medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-024medsovet-7406Research ArticleЦЕРЕБРОВАСКУЛЯРНЫЕ ЗАБОЛЕВАНИЯCEREBROVASCULAR DISEASESУчастие иммунного ответа в патогенезе ишемического инсультаInvolvement immune response in the pathogenesis of ischemic strokehttps://orcid.org/0000-0002-4830-907XВоробьевС. В.VorobyevS. V.

Воробьев Сергей Владимирович доктор медицинских наук, главный научный сотрудник научно-исследовательской лаборатории неврологии и нейрореабилитации, НМИЦ имени В.А. Алмазова; профессор кафедры клинической лабораторной диагностики, Санкт-Петербургский ГПМУ.

197341, Санкт-Петербург, ул. Аккуратова, д. 2; 194100, Санкт-Петербург, ул. Литовская, д. 2

Sergey V. Vorobyev - Dr. Sci. (Med.), Chief Researcher Laboratory of Neurology and Neurorehabilitation, Almazov NMRC; Professor of the Department of Clinical Laboratory Diagnostics, St Petersburg SPMU.

2, Akkuratov St., St Petersburg, 197341; 2, Litovskaya St., St Petersburg, 194100

sergiognezdo@yandex.ruhttps://orcid.org/0000-0002-6484-286XЯнишевскийС. Н.YanishevskiyS. N.

Янишевский Станислав Николаевич доктор медицинских наук, заведующий научно-исследовательской лабораторией неврологии и нейрореабилитации, НМИЦ имени В.А. Алмазова; доцент кафедры нервных болезней, Военно-медицинская академия имени С.М. Кирова.

197341, Санкт-Петербург, ул. Аккуратова, д. 2; 194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

Stanislav N. Yanishevskiy - Dr. Sci. (Med.), Head of the Laboratory of Neurology and Neurorehabilitation, Almazov NMRC; Associate Professor of the Department of Nervous Diseases, MMA named after S.M. Kirov.

2, Akkuratov St., St Petersburg, 197341; 6, Akademik Lebedev St., St Petersburg, 194044

stasya71@yandex.ruhttps://orcid.org/0000-0001-7204-7850КудрявцевИ. В.KudriavtsevI. V.

Кудрявцев Игорь Владимирович - кандидат биологических наук, заведующий лабораторией клеточной иммунологии, Институт экспериментальной медицины; старший научный сотрудник НИЛ аутоиммунных и аутовоспалительных заболеваний Научного центра мирового уровня «Центр персонализированной медицины», НМИЦ имени В.А. Алмазова; доцент кафедры иммунологии, Первый Санкт-Петербургский ГМУ имени академика И.П. Павлова.

197341, Санкт-Петербург, ул. Аккуратова, д. 2; 197376, Санкт-Петербург, ул. Академика Павлова, д. 12; 197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

Igor V. Kudriavtsev - Cand. Sci (Biol.), Head of the Laboratory of Cellular Immunology, Institute of Experimental Medicine; Senior Researcher Research Laboratory of Autoimmune and Autoinflammatory Diseases, Almazov NMRC; Associate Professor of the Department of Immunology, Pavlov First Saint Petersburg SMU.

2, Akkuratov St., St Petersburg, 197341; 12, Academician Pavlova St., St Petersburg, 197376; 6-8, Lev Tolstoy St., St Petersburg, 197022

igorek1981@yandex.ruhttps://orcid.org/0000-0002-7336-3860ШубинаК. М.ShubinaK. M.

Шубина Кристина Максимовна врач-невролог неврологического отделения, Городская Покровская больница.

199106, Санкт-Петербург, Большой проспект Васильевского острова, д. 85

Kristina M. Shubina - Neurologist of the Neurological Department, City Pokrovskaya Hospital.

85, Bolshoy Prospekt of Vasilievsky Island, St Petersburg, 199106

krisschubina@yandex.ruhttps://orcid.org/0000-0002-4456-0398АнтушеваМ. С.AntushevaM. S.

Антушева Мария Сергеевна студентка Института медицинского образования.

197341, Санкт-Петербург, ул. Аккуратова, д. 2

Maria S. Antusheva - Student of the Institute of Medical Education.

2, Akkuratov St., St Petersburg, 197341

mariantusheva@gmail.comhttps://orcid.org/0000-0003-4932-6733КузнецоваР. Н.KuznetsovaR. N.

Кузнецова Раиса Николаевна - кандидат медицинских наук, доцент, доцент кафедры иммунологии, Первый Санкт-Петербургский ГМУ имени академика И.П. Павлова; врач аллерголог-иммунолог медицинского центра, Санкт-Петербургский НИИЭМ им. Пастера.

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8; 197101, Санкт-Петербург, ул. Мира, д. 14

Raisa N. Kuznetsova - Cand. Sci. (Med.), Associate Professor of the Department of Immunology Pavlov First Saint PSMU; Allergisti mmunologist of the Medical Center, Saint-Petersburg PI.

6-8, Lev Tolstoy St., St Petersburg, 197022; 14, Mira St., St Petersburg, 197101

kuznetzova.rais@yandex.ruhttps://orcid.org/0000-0003-2596-4220СеребряковаМ. К.SerebriakovaM. K.

Серебрякова Мария Константиновна научный сотрудник лаборатории общей иммунологии, Институт экспериментальной медицины.

197376, Санкт-Петербург, ул. Академика Павлова, д. 12

Maria K. Serebriakova - Research Officer Laboratories of General Immunology, Institute of Experimental Medicine.

12, Academician Pavlova St., St Petersburg, 197376

m-serebryakova@yandex.ruhttps://orcid.org/0000-0002-5918-7450ПетуховаО. В.PetukhovaO. V.

Петухова Ольга Владимировна врач-невролог, Городская больница № 40.

197706, Санкт-Петербург, Сестрорецк, ул. Борисова, д. 9

Olga V. Petukhova – Neurologist.

