlo S., Luaces J. P., Spampinato S. F., Toro-Urrego N., Caruso G. I., D'Amico F., Capani F., Sortino M. A. SIRT1 mediates melatonin’s effects on microglial activation in hypoxia: in vitro and in vivo evidence // Biomolecules. 2020. 10 (3). 364. DOI: 10.3390/biom10030364</mixed-citation><mixed-citation xml:lang="en">Merlo S., Luaces J. P., Spampinato S. F., Toro-Urrego N., Caruso G. I., D'Amico F., Capani F., Sortino M. A. SIRT1 mediates melatonin’s effects on microglial activation in hypoxia: in vitro and in vivo evidence // Biomolecules. 2020. 10 (3). 364. DOI: 10.3390/biom10030364</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Sadanandan N., Cozene B., Cho J., Park Y. J., Saft M,. Gonzales-Portillo B,. Borlongan C. V. Melatonin-A Potent Therapeutic for Stroke and Stroke-Related Dementia // Antioxidants (Basel). 2020. (8). 672. DOI: 10.3390/antiox9080672</mixed-citation><mixed-citation xml:lang="en">Sadanandan N., Cozene B., Cho J., Park Y. J., Saft M,. Gonzales-Portillo B,. Borlongan C. V. Melatonin-A Potent Therapeutic for Stroke and Stroke-Related Dementia // Antioxidants (Basel). 2020. (8). 672. DOI: 10.3390/antiox9080672</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Wongprayoon P., Govitrapong P. Melatonin receptor as a drug target for neuroprotection // Current Molecular Pharmacology. 2020. 14 (2). 150-164. DOI: 10.2174/1874467213666200421160835</mixed-citation><mixed-citation xml:lang="en">Wongprayoon P., Govitrapong P. Melatonin receptor as a drug target for neuroprotection // Current Molecular Pharmacology. 2020. 14 (2). 150-164. DOI: 10.2174/1874467213666200421160835</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Spellicy S. E., Stice, S. L. Tissue and stem cell sourced extracellular vesicle communications with microglia // Stem Cell Reviews and Reports. 2020. 17 (2). 357-368. DOI: 10.1007/s12015-020-10011-y</mixed-citation><mixed-citation xml:lang="en">Spellicy S. E., Stice, S. L. Tissue and stem cell sourced extracellular vesicle communications with microglia // Stem Cell Reviews and Reports. 2020. 17 (2). 357-368. DOI: 10.1007/s12015-020-10011-y</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Hatakeyama M., Ninomiya I., Otsu Y., Omae K., Kimura Y., Onodera O., Fukushima M., Shimohata T., Kanazawa M. Cell therapies under clinical trials and polarized cell therapies in pre-clinical studies to treat ischemic stroke and neurological diseases: a literature review // International Journal of Molecular Sciences. 2020. 21 (17). 6194. DOI: 10.3390/ijms21176194</mixed-citation><mixed-citation xml:lang="en">Hatakeyama M., Ninomiya I., Otsu Y., Omae K., Kimura Y., Onodera O., Fukushima M., Shimohata T., Kanazawa M. Cell therapies under clinical trials and polarized cell therapies in pre-clinical studies to treat ischemic stroke and neurological diseases: a literature review // International Journal of Molecular Sciences. 2020. 21 (17). 6194. DOI: 10.3390/ijms21176194</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Sotomayor-Sobrino M. A., Ochoa-Aguila, A., Méndez-Cuest L. A., Gómez-Acevedo C. Neuroimmunological interactions in stroke // Neurologia. 2019. 34 (5). 326-335. DOI: 10.1016/j.nrl.2016.08.003</mixed-citation><mixed-citation xml:lang="en">Sotomayor-Sobrino M. A., Ochoa-Aguila, A., Méndez-Cuest L. A., Gómez-Acevedo C. Neuroimmunological interactions in stroke // Neurologia. 2019. 34 (5). 326-335. DOI: 10.1016/j.nrl.2016.08.003</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
