mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2017-1-7-18mimmun-1158Research ArticleОБЗОРЫREVIEWSРОЛЬ МАКРОФАГОВ В ВОССТАНОВЛЕНИИ ПОВРЕЖДЕНИЙ ЦЕНТРАЛЬНОЙ НЕРВНОЙ СИСТЕМЫ: НОВЫЕ ВОЗМОЖНОСТИ В ЛЕЧЕНИИ НЕВРОЛОГИЧЕСКИХ РАССТРОЙСТВTHE ROLE OF MACROPHAGES IN DAMAGE RECOVERY OF CENTRAL NERVOUS SYSTEM: NEW OPTIONS FOR TREATMENT OF NEUROLOGICAL DISORDERSЧерныхЕ. Р.ChernykhE. R.

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

630099, г. Новосибирск, ул. Ядринцевская, 14

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

630099, Novosibirsk, Yadrintsevskaya str. 14

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

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

г. Новосибирск

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

Novosibirsk

ОстанинА. А.OstaninA. A.

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

г. Новосибирск

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

Novosibirsk

ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии»РоссияResearch Institute of Fundamental and Clinical ImmunologyRussian Federation201722012017191718Copyright © Черных Е.Р., Шевела Е.Я., Останин А.А., 20172017Черных Е.Р., Шевела Е.Я., Останин А.А.Chernykh E.R., Shevela E.Y., 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/1158

Смена существующих парадигм относительно регенеративного потенциала центральной нервной системы (ЦНС) и роли иммунных клеток в процессах восстановления поврежденной нервной ткани открывают новые перспективы лечения неврологических расстройств на основе иммуно-терапевтических подходов. Настоящий обзор посвящен анализу роли макрофагов в восстановлении повреждений в ЦНС и включает данные о функциональной гетерогенности клеток микроглии и макрофагов моноцитарного происхождения, путях рекрутирования моноцитов в ЦНС, взаимоотношении клеток микроглии и рекрутируемых макрофагов и балансе М1/М2-клеток при нейропатологии. Кроме того, в обзоре приводится экспериментальное обоснование участия макрофагов в восстановлении повреждений ЦНС и рассматриваются механизмы регенеративной активности макрофагов. Приведенные данные позволяют рассматривать макрофаги в качестве новой мишени терапевтических воздействий для подавления нейровоспалительной реакции и усиления репаративных процессов. Первые шаги в этой области свидетельствуют о перспективности применения моноцитов/ макрофагов или технологий М1→М2 переключения в лечении неврологических расстройств и обосновывают необходимость дальнейших исследований в данном направлении.

Evolution of existing paradigms on regenerative capacity of the central nervous system (CNS) and eventual role of immune cells in restoration of damaged nervous tissue offers new prospectives in treatment of neurological disorders based on immunotherapeutic approaches. Present review article addresses a role of macrophages in restoration of damaged CNS and provides data on functional heterogeneity of resident tissue macrophages (microglia), and monocyte-derived macrophages. We discuss possible ways of monocyte recruitment to CNS, relationships between microglia and recruited macrophages, as well as M1/M2 balance in neurological conditions. Moreover, the review proposes an experimental rationale for macrophage engagement into the CNS damage reconstruction, and concerns the mechanisms of macrophage regenerative activity. In summary, the data presented here allow us to suggest macrophages as a novel therapeutic target for suppression of neuroinflammation and enhancement of reparative processes. The first steps in the field are encouraging, with respect to clinical application of monocytes/macrophages or M1→M2 switching technologies for treatment of the neurological disorders, thus presuming a need for further research in this direction.

