mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2018-1-19-34mimmun-1429Research ArticleОБЗОРЫREVIEWSИММУНОПАТОГЕНЕТИЧЕСКИЕ АСПЕКТЫ ИШЕМИЧЕСКОГО ИНСУЛЬТАIMMUNOPATHOGENETIC ASPECTS OF ISCHEMIC STROKEЧерныхЕ. Р.ChernykhE. R.

д.м.н., профессор, член-корр. РАН, заведующая лабораторией клеточной иммунотерапии

PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Head, Laboratory of Cellular Immunotherapy

ct_lab@mail.ruШевелаЕ. Я.ShevelaE. Ya.

д.м.н., ведущий научный сотрудник лаборатории клеточной иммунотерапии

PhD, MD (Medicine), Leading Research Associate, Laboratory of Cellular Immunotherapy

ct_lab@mail.ruМорозовС. А.MorozovS. A.

аспирант лаборатории клеточной иммунотерапии

Postgraduate Student, Laboratory of Cellular Immunotherapy

ct_lab@mail.ruОстанинА. А.OstaninA. A.

д.м.н., профессор, главный научный сотрудник лаборатории клеточной иммунотерапии

PhD, MD (Medicine), Professor, Main Research Associate, Laboratory of Cellular Immunotherapy

ct_lab@mail.ruФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии», г. НовосибирскРоссияResearch Institute of Fundamental and Clinical Immunology, NovosibirskRussian Federation2018100120182011934Copyright © Черных Е.Р., Шевела Е.Я., Морозов С.А., Останин А.А., 20182018Черных Е.Р., Шевела Е.Я., Морозов С.А., Останин А.А.Chernykh E.R., Shevela E.Y., Morozov S.A., Ostanin A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1429

Иммунная система играет ключевую роль в патогенезе ишемического инсульта. Ишемическое поражение головного мозга приводит к разрушению клеток и белков внеклеточного матрикса и высвобождению молекул «опасности», которые вызывают быструю активацию врожденного иммунитета и индуцируют реакции адаптивного иммунитета с аутоиммунной направленностью. Клетки врожденного иммунитета ответственны за элиминацию клеточного и внеклеточного детрита и тканевую репарацию, однако также вовлечены в запуск постишемического воспаления, вызывающего повреждение мозговой ткани. Развивающиеся через несколько дней реакции адаптивного иммунитета, направленные против собственных антигенов, не имеют отношения к повреждению нервной ткани в остром периоде. Клетки адаптивного иммунитета способны регулировать активность микроглии и стимулировать процессы восстановления в центральной нервной системе. Тем не менее длительная персистенция сенсибилизированных к мозгоспецифическим антигенам лимфоцитов может быть причастна к атрофии коры головного мозга и развитию деменции в отдаленном периоде инсульта. Иммунный ответ на ишемическое поражение мозга имеет как локальные, так и системные проявления. При этом, в отличие от продолжительного интрацеребрального воспаления в зоне инфаркта и окружающих тканях, системный воспалительный ответ на периферии быстро сменяется развитием иммуносупрессии, что подтверждается лимфопенией, атрофией лимфоидных органов и дефектом функциональной активности иммунных клеток. Иммуносупрессия во многом обусловлена активацией симпатоадреналовой системы и направлена на ограничение воспаления и аутоиммунных реакций. Тем не менее, избыточные проявления иммуносупрессии приводят к развитию инфекционных осложнений, часто являющихся причиной летального исхода, а также могут негативно сказываться на эффективности репаративных процессов. В настоящем обзоре представлены экспериментальные и клинические данные, характеризующие реакции врожденного и приобретенного иммунитета в ответ на церебральную ишемию. Кроме того, в обзоре обсуждается патогенетическая значимость иммунных клеток и опосредованных ими позитивных и негативных эффектов, осмысление которых позволит разработать новые подходы к лечению ишемического инсульта.

 

Immune system plays a key role in pathogenesis of ischemic stroke. Ischemic brain injury causes destruction of cells and extracellular matrix proteins, and the release of „danger“ molecules that cause rapid activation of innate immunity, and induce adaptive autoimmune reactions. The cells of innate immunity are responsible for elimination of cellular and extracellular debris and tissue repair, being, however, involved in post-ischemic inflammation causing brain injury. An adaptive immune response which develops within a few days is directed against self-antigens, being not related to nervous tissue damage in acute phase of stroke. The cells of adaptive immunity are able to regulate microglial activity and promote repair processes in the central nervous system. However, long-term persistence of lymphocytes with reactivity for brain-derived antigens may be involved into the atrophy of cerebral cortex, and development of dementia in remote post-stroke period. Immune response following ischemic brain stroke is manifesting by local and systemic reactions. Nevertheless, in contrast to prolonged local intracerebral inflammation in infarction area, and peri-infarction region, a systemic inflammatory response is quickly replaced by development of immunosuppression, as evidenced by lymphopenia, lymphoid organ atrophy and defective functions of immune cells. Immunosuppression is largely due to activation of sympathoadrenal system, aiming for limitation of inflammatory and autoimmune reactions. However, excessive immunosuppression leads to development of infectious complications, which may often cause lethal outcomes, and also may have a negative impact on efficiency of repair processes. The present review provides experimental and clinical data describing the innate and adaptive immune reactions in response to cerebral ischemia. Moreover, this review discusses possible pathogenetic importance of immune cells and their positive or negative effects, thus allowing further development of new therapeutic approaches for treatment of ischemic stroke.