9, Borisov St., Sestroretsk, St Petersburg, 197706

olya.petuchova84@mail.ruНациональный медицинский исследовательский центр имени В.А. Алмазова; Санкт-Петербургский государственный педиатрический медицинский университетРоссияAlmazov National Medical Research Centre; St Petersburg State Pediatric Medical UniversityRussian FederationНациональный медицинский исследовательский центр имени В.А. Алмазова; Военно-медицинская академия имени С.М. КироваРоссияAlmazov National Medical Research Centre; Military Medical Academy named after S.M. KirovRussian FederationНациональный медицинский исследовательский центр имени В.А. Алмазова; Институт экспериментальной медицины; Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. ПавловаРоссияAlmazov National Medical Research Centre; Institute of Experimental Medicine; Pavlov First Saint Petersburg State Medical UniversityRussian FederationГородская Покровская больницаРоссияCity Pokrovskaya HospitalRussian FederationНациональный медицинский исследовательский центр имени В.А. АлмазоваРоссияAlmazov National Medical Research CentreRussian FederationПервый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова; Санкт-Петербургский научно-исследовательский институт эпидемиологии и микробиологии имени ПастераРоссияPavlov First Saint Petersburg State Medical University; Saint-Petersburg Pasteur InstituteRussian FederationИнститут экспериментальной медициныРоссияInstitute of Experimental MedicineRussian FederationГородская больница № 40РоссияCity Hospital No. 40Russian Federation20231004202303816Copyright © Воробьев С.В., Янишевский С.Н., Кудрявцев И.В., Шубина К.М., Антушева М.С., Кузнецова Р.Н., Серебрякова М.К., Петухова О.В., 20232023Воробьев С.В., Янишевский С.Н., Кудрявцев И.В., Шубина К.М., Антушева М.С., Кузнецова Р.Н., Серебрякова М.К., Петухова О.В.Vorobyev S.V., Yanishevskiy S.N., Kudriavtsev I.V., Shubina K.M., Antusheva M.S., Kuznetsova R.N., Serebriakova M.K., Petukhova O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7406

Острые нарушения мозгового кровообращения являются одной из ведущих проблем современной клинической медицины, что обусловлено их значительным распространением в человеческой популяции и крайне негативным влиянием, оказываемым на организм пациента. Имеющиеся в настоящее время данные позволяют говорить о многовекторном характере патогенеза ишемического повреждения головного мозга. В рамках каскада развивающихся патохимических и патофизиологических процессов существенная роль в формировании ишемического инсульта принадлежит воспалительной реакции, протекающей посредством ответа иммунной системы на ишемию мозговой ткани. Одним из мест его реализации является стенка сосуда, находящегося в зоне ишемии, где при помощи белков клеточной адгезии происходит привлечение моноцитов и нейтрофилов. Значительную роль играет активация комплемента, осуществляемая в основном за счет С3 компонента или при инициализации маннозного пути. Непосредственно в очаге ишемии огромная роль принадлежит активации микроглии и астроцитов. При этом необходимо отметить, что в процессе активации как микроглия, так и астроциты способны приобретать провоспалительный или противовоспалительный фенотип. Превалирование провоспалительного варианта способствует пролонгированному повреждению ткани головного мозга, в то время как преобладание противовоспалительного фенотипа оказывает протективный эффект. Большую роль играет нарушение функции гематоэнцефалического барьера, что обеспечивает дополнительный приток лейкоцитов к месту ишемии. Кроме того, отдельные субпопуляции Т-лимфоцитов, проникающие через поврежденный барьер, также имеют существенное значение в организации и динамике иммуновоспалительного ответа. Наиболее изучено действие Th1 и Th2 клеток, гамма-дельта Т-лимфоцитов, естественных клеток-киллеров, а также регуляторных Т-лимфоцитов. Рассматривается роль В-лимфоцитов в формировании очага инсульта.

Acute disorders of cerebral circulation are one of the leading problems of modern clinical medicine, due to their significant spread in the human population and the extremely negative impact exerted on the patient’s body. Currently available data allow us to talk about the multi-vector nature of the pathogenesis of ischemic brain damage. Within the framework of the cascade of developing pathochemical and pathophysiological processes, an essential role in the formation of ischemic stroke belongs to the inflammatory reaction occurring through the immune system’s response to cerebral tissue ischemia. One of the places of its implementation is the vessel wall located in the ischemic zone, where monocytes and neutrophils are attracted with the help of cell adhesion proteins. Complement activation plays a significant role, carried out mainly due to the C3 component or during the initialization of the mannose pathway. Activation of microglia and astrocytes plays a huge role directly in the focus of ischemia. It should be noted that in the process of activation, both microglia and astrocytes are able to acquire a pro-inflammatory or anti-inflammatory phenotype. The prevalence of the pro-inflammatory variant contributes to prolonged damage to brain tissue, while the predominance of the anti-inflammatory phenotype has a protective effect. An important role is played by a violation of the function of the blood-brain barrier, which provides an additional influx of leukocytes to the site of ischemia. In addition, individual subpopulations of T-lymphocytes penetrating through the damaged barrier also play a significant role in the organization and dynamics of the immuno-inflammatory response. The action of Th1 and Th2 cells, gamma-delta T lymphocytes, natural killer cells, as well as regulatory T lymphocytes has been most studied. The role of B-lymphocytes in the formation of a stroke focus is considered.

