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An increased understanding of the pathways that facilitate tissue repair after HI may aid the development of better treatments. Here, we study the role of lactate receptor HCAR1 in tissue repair after neonatal HI in mice. We show that HCAR1 knockout mice have reduced tissue regeneration compared with wildtype mice. Furthermore, proliferation of neural progenitor cells and glial cells, as well as microglial activation was impaired. Transcriptome analysis showed a strong transcriptional response to HI in the subventricular zone of wildtype mice involving about 7300 genes. In contrast, the HCAR1 knockout mice showed a modest response, involving about 750 genes. Notably, fundamental processes in tissue repair such as cell cycle and innate immunity were dysregulated in HCAR1 knockout. Our data suggest that HCAR1 is a key transcriptional regulator of pathways that promote tissue regeneration after HI.<\/jats:p>","DOI":"10.7554\/elife.76451","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T07:15:11Z","timestamp":1656659711000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.76451","source":"Crossref","is-referenced-by-count":81,"title":["Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia"],"prefix":"10.7554","volume":"11","author":[{"given":"Lauritz","family":"Kennedy","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00j9c2840","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Oslo University Hospital and University of Oslo","place":["Oslo, Norway"]},{"id":[{"id":"https:\/\/ror.org\/01xtthb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Physiology, Institute of Basic Medical Sciences, University of 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