ишемический инсультврожденный иммунитетадаптивный иммунитетаутоиммунитетнейровоспалениенейропротекциясистемный иммунный ответлокальный иммунный ответинсульт-индуцированный иммунодефицитischemic strokeinnate immunityadaptive immunityautoimmunityneuroinflammationneuroprotectionsystemic immune responselocal immune responsestroke-induced immunodeficiencyReferencesAjmo C.T. Jr., Vernon D.O., Collier L., Hall A.A., Garbuzova-Davis S., Willing A., Pennypacker K.R. The spleen contributes to stroke-induced neurodegeneration. J. Neurosci. Res., 2008, Vol. 86, no. 10, pp. 2227-2234.Ajmo C.T. Jr., Vernon D.O., Collier L., Hall A.A., Garbuzova-Davis S., Willing A., Pennypacker K.R. The spleen contributes to stroke-induced neurodegeneration. J. Neurosci. Res., 2008, Vol. 86, no. 10, pp. 2227-2234.Al’Qteishat A., Gaffney J., Krupinski J., Rubio F., West D., Kumar S., Kumar P., Mitsios N., Slevin M. Changes in hyaluronan production and metabolism following ischaemic stroke in man. Brain, 2006, Vol. 129, no. 8, pp. 2158-2176Al’Qteishat A., Gaffney J., Krupinski J., Rubio F., West D., Kumar S., Kumar P., Mitsios N., Slevin M. Changes in hyaluronan production and metabolism following ischaemic stroke in man. Brain, 2006, Vol. 129, no. 8, pp. 2158-2176Anne M., Juha K., Timo M., Mikko T., Olli V., Kyosti S., Heikki H., Vilho M. Neurohormonal activation in ischemic stroke: effects of acute phase disturbances on long-term mortality. Curr. Neurovasc. Res., 2007, Vol. 4, no. 3, pp. 170-175.Anne M., Juha K., Timo M., Mikko T., Olli V., Kyosti S., Heikki H., Vilho M. Neurohormonal activation in ischemic stroke: effects of acute phase disturbances on long-term mortality. Curr. Neurovasc. Res., 2007, Vol. 4, no. 3, pp. 170-175.Becker K., Kindrick D., McCarron R., Hallenbeck J., Winn R. Adoptive transfer of myelin basic protein-tolerized splenocytes to naive animals reduces infarct size: a role for lymphocytes in ischemic brain injury? Stroke, 2003, Vol. 34, no. 7, pp. 1809-1815.Becker K., Kindrick D., McCarron R., Hallenbeck J., Winn R. Adoptive transfer of myelin basic protein-tolerized splenocytes to naive animals reduces infarct size: a role for lymphocytes in ischemic brain injury? Stroke, 2003, Vol. 34, no. 7, pp. 1809-1815.Becker K.J., Kalil A.J., Tanzi P., Zierath D.K., Savos A.V., Gee J.M., Hadwin J., Carter K.T., Shibata D., Cain K.C. Autoimmune responses to the brain aſter stroke are associated with worse outcome. Stroke, 2011, Vol. 42, no. 10, pp. 2763-2769.Becker K.J., Kalil A.J., Tanzi P., Zierath D.K., Savos A.V., Gee J.M., Hadwin J., Carter K.T., Shibata D., Cain K.C. Autoimmune responses to the brain aſter stroke are associated with worse outcome. Stroke, 2011, Vol. 42, no. 10, pp. 2763-2769.Becker K.J., Kindrick D.L., Lester M.P., Shea C., Ye Z.C. Sensitization to brain antigens aſter stroke is augmented by lipopolysaccharide. J. Cereb. Blood Flow Metab., 2005, Vol. 25, no.12, pp. 1634-1644.Becker K.J., Kindrick D.L., Lester M.P., Shea C., Ye Z.C. Sensitization to brain antigens aſter stroke is augmented by lipopolysaccharide. J. Cereb. Blood Flow Metab., 2005, Vol. 25, no.12, pp. 1634-1644.Bornstein N.M., Aronovich B., Korczyn A.D., Shavit S., Michaelson D.M., Chapman J. Antibodies to brain antigens following stroke. Neurology, 2001, Vol. 56, no. 4, pp. 529-530.Bornstein N.M., Aronovich B., Korczyn A.D., Shavit S., Michaelson D.M., Chapman J. Antibodies to brain antigens following stroke. Neurology, 2001, Vol. 56, no. 4, pp. 529-530.Bowen K.K., Dempsey R.J., Vemuganti R. Adult interleukin-6 knockout mice show compromised neurogenesis. Neuroreport, 2011, Vol. 22, no. 3, pp. 126-130.Bowen K.K., Dempsey R.J., Vemuganti R. Adult interleukin-6 knockout mice show compromised neurogenesis. Neuroreport, 2011, Vol. 22, no. 3, pp. 126-130.Brait V.H., Arumugam T.V., Drummond G.R., Sobey C.G. Importance of T lymphocytes in brain injury, immunodeficiency, and recovery aſter cerebral ischemia. J. Cereb. Blood Flow Metab., 2012, Vol. 32, no. 4, pp. 598-611.Brait V.H., Arumugam T.V., Drummond G.R., Sobey C.G. Importance of T lymphocytes in brain injury, immunodeficiency, and recovery aſter cerebral ischemia. J. Cereb. Blood Flow Metab., 2012, Vol. 32, no. 4, pp. 598-611.Brait V.H., Jackman K.A., Walduck A.K., Selemidis S., Diep H., Mast A.E., Guida E., Broughton B.R.S., Drummond G.R., Sobey C.G. Mechanisms contributing to cerebral infarct size aſter stroke: gender, reperfusion, T lymphocytes, and Nox2-derived superoxide. J. Cereb. Blood Flow Metab., 2010, Vol. 30, no. 7, pp. 1306-1317.Brait V.H., Jackman K.A., Walduck A.K., Selemidis S., Diep H., Mast A.E., Guida E., Broughton B.R.S., Drummond G.R., Sobey C.G. Mechanisms contributing to cerebral infarct size aſter stroke: gender, reperfusion, T lymphocytes, and Nox2-derived superoxide. J. Cereb. Blood Flow Metab., 2010, Vol. 30, no. 7, pp. 1306-1317.Breckwoldt M.O., Chen J.W., Stangenberg L, Aikawa E., Rodriguez E., Qiu S., Moskowitz M.A., Weissleder R. Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc. Natl. Acad. Sci. USA, 2008, Vol. 105, no. 47, pp. 18584-18589.Breckwoldt M.O., Chen J.W., Stangenberg L, Aikawa E., Rodriguez E., Qiu S., Moskowitz M.A., Weissleder R. Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc. Natl. Acad. Sci. USA, 2008, Vol. 105, no. 47, pp. 18584-18589.Brooks S.D., Spears C., Cummings C., van Gilder R.L., Stinehart K.R., Gutmann L., Domico J., Culp S., Carpenter J., Rai A., Barr T.L. Admission neutrophil–lymphocyte ratio predicts 90 day outcome aſter endovascular stroke therapy. J. Neurointerv. Surg., 2014, Vol. 6, no. 8, pp. 578-583.Brooks S.D., Spears C., Cummings C., van Gilder R.L., Stinehart K.R., Gutmann L., Domico J., Culp S., Carpenter J., Rai A., Barr T.L. Admission neutrophil–lymphocyte ratio predicts 90 day outcome aſter endovascular stroke therapy. J. Neurointerv. Surg., 2014, Vol. 6, no. 8, pp. 578-583.Buisson A., Nicole O., Docagne F., Sartelet H., Mackenzie E.T., Vivien D. Up-regulation of a serine protease inhibitor in astrocytes mediates the neuroprotective activity of transforming growth factor β1. FASEB J., 1998, Vol. 12, no. 15, pp. 1683-1691.Buisson A., Nicole O., Docagne F., Sartelet H., Mackenzie E.T., Vivien D. Up-regulation of a serine protease inhibitor in astrocytes mediates the neuroprotective activity of transforming growth factor β1. FASEB J., 1998, Vol. 12, no. 15, pp. 1683-1691.Caligiuri G., Nicoletti A., Poirier B., Hansson G.K. Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J. Clin. Invest., 2002, Vol. 109, no. 6, pp. 745-753.Caligiuri G., Nicoletti A., Poirier B., Hansson G.K. Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J. Clin. Invest., 2002, Vol. 109, no. 6, pp. 745-753.Carmichael S.T. Translating the frontiers of brain repair to treatments: starting not to break the rules. Neurobiol. Dis., 2010, Vol. 37, no. 2, pp. 237-242.Carmichael S.T. Translating the frontiers of brain repair to treatments: starting not to break the rules. Neurobiol. Dis., 2010, Vol. 37, no. 2, pp. 237-242.Chamorro A., Urra X., Planas A.M. Infection aſter acute ischemic stroke: a manifestation of brain-induced immunodepression. Stroke, 2007, Vol. 38, no. 3, pp. 1097-1103.Chamorro A., Urra X., Planas A.M. Infection aſter acute ischemic stroke: a manifestation of brain-induced immunodepression. Stroke, 2007, Vol. 38, no. 3, pp. 1097-1103.Chamorro A., Meisel A., Planas A.M., Urra X., van de Beek D., Veltkamp R. The immunology of acute stroke. Nat. Rev. Neurol., 2012, Vol. 8, no. 7, pp. 401-410.Chamorro A., Meisel A., Planas A.M., Urra X., van de Beek D., Veltkamp R. The immunology of acute stroke. Nat. Rev. Neurol., 2012, Vol. 8, no. 7, pp. 401-410.Chen S., Wu H., Klebe D., Hong Y., Zhang J., Tang J. Regulatory T cell in stroke: a new paradigm for immune regulation. Clin. Dev. Immunol., 2013, Vol. 2013, Art. ID 689827, 9 p.Chen S., Wu H., Klebe D., Hong Y., Zhang J., Tang J. Regulatory T cell in stroke: a new paradigm for immune regulation. Clin. Dev. Immunol., 2013, Vol. 2013, Art. ID 689827, 9 p.Chen Y., Hallenbeck J.M., Ruetzler C., Bol D., Thomas K., Berman N.E., Vogel S.N. Overexpression of monocyte chemoattractant protein 1 in the brain exacerbates ischemic brain injury and is associated with recruitment of inflammatory cells. J. Cereb. Blood Flow Metab., 2003, Vol. 23, no. 6, pp. 748-755.Chen Y., Hallenbeck J.M., Ruetzler C., Bol D., Thomas K., Berman N.E., Vogel S.N. Overexpression of monocyte chemoattractant protein 1 in the brain exacerbates ischemic brain injury and is associated with recruitment