инсультиммунный ответмикроглияастроцитыишемиягематоэнцефалический барьерТ-лимфоцитыцитокиныstrokeimmune responsemicrogliaastrocytesischemiablood-brain barrierT-lymphocytescytokinesReferencesСтародубцева О.С., Бегичева С.В. Анализ заболеваемости инсультом с использованием информационных технологий. Фундаментальные исследования. 2012;8(2):424-427. Режим доступа: https://fundamental-research.ru/ru/article/view?id=30383.Starodubceva O.S., Begicheva S.V. Analysis of stroke incidence of the use of information technologies. Fundamental Research. 2012;8(2):424-427. (In Russ.) Available at: https://fundamentaL-research.ru/ru/articLe/view?id=30383.Стаховская Л.В., Клочихина О.А., Богатырева М.Д., Коваленко В.В. Эпидемиология инсульта в России по результатам территориально-популяционного регистра (2009 2010). Журнал неврологии и психиатрии им. С.С. Корсакова. 2013;113(5):4-10. Режим доступа: https://www.mediasphera.ru/issues/zhumal-nevrologii-i-psikhiatrii-im-s-s-korsakova/2013/5/031997-7298201351.Stakhovskaya L.V., KLochikhina O.A., Bogatyreva M.D., KovaLenko V.V. EpidemioLogy of stroke in the Russian Federation: resuLts of territory's popuLation registry (2009-2010). Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2013;113(5):4-10. (In Russ.) AvaiLabLe at: https://www.mediasphera.ru/issues/zhurnaL-nevroLogii-i-psikhiatrii-im-s-s-korsakova/2013/5/031997-7298201351.Пирадов М.А., Максимова М.Ю., Домашенко М.А. Инсульт: пошаговая инструкция. М.: ГЭОТАР-Медиа; 2019. 272 с. Режим доступа: https://www.labirint.ru/books/679266/.Piradov M.A., Maksimova M.Y., Domashenko M.A. Stroke: Step-by-step instructions. Moscow: GEOTAR-Media; 2019. 272 p. (In Russ.) AvaiLabLe at: https://www.Labirint.ru/books/679266/.Hall MJ., levant S., DeFrances CJ. Hospitalization for stroke in U.S. hospitals, 1989-2009. NCHS Data Brief. 2012;(95):1-8. Available at: https://www.cdc.gov/nchs/data/databriefs/db95.pdf.HaLL MJ., Levant S., DeFrances CJ. HospitaLization for stroke in U.S. hospitaLs, 1989-2009. NCHS Data Brief. 2012;(95):1-8. AvaiLabLe at: https://www.cdc.gov/nchs/data/databriefs/db95.pdf.Roger V.L., Go A.S., Lloyd-Jones D.M., Benjamin EJ., Berry J.D., Borden W.B. et al. Heart disease and stroke statistics-2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-e220. https://doi.org/10.1161/CIR.0b013e31823ac046.Roger V.L., Go A.S., LLoyd-Jones D.M., Benjamin EJ., Berry J.D., Borden W.B. et aL. Heart disease and stroke statistics-2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-e220. https://doi.org/10.1161/CIR.0b013e31823ac046.Tsivgoulis G., Psaltopoulou T., Wadley V.G., Alexandrov A.V., Howard G., Unverzagt F.W. et al. Adherence to a Mediterranean diet and prediction of incident stroke. Stroke. 2015;46(3):780-785. https://doi.org/10.1161/STROKEAHA.114.007894.TsivgouLis G., PsaLtopouLou T., WadLey V.G., ALexandrov A.V., Howard G., Unverzagt F.W. et aL. Adherence to a Mediterranean diet and prediction of incident stroke. Stroke. 2015;46(3):780-785. https://doi.org/10.1161/STROKEAHA.114.007894.Howard G., Goff D.C. Population shifts and the future of stroke: forecasts of the future burden of stroke. Ann N Y Acad Sci. 2012;1268:14-20. https://doi.org/10.1111/j.1749-6632.2012.06665.x.Howard G., Goff D.C. PopuLation shifts and the future of stroke: forecasts of the future burden of stroke. Ann N Y Acad Sci. 2012;1268:14-20. https://doi.org/10.1111/j.1749-6632.2012.06665.x.Chamorro A., Meisel A., Planas A.M., Urra X., van de Beek D., Veltkamp R. The immunology of acute stroke. Nat Rev Neurol. 2012;8(7):401-410. https://doi.org/10.1038/nrneurol.2012.98.Chamorro A., MeiseL A., PLanas A.M., Urra X., van de Beek D., VeLtkamp R. The immunoLogy of acute stroke. Nat Rev Neurol. 2012;8(7):401-410. https://doi.org/10.1038/nrneuroL.2012.98.De Meyer S.F., Denorme F., langhauser F., Geuss E., Fluri F., Kleinschnitz C. Thromboinflammation in stroke brain damage. Stroke. 2016;47(4):1165-1172. https://doi.org/10.1161/STROKEAHA.115.011238.De Meyer S.F., Denorme F., Langhauser F., Geuss E., FLuri F., KLeinschnitz C. ThromboinfLammation in stroke brain damage. Stroke. 2016;47(4):1165-1172. https://doi.org/10.1161/STROKEAHA.115.011238.Delvaeye M., Conway E.M. Coagulation and innate immune responses: can we view them separately? Blood. 2009;114(12):2367-2374. https://doi.org/10.1182/blood-2009-05-199208.DeLvaeye M., Conway E.M. CoaguLation and innate immune responses: can we view them separateLy? Blood. 2009;114(12):2367-2374. https://doi.org/10.1182/bLood-2009-05-199208.Datsi A., Piotrowski L., Markou M., Koster T., Kohtz I., Lang K. et al. Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular traps. BMC Neurol. 2022;22(1):186. https://doi.org/10.1186/s12883-022-02707-0.Datsi A., Piotrowski L., Markou M., Koster T., Kohtz I., Lang K. et aL. Stroke-derived neutrophiLs demonstrate higher formation potentiaL and impaired resoLution of CD66b + driven neutrophiL extraceLLuLar traps. BMC Neurol. 2022;22(1):186. https://doi.org/10.1186/s12883-022-02707-0.Genchi A., Semerano A., Gullotta G.S., Strambo D., Schwarz G., Bergamaschi A. et al. Cerebral thrombi of cardioembolic etiology have an increased content of neutrophil extracellular traps. J Neurol Sci. 2021;423:117355. https://doi.org/10.1016/j.jns.2021.117355.Genchi A., Semerano A., GuLLotta G.S., Strambo D., Schwarz G., Bergamaschi A. et aL. CerebraL thrombi of cardioemboLic etioLogy have an increased content of neutrophiL extraceLLuLar traps. J Neurol Sci. 2021;423:117355. https://doi.org/10.1016/j.jns.2021.117355.Kim S.W., Lee J.K. Role of HMGB1 in the Interplay between NETosis and Thrombosis in Ischemic Stroke: A Review. Cells. 