Seminars in Immunopathology

, Volume 40, Issue 6, pp 523–538 | Cite as

Pivotal role of innate myeloid cells in cerebral post-ischemic sterile inflammation

  • Jun Tsuyama
  • Akari Nakamura
  • Hiroaki Ooboshi
  • Akihiko Yoshimura
  • Takashi ShichitaEmail author


Inflammatory responses play a multifaceted role in regulating both disability and recovery after ischemic brain injury. In the acute phase of ischemic stroke, resident microglia elicit rapid inflammatory responses by the ischemic milieu. After disruption of the blood-brain barrier, peripheral-derived neutrophils and mononuclear phagocytes infiltrate into the ischemic brain. These infiltrating myeloid cells are activated by the endogenous alarming molecules released from dying brain cells. Inflammation after ischemic stroke thus typically consists of sterile inflammation triggered by innate immunity, which exacerbates the pathologies of ischemic stroke and worsens neurological prognosis. Infiltrating immune cells sustain the post-ischemic inflammation for several days; after this period, however, these cells take on a repairing function, phagocytosing inflammatory mediators and cellular debris. This time-specific polarization of immune cells in the ischemic brain is a potential novel therapeutic target. In this review, we summarize the current understanding of the phase-dependent role of innate myeloid cells in ischemic stroke and discuss the cellular and molecular mechanisms of their inflammatory or repairing polarization from a therapeutic perspective.


Sterile inflammation Ischemic stroke Innate myeloid cells Polarization of mononuclear phagocytes 


Funding information

This research was supported by AMED under grant no. JP18gm5910023 and JP18ek0210100, MEXT Grant-in-Aid for Young Scientists (A) (JP17H05096), Grant-in-Aid for Challenging Exploratory Research (JP17K19571), Grant-in-Aid for Scientific Research on Innovative Areas (JP17H05514), The Naito Foundation, SENSHIN Medical Research Foundation, MSD Life Science Foundation, The Ichiro Kanehara Foundation, Kishimoto Foundation Research Grant, The Tokyo Biochemical Research Foundation (T.S.), and MEXT Grant-in-Aid for Young Scientists (B) (JP17K15204) (J.T.)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jun Tsuyama
    • 1
  • Akari Nakamura
    • 1
  • Hiroaki Ooboshi
    • 2
  • Akihiko Yoshimura
    • 3
  • Takashi Shichita
    • 1
    • 4
    Email author
  1. 1.Stroke Renaissance ProjectTokyo Metropolitan Institute of Medical ScienceTokyoJapan
  2. 2.Department of Internal MedicineFukuoka Dental College Medical and Dental HospitalFukuokaJapan
  3. 3.Department of Microbiology and Immunology, School of MedicineKeio UniversityTokyoJapan
  4. 4.Japan Agency for Medical Research and Development (AMED)TokyoJapan

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