of inflammatory cells. J. Cereb. Blood Flow Metab., 2003, Vol. 23, no. 6, pp. 748-755.Chen Y., Bodhankar S., Murphy S.J., Vandenbark A.A., Alkayed N.J., Offner H. Intrastriatal B-cell administration limits infarct size aſter stroke in B-cell deficient mice. Metab. Brain Dis., 2012, Vol. 27, no. 4, pp. 487-493.Chen Y., Bodhankar S., Murphy S.J., Vandenbark A.A., Alkayed N.J., Offner H. Intrastriatal B-cell administration limits infarct size aſter stroke in B-cell deficient mice. Metab. Brain Dis., 2012, Vol. 27, no. 4, pp. 487-493.Chu H.X., Broughton B.R., Kim H.A., Lee S., Drummond G.R., Sobey C.G. Evidence that Ly6C(hi) monocytes are protective in acute ischemic stroke by promoting M2 macrophage polarization. Stroke, 2015, Vol. 46, no. 7, pp. 1929-1937.Chu H.X., Broughton B.R., Kim H.A., Lee S., Drummond G.R., Sobey C.G. Evidence that Ly6C(hi) monocytes are protective in acute ischemic stroke by promoting M2 macrophage polarization. Stroke, 2015, Vol. 46, no. 7, pp. 1929-1937.Clark W.M., Rinker L.G., Lessov N.S., Hazel K., Hill J.K., Stenzel-Poore M., Eckenstein F. Lack of interleukin-6 expression is not protective against focal central nervous system ischemia. Stroke, 2000, Vol. 31, no. 7, pp. 1715-1720.Clark W.M., Rinker L.G., Lessov N.S., Hazel K., Hill J.K., Stenzel-Poore M., Eckenstein F. Lack of interleukin-6 expression is not protective against focal central nervous system ischemia. Stroke, 2000, Vol. 31, no. 7, pp. 1715-1720.Cuartero M.I., Ballesteros I., Moraga A., Nombela F., Vivancos J., Hamilton J.A., Corbí Á.L., Lizasoain I., Moro M.A. N2 neutrophils, novel players in brain inflammation aſter stroke: modulation by the PPARγ agonist rosiglitazone. Stroke, 2013, Vol. 44, no. 12, pp. 3498-3508,Cuartero M.I., Ballesteros I., Moraga A., Nombela F., Vivancos J., Hamilton J.A., Corbí Á.L., Lizasoain I., Moro M.A. N2 neutrophils, novel players in brain inflammation aſter stroke: modulation by the PPARγ agonist rosiglitazone. Stroke, 2013, Vol. 44, no. 12, pp. 3498-3508,Denes A., McColl B.W., Leow-Dyke S.F., Chapman K.Z., Humphreys N.E., Grencis R.K., Allan S.M., Rothwell N.J. Experimental stroke-induced changes in the bone marrow reveal complex regulation of leukocyte responses. J. Cereb. Blood Flow Metab., 2011, Vol. 31, no. 4, pp. 1036-1050.Denes A., McColl B.W., Leow-Dyke S.F., Chapman K.Z., Humphreys N.E., Grencis R.K., Allan S.M., Rothwell N.J. Experimental stroke-induced changes in the bone marrow reveal complex regulation of leukocyte responses. J. Cereb. Blood Flow Metab., 2011, Vol. 31, no. 4, pp. 1036-1050.Denes A., Vidyasagar R., Feng J., Narvainen J., McColl B.W., Kauppinen R.A., Allan S.M. Proliferating resident microglia aſter focal cerebral ischaemia in mice. J. Cereb. Blood Flow Metab., 2007, Vol. 27, no. 12, pp. 1941-1953.Denes A., Vidyasagar R., Feng J., Narvainen J., McColl B.W., Kauppinen R.A., Allan S.M. Proliferating resident microglia aſter focal cerebral ischaemia in mice. J. Cereb. Blood Flow Metab., 2007, Vol. 27, no. 12, pp. 1941-1953.Dimitrijevic O.B., Stamatovic S.M., Keep R.F., Andjelkovic A.V. Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice. Stroke, 2007, Vol. 38, no. 4, pp. 1345-1353.Dimitrijevic O.B., Stamatovic S.M., Keep R.F., Andjelkovic A.V. Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice. Stroke, 2007, Vol. 38, no. 4, pp. 1345-1353.Dziedzic T., Slowik A., Pera J., Szczudlik A. Beta-blockers reduce the risk of early death in ischemic stroke. J. Neurol. Sci., 2007, Vol. 252, no. 1, pp. 53-56.Dziedzic T., Slowik A., Pera J., Szczudlik A. Beta-blockers reduce the risk of early death in ischemic stroke. J. Neurol. Sci., 2007, Vol. 252, no. 1, pp. 53-56.Easton A.S. Neutrophils and stroke – can neutrophils mitigate disease in the central nervous system? Int. Immunopharmacol., 2013, Vol. 17, no. 4, pp. 1218-1225.Easton A.S. Neutrophils and stroke – can neutrophils mitigate disease in the central nervous system? Int. Immunopharmacol., 2013, Vol. 17, no. 4, pp. 1218-1225.el Ali A., Rivest S. Microglia in Alzheimer’s disease: a multifaceted relationship. Brain Behav. Immun., 2016, Vol. 55, pp. 138-150.el Ali A., Rivest S. Microglia in Alzheimer’s disease: a multifaceted relationship. Brain Behav. Immun., 2016, Vol. 55, pp. 138-150.Emsley H.C., Smith C.J., Georgiou R.F., Vail A., Hopkins S.J., Rothwell N.J., Tyrrell P.J. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. J. Neurol. Neurosurg. Psychiatry, 2005, Vol. 76, no. 10, pp. 1366-1372.Emsley H.C., Smith C.J., Georgiou R.F., Vail A., Hopkins S.J., Rothwell N.J., Tyrrell P.J. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. J. Neurol. Neurosurg. Psychiatry, 2005, Vol. 76, no. 10, pp. 1366-1372.Emsley H.C., Smith C.J., Georgiou R.F., Vail A., Tyrrell P.J., Barberan E.M., Rothwell N.J., Hopkins S.J. Correlation of systemic inflammatory response with infarct volume in acute ischemic stroke patients. Stroke, 2005, Vol. 36, no. 2, pp. 228-229.Emsley H.C., Smith C.J., Georgiou R.F., Vail A., Tyrrell P.J., Barberan E.M., Rothwell N.J., Hopkins S.J. Correlation of systemic inflammatory response with infarct volume in acute ischemic stroke patients. Stroke, 2005, Vol. 36, no. 2, pp. 228-229.Emsley H.C., Smith C.J., Gavin C.M., Georgiou R.F., Vail A., Barberan E.M., Hallenbeck J.M., del Zoppo G.J., Rothwell N.J., Tyrrell P.J., Hopkins S.J. An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. J. Neuroimmunol., 2003, Vol. 139, no. 1-2, pp. 93-101.Emsley H.C., Smith C.J., Gavin C.M., Georgiou R.F., Vail A., Barberan E.M., Hallenbeck J.M., del Zoppo G.J., Rothwell N.J., Tyrrell P.J., Hopkins S.J. An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. J. Neuroimmunol., 2003, Vol. 139, no. 1-2, pp. 93-101.Fonarow G.C., Smith E.E., Saver J.L., Reeves M.J., Bhatt D.L., Grau-Sepulveda M.V., Olson D.M., Hernandez A.F., Peterson E.D., Schwamm L.H. Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. Circulation, 2011, Vol. 123, no. 7, pp. 750-758.Fonarow G.C., Smith E.E., Saver J.L., Reeves M.J., Bhatt D.L., Grau-Sepulveda M.V., Olson D.M., Hernandez A.F., Peterson E.D., Schwamm L.H. Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. Circulation, 2011, Vol. 123, no. 7, pp. 750-758.Gee J.M., Kalil A., Thullbery M., Becker K.J. Induction of immunologic tolerance to myelin basic protein prevents central nervous system autoimmunity and improves outcome aſter stroke. Stroke, 2008, Vol. 39, no. 5, pp. 1575-1582.Gee J.M., Kalil A., Thullbery M., Becker K.J. Induction of immunologic tolerance to myelin basic protein prevents central nervous system autoimmunity and improves outcome aſter stroke. Stroke, 2008, Vol. 39, no. 5, pp. 1575-1582.Geissmann F., Manz M.G, Jung S., Sieweke M.H., Merad M., Ley K. Development of monocytes, macrophages, and dendritic cells. Science, 2010, Vol. 327, no. 5966, pp. 656-661.Geissmann F., Manz M.G, Jung S., Sieweke M.H., Merad M., Ley K. Development of monocytes, macrophages, and dendritic cells. Science, 2010, Vol. 327, no. 5966, pp. 656-661.Ginis I., Jaiswal R., Klimanis D., Liu J., Greenspon J., Hallenbeck J.M. TNF-alpha-induced tolerance to ischemic injury involves differential control of NF-kappaB transactivation: the role of NF-kappaB association with p300 adaptor. J. Cereb. Blood Flow Metab., 2002, Vol. 22, no. 2, pp. 142-152.Ginis I., Jaiswal R., Klimanis D., Liu J., Greenspon J., Hallenbeck J.M. TNF-alpha-induced tolerance to ischemic injury involves differential control of NF-kappaB transactivation: the role of NF-kappaB association with p300 adaptor. J. Cereb. Blood Flow Metab., 2002, Vol. 22, no. 2, pp. 142-152.Gliem M., Schwaninger M., Jander S. Protective features of peripheral monocytes/macrophages in stroke. Biochim. Biophys. Acta, 2016, Vol. 1862, no. 3, pp. 329-338.Gliem M., Schwaninger M., Jander S. Protective features of peripheral monocytes/macrophages in stroke. Biochim. Biophys. Acta, 2016, Vol. 1862, no. 3, pp. 329-338.Gombault A., Baron L., Couillin I. ATP release and purinergic signaling in NLRP3 inflammasome activation. Front. Immunol., 2013, Vol. 3, p. 414.Gombault A., Baron L., Couillin I. ATP release and purinergic signaling in NLRP3 inflammasome activation. Front. Immunol., 2013, Vol. 3, p. 414.Graber J.J., Dhib-Jalbut S. Protective autoimmunity in the nervous system. Pharmacol. Ther., 2009, Vol. 121, no. 2, pp. 147-159.Graber J.J., Dhib-Jalbut S. Protective autoimmunity in the nervous system. Pharmacol. Ther., 2009, Vol. 121, no. 2, pp. 147-159.Greenberg D.A., Jin K. Growth factors and stroke. NeuroRx., 2006, Vol. 3, no. 