2020;9(8):1794. https://doi.org/10.3390/cells9081794.Kim S.W., Lee J.K. RoLe of HMGB1 in the InterpLay between NETosis and Thrombosis in Ischemic Stroke: A Review. Cells. 2020;9(8):1794. https://doi.org/10.3390/ceLLs9081794.Mocco J., Mack WJ., Ducruet A.F., Sosunov S.A., Sughrue M.E., Hassid B.G. et al. Complement component C3 mediates inflammatory injury following focal cerebral ischemia. Circ Res. 2006;99(2):209-217. https://doi.org/10.1161/01.RES.0000232544.90675.42.Mocco J., Mack WJ., Ducruet A.F., Sosunov S.A., Sughrue M.E., Hassid B.G. et aL. CompLement component C3 mediates infLammatory injury foLLowing focaL cerebraL ischemia. Circ Res. 2006;99(2):209-217. https://doi.org/10.1161/01.RES.0000232544.90675.42.Cervera A., Planas A.M., Justicia C., Urra X., Jensenius J.C., Torres F. et al. Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke. PloS ONE. 2010;5(2):e8433. https://doi.org/10.1371/journal.pone.0008433.Cervera A., PLanas A.M., Justicia C., Urra X., Jensenius J.C., Torres F. et aL. GeneticaLLy-defined deficiency of mannose-binding Lectin is associated with protection after experimentaL stroke in mice and outcome in human stroke. PLoS ONE. 2010;5(2):e8433. https://doi.org/10.1371/journaL.pone.0008433.Anrather J., Iadecola C. Inflammation and Stroke: An Overview. Neurotherapeutics. 2016;13(4):661-670. https://doi.org/10.1007/s13311-016-0483-x.Anrather J., IadecoLa C. InfLammation and Stroke: An Overview. Neurotherapeutics. 2016;13(4):661-670. https://doi.org/10.1007/s13311-016-0483-x.Tabet A., Apra C., Stranahan A.M., Anikeeva P. Changes in Brain Neuroimmunology Following Injury and Disease. Front Integr Neurosci. 2022;16:894500. https://doi.org/10.3389/fnint.2022.894500.Tabet A., Apra C., Stranahan A.M., Anikeeva P. Changes in Brain NeuroimmunoLogy FoLLowing Injury and Disease. Front Integr Neurosci. 2022;16:894500. https://doi.org/10.3389/fnint.2022.894500.Gadani S.P., Walsh J.T., lukens J.R., Kipnis J. Dealing with danger in the CNS: the response of the immune system to injury. Neuron. 2015;87(1):47-62. https://doi.org/10.1016/j.neuron.2015.05.019.Gadani S.P., WaLsh J.T., Lukens J.R., Kipnis J. DeaLing with danger in the CNS: the response of the immune system to injury. Neuron. 2015;87(1):47-62. https://doi.org/10.1016/j.neuron.2015.05.019.Kim E., Cho S. CNS and peripheral immunity in cerebral ischemia: partition and interaction. Exp Neurol. 2021;335:113508. https://doi.org/10.1016/j.expneurol.2020.113508.Kim E., Cho S. CNS and peripheraL immunity in cerebraL ischemia: partition and interaction. Exp Neurol. 2021;335:113508. https://doi.org/10.1016/j.expneuroL.2020.113508.Wang Q., Tang X.N., Yenari M.A. The inflammatory response in stroke. J Neuroimmunol. 2007;184(1-2):53-68. https://doi.org/10.1016/j.jneuroim.2006.11.014.Wang Q., Tang X.N., Yenari M.A. The inflammatory response in stroke. J Neuroimmunol. 2007;184(1-2):53-68. https://doi.org/10.1016/j.jneuroim.2006.11.014.Lehnardt S. Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Glia. 2010;58(3):253-263. https://doi.org/10.1002/glia.20928.Lehnardt S. Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Glia. 2010;58(3):253-263. https://doi.org/10.1002/glia.20928.Zhao S.C., Ma L.S., Chu Z.H., Xu H., Wu W.Q., Liu F. Regulation of microglial activation in stroke. Acta Pharmacol Sin. 2017;38(4):445-458. https://doi.org/10.1038/aps.2016.162.Zhao S.C., Ma L.S., Chu Z.H., Xu H., Wu W.Q., Liu F. Regulation of microglial activation in stroke. Acta Pharmacol Sin. 2017;38(4):445-458. https://doi.org/10.1038/aps.2016.162.Frijns CJ, Kappelle LJ. Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke. 2002;33(8):2115-2122. https://doi.org/10.1161/01.str.0000021902.33129.69.Frijns CJ, Kappelle LJ. Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke. 2002;33(8):2115-2122. https://doi.org/10.1161/01.str.0000021902.33129.69.Stuckey S.M., Ong L.K., Collins-Praino L.E., Turner RJ. Neuroinflammation as a Key Driver of Secondary Neurodegeneration Following Stroke? Int J Mol Sci. 2021;22(23):13101. https://doi.org/10.3390/ijms222313101.Stuckey S.M., Ong L.K., Collins-Praino L.E., Turner RJ. Neuroinflammation as a Key Driver of Secondary Neurodegeneration Following Stroke? Int J Mol Sci. 2021;22(23):13101. https://doi.org/10.3390/ijms222313101.Gerhard A., Schwarz J., Myers R., Wise R., Banati R.B. Evolution of microglial activation in patients after ischemic stroke: A [11C](R)-PK11195 PET study. Neurolmage. 2005;24(2):591-595. https://doi.org/10.1016/j.neuroimage.2004.09.034.Gerhard A., Schwarz J., Myers R., Wise R., Banati R.B. Evolution of microglial activation in patients after ischemic stroke: A [11C](R)-PK11195 PET study. Neurolmage. 2005;24(2):591-595. https://doi.org/10.1016/j.neuroimage.2004.09.034.Мокров Г.В., Деева О.А., Яркова М.А., Гудашева Т.А., Середенин С.Б. Трансфокаторный белок TSPO 18 кДа и его лиганды: перспективный подход к созданию новых нейропсихотропных средств. Фармакокинетика и фармакодинамика. 