ЦНСмакрофагимикроглиямакрофаги моноцитарного происхожденияфункциональные фенотипынейропротекциянейрорегенерацияангиогенезДЦПинсультрегенеративная иммунотерапияcentral nervous systemmacrophagesmicrogliamonocyte-derived macrophagesfunctional phenotypesneuroprotectionneuroregenerationangiogenesiscerebral palsystrokeregenerative immunotherapyReferencesBachstetter A.D., Pabon M.M., Cole M.J., Hudson C.E., Sanberg P.R., Willing A.E., Bickford P.C., Gemma C. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain. BMC Neurosci., 2008, Vol. 9, no. 22, 9 p.Bachstetter A.D., Pabon M.M., Cole M.J., Hudson C.E., Sanberg P.R., Willing A.E., Bickford P.C., Gemma C. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain. BMC Neurosci., 2008, Vol. 9, no. 22, 9 p.Beers D.R., Henkel J.S., Zhao W., Wang J., Huang A., Wen S., Liao B., Appel S.H. Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain, 2011, Vol. 134, no. 5, pp. 1293-1314.Beers D.R., Henkel J.S., Zhao W., Wang J., Huang A., Wen S., Liao B., Appel S.H. Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain, 2011, Vol. 134, no. 5, pp. 1293-1314.Brown B.N., Sicari B.M., Badylak S.F. Rethinking regenerative medicine: amacrophage-centered approach. Front Immunol., 2014, Vol. 5, Article 510, 11 p.Brown B.N., Sicari B.M., Badylak S.F. Rethinking regenerative medicine: amacrophage-centered approach. Front Immunol., 2014, Vol. 5, Article 510, 11 p.Burger D., Molnarfi N., Weber M.S., Brandt K.J., Benkhoucha M., Gruaz L., Chofflon M., Zamvil S.S., Lalive P.H. Glatiramer acetate increases IL-1 receptor antagonist but decreases T cell-induced IL-1b in human monocytes and multiple sclerosis. Proc. Natl. Acad. Sci. USA, 2009, Vol. 106, no. 11, pp. 4355-4359.Burger D., Molnarfi N., Weber M.S., Brandt K.J., Benkhoucha M., Gruaz L., Chofflon M., Zamvil S.S., Lalive P.H. Glatiramer acetate increases IL-1 receptor antagonist but decreases T cell-induced IL-1b in human monocytes and multiple sclerosis. Proc. Natl. Acad. Sci. USA, 2009, Vol. 106, no. 11, pp. 4355-4359.Butovsky O., Ziv Y., Schwartz A., Landa G., Talpalar A.E., Pluchino S., Martino G., Schwartz M. Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/ progenitor cells. Mol. Cell. Neurosci., 2006, Vol. 31, no. 1, pp. 149-160.Butovsky O., Ziv Y., Schwartz A., Landa G., Talpalar A.E., Pluchino S., Martino G., Schwartz M. Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/ progenitor cells. Mol. Cell. Neurosci., 2006, Vol. 31, no. 1, pp. 149-160.Chazaud B. Macrophages: supportive cells for tissue repair and regeneration. Immunobiology, 2014, Vol. 219, no. 3, pp. 172-178.Chazaud B. Macrophages: supportive cells for tissue repair and regeneration. Immunobiology, 2014, Vol. 219, no. 3, pp. 172-178.Chen C.T., Foo N.H., Liu W.S., Chen S.H. Infusion of human umbilical cord blood cells ameliorates hind limb dysfunction in experimental spinal cord injury through anti-inflammatory, vasculogenic and neurotrophic mechanisms. Pediatr Neonatol., 2008, Vol. 49, no. 3, pp. 77-83.Chen C.T., Foo N.H., Liu W.S., Chen S.H. Infusion of human umbilical cord blood cells ameliorates hind limb dysfunction in experimental spinal cord injury through anti-inflammatory, vasculogenic and neurotrophic mechanisms. Pediatr Neonatol., 2008, Vol. 49, no. 3, pp. 77-83.Chernykh E.R., Shevela E.Ya., Sakhno L.V., Tikhonova M.A., Petrovsky Ya.L., Ostanin A.A. The generation and properties of human M2-like macrophages: potential candidates for CNS repair? Cell. Ther. Transplant., 2010, Vol. 2, no. 6, e000080.01.Chernykh E.R., Shevela E.Ya., Sakhno L.V., Tikhonova M.A., Petrovsky Ya.L., Ostanin A.A. The generation and properties of human M2-like macrophages: potential candidates for CNS repair? Cell. Ther. Transplant., 2010, Vol. 2, no. 6, e000080.01.Chernykh E.R., Kafanova M.Yu., Shevela E.Y., Adonina E.I., Sakhno L.V., Tikhonova M.A., Ostanin A.A. Autologous M2-like macrophage applications in children with cerebral palsy. Cell. Ther. Transplant., 2011, Vol. 3, no. 11, e000092.01.Chernykh E.R., Kafanova M.Yu., Shevela E.Y., Adonina E.I., Sakhno L.V., Tikhonova M.A., Ostanin A.A. Autologous M2-like macrophage applications in children with cerebral palsy. Cell. Ther. Transplant., 2011, Vol. 3, no. 11, e000092.01.Chernykh E.R., Kafanova M.Yu., Shevela E.Ya., Sirota S.I., Adonina E.A., Ostanin A.A., Kozlov V.A. Clinical experience with autologous M2-macrophages in children with severe cerebral palsy. Cell. Transplant., 2014, Vol. 23, Suppl. 1, pp. 97-104.Chernykh E.R., Kafanova M.Yu., Shevela E.Ya., Sirota S.I., Adonina E.A., Ostanin A.A., Kozlov V.A. Clinical experience with autologous M2-macrophages in children with severe cerebral palsy. Cell. Transplant., 2014, Vol. 23, Suppl. 