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No efficient therapy is currently available, except for the removal of the occluding blood clot during the first hours after symptom onset. Loss of function after stroke is due to cell death in the infarcted tissue, cell dysfunction in the peri-infarct region, as well as dysfunction and neurodegeneration in remote brain areas. Plasticity responses in spared brain regions are a major contributor to functional recovery, while secondary neurodegeneration in remote regions is associated with depression and impedes the long-term outcome after stroke. Hypoxic-ischemic encephalopathy due to birth asphyxia is the leading cause of neurological disability resulting from birth complications. Despite major progress in neonatal care, approximately 50% of survivors develop complications such as mental retardation, cerebral palsy or epilepsy. The C3a receptor (C3aR) is expressed by many cell types including neurons and glia. While there is a body of evidence for its deleterious effects in the acute phase after ischemic injury to the adult brain, C3aR signaling contributes to better outcome in the post-acute and chronic phase after ischemic stroke in adults and in the ischemic immature brain. Here we discuss recent insights into the novel roles of C3aR signaling in the ischemic brain with focus on the therapeutic opportunities of modulating C3aR activity to improve the outcome after ischemic stroke and birth asphyxia.<\/jats:p>","DOI":"10.1007\/s11064-021-03419-6","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T05:04:27Z","timestamp":1628658267000},"page":"2626-2637","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Targeting Complement C3a Receptor to Improve Outcome After Ischemic Brain Injury"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2734-8237","authenticated-orcid":false,"given":"Marcela","family":"Pekna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Stokowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1607-8075","authenticated-orcid":false,"given":"Milos","family":"Pekny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"3419_CR1","doi-asserted-by":"publisher","first-page":"2819","DOI":"10.1161\/STROKEAHA.112.654228","volume":"43","author":"M Pekna","year":"2012","unstructured":"Pekna M, Pekny M, Nilsson M (2012) Modulation of neural plasticity as a basis for stroke rehabilitation. 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