2018;(4):3-27. https://doi.org/10.24411/2587-7836-2018-10026.Mokrov G.V., Deeva O.A., YArkova M.A., Gudasheva T.A., Seredenin S.B. Translocator protein TSPO 18 kDa and its ligands: a promising approach to the creation of new neuropsychotropic drug. Pharmacokinetics and Pharmacodynamics. 2018;(4):3-27. (In Russ.) https://doi.org/10.24411/2587-7836-2018-10026.Selvaraj U.M., Stowe A.M. Long-term T cell responses in the brain after an ischemic stroke. DiscovMed. 2017;24(134):323-333. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893311/.Selvaraj U.M., Stowe A.M. Long-term T cell responses in the brain after an ischemic stroke. DiscovMed. 2017;24(134):323-333. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893311/.Черных Е.Р., Шевела Е.Я., Морозов С.А., Останин А.А. Иммунопатогенетические аспекты ишемического инсульта. Медицинская иммунология. 2018;20(1):19-34. Режим доступа: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893311/10.15789/1563-0625-2018-1-19-34.Chernyh E.R., Shevela E.Y., Morozov S.A., Ostanin A.A. Immunopathogenetic aspects of ischemic stroke. Medical Immunology (Russia). 2018;20(1):19-34. (In Russ.) Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC5893311/10.15789/1563-0625-2018-1-19-34.Biswas S.K., Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11(10):889-896. https://doi.org/10.1038/ni.1937.Biswas S.K., Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11(10):889-896. https://doi.org/10.1038/ni.1937.Klebe D., McBride D., Flores JJ., Zhang J.H., Tang J. Modulating the Immune Response Towards a Neuroregenerative Peri-injury Milieu After Cerebral Hemorrhage. J Neuroimmune Pharmacol. 2015;10(4):576-586. https://doi.org/10.1007/s11481-015-9613-1.Klebe D., McBride D., Flores JJ., Zhang J.H., Tang J. Modulating the Immune Response Towards a Neuroregenerative Peri-injury Milieu After Cerebral Hemorrhage. J Neuroimmune Pharmacol. 2015;10(4):576-586. https://doi.org/10.1007/s11481-015-9613-1.Hu X., Li P., Guo Y., Wang H., Leak R.K., Chen S. et al. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke. 2012;43(11): 3063-3070. https://doi.org/10.1161/STROKEAHA.112.659656.Hu X., Li P., Guo Y., Wang H., Leak R.K., Chen S. et al. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke. 2012;43(11): 3063-3070. https://doi.org/10.1161/STROKEAHA.112.659656.Wang S., Zhang H., Xu Y. Crosstalk between microglia and T cells contributes to brain damage and recovery after ischemic stroke. Neurol Res. 2016;38(6):495-503. https://doi.org/10.1080/01616412.2016.1188473.Wang S., Zhang H., Xu Y. Crosstalk between microglia and T cells contributes to brain damage and recovery after ischemic stroke. Neurol Res. 2016;38(6):495-503. https://doi.org/10.1080/01616412.2016.1188473.Narasimhalu K., Lee J., Leong Y.L., Ma L., De Silva D.A., Wong M.C. et al. Inflammatory markers and their association with post stroke cognitive decline. Int J Stroke. 2015;10(4):513-518. https://doi.org/10.1111/ijs.12001.Narasimhalu K., Lee J., Leong Y.L., Ma L., De Silva D.A., Wong M.C. et al. Inflammatory markers and their association with post stroke cognitive decline. Int J Stroke. 2015;10(4):513-518. https://doi.org/10.1111/ijs.12001.Iadecola C., Buckwalter M.S., Anrather J. Immune responses to stroke: mechanisms, modulation, and therapeutic potential. J Clin Invest. 2020;130(6):2777-2788. https://doi.org/10.1172/JCI135530.Iadecola C., Buckwalter M.S., Anrather J. Immune responses to stroke: mechanisms, modulation, and therapeutic potential. J Clin Invest. 2020;130(6):2777-2788. https://doi.org/10.1172/JCI135530.Doyle K.P., Quach L.N., Sole M., Axtell R.C., Nguyen T.V., Soler-Llavina GJ. et al. B-lymphocyte-mediated delayed cognitive impairment following stroke. J Neurosci. 2015;35(5):2133-2145. https://doi.org/10.1523/JNEUROSCI.4098-14.2015.Doyle K.P., Quach L.N., Sole M., Axtell R.C., Nguyen T.V., Soler-Llavina GJ. et al. B-lymphocyte-mediated delayed cognitive impairment following stroke. J Neurosci. 2015;35(5):2133-2145. https://doi.org/10.1523/JNEUROSCI.4098-14.2015.Wanner I.B., Anderson MA., Song B., Levine J., Fernandez A., Gray-Thompson Z. et al. Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury. J Neurosci. 2013;33(31):12870-12886. https://doi.org/10.1523/JNEUROSCI.2121-13.2013.Wanner I.B., Anderson MA., Song B., Levine J., Fernandez A., Gray-Thompson Z. et al. Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury. J Neurosci. 2013;33(31):12870-12886. https://doi.org/10.1523/JNEUROSCI. 2121-13.2013.Quesseveur G., David DJ., Gaillard M.C., Pla P, Wu M.V., Nguyen H.T. et al. BDNF overexpression in mouse hippocampal astrocytes promotes local neurogenesis and elicits anxiolytic-like activities. Transl Psychiatry. 2013;3(4):e253. https://doi.org/10.1038/tp.2013.30.Quesseveur G., David DJ., Gaillard M.C., Pla P, Wu M.V., Nguyen H.T. et al. BDNF overexpression in mouse hippocampal astrocytes promotes local neurogenesis and elicits anxiolytic-like activities. Transl Psychiatry. 2013;3(4):e253. https://doi.org/10.1038/tp.2013.30.Wang X., Xuan W., Zhu Z.Y., Li Y., Zhu H., Zhu L. et al. The evolving role of neuro-immune interaction in brain repair after cerebral ischemic stroke. CNS Neurosci Ther. 2018;24(12):1100-1114. https://doi.org/10.1111/cns.13077.Wang X., Xuan W., Zhu Z.Y., Li Y., Zhu H., Zhu L. et al. The evolving role of neuro-immune interaction in brain repair after cerebral ischemic stroke. CNS Neurosci Ther. 2018;24(12):1100-1114. https://doi.org/10.1111/cns.13077.Qiu Y.M., Zhang C.L., Chen A.Q., Wang H.L., Zhou Y.F., Li Y.N., Hu B. Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy? Front Immunol. 2021;(12):678744. https://doi.org/10.3389/fimmu.2021.678744.Qiu Y.M., Zhang C.L., Chen A.Q., Wang H.L., Zhou Y.F., Li Y.N., Hu B. Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy? Front Immunol. 2021;(12):678744. https://doi.org/10.3389/fimmu.2021.678744.Ishikawa M., Cooper D., Russell J., Salter J.W., Zhang J.H., Nanda A., Granger D.N. Molecular determinants of the prothrombogenic and inflammatory phenotype assumed by the postischemic cerebral microcirculation. Stroke. 2003;34(7):1777-17782. https://doi.org/10.1161/01.STR.0000074921.17767.F2.Ishikawa M., Cooper D., Russell J., Salter J.W., Zhang J.H., Nanda A., Granger D.N. Molecular determinants of the prothrombogenic and inflammatory phenotype assumed by the postischemic cerebral microcirculation. Stroke. 2003;34(7):1777-17782. https://doi.org/10.1161/01.STR.0000074921.17767.F2.Angiari S., Donnarumma T., Rossi B., Dusi S., Pietronigro E., Zenaro E. et al. TIM-1 glycoprotein binds the adhesion receptor P-selectin and mediates T cell trafficking during inflammation and autoimmunity. Immunity. 2014;40(4):542-553. https://doi.org/10.1016/j.immuni.2014.03.004.Angiari S., Donnarumma T., Rossi B., Dusi S., Pietronigro E., Zenaro E. et al. TIM-1 glycoprotein binds the adhesion receptor P-selectin and mediates T cell trafficking during inflammation and autoimmunity. Immunity. 2014;40(4):542-553. https://doi.org/10.1016/j.immuni.2014.03.004.Zarbock A., Ley K., McEver R.P, Hidalgo A. Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood. 2011;118(26):6743-6751. https://doi.org/10.1182/blood-2011-07-343566.Zarbock A., Ley K., McEver R.P, Hidalgo A. Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood. 2011;118(26):6743-6751. https://doi.org/10.1182/blood-2011-07-343566.Shichita T., Sugiyama Y., Ooboshi H., Sugimori H., Nakagawa R., Takada I. et al. Pivotal role of cerebral interleukin-17-producing gammadeltaT cells in the delayed phase of ischemic brain injury. Nat Med. 2009;15(8):946-950. https://doi.org/10.1038/nm.1999.Shichita T., Sugiyama Y., Ooboshi H., Sugimori H., Nakagawa R., Takada I. et al. Pivotal role of cerebral interleukin-17-producing gammadeltaT cells in the delayed phase of ischemic brain injury. Nat Med. 2009;15(8):946-950. https://doi.org/10.1038/nm.1999.Gelderblom M., Weymar A., Bernreuther C., Velden J., Arunachalam P, Steinbach K. et al. Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke. Blood. 2012;120(18):3793-3802. https://doi.org/10.1182/blood-2012-02-412726.Gelderblom M., Weymar A., Bernreuther C., Velden J., Arunachalam P, Steinbach K. et al. Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke. Blood. 2012;120(18):3793-3802. https://doi.org/10.1182/blood-2012-02-412726.Vindegaard N., Munoz-Briones C., El Ali H.H., Kristensen l.K., Rasmussen R.S., Johansen F.F., Hasseldam H. T-cells and macrophages peak weeks after experimental stroke: Spatial and temporal characteristics. Neuropathology 2017;37(5):407-414. https://doi.org/10.1111/neup.12387.Vindegaard N., Munoz-Briones C., El Ali H.H., Kristensen L.K., Rasmussen R.S., Johansen F.F., Hasseldam H. T-cells and macrophages peak weeks after experimental stroke: Spatial and temporal characteristics. Neuropathology 2017;37(5):407-414. https://doi.org/10.1111/neup.12387.Miro-Mur F., Urra X., Ruiz-Jaen F., Pedragosa J., Chamorro A., Planas A.M. Antigen-Dependent T Cell Response to Neural Peptides After Human Ischemic Stroke. Front Cell Neurosci. 2020;(14):206. https://doi.org/10.3389/fncel.2020.00206.Miro-Mur F., Urra X., Ruiz-Jaen F., Pedragosa J., Chamorro A., Planas A.M. Antigen-Dependent T Cell Response to Neural Peptides After Human Ischemic Stroke. Front Cell Neurosci. 2020;(14):206. https://doi.org/10.3389/fncel.2020.00206.Gu L., Xiong X., Zhang H., Xu B., Steinberg G.K., Zhao H. Distinctive effects of T cell subsets in neuronal injury induced by cocultured splenocytes in vitro and by in vivo stroke in mice. Stroke. 2012;43(7):1941-1946. https://doi.org/10.1161/STROKEAHA.112.656611.Gu L., Xiong X., Zhang H., Xu B., Steinberg G.K., Zhao H. Distinctive effects of T cell subsets in neuronal injury induced by cocultured splenocytes in vitro and by in vivo stroke in mice. Stroke. 2012;43(7):1941-1946. https://doi.org/10.1161/STROKEAHA.112.656611.Gu L., Jian Z., Stary C., Xiong X. T Cells and Cerebral Ischemic Stroke. Neurochem Res. 2015;40(9):1786-1791. https://doi.org/10.1007/s11064-015-1676-0.Gu L., Jian Z., Stary C., Xiong X. T Cells and Cerebral Ischemic Stroke. Neurochem Res. 2015;40(9):1786-1791. https://doi.org/10.1007/s11064-015-1676-0.Wang L., Yao C., Chen J., Ge Y., Wang C., Wang Y. et al. y5 T Cell in Cerebral Ischemic Stroke: Characteristic, Immunity-Inflammatory Role, and Therapy. Front Neurol. 2022;(13):842212. https://doi.org/10.3389/fneur.2022.842212.Wang L., Yao C., Chen J., Ge Y., Wang C., Wang Y. et al. y5 T Cell in Cerebral Ischemic Stroke: Characteristic, Immunity-Inflammatory Role, and Therapy. Front Neurol. 2022;(13):842212. https://doi.org/10.3389/fneur.2022.842212.Hermann D.M., Kleinschnitz C., Gunzer M. Role of polymorphonuclear neutrophils in the reperfused ischemic brain: insights from cell-type-specific immunodepletion and fluorescence microscopy studies. Ther Adv Neurol Disord. 