1, pp. 97-104.Chernykh E.R., Shevela E.Ya., Starostina N.M., Morozov S.A., Davydova M.N., Menyaeva E.V., Ostanin A.A. Safety and therapeutic potential of M2-macrophages in stroke treatment. Cell. Transplant., 2016, Vol. 25, no. 8, pp. 1461-1471.Chernykh E.R., Shevela E.Ya., Starostina N.M., Morozov S.A., Davydova M.N., Menyaeva E.V., Ostanin A.A. Safety and therapeutic potential of M2-macrophages in stroke treatment. Cell. Transplant., 2016, Vol. 25, no. 8, pp. 1461-1471.Corraliza I. Recruiting specialized macrophages across the borders to restore brain functions. Front. Cell. Neurosci., 2014, Vol. 8, Article 262, 7 p.Corraliza I. Recruiting specialized macrophages across the borders to restore brain functions. Front. Cell. Neurosci., 2014, Vol. 8, Article 262, 7 p.Cotten C.M., Murtha A.P., Goldberg R.N., Grotegut C.A., Smith P.B., Goldstein R.F., Fisher K.A., Gustafson K.E., Waters-Pick B., Swamy G.K., Rattray B., Tan S., Kurtzberg J. Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J. Pediatr., 2014, Vol. 164, no. 5, pp. 973-979.Cotten C.M., Murtha A.P., Goldberg R.N., Grotegut C.A., Smith P.B., Goldstein R.F., Fisher K.A., Gustafson K.E., Waters-Pick B., Swamy G.K., Rattray B., Tan S., Kurtzberg J. Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J. Pediatr., 2014, Vol. 164, no. 5, pp. 973-979.Darlington D., Deng J., Giunta B., Hou H., Sanberg C.D., Kuzmin-Nichols N., Zhou H., Mori T., Ehrhart J., Sanberg P.R., Tan J. Multiple low-dose infusions of human umbilical cord blood cells improve cognitive impairments and reduce amyloid-beta-associated neuropathology in Alzheimer mice. Stem Cells Dev., 2013, Vol. 22, no. 3, pp. 412-421.Darlington D., Deng J., Giunta B., Hou H., Sanberg C.D., Kuzmin-Nichols N., Zhou H., Mori T., Ehrhart J., Sanberg P.R., Tan J. Multiple low-dose infusions of human umbilical cord blood cells improve cognitive impairments and reduce amyloid-beta-associated neuropathology in Alzheimer mice. Stem Cells Dev., 2013, Vol. 22, no. 3, pp. 412-421.David S., Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat. Rev. Neurosci., 2011, Vol. 12, no. 7, pp. 388-399.David S., Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat. Rev. Neurosci., 2011, Vol. 12, no. 7, pp. 388-399.Derecki N.C., Quinnies K.V., Kipnis J. Alternatively activated myeloid (M2) cells enhance cognitive function in immune compromised mice. Brain Behav. Immun., 2011, Vol. 25, no. 3, pp. 379-385.Derecki N.C., Quinnies K.V., Kipnis J. Alternatively activated myeloid (M2) cells enhance cognitive function in immune compromised mice. Brain Behav. Immun., 2011, Vol. 25, no. 3, pp. 379-385.Donnelly D.J., Popovich P.G. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp. Neurol., 2008, Vol. 209, no. 2, pp. 378-388. doi: 10.1016/j.expneurol.2007.06.009Donnelly D.J., Popovich P.G. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp. Neurol., 2008, Vol. 209, no. 2, pp. 378-388. doi: 10.1016/j.expneurol.2007.06.009Eggenhofer E., Hoogduijn M.J. Mesenchymal stem cell-educated macrophages. Transplant. Res., 2012, Vol. 1, p. 12.Eggenhofer E., Hoogduijn M.J. Mesenchymal stem cell-educated macrophages. Transplant. Res., 2012, Vol. 1, p. 12.Garbuzova-Davis S., Rodrigues M.C., Mirtyl S., Turner S., Mitha S., Sodhi J. Multiple intravenous administrations of human umbilical cord blood cells benefit in a mouse model of ALS. PLoS One, 2012, Vol. 7, no. 2, e31254.Garbuzova-Davis S., Rodrigues M.C., Mirtyl S., Turner S., Mitha S., Sodhi J. Multiple intravenous administrations of human umbilical cord blood cells benefit in a mouse model of ALS. PLoS One, 2012, Vol. 7, no. 2, e31254.Garbuzova-Davis S., Xie Y., Danias P., Sanberg C.D., Klasko S.K., Sanberg P.R. Transplantation of cord blood monocyte/ macrophage cells to treat Sanfilippo type B. Cell. Transplant., 2008, Vol. 17, no. 4, pp. 466-467.Garbuzova-Davis S., Xie Y., Danias P., Sanberg C.D., Klasko S.K., Sanberg P.R. Transplantation of cord blood monocyte/ macrophage cells to treat Sanfilippo type B. Cell. Transplant., 2008, Vol. 17, no. 4, pp. 466-467.Gensel J.C., Zhang B. Macrophage activation and its role in repair and pathology after spinal cord injury. Brain Res., 2015, Vol. 1619, pp. 1-11.Gensel J.C., Zhang B. Macrophage activation and its role in repair and pathology after spinal cord injury. Brain Res., 2015, Vol. 1619, pp. 1-11.Gong D., Shi W., Yi S.J., Chen H., Groffen J., Heisterkamp N. TGF-beta signaling plays a critical role in promoting alternative macrophage activation. BMC Immunol., 2012, Vol. 13, p. 31.Gong D., Shi W., Yi S.J., Chen H., Groffen J., Heisterkamp N. TGF-beta signaling plays a critical role in promoting alternative macrophage activation. BMC Immunol., 2012, Vol. 13, p. 31.Greenwood J., Heasman S.J., Alvarez J.I., Prat A., Lyck R., Engelhardt B. Leukocyte-endothelial cell crosstalk at the blood–brain barrier: a prerequisite for successful immune cell entry to the brain. Neuropathol. Appl. Neurobiol., 2011, Vol. 37, no. 1, pp. 24-39.Greenwood J., Heasman S.J., Alvarez J.I., Prat A., Lyck R., Engelhardt B. Leukocyte-endothelial cell crosstalk at the blood–brain barrier: a prerequisite for successful immune cell entry to the brain. Neuropathol. Appl. Neurobiol., 2011, Vol. 37, no. 1, pp. 24-39.Guerrero A.R., Uchida K., Nakajima H., Watanabe S., Nakamura M., Johnson W.E., Baba H. Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice. J. Neuroinflammation, 2012, Vol. 9, p. 40.Guerrero A.R., Uchida K., Nakajima H., Watanabe S., Nakamura M., Johnson W.E., Baba H. Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice. J. Neuroinflammation, 2012, Vol. 9, p. 40.Gurtner G.C., Werner S., Barrandon Y., Longaker M.T. Wound repair and regeneration. Nature, 2008, Vol. 453, no. 7193, pp. 314-321.Gurtner G.C., Werner S., Barrandon Y., Longaker M.T. Wound repair and regeneration. Nature, 2008, Vol. 453, no. 7193, pp. 314-321.Hikawa N., Horie H., Takenaka T. Macrophage-enhanced neurite regeneration of adult dorsal root ganglia neurones in culture. Neuroreport., 1993, Vol. 5, no. 1, pp. 41-44.Hikawa N., Horie H., Takenaka T. Macrophage-enhanced neurite regeneration of adult dorsal root ganglia neurones in culture. Neuroreport., 1993, Vol. 5, no. 1, pp. 41-44.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 after 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 after 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.Jacobi А., Bareyre F.M. Regulation of axonal remodeling following spinal cord injury. Neural Regen. Res., 2015, Vol. 10, no. 10, pp. 1555-1557.Jacobi А., Bareyre F.M. Regulation of axonal remodeling following spinal cord injury. Neural Regen. Res., 2015, Vol. 10, no. 10, pp. 1555-1557.Jiang M.H., Chung E., Chi G.F., Ahn W., Lim J.E., Hong H.S., Kim D.W., Choi H., Kim J., Son Y. Substance P induces M2-type macrophages after spinal cord injury. Neuroreport., 2012, Vol. 23, no. 13, pp. 786-792.Jiang M.H., Chung E., Chi G.F., Ahn W., Lim J.E., Hong H.S., Kim D.W., Choi H., Kim J., Son Y. Substance P induces M2-type macrophages after spinal cord injury. Neuroreport., 2012, Vol. 23, no. 13, pp. 786-792.Kang M., Min K., Jang J., Kim S.C., Kang M.S., Jang S.J., Lee J.Y., Kim S.H., Kim M.K., An S.A., Kim M. Involvement of immune responses in the efficacy of cord blood cell therapy for cerebral palsy. Stem Cells Dev., 2015, Vol. 24, no. 19, pp. 2259-2268.Kang M., Min K., Jang J., Kim S.C., Kang M.S., Jang S.J., Lee J.Y., Kim S.H., Kim M.K., An S.A., Kim M. Involvement of immune responses in the efficacy of cord blood cell therapy for cerebral palsy. Stem Cells Dev., 2015, Vol. 24, no. 19, pp. 2259-2268.Kieseier B.C. The mechanism of action of interferon-beta in relapsing multiple sclerosis. CNS Drugs, 2011, Vol. 25, no. 6, pp. 491-502.Kieseier B.C. The mechanism of action of interferon-beta in relapsing multiple sclerosis. CNS Drugs, 2011, Vol. 25, no. 6, pp. 491-502.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.Koh T.J., DiPietro L.A. Inflammation and wound healing: the role of the macrophage. Expert Rev. Mol. Med., 2011, Vol. 13, e23.Koh T.J., DiPietro L.A. Inflammation and wound healing: the role of the macrophage. Expert Rev. Mol. Med., 2011, Vol. 13, e23.Kwon M.J., Kim J., Shin H., Jeong S.R., Kang Y.M., Choi J.Y., Hwang D.H., Kim B.G. Contribution of macrophages to enhanced regenerative capacity of dorsal root ganglia sensory neurons by conditioning injury. J. Neurosci., 2013, Vol. 33, no. 38, pp. 15095-15108.Kwon M.J., Kim J., Shin H., Jeong S.R., Kang Y.M., Choi J.Y., Hwang D.H., Kim B.G. Contribution of macrophages to enhanced regenerative capacity of dorsal root ganglia sensory neurons by conditioning injury. J. Neurosci., 2013, Vol. 33, no. 38, pp. 15095-15108.Kwon M.J., Shin H.Y., Cui Y., Kim H., Thi A.H., Choi J.Y., Kim E.Y., Hwang D.H., Kim B.G. CCL2 Mediates neuron-macrophage interactions to drive proregenerative macrophage activation following preconditioning injury. J. Neurosci., 2015, Vol. 35, no. 48, pp. 15934-15947.Kwon M.J., Shin H.Y., Cui Y., Kim H., Thi A.H., Choi J.Y., Kim E.Y., Hwang D.H., Kim B.G. CCL2 Mediates neuron-macrophage interactions to drive proregenerative macrophage activation following preconditioning injury. J. Neurosci., 2015, Vol. 35, no. 48, pp. 15934-15947.Larochelle C., Alvarez J.I., Prat A. How do immune cells overcome the blood-brain barrier in multiple sclerosis? FEBS Lett., 2011, Vol. 585, no. 23, pp. 3770-3780.Larochelle C., Alvarez J.I., Prat A. How do immune cells overcome the blood-brain barrier in multiple sclerosis? FEBS Lett., 2011, Vol. 585, no. 23, pp. 3770-3780.Lech M., Anders H-J. Macrophages and fibrosis: How resident and infiltrating mononuclear phagocytes orchestrate all phases of tissue injury and repair. Biochim. Biophys. Acta, 2013, Vol. 1832, no. 7, pp. 989-997.Lech M., Anders H-J. Macrophages and fibrosis: How resident and infiltrating mononuclear phagocytes orchestrate all phases of tissue injury and repair. Biochim. Biophys. Acta, 2013, Vol. 1832, no. 7, pp. 989-997.Lee C.H., Park O.K., Yoo K.Y., Byun K., Lee B., Choi J.H., Hwang I.K., Kim Y.M., Won M.H. The role of peroxisome proliferator-activated receptor γ, and effects of its agonist, rosiglitazone, on transient cerebral ischemic damage. J. Neurol. Sci., 2011, Vol. 300, no. 1-2, pp. 120-129.Lee C.H., Park O.K., Yoo K.Y., Byun K., Lee B., Choi J.H., Hwang I.K., Kim Y.M., Won M.H. The role of peroxisome proliferator-activated receptor γ, and effects of its agonist, rosiglitazone, on transient cerebral ischemic damage. J. Neurol. Sci., 2011, Vol. 300, no. 1-2, pp. 120-129.Lo E.H. Degeneration and repair in central nervous system disease. Nat. Med., 2010, Vol. 16, no. 11, pp. 1205-1209.Lo E.H. Degeneration and repair in central nervous system disease. Nat. Med., 2010, Vol. 16, no. 11, pp. 1205-1209.