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Yoshimura et al. Neuroimmunol Neuroinflammation 2020;7:264-76 Neuroimmunology
DOI: 10.20517/2347-8659.2020.22 and Neuroinflammation

Review Open Access

Resolution of inflammation and repair after ischemic
brain injury

Akihiko Yoshimura , Minako Ito 1,2
1
1 Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
2 Division of Allergy and Immunology, Medical Institute of Bioregulation Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka
812-8582, Japan.

Correspondence to: Dr. Minako Ito and Dr. Akihiko Yoshimura, Department of Microbiology and Immunology, Keio University
School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582, Japan. E-mail: minakoito@bioreg.kyushu-u.ac.jp;
yoshimura@keio.jp

How to cite this article: Yoshimura A, Ito M. Resolution of inflammation and repair after ischemic brain injury. Neuroimmunol
Neuroinflammation 2020;7:264-76. http://dx.doi.org/10.20517/2347-8659.2020.22

Received: 9 Mar 2020 First Decision: 27 Apr 2020 Revised: 5 May 2020 Accepted: 29 May 2020 Available Online: 30 Jul 2020
Academic Editor: Christiane Charriaut-Marlangue Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
After ischemic stroke, proinflammatory molecules known as danger-associated molecular patterns (DAMPs)
originating from damaged brain cells recruit and activate immune cells (neutrophils, macrophages, lymphocytes)
further eliciting innate and adaptive immunity. During the acute phase from day 1 to day 3 of the stroke onset,
macrophages play a major role in the progression of inflammation, promoting the destruction of brain tissue.
During the recovery phase, from day 3~4 to day 7 after stroke onset, infiltrating macrophages switch to repairing
macrophages, which clear the DAMPs and promote tissue repair by producing neurotrophic factors. Adaptive
immunity during the late or chronic phase (> day 7) of stroke has not been well investigated. Recent studies have
also indicated that antigen-specific T cells, especially regulatory T cells (Tregs), play major roles in neural repair.
This review focuses mainly on the resolution of inflammation and tissue repair by macrophages and Tregs.

Keywords: DAMPs, tissue repair, macrophages regulatory T cells, amphiregulin, IL-33

INTRODUCTION
Ischemic cerebral infarction accounts for 70% to 80% of all strokes, which is the leading cause of severe
[1]
neuropathy, disability and bedriddenness . Ischemic stroke causes the death of nerve cells as well as
destruction of neuronal circuits, which leads to movement disorders, higher brain dysfunction, and sensory

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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