2018;11:1756286418798607. https://doi.org/10.1177/1756286418798607.Hermann D.M., Kleinschnitz C., Gunzer M. Role of polymorphonuclear neutrophils in the reperfused ischemic brain: insights from cell-type-specific immunodepletion and fluorescence microscopy studies. Ther Adv Neurol Disord. 2018;11:1756286418798607. https://doi.org/10.1177/1756286418798607.Ni P, Dong H., Wang Y., Zhou Q., Xu M., Qian Y., Sun J. IL-17A contributes to perioperative neurocognitive disorders through blood-brain barrier disruption in aged mice. J Neuroinflammation. 2018;15(1):332. https://doi.org/10.1186/s12974-018-1374-3.Ni P, Dong H., Wang Y., Zhou Q., Xu M., Qian Y., Sun J. IL-17A contributes to perioperative neurocognitive disorders through blood-brain barrier disruption in aged mice. J Neuroinflammation. 2018;15(1):332. https://doi.org/10.1186/s12974-018-1374-3.Zhu F., Wang O., Guo C., Wang X., Cao X., Shi Y. et al. IL-17 induces apoptosis of vascular endothelial cells: a potential mechanism for human acute coronary syndrome. Clin Immunol. 2011;141(2):152-160. https://doi.org/10.1016/j.clim.2011.07.003.Zhu F., Wang O., Guo C., Wang X., Cao X., Shi Y. et al. IL-17 induces apoptosis of vascular endothelial cells: a potential mechanism for human acute coronary syndrome. Clin Immunol. 2011;141(2):152-160. https://doi.org/10.1016/j.clim.2011.07.003.Clarkson B.D., Ling C., Shi Y., Harris M.G., Rayasam A., Sun D. et al. T cell-derived interleukin (IL)-21 promotes brain injury following stroke in mice. J Exp Med. 2014;211(4):595-604. https://doi.org/10.1084/jem.20131377.Clarkson B.D., Ling C., Shi Y., Harris M.G., Rayasam A., Sun D. et al. T cell-derived interleukin (IL)-21 promotes brain injury following stroke in mice. J Exp Med. 2014;211(4):595-604. https://doi.org/10.1084/jem.20131377.Dong Y., Hu C., Huang C., Gao J., Niu W., Wang D. et al. Interleukin-22 Plays a Protective Role by Regulating the JAK2-STAT3 Pathway to Improve Inflammation, Oxidative Stress, and Neuronal Apoptosis following Cerebral Ischemia-Reperfusion Injury. Mediators Inflamm. 2021;2021:6621296. https://doi.org/10.1155/2021/6621296.Dong Y., Hu C., Huang C., Gao J., Niu W., Wang D. et al. Interleukin-22 Plays a Protective Role by Regulating the JAK2-STAT3 Pathway to Improve Inflammation, Oxidative Stress, and Neuronal Apoptosis following Cerebral Ischemia-Reperfusion Injury. Mediators Inflamm. 2021;2021:6621296. https://doi.org/10.1155/2021/6621296.Gan Y., Liu Q., Wu W., Yin J.X., Bai X.F., Shen R. et al. Ischemic neurons recruit natural killer cells that accelerate brain infarction. Proc Natl Acad Sci USA. 2014;111(7):2704-2709. https://doi.org/10.1073/pnas.1315943111.Gan Y., Liu Q., Wu W., Yin J.X., Bai X.F., Shen R. et al. Ischemic neurons recruit natural killer cells that accelerate brain infarction. Proc Natl Acad Sci USA. 2014;111(7):2704-2709. https://doi.org/10.1073/pnas.1315943111.Liu Q., Jin W.N., Liu Y., Shi K., Sun H., Zhang F. et al. Brain Ischemia Suppresses Immunity in the Periphery and Brain via Different Neurogenic Innervations. Immunity 2017;46(3):474-487. https://doi.org/10.1016/j.immuni.2017.02.015.Liu Q., Jin W.N., Liu Y., Shi K., Sun H., Zhang F. et al. Brain Ischemia Suppresses Immunity in the Periphery and Brain via Different Neurogenic Innervations. Immunity 2017;46(3):474-487. https://doi.org/10.1016/j.immuni.2017.02.015.Voskoboinik I., Whisstock J.C., Trapani J.A. Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol. 2015;15(6):388-400. https://doi.org/10.1038/nri3839.Voskoboinik I., Whisstock J.C., Trapani J.A. Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol. 2015;15(6):388-400. https://doi.org/10.1038/nri3839.Chu H.X., Kim H.A., Lee S., Moore J.P., Chan C.T., Vinh A. et al. Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia. J Cereb Blood Flow Metab. 2014;34(3):450-459. https://doi.org/10.1038/jcbfm.2013.217.Chu H.X., Kim H.A., Lee S., Moore J.P., Chan C.T., Vinh A. et al. Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia. J Cereb Blood Flow Metab. 2014;34(3):450-459. https://doi.org/10.1038/jcbfm.2013.217.Chaitanya G.V., Eeka P., Munker R., Alexander J.S., Babu P.P. Role of cytotoxic protease granzyme-b in neuronal degeneration during human stroke. Brain Pathol. 2011;21(1):16-30. https://doi.org/10.1111/j.1750-3639.2010.00426.x.Chaitanya G.V., Eeka P., Munker R., Alexander J.S., Babu P.P. Role of cytotoxic protease granzyme-b in neuronal degeneration during human stroke. Brain Pathol. 2011;21(1):16-30. https://doi.org/10.1111/j.1750-3639.2010.00426.x.Liesz A., Hu X., Kleinschnitz C., Offner H. Functional role of regulatory lymphocytes in stroke: facts and controversies. Stroke. 2015;46(5):1422-1430. https://doi.org/10.1161/STROKEAHA.114.008608.Liesz A., Hu X., Kleinschnitz C., Offner H. FunctionaL role of regulatory lymphocytes in stroke: facts and controversies. Stroke. 2015;46(5):1422-1430. https://doi.org/10.1161/STROKEAHA.114.008608.Khantakova J.N., Bulygin A.S., Sennikov S.V. The Regulatory-T-Cell Memory Phenotype: What We Know. Cells. 2022;11(10):1687. https://doi.org/10.3390/cells11101687.Khantakova J.N., Bulygin A.S., Sennikov S.V. The Regulatory-T-Cell Memory Phenotype: What We Know. Cells. 2022;11(10):1687. https://doi.org/10.3390/cells11101687.Jayaraj R.L., Azimullah S., Beiram R., Jalal F.Y., Rosenberg G.A. Neuroinflammation: friend and foe for ischemic stroke. J Neuroinflammation. 