4, pp. 458-465.Greenberg D.A., Jin K. Growth factors and stroke. NeuroRx., 2006, Vol. 3, no. 4, pp. 458-465.Grilli M., Barbieri I., Basudev H., Brusa R., Casati C., Lozza G., Ongini E. Interleukin-10 modulates neuronal threshold of vulnerability to ischaemic damage. Eur. J. Neurosci., 2000, Vol. 12, no. 7, pp. 2265-2272.Grilli M., Barbieri I., Basudev H., Brusa R., Casati C., Lozza G., Ongini E. Interleukin-10 modulates neuronal threshold of vulnerability to ischaemic damage. Eur. J. Neurosci., 2000, Vol. 12, no. 7, pp. 2265-2272.Haeusler K.G., Schmidt W.U., Foehring F., Meisel C., Guenther C., Brunecker P., Kunze C., Helms T., Dirnagl U., Volk H.D., Villringer A. Immune responses aſter acute ischemic stroke or myocardial infarction. Int. J. Cardiol., 2012, Vol. 155, no. 3, pp. 372-377.Haeusler K.G., Schmidt W.U., Foehring F., Meisel C., Guenther C., Brunecker P., Kunze C., Helms T., Dirnagl U., Volk H.D., Villringer A. Immune responses aſter acute ischemic stroke or myocardial infarction. Int. J. Cardiol., 2012, Vol. 155, no. 3, pp. 372-377.Hayakawa K., Pham L.D., Arai K., Lo E.H. High-mobility group box 1: an amplifier of stem and progenitor cell activity aſter stroke. Acta Neurochir. Suppl., 2013, Vol. 118, pp.31-38.Hayakawa K., Pham L.D., Arai K., Lo E.H. High-mobility group box 1: an amplifier of stem and progenitor cell activity aſter stroke. Acta Neurochir. Suppl., 2013, Vol. 118, pp.31-38.Hervé J., Dubreil L., Tardif V., Terme M., Pogu S., Anegon I., Rozec B., Gauthier C., Bach J.M., Blancou P. β2-adrenoreceptor agonist inhibits antigen cross-presentation by dendritic cells. J. Immunol., 2013, Vol. 190, no. 7, pp. 3163-3171.Hervé J., Dubreil L., Tardif V., Terme M., Pogu S., Anegon I., Rozec B., Gauthier C., Bach J.M., Blancou P. β2-adrenoreceptor agonist inhibits antigen cross-presentation by dendritic cells. J. Immunol., 2013, Vol. 190, no. 7, pp. 3163-3171.Hofstetter H.H., Sewell D.L., Liu F., Sandor M., Forsthuber T., Lehmann P.V., Fabry Z. Autoreactive T cells promote post-traumatic healing in the central nervous system. J. Neuroimmunol., 2003, Vol. 134, no. 1-2, pp. 25-34.Hofstetter H.H., Sewell D.L., Liu F., Sandor M., Forsthuber T., Lehmann P.V., Fabry Z. Autoreactive T cells promote post-traumatic healing in the central nervous system. J. Neuroimmunol., 2003, Vol. 134, no. 1-2, pp. 25-34.Hu X., Li P., Guo Y., Wang H., Leak R.K., Chen S., Gao Y., Chen J. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion aſter focal cerebral ischemia. Stroke, 2012, Vol. 43, no. 11, pp. 3063-3070.Hu X., Li P., Guo Y., Wang H., Leak R.K., Chen S., Gao Y., Chen J. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion aſter focal cerebral ischemia. Stroke, 2012, Vol. 43, no. 11, pp. 3063-3070.Hu X., Leak R.K., Shi J., Suenaga J., Gao Y., Zheng P., Chen J. Microglial and macrophage polarization-new prospects for brain repair. Nat. Rev. Neurol., 2015, Vol. 11, no. 1, pp. 56-64.Hu X., Leak R.K., Shi J., Suenaga J., Gao Y., Zheng P., Chen J. Microglial and macrophage polarization-new prospects for brain repair. Nat. Rev. Neurol., 2015, Vol. 11, no. 1, pp. 56-64.Hua F., Ma J., Ha T., Kelley J.L., Kao R.L., Schweitzer J.B., Kalbfleisch J.H., Williams D.L., Li C. Differential roles of TLR2 and TLR4 in acute focal cerebral ischemia/reperfusion injury in mice. Brain Res., 2009, Vol. 1262, pp. 100-108.Hua F., Ma J., Ha T., Kelley J.L., Kao R.L., Schweitzer J.B., Kalbfleisch J.H., Williams D.L., Li C. Differential roles of TLR2 and TLR4 in acute focal cerebral ischemia/reperfusion injury in mice. Brain Res., 2009, Vol. 1262, pp. 100-108.Huang J.M., Hu J., Chen N., Hu M.L. Relationship between plasma high-mobility group box-1 levels and clinical outcomes of ischemic stroke. J. Crit .Care, 2013, Vol. 28, no. 5, pp. 792-797.Huang J.M., Hu J., Chen N., Hu M.L. Relationship between plasma high-mobility group box-1 levels and clinical outcomes of ischemic stroke. J. Crit .Care, 2013, Vol. 28, no. 5, pp. 792-797.Hurn P.D., Subramanian S., Parker S.M., Afentoulis M.E., Kaler L.J., Vandenbark A.A., Offner H. T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J. Cereb. Blood Flow Metab., 2007, Vol. 27, no. 11, pp. 1798-1805.Hurn P.D., Subramanian S., Parker S.M., Afentoulis M.E., Kaler L.J., Vandenbark A.A., Offner H. T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J. Cereb. Blood Flow Metab., 2007, Vol. 27, no. 11, pp. 1798-1805.Iadecola С., Anrather J. The immunology of stroke: from mechanisms to translation. Nat. Med., 2012, Vol. 17, no. 7, pp. 796-808.Iadecola С., Anrather J. The immunology of stroke: from mechanisms to translation. Nat. Med., 2012, Vol. 17, no. 7, pp. 796-808.Jauch E.C., Lindsell C., Broderick J., Fagan S.C., Tilley B.C., Levine S.R., NINDS rt-PA Stroke Study Group. Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study. Stroke, 2006, Vol. 37, no. 10, pp. 2508-2513.Jauch E.C., Lindsell C., Broderick J., Fagan S.C., Tilley B.C., Levine S.R., NINDS rt-PA Stroke Study Group. Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study. Stroke, 2006, Vol. 37, no. 10, pp. 2508-2513.Jin R., Zhu X., Liu L., Nanda A., Granger D.N., Li G. Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice. Stroke, 2013, Vol. 44, no. 4, pp. 1135-1143.Jin R., Zhu X., Liu L., Nanda A., Granger D.N., Li G. Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice. Stroke, 2013, Vol. 44, no. 4, pp. 1135-1143.Jin R., Yang G., Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J. Leukoc. Biol., 2010, Vol. 87, no. 5, pp. 779-789.Jin R., Yang G., Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J. Leukoc. Biol., 2010, Vol. 87, no. 5, pp. 779-789.Kaito M., Araya S., Gondo Y., Fujita M., Minato N., Nakanishi M., Matsui M. Relevance of distinct monocyte subsets to clinical course of ischemic stroke patients. PLoS ONE, 2013, Vol. 8, no. 8, e69409. doi: 10.1371/journal. pone.0069409Kaito M., Araya S., Gondo Y., Fujita M., Minato N., Nakanishi M., Matsui M. Relevance of distinct monocyte subsets to clinical course of ischemic stroke patients. PLoS ONE, 2013, Vol. 8, no. 8, e69409. doi: 10.1371/journal. pone.0069409Keimpema E., Fokkens M.R., Nagy Z., Agoston V., Luiten P.G., Nyakas C., Boddeke H.W., Copray J.C. Early transient presence of implanted bone marrow stem cells reduces lesion size aſter cerebral ischemia in adult rats. Neuropathol. Appl. Neurobiol., 2009, Vol. 35, no. 1, pp. 89-102.Keimpema E., Fokkens M.R., Nagy Z., Agoston V., Luiten P.G., Nyakas C., Boddeke H.W., Copray J.C. Early transient presence of implanted bone marrow stem cells reduces lesion size aſter cerebral ischemia in adult rats. Neuropathol. Appl. Neurobiol., 2009, Vol. 35, no. 1, pp. 89-102.Kigerl K.A., Gensel J.C., Ankeny D.P., Alexander J.K., Donnelly D.J., Popovich P.G. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J. Neurosci., 2009, Vol. 29, no. 43, pp. 13435-13444.Kigerl K.A., Gensel J.C., Ankeny D.P., Alexander J.K., Donnelly D.J., Popovich P.G. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J. Neurosci., 2009, Vol. 29, no. 43, pp. 13435-13444.Kim E., Yang J., Beltran C.D., Cho S. Role of spleen-derived monocytes/macrophages in acute ischemic brain injury. J. Cereb. Blood Flow Metab., 2014, Vol. 34, no. 8, pp. 1411-1419.Kim E., Yang J., Beltran C.D., Cho S. Role of spleen-derived monocytes/macrophages in acute ischemic brain injury. J. Cereb. Blood Flow Metab., 2014, Vol. 34, no. 8, pp. 1411-1419.Kleinschnitz C., Schwab N., Kraſt P., Hagedorn I., Dreykluſt A., Schwarz T., Austinat M., Nieswandt B., Wiendl H., Stoll G. Early detrimental T-cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor thrombus formation. Blood, 2010, Vol. 115, no. 18, pp. 3835-3842.Kleinschnitz C., Schwab N., Kraſt P., Hagedorn I., Dreykluſt A., Schwarz T., Austinat M., Nieswandt B., Wiendl H., Stoll G. Early detrimental T-cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor thrombus formation. Blood, 2010, Vol. 115, no. 18, pp. 3835-3842.Kleinschnitz C., Kraſt P., Dreykluſt A., Hagedorn I., Gobel K., Schuhmann M. K., Nieswandt B., Stoll G., Wiendl H. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood, 2013, Vol. 121, no. 4, pp. 679-691.Kleinschnitz C., Kraſt P., Dreykluſt A., Hagedorn I., Gobel K., Schuhmann M. K., Nieswandt B., Stoll G., Wiendl H. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood, 2013, Vol. 121, no. 4, pp. 679-691.Koizumi S., Shigemoto-Mogami Y., Nasu-Tada K., Shinozaki Y., Ohsawa K., Tsuda M., Joshi B.V., Jacobson K.A., Kohsaka S., Inoue K. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature, 2007, Vol. 446, no. 7139, pp. 1091-1095.Koizumi S., Shigemoto-Mogami Y., Nasu-Tada K., Shinozaki Y., Ohsawa K., Tsuda M., Joshi B.V., Jacobson K.A., Kohsaka S., Inoue K. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature, 2007, Vol. 446, no. 7139, pp. 1091-1095.Kono H., Rock K.L. How dying cells alert the immune system to danger. Nat. Rev. Immunol., 2008, Vol. 8, no. 4, pp. 279-289.Kono H., Rock K.L. How dying cells alert the immune system to danger. Nat. Rev. Immunol., 2008, Vol. 8, no. 4, pp. 279-289.Lambertsen K.L., Biber K., Finsen B. Inflammatory cytokines in experimental and human stroke. J. Cereb. Blood Flow Metab., 2012, Vol. 32, no. 9, pp. 1677-1698.Lambertsen K.L., Biber K., Finsen B. Inflammatory cytokines in experimental and human stroke. J. Cereb. Blood Flow Metab., 2012, Vol. 32, no. 9, pp. 1677-1698.Lawrence A.J., Patel B., Morris R.G., MacKinnon A.D., Rich P.M., Barrick T.R., Markus H.S. Mechanisms of cognitive impairment in cerebral small vessel disease: multimodal MRI results from the St George’s cognition and neuroimaging in stroke (SCANS) study. PLoS ONE, 2013, Vol. 8, no. 4, e61014. doi: 10.1371/journal.pone.0061014.Lawrence A.J., Patel B., Morris R.G., MacKinnon A.D., Rich P.M., Barrick T.R., Markus H.S. Mechanisms of cognitive impairment in cerebral small vessel disease: multimodal MRI results from the St George’s cognition and neuroimaging in stroke (SCANS) study. PLoS ONE, 2013, Vol. 8, no. 4, e61014. doi: 10.1371/journal.pone.0061014.Leys D., Henon H., Mackowiak-Cordoliani M.A., Pasquier F. Poststroke dementia. Lancet Neurol., 2005, Vol. 4, no. 11, pp. 752-759.Leys D., Henon H., Mackowiak-Cordoliani M.A., Pasquier F. Poststroke dementia. Lancet Neurol., 2005, Vol. 4, no. 11, pp. 752-759.Li P., Gan Y., Sun B.L., Zhang F., Lu B., Gao Y., Liang W., Thomson A.W., Chen J., Hu X. Adoptive regulatory T-cell therapy protects against cerebral ischemia. Ann. Neurol., 2013, Vol. 74, no. 3, pp. 458-471.Li P., Gan Y., Sun B.L., Zhang F., Lu B., Gao Y., Liang W., Thomson A.W., Chen J., Hu X. Adoptive regulatory T-cell therapy protects against cerebral ischemia. Ann. Neurol., 2013, Vol. 74, no. 3, pp. 458-471.Liesz A., Zhou W., Mracsko E., Karcher S., Bauer H., Schwarting S., Sun L., Bruder D., Stegemann S., Cerwenka A., Sommer C., Dalpke A.H., Veltkamp R. Inhibition of lymphocyte trafficking shields the brain against deleterious neuroinflammation aſter stroke. Brain, 2011, Vol. 134, no. 3, pp. 704-720.Liesz A., Zhou W., Mracsko E., Karcher S., Bauer H., Schwarting S., Sun L., Bruder D., Stegemann S., Cerwenka A., Sommer C., Dalpke A.H., Veltkamp R. Inhibition of lymphocyte trafficking shields the brain against deleterious neuroinflammation aſter stroke. Brain, 2011, Vol. 134, no. 3, pp. 704-720.Liesz A., Suri-Payer E., Veltkamp C., Doerr H., Sommer C., Rivest S., Giese T., Veltkamp R. Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat. Med., 2009, Vol. 15, pp. 192-199.Liesz A., Suri-Payer E., Veltkamp C., Doerr H., Sommer C., Rivest S., Giese T., Veltkamp R. Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat. Med., 2009, Vol. 15, pp. 192-199.Liesz A., Zhou W., Na S.Y., Hammerling G.J., Garbi N., Karcher S., Mracsko E., Backs J., Rivest S., Veltkamp R. Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke. J. Neurosci., 2013, Vol. 33, no. 44, pp. 17350-17362.Liesz A., Zhou W., Na S.Y., Hammerling G.J., Garbi N., Karcher S., Mracsko E., Backs J., Rivest S., Veltkamp R. Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke. J. Neurosci., 2013, Vol. 33, no. 44, pp. 17350-17362.Liu Z., Fan Y., Won S.J., Neumann M., Hu D., Zhou L., Weinstein P.R., Liu J. Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment aſter focal cerebral ischemia. Stroke, 2007, Vol. 38, no. 1, pp. 146-152.Liu Z., Fan Y., Won S.J., Neumann M., Hu D., Zhou L., Weinstein P.R., Liu J. Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment aſter focal cerebral ischemia. Stroke, 2007, Vol. 38, no. 1, pp. 146-152.London A., Cohen M., Schwartz M. Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair. Front Cell Neurosci., 2013, Vol. 7, Art. 34, 10 p.London A., Cohen M., Schwartz M. Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair. Front Cell Neurosci., 2013, Vol. 7, Art. 34, 10 p.Lopes Pinheiro M.A., Kooij G., Mizee M.R., Kamermans A., Enzmann G., Lyck R., Schwaninger M,. Engelhardt B., de Vries H.E. Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke. Biochim. Biophys. Acta, 2016, Vol. 1862, no. 3, pp. 461-471.Lopes Pinheiro M.A., Kooij G., Mizee M.R., Kamermans A., Enzmann G., Lyck R., Schwaninger M,. Engelhardt B., de Vries H.E. Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke. Biochim. Biophys. Acta, 2016, Vol. 1862, no. 3, pp. 461-471.Macrez R., Ali C., Toutirais O., Le Mauff B., Defer G., Dirnagl U., Vivien D. Stroke and the immune system: from pathophysiology to new therapeutic strategies. Lancet Neurol., 2011, Vol. 10, no. 5, pp. 471-480.Macrez R., Ali C., Toutirais O., Le Mauff B., Defer G., Dirnagl U., Vivien D. Stroke and the immune system: from pathophysiology to new therapeutic strategies. Lancet Neurol., 2011, Vol. 10, no. 5, pp. 471-480.Malm T., Koistinaho M., Muona A., Magga J., Koistinaho J. The role and therapeutic potential of monocytic cells in Alzheimer’s disease. Glia, 2010, Vol. 58, no. 8, pp. 889-900.Malm T., Koistinaho M., Muona A., Magga J., Koistinaho J. The role and therapeutic potential of monocytic cells in Alzheimer’s disease. Glia, 2010, Vol. 58, no. 8, pp. 889-900.McColl B.W., Rothwell N.J., Allan S.M. Systemic inflammatory stimulus potentiates the acute phase and CXC chemokine responses to experimental stroke and exacerbates brain damage via interleukin-1- and neutrophil-dependent mechanisms. J. Neurosci., 2007, Vol. 27, no. 16, pp. 4403-4412.McColl B.W., Rothwell N.J., Allan S.M. Systemic inflammatory stimulus potentiates the acute phase and CXC chemokine responses to experimental stroke and exacerbates brain damage via interleukin-1- and neutrophil-dependent mechanisms. J. Neurosci., 2007, Vol. 27, no. 16, pp. 4403-4412.Meisel C., Schwab J., Prass K., Meisel A., Dirnagl U. Central nervous system injury-induced immune deficiency syndrome. Nat. Rev. Neurosci., 2005, Vol. 6, no. 10, pp. 775-786.Meisel C., Schwab J., Prass K., Meisel A., Dirnagl U. Central nervous system injury-induced immune deficiency syndrome. Nat. Rev. Neurosci., 2005, Vol. 6, no. 10, pp. 775-786.Moalem G., Gdalyahu A., Shani Y., Otten U., Lazarovici P., Cohen I.R., Schwartz M. Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J. Autoimmun., 2000, Vol. 15, no. 3, pp. 331-345.Moalem G., Gdalyahu A., Shani Y., Otten U., Lazarovici P., Cohen I.R., Schwartz M. Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J. Autoimmun., 2000, Vol. 15, no. 3, pp. 331-345.Moalem G., Leibowitz-Amit R., Yoles E., Mor F., Cohen I.R., Schwartz M. Autoimmune T cells protect neurons from secondary degeneration aſter central nervous system axotomy. Nat. Med., 1999, Vol. 5, no. 1, pp. 49-55.Moalem G., Leibowitz-Amit R., Yoles E., Mor F., Cohen I.R., Schwartz M. Autoimmune T cells protect neurons from secondary degeneration aſter central nervous system axotomy. Nat. Med., 1999, Vol. 5, no. 1, pp. 49-55.Moskowitz M.A., Lo E.H., Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron, 2010, Vol. 67, no. 2, pp. 181-198.Moskowitz M.A., Lo E.H., Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron, 2010, Vol. 67, no. 2, pp. 181-198.Mulcahy N.J., Ross J., Rothwell N.J., Loddick S.A. Delayed administration of interleukin-1 receptor antagonist protects against transient cerebral ischaemia in the rat. Br. J. Pharmacol., 2003, Vol. 140, no. 3, pp. 471-476.Mulcahy N.J., Ross J., Rothwell N.J., Loddick S.A. Delayed administration of interleukin-1 receptor antagonist protects against transient cerebral ischaemia in the rat. Br. J. Pharmacol., 2003, Vol. 140, no. 3, pp. 471-476.Napoli I., Neumann H. Microglial clearance function in health and disease. Neuroscience, 2009, Vol. 158, no. 3, pp. 1030-1038.Napoli I., Neumann H. Microglial clearance function in health and disease. Neuroscience, 2009, Vol. 158, no. 3, pp. 1030-1038.Nathan C., Ding A. Nonresolving inflammation. Cell, 2010, Vol. 140, no. 6, pp. 871-882.Nathan C., Ding A. Nonresolving inflammation. Cell, 2010, Vol. 140, no. 6, pp. 871-882.Nave K.A. Myelination and support of axonal integrity by glia. Nature, 2010, Vol. 468, no. 7321, pp. 244-252.Nave K.A. Myelination and support of axonal integrity by glia. Nature, 2010, Vol. 468, no. 7321, pp. 244-252.Neumann H. Control of glial immune function by neurons. Glia, 2001, Vol. 36, no. 2, pp. 191-199.Neumann H. Control of glial immune function by neurons. Glia, 2001, Vol. 36, no. 2, pp. 191-199.Neumann S., Shields N.J., Balle T., Chebib M., Clarkson A.N. Innate immunity and inflammation post-stroke: an α7-nicotinic agonist perspective. Int. J. Mol. Sci., 2015, Vol. 16, no. 12, pp. 29029-29046.Neumann S., Shields N.J., Balle T., Chebib M., Clarkson A.N. Innate immunity and inflammation post-stroke: an α7-nicotinic agonist perspective. Int. J. Mol. Sci., 2015, Vol. 16, no. 12, pp. 29029-29046.Offner H., Subramanian S., Parker S.M., Afentoulis M.E., Vandenbark A.A., Hurn P.D. Experimental stroke induces massive, rapid activation of the peripheral immune system. J. Cereb. Blood Flow Metab., 2006, Vol. 26, no. 5, pp. 654-665.Offner H., Subramanian S., Parker S.M., Afentoulis M.E., Vandenbark A.A., Hurn P.D. Experimental stroke induces massive, rapid activation of the peripheral immune system. J. Cereb. Blood Flow Metab., 2006, Vol. 26, no. 5, pp. 654-665.Offner H., Subramanian S., Parker S.M., Wang C., Afentoulis M.E., Lewis A., Vandenbark A.A., Hurn P.D. Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages. J. Immunol., 2006, Vol. 176, no. 11, pp. 6523-6531.Offner H., Subramanian S., Parker S.M., Wang C., Afentoulis M.E., Lewis A., Vandenbark A.A., Hurn P.D. Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages. J. Immunol., 2006, Vol. 176, no. 11, pp. 6523-6531.Offner H., Vandenbark A.A., Hurn PD. Effect of experimental stroke on peripheral immunity: CNS ischemia induces profound immunosuppression. Neuroscience, 2009, Vol. 158, no. 3, pp. 1098-1111.Offner H., Vandenbark A.A., Hurn PD. Effect of experimental stroke on peripheral immunity: CNS ischemia induces profound immunosuppression. Neuroscience, 2009, Vol. 158, no. 3, pp. 1098-1111.Oppenheim J.J., Tewary P., de la Rosa G., Yang D. Alarmins initiate host defense. Adv. Exp. Med. Biol., 2007, Vol. 601, pp. 185-194.Oppenheim J.J., Tewary P., de la Rosa G., Yang D. Alarmins initiate host defense. Adv. Exp. Med. Biol., 2007, Vol. 601, pp. 185-194.Ostrowski R.P., Schulte R.W., Nie Y., Ling T., Lee T., Manaenko A., Gridley D.S., Zhang J.H. Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke model. Transl. Stroke Res., 2012, Vol. 3, no. 4, pp. 473-481.Ostrowski R.P., Schulte R.W., Nie Y., Ling T., Lee T., Manaenko A., Gridley D.S., Zhang J.H. Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke model. Transl. Stroke Res., 2012, Vol. 3, no. 4, pp. 473-481.Pennypacker K.R., Offner H. The role of the spleen in ischemic stroke. J. Cereb. Blood Flow Metab., 2015, Vol. 35, no. 2, pp. 186-187.Pennypacker K.R., Offner H. The role of the spleen in ischemic stroke. J. Cereb. Blood Flow Metab., 2015, Vol. 35, no. 2, pp. 186-187.Pettigrew L.C., Kindy M.S., Scheff S., Springer J.E., Kryscio R.J., Li Y., Grass D.S. Focal cerebral ischemia in the TNFalpha-transgenic rat. J. Neuroinflammation, 2008, Vol. 5, p. 47.Pettigrew L.C., Kindy M.S., Scheff S., Springer J.E., Kryscio R.J., Li Y., Grass D.S. Focal cerebral ischemia in the TNFalpha-transgenic rat. J. Neuroinflammation, 2008, Vol. 5, p. 47.Planas A.M., Gomez-Choco M., Urra X., Gorina R., Caballero M., Chamorro A. Brain-derived antigens in lymphoid tissue of patients with acute stroke. J. Immunol., 2012, Vol. 188, no. 5, pp. 2156-2163.Planas A.M., Gomez-Choco M., Urra X., Gorina R., Caballero M., Chamorro A. Brain-derived antigens in lymphoid tissue of patients with acute stroke. J. Immunol., 2012, Vol. 188, no. 5, pp. 2156-2163.Prass K., Meisel C., Höflich C., Braun J., Halle E., Wolf T., Ruscher K., Victorov I.V., Priller J., Dirnagl U., Volk H.D., Meisel A. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by post- stroke T helper cell type 1-like immunostimulation. J. Exp. Med., 2003, Vol. 198, no. 5, pp. 725-736.Prass K., Meisel C., Höflich C., Braun J., Halle E., Wolf T., Ruscher K., Victorov I.V., Priller J., Dirnagl U., Volk H.D., Meisel A. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by post- stroke T helper cell type 1-like immunostimulation. J. Exp. Med., 2003, Vol. 198, no. 5, pp. 725-736.Qiu J., Xu J., Zheng Y., Wei Y., Zhu X., Lo E.H., Moskowitz M.A., Sims J.R. High-mobility group box 1 promotes metalloproteinase-9 upregulation through Toll-like receptor 4 aſter cerebral ischemia. Stroke, 2010, Vol. 41, no. 9, pp. 2077-2082.Qiu J., Xu J., Zheng Y., Wei Y., Zhu X., Lo E.H., Moskowitz M.A., Sims J.R. High-mobility group box 1 promotes metalloproteinase-9 upregulation through Toll-like receptor 4 aſter cerebral ischemia. Stroke, 2010, Vol. 41, no. 9, pp. 2077-2082.Rasouli J., Lekhraj R., Ozbalik M., Brain-spleen inflammatory coupling: a literature review. Einstein J. Biol. Med., 2011, Vol. 27, no. 2, pp. 74-77.Rasouli J., Lekhraj R., Ozbalik M., Brain-spleen inflammatory coupling: a literature review. Einstein J. Biol. Med., 2011, Vol. 27, no. 2, pp. 74-77.Ren X., Akiyoshi K., Dziennis S., Vandenbark A.A., Herson P.S., Hurn P.D., Offner H. Regulatory B cells limit CNS inflammation and neurologic deficits in murine experimental stroke. J. Neurosci., 2011, Vol. 31, no. 23, pp. 8556-8563.Ren X., Akiyoshi K., Dziennis S., Vandenbark A.A., Herson P.S., Hurn P.D., Offner H. Regulatory B cells limit CNS inflammation and neurologic deficits in murine experimental stroke. J. Neurosci., 2011, Vol. 31, no. 23, pp. 8556-8563.Ren X., Akiyoshi K., Vandenbark A.A., Hurn P.D., Offner H. CD4+FoxP3+ regulatory T-cells in cerebral ischemic stroke. Metab. Brain Dis., 2011, Vol. 26, no. 1, pp. 87-90.Ren X., Akiyoshi K., Vandenbark A.A., Hurn P.D., Offner H. CD4+FoxP3+ regulatory T-cells in cerebral ischemic stroke. Metab. Brain Dis., 2011, Vol. 26, no. 1, pp. 87-90.Ren X., Akiyoshi K., Grafe M.R., Vandenbark A.A., Hurn P.D., Herson P.S., Offner H. Myelin specific cells infiltrate MCAO lesions and exacerbate stroke severity. Metab. Brain Dis., 2012, Vol. 27, no. 1, pp. 7-15.Ren X., Akiyoshi K., Grafe M.R., Vandenbark A.A., Hurn P.D., Herson P.S., Offner H. Myelin specific cells infiltrate MCAO lesions and exacerbate stroke severity. Metab. Brain Dis., 2012, Vol. 27, no. 1, pp. 7-15.Ritzel R.M., Patel A.R., Grenier J.M., Crapser J., Verma R., Jellison E.R., McCullough L.D. Functional differences between microglia and monocytes aſter ischemic stroke. J. Neuroinflammation, 2015, Vol. 12, p. 106.Ritzel R.M., Patel A.R., Grenier J.M., Crapser J., Verma R., Jellison E.R., McCullough L.D. Functional differences between microglia and monocytes aſter ischemic stroke. J. Neuroinflammation, 2015, Vol. 12, p. 106.Römer C., Engel O., Winek K., Hochmeister S., Zhang T., Royl G., Klehmet J., Dirnagl U., Meisel C., Meisel A. Blocking stroke-induced immunodeficiency increases CNS antigen-specific autoreactivity but does not worsen functional outcome aſter experimental stroke. J. Neurosci., 2015, Vol. 35, no. 20, pp. 7777-7794.Römer C., Engel O., Winek K., Hochmeister S., Zhang T., Royl G., Klehmet J., Dirnagl U., Meisel C., Meisel A. Blocking stroke-induced immunodeficiency increases CNS antigen-specific autoreactivity but does not worsen functional outcome aſter experimental stroke. J. Neurosci., 2015, Vol. 35, no. 20, pp. 7777-7794.Rosamond W., Flegal K., Friday G., Furie K., Go A., Greenlund K., Haase N., Ho M., Howard V., Kissela B., Kittner S., Lloyd-Jones D., McDermott M., Meigs J., Moy C., Nichol G., O’Donnell C.J., Roger V., Rumsfeld J., Sorlie P., Steinberger J., Thom T., Wasserthiel-Smoller S., Hong Y. Heart disease and stroke statistics – 2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation, 2007, Vol. 115, no. 5, e69-e171.Rosamond W., Flegal K., Friday G., Furie K., Go A., Greenlund K., Haase N., Ho M., Howard V., Kissela B., Kittner S., Lloyd-Jones D., McDermott M., Meigs J., Moy C., Nichol G., O’Donnell C.J., Roger V., Rumsfeld J., Sorlie P., Steinberger J., Thom T., Wasserthiel-Smoller S., Hong Y. Heart disease and stroke statistics – 2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation, 2007, Vol. 115, no. 5, e69-e171.Ruhnau J., Schulze J., von Sarnowski B., Heinrich M., Langner S., Pötschke C., Wilden A., Kessler C., Bröker B.M. Vogelgesang A., Dressel A. Reduced numbers and impaired function of regulatory T cells in peripheral blood of ischemic stroke patients. Mediators Inflamm., 2016, Vol. 2016, Art. ID 2974605, 9 p.Ruhnau J., Schulze J., von Sarnowski B., Heinrich M., Langner S., Pötschke C., Wilden A., Kessler C., Bröker B.M. Vogelgesang A., Dressel A. Reduced numbers