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Microglia and macrophages are the professional phagocytes of the CNS. By clearing toxic cellular debris and reshaping the extracellular matrix, microglia\/macrophages help pilot the brain repair and functional recovery process. However, CNS resident and invading immune cells can also magnify tissue damage by igniting runaway inflammation and phagocytosing stressed\u2014but viable\u2014neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Microglia\/macrophages help mediate intercellular communication and react quickly to the \u201cfind\u2010me\u201d signals expressed by dead\/dying neurons. The activated microglia\/macrophages then migrate to the injury site to initiate the phagocytic process upon encountering \u201ceat\u2010me\u201d signals on the surfaces of endangered cells. Thus, healthy cells attempt to avoid inappropriate engulfment by expressing \u201cdo not\u2010eat\u2010me\u201d signals. Microglia\/macrophages also have the capacity to phagocytose immune cells that invade the injured brain (e.g., neutrophils) and to regulate their pro\u2010inflammatory properties. During brain recovery, microglia\/macrophages engulf myelin debris, initiate synaptogenesis and neurogenesis, and sculpt a favorable extracellular matrix to support network rewiring, among other favorable roles. Here, we review the multilayered nature of phagocytotic microglia\/macrophages, including the molecular and cellular mechanisms that govern microglia\/macrophage\u2010induced phagocytosis in acute brain injury, and discuss strategies that tap into the therapeutic potential of this engulfment process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Identification of biological targets that can temper neuroinflammation after brain injury without hindering the essential phagocytic functions of microglia\/macrophages will expedite better medical management of the stroke recovery stage.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13899","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T13:49:20Z","timestamp":1656164960000},"page":"1279-1293","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":207,"title":["Phagocytic microglia and macrophages in brain injury and repair"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4317-5698","authenticated-orcid":false,"given":"Fang","family":"Yu","sequence":"first","affiliation":[{"name":"Geriatric Research, Education and Clinical Center Veterans Affairs Pittsburgh Health Care System  Pittsburgh Pennsylvania USA"},{"name":"Pittsburgh Institute of Brain Disorders &amp; Recovery and Department of Neurology University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangfan","family":"Wang","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education and Clinical Center Veterans Affairs Pittsburgh Health Care System  Pittsburgh Pennsylvania USA"},{"name":"Pittsburgh Institute of Brain Disorders &amp; Recovery and Department of Neurology University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne 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