2019;16(1):142. https://doi.org/10.1186/s12974-019-1516-2.Jayaraj R.L., Azimullah S., Beiram R., Jalal F.Y., Rosenberg G.A. Neuroinflammation: friend and foe for ischemic stroke. J Neuroinflammation. 2019;16(1):142. https://doi.org/10.1186/s12974-019-1516-2.Liesz A., Zhou W., Na S.Y., Hammerling GJ., Garbi N., Karcher S. et al. Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke. J Neurosci. 2013;33(44):17350-17362. https://doi.org/10.1523/JNEUROSCI.4901-12.2013.Liesz A., Zhou W., Na S.Y., Hammerling GJ., Garbi N., Karcher S. et al. Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke. J Neurosci. 2013;33(44):17350-17362. https://doi.org/10.1523/JNEUROSCI.4901-12.2013.Protti G.G., Gagliardi RJ., Forte W.C., Sprovieri S.R. Interleukin-10 may protect against progressing injury during the acute phase of ischemic stroke. Arq Neuropsiquiatr. 2013;71(11):846-851. https://doi.org/10.1590/0004-282X20130168.Protti G.G., Gagliardi RJ., Forte W.C., Sprovieri S.R. Interleukin-10 may protect against progressing injury during the acute phase of ischemic stroke. Arq Neuropsiquiatr. 2013;71(11):846-851. https://doi.org/10.1590/0004-282X20130168.Ooboshi H., Ibayashi S., Shichita T., Kumai Y, Takada J., Ago T. et al. Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia. Circulation. 2005;111(7):913-919. https://doi.org/10.1161/01.CIR.0000155622.68580.DC.Ooboshi H., Ibayashi S., Shichita T., Kumai Y, Takada J., Ago T. et al. Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia. Circulation. 2005;111(7):913-919. https://doi.org/10.1161/01.CIR.0000155622.68580.DC.Xie L., Choudhury G.R., Winters A., Yang S.H., Jin K. Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10. Eur J Immunol. 2015;45(1):180-191. https://doi.org/10.1002/eji.201444823.Xie L., Choudhury G.R., Winters A., Yang S.H., Jin K. Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10. Eur J Immunol. 2015;45(1):180-191. https://doi.org/10.1002/eji.201444823.Ramiro L., Simats A., Garcia-Berrocoso T., Montaner J. Inflammatory molecules might become both biomarkers and therapeutic targets for stroke management. Ther Adv Neurol Disord. 2018;11:1756286418789340. https://doi.org/10.1177/1756286418789340.Ramiro L., Simats A., Garcia-Berrocoso T., Montaner J. Inflammatory molecules might become both biomarkers and therapeutic targets for stroke management. Ther Adv Neurol Disord. 2018;11:1756286418789340. https://doi.org/10.1177/1756286418789340.Maida C.D., Norrito R.L., Daidone M., Tuttolomondo A., Pinto A. Neuroinflammatory Mechanisms in Ischemic Stroke: Focus on Cardioembolic Stroke, Background, and Therapeutic Approaches. Int J Mol Sci. 2020;21(18):6454. https://doi.org/10.3390/ijms21186454.Maida C.D., Norrito R.L., Daidone M., Tuttolomondo A., Pinto A. Neuroinflammatory Mechanisms in Ischemic Stroke: Focus on Cardioembolic Stroke, Background, and Therapeutic Approaches. Int J Mol Sci. 2020;21(18):6454. https://doi.org/10.3390/ijms21186454.Monson N.L., Ortega S.B., Ireland SJ., Meeuwissen AJ., Chen D., Plautz EJ. et al. Repetitive hypoxic preconditioning induces an immunosuppressed B cell phenotype during endogenous protection from stroke. J Neuroinflammation. 2014;(11):22. https://doi.org/10.1186/1742-2094-11-22.Monson N.L., Ortega S.B., Ireland SJ., Meeuwissen AJ., Chen D., Plautz EJ. et al. Repetitive hypoxic preconditioning induces an immunosuppressed B cell phenotype during endogenous protection from stroke. J Neuroinflammation. 2014;(11):22. https://doi.org/10.1186/1742-2094-11-22.Esen N., Rainey-Barger E.K., Huber A.K., Blakely P.K., Irani D.N. Type-I interferons suppress microglial production of the lymphoid chemokine, CXCL13. Glia. 2014;62(9):1452-1462. httpsv7doi.org/10.1002/glia.22692.Esen N., Rainey-Barger E.K., Huber A.K., Blakely P.K., Irani D.N. Type-I interferons suppress microglial production of the lymphoid chemokine, CXCL13. Glia. 2014;62(9):1452-1462. httpsv7doi.org/10.1002/glia.22692.Pitzalis C., Jones G.W., Bombardieri M., Jones S.A. Ectopic lymphoid-like structures in infection, cancer and autoimmunity. Nat Rev Immunol. 2014;14(7):447-462. https://doi.org/10.1038/nri3700Pitzalis C., Jones G.W., Bombardieri M., Jones S.A. Ectopic lymphoid-like structures in infection, cancer and autoimmunity. Nat Rev Immunol. 2014;14(7):447-462. https://doi.org/10.1038/nri3700Doyle K.P., Buckwalter M.S. Does B lymphocyte-mediated autoimmunity contribute to post-stroke dementia? Brain Behav Immun. 2017;(64):1-8. https://doi.org/10.1016/j.bbi.2016.08.009.Doyle K.P., Buckwalter M.S. Does B lymphocyte-mediated autoimmunity contribute to post-stroke dementia? Brain Behav Immun. 2017;(64):1-8. https://doi.org/10.1016/j.bbi.2016.08.009.Kim E., Cho S. CNS and peripheral immunity in cerebral ischemia: partition and interaction. Exp Neurol. 2021;(335):113508. https://doi.org/10.1016/j.expneurol.2020.113508.Kim E., Cho S. CNS and peripheral immunity in cerebral ischemia: partition and interaction. Exp Neurol. 2021;(335):113508. https://doi.org/10.1016/j.expneurol.2020.113508.Seifert H.A., Vandenbark AA., Offner H. Regulatory B cells in experimental stroke. Immunology. 2018;154(2):169-177. https://doi.org/10.1111/imm.12887.Seifert H.A., Vandenbark AA., Offner H. Regulatory B cells in experimental stroke. Immunology. 2018;154(2):169-177. https://doi.org/10.1111/imm.12887.

The authors declare that there are no conflicts of interest present.