and impaired function of regulatory T cells in peripheral blood of ischemic stroke patients. Mediators Inflamm., 2016, Vol. 2016, Art. ID 2974605, 9 p.Saino O., Taguchi A., Nakagomi T., Nakano-Doi A., Kashiwamura S., Doe N., Nakagomi N., Soma T., Yoshikawa H., Stern D.M., Okamura H., Matsuyama T. Immunodeficiency reduces neural stem/progenitor cell apoptosis and enhances neurogenesis in the cerebral cortex aſter stroke. J. Neurosci. Res., 2010, Vol. 88, no. 11, pp. 2385-2389.Saino O., Taguchi A., Nakagomi T., Nakano-Doi A., Kashiwamura S., Doe N., Nakagomi N., Soma T., Yoshikawa H., Stern D.M., Okamura H., Matsuyama T. Immunodeficiency reduces neural stem/progenitor cell apoptosis and enhances neurogenesis in the cerebral cortex aſter stroke. J. Neurosci. Res., 2010, Vol. 88, no. 11, pp. 2385-2389.Schilling M., Besselmann M., Muller M., Strecker J.K., Ringelstein E.B., Kiefer R. Predominant phagocytic activity of resident microglia over hematogenous macrophages following transient focal cerebral ischemia: an investigation using green fluorescent protein transgenic bone marrow chimeric mice. Exp. Neurol., 2005, Vol. 196, no. 2, pp. 290-297.Schilling M., Besselmann M., Muller M., Strecker J.K., Ringelstein E.B., Kiefer R. Predominant phagocytic activity of resident microglia over hematogenous macrophages following transient focal cerebral ischemia: an investigation using green fluorescent protein transgenic bone marrow chimeric mice. Exp. Neurol., 2005, Vol. 196, no. 2, pp. 290-297.Schilling M., Strecker J.K., Schabitz W.R., Ringelstein E.B., Kiefer R. Effects of monocyte chemoattractant protein 1 on blood-borne cell recruitment aſter transient focal cerebral ischemia in mice. Neuroscience, 2009, Vol. 161, no. 3, pp. 806-812.Schilling M., Strecker J.K., Schabitz W.R., Ringelstein E.B., Kiefer R. Effects of monocyte chemoattractant protein 1 on blood-borne cell recruitment aſter transient focal cerebral ischemia in mice. Neuroscience, 2009, Vol. 161, no. 3, pp. 806-812.Schulze J., Zierath D., Tanzi P., Cain K., Shibata D., Dressel A., Becker K. Severe stroke induces long-lasting alterations of high-mobility group box 1. Stroke, 2013, Vol. 44, no. 1, pp. 246-248.Schulze J., Zierath D., Tanzi P., Cain K., Shibata D., Dressel A., Becker K. Severe stroke induces long-lasting alterations of high-mobility group box 1. Stroke, 2013, Vol. 44, no. 1, pp. 246-248.Schwarting S., Litwak S., Hao W., Bähr M., Weise J., Neumann H. Hematopoietic stem cells reduce postischemic inflammation and ameliorate ischemic brain injury. Stroke, 2008, Vol. 39, no. 10, pp. 2867-2875.Schwarting S., Litwak S., Hao W., Bähr M., Weise J., Neumann H. Hematopoietic stem cells reduce postischemic inflammation and ameliorate ischemic brain injury. Stroke, 2008, Vol. 39, no. 10, pp. 2867-2875.Schwartz M., London A., Shechter R. Boosting T-cell immunity as a therapeutic approach for neurodegenerative conditions: the role of innate immunity. Neuroscience, 2009, Vol. 158, no. 3, pp. 1133-1142.Schwartz M., London A., Shechter R. Boosting T-cell immunity as a therapeutic approach for neurodegenerative conditions: the role of innate immunity. Neuroscience, 2009, Vol. 158, no. 3, pp. 1133-1142.Seifert H.A., Hall A.A., Chapman C.B., Collier L.A., Willing A.E., Pennypacker K.R. A transient decrease in spleen size following stroke corresponds to splenocyte release into systemic circulation. J. Neuroimmune Pharmacol., 2012, Vol. 7, no. 4, pp. 1017-1024.Seifert H.A., Hall A.A., Chapman C.B., Collier L.A., Willing A.E., Pennypacker K.R. A transient decrease in spleen size following stroke corresponds to splenocyte release into systemic circulation. J. Neuroimmune Pharmacol., 2012, Vol. 7, no. 4, pp. 1017-1024.Seifert H.A., Leonardo C.C., Hall A.A., Rowe D.D., Collier L.A., Benkovic S.A., Willing A.E., Pennypacker K.R. The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling. Metab. Brain Dis., 2012, Vol. 27, no. 2, pp. 131-141.Seifert H.A., Leonardo C.C., Hall A.A., Rowe D.D., Collier L.A., Benkovic S.A., Willing A.E., Pennypacker K.R. The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling. Metab. Brain Dis., 2012, Vol. 27, no. 2, pp. 131-141.Sherman D., Bes A., Easton J.D., Hacke W., Kaste M., Polmar S.H. Use of anti-ICAM-1 therapy in ischemic stroke: Results of the enlimomab acute stroke trial. Neurology, 2001, Vol. 57, no. 8, pp. 1428-1434.Sherman D., Bes A., Easton J.D., Hacke W., Kaste M., Polmar S.H. Use of anti-ICAM-1 therapy in ischemic stroke: Results of the enlimomab acute stroke trial. Neurology, 2001, Vol. 57, no. 8, pp. 1428-1434.Shichita T., Sugiyama Y., Ooboshi H., Sugimori H., Nakagawa R., Takada I., Iwaki T., Okada Y., Iida M., Cua D.J., Iwakura Y., Yoshimura A. Pivotal role of cerebral interleukin-17-producing gammadelta T cells in the delayed phase of ischemic brain injury. Nat. Med., 2009, Vol. 15, no. 8, pp. 946-950.Shichita T., Sugiyama Y., Ooboshi H., Sugimori H., Nakagawa R., Takada I., Iwaki T., Okada Y., Iida M., Cua D.J., Iwakura Y., Yoshimura A. Pivotal role of cerebral interleukin-17-producing gammadelta T cells in the delayed phase of ischemic brain injury. Nat. Med., 2009, Vol. 15, no. 8, pp. 946-950.Siniscalchi A., Gallelli L., Malferrari G., Pirritano D., Serra R., Santangelo E., De Sarro G. Cerebral stroke injury: the role of cytokines and brain inflammation. J. Basic Clin. Physiol. Pharmacol., 2014, Vol. 25, no. 2, pp. 131-137.Siniscalchi A., Gallelli L., Malferrari G., Pirritano D., Serra R., Santangelo E., De Sarro G. Cerebral stroke injury: the role of cytokines and brain inflammation. J. Basic Clin. Physiol. Pharmacol., 2014, Vol. 25, no. 2, pp. 131-137.Spite M., Serhan C.N. Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins. Circ. Res., 2010, Vol. 107, no. 10, pp. 1170-1184.Spite M., Serhan C.N. Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins. Circ. Res., 2010, Vol. 107, no. 10, pp. 1170-1184.Stubbe T., Ebner F., Richter D., Engel O., Klehmet J., Royl G., Meisel A., Nitsch R., Meisel C., Brandt C. Regulatory T cells accumulate and proliferate in the ischemic hemisphere for up to 30 days aſter MCAO. J. Cereb. Blood Flow Metab., 2013, Vol. 33, no. 1, pp. 37-47.Stubbe T., Ebner F., Richter D., Engel O., Klehmet J., Royl G., Meisel A., Nitsch R., Meisel C., Brandt C. Regulatory T cells accumulate and proliferate in the ischemic hemisphere for up to 30 days aſter MCAO. J. Cereb. Blood Flow Metab., 2013, Vol. 33, no. 1, pp. 37-47.Tarkowski E., Ekelund P., Tarkowski A. Enhancement of antigen- specific T-cell reactivity on the affected side in stroke patients. J. Neuroimmunol., 1991, Vol. 34, no. 1, pp. 61-67.Tarkowski E., Ekelund P., Tarkowski A. Enhancement of antigen- specific T-cell reactivity on the affected side in stroke patients. J. Neuroimmunol., 1991, Vol. 34, no. 1, pp. 61-67.Taylor A., Verhagen J., Blaser K., Akdis M., Akdis C.A. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology, 2006, Vol. 117, no. 4, pp. 433-442.Taylor A., Verhagen J., Blaser K., Akdis M., Akdis C.A. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology, 2006, Vol. 117, no. 4, pp. 433-442.Taylor R.A., Sansing L.H. Microglial responses aſter ischemic stroke and intracerebral hemorrhage. Clin. Dev. Immunol., 2013, Vol. 2013, Art. ID 746068, 10 p.Taylor R.A., Sansing L.H. Microglial responses aſter ischemic stroke and intracerebral hemorrhage. Clin. Dev. Immunol., 2013, Vol. 2013, Art. ID 746068, 10 p.Tokgoz S., Kayrak M., Akpinar Z., Seyithanoğlu A., Güney F., Yürüten B. Neutrophil lymphocyte ratio as a predictor of stroke. J. Stroke Cerebrovasc. Dis., 2013, Vol. 22, no. 7, pp. 1169-1174.Tokgoz S., Kayrak M., Akpinar Z., Seyithanoğlu A., Güney F., Yürüten B. Neutrophil lymphocyte ratio as a predictor of stroke. J. Stroke Cerebrovasc. Dis., 2013, Vol. 22, no. 7, pp. 1169-1174.Urra X., Cervera A., Obach V., Climent N., Planas A.M., Chamorro A. Monocytes are major players in the prognosis and risk of infection aſter acute stroke. Stroke, 2009, Vol. 40, no. 4, pp. 1262-1268.Urra X., Cervera A., Obach V., Climent N., Planas A.M., Chamorro A. Monocytes are major players in the prognosis and risk of infection aſter acute stroke. Stroke, 2009, Vol. 40, no. 4, pp. 1262-1268.Urra X., Cervera A., Villamor N., Planas A.M., Chamorro A. Harms and benefits of lymphocyte subpopulations in patients with acute stroke. Neuroscience, 2009, Vol. 158, no. 3, pp. 1174-1183.Urra X., Cervera A., Villamor N., Planas A.M., Chamorro A. Harms and benefits of lymphocyte subpopulations in patients with acute stroke. Neuroscience, 2009, Vol. 158, no. 3, pp. 1174-1183.Urra X., Miro F., Chamorro A., Planas A.M. Antigen-specific immune reactions to ischemic stroke. Front Cell Neurosci., 2014, Vol. 8, Art. 278.Urra X., Miro F., Chamorro A., Planas A.M. Antigen-specific immune reactions to ischemic stroke. Front Cell Neurosci., 2014, Vol. 8, Art. 278.Vahidy F.S., Parsha K.N., Rahbar M.H., Lee M.J., Bui T-T., Nguyen C., Barreto A.D, Bambhroliya A.B, Sahota P., Yang B., Aronowski J., Savitz S.I. Acute splenic responses in patients with ischemic stroke and intracerebral hemorrhage. J. Cereb. Blood Flow Metab., 2016, Vol. 36, no. 6, pp. 1012-1021.Vahidy F.S., Parsha K.N., Rahbar M.H., Lee M.J., Bui T-T., Nguyen C., Barreto A.D, Bambhroliya A.B, Sahota P., Yang B., Aronowski J., Savitz S.I. Acute splenic responses in patients with ischemic stroke and intracerebral hemorrhage. J. Cereb. Blood Flow Metab., 2016, Vol. 36, no. 6, pp. 1012-1021.van Zwam M., Huizinga R., Melief M.J., Wierenga-Wolf A.F., van Meurs M., Voerman J.S., Biber K.P., Boddeke H.W., Höpken U.E., Meisel C., Meisel A., Bechmann I., Hintzen R.Q., Hart B.A., Amor S., Laman J.D., Boven L.A. Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE. J. Mol. Med. (Berl.), 2009, Vol. 87, no. 3, pp. 273-286.van Zwam M., Huizinga R., Melief M.J., Wierenga-Wolf A.F., van Meurs M., Voerman J.S., Biber K.P., Boddeke H.W., Höpken U.E., Meisel C., Meisel A., Bechmann I., Hintzen R.Q., Hart B.A., Amor S., Laman J.D., Boven L.A. Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE. J. Mol. Med. (Berl.), 2009, Vol. 87, no. 3, pp. 273-286.Varga G., Ehrchen J., Brockhausen A., Weinhage T., Nippe N., Belz M. Immune suppression via glucocorticoid-stimulated monocytes: a novel mechanism to cope with inflammation. J. Immunol., 2014, Vol. 193, no. 3, pp. 1090-1099.Varga G., Ehrchen J., Brockhausen A., Weinhage T., Nippe N., Belz M. Immune suppression via glucocorticoid-stimulated monocytes: a novel mechanism to cope with inflammation. J. Immunol., 2014, Vol. 193, no. 3, pp. 1090-1099.Vogelgesang A., May V.E., Grunwald U., Bakkeboe M., Langner S., Wallaschofski H., Kessler C., Bröker B.M., Dressel A. Functional status of peripheral blood T-cells in ischemic stroke patients. PLoS ONE, 2010, Vol. 5, no. 1, e8718. doi: 10.1371/journal.pone.0008718.Vogelgesang A., May V.E., Grunwald U., Bakkeboe M., Langner S., Wallaschofski H., Kessler C., Bröker B.M., Dressel A. Functional status of peripheral blood T-cells in ischemic stroke patients. PLoS ONE, 2010, Vol. 5, no. 1, e8718. doi: 10.1371/journal.pone.0008718.Waje-Andreassen U., Krakenes J., Ulvestad E., Thomassen L., Myhr K.M., Aarseth J., Vedeler C.A. IL-6: an early marker for outcome in acute ischemic stroke. Acta Neurol. Scand., 2005, Vol. 111, no. 6, pp. 360-365.Waje-Andreassen U., Krakenes J., Ulvestad E., Thomassen L., Myhr K.M., Aarseth J., Vedeler C.A. IL-6: an early marker for outcome in acute ischemic stroke. Acta Neurol. Scand., 2005, Vol. 111, no. 6, pp. 360-365.Wattananit S., Tornero D., Graubardt N., Memanishvili T., Monni E., Tatarishvili J., Miskinyte G., Ge R., Ahlenius H., Lindvall O., Schwartz M., Kokaia Z.. Monocyte-derived macrophages contribute to spontaneous longterm functional recovery aſter stroke in mice. J. Neurosci., 2016, Vol. 36, no. 15, pp. 4182-4195.Wattananit S., Tornero D., Graubardt N., Memanishvili T., Monni E., Tatarishvili J., Miskinyte G., Ge R., Ahlenius H., Lindvall O., Schwartz M., Kokaia Z.. Monocyte-derived macrophages contribute to spontaneous longterm functional recovery aſter stroke in mice. J. Neurosci., 2016, Vol. 36, no. 15, pp. 4182-4195.Westendorp W.F., Nederkoorn P.J., Vermeij J.D., Dijkgraaf M.G., van de Beek D. Post-stroke infection: a systematic review and meta-analysis. BMC Neurol., 2011, Vol. 11, p. 110.Westendorp W.F., Nederkoorn P.J., Vermeij J.D., Dijkgraaf M.G., van de Beek D. Post-stroke infection: a systematic review and meta-analysis. BMC Neurol., 2011, Vol. 11, p. 110.Wolf S.A., Steiner B., Akpinarli A., Kammertoens T., Nassenstein C., Braun A., Blankenstein T., Kempermann G. CD4-positive T lymphocytes provide a neuroimmunological link in the control of adult hippocampal neurogenesis. J. Immunol., 2009, Vol. 182, no. 7, pp. 3979-3984.Wolf S.A., Steiner B., Akpinarli A., Kammertoens T., Nassenstein C., Braun A., Blankenstein T., Kempermann G. CD4-positive T lymphocytes provide a neuroimmunological link in the control of adult hippocampal neurogenesis. J. Immunol., 2009, Vol. 182, no. 7, pp. 3979-3984.Wong C.H., Jenne C.N., Lee W.Y., Leger C., Kubes P. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science, 2011, Vol. 334, no. 6052, pp. 101-105.Wong C.H., Jenne C.N., Lee W.Y., Leger C., Kubes P. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science, 2011, Vol. 334, no. 6052, pp. 101-105.Xiong X.Y., Liu L., Yang Q.W. Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis aſter stroke. Prog. Neurobiol., 2016, Vol. 142, pp. 23-44.Xiong X.Y., Liu L., Yang Q.W. Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis aſter stroke. Prog. Neurobiol., 2016, Vol. 142, pp. 23-44.Xu Х., Jiang Y. The Yin and Yang of innate immunity in stroke. Biomed. Res. Int., 2014, Vol. 2014, Art. ID 807978, 8 p.Xu Х., Jiang Y. The Yin and Yang of innate immunity in stroke. Biomed. Res. Int., 2014, Vol. 2014, Art. ID 807978, 8 p.Yan J., Read S.J., Henderson R.D., Hull R., O’Sullivan J.D., McCombe P.A., Greer J.M. Frequency and function of regulatory T cells aſter ischaemic stroke in humans. J. Neuroimmunol., 2012, Vol. 243, no. 1-2, pp. 89-94.Yan J., Read S.J., Henderson R.D., Hull R., O’Sullivan J.D., McCombe P.A., Greer J.M. Frequency and function of regulatory T cells aſter ischaemic stroke in humans. J. Neuroimmunol., 2012, Vol. 243, no. 1-2, pp. 89-94.Zahorec R. Ratio of neutrophil to lymphocyte counts – rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl. Lek. Listy, 2001, Vol. 102, no. 1, pp. 5-14.Zahorec R. Ratio of neutrophil to lymphocyte counts – rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl. Lek. Listy, 2001, Vol. 102, no. 1, pp. 5-14.Zhang B.J., Men X.J., Lu Z.Q., Li H.Y., Qiu W., Hu X.Q. Splenectomy protects experimental rats from cerebral damage aſter stroke due to anti-inflammatory effects. Chin. Med. J. (Engl.), 2013, Vol. 126, no. 12, pp. 2354-2360.Zhang B.J., Men X.J., Lu Z.Q., Li H.Y., Qiu W., Hu X.Q. Splenectomy protects experimental rats from cerebral damage aſter stroke due to anti-inflammatory effects. Chin. Med. J. (Engl.), 2013, Vol. 126, no. 12, pp. 2354-2360.Ziegler-Heitbrock H.W. Definition of human blood monocytes. J. Leukoc. Biol., 2000, Vol. 67, no. 5, pp. 603-606.Ziegler-Heitbrock H.W. Definition of human blood monocytes. J. Leukoc. Biol., 2000, Vol. 67, no. 5, pp. 603-606.Zierath D., Thullbery M., Hadwin J., Gee J.M., Savos A., Kalil A., Becker K.J. CNS immune responses following experimental stroke. Neurocrit. Care, 2010, Vol. 12, no. 2, pp. 274-284.Zierath D., Thullbery M., Hadwin J., Gee J.M., Savos A., Kalil A., Becker K.J. CNS immune responses following experimental stroke. Neurocrit. Care, 2010, Vol. 12, no. 2, pp. 274-284.Ziv Y., Ron N., Butovsky O., Landa G., Sudai E., Greenberg N., Cohen H, Kipnis J., Schwartz M. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat. Neurosci., 2006, Vol. 9, no. 2, pp. 268-275.Ziv Y., Ron N., Butovsky O., Landa G., Sudai E., Greenberg N., Cohen H, Kipnis J., Schwartz M. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat. Neurosci., 2006, Vol. 9, no. 2, pp. 268-275.Zouggari Y., Ait-Oufella H., Waeckel L., Vilar J., Loinard C., Cochain C., Recalde A., Duriez M., Levy B.I., Lutgens E., Mallat Z., Silvestre J.S. Regulatory T cells modulate postischemic neovascularization. Circulation, 2009, Vol. 120, no. 14, pp. 1415-1425.Zouggari Y., Ait-Oufella H., Waeckel L., Vilar J., Loinard C., Cochain C., Recalde A., Duriez M., Levy B.I., Lutgens E., Mallat Z., Silvestre J.S. Regulatory T cells modulate postischemic neovascularization. Circulation, 2009, Vol. 120, no. 14, pp. 1415-1425.Vendrame M., Gemma C., Pennypacker K.R., Bickford P.C., Davis Sanberg C., Sanberg P.R., Willing A.E. Cord blood rescues stroke-induced changes in splenocyte phenotype and function. Exp. Neurol., 2006, Vol. 199, no. 1, pp. 191-200.Vendrame M., Gemma C., Pennypacker K.R., Bickford P.C., Davis Sanberg C., Sanberg P.R., Willing A.E. Cord blood rescues stroke-induced changes in splenocyte phenotype and function. Exp. Neurol., 2006, Vol. 199, no. 1, pp. 191-200.

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