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Role of alarmins in poststroke inflammation and neuronal repair

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Abstract

Severe loss of cerebral blood flow causes hypoxia and glucose deprivation in the brain tissue, resulting in necrotic cell death in the ischemic brain. Several endogenous molecules, called alarmins or damage-associated molecular patterns (DAMPs), are extracellularly released from the dead cells to activate pattern recognition receptors (PRRs) in immune cells that infiltrate into ischemic brain tissue following the disruption of the blood–brain barrier (BBB) after stroke onset. The activated immune cells produce various inflammatory cytokines and chemokines, triggering sterile cerebral inflammation in the ischemic brain that causes further neuronal cell death. Poststroke inflammation is resolved within several days after stroke onset, and neurological functions are restored to some extent as neural repair occurs around peri-infarct neurons. Clearance of DAMPs from the injured brain is necessary for the resolution of poststroke inflammation. Neurons and glial cells also express PRRs and receive DAMP signaling. Although the role of PRRs in neural cells in the ischemic brain has not yet been clarified, the signaling pathway is likely to be contribute to stroke pathology and neural repair after ischemic stroke. This review describes the molecular dynamics, signaling pathways, and functions of DAMPs in poststroke inflammation and its resolution.

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Funding

This work was supported by the Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST, JP21gm1210010), the Japan Society for the Promotion of Science (JSPS) KAKENHI (21H02820, 21K06386), Takeda Science Foundation, and the Uehara Memorial Foundation.

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  1. Stroke Renaissance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo, 156-8506, Japan

    Seiichiro Sakai & Takashi Shichita

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Sakai, S., Shichita, T. Role of alarmins in poststroke inflammation and neuronal repair. Semin Immunopathol 45, 427–435 (2023). https://doi.org/10.1007/s00281-022-00961-5

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