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, Article 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, Article 34, 10 p.London A., Itskovich E., Benhar I., Kalchenko V., Mack M., Jung S. Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J. Exp. Med., 2011, Vol. 208, no. 1, pp. 23-39.London A., Itskovich E., Benhar I., Kalchenko V., Mack M., Jung S. Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J. Exp. Med., 2011, Vol. 208, no. 1, pp. 23-39.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.Lu D., Sanberg P.R., Mahmood A., Li Y., Wang L., Sanchez-Ramos J., Chopp M. Intravenous administration of human umbilical cord blood reduces neurological deficit in the rat after traumatic brain injury. Cell. Transplant., 2002, Vol. 11, no. 3, pp. 275-281.Lu D., Sanberg P.R., Mahmood A., Li Y., Wang L., Sanchez-Ramos J., Chopp M. Intravenous administration of human umbilical cord blood reduces neurological deficit in the rat after traumatic brain injury. Cell. Transplant., 2002, Vol. 11, no. 3, pp. 275-281.Lu W., Fu C., Song L., Yao Y., Zhang X., Chen Z., Li Y., Ma G., Shen C. Exposure to supernatants of macrophages that phagocytized dead mesenchymal stem cells improves hypoxic cardiomyocytes survival. Int. J. Cardiol., 2013, Vol. 165, no. 2, pp. 333-340Lu W., Fu C., Song L., Yao Y., Zhang X., Chen Z., Li Y., Ma G., Shen C. Exposure to supernatants of macrophages that phagocytized dead mesenchymal stem cells improves hypoxic cardiomyocytes survival. Int. J. Cardiol., 2013, Vol. 165, no. 2, pp. 333-340Lucas S.-M., Rothwell N.J., Gibson R.M. The role of inflammation in CNS injury and disease. Br. J. Pharmacol., 2006, Vol. 147, Suppl. 1, S232-S240.Lucas S.-M., Rothwell N.J., Gibson R.M. The role of inflammation in CNS injury and disease. Br. J. Pharmacol., 2006, Vol. 147, Suppl. 1, S232-S240.Lv Y.T., Zhang Y., Liu M., Qiuwaxi J.N., Ashwood P., Cho S.C., Huan Y., Ge R.C., Chen X.W., Wang Z.J., Kim B.J., Hu X. Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. J. Transl. Med., 2013, Vol. 11, p. 196.Lv Y.T., Zhang Y., Liu M., Qiuwaxi J.N., Ashwood P., Cho S.C., Huan Y., Ge R.C., Chen X.W., Wang Z.J., Kim B.J., Hu X. Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. J. Transl. Med., 2013, Vol. 11, p. 196.Maiorino C., Khorooshi R., Ruffini F., Løbner M., Bergami A., Garzetti L., Martino G., Owens T., Furlan R. Lentiviral-mediated administration of IL-25 in the CNS induces alternative activation of microglia. Gene Ther., 2013, Vol. 20, no. 5, pp. 487-496.Maiorino C., Khorooshi R., Ruffini F., Løbner M., Bergami A., Garzetti L., Martino G., Owens T., Furlan R. Lentiviral-mediated administration of IL-25 in the CNS induces alternative activation of microglia. Gene Ther., 2013, Vol. 20, no. 5, pp. 487-496.Mandrekar-Colucci S., Sauerbeck A., Popovich P.G., McTigue D.M. PPAR agonists as therapeutics for CNS trauma and neurological diseases. ASN Neuro, 2013, Vol. 5, no. 5, e00129.Mandrekar-Colucci S., Sauerbeck A., Popovich P.G., McTigue D.M. PPAR agonists as therapeutics for CNS trauma and neurological diseases. ASN Neuro, 2013, Vol. 5, no. 5, e00129.Marchetti V., Yanes O., Aguilar E., Wang M., Friedlander D., Moreno S., Storm K, Zhan M., Naccache S., Nemerow G., Siuzdak G., Friedlander M. Differential macrophage polarization promotes tissue remodeling and repair in a model of ischemic retinopathy. Sci Rep., 2011, Vol. 1, p. 76.Marchetti V., Yanes O., Aguilar E., Wang M., Friedlander D., Moreno S., Storm K, Zhan M., Naccache S., Nemerow G., Siuzdak G., Friedlander M. Differential macrophage polarization promotes tissue remodeling and repair in a model of ischemic retinopathy. Sci Rep., 2011, Vol. 1, p. 76.Martinez F.O., Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep., 2014, Vol. 6, p. 13.Martinez F.O., Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep., 2014, Vol. 6, p. 13.Meeker R.B., Williams K., Killebrew D.A., Hudson L.C. Cell trafficking through the choroid plexus. Cell Adhes Migr., 2012, Vol. 6, no. 5, pp. 390-396.Meeker R.B., Williams K., Killebrew D.A., Hudson L.C. Cell trafficking through the choroid plexus. Cell Adhes Migr., 2012, Vol. 6, no. 5, pp. 390-396.Meier C., Middelanis J., Wasielewski B., Neuhoff S., Roth-Haerer A., Gantert M., Dinse H.R., Dermietzel R., Jensen A. Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells. Pediatr Res., 2006, Vol. 59, no. 2, pp. 244-249.Meier C., Middelanis J., Wasielewski B., Neuhoff S., Roth-Haerer A., Gantert M., Dinse H.R., Dermietzel R., Jensen A. Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells. Pediatr Res., 2006, Vol. 59, no. 2, pp. 244-249.Mikita J., Dubourdieu-Cassagno N., Deloire M.S., Vekris A., Biran M., Raffard G., Brochet B., Canron M.H., Franconi J.M., Boiziau C., Petry K.G. Altered M1/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration. Mult. Scler., 2011, Vol.17, no. 1, pp. 2-15.Mikita J., Dubourdieu-Cassagno N., Deloire M.S., Vekris A., Biran M., Raffard G., Brochet B., Canron M.H., Franconi J.M., Boiziau C., Petry K.G. Altered M1/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration. Mult. Scler., 2011, Vol.17, no. 1, pp. 2-15.Mildner A., Mack M., Schmidt H., Bruck W., Djukic M., Zabel M.D., Hille A., Priller J., Prinz M. CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain, 2009, Vol. 132, pp. 2487-2500.Mildner A., Mack M., Schmidt H., Bruck W., Djukic M., Zabel M.D., Hille A., Priller J., Prinz M. CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain, 2009, Vol. 132, pp. 2487-2500.Min K., Song J., Kang J.Y., Ko J., Ryu J.S., Kang M.S., Jang S.J., Kim S.H., Oh D., Kim M.K., Kim S.S., Kim M. Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: a double-blind, randomized, placebo-controlled trial. Stem Cells, 2013, Vol. 31, no. 3, pp. 581-591.Min K., Song J., Kang J.Y., Ko J., Ryu J.S., Kang M.S., Jang S.J., Kim S.H., Oh D., Kim M.K., Kim S.S., Kim M. Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: a double-blind, randomized, placebo-controlled trial. Stem Cells, 2013, Vol. 31, no. 3, pp. 581-591.Miron V.E., Boyd A., Zhao J.W., Yuen T.J., Ruckh J.M., Shadrach J.L., van Wijngaarden P., Wagers A.J., Williams A., Franklin R.J. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat. Neurosci., 2013, Vol. 16, no. 9, pp. 1211-1218.Miron V.E., Boyd A., Zhao J.W., Yuen T.J., Ruckh J.M., Shadrach J.L., van Wijngaarden P., Wagers A.J., Williams A., Franklin R.J. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat. Neurosci., 2013, Vol. 16, no. 9, pp. 1211-1218.Moehle M.S., West A.B. M1 and M2 immune activation in Parkinson’s Disease: Foe and ally? Neuroscience, 2015, Vol. 302, pp. 59-73.Moehle M.S., West A.B. M1 and M2 immune activation in Parkinson’s Disease: Foe and ally? Neuroscience, 2015, Vol. 302, pp. 59-73.Mosser D.M., Edwards J.P. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol., 2008, Vol. 8, no. 12, pp. 958-969.Mosser D.M., Edwards J.P. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol., 2008, Vol. 8, no. 12, pp. 958-969.Narantuya D., Nagai A., Sheikh A.M., Masuda J., Kobayashi S., Yamaguchi S., Kim S.U. Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement. PLoS One, 2010, Vol. 5, no. 7, e11746.Narantuya D., Nagai A., Sheikh A.M., Masuda J., Kobayashi S., Yamaguchi S., Kim S.U. Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement. PLoS One, 2010, Vol. 5, no. 7, e11746.Pimentel-Coelho P.M., Magalhaes E.S., Lopes L.M., de Azevedo L.C., Santiago M.F., Mendez-Otero R. Human cord blood transplantation in a neonatal rat model of hypoxic-ischemic brain damage: functional outcome related to neuroprotection in the striatum. Stem Cells Dev., 2010, Vol. 19, no. 3, pp. 351-358.Pimentel-Coelho P.M., Magalhaes E.S., Lopes L.M., de Azevedo L.C., Santiago M.F., Mendez-Otero R. Human cord blood transplantation in a neonatal rat model of hypoxic-ischemic brain damage: functional outcome related to neuroprotection in the striatum. Stem Cells Dev., 2010, Vol. 19, no. 3, pp. 351-358.Prinz M., Priller J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat. Rev. Neurosci., 2014, Vol. 15, no. 5, pp. 300-312.Prinz M., Priller J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat. Rev. Neurosci., 2014, Vol. 15, no. 5, pp. 300-312.Protti A. , Mongue-Din H., Mylonas K.J., Sirker A., Sag C.M., Swim M.M., Maier L., Sawyer G., Dong X, Botnar R., Salisbury J., Gray J.A., Shah A.M. Bone marrow transplantation modulates tissue macrophage phenotype and enhances cardiac recovery after subsequent acute myocardial infarction. J. Mol. Cell. Cardiol., 2016, Vol. 90, pp. 120-128.Protti A. , Mongue-Din H., Mylonas K.J., Sirker A., Sag C.M., Swim M.M., Maier L., Sawyer G., Dong X, Botnar R., Salisbury J., Gray J.A., Shah A.M. Bone marrow transplantation modulates tissue macrophage phenotype and enhances cardiac recovery after subsequent acute myocardial infarction. J. Mol. Cell. Cardiol., 2016, Vol. 90, pp. 120-128.Rapalino O., Lazarov-Spiegler O., Agranov E., Velan G.J., Yoles E., Fraidakis M., Solomon A., Gepstein R., Katz A., Belkin M., Hadani M., Schwartz M. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat. Med., 1998, Vol. 4, no. 7, pp. 814-821.Rapalino O., Lazarov-Spiegler O., Agranov E., Velan G.J., Yoles E., Fraidakis M., Solomon A., Gepstein R., Katz A., Belkin M., Hadani M., Schwartz M. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat. Med., 1998, Vol. 4, no. 7, pp. 814-821.Rawji K.S., Yong. V.W. The benefits and detriments of macrophages/microglia in models of multiple sclerosis. Clin. Dev. Immunol., 2013, Vol. 2013, Article 948976, 13 p.Rawji K.S., Yong. V.W. The benefits and detriments of macrophages/microglia in models of multiple sclerosis. Clin. Dev. Immunol., 2013, Vol. 2013, Article 948976, 13 p.Rawji K.S., Mishra M.K., Yong V.W. Regenerative capacity of macrophages for remyelination. Front Cell Dev. Biol., 2016, Vol. 4, p. 47.Rawji K.S., Mishra M.K., Yong V.W. Regenerative capacity of macrophages for remyelination. Front Cell Dev. Biol., 2016, Vol. 4, p. 47.Rocher C., Singla D.K. SMAD-PI3K-Akt-mTOR pathway mediates BMP-7 polarization of monocytes into M2 macrophages. PLoS One, 2013, Vol. 8, no. 12, e84009.Rocher C., Singla D.K. SMAD-PI3K-Akt-mTOR pathway mediates BMP-7 polarization of monocytes into M2 macrophages. PLoS One, 2013, Vol. 8, no. 12, e84009.Rolls A. Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation. PLoS Med., 2008, Vol. 5, no. 8, e171.Rolls A. Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation. PLoS Med., 2008, Vol. 5, no. 8, e171.Sakhno L.V., Shevela E.Y., Tikhonova M.A., Ostanin A.A., Chernykh E.R. The phenotypic and functional features of human M2 macrophages generated under low serum conditions. Scand. J. Immunol., 2016, Vol. 83, no. 2, pp. 151-159.Sakhno L.V., Shevela E.Y., Tikhonova M.A., Ostanin A.A., Chernykh E.R. The phenotypic and functional features of human M2 macrophages generated under low serum conditions. Scand. J. Immunol., 2016, Vol. 83, no. 2, pp. 151-159.Sanberg P.R., Park D-H., Kuzmin-Nichols N., Cruz E., Hossne N.A. Jr, Buffolo E., Willing A.E. Monocyte transplantation for neural and cardiovascular ischemia repair. J. Cell. Mol. Med., 2010, Vol. 14, no. 3, pp. 553-563.Sanberg P.R., Park D-H., Kuzmin-Nichols N., Cruz E., Hossne N.A. Jr, Buffolo E., Willing A.E. Monocyte transplantation for neural and cardiovascular ischemia repair. J. Cell. Mol. Med., 2010, Vol. 14, no. 3, pp. 553-563.Shahaduzzaman M.D., Mehta V., Golden J.E., Rowe D.D., Green S., Tadinada R., Foran E.A., Sanberg P.R., Pennypacker R.R., Willing A.E. Human umbilical cord blood cells induce neuroprotective change in gene expression profile in neurons after ischemia through activation of Akt pathway. Cell. Transplant., 2015, Vol. 24, no. 4, pp. 721-735.Shahaduzzaman M.D., Mehta V., Golden J.E., Rowe D.D., Green S., Tadinada R., Foran E.A., Sanberg P.R., Pennypacker R.R., Willing A.E. Human umbilical cord blood cells induce neuroprotective change in gene expression profile in neurons after ischemia through activation of Akt pathway. Cell. Transplant., 2015, Vol. 24, no. 4, pp. 721-735.Shechter R., London A., Schwartz M. Orchestrated leukocyte recruitment to immune-privileged sites: absolute barriers versus educational gates. Nat. Rev. Immunol., 2013, Vol. 13, no. 3, pp. 206-218.Shechter R., London A., Schwartz M. Orchestrated leukocyte recruitment to immune-privileged sites: absolute barriers versus educational gates. Nat. Rev. Immunol., 2013, Vol. 13, no. 3, pp. 206-218.Shechter R., London A., Varol C., Raposo C., Cusimano M., Yovel G., Rolls A., Mack M., Pluchino S., Martino G., Jung S., Schwartz M. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med., 2009, Vol. 6, no. 7, e1000113.Shechter R., London A., Varol C., Raposo C., Cusimano M., Yovel G., Rolls A., Mack M., Pluchino S., Martino G., Jung S., Schwartz M. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med., 2009, Vol. 6, no. 7, e1000113.Shechter R., Miller O., Yovel G., Rosenzweig N., London A., Ruckh J., Kim K.W., Klein E., Kalchenko V., Bendel P., Lira S.A., Jung S., Schwartz M. Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Immunity, 2013, Vol. 38, no. 3, pp. 555-569.Shechter R., Miller O., Yovel G., Rosenzweig N., London A., Ruckh J., Kim K.W., Klein E., Kalchenko V., Bendel P., Lira S.A., Jung S., Schwartz M. Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Immunity, 2013, Vol. 38, no. 3, pp. 555-569.Shechter R., Schwartz M. Harnessing monocyte-derived macrophages to control central nervous system pathologies: no longer ‘if ’ but ‘how’. J. Pathol., 2013, Vol. 229, pp. 332-346.Shechter R., Schwartz M. Harnessing monocyte-derived macrophages to control central nervous system pathologies: no longer ‘if ’ but ‘how’. J. Pathol., 2013, Vol. 229, pp. 332-346.Simard A.R., Soulet D., Gowing G., Julien J.P., Rivest S. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron, 2006, Vol. 49, no. 4, pp. 489-502.Simard A.R., Soulet D., Gowing G., Julien J.P., Rivest S. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron, 2006, Vol. 49, no. 4, pp. 489-502.Starossom S.C., Mascanfroni I.D., Imitola J., Cao L., Raddassi K., Hernandez S.F., Bassil R., Croci D.O., Cerliani J.P., Delacour D., Wang Y., Elyaman W., Khoury S.J., Rabinovich G.A. Galectin-1 deactivates classically activated microglia and protects from inflammation-induced neurodegeneration. Immunity, 2012, Vol. 37, no. 2, pp. 249-263.Starossom S.C., Mascanfroni I.D., Imitola J., Cao L., Raddassi K., Hernandez S.F., Bassil R., Croci D.O., Cerliani J.P., Delacour D., Wang Y., Elyaman W., Khoury S.J., Rabinovich G.A. Galectin-1 deactivates classically activated microglia and protects from inflammation-induced neurodegeneration. Immunity, 2012, Vol. 37, no. 2, pp. 249-263.Stefater J.A., Ren S., Lang R.A., Duffield J.S. Metchnikoff ’s policemen: macrophages in development, homeostasis and regeneration. Trends Mol. Med., 2011, Vol. 17, no. 12, pp. 743-752.Stefater J.A., Ren S., Lang R.A., Duffield J.S. Metchnikoff ’s policemen: macrophages in development, homeostasis and regeneration. Trends Mol. Med., 2011, Vol. 17, no. 12, pp. 743-752.Thored P., Heldmann U., Gomes-Leal W., Gisler R., Darsalia V., Taneera J., Nygren J.M., Jacobsen S.E., Ekdahl C.T., Kokaia Z., Lindvall O. Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia, 2009, Vol. 57, no. 8, pp. 835-849.Thored P., Heldmann U., Gomes-Leal W., Gisler R., Darsalia V., Taneera J., Nygren J.M., Jacobsen S.E., Ekdahl C.T., Kokaia Z., Lindvall O. Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia, 2009, Vol. 57, no. 8, pp. 835-849.Vendrame M., Gemma C., de Mesquita D., Collier L., Bickford P.C., Sanberg C.D., Sanberg P.R., Pennypacker K.R., Willing A.E. Anti-inflammatory effects of human cord blood cells in a rat model of stroke. Stem Cells Dev., 2005, Vol. 14, no. 5, pp. 595-604.Vendrame M., Gemma C., de Mesquita D., Collier L., Bickford P.C., Sanberg C.D., Sanberg P.R., Pennypacker K.R., Willing A.E. Anti-inflammatory effects of human cord blood cells in a rat model of stroke. Stem Cells Dev., 2005, Vol. 14, no. 5, pp. 595-604.Verma S., Nakaoke R., Dohgu S., Banks W.A. Release of cytokines by brain endothelial cells: A polarized response to lipopolysaccharide. Brain Behav. Immun., 2006, Vol. 20, no. 5, pp. 449-455.Verma S., Nakaoke R., Dohgu S., Banks W.A. Release of cytokines by brain endothelial cells: A polarized response to lipopolysaccharide. Brain Behav. Immun., 2006, Vol. 20, no. 5, pp. 449-455.Walker P.A., Shah S.K., Jimenez F., Aroom K.R., Harting M.T., Cox C.S. Jr. Bone marrow-derived stromal cell therapy for traumatic brain injury is neuroprotective via stimulation of non-neurologic organ systems. Surgery, 2012, Vol. 152, no. 5, pp. 790-793.Walker P.A., Shah S.K., Jimenez F., Aroom K.R., Harting M.T., Cox C.S. Jr. Bone marrow-derived stromal cell therapy for traumatic brain injury is neuroprotective via stimulation of non-neurologic organ systems. Surgery, 2012, Vol. 152, no. 5, pp. 790-793.Wang G., Zhang J., Hu X., Zhang L., Mao L., Jiang X., Chen J. Microglia/macrophage polarization dynamics in white matter after traumatic brain injury. J. Cereb. Blood Flow Metab., 2013, Vol. 33, no. 12, pp. 1864-1874.Wang G., Zhang J., Hu X., Zhang L., Mao L., Jiang X., Chen J. Microglia/macrophage polarization dynamics in white matter after traumatic brain injury. J. Cereb. Blood Flow Metab., 2013, Vol. 33, no. 12, pp. 1864-1874.Wang X., Cao K., Sun X., Chen Y., Duan Z., Sun L., Guo L., Bai P., Sun D., Fan J., He X., Young W., Ren Y. Macrophages in spinal cord injury: phenotypic and functional change from exposure to myelin debris. Glia, 2015, Vol. 63, no. 4, pp. 635-651.Wang X., Cao K., Sun X., Chen Y., Duan Z., Sun L., Guo L., Bai P., Sun D., Fan J., He X., Young W., Ren Y. Macrophages in spinal cord injury: phenotypic and functional change from exposure to myelin debris. Glia, 2015, Vol. 63, no. 4, pp. 635-651.Womble T.A., S. Green M., Shahaduzzaman J., Grieco P.R., Sanberg K.R., Pennypacker A.E., Willing A.E. Monocytes are essential for the neuroprotective effect of human cord blood cells following middle cerebral artery occlusion in rat. Mol. Cell. Neurosci., 2014, Vol. 59, pp. 76-84.Womble T.A., S. Green M., Shahaduzzaman J., Grieco P.R., Sanberg K.R., Pennypacker A.E., Willing A.E. Monocytes are essential for the neuroprotective effect of human cord blood cells following middle cerebral artery occlusion in rat. Mol. Cell. Neurosci., 2014, Vol. 59, pp. 76-84.Wynn T.A., Vannella K.M. Macrophages in tissue repair, regeneration, and fibrosis. Immunity, 2016, Vol. 44, no. 3, pp. 450-462.Wynn T.A., Vannella K.M. Macrophages in tissue repair, regeneration, and fibrosis. Immunity, 2016, Vol. 44, no. 3, pp. 450-462.Xiong X.Y., Liu L., Yang Q.W. Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after 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 after stroke. Prog. Neurobiol., 2016, Vol. 142, pp. 23-44.Yang J., Ding S., Huang W., Hu J., Huang S., Zhang Y., Zhuge Q. Interleukin-4 ameliorates the functional recovery of intracerebral hemorrhage through the alternative activation of microglia/macrophage. Front Neurosci., 2016, Vol. 10, p. 61.Yang J., Ding S., Huang W., Hu J., Huang S., Zhang Y., Zhuge Q. Interleukin-4 ameliorates the functional recovery of intracerebral hemorrhage through the alternative activation of microglia/macrophage. Front Neurosci., 2016, Vol. 10, p. 61.Yin Y., Henzl M.T., Lorber B., Nakazawa T., Thomas T.T., Jiang F., Langer R., Benowitz L.I. Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat. Neurosci., 2006, Vol. 9, no. 6, pp. 843-852.Yin Y., Henzl M.T., Lorber B., Nakazawa T., Thomas T.T., Jiang F., Langer R., Benowitz L.I. Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat. Neurosci., 2006, Vol. 9, no. 6, pp. 843-852.Zhu W., Fan Y., Frenzel T., Gasmi M., Bartus R. T., Young W. L., Chen, Y. Insulin growth factor-1 gene transfer enhances neurovascular remodeling and improves long-term stroke outcome in mice. Stroke, 2008, Vol. 39, no. 4, pp. 1254-1261.Zhu W., Fan Y., Frenzel T., Gasmi M., Bartus R. T., Young W. L., Chen, Y. Insulin growth factor-1 gene transfer enhances neurovascular remodeling and improves long-term stroke outcome in mice. Stroke, 2008, Vol. 39, no. 4, pp. 1254-1261.

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